Pneumonia (community-acquired): clinical guidelines

List of Abbreviations

ABR – antibiotic resistance

ABT – antibiotic therapy

AMD – systemic antimicrobial drug (J)

URT – upper respiratory tract

CAP – community-acquired pneumonia

HFOV – high-frequency oscillatory artificial lung ventilation

ECE – early childhood educational establishment

RF – respiratory failure

TV – tidal volume

IMV — invasive mechanical ventilation

IBW – ideal body weight

OI – oxygenation index

SI – saturation index

LRTD – lower respiratory tract diseases

CG — clinical guidelines

ARVI – acute respiratory viral infection

ARDS – acute respiratory distress syndrome

PEEP – positive end-expiratory pressure

RSV — respiratory syncytial virus

RR — respiratory rate

HR — heart rate

ESR — erythrocyte sedimentation rate

CRP — C-reactive protein

CS – (Other beta-lactam antibacterial drugs: First-generation cephalosporins, Second-generation cephalosporins, Third-generation cephalosporins, Fourth-generation cephalosporins)

ECMO – extracorporeal membrane oxygenation

BiPAP (Biphasic Positive Airway Pressure) — bi-level positive airway pressure in the respiratory organs (artificial lung ventilation / non-invasive artificial lung ventilation)

B. pertussis – Bordetella pertussis                                       

C. pneumoniae – Chlamydophila pneumoniae

CPAP (Constant Positive Airway Pressure) — continuous positive airway pressure mechanical ventilation mode (artificial lung ventilation / non-invasive artificial lung ventilation)

FiO₂ - fractional concentration of oxygen in the inspired gas mixture

H. influenzae – Haemophilus influenzae                                          

IgG – class G immunoglobulins

IgM – class M immunoglobulins

M. pneumoniae – Mycoplasma pneumoniae                                               

MAP (mean airway pressure) - mean airway pressure

MRSA – methicillin-resistant Staphylococcus aureus

MSSA – methicillin-susceptible Staphylococcus aureus

.NO – nitric oxide.

PEEP – positive end-expiratory pressure

P plateau – plateau pressure

S. aureus – Staphylococcus aureus   

PaO₂ partial pressure of oxygen in arterialized capillary blood

SIRS – systemic inflammatory response syndrome

S. pneumoniae – Streptococcus pneumoniae

SaO₂ - arterial blood oxygen saturation (an indicator reflecting the fraction of oxygen-saturated hemoglobin relative to total hemoglobin in the blood)

SpO₂ – peripheral capillary oxygen saturation (measured using a pulse oximeter)

** – a medicinal product included in the Order of the Government of the Russian Federation dated October 12, 2019, No. 2406-r (as amended) "On Approval of the List of Vital and Essential Drugs, as well as Lists of Medicinal Products for Medical Use and the Minimum Assortment of Medicinal Products Necessary for the Provision of Medical Care"

# - The use of a medicinal product in accordance with indicators (characteristics) not specified in its instructions for use (off-label) is carried out subject to a signed informed voluntary consent (pursuant to Federal Law No. 323-FZ dated November 21, 2011, as amended) and/or by decision of the medical commission

Terms and Definitions

New and narrowly focused professional terms are not used in these clinical guidelines.

1. Brief information on the disease or condition

1.1 Definition of the disease or condition

In Russian pediatrics, as in most countries of the world, pneumonia is defined as "an acute infectious disease of the lung parenchyma, diagnosed by respiratory distress syndrome and/or physical examination data, as well as infiltrative changes on a radiograph" [1,2]. Such a definition implies the diagnosis of pneumonia only in "X-ray positive" cases of lower respiratory tract infections. This approach makes it possible to exclude diseases such as bronchitis and bronchiolitis, which are viral in most cases and do not require antibacterial treatment.

It should be noted that World Health Organization (WHO) guidelines allow the diagnosis of pneumonia based solely on clinical data from the examination of the child and respiratory rate counting [3]. This is due to the lack of routine radiography in developing healthcare settings.

Pneumonia is an acute polyetiological infectious disease with primary involvement of the respiratory divisions of the lungs and accumulation of inflammatory exudate in the alveoli, manifested by varying degrees of intoxication, respiratory disorders, local physical changes in the lungs, and the presence of an infiltrative shadow on a chest X-ray [4].

The most clinically relevant principle provides for the subdivision of pneumonia into community-acquired (CAP) and nosocomial. Community-acquired pneumonia is pneumonia that developed outside a hospital, including that diagnosed within the first 48 hours from the moment of hospitalization.

Community-acquired pneumonia is an acute infectious disease, so the definition "acute" before the diagnosis of "pneumonia" is redundant.

A special form of pneumonia in the pediatric population is congenital pneumonia, which develops in newborns, as a rule, in the first 72 hours of life; this form of the disease is considered in the relevant clinical guidelines.

CAP in patients with severe immunosuppression (children with HIV infection, primary immunodeficiencies, receiving chemotherapy and/or immunosuppressive therapy, recipients of donor organ and tissue transplants) differs from the general population in etiology, clinical course, and prognosis and is not considered within the framework of these guidelines.

1.2 Etiology and pathogenesis of the disease or condition (group of diseases or conditions)

1.2.1 Etiology of pneumonia in children

According to etiology, CAP can be viral and bacterial. The etiological structure of pneumonia in children is very diverse and depends on the child's age (Table 1). Data on the etiology of CAP in children vary greatly, which can be explained by epidemiological conditions and methodological features of the studies.

In a prospective multicenter study of 154 hospitalized children with CAP who underwent a thorough etiological search, a pathogen was identified in 79% of children [5]. A bacterial etiology of CAP was established in 60% of patients (Streptococcus pneumoniae was isolated in 73% of cases); Mycoplasma pneumoniae and Chlamydophila pneumoniae were detected in 14% and 9% of cases, respectively. Viruses were identified in 45% of children. Notably, viral-bacterial co-infection was diagnosed in 23% of children.

According to a large-scale population-based study conducted in the USA in children under 18 years of age hospitalized with clinical symptoms of CAP who had radiological confirmation of CAP and from whom samples for etiological study were obtained (n=2222), viruses were detected in 66.2%: respiratory syncytial virus (RSV) (28.0%), rhinovirus (27.3%), and metapneumovirus (12.8%). It should be noted that RSV was most frequently isolated in children under 5 years of age compared to older patients (37% vs 8%), with a similar situation for adenovirus (15% vs 3%) and metapneumovirus (15% vs 8%). Typical bacterial pathogens were isolated in 7.3% of children: S. pneumoniae – 3.6%, Staphylococcus aureus – 1.0%, Streptococcus pyogenes – 0.7%, M. pneumoniae – 8.0% (mycoplasmas were more frequently isolated in children older than 5 years compared to younger children – 19% vs 3%) [6]. In another study involving 441 children aged 2 months to 18 years with CAP (13.8% received outpatient treatment, 86.2% were hospitalized), viruses were detected in 55.6%, typical bacterial pathogens in 3.6% of cases, and atypical pathogens in 8.8% [7].

In most cases, the etiology of CAP cannot be reliably established [2]. In healthy children, especially those under 5 years of age, asymptomatic carriage of commensal microbiota (bacteria and viruses) in the nasopharynx is widespread, which inevitably interferes with the analysis of respiratory samples and does not always allow distinguishing a true etiological agent from a contaminating organism. A study conducted in the Netherlands [8] showed nasopharyngeal carriage of at least one species of typical opportunistic bacteria among S. pneumoniae, H. influenzae, M. catarrhalis, and S. aureus in 91% (900/986) of healthy children aged 6 to 24 months, with 63% (639/986) of children colonized by multiple bacterial species simultaneously. An analysis of nasopharyngeal carriage in healthy children under 5 years of age in the Republic of Khakassia revealed pneumococcus in 51.6% (257/498) of those examined [9].

Asymptomatic carriage of at least one of the 20 studied viruses was detected in 67% (663/986) of children from the Dutch study cited above [8], and a combination of viruses was observed in 29% (285/986) of children. Rhinoviruses (38%) and enteroviruses (15%) were detected more often than others. A large Russian study showed similar results, where any virus (13 viruses tested in total) was identified in 35% (204/583) of healthy children aged 1 month to 17 years, with a predominance of rhinoviruses [66].

Viruses usually act as factors promoting lower respiratory tract infection by the bacterial microbiota. Their etiological significance is indicated by the more frequent isolation of certain viruses in patients with CAP compared to healthy children. These include influenza viruses, metapneumovirus, and RSV, which are detected multifold more frequently in CAP. In contrast, the etiological significance of rhinoviruses, enteroviruses, parainfluenza viruses, bocaviruses, and seasonal coronaviruses is questionable, as they are detected in CAP and in healthy individuals with approximately the same frequency [10].

Thus, the high carriage rate of typical bacterial pathogens and viruses in healthy children in most cases does not allow for a reliable determination of CAP etiology when analyzing upper respiratory tract biomaterial.

Acute respiratory viral infections (ARVI) frequently precede CAP in young children in their first years of life; their triggering role decreases with age [11]. The clinical picture of pneumonia itself depends little on the presence of ARVI, apart from catarrhal syndrome and influenza intoxication. This makes the term "viral-bacterial pneumonia" largely unjustified, although signs of viral co-infection should be noted when present.

"Purely" viral lung lesions are observed more frequently in infants, patients with immunodeficiencies in influenza, parainfluenza, RSV, adeno-, entero-, rhinovirus, and SARS-CoV-2 infections. Unlike bacterial pathogens, viruses predominantly affect the interstitium with alveolar edema, fibrin deposition, and hyaline membrane formation in the absence of alveolar and polynuclear exudate [12]. The SARS-CoV-2 virus also affects capillaries and branches of the pulmonary arteries with the development of thrombosis, often with the addition of a bacterial infiltrate, including as a result of nosocomial infection [13]. Respiratory viruses (most commonly rhinovirus) serve as etiological agents of bronchial asthma exacerbations, which must be ruled out in children older than one year with LRTI of this etiology accompanied by symptoms of bronchial obstruction.

Infants in the first months of life

In infants in the first months of life, CAP can be caused by pathogens acquired in the perinatal period, but the frequency of community-acquired bacterial pathogens is increasing (S. pneumoniae, S. aureus, nontypeable strains of H. influenzae). S. pneumoniae is the leader in the etiological structure of pneumonia in this age group (Table 1). S. pneumoniae and S. aureus frequently cause a complicated course of pneumonia in infants [15]. The spectrum of community-acquired pneumonia pathogens at this age is determined, among other factors, by incomplete vaccination against pneumococcus and H. influenzae type b. A significant place in this age group also belongs to viruses, primarily RSV, influenza and parainfluenza viruses, adenoviruses, and human metapneumovirus. Atypical microorganisms are rare at this age. However, pneumonia caused by Bordetella pertussis can develop in 20% of children who contract pertussis at this age. The role of pathogens such as Ureaplasma urealyticum and U. parvum, which are isolated in tracheal aspirates of newborns with extremely low birth weight and children with bronchopulmonary dysplasia, is being discussed [16]. In rare cases, pneumonia in children of this age group is caused by C. trachomatis (perinatal transmission) [1].

Children aged 3 months to 5 years

The main etiological factor of LRTI in this age group is viruses [2] (Table 1). In children in the first two years of life, viral LRTI usually occurs in the form of acute bronchiolitis, which is practically impossible to differentiate from viral pneumonia either clinically or radiologically. In rare cases, viral bronchiolitis is complicated by the addition of a bacterial infection with the development of typical bacterial CAP.

In the structure of bacterial pneumonia at this age, S. pneumoniae is the leader, accounting for 21–44% according to various sources [5, 18]. Other pathogens are H. influenzae type b (an extremely rare cause of CAP in immunized children), S. pyogenes, and very rarely S. aureus [19]. In recent years, against the background of mass vaccination against pneumococcal infections, the proportion of Mycoplasma pneumonia is also increasing in this age group.

Children over 5 years and adolescents

M. pneumoniae is the most frequent etiological agent of CAP in this age group, accounting for 14–35% of hospitalizations (Table 1). The incidence of Mycoplasma infection is characterized by periodicity with epidemic peaks every 4–7 years, predominantly from September to December. During the peak period, the proportion of M. pneumoniae infection in the CAP structure reaches 30–40%. Another epidemiological feature of M. pneumoniae is the ability to cause outbreaks of LRTI (including CAP) in organized groups with close contacts (in preschool, school, and student groups, among military personnel, etc.) and familial cases of infection.

S. pneumoniae also plays a significant role in the etiological structure of CAP, especially in patients requiring hospitalization. Pneumonia in children can very rarely be caused by S. pyogenes. Pneumonia caused by S. aureus may be associated with immunodeficiency states in children [15]. Viral pneumonias are rare, usually proceed relatively mildly [20, 21], and are caused by RSV, parainfluenza and influenza viruses, adenoviruses, and human metapneumovirus.

In children in low- and middle-income countries, B. pertussis is also one of the etiological factors of pneumonia. Risk factors for pertussis include low vaccination coverage for this infection, incomplete vaccination, underweight, and HIV infection [22].

CAP caused by C. pneumoniae is observed mainly in collectives (recruits, students in dormitories); sporadic cases, as well as pneumonia caused by Legionella pneumophila, are very rare.

Table 1. Age structure of bacterial pneumonia etiology [23].

++++ very frequent, +++ frequent, ++ relatively infrequent, + rare, ± very rare, — none.

Table 2. Main CAP pathogens in children based on international studies [24].

1.2.2. Susceptibility of CAP pathogens to systemic antimicrobial drugs (AMDs)

The situation regarding AMR of respiratory pathogens isolated in the Russian Federation is presented based on the analytical report "State of Antibiotic Resistance of Bacterial Pathogens of Infections in the Russian Federation" by the Methodological Verification Center for Antimicrobial Resistance Issues – the Reference Center for Clinical Pharmacology of the Russian Ministry of Health for 2024 [25].

S. pneumoniae (pneumococcus) is the most clinically significant pathogen of community-acquired pneumonia (CAP), against which the most effective antimicrobial therapy (AMT) should be administered [26]. A consistent trend observed over the past 10–15 years is the widespread decrease in pneumococcal susceptibility to macrolides, as well as the emergence and spread over the past decade of isolates with reduced susceptibility and resistance to benzylpenicillin**, amoxicillin**, ampicillin**, and ceftriaxone**.

The resistance rates of S. pneumoniae were as follows: to amoxicillin**, ampicillin**, and benzylpenicillin** — 13.89%, 18.33%, and 7.41%, respectively; to ceftriaxone**, ceftaroline fosamil**, and ceftobiprole medocaril — 1.3%, 0.56%, and 1.42%, respectively; to ertapenem** — 14.07%; to macrolides (azithromycin**, clarithromycin**, erythromycin) — 27.59%, 27.96%, and 23.89%, respectively; to lincosamides (clindamycin**) — 15.56%; to fluoroquinolones (levofloxacin** and moxifloxacin**) — 0.74% and 0.56%, respectively; to tetracycline — 30%; to chloramphenicol** — 3.89%; to co-trimoxazole [sulfamethoxazole + trimethoprim]** — 26.3%. No isolates resistant to vancomycin** and linezolid** were identified (Fig. 1).

