List of Abbreviations
ASLO – antistreptolysin O
AMT – antimicrobial therapy
GAS – group A beta-hemolytic streptococcus
EBV – Epstein-Barr virus
ICD-10 – International Classification of Diseases 10th Revision
NSAIDs – nonsteroidal anti-inflammatory drugs (medicines of the groups Nonsteroidal anti-inflammatory and antirheumatic products (ibuprofen**, ketoprofen**)
ATP – acute tonsillopharyngitis
PCR – polymerase chain reaction
PANDAS – Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infections
Strep TSS (Toxic shock syndrome) – streptococcal toxic shock syndrome
Terms and Definitions
Acute tonsillopharyngitis (ATP) – acute infectious inflammation of the mucous membrane and lymphoid structures of the oropharynx (palatine tonsils, lymphoid follicles of the posterior pharyngeal wall).
Group A beta-hemolytic streptococcus rapid test – an immunochromatographic point-of-care rapid diagnostic method for the qualitative assessment of GAS antigen in oropharyngeal mucosal specimens, performed within 5–15 minutes.
1. Brief information on the disease or condition
1.1 Definition of the disease or condition
Acute tonsillopharyngitis – acute infectious inflammation of the mucous membrane and lymphoid structures of the oropharynx (palatine tonsils, lymphoid follicles of the posterior pharyngeal wall). The term ATP itself is an umbrella term encompassing acute inflammation of the palatine tonsils (acute tonsillitis) and acute inflammation of the posterior and lateral pharyngeal walls (acute pharyngitis); however, in the vast majority of cases, particularly with viral etiology, inflammation involves both locations (except for pharyngitis in a patient who has undergone tonsillectomy) [1].
1.2 Etiology and pathogenesis of the disease or condition (group of diseases or conditions)
The most frequent causative agents of ATP are respiratory viruses (adenovirus, Epstein-Barr virus, parainfluenza virus, respiratory syncytial virus, rhinovirus, bocavirus, metapneumovirus). Enteroviruses (Coxsackie B) may also play a role [2]. Novel coronavirus infection (caused by SARS-CoV-2) is frequently accompanied by severe sore throat and manifestations of acute tonsillopharyngitis [3-5].
Among bacterial pathogens, group A beta-hemolytic streptococcus (GAS, or Streptococcus pyogenes) is of paramount importance. All strains of pyogenic streptococcus are susceptible to penicillin and all other beta-lactam antibiotics. In the Russian Federation, macrolide-resistant strains of S. pyogenes are also reported (in approximately every fifth isolate), and 22% of strains from adult patients and 13% of isolates from children exhibit tetracycline resistance mechanisms. Lincosamides, particularly clindamycin, retain high activity against GAS (resistance rate of 3–4%) [6].
A number of authors point to a certain role of other bacterial pathogens, such as groups C and G streptococci, Arcanobacterium haemolyticum, etc. The isolation of other microorganisms (Staphylococcus aureus, Streptococcus pneumoniae and others) from the posterior pharyngeal wall/tonsils in patients with clinical ATP is regarded as colonization and does not require antimicrobial therapy.
Even rarer bacterial causative agents of acute tonsillitis include spirochetes (Simanovskiy-Plaut-Vincent angina) and anaerobes. It must not be forgotten that acute tonsillitis is one of the possible symptoms of diseases such as diphtheria (Corynebacterium diphtheriae) and gonorrhea (Neisseria gonorrhoeae) [7,8].
1.3 Epidemiology of the Disease or Condition
ATP is one of the most common conditions in outpatient practice among children and adults. GAS accounts for 5 to 15% of acute tonsillopharyngitis cases in the adult population and 15–37% in children [9-12]. In children under 3 years of age, ATP is most often of viral etiology, while the probability of GAS tonsillitis at this age is minimal (3%). The highest incidence of GAS-induced ATP is observed in children aged 5–15 years [13]. In patients older than 45 years, the probability of streptococcal etiology becomes minimal [7,10]. GAS-induced ATP is characterized by seasonality (late winter - early spring) [14].
1.4 Features of Coding the Disease or Condition
J02 – Acute pharyngitis
J02.0 – Streptococcal pharyngitis
J02.8 – Acute pharyngitis due to other specified organisms
J02.9 – Acute pharyngitis, unspecified
J03 – Acute tonsillitis
J03.0 – Streptococcal tonsillitis
J03.8 – Acute tonsillitis due to other specified organisms
J03.9 – Acute tonsillitis, unspecified
1.5 Classification of the disease or condition
By localization: acute tonsillitis, acute pharyngitis, acute tonsillopharyngitis (diagnosis formulation and coding may be based on determining the predominance of inflammation severity in a particular section of the oropharynx).
By etiology: streptococcal, non-streptococcal (or viral). At the same time, etiological diagnosis of the disease is of paramount importance for choosing treatment tactics and further patient management.
1.6 Clinical presentation of the disease or condition
ATP of any etiology is characterized by:
acute onset,
febrile fever (>380C; ATP less frequently presents with normal or subfebrile temperature),
discomfort and/or sore throat, aggravated by swallowing, with possible radiation to the ear,
possible bilateral enlargement and tenderness of regional lymph nodes,
in early childhood, refusal to eat (avoiding swallowing any food, even liquid) is possible,
satisfactory or moderate general condition.
2. Diagnostics, medical indications and contraindications for diagnostic methods
Criteria for Establishing the Diagnosis/Condition
The diagnosis is established based on the patient's complaints of severe sore throat aggravated by swallowing (odynophagia), physical examination findings (hyperemia, infiltration, edema of the palatine tonsils, enlargement of regional lymph nodes), and the results of rapid testing for GAS / microbiological examination to confirm or exclude streptococcal etiology of ATP.
2.1 Complaints and Anamnesis
The main complaints in ATP are sore throat aggravated by swallowing, and fever. In uncomplicated cases, the pain is generally symmetrical. In early childhood, when it is impossible to verbalize or correctly describe pain sensations, attention is drawn to the child's refusal to eat or swallow food, with a preference for homogeneous or liquid food.
Specific history is generally absent, except for epidemiological data regarding a focus of acute streptococcal infection (however, outbreaks of acute streptococcal tonsillopharyngitis have been quite rare recently).
2.2 Physical Examination
It is recommended that all patients with ATP undergo an initial examination (inspection, consultation) by an otorhinolaryngologist, and/or initial examination (inspection, consultation) by a pediatrician, and/or initial examination (inspection, consultation) by a general practitioner (family physician), and/or initial examination (inspection, consultation) by a therapist to assess the patient's condition, establish a diagnosis, and choose treatment tactics [1,20,21]
GCR CLEL 5Grade of Recommendation C (Level of Evidence – 5)
Comments: During pharyngoscopy, the palatine tonsils are hyperemic, infiltrated, and edematous; white, off-white, or yellow exudate (patches) may appear; the posterior pharyngeal wall is hyperemic, and the uvula is edematous. The tonsils, especially in children, may increase in size. Tonsillar enlargement in ATP is symmetrical, which helps differentiate ATP from a peritonsillar abscess.
It is not possible to unambiguously differentiate viral and bacterial ATP based on the clinical picture alone.
ATP caused by GAS is characterized by enlargement of the submandibular and/or anterior cervical lymph nodes. The course of GAS-induced ATP is characterized by febrile fever (GAS tonsillopharyngitis rarely presents with subfebrile or normal body temperature), acute sore throat, and pharyngoscopic changes (bright hyperemia, "fiery throat", presence of exudate on the tonsils in the majority of cases, and absence of catarrhal phenomena).
The appearance of petechiae on the soft palate is possible in both GAS- and EBV-induced ATP.
As a rule, viral ATP is accompanied by other catarrhal symptoms (rhinitis, conjunctivitis, cough).
In EBV-induced ATP, generalized lymphadenopathy as well as hepatomegaly and splenomegaly are possible, which can aid in differential diagnosis.
For the differential diagnosis of viral and streptococcal acute pharyngitis based on clinical presentation, several practical guidelines and manuals recommend using the Centor, McIsaac, or FeverPAIN scales (Appendix G1) [8,9,15,16]
Evaluation using scoring scales helps identify patients with a high probability of GAS infection, but does not establish the diagnosis with absolute accuracy [17-19].
2.3 Laboratory Diagnostics
It is recommended that all patients with ATP undergo differential diagnosis between the streptococcal and viral etiology of the disease [1,20,21].
GCR CLEL 5Grade of Recommendation C (Level of Evidence – 5)
It is recommended that patients with ATP over 3 years of age undergo testing for group A streptococcus (S. pyogenes) antigen in upper respiratory tract secretions (Immunochromatographic rapid swab test for group A streptococci from the throat) to confirm or exclude the streptococcal etiology of the disease [8,9,22,23].
GCR ALEL 1Grade of Recommendation A (Level of Evidence – 1)
Comments: Rapid testing is based on enzyme immunoassay or immunochromatography and provides a result at the bedside within 5–15 minutes. The analysis does not require a specialized laboratory. The average specificity and sensitivity of modern test systems are 94% and 97%, respectively.
If the rapid test results are positive, it is impractical to perform a culture test (bacteriological examination of throat swabs for group A Streptococcus) due to the high specificity of rapid diagnostics for GAS infection [9,21].
