List of Abbreviations
ESBL — extended-spectrum beta-lactamases
HIV – human immunodeficiency virus
SWL — shock wave lithotripsy
VLEL – vital and essential drugs
CFU — colony-forming unit
CT – computed tomography
ICD-10 – International Classification of Diseases 10th Revision
MRI – magnetic resonance imaging
ESR – erythrocyte sedimentation rate
CRP – C-reactive protein
US — ultrasound
CKD — chronic kidney disease
CRF — chronic renal failure
PCN – percutaneous nephrostomy
UTI — urinary tract infection
99m Tc-DMSA – Technetium [99mTc] succimer (99m Tc-dimercaptosuccinic acid)
Terms and Definitions
Chronic kidney disease — kidney damage or a decrease in kidney function lasting for 3 months or more.
Chronic renal failure — a syndrome of impaired renal function leading to disorders of water, electrolyte, nitrogen, and other types of metabolism.
Percutaneous puncture nephrostomy — a minimally invasive surgical intervention aimed at placing an external drainage (nephrostomy tube) into the pelvicalyceal system of the kidney.
Pasternatsky's sign — tenderness in the renal area upon percussion, followed by the brief appearance or intensification of
erythrocyturia.
Rehberg test — a method used to assess the excretory function of the kidneys by the clearance of endogenous creatinine in blood and urine.
1. Brief information on the disease or condition
1.1 Definition of the disease or condition
Acute pyelonephritis — is an acute nonspecific infectious and inflammatory process characterized by simultaneous or sequential involvement of the pelvicalyceal system and renal parenchyma (predominantly the interstitial tissue) [1].
1.2 Etiology and pathogenesis of the disease or condition (group of diseases or conditions)
Uncomplicated pyelonephritis can be caused by Escherichia coli (75–95%), Staphylococcus saprophyticus (5–10%), and other pathogens: Enterobacteriaceae (except E. coli), Proteus mirabilis, Klebsiella pneumoniae. Complicated pyelonephritis is caused by all of the above, as well as P. aeruginosa, Serratia spp. and Providencia spp., staphylococci, and fungi [2, 3]. Kidney infection can occur via hematogenous or ascending routes. The hematogenous route is observed in the presence of upper urinary tract obstruction or in debilitated, immunocompromised patients. In the majority of cases, the ascending route of infection predominates.
1.3 Epidemiology of the Disease or Condition
The incidence of acute pyelonephritis is 15–39 patients per 10,000 population [1, 4, 5]. The annual incidence is 250,000 cases in the USA, and the hospitalization rate is 11.7 cases per 10,000 population among women and 2.4 cases per 10,000 population among men. The prevalence of complicated acute pyelonephritis approaches 35%. The incidence of acute pyelonephritis is higher in young women than in men, but the incidence in men older than 65 years is similar to that in older women. Women have up to a 10% risk of recurrent acute pyelonephritis per year after the first acute episode. The equivalent risk for men is 6%.
1.4 Features of Coding the Disease or Condition
N10 — Acute tubulointerstitial nephritis
N13.6 — Pyonephrosis
N15.1 — Renal and perinephric abscess
N39.0 — Urinary tract infection, site not specified
1.5 Classification of the disease or condition
A distinction is made between primary acute pyelonephritis (uncomplicated), developing in an intact kidney (without developmental anomalies and visible urodynamic disorders of the upper urinary tract), and secondary acute pyelonephritis (complicated), occurring against the background of diseases that disrupt urine flow: renal and urinary tract developmental anomalies; urolithiasis; ureteral strictures of various etiologies; Ormond's disease; vesicoureteral reflux and reflux nephropathy; prostate adenoma and sclerosis; bladder neck sclerosis; neurogenic bladder (especially of the hypotonic type); urinary tract tumors.
Depending on the localization, the process can be unilateral or bilateral.
The following stages of acute pyelonephritis are also distinguished:
serous inflammation,
purulent inflammation,
apostematous pyelonephritis,
renal carbuncle,
renal abscess [6–8].