Fig. 1. Antimicrobial activity against S. pneumoniae strains in the Russian Federation (n=540)

According to the international SOAR (Survey of Antibiotic Resistance) study published in 2018, which tested 279 S. pneumoniae strains isolated from patients in 3 cities of the Russian Federation (Moscow, Saint Petersburg, and Smolensk) in 2014–2016, the rate of non-susceptibility to benzylpenicillin** was 33%, and 31.2% of strains were resistant to macrolides. At the same time, the vast majority of isolated pneumococcal strains (95%) were susceptible to amoxicillin** and amoxicillin/clavulanate** [28].

H.influenzae

The resistance rates of H. influenzae were as follows: to ampicillin** — 19.67%; to ceftriaxone**, cefixime, and ceftaroline fosamil** — 0.82%, 4.92%, and 6.56%, respectively; to macrolides (azithromycin** and clarithromycin**) — 0.82% for each antimicrobial; to tetracycline — 1.64%; to co-trimoxazole [sulfamethoxazole + trimethoprim]** — 34.43%; to chloramphenicol** — 1.64%; to fluoroquinolones (ciprofloxacin**, levofloxacin**, and moxifloxacin**) — 14.75%, 14.75%, and 13.93%, respectively. No isolates resistant to amoxicillin/clavulanate** and ertapenem** were identified.

The SOAR study (2014–2016) also tested 279 H. influenzae strains isolated from patients in the Russian Federation [28]. Non-susceptibility to amoxicillin** was observed in 19% of isolates, with β-lactamase production detected in 15.4% of strains. ≥97.5% of Haemophilus influenzae isolates were susceptible to amoxicillin/clavulanate** [28].

Thus, alarming trends have been identified, in particular, an increase in the number of H. influenzae strains producing β-lactamase and resistant to ampicillin** and amoxicillin** (15–20%), a rise in pneumococcal resistance to macrolides (~25–30%), the spread of strains with reduced susceptibility and resistance to benzylpenicillin** (>30%), as well as the spread in certain regions of S. pneumoniae isolates with reduced susceptibility to parenteral 3rd-generation cephalosporins (cefotaxime** and ceftriaxone**).

M. pneumoniae and C. pneumoniae are naturally highly susceptible to macrolides and tetracyclines; however, publications have recently emerged regarding the spread of genetic determinants of macrolide resistance (mutations in domain V of the 23S rRNA gene) among mycoplasmas [29]. Thus, according to the DeMaRes study, 20.6% of M. pneumoniae strains isolated between 2016 and 2020 in patients under 18 years of age (1,154 strains analyzed in total) carried macrolide resistance genes. The average macrolide resistance rate of M. pneumoniae (n=2,123) in the Russian Federation is 22.7%, although the clinical significance of this phenomenon is not yet fully understood (in particular, the clinical efficacy of macrolides in children with lower respiratory tract infections caused by M. pneumoniae did not depend on the presence of the resistance gene) [30].

1.2.3. Pathogenesis of CAP

Pneumonia is characterized by an inflammatory process of infectious origin in the lungs with predominant involvement of the alveoli and/or interstitial tissue. The pathogen enters the lungs via inhalation, aspiration, or by hematogenous and lymphatic routes. Disruptions in lung elasticity, alveolar ventilation, and perfusion occur. These processes can significantly impair pulmonary gas exchange. As with any infectious disease, the severity of pathophysiological changes is determined by the balance between the virulence of the microorganism and the adequacy of human immune and non-immune defense mechanisms.

For the features of pathogenesis and the clinical course of lung damage in novel coronavirus infection (COVID-19), please refer to the relevant temporary guidelines of the Russian Ministry of Health.

1.3 Epidemiology of the Disease or Condition

CAP can develop at any age, but it most commonly occurs in young children. Approximately 150 million cases of pneumonia are registered globally each year in children under 5 years of age. Severe pneumonia is observed in 7–13% of cases and accounts for 11–20 million hospitalizations annually [31].

According to the Russian Ministry of Health, between 1999 and 2008, the incidence of pneumonia in the Russian Federation was 7.95–8.86 per 1,000 children per year [32]. According to a study conducted in 2011–2012 in three regions of Russia with proper radiological control, the incidence of CAP in children aged 6 months to 5 years in our country is 5.3 per 1,000 children per year [33]. These figures are consistent with data from foreign authors using radiological diagnostic criteria [34]. According to statistical reporting, in 2023, the incidence of pneumonia was 188,715 cases (738.9 per 100,000 child population) among children aged 0–14 years and 28,947 cases (624.9 per 100,000 relevant population) among children aged 15–17 years [164].

According to the State Report "On the State of Sanitary and Epidemiological Welfare of the Population in the Russian Federation in 2024", a significant increase in the incidence of community-acquired pneumonia was registered in the Russian Federation (the overall rate in the Russian Federation was 866.62 per 100,000 population), representing a 1.7-fold increase compared to 2023 (498.02 per 100,000 population) and more than a 2-fold increase compared to long-term average values (416.7 per 100,000 population). This situation is primarily driven by a cyclic surge in the incidence of community-acquired pneumonia caused by Mycoplasma pneumoniae. It should be noted that the increase in CAP incidence in 2024 was mainly driven by an increase in the pediatric population — a 2.2-fold increase compared to the 2023 level (the pediatric incidence rate in 2024 was 1,790.94 per 100,000 child population, versus 803.62 per 100,000 child population in 2023) and a 2.5-fold increase compared to long-term average values (715.3 per 100,000 child population). The peak incidence rate of CAP, as in previous years, was observed in the 1–2 year old age group (2,357.48 per 100,000 population of this age group) [176].

CAP incidence increases during influenza epidemics. Rickets and malnutrition are no longer significant predisposing factors for pneumonia in our country, whereas food aspiration (in the first year of life), immunodeficiencies, cystic fibrosis, neuromuscular disorders, and congenital heart disease with excessive pulmonary blood flow continue to play a major role. These same conditions significantly increase the likelihood of an unfavorable outcome of pneumonia. Incidence is also increased by passive and active smoking (including vaping), poor living conditions, household crowding, comorbid conditions, and having an older sibling in the household, especially one attending a childcare facility.

Pneumonia remains the most frequent cause of death in children under 5 years of age worldwide. Although the effective use of antimicrobial drugs (AMDs) over recent decades has drastically reduced childhood mortality from pneumonia, today up to 20% of deaths in the first 5 years of life globally are still attributed to pneumonia [16, 35].

In the Russian Federation, respiratory diseases in children aged 0–17 years rank third in the structure of causes of death, after external causes and congenital malformations.

1.4 Features of Coding the Disease or Condition

ICD classifies pneumonia etiologically, providing corresponding categories for viral, bacterial, parasitic, and unspecified pneumonias:

J12 Viral pneumonia, not elsewhere classified

Includes: bronchopneumonia due to viruses other than influenza virus

J12.0 Adenoviral pneumonia

J12.1 Respiratory syncytial virus pneumonia

J12.2 Parainfluenza virus pneumonia

J12.3 Human metapneumovirus pneumonia

J12.8 Other viral pneumonia

J12.9 Viral pneumonia, unspecified

J13 Pneumonia due to Streptococcus pneumoniae

J14 Pneumonia due to Haemophilus influenzae [bacillus of Pfeiffer]

J15 Bacterial pneumonia, not elsewhere classified

Includes: bronchopneumonia caused by bacteria other than S. pneumoniae and H. influenzae

J15.0 Pneumonia due to Klebsiella pneumoniae

J15.1 Pneumonia due to Pseudomonas

J15.2 Pneumonia due to staphylococcus

J15.3 Pneumonia due to streptococcus, group B

J15.4 Pneumonia due to other streptococci

J15.5 Pneumonia due to Escherichia coli

J15.6 Pneumonia due to other gram-negative bacteria

J15.7 Pneumonia due to Mycoplasma pneumoniae

J15.8 Other bacterial pneumonias

J15.9 Bacterial pneumonia, unspecified

J16 Pneumonia due to other infectious agents, not elsewhere classified

J16.0 Chlamydial pneumonia

J16.8 Pneumonia due to other specified infectious agents

J18 Pneumonia, organism unspecified

J18.0 Bronchopneumonia, unspecified

J18.1 Lobar pneumonia, unspecified

J18.2 Hypostatic pneumonia, unspecified

J18.8 Other pneumonia, organism unspecified

J18.9 Pneumonia, unspecified

1.5 Classification of the disease or condition

ICD classifies pneumonias by etiology (see above). However, objective difficulties in obtaining biomaterial directly from the inflammation site, significant duration of microbiological tests, and the widespread practice of antimicrobial therapy before seeking medical attention or diagnostic procedures result in the lack of an etiological diagnosis in 50–70% of patients. In clinical practice, bacterial pneumonias are also frequently classified into "typical" ones, i.e., caused by typical bacterial flora, primarily S. pneumoniae, H. influenzae, less commonly S. aureus and S. pyogenes, and "atypical" ones, caused by atypical bacteria - M. pneumoniae and C. pneumoniae.

Based on the radiological findings, the following are distinguished focal, focal-confluent, lobar(lobar),segmental, polysegmentaliinterstitial pneumonias (Table 3).

Depending on the severity, a distinction is made between non-severe (moderate) and severe pneumonias (Table 3). Severity criteria are based on the severity of respiratory failure (RF) and the presence of systemic danger signs in the patient. This classification of pneumonia severity is recommended by WHO and is considered optimal for organizing effective medical care [36,37].

Table 3. Classification of pneumonia

Pneumonias can be complicated and uncomplicated. Pulmonary and systemic complications of pneumonia are distinguished (Table 4). The most frequent complications of CAP are pleurisy (parapneumonic and metapneumonic) and destruction of lung tissue (leading to destructive (necrotizing) pneumonia or lung abscess) [38].

Table 4. Most frequent CAP complications

* in foreign literature, the term "necrotizing pneumonia" is more frequently used

With adequate treatment, most uncomplicated cases of pneumonia resolve within 2—4 weeks, and complicated cases within 1—2 months. Protracted pneumonia is defined as lasting longer than 6 weeks. A chronic course of pneumonia is currently not considered.

1.6 Clinical presentation of the disease or condition

Symptoms of CAP are often nonspecific and depend on the patient's age and the infectious agent. Pneumonia is an acute disease, typically presenting with a body temperature above 38.0°C and a cough. A meta-analysis of studies on the diagnostic value of clinical symptoms of pneumonia, published in 2015, showed that the most significant are tachypnea with a respiratory rate of more than 50 per minute, grunting respiration, chest retractions, and nasal flaring during breathing [39]. Early and important clinical signs of pneumonia are symptoms of respiratory failure (RF) (Table 5); in severe cases, hypoxemia and hypercapnia develop. However, dyspnea and tachypnea occur in only 50–70% of children, and their absence does not rule out pneumonia [40]. Fever and cough do not necessarily indicate pneumonia, but the absence of fever usually excludes pneumonia in a child older than 6 months. Blood oxygen saturation assessment using pulse oximetry should be performed in all children with respiratory symptoms. Acrocyanosis usually occurs in severe cases. Central cyanosis is assessed by the color of the oral mucosa; its presence indicates severe impairment of gas exchange. Chest pain occurs with pleural inflammation. Pleural pain often radiates, and patients may complain of abdominal pain.

A characteristic sign of CAP caused by both typical and atypical pathogens is the persistence of a temperature ≥38.0° for more than 3 days, whereas in acute respiratory viral infections (ARVI) such a temperature occurs in only 18% of patients (in influenza, adeno-, and enteroviral infections) [11]. The presence or absence of RF symptoms is assessed (Table 5), and if present, the severity of RF is determined (Table 6).

Table 5. Symptoms of respiratory failure in children (WHO, 2015)

Note:

¹ - Fleming S, Thompson M, Stevens R, et al. Normal ranges of heart

rate and respiratory rate in children from birth to 18 years of age: A systematic review of

observational studies. Lancet. 2011;377:1011.

Respiratory failure is the inability of the respiratory system to maintain oxygenation or ventilation, or the inability to perform both functions. Respiratory failure occurs when the lungs are unable to adequately perform gas exchange. Tachypnea, chest retractions, grunting respiration, and nasal flaring are clinical signs indicating the presence of respiratory distress. The child may be restless and even aggressive upon the onset of hypoxia. As acute respiratory failure progresses, respiratory muscle fatigue is observed, breathing becomes irregular, and bradypnea and apnea develop. Hypoxemia and/or hypercapnia are considered classic signs of respiratory failure.

A distinction should be made between the concepts of hypoxemia and hypoxia. Hypoxia is defined as a decreased amount of oxygen delivered to or utilized by the body's tissues and cells. Hypoxemia is a decrease in blood oxygen levels. The universally accepted threshold of hypoxemia in acute respiratory failure is an arterial partial pressure of oxygen (PaO2) of less than 60 mm Hg or (more commonly used in routine clinical practice) a decrease in blood oxygen saturation measured by a pulse oximeter (SpO2): less than 94% is considered abnormal, and less than 90% is considered significant hypoxemia [59].

The classification of acute RF by severity is based on blood gas values (Table 6). This classification is universal for patients of all ages; in pediatrics, it can determine patient routing: patients with RF 0 can be treated in an outpatient setting, patients with RF grade 1–2 are hospitalized, and patients with RF grade 3 require respiratory support in an ICU [144].

Table 6. Classification of acute RF by severity based on PaO₂ and SаO₂ [144]

Note: Grade II RF requires the mandatory prescription of oxygen therapy (although patients with pulmonary hypertension or fever are prescribed oxygen at SpO₂ ≤ 92%), and Grade III most frequently warrants invasive respiratory support.

Since the determination of PaO₂ and SаO₂ is not always available, it is possible to rely on pulse oximetry values SpO₂

In practice, acute RF is traditionally provisionally classified by clinical signs:

• RF0 — no signs of respiratory failure, SpO₂ ≥ 95%;

• RF1 (compensated or latent, when there is no hypoxemia due to the engagement of compensatory mechanisms), mildly pronounced clinical manifestations (dyspnea, chest retractions during breathing) at SpO₂ > 90%;

• RF2 (subcompensated — incomplete compensation due to strain on compensatory mechanisms). Clinically pronounced symptoms: dyspnea, grunting respiration, acrocyanosis, chest retractions, nasal flaring, SpO₂ < 90%, normalizing with oxygen supplementation;

• RF3 (decompensated — severe arterial hypoxemia and/or hypercapnia). May be accompanied by pathological breathing patterns, apnea. Oxygen therapy is ineffective. Invasive respiratory support is required.

Pneumonia caused by typical pathogens. The differential diagnosis of typical and atypical pneumonia is presented in Table 7. Grunting respiration, inspiratory lower ribcage retractions, and hypoxemia (central cyanosis, SaO₂ ≤ 90%) are specific for severe pneumonias [3], but absent in most CAP cases [11]. Percussion and auscultatory findings are specific but have low sensitivity, which can lead to underdiagnosis; decreased percussion note, even in lobar processes, occurs in only 75% of cases, localized diminished or bronchial breath sounds in 53%, and fine crepitations in only 39%. At least one of these 3 signs is detected in only 70% of patients; in the rest, pneumonia presents as "silent" [11]. Even children aged 0–5 years with fever, leukocytosis above 20x10⁹/L, and an alveolar infiltrate on an X-ray had no physical signs of pneumonia in 26% of cases [39].

Overdiagnosis of pneumonia is associated with the misinterpretation of scattered rales, as well as bronchospastic syndrome, which is atypical for typical pneumonia, allowing it to be reliably ruled out in children with wheezing and other signs of bronchial obstruction [3,11].