In adults with negative rapid antigen test results, performing a throat culture is not advisable due to the low prevalence of GAS tonsillopharyngitis and the low risk of subsequent rheumatic fever in this category of patients [9]. A negative rapid test result in children and adolescents with suspected GAS-induced acute tonsillopharyngitis should be confirmed by a culture (bacteriological examination of throat swab for group A Streptococcus (Streptococcus gr. A) [9].
Routine rapid antigen testing (rapid immunochromatographic assay of throat swab for group A streptococci) should not be performed in children under 3 years of age due to the rare occurrence of GAS-induced acute tonsillopharyngitis in this age group. An exception is the presence of risk factors for GAS tonsillitis in a child under 3 years of age (e.g., a case of GAS-induced acute tonsillopharyngitis in an older sibling, i.e., a relevant epidemiological environment) [9].
It is recommended that patients over 3 years of age who have not undergone group A streptococcus (S. pyogenes) antigen testing in upper respiratory tract secretions (rapid immunochromatographic assay of throat swab for group A streptococci) or whose test result is negative undergo bacteriological examination of throat swab for group A Streptococcus (Streptococcus gr. A) to confirm/exclude a streptococcal etiology of the disease [9,24,25].
GCR CLEL 5Grade of Recommendation C (Level of Evidence – 5)
Comments: Clinical data alone are not reliable criteria in the differential diagnosis of acute tonsillopharyngitis caused by GAS versus viruses
Routine bacteriological examination should not be performed in children under 3 years of age due to the rare occurrence of GAS-induced acute tonsillopharyngitis in this age group. An exception is the presence of risk factors for GAS tonsillopharyngitis in a child under 3 years of age (e.g., a case of GAS-induced acute tonsillopharyngitis in an older sibling, i.e., a relevant epidemiological environment) [9].
The sensitivity and specificity of microbiological (culture) examination (bacteriological examination of throat swab for group A Streptococcus (Streptococcus gr. A) are estimated to be close to 100% provided all conditions for specimen collection, transport, and incubation are met. The disadvantage of culture is the long turnaround time to results (up to 72 hours).
Given the consistently favorable epidemiological situation regarding diphtheria incidence in Russia, a microbiological (culture) examination of mucus and membranes from the tonsils for the diphtheria bacillus (Corynebacterium diphtheriae) in patients with acute tonsillopharyngitis is advisable only in cases of unfavorable epidemiological or vaccination history and/or characteristic clinical symptoms [26].
It is recommended to obtain material for bacteriological examination of throat swab for group A Streptococcus (Streptococcus gr. A) or group A streptococcus (S. pyogenes) antigen testing in upper respiratory tract secretions (rapid immunochromatographic assay of throat swab for group A streptococci) under the following conditions [9,27,28]:
- prior to initiating antibacterial therapy;
- before morning oral hygiene, on an empty stomach or 2 hours after a meal;
- under oropharyngoscopic control;
- contact with teeth and tongue should be avoided;
- material is obtained from the crypt openings of the palatine tonsils and the posterior pharyngeal wall.
GDR CLE 5Grade of recommendation C (level of evidence – 5)
Comments: If the conditions described above are not met, the informativity of diagnostic methods decreases.
It is not recommended to routinely test for inflammatory markers (serum C-reactive protein (CRP) level testing, blood procalcitonin (PCT) level testing) in outpatients with acute tonsillopharyngitis due to insufficient clinical utility in differentiating viral from bacterial inflammation, in order to optimize diagnostics [8,9].
GCR CLEL 5Grade of Recommendation C (Level of Evidence – 5)
Comments: Numerous domestic and international studies have demonstrated extremely low diagnostic utility of inflammatory markers (leukocytosis, neutrophilia, left shift, ESR, C-reactive protein, procalcitonin) [7,11]. Although elevated inflammatory marker levels are somewhat more common in bacterial acute tonsillopharyngitis, they can also occur with viral inflammation, whereas low levels do not rule out a streptococcal etiology. Establishing the etiology of the disease is paramount in determining management strategy.
Nevertheless, CRP testing should be performed upon hospital admission, and procalcitonin testing should be performed selectively in severe inpatients for diagnostic purposes, inflammation monitoring, and treatment efficacy evaluation.
It is not recommended to routinely perform a complete blood count in outpatients with acute tonsillopharyngitis in order to optimize diagnostics [29,30].
GCR CLEL 5Grade of Recommendation C (Level of Evidence – 5)
Comments: the test may be performed if necessary, including upon hospital admission and/or as part of the differential diagnosis of infectious mononucleosis
It is not recommended to routinely determine serum antistreptolysin-O in all patients with acute tonsillopharyngitis in order to optimize diagnostics [9].
GDR CLE 5Grade of recommendation C (level of evidence – 5)
Comments: The determination of serum antistreptolysin-O (ASO) level is a tool for retrospective diagnosis, as it rises only by the 7th–9th day of streptococcal infection and may also reflect previous infections or chronic infection [9,31].
In addition, ASO should be measured in patients with suspected immunopathological complications, such as post-streptococcal glomerulonephritis, rheumatic fever, and PANDAS syndrome (see relevant clinical guidelines).
It is not recommended to routinely perform follow-up GAS testing (bacteriological examination of throat swab for group A Streptococcus (Streptococcus gr. A) and/or rapid test (rapid immunochromatographic assay of throat swab for group A streptococci)) to assess cure in convalescents of acute tonsillopharyngitis who do not belong to high-risk groups for acute rheumatic fever and/or do not have recurrent symptoms similar to GAS acute tonsillopharyngitis, in order to optimize diagnostics [8,9].
GDR CLE 5Grade of recommendation C (level of evidence – 5)
2.4 Instrumental Diagnostics
Not required.
2.5 Other Procedures
Differential diagnosis
It is recommended in children with acute tonsillopharyngitis older than 3 years to check for catarrhal signs (nasal discharge, cough, hoarseness, conjunctivitis) characteristic of viral respiratory infections presenting with tonsillopharyngitis (such a presentation is observed in no more than 10% of patients with GAS tonsillopharyngitis in the presence of viral co-infection), in order to improve the accuracy of differential diagnosis between viral and bacterial acute tonsillopharyngitis [20].
GDR CLE 5Grade of recommendation C (level of evidence – 5)
Comment: the following conditions may also present with signs of acute tonsillopharyngitis:
- Infectious mononucleosis is a viral infection presenting with acute tonsillopharyngitis, most commonly seen in adolescents and young adults (under 30 years). Infectious mononucleosis is also characterized by fatigue, lymphadenopathy involving cervical and frequently other lymph node groups, hepatosplenomegaly, and characteristic hematological findings (lymphocytic leukocytosis, appearance of atypical mononuclear cells) [32]. Detection of Epstein-Barr virus DNA in a posterior pharyngeal swab (saliva) and/or blood by PCR, and serological methods (presence of IgM to Epstein-Barr virus capsid antigen complex) allow for the diagnosis of infectious mononucleosis.
- Enteroviral vesicular stomatitis (hand, foot and mouth disease) is typical for young children (under 5 years), usually occurs in summer months, and presents with mild fever, oral vesicular rashes without tonsillar exudates, and exanthema on the hands and feet.
- Plaut-Vincent angina (causative agent: Fusobacterium necrophorum) presents with unilateral necrotic ulceration of the tonsil, sometimes also involving the palate and oral mucosa, with a characteristic putrid odor.
- Pharyngeal diphtheria, which causes dense plaque on the tonsils that is difficult to remove, leaving a bleeding surface.
- Marshall syndrome or PFAPA (periodic fever, aphthous stomatitis, pharyngitis, and adenitis). Marshall syndrome belongs to the periodic fever group and is characterized by a relapsing course with a clear periodicity. The attack begins with high fever (up to 39–40 ºC), accompanied by symptoms of tonsillitis or pharyngitis (sore throat, tonsillar hyperemia), aphthous stomatitis (oral ulcers), and enlarged cervical lymph nodes. Joint pain, abdominal pain, headaches, and general intoxication symptoms may also be observed. The attack lasts for several days, and relapses occur every 1–2 months. The average age of onset is 5 years, and children usually recover by age 10, although symptoms persist into adulthood in some patients. Laboratory findings show leukocytosis, an elevated ESR, and increased CRP levels. A characteristic feature is the rapid resolution of the attack with systemic corticosteroids [33].
3. Treatment, including drug and non-drug therapies, diet therapy, and pain management
3.1. Conservative management
For viral infections, systemic antibacterial drugs are not recommended. Systemic antibiotic therapy is ineffective against viral tonsillopharyngitis and does not prevent bacterial superinfection. [2, 34].
GDR CLE 5Grade of recommendation C (level of evidence – 5)
It is recommended to prescribe systemic antibacterial drugs only in cases of proven [8, 9, 24] or highly probable streptococcal etiology of acute tonsillopharyngitis [2, 8, 9].
GDR CLE 5Grade of recommendation C (level of evidence – 5)
Considering the 100% susceptibility of S. pyogenes to beta-lactam antibacterial drugs, penicillins are recommended as the first-line systemic antibacterial drug for group A streptococcal (GAS) tonsillopharyngitis – amoxicillin** (ATX code: J01CA04) [6, 9, 35–41].
GDR CLE 5Grade of recommendation C (level of evidence – 5)
Comment: Dosages of amoxicillin** (ATX code: J01CA04): 500 mg 2–3 times daily in adults and 50 mg/kg/day divided into 2 doses, but not exceeding 1000 mg daily, orally in children, for 10 days (Table 1).