1.6 Clinical presentation of the disease or condition
The clinical presentation of acute pyelonephritis, in addition to pain in the lumbar region in the projection of the affected kidney, consists of symptoms of systemic inflammation (fever, chills, malaise, nausea, vomiting) and bladder inflammation (frequent urination, urinary urgency, and dysuria). At the same time, approximately 20% of patients lack bladder symptoms, and in a number of studies, the presence of lumbar pain and anterior abdominal wall muscle guarding were not considered inclusion criteria [9–11]. The severity of the disease and its clinical manifestations vary widely from moderate lumbar pain or absence of fever to septic shock. The frequency of bacteremia ranges from <10 to >50% and depends on the patient's age (65 years and older), presence of comorbidities, immune status, and urinary tract obstruction [12].
2. Diagnostics, medical indications and contraindications for diagnostic methods
Criteria for establishing the diagnosis of acute pyelonephritis based on pathognomonic data:
presence of pain in the lumbar region and costovertebral angle, usually accompanied by fever, and dysuria.
laboratory examinations (changes in the general (clinical) urinalysis with a predominance of leukocyturia and bacteriuria; in obstructive pyelonephritis, urinalysis results may be unchanged)
instrumental examinations (specific renal changes on ultrasound examination of the kidneys or computed tomography (computed tomography of the retroperitoneal space with intravenous bolus contrast enhancement) [2, 8, 14, 15, 24, 27, 28].
2.1 Complaints and Anamnesis
In addition to lumbar pain, fever, and chills, nonspecific complaints of generalized weakness, headache, thirst, nausea, vomiting, abdominal distension, etc., are possible. The development of dysuria — frequent painful urination of varying severity — is observed if the course of acute pyelonephritis is accompanied by cystitis.
When taking the medical history, it must be taken into account that primary acute pyelonephritis can occur in practically healthy individuals after hypothermia or stressful situations. Secondary acute pyelonephritis (complicated), occurring against the background of diseases that impair urine flow (primarily urolithiasis), may be accompanied by pronounced lumbar pain
It is recommended to clarify the presence of the following during questioning in all patients to verify the diagnosis of acute pyelonephritis:
- foci of chronic infection; renal and urinary tract anomalies;
- diseases capable of causing impaired urine flow from the kidneys;
- carbohydrate metabolism disorders and the degree of their correction;
- immunodeficiency resulting from any disease or induced by medicinal products [11–15].
Level of Recommendation CLevel of Evidence 4Level of Recommendation C (level of evidence – 4)
Comments: Chronic infectious diseases of the urinary tract can lead to the development of pyelonephritis. If the patient has conditions that impair urine flow through the upper urinary tract (kidney stones, ureteral stones, ureteral strictures), attention should be paid to relieving the obstruction and draining the urinary tract. In patients with metabolic disorders and immunodeficiency, pyelonephritis may have a more severe clinical course.
It is recommended in all patients with suspected acute pyelonephritis to collect information on past inflammatory diseases of infectious etiology, the use of antibacterial drugs and their effectiveness, and to ascertain the gestational age and course of pregnancy in pregnant women in order to select the optimal regimen of empirical antibiotic therapy [16, 26, 56]
GRC CLeE 5Grade of Recommendation C (Level of Evidence – 5)
Comments: data on previously used antibacterial agents can help in prescribing empirical antibiotic therapy. The prescription of safe medical treatment for pregnant women is directly related to the gestational age.
2.2 Physical Examination
All patients with suspected acute pyelonephritis are recommended to undergo palpation of the renal area during physical examination to detect tenderness and muscle guarding in the costovertebral angle [11–15].
LeRR CLoE 4Level of recommendation confidence C (level of evidence – 4)
Comments: with a fully developed clinical picture of acute pyelonephritis, the following are noted:
- elevation of body temperature >38 °C (sometimes with chills);
- tenderness upon palpation in the renal area on the affected side (positive symptom of acute pyelonephritis);
- positive Pasternatsky's sign on the affected side.
The severity of symptoms can range from mild lumbar pain and subfebrile temperature to hectic fever and marked tenderness upon palpation in the renal area (in purulent pyelonephritis).
2.3 Laboratory Diagnostics
It is recommended for all patients with suspected acute pyelonephritis to perform a general (clinical) urinalysis to detect leukocyturia and bacteriuria at the stage of initial diagnosis [11–15].