Therefore, the WHO proposed diagnosing pneumonia taking into account systemic disorders, in particular, life-threatening signs (microcirculatory disorders, severe respiratory failure, dehydration, impaired consciousness), which are characteristic of severe pneumonias [3].

The frequently used term "signs of intoxication" is less specific, as it usually describes disturbances caused by fever in patients with both viral and bacterial infections.

For Mycoplasma pneumoniae pneumonia, the incidence of which increases starting from the age of 5 years, fever is also characteristic, but intoxication is usually less pronounced: the general condition of patients is not severely affected, and daily routines are little disrupted, which often leads to late medical presentation (on days 6–9 of the febrile period) (Table 7). Auscultation is characterized by an abundance of dry and moist rales of various calibers, which may be asymmetric—more prominent on the affected side; signs of bronchial obstruction are sometimes detected. Extrapulmonary symptoms are frequently noted: nausea, vomiting (33%), skin rashes (25%), myalgia, sore throat, headache, catarrhal conjunctivitis, photophobia [41, 42].

Table 7. Symptoms of typical and mycoplasmal CAP

Sporadic cases of CAP caused by C. pneumoniae are characterized by a gradual onset with pharyngitis, often accompanied by bronchospastic syndrome, against the background of systemic disorders and persistent fever, which distinguishes atypical pneumonias from viral bronchitis [43].

Most patients experience an uncomplicated course of pneumonia. In these cases, body temperature normalizes within the first two days of starting antimicrobial therapy, physical signs disappear within 7 days, and radiological resolution is noted in 2–3 weeks.

Complicated CAP

A list of CAP complications is given in Table 4. Pleurisy is the leading CAP complication (up to 83%) [43]. A distinction is made between sinpneumonic pleurisy, which occurs simultaneously with pneumonia, and metapneumonic pleurisy, which usually develops a few days after the start of treatment (Table 8) [44].

Sinpneumonic pleurisy usually presents as an accumulation of exudate in the pleural cavity during the first five days of CAP and can develop in bacterial pneumonia of virtually any etiology. Depending on the pathogen and the duration of the disease, pleurisy can be fibrinous ("dry"), serofibrinous, or purulent. Prolonged fever, chest pain, abdominal pain, dullness on percussion, and weakened respiratory sounds are characteristic. In the absence of treatment, the purulent exudate thickens and adhesions form—pleural empyema.

Metapneumonic pleurisy occurs after the start of treatment, usually in pneumococcal pneumonia, and less commonly in infection caused by H. influenzae type b. Criteria for metapneumonic (immuno-mediated) pleurisy: recurrence of fever after 1–2 days of normal body temperature or its persistence during adequate antimicrobial therapy. The fever persists for 7–12 days and is refractory to ongoing treatment. The pleurisy is serofibrinous in nature, with a characteristic significant increase in CRP.

Table 8. Characteristics of two types of pleurisy [44].

Intrapulmonary destructive processes with the formation of bullae or abscess formation occur at the site of massive focal-confluent infiltrates in the lungs.

Bullae appear when foci clear during the resolution phase of pneumonia, usually with a satisfactory patient condition, and spontaneously disappear within 1–4 weeks.

Emptying of lung tissue destruction foci against the background of fever is accompanied by an episode of productive cough, chest pain, and anxiety; if perforation through the pleura occurs, pneumothorax may develop. The development of a lung abscess may be associated with anaerobic superinfection and is accompanied by high fever lasting over 5 days, a grey skin tint, grunting and groaning respiration, leukocytosis, and an increase in CRP. In most cases, the abscess also drains spontaneously through the bronchus, but sometimes bronchoscopic drainage of the abscess with transbronchial or transthoracic drainage is required.

Risk factors and symptoms for the development of lung destruction are [45]:

• lobar infiltrate;

• sinpneumonic pleurisy;

• young age;

• delayed start of antibiotic therapy (≥3 days from the onset of the disease);

• persistence of fever ≥3 days with adequate antibiotic therapy;

• grey skin color;

• leukocytosis greater than 15 × 10³/µL;

• "frozen" infiltrate on the chest radiograph.

However, it should be noted that inflammatory markers, including WBC, CRP, and PCT, cannot predict CAP severity due to low specificity [46].

Destruction occurs more frequently with infection by certain pneumococcal serotypes. Thus, more than half of pneumonias caused by serotypes 1, 3, 5, 7, 14, and 15 proceed with destruction even with early treatment initiation. However, if antimicrobial therapy is started late (on days 5–6 of the disease), other pneumococcal serotypes can also cause severe local (destruction, pleural empyema, abscess) and systemic (septic shock, HUS) complications.

The most severe complication of CAP is septic shock (its frequency is < 1%), and the risk of a fatal outcome increases significantly in this case. It develops extremely rarely, in massive lung lesions.

Signs of septic shock in pneumonia [47]:

• peripheral hemodynamic disorders (cold extremities, mottling, acrocyanosis, decreased diuresis);

• arterial hypotension;

• cyanosis of mucous membranes uncorrectable by nasal or mask oxygen delivery;

• respiratory rate significantly exceeding the age norm;

• decrease in SpO₂ < 92% or PaO₂/FiO₂ < 250;

• impaired consciousness;

• leukocytosis or leukopenia, thrombocytopenia, lactic acidosis.

2. Diagnostics, medical indications and contraindications for diagnostic methods

Criteria for establishing a CAP diagnosis are:

presence of an acute infectious disease of the pulmonary parenchyma, diagnosed by respiratory distress syndrome and/or physical findings, as well as infiltrative changes on the radiograph.

2.1 Complaints and Anamnesis

If CAP is suspected, it is necessary to collect an anamnesis and complaints regarding diseases of the lungs and bronchi in order to make a diagnosis (for details, see "Section 1.6. Clinical Presentation") [2].

2.2 Physical Examination

• All patients with suspected pneumonia are recommended to undergo a therapeutic visual inspection, therapeutic palpation, therapeutic auscultation, therapeutic percussion (standard general examination, assessment of signs of intoxication, respiratory failure): initial consultation (examination) by a pediatrician or initial consultation (examination) by a district pediatrician or initial consultation (examination) by a general practitioner (family physician) (with assessment of the degree of respiratory failure) (for primary health care) / initial diagnostic consultation (examination) by a pediatrician or initial consultation (examination) by an infectious disease physician (with assessment of the degree of respiratory failure) (for specialized medical care) in order to establish a diagnosis [48].

GCR CLEL 5Grade of Recommendation C (Level of Evidence – 5)

Comments:

Action algorithm:

- assess signs of intoxication (lethargy, refusal to eat and especially drink, adynamia, hyperesthesia, irritability, inconsolable crying, presence of eye contact with the child);

- assess the nature of the cough (dry, wet/productive);

- visual examination of the upper respiratory tract (examine the upper respiratory tract);

- assess signs of restrictive respiratory failure (participation of accessory muscles in the act of breathing and retraction of compliant areas of the chest during breathing: nasal flaring, retractions of the subcostal regions and intercostal spaces, jugular notch);

- measure the respiratory rate, measure the heart rate for at least 1 minute;

- perform percussion of the lungs;

- perform therapeutic auscultation (lung auscultation), paying attention to the symmetry of auscultatory changes.

If grunting respiration, pronounced tachypnea, nasal flaring, and retractions of compliant chest areas during breathing are detected, supplemental oxygen must be immediately provided to the child.

Symptoms of sinpneumonic pleurisy may include chest pain and abdominal pain against the background of fever. On examination, signs such as dullness to percussion over fluid accumulation and weakened breath sounds may be detected.

(for details, see the section "Clinical Presentation") [49].

Diagnosis and treatment of pneumonia in children are usually carried out by a pediatrician/district pediatrician/general practitioner (family physician) or an infectious disease physician/pulmonologist, etc., depending on the clinical situation (Consultation (examination) by a pediatrician / district pediatrician / general practitioner (family physician) / infectious disease physician, pulmonologist, etc.)

2.3 Laboratory Diagnostics

2.3.1. Complete Blood Count with Differential and Inflammatory Markers

• Children with suspected CAP are recommended to undergo a complete blood count (CBC) with differential and a serum C-reactive protein (CRP) test [21,50,51]. Level of evidence B (confidence level of evidence – 3)

Comment:

The results of the complete blood count are interpreted taking into account age-related differences in leukocyte counts (Table 9). In young children, the threshold value of leukocytosis will be higher compared to older children.

Table 9. Threshold values of hemogram parameters and CRP in the diagnosis of acute infection [52, 53, 54, 55]

Fever above 39°C with signs of intoxication, respiratory failure, and suspected bacterial infection are indications for an immediate complete blood count with differential and serum C-reactive protein (CRP) testing (usually in an inpatient or day hospital setting); CRP is not tested in outpatients with non-severe pneumonia in routine practice [56].

In CAP caused by typical bacterial pathogens, changes in the complete blood count are generally represented by leukocytosis (Table 9), which can reach 25–30 × 10⁹/L, with neutrophilia and an elevated CRP level >40 mg/L; an increase in CRP up to 200–300 mg/L is frequently recorded. In atypical pneumonia, the increase in CRP is usually moderate, and leukocytosis may be absent.

Currently, there are no reliable biomarkers for the differential diagnosis of bacterial and viral etiology of CAP. Serum procalcitonin, which was perceived as a specific marker of bacterial infection, in most standard situations turned out to be no more specific than CRP. Like other acute-phase reactants, procalcitonin increases in both viral infections and non-infectious inflammatory reactions (trauma, surgery, tumors, etc.). In terms of diagnostic performance in CAP, procalcitonin has no advantages over CRP; however, the cost of the procalcitonin test is an order of magnitude higher, and it requires more complex equipment (CRP is tested on a standard biochemical analyzer).

A combination of clinical, laboratory, and instrumental methods may be important in the differential diagnosis of bacterial and viral CAP. Thus, for bacterial etiology of CAP, a higher specificity of the combination of a high CRP level (≥72 mg/L) with fever or absence of rhinorrhea was demonstrated compared to evaluating the CRP level alone [57].

• In hospitalized patients with severe CAP, to assess the effectiveness of ongoing antibiotic therapy, it is recommended to measure blood procalcitonin levels [48,51].

GDR CLE 5Grade of recommendation C (level of evidence – 5)

Comments: this should be performed before initiating therapy and dynamically, especially in complicated pneumonia. A PCT value in the range of 0.5–1.5 ng/mL is common in acute respiratory viral infections and atypical pneumonia, while a PCT level >2 ng/L indicates typical pneumonia [48].

The frequency of repeated blood procalcitonin tests is determined by clinical indications.

2.3.2. Microbiological studies

• A child with severe CAP and/or with no response to treatment (persistence or progression of symptoms after the initiation of antibiotic therapy) is recommended to undergo a blood culture test for sterility with antimicrobial susceptibility testing (blood must be drawn before starting antibiotic therapy). Blood culture testing (from an intact vein) is also recommended for patients with a severe course of the disease. The test is performed to identify the etiologically significant pathogen [51,56, 58].

GDR CLE 5Grade of recommendation C (level of evidence – 5)

• Repeat blood culture tests for sterility in children with clinical improvement or recovery who had bacteremia (including that caused by S. pneumoniae) at the time of hospitalization are not recommended [51].

GDR CLE 5Grade of recommendation C (level of evidence – 5)

• Repeat blood culture tests for sterility are recommended in children with bacteremia caused by S. aureus, regardless of clinical status and dynamics, in order to timely adjust therapy and confirm the resolution of bacteremia [2].

GDR CLE 5Grade of recommendation C (level of evidence – 5)

Comment: A positive blood culture result for sterility in children with CAP occurs with a frequency of 4% to 10%, with S. pneumoniae (76.7%), H. influenzae (3.1%), and S. aureus (2.1%) being isolated most frequently. In 14.7% of cases, microorganisms that appeared as a result of accidental blood sample contamination are cultured [58].

The timing of repeat blood culture tests is determined by the clinical situation: usually after the completion of clinically effective treatment (in bacteremia caused by S. aureus), or in the absence of a significant clinical and paraclinical effect from therapy, or upon deterioration of the patient's condition, even with initially negative blood culture results [145].

• Sputum culture for aerobic and facultatively anaerobic microorganisms with antimicrobial susceptibility testing is recommended to be performed in hospitalized children with suspected pneumonia/confirmed pneumonia who are able to follow sputum collection instructions: in the morning, before meals, and after thorough teeth brushing and rinsing the oral cavity with boiled water, sputum produced after a deep cough (not from throat-clearing) should be collected into a special plastic container for collection, storage, and transportation of biological samples for analysis [59].

GDR CLE 5Grade of recommendation C (level of evidence – 5)

Comment Sputum culture for aerobic and facultatively anaerobic microorganisms in children very rarely allows establishing the etiological role of a microorganism due to the difficulties in obtaining this biomaterial. The test is not performed in outpatients in routine practice. In younger children, as well as when the amount of sputum is small, obtaining a high-quality sample is practically impossible, and nasal and posterior pharyngeal secretions or saliva are collected instead. If there are doubts about the quality of sputum collection (evaluated in the laboratory by microscopy), microbiological testing of the obtained material is not performed. Microbiological testing of the so-called "tracheal aspirate" collected from a child by vacuum aspiration of mucus from the oropharynx without endoscopic examination of the trachea and bronchi is unreliable and inappropriate for determining the etiology of pneumonia.

Comments: although routine puncture for pleural effusion complicating pneumonia (see subsection 2.4 Instrumental diagnostic procedures) is not performed, when it is performed in patients with pleural effusion— it is necessary to perform bacterioscopic examination of pleural fluid with Gram staining (Microscopic examination of native and stained pleural fluid smears) and microbiological (culture) examination of pleural fluid (Microbiological culture of pleural fluid for aerobic and facultatively anaerobic microorganisms. Microbiological culture of pleural fluid for non-spore-forming anaerobic microorganisms, regardless of the timing of the puncture) [2].

GDR CLE 5Grade of recommendation C (level of evidence – 5)

Comment: Bacterioscopic examination of pleural fluid with Gram staining and pleural fluid culture allow identifying the etiological agent in 25–49% of cases [2]. If a bacterial pathogen is identified in the pleural fluid, antibacterial therapy can be adjusted.

• When performing a pleural puncture in patients with pleural effusion, it is recommended to perform PCR testing of the pleural fluid to identify a potential pathogen (primarily S. pneumoniae) [2, 62].

GCR CLoE 3Grade of Recommendation C (Level of Evidence – 3)

Comment: this test allows identifying the causative agent even with a negative result of microbiological examination of the pleural fluid. It is advisable to screen for the DNA of typical bacterial pathogens, including S. pneumoniae, H. influenzae, S. aureus, S. pyogenes, as well as other pathogens in accordance with the clinical situation. The following may be performed: Molecular biological examination of bronchoalveolar lavage fluid for Streptococcus pneumoniae, Determination of Streptococcus pneumoniae DNA in bronchoalveolar lavage fluid by PCR, quantitative assay, Molecular biological examination of bronchoalveolar lavage fluid for Haemophilus influenzae, Determination of Haemophilus influenzae DNA in bronchoalveolar lavage fluid by PCR, quantitative assay, Molecular biological examination of bronchoalveolar lavage fluid for Staphylococcus aureus, Determination of Staphylococcus aureus DNA in bronchoalveolar lavage fluid by PCR, quantitative assay, Molecular biological examination of bronchoalveolar lavage fluid for Streptococcus pyogenes, Determination of Streptococcus pyogenes DNA in bronchoalveolar lavage fluid by PCR, quantitative assay, or others depending on the clinical situation.