Currently, almost the only indication for prescribing systemic antibacterial drugs in immunocompetent individuals is the GAS etiology of acute tonsillopharyngitis (except for extremely rare cases of diphtheria, gonococcal tonsillitis, and Vincent's angina).
The objectives of prescribing systemic antibacterial drugs in acute streptococcal tonsillopharyngitis are:
eradication of the pathogen (GAS);
prevention of complications ("early" purulent and "late" autoimmune);
containment of the infection focus (reduction of contagiousness);
clinical recovery.
It must be kept in mind that infectious mononucleosis may be complicated by the development of the so-called "ampicillin" or "amoxicillin" rash. However, research data indicate that the rash in mononucleosis can occur during the use of other systemic antibacterial drugs and even if the patient has not used drugs of this group. To minimize the likelihood of a rash in mononucleosis, the prescription of any systemic antibacterial drugs should be avoided [42, 43].
It is recommended in recurrent cases of acute streptococcal tonsillopharyngitis, in order to overcome the mechanisms causing microbiological failure of previous treatment, to prescribe amoxicillin + [clavulanic acid]** (ATX code: J01CR02) or clindamycin** (ATX code: J01FF01) (in children older than 3 years) for a 10-day course [9, 38, 41, 44, 45].
Strength of recommendation B (level of evidence – 2)
Comment: in case of recurrent acute tonsillopharyngitis, a consultation with an otorhinolaryngologist is required to confirm/exclude chronic tonsillitis, and in some cases, especially in children with an appropriate clinical presentation, differential diagnosis with Marshall syndrome (PFAPA) should be performed.
Dosages of amoxicillin + [clavulanic acid]** (ATX code: J01CR02): adults and children 12 years and older or weighing 40 kg or more at a dose of 875/125 mg twice daily (for children under 12 years, 40 mg/kg/day based on amoxicillin**).
Dosages of clindamycin** (ATX code: J01FF01): adults and children 12 years and older, 300 mg twice daily; children aged 3 to 12 years, 20–30 mg/kg/day divided into 3 doses (Table 1).
It is recommended if there is no positive clinical response (persistence of fever and pain syndrome) within 48–72 hours from the start of antibiotic therapy to reassess the diagnosis (probable acute respiratory viral infection, infectious mononucleosis) [9, 20, 37].
GDR CLE 5Grade of recommendation C (level of evidence – 5)
It is recommended in the presence of a history of allergic reactions (excluding severe allergic reactions: anaphylactic shock, laryngeal angioedema (Quincke's edema), severe allergic urticaria) to beta-lactam antibacterial drugs, penicillins, to use second-generation and third-generation cephalosporins [9, 11, 46]:
Cefuroxime** (ATX code: J01DC02) 250 mg twice daily orally in adults and 20 mg/kg/day, not exceeding 500 mg/day, divided into 2 doses in children. Duration of therapy is 10 days [9, 11, 31].
GDR CLE 5Grade of recommendation C (level of evidence – 5)
Cefixime (ATX code: J01DD08) 200 mg twice daily or 400 mg once daily orally in adults and 8 mg/kg/day, not exceeding 400 mg/day, divided into 1 or 2 doses in children. Duration of therapy is 10 days [9, 11, 38].
SOR CLOE 5Strength of recommendation C (level of evidence 5) – in pediatric practice.
SOR BLOE 1Strength of recommendation B (level of evidence 1) – in adult practice.
Cefditoren (ATC code: J01DD16) – adults and children over 12 years of age, 200 mg orally twice daily. Duration of therapy – 10 days [47]
Leveled of Evidence CLevel of Data Reliability 2Level of evidence C (level of data reliability – 2)
Cefpodoxime (ATX code: J01DD13) – adults and children older than 12 years, 100 mg twice daily orally. Duration of therapy – 10 days. [46, 48]
GCR BLEL 2Grade of Recommendations B (Level of Evidence – 2)
Comments: The probability of cross-allergic reactions with drugs of the "Beta-lactam antibacterial drugs, penicillins" group is less than 2% and less than 1% for second- and third-generation cephalosporins, respectively [9, 46, 49-51, 52-57].
It is recommended in case of a history of hypersensitivity to cephalosporins and/or severe allergic reactions (anaphylactic shock, laryngeal angioedema (Quincke's edema), severe urticaria) to any drug from the "Beta-lactam antibacterial drugs, penicillins" and "Other beta-lactam antibacterial drugs" groups to use macrolides or lincosamides [9, 20, 58-61].
GDR CLE 5Grade of recommendation C (level of evidence – 5)
Comments: Erythromycin is characterized by a higher frequency of adverse reactions, especially from the gastrointestinal tract, compared to other macrolides [62, 63].
One must keep in mind the potential resistance of GAS to macrolides. Moreover, resistance to 14-membered (erythromycin, clarithromycin**, roxithromycin) and 15-membered (azithromycin**) macrolides may be somewhat higher than to 16-membered (josamycin**, spiramycin, midecamycin) macrolides due to strains with the M-resistance phenotype [64].
The susceptibility of S. pyogenes to azithromycin** in the Russian Federation is 80% and 78% in adults and children, respectively [6]. Some North American consensus documents indicate a higher efficacy of a 3-day course of #azithromycin** at a dose of 500 mg once daily in adults and 12 mg/kg/day for 5 days in children compared to a 3-day course [65, 66]. However, the instructions for medical use of azithromycin** formulations registered in the Russian Federation permit only a 3-day course in patients with acute tonsillopharyngitis. Therefore, a physician's decision in the Russian Federation to use a potentially more effective off-label course requires convincing justifications and a medical board conclusion recorded in the medical documentation.
A ten-day course of clarithromycin** therapy proved more effective for the eradication of group A streptococci in adults than a 5-day course of azithromycin**. [70]
The use of lincosamides is most frequently associated with the development of pseudomembranous colitis [67, 68]; with the MLSB resistance phenotype, simultaneous lack of susceptibility to all macrolides and lincosamides is observed [64].
It is recommended in acute streptococcal tonsillopharyngitis to adhere to the duration of systemic antibacterial therapy required for GAS eradication [11, 20, 30, 31, 38, 39, 65].
GCR CLEL 5Grade of Recommendation C (Level of Evidence – 5)
Comment: the duration of the eradication course of antibiotic therapy with drugs of the groups "Beta-lactam antibacterial drugs, penicillins" (aminopenicillins), "Other beta-lactam antibacterial drugs" (first-, second-, and third-generation cephalosporins), lincosamides, and macrolides (except for azithromycin**) is 10 days [2, 8, 9, 69] (Table 1).
It is recommended to use benzathine benzylpenicillin** (ATC code: J01CE08) only if there are doubts about patient compliance, as an alternative to a course of oral antibiotic therapy [9].
GDR CLE 5Grade of recommendation C (level of evidence – 5)
Comments: Dose of benzathine benzylpenicillin** (ATC code: J01CE08): ≤27 kg – 600,000 IU single dose i.m., >27 kg – 1,200,000 IU single dose intramuscularly.
Table 1. Systemic antibiotic therapy for acute streptococcal tonsillitis (oral)
Systemic antibacterial drug | Dose | Relation to food intake | Course duration | |
|---|---|---|---|---|
Adults | Pediatric population | |||
First-line therapy | ||||
Amoxicillin**1 (ATC code: J01CA04) | 1.5 g/day in 3 divided doses or 1.0 g/day in 2 divided doses | 50 mg/kg/day in 2-3 divided doses | Regardless of meals | 10 days |
Alternative option | ||||
Benzathine benzylpenicillin** 2 (ATC code: J01CE08) | 2.4 million IU intramuscularly | In patients over 12 years of age with m<27 kg – 600,000 IU, with m>27 kg – 1.2 million IU intramuscularly | Not applicable | Once |
Cefalexin** | Adults and children over 10 years – 500-1000 mg daily in 2 divided doses | Children aged 3 to 10 years only in film-coated tablet formulation – 25-50 mg/kg/day in 4 divided doses, but not exceeding 1000 mg per day | Regardless of meals | 10 days |
In case of recurrent course and/or clinical ineffectiveness of amoxicillin therapy** | ||||
Amoxicillin+[clavulanic acid]**1,3 (ATC code: J01CR02) | 1750 mg (calculated as amoxicillin) in 2 divided doses | 50 mg/kg/day (calculated as amoxicillin) in 2-3 divided doses | During meals | 10 days |
In case of a history of non-severe allergic reactions to penicillins | ||||
Cefuroxime** (ATC code: J01DC02) | 1.0 g/day in 2 divided doses | 20 mg/kg/day in 2 divided doses | Immediately after a meal | 10 days |
Cefixime (ATC code: J01DD08) | 400 mg/day in 1 or 2 divided doses | 8 mg/kg/day in 1 or 2 divided doses | Regardless of meals | 10 days |
Cefditoren (ATC code: J01DD16) | 400 mg/day in 2 divided doses | 400 mg/day in 2 divided doses (from 12 years of age) | After meals | 10 days |
Cefpodoxime (ATC code: J01DD13) | 200 mg/day in 2 divided doses | 200 mg/day in 2 divided doses (from 12 years of age) | During meals | 10 days |
In case of allergy to second- and third-generation cephalosporins and/or a history of severe allergic reactions4 to any drugs of the beta-lactam antibacterial drugs or penicillins classes | ||||
Clarithromycin**6 (ATC code: J01FA09) | 500-1000 mg/day in 2 divided doses | 15 mg/kg/day in 2 divided doses | Regardless of meals | 10 days |
Josamycin (ATC code: J01FA07) | 1.0 g/day in 2 divided doses | 40-50 mg/kg/day in 2 divided doses | Between meals | 10 days |
Azithromycin**6,7,8 (ATC code: J01FA10) | 500 mg/day once daily | 20 mg/kg/day once daily | 1 hour before meals | 3 days (#5 days)8 |
Midecamycin (ATC code: J01FA03) | 1.2 g/day in 3 divided doses | In children over 3 years of age, 50 mg/kg/day in 2 divided doses | 1 hour before meals | 10 days |
Spiramycin (ATC code: J01FA02) | 6 million IU/day in 2 divided doses | In children over 6 years with m>20 kg, 300,000 IU/kg/day in 2 divided doses | Regardless of meals | 10 days |
Clindamycin**9 (ATC code: J01FF01) | 0.6 g/day in 4 divided doses | 20 mg/kg/day in 3 divided doses | With a large volume of water | 10 days |
1with caution if infectious mononucleosis is suspected
2it is advisable to prescribe in cases of: a) doubtful patient compliance with oral systemic antibacterial therapy; b) a history of rheumatic fever in the patient or close relatives; c) adverse social and living conditions; d) outbreaks of GAS infection in closed communities (preschools, schools, boarding schools, vocational schools, military units, etc.)