Level of Evidence CGrade of Recommendation 4Level of Evidence C (grade of recommendation – 4)
Comments: The general (clinical) urinalysis allows the detection of an increased leukocyte count (mostly neutrophils) and bacteriuria. Mild proteinuria (up to 1 g/day) and microhematuria are possible. It is advisable to perform the test no later than 2 hours from the moment of admission to the hospital.
It is recommended for all patients prior to initiating empirical antimicrobial therapy to perform microbiological (culture) urinalysis for aerobic and facultatively anaerobic opportunistic microorganisms, and determine the sensitivity of microorganisms to antimicrobial chemotherapeutic drugs to identify the causative agent of the disease and select antibacterial therapy [12, 24, 57, 58]
Level of Recommendation CLevel of Evidence 4Level of Recommendation C (level of evidence – 4)
Comments: this test is of particular importance in cases of ineffectiveness of ongoing therapy [12, 13].
Bacteriuria exceeding 10×4 CFU/mL in acute pyelonephritis is recommended to be considered clinically significant [11-15]. In 80% of cases, the causative agent is E. coli (strains possessing additional virulence factors, especially P. pili). Other uropathogens, particularly in cases of nosocomial microflora, may include Klebsiella spp., Proteus spp., and Pseudomonas spp. Gram-positive flora (Enterococcus spp., etc.) cannot be excluded as a causative agent of the disease either.
It is recommended that all patients with acute secondary pyelonephritis undergo urine collection from the renal pelvis during kidney drainage (nephrostomy) for microbiological (culture) testing for aerobic and facultatively anaerobic opportunistic microorganisms, and determination of microorganism susceptibility to antimicrobial chemotherapeutic agents in order to select adequate drug therapy [15, 27, 58, 59].
GCR CLEL 5Grade of Recommendation C (Level of Evidence – 5)
It is recommended that all patients undergo a complete blood count (CBC) and general biochemical blood test (assessment of blood creatinine levels, blood glucose levels, and serum C-reactive protein levels) during the initial diagnosis of acute pyelonephritis to clarify the activity of the inflammatory process and the functional state of the kidneys [11-15].
GGR CLEL 4Grade of Recommendations C (Level of Evidence – 4)
Comments: A complete blood count (CBC) will reveal the hematological signs of acute pyelonephritis: neutrophilic leukocytosis with a left shift and an elevated erythrocyte sedimentation rate (ESR).
The general biochemical blood test helps clarify the functional state of the kidneys and liver; the blood concentration of C-reactive protein (CRP) correlates strongly with disease activity and the stage of the process. The CRP test is compared with the ESR (erythrocyte sedimentation rate). Both indicators rise sharply at the onset of the disease, but CRP appears and disappears earlier than changes occur in the ESR. It is advisable to perform these tests no later than 2 hours after admission to the hospital.
It is recommended that patients with a history of chronic kidney disease (CKD) undergo an assessment of nephron function via creatinine clearance (Rehberg's test), determining the glomerular filtration rate (mL/min) and tubular reabsorption (%) based on the clearance of endogenous blood and urine creatinine, taking into account the urine output volume (per unit of time) to evaluate the excretory capacity of the kidneys [14].
Level of Recommendation CLevel of Evidence 4Level of Recommendation C (level of evidence – 4)
It is recommended that all patients undergo an evaluation of the efficacy of empirical antibacterial therapy no later than 72 hours from its initiation to determine the need for adjustments to the treatment regimen [15, 24, 13, 60, 61].
GGR CLEL 5Grade of Recommendations C (Level of Evidence – 5) Comments: serial complete blood counts and urinalyses make it possible to assess the degree of reduction in leukocyturia, the severity of leukocytosis, lymphocytopenia, decreased ESR, and other laboratory signs of the inflammatory process.
After completing a course of treatment for acute uncomplicated pyelonephritis, in the absence of pyelonephritis symptoms, it is not recommended to perform a follow-up microbiological (culture) urine test for aerobic and facultatively anaerobic opportunistic microorganisms in all patients, with the exception of pregnant women, due to the achievement of clinical cure [15, 27, 56].
GCR CLOE 5Grade of Recommendation C (Level of Evidence – 5)
2.4 Instrumental Diagnostics
It is recommended that patients with a complicated course of acute pyelonephritis undergo an ultrasound examination (ultrasound) of the kidneys to rule out upper urinary tract obstruction and the presence of calculi [15, 24, 27, 45].