• When performing pleural puncture in patients with pleural effusion, biochemical and cytological examination of the pleural fluid is recommended (see Table 8) [62].

GCR CLoE 3Grade of Recommendation C (Level of Evidence – 3)

Comment: this test helps perform differential diagnosis of the cause of pleural effusion.

2.3.3. Viral tests

• In the presence of clinical and anamnestically relevant data favoring influenza, especially during the epidemic rise of this disease, children with suspected community-acquired pneumonia are recommended to undergo rapid immunochromatographic testing for influenza A and B virus (nasopharyngeal swab, nasopharyngeal wash, or bronchoalveolar lavage) (service names according to Order of the Russian Ministry of Health No. 804n dated October 13, 2017 'On Approval of the Nomenclature of Medical Services': Rapid immunochromatographic testing of a nasopharyngeal swab for influenza A virus, Rapid immunochromatographic testing of a nasopharyngeal swab for influenza B virus, / Rapid immunochromatographic testing of a nasopharyngeal swab, endotracheal aspirate, bronchoalveolar lavage fluid for influenza A virus, Rapid immunochromatographic testing of a nasopharyngeal swab, endotracheal aspirate, bronchoalveolar lavage fluid for influenza B virus) [59].

GDR CLE 5Grade of recommendation C (level of evidence – 5)

Comment: Rapid immunochromatographic testing of a nasopharyngeal swab for influenza virus helps reduce the frequency of unjustified prescription of antibacterial therapy (in the absence of signs of bacterial superinfection), predict the course of the disease, improve the effectiveness of anti-epidemic measures, and increase the level of the patient's parents' trust in the physician. In the early stages of the disease, the rapid test also allows for etiotropic therapy to be prescribed.

Tests for suspected novel coronavirus infection (COVID-19) are carried out in accordance with the current version of the interim guidelines 'Prevention, diagnosis, and treatment of novel coronavirus infection (COVID-19)', as well as 'Specific clinical manifestations and treatment of disease caused by novel coronavirus infection (COVID-19) in children', current version [63,64].

2.3.4. Diagnosis of atypical community-acquired pneumonia

• Children with suspected mycoplasma etiology of community-acquired pneumonia are recommended to undergo selective laboratory tests to detect M. pneumoniae infection — determination of M. pneumoniae DNA in sputum (induced sputum, pharyngotracheal aspirates) by PCR, determination of M. pneumoniae DNA in nasopharyngeal mucosa swabs by PCR, determination of Mycoplasma pneumoniae DNA in oropharyngeal mucosa swabs by PCR; no earlier than the second week of the disease — testing for IgM antibodies to M. pneumoniae (Determination of classes M, G antibodies (IgM, IgG) to Mycoplasma pneumoniae in blood) for the etiological diagnosis of pneumonia [2].

GDR CLE 5Grade of recommendation C (level of evidence – 5)

Comment: The 'gold standard' for diagnosing M. pneumoniae infection is a 4-fold or greater increase in the titer of IgG antibodies to mycoplasma in paired sera taken in the acute phase of the disease and 3–4 weeks later. In most cases, titer increases are recorded retrospectively, which reduces the clinical value of serological diagnosis of mycoplasma infection, but does not cancel its epidemiological significance. A single IgG antibody test is uninformative. IgM antibodies usually appear in the 2nd–3rd week of the disease, which increases the risk of a false-negative result at the onset of community-acquired pneumonia, since the absence of IgM antibodies does not rule out acute infection. IgM antibodies to mycoplasma are also detected in healthy children (false-positive result) with a frequency of 10–20% [66, 67]. IgA class antibodies appear in the early stages and may indicate a recent infection; however, they are extremely nonspecific and do not allow verifying the diagnosis. Therefore, the results of serological tests should always be evaluated critically, checking them against the clinical context.

Cases of asymptomatic carriage of M. pneumoniae and C. pneumoniae are frequent, i.e., a positive PCR result in a healthy child, which is observed predominantly during epidemic outbreaks of the infection. Depending on the year and season, the frequency of asymptomatic carriage varies widely, ranging from fractions of a percent to tens of percent [64,66,67].

Testing for atypical infections is not mandatory in the appropriate epidemiological situation, in mild pneumonia, including when making a decision on empirical switching of antimicrobial drugs (e.g., from the 'beta-lactam antibacterial drugs, penicillins' group to macrolides).

Antibacterial therapy should be initiated without waiting for the results of the examination.

• Patients with suspected pneumonia caused by atypical pathogens are not recommended to routinely undergo tests to detect C. pneumoniae — PCR tests (molecular genetic study) and determination of classes A, M, G antibodies (IgA, IgM, IgG) to Chlamydia pneumoniae in the blood due to their insufficient informativeness [2].

GDR CLE 5Grade of recommendation C (level of evidence – 5)

Comment: In the presence of characteristic clinical signs of pneumonia associated with C. pneumoniae, PCR diagnostics combined with serological methods may be considered:

1. Molecular biological examination of nasopharyngeal/oropharyngeal mucosa swabs or sputum (induced sputum, pharyngotracheal aspirates) for Chlamydophila pneumoniae (or Determination of Chlamydophila pneumoniae DNA in nasopharyngeal mucosa swabs by PCR;

2. Determination of classes A, M, G antibodies (IgA, IgM, IgG) to Chlamydia pneumoniae in the blood (or determination of antibodies to Chlamydophila pneumoniae in the blood. It should be taken into account that reliable tests verifying this infection currently do not exist: Chlamydophila pneumoniae antigens can be detected even without respiratory symptoms, and antibodies can persist for a long time after a past infection.

• Patients with suspected pneumonia caused by B. pertussis are recommended determination of pertussis and parapertussis pathogen DNA (B. pertussis, B. parapertussis, B. bronchiseptica) in nasopharyngeal mucosa swabs by PCR in the first 3 weeks from the onset of cough [69,70]. Serological tests (examination of paired sera) are useful primarily for retrospective diagnosis and are not used in routine practice.

GCR CLEL 5Grade of Recommendation C (Level of Evidence – 5)

Comment: Serological testing allows detecting IgM antibodies to B. pertussis in the blood 1–8 weeks after the onset of cough, but the sensitivity of this test is low. The historical 'gold standard' of diagnosis — a 4-fold or greater increase in the titer of IgG antibodies to the pertussis pathogen in paired sera from the 2nd week from the onset of cough and 2–4 weeks later — is inferior in clinical significance to PCR methods. A confirmed case of pertussis is considered to be the presence of acute infection with cough in combination with a positive PCR result for B. pertussis.

2.3.5 Biochemical tests

Comments: hyponatremia is associated with a more severe course of CAP, higher fever, and complications; tests are performed initially and dynamically, for example, at least daily when administering intravenous solutions that affect the water-electrolyte balance.

For blood lactic acid testing — Recommendation grade B (evidence level – 3)

For blood ionized calcium testing — Recommendation grade C (evidence level – 4).

Comment: the test may be performed dynamically, with the frequency determined individually.

An elevated blood lactate concentration is associated with higher mortality. To assess the effectiveness of ongoing intensive care for septic shock, the test is performed initially and dynamically — at least twice a day (more frequently in case of hemodynamic or respiratory instability) until the shock is resolved

Comment: the test may be performed dynamically, with the frequency determined individually

• In case of vomiting or intravenous fluid administration, it is recommended to determine blood urea and/or blood creatinine levels to monitor renal function [56].

GCR CLEL 5Grade of Recommendation C (Level of Evidence – 5)

2.3.6 Acid-Base Balance Testing

Comments: metabolic acidosis is associated with increased mortality in hospitalized children with CAP.

2.4 Instrumental Diagnostics

2.4.1. Assessment of Blood Gas Disturbances

• Pulse oximetry is recommended for all children with respiratory symptoms and suspected pneumonia for a comprehensive assessment of their condition and determination of hospitalization indications [59].

GCR CLEL 5Grade of Recommendation C (Level of Evidence – 5)

Comment: Detection of hypoxemia should be one of the criteria for deciding on further patient management tactics.

It is important to remember that hypoxemia may not be visually manifested by skin discoloration. For noticeable cyanosis to appear, the concentration of unsaturated hemoglobin must reach 3–5 g per 100 ml of blood, and thus, if the hemoglobin level is 120 g/L, cyanosis will only be noticeable at SpO₂ < 75%. In inpatient settings, blood oxygen and carbon dioxide levels may be measured if necessary.

2.4.2. Diagnostic Imaging

• Chest radiography (lung radiography or digital lung radiography) is recommended for diagnosing pneumonia and/or its complications in the following cases:

- If there are signs of respiratory failure (Tables 5, 6).

- In fever without a source of infection (in the presence of laboratory markers of bacterial infection and/or signs of severe illness)

- In the presence of local and/or asymmetric auscultation and percussion abnormalities in the lungs

- In children with radiographically confirmed pneumonia who show an inadequate response to antibacterial therapy (to rule out complications such as pleurisy, destructive (necrotizing) pneumonia, pneumothorax) [2,38].

GCR CLEL 5Grade of Recommendation C (Level of Evidence – 5)

Comment: Chest radiography should not be routinely ordered for children without intoxication who are in good general condition. The diffuse nature of rales, low-grade fever, absence of toxicosis, percussion changes, and leukocytosis allow pneumonia to be ruled out and a diagnosis of bronchitis/bronchiolitis to be made without resorting to chest radiography [73,74,75,76]. Radiological overdiagnosis of community-acquired pneumonia is associated with misinterpretation of diffuse changes on the radiograph (accentuation of bronchovascular markings, hyperinflation) or patient positioning errors during imaging. Even in large hospitals, infiltrative changes were not detected on radiographs of children diagnosed with "pneumonia" in 73% of cases [77].

Comment: it may be necessary in children with complicated pneumonia (pleurisy, pleural empyema, destruction focus, lung abscess), and in cases where, within 48–72 hours from the start of antibacterial therapy, there is little positive clinical response or progression of symptoms, in order to timely diagnose complications and/or disease progression

Repeat chest radiography should be selectively performed 4–6 weeks after the onset of pneumonia in patients with recurrent pneumonia in the same lung lobe, in patients with lobar collapse on the initial radiograph, as well as when bronchopulmonary malformation, intrathoracic mass, or foreign body aspiration is suspected.

• suspected development of complications (pleural effusion, lung abscess, atelectasis, pneumothorax) when radiographic findings are difficult to interpret in order to decide on surgical intervention;

• differential diagnosis with congenital malformation of the lungs and/or vessels, interstitial lung disease, or tumor;

• recurrent pneumonia (infiltrative changes occurring in the same location);

• protracted pneumonia (not resolving on therapy for more than 4 weeks).

Level of Recommendations CLevel of Evidence 3Level of Recommendation C (Level of Evidence – 3)

Comment: the scan is performed, if possible, with intravenous contrast enhancement to visualize the pleura (contrast-enhanced computed tomography of the chest organs).

Computed tomography in children should not be used routinely, as it increases the risk of oncohematological diseases and CNS tumors.

MRI has high sensitivity in complicated pneumonia (necrotizing, abscessing pneumonia).

Comment: recently, ultrasound has gained increasing interest for the diagnosis and follow-up assessment of pneumonia and pleurisy (even with small effusion volumes), and for guiding thoracentesis.

Ultrasound allows visualization of air, fluid, and the "air bronchogram", enabling early diagnosis of potential or existing complications.

Lung ultrasound allows for the timely diagnosis of necrotic changes (earlier than computed tomography) and also helps evaluate the effectiveness of ongoing therapy [62].

Ultrasound is a very promising modality for lung imaging, although currently the diagnostic yield depends on the operator's expertise [78].

• Children with clinical and anamnestic signs of pleurisy are recommended to undergo chest X-ray to confirm the presence of fluid in the pleural cavity [62].

Level of Recommendations CLevel of Evidence 3Level of Recommendation C (Level of Evidence – 3)

Comments: In a child with pleurisy, a chest X-ray is performed in the lateral decubitus position.

• If clinical and anamnestic data suggest pleurisy but the X-ray result is doubtful, it is recommended to perform a lung ultrasound (ultrasound of the pleural cavity) or chest computed tomography for diagnostic purposes [62].

Level of Recommendations CLevel of Evidence 3Level of Recommendation C (Level of Evidence – 3)

• In children with very severe pneumonia, in exceptional cases (with persistent fever and lack of positive clinical dynamics), selective bronchoscopy (tracheobronchoscopy) with bronchoalveolar lavage fluid analysis (cytological examination of lavage fluid, microscopic examination of lavage fluid, microbiological (culture) examination of lavage fluid for aerobic and facultatively anaerobic microorganisms, determination of microorganism susceptibility to antimicrobial chemotherapy drugs), percutaneous lung biopsy, or open lung biopsy (lung biopsy during bronchoscopy) is recommended for diagnostic purposes if other studies fail to clarify the etiology of the disease [2].

GCR CLEL 5Grade of Recommendation C (Level of Evidence – 5)

Comments: protracted and recurrent pneumonia may occasionally serve as an indication for tracheobronchoscopy.

2.5 Other Procedures

Comments: diagnosis and management of patients with pneumonia are usually carried out by a pediatrician/general practitioner (family doctor) and, if necessary, consultations (examinations) by a pulmonologist, pediatric surgeon/thoracic surgeon are performed.

3. Treatment, including drug and non-drug therapies, diet therapy, and pain management

The effectiveness of CAP treatment depends on the appropriate choice of empirical antibiotic therapy (see Tables 10, 12), taking into account the most common pathogens and their susceptibility to antimicrobial drugs. It is important to adhere to the antimicrobial drug dosing regimen (dose and administration frequency) (see Table 13).

Comment: Principles of antibiotic therapy in children:

- Antimicrobial drugs are prescribed only for a highly probable or proven bacterial etiology of the disease.

- In outpatient settings, antimicrobial drugs are prescribed orally.

- In inpatient settings, oral administration of antimicrobial drugs should be considered; if oral administration is not feasible, parenteral administration is used.

- Antimicrobial drugs are discontinued when data indicate that the infection is not bacterial, without waiting for the scheduled course of therapy to be completed.

- Step-down therapy is performed: patients are switched from parenteral to oral antimicrobial administration once their condition stabilizes, usually within 2-5 days.

- Antimicrobial drugs should not be prescribed in combination with systemic antihistamines, systemic antifungals, or immunostimulants – there is no evidence of benefits from such combined use [1].

3.1. Conservative treatment of pneumonia

3.1.1. Antibiotic therapy for community-acquired pneumonia

Comment:

Amoxicillin** remains the preferred initial therapy at a dose of 45-90 mg/kg/day orally (maximum 2 g/day) in 2-3 doses; for children older than 12 years or weighing >40 kg, 1.5-3 g/day [82] in 2-3 doses for patients with mild-to-moderate disease

CAP without risk factors for infection caused by antibiotic-resistant pathogens (e.g., H. influenzae, S. aureus, E. coli). In the presence of risk factors for infection caused by resistant pathogens, as well as in case of initial antibiotic therapy failure, the use of amoxicillin + clavulanic acid** 45-90 mg/kg/day (calculated as amoxicillin**) orally in 2-3 doses; for children older than 12 years, 1.5-3 g/day (calculated as amoxicillin**) in 2-3 doses should be considered [84].