3the dose of clavulanic acid should not exceed 10 mg/kg/day to avoid increasing the risk of adverse events (diarrhea)
4severe allergic reactions include anaphylactic shock, laryngeal angioedema (Quincke's edema), severe urticaria
5erythromycin is characterized by the most frequent occurrence of adverse reactions, especially from the gastrointestinal tract, compared to other macrolides
6it is necessary to keep in mind the potential resistance of GAS to macrolides. Furthermore, resistance to 14-membered (erythromycin, clarithromycin**, roxithromycin) and 15-membered (azithromycin) macrolides may be somewhat higher than to 16-membered ones (josamycin, spiramycin, midecamycin) due to strains with the M-phenotype of resistance [64]
7the susceptibility of S. pyogenes to azithromycin** in the Russian Federation is 80% and 78% in adults and children, respectively [6].
8 some publications have noted greater efficacy of a 5-day course of azithromycin** compared to a 3-day course [65,66], however, the instructions for medical use of azithromycin** formulations registered in the Russian Federation only permit a 3-day course in patients with acute tonsillopharyngitis, which requires justification for the use of a more effective off-label course and approval by a medical board. A ten-day course of clarithromycin therapy proved more effective for group A streptococcal eradication in adults than 5 days of azithromycin therapy at a dose of 500 mg once daily on the first day of treatment, followed by 250 mg once daily for the subsequent 4 days. [70]
9the development of pseudomembranous colitis is most frequently associated with lincosamides; the MLSB resistance phenotype is characterized by concurrent resistance to all macrolides and lincosamides.
If systemic antibacterial therapy cannot be taken orally or the patient refuses oral administration, parenteral administration (IV or IM) is prescribed until the patient's condition stabilizes and/or oral administration can be resumed, with the aim of eradicating GAS (Table 2).
Table 2. Parenteral antimicrobial therapy for acute tonsillopharyngitis caused by GAS1
Systemic antibacterial drug | Dosage, route of administration | |
|---|---|---|
Pediatric population | Adults | |
Drugs of choice | ||
Ampicillin** (ATC code: J01CA01) | Under 1 year: 100 mg/kg/day; 1–4 years: 100–150 mg/kg/day; children from 4 years: 1–2 g/day in 4 doses IV or IM | Adults and children weighing over 40 kg: 250–500 mg every 6 h IV or IM |
Amoxicillin+[Clavulanic acid]** (ATC code: J01CR02) | 90 mg/kg/day in 3 doses IV | Children over 12 years and adults: 1.2 g IV every 8 h |
Ampicillin+[Sulbactam]** (ATC code: J01CR01) | Children under 12 years (or weighing <40 kg): 150 mg/kg/day in 3–4 doses IV or IM | 1.5–3 g every 6–8 h IV or IM |
Cefazolin** (ATC code: J01DB04) | Children from 1 month to 18 years: 25–50 mg/kg/day (in severe cases 100 mg/kg/day) in 3–4 doses IV or IM | Adults: 2.0 g every 8 h IV or IM |
Ceftriaxone** (ATC code: J01DD04) | Children under 12 years: 20–80 mg/kg/day once daily (for children weighing over 50 kg – up to 2 g/day) IV or IM | Adults and children over 12 years: 2 g once daily IV or IM |
Cefotaxime** (ATC code: J01DD01) | Children under 12 years: 100–150 mg/kg/day in 2–4 parenteral doses, children over 12 years – 1 g twice daily, in severe cases – 3–4 g/day divided into 3–4 doses IV or IM | Adults and children over 12 years (or weighing >50 kg): 1–2 g every 6–8 h IV or IM |
Alternative drugs (in case of intolerance to beta-lactam antibacterials, penicillins and/or other beta-lactam antibacterials) | ||
Clindamycin** (ATC code: J01FF01) | 20–40 mg/kg/day in 3–4 doses IV or IM | 0.4–0.6 g every 6–8 h IV or IM |
1When the patient's condition stabilizes, one should switch to oral systemic antibacterial therapy to minimize invasive procedures (for the list of oral drugs and dosing regimens, see Table 1) while maintaining efficacy and minimizing patient pain.
Prophylactic prescription of systemic antibacterial drugs is not recommended for viral acute tonsillopharyngitis [9,11,20,71,72].
GCR ALEL 1Grade of Recommendation A (Level of Evidence – 1)
It is recommended to administer symptomatic systemic therapy to relieve fever and/or pain. Systemic drugs from the following groups may be used: non-steroidal anti-inflammatory and antirheumatic drugs (ibuprofen** (ATC code: M01AE01), and/or other analgesics and antipyretics (paracetamol** (ATC code: N02BE01) and/or acetylsalicylic acid** (ATC code: N02BA01) (in patients over 15 years of age) [1,9,73–76].
GCR CLEL 5Grade of Recommendation C (Level of Evidence – 5)
Comments: Unjustified administration of antipyretic drugs should be discouraged: in healthy children older than 3 months, they should be prescribed if the child's body temperature exceeds 39.0°C (measured rectally) or 38.5°C (measured subaxillary) and/or in the presence of myalgia and headache [77,78]. Unjustified pharmacological fever management can impede the objective assessment of the efficacy of initiated antimicrobial therapy in streptococcal acute tonsillopharyngitis. In pediatric practice, one should be limited to the use of paracetamol** and ibuprofen**.
Doses of ibuprofen** (ATC code: M01AE01) – 200–400 mg in adults and 7.5 mg/kg in children every 6–8 h (maximum 30 mg/kg/day)
Doses of paracetamol** (ATC code: N02BE01) – 500–1000 mg in adults and 10–15 mg/kg in children every 6 h (maximum 60 mg/kg/day)
Doses of acetylsalicylic acid** (ATC code: N02BA01) – in children over 15 years and adults 0.5–1 g (no more than 3 g per day)
Doses of ketoprofen** (ATC code: M01AE03) 100 mg 1–2 times daily orally and/or rectally in adults and children over 15 years
Doses of ketoprofen** (as lysine salt, oral powder for oral solution) (ATC code: M01AE03): 80 mg 2–3 times daily orally in adults and children over 14 years, 40 mg 2–3 times daily orally in children from 6 to 14 years
Routine use of systemic corticosteroids for sore throat is not recommended [9,79,80],
GCR BLoE 1Grade of Recommendation B (Level of Evidence – 1)
except in special situations (severe discomfort, risk of asphyxia (e.g., in infectious mononucleosis) – #dexamethasone** at a single oral dose of 0.3 or 0.6 mg/kg or #prednisolone** 1 mg/kg may be prescribed once [79–83]
LeR BLoE 1Level of Evidence B (Level of Evidence – 1).
Comment: A single dose of a systemic corticosteroid drug does not cause serious adverse reactions. At the same time, there is currently insufficient high-quality research to definitively recommend these drugs for sore throat, as well as regarding the duration of their use. The rapid effect of systemic antibacterial drugs in streptococcal acute tonsillopharyngitis and the potential for adverse effects of systemic corticosteroids are arguments against the use of systemic corticosteroids in this clinical situation.
It is recommended to use herbal preparations that exert a complex effect on key links of the pathogenesis of acute tonsillopharyngitis as adjunctive treatment for acute tonsillopharyngitis, including recurrent tonsillopharyngitis, in courses during the inter-recidive period to prevent recurrences of acute tonsillitis [84–86].
RG CLE 5Recommendation Grade C (Level of Evidence 5).
Comments: to achieve the predictable clinical effect and minimize adverse events, preparations containing marshmallow root, chamomile flowers, yarrow herb, oak bark, horsetail herb, walnut leaves, and common dandelion herb are used (ATC code: R02AA20 Other antiseptics). The complex effect includes anti-inflammatory, immunomodulatory, antibacterial, and antiviral properties. Recommended dosages, frequency, duration of administration, and age restrictions should be observed.