GGR CLEL 2Grade of Recommendations C (Level of Evidence – 2)
Comments: Performing an ultrasound no later than 2 hours after hospital admission makes it possible to diagnose renal parenchymal edema and focal changes, while Doppler ultrasonography allows for the assessment of the degree of blood flow impairment. Dilatation of the pelvicalyceal system indicates impaired urine outflow from the kidney and the secondary nature of the disease.
It is recommended that patients with suspected or confirmed urolithiasis, pronounced clinical signs of systemic inflammation (fever >38°, chills, vomiting), and decreased diuresis (glomerular filtration rate <40 mL/min) undergo computed tomography (CT) of the kidneys and upper urinary tracts with intravenous bolus contrast enhancement, or plain urography (X-ray of the urinary system) and intravenous urography (excretory) to determine the anatomical and functional state of the upper urinary tracts and to detect urolithiasis, abscess, or renal infarction [11, 14, 15, 28, 56].
GRC CLeE 5Grade of Recommendation C (Level of Evidence – 5)
Comments: performing plain urography makes it possible to diagnose the calculous nature of acute pyelonephritis, whereas intravenous (excretory) urography evaluates the condition of the kidneys and urinary tract, as well as urine passage. In patients with prolonged fever (72 hours) or suspected urinary tract calculi, a CT scan of the kidneys and upper urinary tracts with intravenous bolus contrast enhancement should mandatory be performed to identify complicating factors.
It is recommended that pregnant patients with suspected acute pyelonephritis, or patients with high blood creatinine levels, undergo magnetic resonance imaging (MRI) of the kidneys to detect destructive processes in the kidney [14-21].
GRC CLeE 5Grade of Recommendation C (Level of Evidence – 5)
Comments:CT and MRI can help detect a destructive process in the kidney and the secondary nature of acute pyelonephritis if the diagnosis cannot be clarified by ultrasound and excretory urography (e.g., acute pyelonephritis against the background of a radiolucent ureteral stone). In patients with high blood creatinine levels, performing a CT scan of the kidneys and upper urinary tracts with intravenous bolus contrast enhancement to visualize the upper urinary tract is not always feasible due to impaired renal excretory function. In such cases, magnetic resonance urography (MRI of the kidneys and urinary tract) is preferred.
2.5 Other Procedures
Patients with suspected acute pyelonephritis and an allergic reaction to iodine-containing radiocontrast agents are recommended to undergo renal and urinary tract scintigraphy for radionuclide visualization of renal lesions [43-46].
Leveled of Evidence CLevel of Data Reliability 2Level of evidence C (level of data reliability – 2)
Comment: In acute pyelonephritis, renal cortical defects manifest as a decrease or absence of radiotracer uptake without deforming the renal contour. An increase in the volume of the affected area or the entire kidney is possible. Studies have shown that renal and urinary tract scintigraphy is more sensitive than renal ultrasound for detecting acute and chronic pyelonephritis [43]. 99mTc-DMSA scanning detects more defects than ultrasound or X-ray imaging.
3. Treatment, including drug and non-drug therapies, diet therapy, and pain management
The treatment of acute pyelonephritis should consist of eliminating the infectious-inflammatory process and sanitizing the urinary tract while maintaining adequate urine outflow from the kidney. The principles of empirical antibacterial therapy include:
o Relief of urinary tract obstruction in case of impaired urine outflow.
o Anticipating the potential causative agent (or multiple pathogens) to determine the intrinsic susceptibility of this microorganism to antibacterial drugs.
o Analyzing prior antibacterial therapy, taking into account gaps in the spectrum of activity of previously ineffective drugs.
o Accounting for the functional state of the kidneys and liver (in chronic renal failure (CRF) and/or liver cirrhosis, the treatment regimen may change significantly).
o Preventing the development of antimicrobial resistance (administering adequate drug doses, limiting the use of systemic antipseudomonal antibacterial agents).
o Considering economic aspects (avoiding the prescription of expensive antibacterial drugs whenever possible).
3.1 Non-pharmacological therapy
In acute pyelonephritis with restored urine passage, all patients are recommended to maintain adequate diuresis to restore urodynamics [28].