Amoxicillin** is the initial drug of choice in patients without risk factors for infection with drug-resistant and/or β-lactamase-producing pathogens (H. influenzae, S. aureus, E. coli):

• Children aged > 2 years

• Not attending preschool institutions

• No contact with children attending preschool institutions

• No systemic antibiotic therapy in the preceding 3 months

Amoxicillin + clavulanic acid** is the initial drug of choice in patients with risk factors for infection with drug-resistant and/or β-lactamase-producing pathogens (H. influenzae, S. aureus, E. coli). Dosing at 45-60 mg/kg/day (calculated as amoxicillin**) is acceptable in the following patient groups:

• Use of systemic antibiotics within the preceding 3 months

• Attending a preschool institution

• Contact with children attending preschool institutions

• Hospitalization in the preceding 3 months

• Diabetes mellitus

• Recent travel

Isolation of benzylpenicillin**-resistant H. influenzae strains by bacteriological examination

Amoxicillin + clavulanic acid** dosing of 90 mg/kg/day (calculated as amoxicillin**) is appropriate in the following cases:

• Living in boarding schools, orphanages, or 24-hour residential care facilities

• Immunodeficiency diseases/conditions

• Use of glucocorticoids/immunosuppressants

• Refusal of pneumococcal vaccination or incomplete immunization course

• Chronic respiratory diseases

• Isolation of benzylpenicillin**-resistant S. pneumoniae strains by bacteriological examination [84].

• In children aged ≥ 5 years with mild-to-moderate outpatient CAP, due to the frequent "atypical" etiology in this age group, macrolides (e.g., azithromycin** (in children older than 6 months), clarithromycin**, or other macrolides with relevant indications in their package leaflets) are recommended as drugs of choice alongside beta-lactam antibacterials and penicillins. It is advisable to choose macrolides when an atypical etiology of CAP is suspected (e.g., based on epidemiological data) or confirmed (Tables 10, 12) [85, 86, 87].

GCR BLEL 2Grade of Recommendations B (Level of Evidence – 2)

Comments: In children with mild reactions exclusively to group J01C (beta-lactam antibacterials, penicillins), 2nd- and 3rd-generation cephalosporins are prescribed, and for all beta-lactam antibacterials, macrolides are used [148, 149].

• As an alternative (in case of macrolide allergy), the administration of doxycycline** (for children older than 8 years!) is recommended for children with community-acquired pneumonia caused by atypical pathogens (confirmed or suspected) (Tables 10, 12) [88].

GCR CLEL 5Grade of Recommendation C (Level of Evidence – 5)

• If initial therapy with beta-lactam antibacterials at the above doses fails (a factor pointing to an atypical nature of pneumonia), it is recommended to prescribe macrolides or doxycycline** (Tables 10, 12); however, complications of pneumonia must be ruled out prior to administration [89, 90].

GCR CLEL 5Grade of Recommendation C (Level of Evidence – 5)

Comment: for example:

• In children older than 12 years with non-severe hypersensitivity reactions to other beta-lactam antibacterial drugs, penicillins, it is recommended to selectively use (with caution) oral cephalosporins (cefditoren, cefpodoxime) (Tables 10, 12) [93, 148, 150].

GCR CLEL 5Grade of Recommendation C (Level of Evidence – 5)

Comment:

Cefditoren in children older than 12 years – 200–400 mg twice daily orally.

Cefpodoxime in children older than 12 years – 200 mg twice daily orally.

Macrolides whose instructions for use contain relevant indications may be used.

As for other cephalosporins and carbapenems, in patients with a history of any hypersensitivity reactions to beta-lactam antibacterial drugs, penicillins, or other beta-lactam antibacterial drugs, the instructions for medical use of cephalosporins state they are contraindicated; carbapenems are contraindicated in the presence of severe hypersensitivity reactions (e.g., anaphylactic reactions, severe cutaneous adverse reactions) to any other beta-lactam antibacterial drugs (e.g., beta-lactam antibacterial drugs, penicillins, or cephalosporins) [95].

Comments:

Ampicillin** Up to 1 year: 100 mg/kg/day, 1–4 years – 100–150 mg/kg/day, children older than 4 years – 1–2 g/day divided into 4 administrations IV or IM ([97]

Amoxicillin + clavulanic acid** 90 mg/kg/day IV (divided into 3 administrations per day). In children older than 12 years — 3.6 g/day (1.2 g 3 times a day), children under 3 months and weighing less than 4 kg: (30 mg/kg every 12 hours).

Ceftriaxone** 20–80 mg/kg/day once daily (in children weighing more than 50 kg — up to 2 g/day) parenterally (preferably IV).

Cefotaxime** children under 12 years: 100–150 mg/kg/day in 2–4 administrations parenterally (preferably IV), children older than 12 years – 1 g twice daily, in severe cases – 3–4 g/day divided into 3–4 administrations.

GCR CLEL 5Grade of Recommendation C (Level of Evidence – 5)

Comment: Oral macrolides may be used, and parenterally (IV) from the age of 18 years. Alternatively, in case of macrolide allergy, doxycycline** orally can be used (for children over 8 years old).

The combination should not be used routinely due to the potential selection for resistance and an increase in adverse events [154].

• In children with severe community-acquired pneumonia and comorbid conditions, it is recommended to use ceftaroline fosamil**/ ertapenem**/ imipenem + cilastatin or meropenem** (Tables 10, 12) [24, 108, 155, 156]

GDR CLE 5Grade of recommendation C (level of evidence – 5)

Comments: in children with a history of severe hypersensitivity reactions to beta-lactam antibacterial drugs, penicillins, or other beta-lactam antibacterial drugs, linezolid** or vancomycin** IV may be used for the treatment of community-acquired pneumonia in a hospital setting

• In children with severe community-acquired pneumonia and risk factors for infection with microorganisms of the order Enterobacterales or P. aeruginosa (e.g., immunocompromised patients, patients with bronchiectasis, cystic fibrosis), it is recommended to use cefepime**/ cefepime + [sulbactam]**/piperacillin + [tazobactam], imipenem + cilastatin** or meropenem**) with the possible addition of amikacin** (Tables 10, 12) [108, 155, 156, 170].

GDR CLE 5Grade of recommendation C (level of evidence – 5)

Comments: for more information on the treatment of special patient groups, see the relevant clinical guidelines

• In the course of severe influenza complicated by pneumonia, it is recommended to prescribe the combination of amoxicillin + clavulanic acid** orally or intravenously, depending on the severity of the condition, for the treatment of bacterial complications [51].

• All patients hospitalized with a diagnosis of community-acquired pneumonia are recommended to receive empirical antibacterial therapy as early as possible (the first dose of antimicrobial drugs should be administered no later than 4 hours from the moment of diagnosis, and within 1 hour in severe community-acquired pneumonia) [98, 99, 100].

GCR CLEL 5Grade of Recommendation C (Level of Evidence – 5)

• Upon identification of the etiological agent and determination of its susceptibility to antimicrobial chemotherapeutic drugs via microbiological (cultural) blood or pleural fluid culture for sterility with determination of pathogen susceptibility to antimicrobial chemotherapeutic drugs, it is recommended to adjust the antibacterial therapy for etiotropic treatment (see Table 12). [2].

GCR CLEL 5Grade of Recommendation C (Level of Evidence – 5)

Comment: When negative results of microbiological (cultural) blood (pleural fluid) culture for sterility are obtained, the baseline recommendations given above should be followed.

In hospitalized patients, antimicrobial therapy is generally initiated with the parenteral (IM or IV) route of administration of antimicrobial drugs in the first 48–72 hours (Table 10), followed by a switch to oral administration. In the absence of pronounced intoxication and if the child retains the ability to take the drug orally, oral administration of antimicrobial drugs from the first day should be considered.

Table 10. Empirical antibacterial therapy for community-acquired pneumonia in children older than 1 month¹.

^{1 –} The table presents the most common treatment options, including the emphasis that outpatients who are children should receive oral administration. Nevertheless, the physician may change the route of administration depending on the clinical situation, including oral administration in a hospital setting for both initial and step-down therapy (see Table 12)

² - see Appendix A3.1

• When strains of S. pneumoniae highly resistant to benzylpenicillin** and/or ceftriaxone** are isolated, it is recommended to prescribe either ceftaroline fosamil** or linezolid** IV. [101, 24] (For the profile of a hospitalized patient with severe CAP indicated for ceftaroline fosamil**, see Appendix A3.1)

GCR CLEL 5Grade of Recommendation C (Level of Evidence – 5)

Table 11. Main options for step-down antibiotic therapy

Note: selection and doses of EAMs – see Table 13.

¹ Can be substituted with amoxicillin + clavulanic acid** in the absence of second-generation or third-generation cephalosporins

Table 12. Recommendations for etiology-directed antibiotic therapy of CAP.

 Table 13. Recommended drug doses in children with CAP and normal function

• It is recommended in most cases to continue antibacterial therapy for pneumonia for 5–7 days to achieve optimal therapeutic efficacy. Both shorter (4–6 days) and longer courses of antibacterial therapy are possible depending on the clinical situation [2, 82, 102, 103].

  Recommendation grade C (Level of evidence – 5)

  Comments:

  There is no consensus on the duration of antibacterial therapy for community-acquired pneumonia in children.

  With correctly prescribed antibacterial therapy for community-acquired pneumonia, clinical and laboratory improvement occurs within 48–72 hours: body temperature drops < 38.0°C, appetite returns, and CRP levels decrease. In destructive pneumonias, this effect may occur within 72–96 hours or later.

  - The treatment course for non-severe community-acquired pneumonia is 5–10 days. 10-day courses of antibacterial drugs have been studied the most, but the efficacy of short courses of therapy (5–7 days) has also been proven [96, 104, 105].

  - Severe pneumonias, including non-pneumococcal pneumonias (especially of MRSA etiology), may require longer courses of antibacterial therapy — 14 days or more [106].

  - In the absence of bacteremia, or in children with bacteremia but without secondary foci of infection, it is possible to switch from intravenous antibacterial therapy to oral administration 2–3 days after starting parenteral therapy. The switch from parenteral to oral antibacterial therapy depends on the dynamics of clinical and paraclinical symptoms (fever, cough, tachypnea, need for supplemental oxygen, increased activity and appetite, resolution of leukocytosis, decrease in CRP levels, and the child's ability to take the drug orally) [107].

  - In the absence of positive dynamics or if symptoms worsen within 48–72 hours after starting antibacterial therapy, additional investigations should be performed (see the "Diagnostics" section).

• In synpneumonic pleural effusion or empyema, it is recommended to continue antibacterial therapy for 2–3 weeks to achieve an optimal effect [62, 108].

  Recommendation grade C (Level of evidence – 3)

  Comment: The duration of antibacterial therapy for pleurisy and empyema depends on the adequacy of pleural cavity drainage (if necessary) and the overall response to treatment.

  3.1.2. Antiviral therapy

• It is recommended to prescribe pathogen-directed antiviral therapy with neuraminidase inhibitors (oseltamivir** starting from 1 year of age for 5 days, or zanamivir for children with severe community-acquired pneumonia older than 5 years) as early as possible when influenza A and B are suspected during an epidemic rise in influenza incidence, in order to achieve maximum therapeutic efficacy [2, 51, 109].

  Level of recommendation C (evidence level – 5)

• For the treatment of uncomplicated influenza in children with a body weight ≥20 kg, it is recommended to selectively prescribe baloxavir marboxil, which inhibits influenza virus genome transcription, thereby suppressing viral replication [157, 158, 159].

  Recommendation grade A (Level of evidence – 2).

  (Recommendation grade — C; Level of evidence — 5)

  Comment: since early antiviral therapy within the first 24–48 hours of illness is the most effective, treatment should not be delayed until influenza test results are available. Negative influenza test results (especially rapid tests) do not completely rule out influenza. Treatment initiated after 48 hours from the onset of clinical signs may be effective in the most severe forms of the disease.

  Oseltamivir** and zanamivir have shown a small reduction in time to alleviation of influenza symptoms in adults. Post-marketing use of oseltamivir** has shown an increased risk of nausea, vomiting, and psychiatric disorders in adults, and vomiting in children [110].

  When using zanamivir, bronchospasm and other allergic reactions are possible [111].

  When deciding to use neuraminidase inhibitors, caution should be exercised and the balance between benefits and harms must be considered.

  3.1.3. Other treatment modalities for community-acquired pneumonia

  When systemic antibacterial drugs show a rapid effect, other therapies should be prescribed based on strict indications, avoiding polypharmacy.

• In children with community-acquired pneumonia and body temperature > 39–39.5°C, it is recommended to use antipyretic therapy: drugs from the group of "Non-steroidal anti-inflammatory and antirheumatic drugs" (ibuprofen** from 3 months (from 5 kg), dosage according to the instructions [112], administration possible every 6–8 hours (maximum 30 mg/kg/day)) or drugs from the group of "Other analgesics and antipyretics" (paracetamol** from 2–3 months at a dose of 10–15 mg/kg as needed, possible every 6 hours (maximum 60 mg/kg/day)). Antipyretic therapy is prescribed in case of seizures or if the patient tolerates fever poorly [113].

  Level of recommendation C (evidence level – 5)

  Comment: In children with chronic pathology and/or pronounced discomfort associated with fever, it is possible to prescribe antipyretic drugs at a temperature of 38 °C and above. To date, there are no exact body temperature thresholds at which antipyretic therapy should be used [173]. In practice, the drug is most often prescribed at 38–38.5° [174, 175].

  If fever cannot be controlled, one can switch from one antipyretic drug to another while continuing monotherapy. Alternating these two antipyretic drugs or using combination drugs has no significant advantages over monotherapy with either of these agents.

  Scheduled administration of antipyretic drugs should not be prescribed.

  Antipyretic drugs may obscure the evaluation of treatment efficacy, creating a false sense of security.

• Increased secretion of antidiuretic hormone in patients with pneumonia creates a risk of hyperhydration and pulmonary edema, especially with intravenous administration. In this regard, it is recommended to restrict daily fluid intake to 50–80% of physiological requirements or reduce fluid intake calculated as 300–400 ml/m²/24 hours plus the volume equivalent to urine output [114].

  Recommendation grade C (Level of evidence – 5)

  Comments:

  To prevent dehydration, enteral fluid intake is indicated in the volume of age-related requirements. Physiological requirements in children according to the Holliday-Segar formula are:

  • up to 10 kg: 100 ml/kg/day;

  • from 10 to 20 kg: 1000 ml + 50 ml for each kg of body weight over 10 kg;

  • more than 20 kg: 1500 ml + 20 ml for each kg of body weight over 20 kg. For children over 40 kg: 1500 ml/m² of body surface area.

  In respiratory failure and/or acute respiratory distress syndrome, it is advisable to limit the administered fluid volume to 50% of physiological requirements.

  If gastrointestinal function is not impaired, the majority of fluids should be administered enterally (orally or via a tube).

  Efforts should be made to achieve a "zero fluid balance", meaning that the urine output (or other losses) should be approximately equal to the volume of fluid administered per day.

  In hemodynamically stable patients, fluid restriction is applied, titrated starting from 50% of the total calculated daily requirement.

  In patients with fluid retention, the administration of "loop" diuretics is justified. Hyperhydration is life-threatening for patients. The optimal solutions for infusion therapy are solutions that affect the water-electrolyte balance (balanced iso-osmolar isooionic crystalloid solutions).