It is recommended to prescribe topical local anesthetics (ATX code: R02AD) and non-steroidal anti-inflammatory drugs (ATX code: R02AX Other throat preparation products) as single agents or in fixed combinations for patients with acute tonsillopharyngitis experiencing severe sore throat, taking into account necessity, tolerability, and the patient's age, for example:
- benzydamine (contraindicated in children under 3 years of age) (ATX code: A01AD02)
- benzocaine + chlorhexidine (ATX code: D04AB04) (for patients over 4 years of age)
- amylmetacresol + dichlorobenzyl alcohol + lidocaine (ATX code: R02AA03 Dichlorobenzyl alcohol and R02AA20 Other antiseptics) (for patients over 12 years of age); lidocaine + lysozyme + cetylpyridinium chloride (ATX code: R02AA Antiseptics) (for patients over 18 years of age); benzoxonium chloride + lidocaine (ATX code: R02AA20) (for patients over 4 years of age);
- flurbiprofen (ATX code: R02AX01) (for patients over 12 years of age); flurbiprofen + cetylpyridinium chloride (ATX code: R02A Throat preparation products) (for patients over 18 years of age); benzyldimethyl-myristoylamino-propylammonium + flurbiprofen (ATX code: R02AX Other throat preparation products) (for patients over 18 years of age);
- ketoprofen** (contraindicated in children under 12 years of age) (ATX code: A01AD11), etc. [74-76,87-89].
GCR CLEL 5Grade of Recommendation C (Level of Evidence – 5).
Comments: The purpose of local treatment for acute tonsillopharyngitis is to relieve disease symptoms as quickly as possible.
Topical medications (ATX code: R02A Throat preparation products) are available as sprays, gargle solutions, or lozenges. In children lacking gargling skills and due to the risk of aspiration from lozenges, the spray form is preferred. Due to the risk of reactive laryngospasm, topical throat preparations (ATX code: R02A Throat preparation products) are prescribed starting from the age of – 3–4 years. Local remedies in the form of "rubbing" or "lubricating" the tonsils should not be routinely used for sore throat, and plaque should not be removed mechanically.
It should be remembered that local treatment cannot replace systemic antibacterial drugs in acute tonsillopharyngitis caused by group A beta-hemolytic streptococcus [9].
3.1.1. Diet therapy.
Patients suffering from acute tonsillopharyngitis are advised to limit irritating foods. Food should have a soft consistency.
It is recommended for all patients suffering from acute tonsillopharyngitis to limit irritating foods (spicy, sour, salty, hot, cold, etc., while food should have a soft consistency) [90,91].
GCR CLEL 5Grade of Recommendation C (Level of Evidence – 5)
3.2. Surgical treatment
It is not recommended to perform surgical treatment in uncomplicated acute tonsillopharyngitis [9,35,89,92].
GCR CLEL 5Grade of Recommendation C (Level of Evidence – 5)
4. Medical Rehabilitation and Sanatorium-Resort Treatment
Not required.
5. Prevention and Dispensary Observation
5.1. Prevention
Specific prophylaxis for group A beta-hemolytic streptococcus acute tonsillopharyngitis does not exist.
It is recommended to limit contacts of patients with acute tonsillopharyngitis to prevent airborne transmission of the infection [5].
GCR CLEL 5Grade of Recommendation C (Level of Evidence – 5)
It is recommended to isolate patients with acute streptococcal tonsillopharyngitis from organized groups to avoid outbreaks of streptococcal infection (scarlet fever in cases caused by toxigenic strains of group A beta-hemolytic streptococcus) [5].
GCR CLEL 5Grade of Recommendation C (Level of Evidence – 5)
It is recommended to prophylactically prescribe systemic antibacterial drugs to certain categories of patients in close household contact with a patient suffering from group A beta-hemolytic streptococcus infection, in order to prevent the disease in highly vulnerable populations and prevent the development of invasive forms of group A beta-hemolytic streptococcus infection [93].
GCR CLEL 5Grade of Recommendation C (Level of Evidence – 5)
Comments: Household contact is defined as prolonged contact with a patient at home within 7 days prior to symptom onset and/or within the first 24 hours after starting antibacterial therapy upon diagnosis of group A beta-hemolytic streptococcus infection. Antibiotic prophylaxis after close contact is indicated for:
- Pregnant women with a gestational age of ≥37 weeks;
- Newborns and women within the first 28 days postpartum;
- Elderly patients (≥75 years).
It is recommended for patients with recurrent forms of acute tonsillopharyngitis to use dietary supplements containing microorganisms belonging to the indigenous bacteria of the oropharyngeal mucosa, in order to prevent recurrences and restore the normal oropharyngeal mucosal microbiome after the illness [94-96].
GRC CLEL 4Grade of Recommendation C (Level of Evidence – 4)
Comments: Such remedies include those containing S. salivarius strain K12, which produces inhibitory substances (BLIS) – antimicrobial peptides [94-96].
It is recommended for patients with recurrent forms of acute tonsillopharyngitis to prescribe drugs from the other immunostimulants group (ATX code: L03AX) (from the bacterial lysates group) for the prevention of relapses [97,98]
GCR BLoE 3Level of Evidence B (Level of Confidence of Evidence – 3)
5.2. Dispensary follow-up
Carried out as necessary in accordance with Sanitary and Epidemiological Rules SP 3.1.2. 3149-13 [99]:
after discharge from the hospital (recovery) from group A beta-hemolytic streptococcus acute tonsillopharyngitis, establish clinical follow-up (dispensary observation) for one month with a complete blood count (CBC) and urinalysis checked after 7–10 days and 3 weeks; if there are complaints or clinical manifestations of (or suspected) cardiovascular complications, perform an electrocardiography additionally
if no abnormalities are found, patients are removed from clinical follow-up after one month.
For children discharged from the hospital after group A beta-hemolytic streptococcus acute tonsillopharyngitis, if abnormalities are detected during physical examination, laboratory, and/or instrumental studies, consultation and/or monitoring by an appropriate specialist is required (a nephrologist for urinalysis abnormalities, a rheumatologist for clinical and/or laboratory signs of rheumatic fever, a pediatric cardiologist for signs of cardiovascular involvement)
6. Organization of Medical Care
Organization of medical care, indications for hospitalization and discharge
Medical care is organized in accordance with the Patient Management Algorithm (Appendix B).
Treatment in most cases is carried out on an outpatient basis by a pediatrician, general practitioner (family doctor), therapist, or infectious disease specialist.
Improvement after the start of antimicrobial therapy in acute tonsillitis caused by group A beta-hemolytic streptococcus is observed within 12–24 hours. The patient is not required to stay at home for the entire duration of antibiotic intake (10 days). According to Methodological Guidelines MU 3.1.1885-04 "Epidemiological surveillance and prevention of group A streptococcal infection": "Admission to childcare facilities is permitted after complete clinical recovery" [100].
Hospitalization in an infectious diseases department, or in a boxed pediatric department if unavailable, is required for patients in serious condition and when infusion therapy is necessary due to the child's refusal of food and drink.
Treatment failure, suspicion of a purulent complication (peritonsillar, parapharyngeal, retropharyngeal abscess, purulent lymphadenitis), atypical pharyngoscopic picture (suspicion of a neoplasm), and the need for surgical intervention (abscess drainage, biopsy, tonsillectomy) are indications for a consultation with an otorhinolaryngologist and hospitalization in the appropriate surgical department.
Discharge from the hospital is carried out with stable relief of disease manifestations and the absence of a threat to the patient's life and health.
7. Additional Information
The prognosis of acute tonsillopharyngitis is favorable in most cases.
The risk of purulent complications increases in the presence of primary and acquired immunodeficiency states (congenital immunodeficiency, immunosuppressive and cytostatic therapy, HIV infection). The risk of autoimmune complications increases in patients with a history of acute rheumatic fever and in their close relatives.
Complications
Lack of treatment or inadequate treatment of streptococcal tonsillitis is fraught with a high probability of developing serious purulent complications:
peritonsillar, parapharyngeal, retropharyngeal abscesses,
purulent lymphadenitis;
as well as non-purulent complications:
acute rheumatic fever,
rheumatic heart disease,
post-streptococcal glomerulonephritis,
streptococcal toxic shock syndrome (Strep TSS),
PANDAS syndrome.
Any case of acute tonsillopharyngitis with a probable group A beta-hemolytic streptococcus etiology requires etiological diagnosis.
Criteria for Evaluating the Quality of Medical Care
Criteria for evaluating the quality of primary health care in adults and children with acute tonsillitis and pharyngitis (ICD-10 codes: J02, J02.0, J02.8, J02.9, J03, J03.0, J03.8, J03.9)
No. | Quality assessment criteria | Performance evaluation |
|---|---|---|
1. | An initial examination (inspection, consultation) by an otorhinolaryngologist and/or an initial examination (inspection, consultation) by a pediatrician, and/or an initial examination (inspection, consultation) by a general practitioner (family doctor), and/or an initial examination (inspection, consultation) by a therapist was performed | Yes/No |
2. | Systemic antibacterial drugs were prescribed (upon confirmation of the etiological factor of group A beta-hemolytic streptococcus etiology or high probability thereof, depending on medical indications and in the absence of medical contraindications) | Yes/No |
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Shpynev K.V., Krechikova O.I., Krechikov V.A., Kozlov R.S. Streptococcus pyogenes: microorganism characteristics, isolation, identification, and determination of susceptibility to antibacterial drugs. Klinicheskaya mikrobiologiya i antimikrobnaya khimioterapiya. 2007;9(2):104-120
Andreeva I.V., Stetsyuk O.U., Azovskova O.V., Kozlov R.S. Therapy of acute tonsillopharyngitis: current guidelines and Russian specifics. Klinicheskaya mikrobiologiya i antimikrobnaya khimioterapiya. 2013;15(3):198-211
Casey J.R., Pichichero M.E. Higher dosages of azithromycin are more effective in treatment of group A streptococcal tonsillopharyngitis. Clin Infect Dis. 2005; 40 (12): 1748-55].