Grade of Recommendations B (Level of Evidence - 2)
Comments: The volume of fluid intake should be 2000–2500 mL/day.
It is recommended that all patients with acute pyelonephritis use diuretic herbal preparations and decoctions (berry morses) with antiseptic properties to enhance the anti-inflammatory and antibacterial effect as part of combination therapy [38-40].
GGR CLEL 5Grade of Recommendations C (Level of Evidence - 5)
Comment: Herbal preparations are used (cranberry).
Leveled CEvid 5Level of recommendation confidence C (level of evidence reliability - 5)
Comments: in case of carbohydrate metabolism disorders, the ingested fluid must not contain sugar.
3.2 Pharmacotherapy
All patients with acute pyelonephritis are recommended to receive antibacterial therapy for medical treatment [22-28].
GGR ALEL 1Grade of Recommendation A (Level of Evidence - 1)
Patients with secondary (obstructive) acute pyelonephritis are recommended to initiate antibacterial therapy only after obstruction relief and restoration of adequate urine outflow from the kidney to increase treatment efficacy [15, 22-28, 56].
GGR CLEL 5Grade of Recommendations C (Level of Evidence - 5)
Comments: in acute pyelonephritis, success directly depends on the empirical selection of antibacterial treatment.
Drug selection should be determined by:
o spectrum and susceptibility of etiological uropathogen strains;
o efficacy of their use for specific indications in clinical trials;
o tolerability and adverse reactions;
o cost;
o availability.
Prior to obtaining the results of microbiological (culture) urine tests for aerobic and facultatively anaerobic opportunistic microorganisms, all patients with acute pyelonephritis are recommended to undergo empirical antibacterial therapy to achieve maximum treatment efficacy [22-28].
GRC CLeE 5Grade of Recommendation C (Level of Evidence – 5)
All patients, following a microbiological (culture) urine test for aerobic and facultatively anaerobic opportunistic microorganisms, pathogen identification, and antibiotic susceptibility testing, are recommended to receive adjusted antibacterial therapy for acute pyelonephritis with correction of empirical therapy to achieve maximum treatment efficacy [12, 24-28].
GRC CLeE 5Grade of Recommendation C (Level of Evidence – 5)
It is recommended that all patients with acute uncomplicated mild-to-moderate pyelonephritis receive oral fluoroquinolones (levofloxacin**, ciprofloxacin**) as first-line therapy for 7–10 days as drugs of choice, provided the regional resistance rate of E. coli to them is <10%, in order to achieve the maximum therapeutic effect [22, 30, 31, 44, 50].
Level of Recommendation ALevel of Evidence 1Level of recommendation A (level of evidence – 1)
It is recommended to administer parenteral antibiotics in case of inability to take oral medications, treatment failure, or presence of risk factors for multiple drug resistance in the pathogen, in order to achieve the maximum therapeutic effect [15, 23, 29-31, 41, 42, 44, 60].
Level of Recommendation BLevel of Evidence 2Level of recommendation B (level of evidence – 2)
Comments: Drugs for intravenous administration in acute non-obstructive pyelonephritis include fluoroquinolones (levofloxacin**, ciprofloxacin**), aminoglycosides (gentamicin**, amikacin** combined with ampicillin**) or first-to-fourth generation cephalosporins (ceftriaxone**, cefepime**, ceftazidime+[avibactam]**) (Appendix A3, cl. 2). When increasing the daily dose of fluoroquinolones, the treatment course can be shortened to 5 days. The increasing number of E. coli strains resistant to fluoroquinolones currently limits the empirical use of drugs from this group. It must be remembered that fluoroquinolones are contraindicated during pregnancy.
It is recommended to switch to oral therapy with the same systemic antibacterial drug (or a drug from the same group) upon patient improvement after 72 hours of parenteral antibacterial therapy for acute uncomplicated pyelonephritis, in order to achieve the maximum therapeutic effect [15, 22, 27, 28].
GCR CLEL 5Grade of Recommendation C (Level of Evidence – 5)
In case of allergy and other contraindications to fluoroquinolones, it is recommended to prescribe oral third-generation cephalosporins to achieve the maximum therapeutic effect [15, 27-29, 42, 50, 56].