  In the presence of signs of severe hypovolemia, a fluid challenge with solutions affecting the electrolyte balance (balanced crystalloid solution) is indicated in a volume of 20 ml/kg over 30–60 minutes with an evaluation of the effect. If necessary, repeat up to 3 times. After each bolus, the effect of the therapy must be evaluated.

  The main goal of infusion therapy is to maintain an adequate circulating blood volume and normalize perfusion.

  Criteria for adequate tissue perfusion include:

  - Capillary refill time < 2 s.

  - Satisfactory pulse volume on peripheral and major arteries

  - Warm extremities

  - Hourly urine output rate > 1 ml/kg/h

  - Blood pressure values correspond to the age norm (absence of arterial hypotension and hypertension)

  - Normal blood glucose concentration values

  - Normal blood ionized calcium concentration values

• Infusion therapy is recommended selectively in patients with community-acquired pneumonia and should be no more than 20–30 ml/kg/day or no more than ⅓ of the daily physiological requirement, monitored by urine output, serum electrolytes (testing blood sodium levels, blood potassium levels, blood chloride levels), and hematocrit evaluation. In pronounced hyponatremia, intravenous administration of 0.9% sodium chloride solution is sufficient [11, 38].

  Level of recommendation C (evidence level – 5)

  Comment: In patients with community-acquired pneumonia, especially severe cases, due to the release of antidiuretic hormone, water retention reduces fluid requirements. Infusions even at the estimated daily requirement can lead to hyperhydration, pulmonary edema, and cerebral edema, which is often revealed at autopsy in such children who died from pneumonia as the direct cause of death.

• Correction of metabolic acidosis is recommended when base excess (BE) is -10 mmol/L and below [115,116].

  Level of recommendation C (evidence level – 5)

  Comments: alkaline solutions (solutions affecting water-electrolyte balance) must not be administered without examining the acid-base status and blood gases!

• It is not recommended to routinely use inhalation therapy in children with community-acquired pneumonia, as it lacks justification. The efficacy of glucocorticoid inhalations has not been proven, and the use of selective beta-2 agonists in marked restrictive changes can be dangerous [117,118].

  Level of recommendation C (evidence level – 5)

  Comment: the use of aminophylline** is also not indicated.

• It is not recommended to routinely use antitussive drugs, cold remedies, expectorants, mucolytics, including proprietary herbal preparations, in children with community-acquired pneumonia in the absence of chronic airway pathology [81,119,120].

  Level of recommendation C (evidence level – 5)

• In metapneumonic pleural effusion, glucocorticoids are recommended — usually #prednisolone** (orally at 1 mg/kg/day for 3–4 days), which helps reduce fever and ESR within 1–2 days, improves general condition, and allows for early discharge of patients [11,38,44,91,92,121].

  Level of recommendation C (evidence level – 5)

  Comment: discussions in the global literature regarding steroid therapy for pneumonia and pleural effusion have not yet yielded a consensus. The efficacy of #dexamethasone** (0.25 mg/kg every 6 hours intravenously — 8 doses) has been demonstrated in children with "simple" pleural effusion (its characteristics coincide with those of metapneumonic pleural effusion) [122].

• It is not recommended to routinely use vitamin A and ascorbic acid (vitamin C) in the treatment of pneumonia in children due to the lack of evidence of their efficacy in this situation [124,125,126,127].

  For Vitamin A - Level of recommendation evidence C (confidence level of data – 1)

  For Ascorbic acid (vitamin C) - Level of recommendation evidence B (confidence level of data – 1)

  3.1.4 Treatment of complicated pneumonia.

  3.1.4.1 Oxygen therapy and respiratory support

• Children diagnosed with pneumonia presenting with hypoxemia (at SpO2 ≤ 92% breathing room air) are recommended to be prescribed supplemental (humidified) oxygen via nasal cannula, mechanical ventilator, or face mask for additional oxygen delivery and to reduce the workload on the respiratory and cardiovascular systems. The target SpO₂ value is greater than 92% [128].

  Level of recommendation evidence C (confidence level of data – 4)

  Comment: If nasal breathing is obstructed due to mucous secretions, the nasal passages must be carefully cleared with an aspirator. Agitation may be a sign of hypoxia! High-flow nasal cannula oxygen therapy or CPAP therapy is increasingly, albeit cautiously, used in children with respiratory distress to avoid intubation and mechanical ventilation. Mechanical ventilation is performed when it is impossible to raise SpO₂ above 90-92% using the methods mentioned above.

  Indications for oxygen therapy (Oxygen therapy):

  a) tachypnea, an increase in respiratory rate by more than 15% from the age norm

  b) hemoglobin saturation according to pulse oximetry on ambient air below 92%

  c) presence of cyanosis and dyspnea detected upon visual inspection

  d) hypoxemia (partial pressure of oxygen in arterial blood less than 80 mm Hg, in capillary blood – less than 60 mm Hg)

  The criterion for the effectiveness of oxygen therapy (Oxygen therapy) is an increase in SpO₂ to 95% and above, or a noticeable and sustained increase in this parameter. At the same time, the lower threshold of PaO₃ [sic] should not be less than 55 - 60 mm Hg. If there are no indications for tracheal intubation, re-evaluate the patient every hour.

• Patients with severe pneumonia are recommended to undergo respiratory support (oxygen therapy (high-flow), CPAP/BiPAP/mechanical ventilation) or extracorporeal membrane oxygenation according to indications in the intensive care unit to maintain vital body functions [62].

  Level of recommendation C (evidence level – 5)

  Comments:

  In the absence of an effect from oxygen therapy (Oxygen therapy), it is advisable to consider escalating respiratory support. Initiating respiratory support in the form of non-invasive mechanical ventilation (NIMV) via face mask or helmet is possible while maintaining consciousness and contact with the patient. In case of low efficacy and/or poor tolerance of non-invasive mechanical ventilation, high-flow nasal cannula oxygen therapy (HFNC) can serve as an alternative

  The question of using HFNC or NIMV should be considered individually each time. Adult HFNC systems can provide a gas flow of up to 60 L/min and an FiO2 of up to 1.0. Pediatric circuits usually provide only up to 40 L/min. Compared to standard oxygen therapy (Oxygen therapy), HFNC reduces the need for intubation. Patients with decompensated acidosis, hemodynamic instability, multiorgan failure, or decreased level of consciousness (Glasgow Coma Scale score (Appendix G1) less than 9 points) are contraindicated for HFNC.

  Absolute contraindications to NIMV: severe encephalopathy, unconsciousness; facial skeleton anomalies and deformities preventing mask placement; early childhood (inability to cooperate with the child) (Table 14).

  In case of failure of non-invasive mechanical ventilation — hypoxemia, metabolic acidosis, or failure to increase the PaO₂/FiO₂ ratio within 2 hours, high work of breathing (patient-ventilator dyssynchrony, engagement of accessory muscles, "dips" during inspiratory triggering on the "pressure-time" curve) — tracheal intubation and transfer to invasive mechanical ventilation (Mechanical ventilation) are indicated.

  Indications for mechanical ventilation:

  a) tachypnea, increase in respiratory rate by more than 25% above the age-norm

  b) signs of severe respiratory distress (grunting respiration, chest retractions, "head bobbing", paradoxical breathing, etc.)

  c) presence of hypercapnia (pCO2 > 60 mmHg)

  d) SpO₂/FiO₂ ratio < 300 mmHg

  e) decompensated acid-base disorders (pH < 7.25)

  Table 14 The choice of respiratory support method is based on the severity of the patient's respiratory failure:

  						Consider ECMO
  				Consider HFJV (in infants under one year of age)
  				Consider NO inhalation
  			Neuromuscular blockade
  Oxygen therapy High-flow nasal cannula oxygen therapy CPAP or BiPAP		Invasive mechanical ventilation Vt 5-8 mL/kg of IBW PEEP 10-15 cmH2O 28 cmH2O
  prone positioning
  Mild ARDS 4≤OI≤8 5≤SI<7.5	Moderate ARDS 8≤OI<16 7.5≤SI<12.3				Severe ARDS OI≥16 SI≥12.3

  OI = (FiO₂ × MAP × 100)/PaO_2, where OI is oxygenation index; MAP is mean airway pressure; FiO₂ is fraction of inspired oxygen; PaO₂ is arterial partial pressure of oxygen. HFJV = high-frequency mechanical ventilation. PEEP = positive end-expiratory pressure. Vt = tidal volume. NO = nitric oxide. ECMO = extracorporeal membrane oxygenation. P plat = plateau pressure. IBW = ideal body weight. CPAP or BiPAP = ventilation modes.

  SI = (FiO₂ × MAP × 100)/SpO_{2, where} SI = saturation index; MAP = mean airway pressure; SpO_{2 =} blood oxygen saturation

• Children with destructive pneumonias are not recommended to have their prescribed adequate intravenous systemic antibacterial drug changed; after defervescence, they should be switched to an oral drug [62, 117].

  Level of recommendation C (evidence level – 5)

  Comment: body temperature usually decreases only after the evacuation of necrotic cavities, which is accompanied by a fit of coughing, pain, and dyspnea (if pneumothorax develops). Persistence of fever after the appearance of bullae and a decrease in inflammatory marker levels is associated with the development of metapneumonic (immunopathological) pleurisy (marker: rising CRP). Changing antimicrobial agents, as well as drainage and fibrinolysis procedures, are ineffective; temperature and CRP normalize rapidly after the administration of glucocorticoids. Previously initiated antibacterial therapy should be continued.

  3.1.4.2 Management of patients with lung abscess

• Children with pneumonia-associated lung abscess are recommended to be prescribed initial therapy with intravenous antimicrobial agents (active against staphylococci and anaerobes) [2].

  Level of recommendation evidence C (level of data reliability – 5)Comment: A persisting peripheral abscess not communicating with a bronchus can be drained using endoscopic aspiration under fluoroscopic guidance. However, in most cases, spontaneous drainage of the abscess into the bronchi occurs, and surgical intervention is not required.

  For drug selection see Table 12, correction according to microbiological testing data.

  3.2. Surgical treatment of pneumonia

• In children with pneumonia complicated by sinpneumonic pleurisy, pleural cavity puncture is generally not indicated; it is recommended to consider performing a pleural puncture in cases of a significant volume of pleural effusion causing pronounced cardiorespiratory disorders, including for the purpose of clarifying the diagnosis and indications for pleural cavity drainage (Table 15) [2].

  Level of recommendation C (evidence level – 5)

  Comment: with a small or moderate effusion (less than 10 ml), as well as with a positive treatment response, puncture is not indicated. In massive effusion, pleural puncture with fluid removal helps alleviate lung and heart function. If the nature of the effusion is unclear, this makes it possible to assess its quality (synpneumonic or metapneumonic pleurisy, cytological examination of pleural fluid – determination of cell count per 1 µl) and etiology (Microbiological (culture) examination of pleural fluid for aerobic and facultatively anaerobic microorganisms, Microbiological (culture) examination of pleural fluid for non-spore-forming anaerobic microorganisms with determination of microorganism susceptibility to antimicrobial chemotherapeutic agents, microscopic examination of native and stained pleural fluid preparations), as well as PCR testing of the pleural fluid. Drainage is indicated if, after 1–2 punctures, symptoms of lung compression by rapidly accumulating purulent exudate recur [11, 38, 129]. Metapneumonic pleurisy is not subject to drainage; the administration of glucocorticoids is effective.

  Table 15. Indications for pleural puncture and drainage in pleurisy [2].

^a on a direct lateral decubitus radiograph on the affected side

^b on an upright anteroposterior radiograph

4. Medical Rehabilitation and Sanatorium-Resort Treatment

With timely and adequate treatment of uncomplicated community-acquired pneumonia, rehabilitation is not required. Hardening procedures can be resumed after 2 weeks, and sports — after 6 weeks (after complicated pneumonia — after 12 weeks).

• Children who have suffered from complicated community-acquired pneumonia are recommended to be followed up for 4–6 months (dispensary examination (assessment, consultation) by a pediatrician / district pediatrician) in order to monitor their condition and promptly adjust therapeutic measures, if necessary. [130]

GCR CLEL 5Grade of Recommendation C (Level of Evidence – 5)

Comments: the frequency of visits and the need for examinations are determined individually depending on the severity of the disease and the patient's condition. In doubtful cases, the patient should be referred to a pulmonologist and/or thoracic surgeon/pediatric surgeon.

• Children who have suffered from pleurisy are recommended therapeutic physical training for bronchopulmonary diseases in order to improve lung aeration and strengthen the respiratory muscles [130]

GCR CLEL 5Grade of Recommendation C (Level of Evidence – 5)

5. Prevention and Dispensary Observation

One of the main areas in the prevention of pneumonia, including severe forms, is timely vaccination

Comments: vaccination against *H. influenzae* b infection carried out in more than 184 countries has reduced the incidence of its invasive forms to <1–2 per 100,000 children aged 0–5 years [132].

The elimination of *H. influenzae* type b has caused a certain increase in the proportion of other types of *H. influenzae*, primarily *H. influenzae* type a (Hia), especially among the northern peoples of the US and Canada, where the issue of creating an Hia vaccine has been raised and relevant development is underway [133].

Comment: vaccination reduced the incidence of vaccine serotype-caused bacteremic pneumonia in children in the US by 74–91%, all pneumococcal pneumonia by 63% (with pleurisy — by 53%), all community-acquired pneumonia — by 16%, and outpatient visits of children ≤5 years for pneumonia — by 68%. Following the introduction of the 13-valent pneumococcal conjugate vaccine**, the reduction in hospitalization rates was up to 21% for children under 2 years old, 17% for children aged 2–5 years, and 4% for those > 5 years.    3–5 years after the start of vaccination, the incidence of invasive pneumonia increases due to non-vaccine serotypes (most commonly serotypes 10A, 11A, 12, 35B, and serogroup 15), without reaching the pre-vaccination level. This prompts the development of vaccines containing 15–20 serotypes.

• Parents and adults caring for children under 6 months of age are recommended to be vaccinated against the influenza virus in order to prevent influenza, including pneumonia in children [2]

GCR CLEL 5Grade of Recommendation C (Level of Evidence – 5)

• Children under 2 years of age from high-risk groups for severe RSV infection are recommended to undergo seasonal immunoprophylaxis with palivizumab** (see clinical guidelines for "Acute Bronchiolitis") [2]

GCR CLEL 5Grade of Recommendation C (Level of Evidence – 5)

Comment: Influenza vaccines (trivalent or quadrivalent inactivated vaccines without preservatives) are used during pregnancy.

6. Organization of Medical Care

Depending on the requirements, patients with pneumonia may receive any type, conditions, and forms of medical care provided for by the legislation of the Russian Federation.

Treatment of uncomplicated community-acquired pneumonia is carried out on an outpatient basis in the majority of cases. Hospitalization is required for children with severe pneumonia, signs of complicated pneumonia, or after ineffective initial primary healthcare antimicrobial therapy.

• Before the therapeutic effect is achieved, patients with severe pneumonia should be prescribed strict bed rest, semi-bed rest after the fever subsides, and general activity with walks after 3–5 days. Room ventilation is important.