Addy LD, Martin MV. Clindamycin and dentistry. Br Dent J. 2005 Jul 9;199(1):23-6. doi: 10.1038/sj.bdj.4812535.
Bombassaro AM, Wetmore SJ, John MA. Clostridium difficile colitis following antibiotic prophylaxis for dental procedures. J Can Dent Assoc. 2001 Jan;67(1):20-2.
Seppala H, Nissinen A, Jarvinen H, et al. Resistance to erythromycin in group A streptococci. N Engl J Med 1992; 326:292–7.
Kaplan EL, Gooch III WM, Notario GF, Craft JC. Macrolide therapy of group A streptococcal pharyngitis: 10 days of macrolide therapy (clarithromycin) is more effective in streptococcal eradication than 5 days (azithromycin). Clin Infect Dis. 2001 Jun 15;32(12):1798-802. doi: 10.1086/320745.
Spinks A, Glasziou PP, Del Mar CB. Antibiotics for sore throat. Cochrane Database Syst Rev. 2013 Nov 5;2013(11):CD000023.
Linder JA, Bates DW, Lee GM, Finkelstein JA. Antibiotic treatment of children with sore throat. JAMA 2005; 294:2315–22.
ESCMID Sore Throat Guideline Group, Pelucchi C, Grigoryan L, Galeone C, Esposito S, Huovinen P, Little P, Verheij T. Guideline for the management of acute sore throat. Clin Microbiol Infect. 2012 Apr;18 Suppl 1:1-28. doi: 10.1111/j.1469-0691.2012.03766.x. PMID: 22432746.
Passali D., Volonte M., Passali G.S. et al. Efficacy and safety of ketoprofen lysine salt mouthwash versus benzydamine hydrochloride mouthwash in acute pharyngeal inflammation: a randomized, single-blind study//Clin Ther.-2001;23(9):1508-1518.
Bellussi L., Biagini C. Antiphlogistic therapy with ketoptofen lisyne salt vs nimesulide in secretive otitis media, rhinitis, pharyngitis/tonsillitis/tracheitis //Otorinolaringol.-1996.- 46.- 49-57
Passàli D, Volonté M, Passàli GC, Damiani V, Bellussi L; MISTRAL Italian Study Group. Efficacy and safety of ketoprofen lysine salt mouthwash versus benzydamine hydrochloride mouthwash in acute pharyngeal inflammation: a randomized, single-blind study. Clin Ther. 2001;23(9):1508-1518. doi:10.1016/s0149-2918(01)80123-5.
Hospital care for children. Guidelines for the management of common childhood illnesses. Pocket book, 2nd edition, 2013. 438 p., available at: https://apps.who.int/iris/bitstream/handle/10665/81170/9789244548370_rus.pdf;jsessionid=E08C86828B1316B6889FF0F714AD83B2?sequence=7
Federal clinical guidelines for providing emergency medical care for acute fever in children. Ministry of Health of the Russian Federation. Union of Pediatricians of Russia. Russian Society of Emergency Medical Care. Moscow: 2015. 10 p.
Sadeghirad B, Siemieniuk RAC, Brignardello-Petersen R, et al. Corticosteroids for treatment of sore throat: systematic review and meta-analysis of randomised trials. BMJ. 2017;358:j3887. Published 2017 Sep 20. doi:10.1136/bmj.j3887
de Cassan S, Thompson MJ, Perera R, et al. Corticosteroids as standalone or add-on treatment for sore throat. Cochrane Database Syst Rev. 2020;5(5):CD008268. Published 2020 May 1. doi:10.1002/14651858.CD008268.pub3
Rezk E, Nofal YH, Hamzeh A, Aboujaib MF, AlKheder MA, Al Hammad MF. Steroids for symptom control in infectious mononucleosis. Cochrane Database Syst Rev. 2015;2015(11):CD004402. Published 2015 Nov 8. doi:10.1002/14651858.CD004402.pub3
Olympia RP, Khine H, Avner JR. Effectiveness of oral dexamethasone in the treatment of moderate to severe pharyngitis in children. Arch Pediatr Adolesc Med. 2005;159(3):278-282. doi:10.1001/archpedi.159.3.278
Thomas M, Del Mar C, Glasziou P. How effective are treatments other than antibiotics for acute sore throat? Br J Gen Pract. 2000;50(459):817-820
V. Popovych, I. Koshel, A. Malofiichuk et al. A randomized, open-label, multicenter, comparative study of therapeutic efficacy, safety and tolerability of BNO 1030 extract, containing marshmallow root, chamomile flowers, horsetail herb, walnut leaves, yarrow herb, oak bark, dandelion herb in the treatment of acute nonbacterial tonsillitis in children aged 6 to 18 years. Am J Otolaryngol 40 (2019) 265–273.
Dronov I.A., Geppe N.A., Kolosova N.G., Velikoretskaya M.D. Use of a complex herbal medicinal product in the treatment of recurrent tonsillopharyngitis in children. Voprosy prakticheskoy pediatrii. 2020;15(4):16–24. DOI: 10.20953/1817-7646-2020-4-16-
Vavilova V.P., Abramov-Sommariva D., Steindl G. et al. Clinical efficacy and tolerability of Tonsilgon® N in the treatment of recurrent upper respiratory tract infections in children: a non-interventional study in Russia. RMZh. 2017;5:350–358
Namazova-Baranova L.S., Kharit S.M., Tuzankina I.A., Kozhevnikova T.N., Taranushenko T.E., Alekseeva A.A. Results of a multicenter study on the use of pidotimod for the prevention of acute respiratory infections in frequently ill children. Voprosy sovremennoy pediatrii. 2010;9(2):40-44
Nikiforova G.N., Volkova K.B. New therapeutic options for inflammatory pharyngeal diseases. Consilium Medicum. 2015;17(11):103-107.
Katharine C. Degeorge, MD, MS; Daniel J. Ring, MD; and Sarah N. Dalrymple, MD, Treatment of the Common Cold. Am Fam Physician. 2019 Sep 1;100(5):281-289.
Palchun V.T. et al. Inflammatory diseases of the pharynx: a guide for physicians / V.T. Palchun, L.A. Luchikhin, A.I. Kryukov. – Moscow: GEOTAR-Media, 2012. – 288 p.
Klyaritskaya I.L., Maksimova E.V., Grigorenko E.I. et al. Modern aspects of dietotherapy in the Russian Federation. Krymskiy terapevticheskiy zhurnal. 2018;2:26-31.
Daikhes N.A., Davudov Kh.Sh., Shkoda A.S., Elkun G.B. Rational choice of analgesic therapy in patients after tonsillectomy. Vestnik otorinolaringologii. 2006;6:66-68
Jain N, Lansiaux E, Reinis A. Group A streptococcal (GAS) infections amongst children in Europe: Taming the rising tide. New Microbes New Infect. 2022 Dec 15;51:101071. doi: 10.1016/j.nmni.2022.101071.
Gregori G., Righi O., Risso P. et al. Reduction of group A beta-hemolytic streptococcus pharyngo-tonsillar infections associated with use of the oral probiotic Streptococcus salivarius K12: a retrospective observational study // Ther. Clin. Risk Manag. 2016. Vol. 12. P. 87–92.
Di Pierro F., Adami T., Rapacioli G. et al. Clinical evaluation of the oral probiotic Streptococcus salivarius K12 in the prevention of recurrent pharyngitis and/or tonsillitis caused by Streptococcus pyogenes in adults // Expert Opin. Biol. Ther. 2013. Vol. 13. № 3. P. 339–343.
Di Pierro F, Colombo M, Zanvit A, Risso P, Rottoli AS. Use of Streptococcus salivarius K12 in the prevention of streptococcal and viral pharyngotonsillitis in children. Drug Healthc Patient Saf. 2014 Feb 13;6:15-20. doi: 10.2147/DHPS.S59665.
Bitar MA, Saade R. The role of OM-85 BV (Broncho-Vaxom) in preventing recurrent acute tonsillitis in children. Int J Pediatr Otorhinolaryngol. 2013;77(5):670-3. doi: 10.1016/j.ijporl.2013.01.009;
Schaad UB. OM-85 BV, an immunostimulant in pediatric recurrent respiratory tract infections: a systematic review. World J Pediatr. 2010 Feb;6(1):5-12. doi: 10.1007/s12519-010-0001-x.
Prevention of streptococcal (group A) infection. Sanitary and epidemiological rules SP 3.1.2.3149-13. Approved by the Resolution of the Acting Chief State Sanitary Doctor of the Russian Federation dated December 18, 2013, No. 66. https://www.rospotrebnadzor.ru/documents/details.php?ELEMENT_ID=1773.