• Children with CAP must be hospitalized in an inpatient department in the following cases:

‒ age under 3 months;

‒ apnea or cyanosis;

‒ capillary refill time greater than 2 seconds; ‒ SpO2 < 90% on room air, PaCO2 > 50 mm Hg;

‒ dehydration, feeding difficulties (decrease in fluid intake to 50–75% of the usual volume or absence of urination for 12 hours);

‒ potential aspiration;

‒ home oxygen-dependent patients, e.g., with bronchopulmonary dysplasia, pulmonary fibrosis;

‒ ineffectiveness of home-based therapy or inability to provide it (hospitalization for social reasons);

‒ ineffectiveness of antibacterial therapy within 48 hours (persistence of febrile fever);

‒ inability to feed and take systemic antimicrobials orally;

‒ development of complications (significant pleural effusion, pneumothorax, lung abscess, etc.);

‒ involvement of multiple lung lobes according to chest X-ray data; ‒ leukopenia (x10⁹/L) depending on age: under 1 year < 5, 1–5 years < 6, older than 5 years < 4.5;

‒ comorbid conditions (bronchial asthma, bronchopulmonary dysplasia, cystic fibrosis, hemodynamically significant congenital heart disease, myocardial diseases, circulatory failure, immunodeficiency, Down syndrome, neuromuscular diseases, cerebral palsy, bronchiectasis, diabetes mellitus, oncohematological diseases);

‒ extrapulmonary foci of infection (meningitis, sepsis, purulent otitis media, etc.).

Comment: children with non-severe pneumonia, without hypoxemia (SpO₂ > 92%), having no "danger" signs (able to drink, no repeated vomiting, no convulsions, no impaired consciousness, no severe malnutrition) may receive treatment with oral antimicrobials at home.

• Children with CAP should be admitted to the intensive care unit with 24-hour cardiorespiratory monitoring in the following cases:

- recurrent apnea (documented by a physician or described by caregivers);

- inability to maintain SpO₂ above 92% despite oxygen therapy;

- acute renal injury (oliguria - a decrease in diuresis to below 50% of the age-appropriate normal value and less, urea > 15 mmol/L, creatinine > 177 µmol/L);

- disseminated intravascular coagulation (DIC) syndrome;

- impaired consciousness (14 points or less on the Glasgow Coma Scale (Appendix G1) for the respective age category) or unexplained marked agitation (crying, screaming) during an acute respiratory infection;

- grade III respiratory failure, or grade II respiratory failure in patients with comorbid conditions;

- cyanosis (in the absence of "blue" congenital heart disease) and tachypnea (respiratory rate greater than 70 breaths per minute in a child under one year of age) determined upon visual inspection, significant chest retractions, nasal flaring, or paradoxical breathing in infants under one year of age;

- decompensated acidosis (pH < 7.30);

- shock: hypotension requiring fluid boluses and/or administration of adrenergic and dopaminergic agents (vasopressors), as well as signs of severe hypoperfusion (mottling of extremities, acrocyanosis, cold extremities, capillary refill time of 4 seconds or more);

- lactic acidosis (blood lactate concentration greater than 3 mmol/L);

Management of patients with an inadequate response to ongoing therapy

• The main criterion for the effectiveness of antibacterial therapy is a decrease in fever to below 38°C and relief of respiratory failure.

• Children who do not respond to initial treatment administered for 48–72 hours require the following:

- clinical and laboratory evaluation to assess the dynamics of the condition (complete blood count with differential, C-reactive protein level in blood serum, other tests as indicated)

- chest X-ray / lung ultrasound to evaluate the dynamics of pulmonary and pleural changes

- if indicated, addressing the need for pleural puncture or switching antimicrobial drugs.

• Children whose temperature does not decrease despite the drainage of purulent cavities in the lungs and normalization of markers upon the appearance or progression of pleural effusion, as well as an increasing C-reactive protein (CRP), receive therapy with systemic glucocorticoids.

Discharge criteria from the hospital

• A patient may be discharged from the hospital upon documented general improvement, including activity, appetite, subsided fever, and SpO₂ greater than 95% on room air for at least 12–24 hours. A patient cannot be discharged if respiratory failure, tachypnea, or tachycardia persists. A mandatory condition for early discharge of a child is that parents are able to ensure adequate completion of treatment at home.

Comment: early discharge from the hospital in case of a rapid therapeutic response (on days 3–4, if home conditions permit) – including in the presence of elevated CRP, persistent cough, and auscultatory changes in the lungs – helps avoid superinfection.

• Children who have undergone mechanical ventilation may be transferred from the intensive care unit no earlier than 12–24 hours after extubation, provided their condition is stable and radiological confirmation shows no progression of pleural effusion or pneumothorax.

  Organization of dietary nutrition for patients during inpatient treatment in medical organizations is carried out in accordance with Appendix 3 of the Order of the Russian Ministry of Health No. 1008n dated September 23, 2020, "On approval of the procedure for providing patients with therapeutic nutrition"

7. Additional Information

Outcomes and prognosis of CAP depend on the severity of the course, presence of complications, and the patient's immune status. In most cases, with timely and appropriate treatment, the prognosis is favorable. Untimely or improper treatment of CAP can result in the development of pneumosclerosis and bronchial deformation in the affected area. Such outcomes are currently rare and are observed mainly in children with cystic fibrosis, bronchial developmental anomalies, primary ciliary dyskinesia, and immunodeficiency states. At the same time, mortality from pneumonia remains high, especially in developing countries (see the "Epidemiology" section).

Analysis of factors influencing the prognosis of CAP demonstrates the key role of practical application and adherence to national guidelines when choosing therapeutic tactics [140]. The earliest possible administration of antimicrobials plays a crucial role [141,142]. Late seeking of medical attention can significantly worsen the prognosis of pneumonia. A serious cause of an unfavorable outcome is

Criteria for Evaluating the Quality of Medical Care

Quality assessment criteria for primary health care provided to children with pneumonia (community-acquired) (ICD-10 codes: J12, J13, J14, J15, J16, J18)

Quality assessment criteria for specialized medical care provided to children with pneumonia (community-acquired) (ICD-10 codes: J12; J13, J14; J15; J16; J18)

References

Appendix A1. Working Group Composition

Baranov A.A., Academician of the Russian Academy of Sciences, Professor, Doctor of Medical Sciences; Honorary President of the Union of Pediatricians of Russia, Advisor to the Head of the Research Institute of Pediatrics and Child Health of the Petrovsky National Research Centre of Surgery, Professor at the Department of Pediatrics and Pediatric Rheumatology, I.M. Sechenov First Moscow State Medical University of the Ministry of Health of Russia (Sechenov University), Chief freelance pediatric specialist of the Russian Ministry of Health

Kozlov R.S., Corresponding Member of the RAS, Professor, MD, Rector of the Smolensk State Medical University of the Ministry of Health of Russia, Chief freelance specialist of the Ministry of Health of Russia in Clinical Microbiology and Antimicrobial Resistance, President of ISCMR

Namazova-Baranova L.S., Academician of the Russian Academy of Sciences, Professor, Doctor of Medical Sciences, President of the Union of Pediatricians of Russia; Past President of EPA/UNEPSA; Head of the Research Institute of Pediatrics and Child Health of the Petrovsky National Research Centre of Surgery, Head of the Department of Faculty Pediatrics at the Institute of Motherhood and Childhood, Pirogov Russian National Research Medical University of the Ministry of Health of Russia (Pirogov University), Chief freelance pediatric specialist in preventive medicine of the Russian Ministry of Health

Malakhov A.B. — Professor, Doctor of Medical Sciences, Chairman of the Pediatric Respiratory Society, Chief Pediatric Pulmonologist of the Moscow Healthcare Department and the Ministry of Health of the Moscow Region, Professor at the Department of Child Diseases of the N.F. Filatov Clinical Institute of Child Health, I.M. Sechenov First Moscow State Medical University of the Ministry of Health of Russia (Sechenov University), Head of the Pediatrics Department at the Research Institute of Childhood of the Ministry of Health of the Moscow Region, International Academic Expert

Alekseeva A.A. – Candidate of Medical Sciences, Deputy Head of the Consultative and Diagnostic Center for Children - Pediatrician, Head of the Multidisciplinary Pediatric Day Hospital - Allergist-Immunologist, Leading Research Fellow at the Department of Clinical Immunology and Allergology, Research Institute of Pediatrics and Child Health, Petrovsky National Research Centre of Surgery, Member of the Union of Pediatricians of Russia

Andreeva I.V., Senior Research Fellow, Associate Professor, Institute of Antimicrobial Chemotherapy, Smolensk State Medical University of the Ministry of Health of Russia, Member of MACMA

Bakradze M.D., Doctor of Medical Sciences, Professor, Chief Research Fellow, Infectious Disease Physician at the Consultative Department of the National Medical Research Center for Children's Health of the Ministry of Health of Russia, Member of the Union of Pediatricians of Russia

Berezhansky P.V. — Doctor of Medical Sciences, Board Member of the Pediatric Respiratory Society, Professor at the Department of Child Diseases, N.F. Filatov Clinical Institute of Child Health, I.M. Sechenov First Moscow State Medical University of the Ministry of Health of Russia (Sechenov University), Senior Research Fellow at the Pediatrics Department, Research Institute of Childhood of the Ministry of Health of the Moscow Region

Vishneva E.A., Doctor of Medical Sciences, Professor of the Russian Academy of Sciences, Deputy Head of the Research Institute of Pediatrics and Child Health, Petrovsky National Research Centre of Surgery, Professor at the Department of Faculty Pediatrics, Institute of Motherhood and Childhood, Pirogov Russian National Research Medical University (Pirogov University) of the Ministry of Health of Russia, Member of the Union of Pediatricians of Russia

Geppe N.A. – Professor, Doctor of Medical Sciences, Chairman of the Expert Council of the Pediatric Respiratory Society, Chairman of the Moscow City Society of Pediatricians, Head of the Department of Child Diseases, N.F. Filatov Clinical Institute of Child Health, I.M. Sechenov First Moscow State Medical University of the Ministry of Health of Russia (Sechenov University), Honored Doctor of the Russian Federation.

Ivanov A.A., Expert Analyst at the Management Department for the Implementation of Functions of the National Medical Research Center for Pediatrics, Pirogov Russian National Research Medical University (Pirogov University) of the Ministry of Health of Russia, Member of the Union of Pediatricians of Russia

Ivardava M.I., Candidate of Medical Sciences, Head of the General Pediatrics Department, Pediatrician, Head of the Department for the Development of Scientific Approaches to the Management of Children with Motor Disorders, Research Institute of Pediatrics and Child Health, Petrovsky National Research Centre of Surgery, Member of the Union of Pediatricians of Russia

Kaitukova E.V. – Candidate of Medical Sciences, Deputy Head for Medical Activities - Head of the Consultative and Diagnostic Center for Children, Gastroenterologist, Leading Research Fellow at the Department of Orphan Diseases and Prevention of Disabling Conditions, Research Institute of Pediatrics and Child Health, Petrovsky National Research Centre of Surgery, Associate Professor at the Department of Faculty Pediatrics, Institute of Motherhood and Childhood, Pirogov Russian National Research Medical University of the Ministry of Health of Russia (Pirogov University), Member of the Union of Pediatricians of Russia

Karaseva M.S. – Junior Research Fellow, Pediatrician at the Scientific and Practical Center for Specialized Medical Care for Children of the Moscow Healthcare Department, Member of the Union of Pediatricians of Russia

Kolosova N.G. – Candidate of Medical Sciences, Board Member of the Pediatric Respiratory Society, Associate Professor at the Department of Child Diseases, N.F. Filatov Clinical Institute of Child Health, I.M. Sechenov First Moscow State Medical University of the Ministry of Health of Russia (Sechenov University)

Komarova E.V. - Doctor of Medical Sciences, Deputy Head for the Expertise of Innovative Treatment and Rehabilitation Methods, Gastroenterologist, Chief Research Fellow at the Department of Orphan Diseases and Prevention of Disabling Conditions, Research Institute of Pediatrics and Child Health, Petrovsky National Research Centre of Surgery, Professor at the Department of Faculty Pediatrics, Institute of Motherhood and Childhood, Pirogov Russian National Research Medical University of the Ministry of Health of Russia (Pirogov University), Member of the Union of Pediatricians of Russia

Kuznetsova T.A., Doctor of Medical Sciences, Professor, Member of the Union of Pediatricians of Russia

Kulichenko T.V., Doctor of Medical Sciences, Professor of the Russian Academy of Sciences, Head of the National Medical Research Center, Pirogov Russian National Research Medical University of the Ministry of Health of Russia, World Health Organization Expert, Member of the Union of Pediatricians of Russia

Lashkova Yu.S., Candidate of Medical Sciences, Head of the Pediatric Diagnostic Department, Russian Children's Clinical Hospital — branch of the Pirogov Russian National Research Medical University of the Ministry of Health of Russia, Member of the Union of Pediatricians of Russia

Levina Yu.G., Doctor of Medical Sciences, Head of the Department of Clinical Immunology and Allergology, Allergist-Immunologist, Research Institute of Pediatrics and Child Health, Petrovsky National Research Centre of Surgery of the Ministry of Science and Higher Education of Russia, Associate Professor at the Department of Faculty Pediatrics, Institute of Motherhood and Childhood, Pirogov Russian National Research Medical University of the Ministry of Health of Russia (Pirogov University), Member of the Union of Pediatricians of Russia

Lutina E.I., Candidate of Medical Sciences, Professor, Member of the Union of Pediatricians of Russia

Manerov F.K., Candidate of Medical Sciences, Professor, Member of the Union of Pediatricians of Russia

Mayansky N.A., Doctor of Medical Sciences, Professor of the Russian Academy of Sciences, Head of the Center for Laboratory Diagnostics, Russian Children's Clinical Hospital, Pirogov Russian National Research Medical University

Miropolskaya N.Yu., Candidate of Medical Sciences, Infectious Disease Physician, Associate Professor at the Department of Polyclinic and Social Pediatrics, Institute of Continuing Professional Education, Pirogov Russian National Research Medical University (Pirogov University)

Ovsiannikov D.Yu. — Doctor of Medical Sciences, Professor, Head of the Department of Pediatrics, Peoples' Friendship University of Russia named after Patrice Lumumba

Platonova M.M. – Candidate of Medical Sciences, Researcher at the Research Institute of Pediatrics and Child Health, Petrovsky National Research Centre of Surgery, Pulmonologist

Polyakova A.S., Candidate of Medical Sciences, Member of the Union of Pediatricians of Russia

Prometnoy D.V., Doctor of Medical Sciences, Head of the Anesthesiology and Intensive Care Center of the Russian Children's Clinical Hospital, Expert Analyst at the Management Department for the Implementation of Functions of the National Medical Research Center for Pediatrics, Pirogov Russian National Research Medical University of the Ministry of Health of Russia (Pirogov University), Member of the Union of Pediatricians of Russia

Pytal A.V. – Anesthesiologist-Intensivist at the Russian Children's Clinical Hospital, Expert Analyst at the Management Department for the Implementation of Functions of the National Medical Research Center for Pediatrics, Pirogov Russian National Research Medical University of the Ministry of Health of Russia (Pirogov University), Member of the Union of Pediatricians of Russia

Rychkova L.V. – Corresponding Member of the Russian Academy of Sciences, Doctor of Medical Sciences, Professor at the Basic Department of Medical Psychology, Director of the Scientific Centre for Family Health and Human Reproduction Problems, Irkutsk State University, Secretary of the Commission of the Scientific Council on Pediatrics of the Clinical Medicine Section, Department of Medical Sciences of the Russian Academy of Sciences, President of the Irkutsk Regional Branch of the Union of Pediatricians of Russia.

Rychkova O.A. - Doctor of Medical Sciences, Associate Professor, Head of the Department of Infectious Diseases, Allergology and Immunology, Tyumen State Medical University of the Ministry of Health of the Russian Federation, Chief Allergist-Immunologist of the Tyumen Region Healthcare Department

Selimzyanova L.R., Candidate of Medical Sciences, Head of the Department of Standardization and Study of Evidence-Based Medicine Foundations, Research Institute of Pediatrics and Child Health, Petrovsky National Research Centre of Surgery, Associate Professor at the Department of Pediatrics and Pediatric Rheumatology, I.M. Sechenov First Moscow State Medical University of the Ministry of Health of Russia (Sechenov University), Associate Professor at the Department of Faculty Pediatrics, Institute of Motherhood and Childhood, Pirogov Russian National Research Medical University of the Ministry of Health of Russia (Pirogov University), Member of the Union of Pediatricians of Russia

Solodovnikova O.N. Candidate of Medical Sciences, Deputy Chief Physician for Pediatrics, Kommunarka Moscow Multidisciplinary Clinical Center of the Moscow Healthcare Department, Pediatrician, Infectious Disease Physician, Associate Professor at the Department of Polyclinic and Social Pediatrics, Institute of Continuing Professional Education, Pirogov Russian National Research Medical University (Pirogov University)

Starovoytova E.V., PhD in Medicine, Expert Analyst, Directorate for the Implementation of Functions of the National Medical Research Center for Pediatrics, Pirogov Russian National Research Medical University (Pirogov University) of the Russian Ministry of Health, Member of the Union of Pediatrists of Russia

Stetsyuk O.U., Senior Researcher, Institute of Antimicrobial Chemotherapy of the Smolensk State Medical University of the Ministry of Health of Russia, Member of ISCMR

Tatochenko V.K., DSc in Medicine, Professor, Director's Advisor, National Medical Research Center for Children's Health of the Russian Ministry of Health, Member of the Union of Pediatrists of Russia

Tyurin I.N. – DSc in Medicine, Honored Physician of the Russian Federation, Chief Physician, Infectious Clinical Hospital No. 1 of the Moscow Healthcare Department, Department of Anesthesiology and Intensive Care, Institute of Continuing Professional Education, Pirogov Russian National Research Medical University (Pirogov University)

Fedoseenko M.V., PhD in Medicine, Head of the Department for the Development of Scientific Approaches to Immunization of Patients with Health Deviations and Chronic Diseases, Leading Research Fellow, Pediatrician, Research Institute of Pediatrics and Child Health, Central Clinical Hospital of the Russian Academy of Sciences of the Ministry of Science and Higher Education of the Russian Federation, Associate Professor at the Department of Faculty Pediatrics, Pediatric Faculty, Pirogov Russian National Research Medical University (Pirogov University) of the Russian Ministry of Health, Member of the Union of Pediatrists of Russia

Chashchina I.L., Member of the Union of Pediatrists of Russia

Kharkin A.V., DSc in Medicine, Expert Analyst, Directorate for the Implementation of Functions of the National Medical Research Center for Pediatrics, Member of the Union of Pediatrists of Russia

Efendieva K.E. – PhD in Medicine, Deputy Head for International Relations and Educational Activities, Leading Research Fellow, Allergist-Immunologist, Research Institute of Pediatrics and Child Health, Academician B.V. Petrovsky National Research Center of Surgery, Associate Professor at the Department of Faculty Pediatrics, Institute of Motherhood and Childhood, Pirogov Russian National Research Medical University (Pirogov University) of the Russian Ministry of Health, Member of the Union of Pediatrists of Russia

Ponomareva Yu.V. – PhD in Medicine, Associate Professor at the Department of Pediatrics and Neonatology, Institute of Continuing Medical and Pharmaceutical Education, Volgograd State Medical University of the Russian Ministry of Health; Tomilova A.Yu., PhD in Medicine, Associate Professor at the Department of Faculty Pediatrics, Institute of Motherhood and Childhood, Pirogov Russian National Research Medical University (Pirogov University) of the Russian Ministry of Health, Allergist-Immunologist at the Department of Allergology, Federal Clinical Research Center for Children and Adolescents of the FMBA of Russia, Member of the Union of Pediatrists of Russia;

Tomilova A.Yu., PhD in Medicine, Associate Professor at the Department of Faculty Pediatrics, Institute of Motherhood and Childhood, Pirogov Russian National Research Medical University (Pirogov University) of the Russian Ministry of Health, Allergist-Immunologist at the Department of Allergology, Federal Clinical Research Center for Children and Adolescents of the FMBA of Russia, Member of the Union of Pediatrists of Russia;

Rtishchev A.Yu. – PhD in Medicine, Associate Professor at the Department of Infectious Diseases in Children, Institute of Motherhood and Childhood, Pirogov Russian National Research Medical University (Pirogov University), Infectious Diseases Physician, Morozov Children's City Clinical Hospital of the Moscow Healthcare Department, Chief freelance Specialist in Pediatric Infectious Diseases for the Central and Southeastern Administrative Districts of Moscow;

Shishimorov I.N. – DSc in Medicine, Head of the Department of Pediatrics and Neonatology, Institute of Continuing Medical and Pharmaceutical Education, Volgograd State Medical University of the Russian Ministry of Health, President of the Volgograd Regional Branch of the Union of Pediatrists of Russia.

The authors declare no financial support or conflicts of interest that need to be disclosed.

Appendix A2. Methodology for Developing Clinical Guidelines

Target audience for these clinical guidelines:

• Pediatricians

• Infectious diseases physicians

• General practitioners (family physicians)

• Allergists-immunologists

• Radiologists

• Functional diagnostics physicians

• Pulmonologists

• Medical students

• Residents

The development of the clinical guidelines adhered to the principles that ensure high-quality and reliable clinical guidelines.

Methods used for collecting/selecting evidence

Search in electronic databases.

Description of methods used for collecting/selecting evidence

The evidence base for the publication includes publications from the Cochrane Library, EMBASE, and MEDLINE databases. The search depth was 10 years.

Methods used for assessing the quality and strength of evidence

Expert consensus.

Significance assessment according to the grading scheme (Table 1).

Methods used for evidence analysis:

Reviews of published meta-analyses;

Systematic reviews with evidence tables.

Description of methods used for evidence analysis

To eliminate the influence of subjective factors and minimize potential errors, each study was evaluated independently by at least two independent members of the working group. Any discrepancies in evaluations were discussed by the full working group. If consensus could not be reached, an independent expert was involved.

Methods used for formulating recommendations

Expert consensus.

Recommendation validation method

- External peer review

- Internal peer review

Description of the recommendation validation method

The draft version of these recommendations was reviewed by independent experts who determined that the evidence underlying these recommendations is comprehensible.

These recommendations were reviewed by pediatricians who noted the clarity of presentation and their importance as a working tool in daily practice.

All comments received from experts were carefully systematized and discussed by the chair and members of the working group, and amendments were made to the clinical guidelines where necessary.

Economic analysis

Cost analysis was not performed, and pharmacoeconomic publications were not analyzed.

Consultation and peer review

The draft guidelines were also peer-reviewed by independent experts who were asked to comment on the clarity and accuracy of the interpretation of the evidence base underlying the guidelines.

Working Group

For the final edition and quality control, the guidelines were re-analyzed by the members of the working group, who concluded that all comments and remarks from the experts had been taken into account and the risk of bias in the development of the guidelines had been minimized.

Table 1. Scale for assessing levels of evidence (LE) for diagnostic methods (diagnostic interventions)

Table 2. Scale for assessing levels of evidence (LE) for prevention, treatment and rehabilitation methods (preventive, therapeutic, rehabilitation interventions)

Table 3. Scale for assessing grades of recommendation (GR) for prevention, diagnosis, treatment and rehabilitation methods (preventive, diagnostic, therapeutic, rehabilitation interventions)

The mechanism for updating clinical guidelines provides for their systematic revision at least once every three years, as well as upon the emergence of new evidence-based medicine data on the diagnosis, treatment, prevention, and rehabilitation of specific diseases, or in the presence of justified additions/comments to previously approved clinical guidelines, but no more frequently than once every 6 months.

Appendix A3. Reference Materials

Rules for the provision of medical care: Order of the Ministry of Health and Social Development of the Russian Federation No. 366n dated April 16, 2012 "On approval of the Procedure for the provision of pediatric care"

Instructions for medical use of medicinal products: https://grls.rosminzdrav.ru/

Examples of diagnosis formulation:

The formulation of the diagnosis of community-acquired pneumonia must reflect the nosological form indicating the presumed or verified etiology, localization and extent of pulmonary inflammation, severity, presence of complications, and comorbid conditions.

• Community-acquired pneumonia, pneumococcal, segmental (S5) of the right lung, mild course.

• Community-acquired pneumonia, mycoplasmal etiology, bilateral polysegmental (S7,8 of the right lung, S5,6 of the left lung), severe course.

• Community-acquired pneumonia of unknown etiology, left lower lobar, severe course. Metapneumonic pleurisy.

Appendix A3.1. Profile of a hospitalized patient with severe CAP for whom ceftaroline fosamil** or carbapenems are indicated [24].

Appendix B. Physician Action Algorithms

Appendix C. Patient Information

What is pneumonia?

Pneumonia is an inflammation of the lungs caused by an infection. In pneumonia, the alveoli (the tiny air sacs that make up the lungs) fill with fluid and pus, making it harder for oxygen to pass into the bloodstream during breathing.

What are the symptoms of pneumonia?

A person with pneumonia may experience fever (elevated body temperature), cough, and difficulty breathing.

Symptoms of pneumonia depend on age and the infectious agent that caused it. Symptoms of pneumonia include:

- rapid breathing (sometimes the only symptom);

- grunting respiration, sometimes wheezing (wheezing is more common in bronchitis than in pneumonia);

- labored breathing (may be accompanied by nasal flaring, abdominal breathing, and increased use of intercostal muscles);

- cough;

- abdominal pain (caused by coughing and labored breathing);

- fever, often with chills (the child feels hot and shivers from the cold);

- vomiting;

- chest pain;

- lethargy;

- loss of appetite and thirst (in older children), poor suckling (in infants), which can lead to dehydration;

- in severe cases, a bluish or grayish tint to the lips and nail beds.

If pneumonia develops in the lower lobes of the lungs (closer to the abdomen), fever, abdominal pain, or vomiting may occur without respiratory distress.

What causes pneumonia?

Pneumonia is caused by various microorganisms, including viruses, bacteria, fungi, and parasites. Bacterial pneumonia is the most common.

Certain symptoms indicate which specific infectious agent caused the pneumonia. For example, in school-age children, pneumonia is frequently associated with Mycoplasma infection, which, in addition to standard pneumonia symptoms, presents with a sore throat, headache, and rash. In infants under one year of age, chlamydial pneumonia occurs, which is characterized by a generally good condition without fever, but with conjunctival injection (redness of the eyes). If pneumonia is associated with pertussis (whooping cough), the child may experience prolonged coughing fits where the face turns blue due to oxygen deprivation, followed by a characteristic whoop sound as the child takes a noisy breath in.

The incubation period between pathogen entry and the onset of symptoms varies depending on the microbe (for instance, it is 4–6 days for respiratory syncytial virus, and 18 to 72 hours for the influenza virus).

How do physicians diagnose pneumonia?

A physician may suspect pneumonia in a child after a physical examination. They will assess the child's general condition and perform lung auscultation. A chest X-ray and blood tests may be required.

How is pneumonia treated?

If the physician diagnoses bacterial pneumonia, antibiotic therapy will be required. In most cases, antibiotics can be taken orally at home. The specific antibiotic will be prescribed by the pediatrician, general practitioner/family physician, infectious disease specialist, or pulmonologist, depending on the suspected pathogen.

If pneumonia is associated with the influenza virus and caught early, the physician will prescribe an antiviral medication effective against this virus.

It is exceptionally important to follow the dosages, administration schedule, and the full duration of the prescribed course of antibiotics to ensure the child recovers fully.

A child with pneumonia must be hospitalized if:

- supplemental oxygen therapy is required;

- the child has complications of pneumonia;

- the infection has spread from the lungs into the bloodstream;

- the child has a chronic condition affecting the immune system;

- the child has recurrent vomiting and cannot take oral medications;

- the child has pertussis;

- there is no improvement within 48 hours of starting pneumonia treatment.

In the hospital, the child will be administered intravenous antibiotics and, if necessary, inhalations. In the most severe cases, treatment in a pediatric intensive care unit (PICU) may be required.

How can parents help their child?

A person with pneumonia should rest and drink plenty of fluids while the body fights the infection. Follow all medical instructions, including the duration of the treatment course, as well as the frequency and timing of medication administration. Do not administer medications without consulting a physician. Measure the child's body temperature in the morning and evening, and inform the physician if it remains above 38 °C in a child under 6 months and above 38.9 °C in older children.

Ensure that your child's lips and nail beds remain pink. If they turn bluish or grayish, seek medical attention immediately! This indicates that the body is not receiving enough oxygen through the lungs.

How long does pneumonia last?

With proper treatment, a person usually recovers from bacterial pneumonia within 1–2 weeks. Full recovery from mycoplasma or viral pneumonia may take 4–6 weeks.

Is pneumonia contagious?

Pneumonia itself is not contagious, but the viral and bacterial infections that can cause it are contagious. When microbes are present in the oral or nasal secretions of an infected person, they can spread through coughing and sneezing. Microbes can also spread via shared dishware, cutlery, towels, and handkerchiefs.

Can pneumonia be prevented?

In some cases, pneumonia can be prevented through vaccination (e.g., pneumonia associated with Haemophilus influenzae type b, Streptococcus pneumoniae, influenza, and pertussis). Influenza vaccination is particularly important for individuals with chronic heart and lung conditions, as well as bronchial asthma. Premature infants should receive protection against RSV through pre-formed antibodies (passive immunization), as RSV infection can also lead to pneumonia in infants.

When should you see a doctor?

You should consult a physician if a child exhibits any symptoms of pneumonia, particularly if:

- the child has difficulty breathing or rapid breathing;

- the lips or nail beds are bluish or grayish;

- body temperature is above 38 °C in an infant under 6 months or above 38.9 °C in a child older than 6 months.

Appendix G. Assessment Scales, Questionnaires, and Other Evaluation Tools

Appendix G1 — Modified Glasgow Coma Scale for children under 1 year and children older than 1 year

Source: [Adapted from Davis RJ et al: Head and spinal cord injury. In Textbook of Pediatric Intensive Care, edited by MC Rogers. Baltimore, Williams & Wilkins, 1987; James H, Anas N, Perkin RM: Brain Insults in Infants and Children. New York, Grune & Stratton, 1985; and Morray JP, Tyler DC, Jones TK, et al: Coma scale for use in brain-injured children. Critical Care Medicine 12:1018–1020, 1984. doi: 10.1097/00003246-198412000-00002; and Carney N, Totten AM, O'Reilly C, et al: Guidelines for the management of severe traumatic brain injury, fourth edition. Neurosurgery 80(1):6-15. doi: 10.1227/NEU.0000000000001432].

Type: rating scale

Purpose: Coma scale for children under 1 year and children older than 1 year

Contents:

Key (interpretation):

¹ A score of less than or equal to (≤) 12 indicates severe head injury. A score of ≤ 8 suggests a potential need for intubation and initiation of mechanical ventilation, as well as intracranial pressure monitoring

² If the patient is intubated, unconscious, or preverbal, the motor response is the most critical part of this scale. This section should be evaluated thoroughly

Notes: -