"Epidemiological surveillance and prevention of streptococcal (group A) infection. Guidelines. MU 3.1.1885-04" (approved by Rospotrebnadzor on 04.03.2004).
Centor RM, Witherspoon JM, Dalton HP, Brody CE, Link K. The diagnosis of strep throat in adults in the emergency room. Med Decis Making 1981; 1: 239–246.
Appendix A1. Working Group Composition
Daikhes N.A., DSc, Professor, Corresponding Member of the Russian Academy of Sciences, Member of the National Medical Association of Otorhinolaryngologists
Baranov A.A., Academician of the Russian Academy of Sciences, Professor, DSc, Honorary President of the Union of Pediatricians of Russia
Lobzin Yu.V., Academician of the Russian Academy of Sciences, Professor, DSc, President of the International Public Organization "Euro-Asian Society of Infectious Diseases" (EASID)
Namazova-Baranova L.S., Academician of the Russian Academy of Sciences, Professor, DSc, President of the Union of Pediatricians of Russia
Kozlov R.S., Corresponding Member of the Russian Academy of Sciences, Professor, DSc, President of the Interregional Association for Clinical Microbiology and Antimicrobial Chemotherapy (MACMAH)
Polyakov D.P., PhD, Member of the National Medical Association of Otorhinolaryngologists
Karneeva O.V., DSc, Professor, Member of the National Medical Association of Otorhinolaryngologists
Gurov A.V., DSc, Professor, Member of the National Medical Association of Otorhinolaryngologists, Member of the Alliance of Clinical Chemotherapists and Microbiologists
Tulupov D.A., PhD, Member of the National Medical Association of Otorhinolaryngologists
Ryazantsev S.V., DSc, Professor, Member of the National Medical Association of Otorhinolaryngologists
Garashchenko T.I., DSc, Professor, Member of the National Medical Association of Otorhinolaryngologists
Kim I.A., DSc, Professor, Member of the National Medical Association of Otorhinolaryngologists
Andreeva I.V., Senior Researcher, Associate Professor, Member of MACMAH
Bakradze M.D., DSc, Professor, Member of the Union of Pediatricians of Russia
Polyakova A.S., PhD, Member of the Union of Pediatricians of Russia
Vishneva E.A., DSc, Professor of the Russian Academy of Sciences, Member of the Union of Pediatricians of Russia
Selimzyanova L.R., PhD, Member of the Union of Pediatricians of Russia
Tatochenko V.K., DSc, Professor, Member of the Union of Pediatricians of Russia
Kulichenko T.V., DSc, Professor of the Russian Academy of Sciences, Member of the Union of Pediatricians 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
General practitioners (family physicians)
Infectious disease specialists
Otolaryngologists
Medical students
Residents
The methodology for developing clinical guidelines is based on a comprehensive analysis of the current state of the problem, literature data, and regulatory legal acts, followed by discussion within the professional community and amendments based on the results of resolutions of conferences and national congresses, provided they are approved by the Ministry of Health.
These clinical guidelines summarize the authors' experience in the diagnosis and treatment of patients with acute sinusitis. The clinical guidelines contain information necessary for the diagnosis, differential diagnosis, and selection of treatment methods for patients with acute sinusitis.
Methods used for evidence collection/selection:
electronic database searching.
Description of methods used for evidence collection/selection:
the evidence base for the guidelines includes publications included in the Cochrane Library, EMBASE, and MEDLINE databases. The search depth was 10 years.
Methods used to assess the quality and strength of evidence:
Expert consensus;
Assessment of significance in accordance with the rating scale.
Target audience of the clinical guidelines:
general practitioners (family doctors);
otorhinolaryngologists;
otorhinolaryngologist-audiologists;
pediatricians;
urban (district) pediatricians; district pediatricians;
emergency medicine physicians;
senior physicians of emergency medical service stations (departments);
general practitioners (internal medicine);
adolescent general practitioners;
district general practitioners;
district internists of occupational medical districts; infectious disease specialists; ship doctors.
Table 1.Scale for assessing levels of evidence (LE) for diagnostic methods (diagnostic interventions)
LoE | Definition |
|---|---|
1 | Systematic reviews of studies with reference standard control or systematic reviews of randomized controlled trials with meta-analysis |
2 | Individual studies with reference standard control or individual randomized controlled trials and systematic reviews of studies of any design, except randomized controlled trials, with meta-analysis |
3 | Studies without consecutive reference standard control or studies with a reference standard not independent of the test method, or non-randomized comparative studies, including cohort studies |
4 | Non-comparative studies, case report |
5 | Only justification of mechanism of action or expert opinion is available |
Table 2. Scale for grading levels of evidence certainty (LEC) for prevention, treatment, and rehabilitation methods (preventive, therapeutic, and rehabilitative interventions)
LoE | Definition |
|---|---|
1 | Systematic review of RCTs with meta-analysis |
2 | Individual RCTs and systematic reviews of studies of any design except RCTs, with meta-analysis |
3 | Non-randomized comparative studies, including cohort studies |
4 | Non-comparative studies, case reports or case series, case-control studies |
5 | Only justification of the mechanism of action of the intervention (preclinical studies) or expert opinion is available |
Methods used for evidence analysis:
Reviews of published meta-analyses;
Systematic reviews with evidence tables.
Description of methods used for evidence analysis:
When selecting publications as potential sources of evidence, the methodology used in each study is examined to ensure its validity. The result of this examination affects the level of evidence assigned to the publication, which in turn affects the strength of the recommendations derived from it.
The subjective factor can undoubtedly influence the assessment process. To minimize potential errors, each study was evaluated independently, i.e., by at least two independent members of the working group. Any discrepancies in assessments were discussed by the full working group. If consensus could not be reached, an independent expert was involved.
Evidence tables:
Evidence tables were completed by the members of the working group.
Methods used to formulate the recommendations:
Expert consensus.
Economic analysis:
Cost analysis was not performed, and pharmacoeconomic publications were not analyzed.
Method of recommendation validation:
External peer review;
Internal expert review.
Description of the guideline validation method:
The preliminary version of these guidelines was reviewed by independent experts, who were asked to comment primarily on how accessible the interpretation of the evidence underlying the recommendations is for understanding.
Comments were received from primary care physicians regarding the clarity of the presentation of the guidelines and their assessment of the importance of the recommendations as a working tool in daily practice.
The preliminary version was also sent to a non-medical reviewer for comments from the patients' perspective.
Comments received from experts were carefully systematized and discussed by the chair and members of the working group. Each point was discussed, and the resulting changes made to the recommendations were logged. If no changes were made, the reasons for refusing to make changes were logged.
Consultation and peer review:
The draft guidelines were reviewed by independent experts, who were asked to comment primarily on the clarity and accuracy of the interpretation of the evidence base underlying the recommendations.
Working Group:
For the final revision and quality control, the recommendations were re-evaluated by the members of the working group, who concluded that all comments and feedback from the experts had been taken into account and the risk of bias in the development of the recommendations was minimized.
Procedure for updating clinical guidelines.
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.
Table 3. Scale for grading levels of recommendation certainty (LRC) for prevention, diagnostic, treatment, and rehabilitation methods (preventive, diagnostic, therapeutic, and rehabilitative interventions)
GoR | Definition |
|---|---|
A | Strong recommendation (all considered efficacy criteria (outcomes) are important, all studies are of high or acceptable methodological quality, and their conclusions on the outcomes of interest are consistent) |
B | Conditional recommendation (not all considered efficacy criteria (outcomes) are important, not all studies are of high or acceptable methodological quality, and/or their conclusions on the outcomes of interest are inconsistent) |
C | Weak recommendation (lack of adequate quality evidence (all considered efficacy criteria (outcomes) are unimportant, all studies have low methodological quality, and their conclusions on the outcomes of interest are inconsistent)) |
Economic analysis:
Cost analysis was not performed, and pharmacoeconomic publications were not analyzed.
Method of recommendation validation:
External peer review;
Internal expert review.
Description of the guideline validation method:
The preliminary version of these guidelines was reviewed by independent experts, who were asked to comment primarily on how accessible the interpretation of the evidence underlying the recommendations is for understanding.
Feedback was obtained from primary care physicians and district therapists regarding the clarity of the recommendations and their assessment of the recommendations as a practical tool for daily practice.
The preliminary version was also sent to a non-medical reviewer for comments from the patients' perspective.
Comments received from experts were carefully systematized and discussed by the chair and members of the working group. Each point was discussed, and the resulting changes made to the recommendations were logged. If no changes were made, the reasons for refusing to make changes were logged.
Consultation and peer review:
The draft guidelines were reviewed by independent experts, who were asked to comment primarily on the clarity and accuracy of the interpretation of the evidence base underlying the recommendations.
Working Group:
For the final revision and quality control, the recommendations were re-evaluated by the members of the working group, who concluded that all comments and feedback from the experts had been taken into account and the risk of bias in the development of the recommendations was minimized.
Procedure for updating clinical guidelines.
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
Regulatory and legal documents
Procedure for the provision of medical care in the specialty of "otorhinolaryngology": Order of the Ministry of Health of the Russian Federation No. 905n dated November 12, 2012, "On Approval of the Procedure for the Provision of Medical Care to the Population in the Specialty of 'Otorhinolaryngology'." 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";
Order of the Ministry of Health and Social Development of the Russian Federation dated May 5, 2012, No. 521n "On approval of the Procedure for providing medical care to children with infectious diseases"
State Register of Medicinal Products: https://grls.rosminzdrav.ru
Order of the Ministry of Health of the Russian Federation dated May 2, 2023, No. 205n "On approval of the nomenclature of positions of medical workers and pharmaceutical workers".
Order of the Ministry of Health of the Russian Federation No. 541n dated July 23, 2010. "Unified Qualification Handbook of Positions of Managers, Specialists, and Employees, Section: Qualification Characteristics of Positions of Healthcare Workers."
Federal Law No. 489-FZ dated December 25, 2018, "On Amendments to Article 40 of the Federal Law 'On Compulsory Medical Insurance in the Russian Federation' and the Federal Law 'On the Basics of Protecting the Health of Citizens in the Russian Federation' regarding Clinical Guidelines."
Order of the Russian Ministry of Health No. 103n dated February 28, 2019, "On approval of the procedure and timelines for the development of clinical guidelines, their revision, the standard template of clinical guidelines, and requirements for their structure, composition, and scientific validity of the information included in the clinical guidelines."
Order of the Ministry of Health of the Russian Federation No. 804n dated October 13, 2017 "On approval of the nomenclature of medical services".
Order of the Ministry of Health of the Russian Federation No. 1094n dated November 24, 2021 "On approval of the Procedure for prescribing medicinal products, prescription forms for medicinal products, the Procedure for issuing said forms, their accounting and storage, forms of prescriptions containing appointments of narcotic drugs or psychotropic substances, the Procedure for their manufacture, distribution, registration, accounting and storage, as well as the Rules for issuing prescription forms, including in the form of electronic documents"
"Epidemiological surveillance and prevention of streptococcal (group A) infection". Guidelines. MU 3.1.1885-04 (Approved by the Chief State Sanitary Doctor of the RF on 04.03.2004).
"Epidemiological surveillance of diphtheria infection". Guidelines. MU 3.1.1082-01 (Approved by the Chief State Sanitary Doctor of the RF on 09.11.2001).
Prevention of streptococcal (group A) infection. Sanitary and epidemiological rules SP 3.1.2.3149-13. Approved by the Resolution of the Acting Chief State Sanitary Doctor of the Russian Federation dated December 18, 2013, No. 66. https://www.rospotrebnadzor.ru/documents/details.php?ELEMENT_ID=1773
Note legend
** – a medicinal product included in the Decree of the Government of the Russian Federation No. 2406-r dated October 12, 2019 (as amended on June 9, 2023) "On Approval of the List of Vital and Essential Medicines, 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 by decision of the medical commission provided that signed informed voluntary consent is obtained (pursuant to Federal Law No. 323-FZ dated November 21, 2011, as amended). Requires the following procedure:
Justification of the need to prescribe an "off-label" medicinal product in the medical record.
Conduction of the medical commission of the medical organization.
Signing of voluntary informed consent by the patient/patient's legal representative (for minors). The consent form must be approved within the medical organization.
According to:
- clause 5 of Federal Law No. 323-FZ dated November 21, 2011, "On the fundamentals of protecting the health of citizens in the Russian Federation"
- Order of the Ministry of Health and Social Development of the Russian Federation dated August 9, 2005, No. 494 "On the procedure for the use of medicinal products in patients for vital indications"
- Order dated May 5, 2012, No. 502n "On approval of the Procedure for the establishment and activities of the medical commission of a medical organization"
Appendix B. Physician Action Algorithms
Appendix C. Patient Information
Acute tonsillitis (throat inflammation, sometimes also called «angina») is inflammation of the tonsils, usually accompanied by a sore throat and fever, and possibly the appearance of plaque on the tonsils. Acute pharyngitis is inflammation of the posterior pharyngeal wall. As a rule, these two processes occur concurrently, which is why doctors use the term acute tonsillopharyngitis. Acute tonsillopharyngitis can be caused by viruses or bacteria. The only bacterial tonsillopharyngitis that requires antibacterial therapy is tonsillitis caused by group A beta-hemolytic streptococcus (or Streptococcus pyogenes). Other microbes may be present in the oral cavity normally (e.g., Staphylococcus aureus).
Viral acute tonsillopharyngitis resolves on its own within 1–2 weeks. Antibiotics do not speed up recovery in this disease. Moreover, taking antibiotics unnecessarily can cause harm by promoting the emergence of resistant bacteria and increasing the risk of adverse reactions.
Streptococcal tonsillopharyngitis presents with a sore throat, a significant fever (38°C and above), tonsillar swelling, and in most cases, white spots or purulent plaque on the mucosa of the tonsils, palate, and posterior pharyngeal wall, as well as enlarged and tender cervical lymph nodes. The disease is contagious and most common in children aged 5 to 15 years.
Based on external signs alone, it is difficult to determine precisely whether the disease is caused by a virus or bacteria, as the clinical presentation can be similar. Based on clinical manifestations, a physician may suspect a streptococcal etiology, but a special microbiological examination is required to confirm the diagnosis. There are classical diagnostic methods and rapid testing that allow for a quick diagnosis and prescription of treatment.
If you or your child has been prescribed antibiotics, it is very important to take the medication exactly as prescribed by the doctor, strictly observing the full course of treatment, even if you or your child feels significantly better much earlier or all symptoms have disappeared. The standard course of antibiotics for acute streptococcal tonsillitis is 10 days. Only this duration of treatment ensures the eradication of the streptococcus (i.e., helps to get rid of it completely).
In most cases, acute tonsillopharyngitis is accompanied by pain upon swallowing, so patients are recommended to consume warm, soft foods that are easier to swallow.
In case of fever or severe sore throat, paracetamol** or ibuprofen** may be used. Gargling with analgesic solutions is also effective. Anti-inflammatory and analgesic medications in the form of sprays or lozenges/pastilles for resorption may be used (depending on the patient's age and preferences). Consult a doctor to choose the most appropriate medication for you or your child and to determine the necessity of such treatment.
Viruses and bacteria spread when hands touch the mouth, nose, or eyes. Frequent handwashing with warm water and soap helps prevent infection.
Appendix G. Assessment Scales, Questionnaires, and Other Evaluation Tools
Appendix G1. Modified Centor score and McIsaac score [16,101]
Source: Fine AM, Nizet V, Mandl KD. Large-scale validation of the Centor and McIsaac scores to predict group A streptococcal pharyngitis. Arch Intern Med. 2012;172(11):847-852. doi:10.1001/archinternmed.2012.950.
Type: rating scale
Indication: differential diagnosis of viral and streptococcal ATP based on clinical presentation
Content (template):
Table 1 Point scoring system for symptoms in a patient with a sore throat
Symptoms of acute tonsillopharyngitis | Score | |
|---|---|---|
Body temperature >38°C | 1 point | |
Tonsillar swelling and hyperemia, exudate on the posterior pharyngeal wall and tonsils | 1 point | |
Absence of catarrhal symptoms and cough | 1 point | |
Anterior cervical and/or submandibular lymphadenitis (enlarged and tender lymph nodes) | 1 point | |
Age | 5-14 years 15-44 years ≥45 years | 1 point 0 points - 1 point |
Key (interpretation):
Table 2 McIsaac score: Patient management strategy based on the score in ATP
Point score | Probability of streptococcal infection | Suggested patient management strategy | |
|---|---|---|---|
Patients ≥15 years | Patients 3-14 years | ||
0 points | 7% | 8% | No indication for bacteriological examination and/or antibiotic prescription |
1 point | 12% | 14% | |
2 points | 21% | 23% | Antibiotic therapy based on rapid test and/or bacteriological examination results |
3 points | 38% | 37% | |
≥ 4 points | 57% | 55% | Antibiotic therapy based on clinical presentation |
Explanations
First, it is recommended to evaluate the symptoms of a patient with a sore throat using the point scale (Table 1), assess the probability of GAS, and then decide whether to prescribe antibiotic therapy (Table 2) [16].
Appendix G2. Modified FeverPAIN Score [15]
Source: Little P, Hobbs FD, Moore M, Mant D, Williamson I, McNulty C, Cheng YE, Leydon G, McManus R, Kelly J, Barnett J, Glasziou P, Mullee M; PRISM investigators. Clinical score and rapid antigen detection test to guide antibiotic use for sore throats: randomised controlled trial of PRISM (primary care streptococcal management). BMJ. 2013 Oct 10;347:f5806. doi: 10.1136/bmj.f5806. Erratum in: BMJ. 2018 Mar 5;360:k1068. doi: 10.1136/bmj.k1068. PMID: 24114306; PMCID: PMC3805475.
Type: rating scale
Indication: differential diagnosis of viral and streptococcal ATP based on clinical presentation
Content (template):
Table 2 Point scoring system for symptoms in a patient with a sore throat
Clinical sign | Points |
|---|---|
Fever within the last 24 hours | +1 |
Exudate on the tonsils | +1 |
Seeking medical attention within the last 3 days due to symptom severity | +1 |
Pronounced hyperemia and edema of the palatine tonsils | +1 |
Absence of cough or rhinitis | +1 |
Key (interpretation):
Interpretation (probability of ATP caused by group A, C, G beta-hemolytic streptococci)
0-2 points – 16% probability of GAS/C/G |
|---|
3 points – 43% probability of GAS/C/G |
4-5 points – 63% probability of GAS/C/G |