GRC CLeE 5Grade of Recommendation C (Level of Evidence – 5)
Comments: however, studies have shown only equivalent clinical, but not microbiological, efficacy compared to ciprofloxacin**.
In regions with a high prevalence of fluoroquinolone-resistant and extended-spectrum beta-lactamase (ESBL)-producing E. coli strains (>10%), it is recommended to initiate empirical therapy with aminoglycosides or carbapenems until bacteriological data on susceptibility to other systemic antibacterial drugs are obtained, in order to achieve the maximum therapeutic effect [15, 16, 26-28, 50].
GCR CLOE 5Grade of Recommendation C (Level of Evidence – 5)
Comments: this is necessary to rule out complicating factors and administer parenteral antibacterial therapy. Following patient improvement, further oral administration of systemic antibacterial drugs (step-down therapy) is possible.
Data on antibacterial therapy for acute uncomplicated mild-to-moderate and severe pyelonephritis are presented in Appendix A3, Tables 1, 2.
Regardless of the severity of chronic kidney disease, the use of nephrotoxic antibiotics—aminoglycosides and glycopeptide antibiotics—is not recommended to increase treatment safety and reduce the risk of adverse effects [14-16, 50, 58, 60, 62].
GRC CLeE 5Grade of Recommendation C (Level of Evidence – 5)
In acute pyelonephritis in immunocompromised patients, it is recommended to use broad-spectrum antibacterial regimens that are not metabolized in the body and have a renal route of elimination—fluoroquinolones (especially ofloxacin** and levofloxacin**), aminoglycosides, first-to-fourth generation cephalosporins (except cefotaxime**, ceftriaxone**, and cefoperazone) to achieve the maximum therapeutic effect and improve treatment safety [16, 26, 28, 32-34, 61].
GPP CLOE 4Strength of Recommendation C (Level of Evidence – 4)
Comments: acute pyelonephritis in immunocompromised patients (including HIV-infected patients, as well as intravenous drug users) is often caused by rare and unusual pathogens, especially Gram-positive ones. It should also be borne in mind that antiretroviral drugs prescribed to suppress HIV replication are rather toxic and have numerous drug interactions, which determines the choice of antibacterial therapy.
Patients with acute pyelonephritis caused by nosocomial multiresistant strains are recommended to receive ceftazidime** as monotherapy or combined with amikacin** to achieve the maximum therapeutic effect and improve treatment safety [15, 24-28, 56].
GRC CLeE 5Grade of Recommendation C (Level of Evidence – 5)
In case of failure of empirical initial therapy (when results indicate pathogen drug resistance to the previously prescribed empirical antibacterial therapy), it is recommended to prescribe reserve drugs from the carbapenem group (except ertapenem**) to achieve the maximum therapeutic effect and prevent antibiotic resistance [15, 24, 27, 28, 56].
Level of Recommendation CLevel of Evidence 5 Level of recommendation C (level of evidence – 5)
Piperacillin+[tazobactam] is recommended for the treatment of patients with acute pyelonephritis whose urine contains ESBL-producing uropathogens, in order to achieve the maximum therapeutic effect [41, 42].
Level of Recommendation CLevel of Evidence 2Level of recommendation C (level of evidence – 2)
Comments: the drug continues to show high activity against Enterobacteriaceae, including extended-spectrum beta-lactamase producers, and can serve as an alternative to carbapenems.
In case of carbapenem failure in the treatment of patients with acute pyelonephritis, it is recommended to use the combination of ceftazidime+[avibactam]** to achieve maximum treatment efficacy [23, 27, 28].
GGR ALEL 2Grade of Recommendation A (Level of Evidence — 2)
Comments: in clinical practice, acute pyelonephritis caused by nosocomial multiresistant strains is in most cases the result of a prolonged hospital stay, erroneous antibiotic prophylaxis, or inadequate drainage function following urogenital surgery. One of the reasons for carbapenem failure may be the production of carbapenemases by uropathogens. The combination of ceftazidime+[avibactam]** has proven high efficacy [28].
If neutropenia is detected against the background of urosepsis in patients with acute pyelonephritis, it is recommended to prescribe ceftazidime** or a carbapenem group drug with vancomycin** due to the possible presence of Enterococcus spp. for pathogen eradication [15, 16, 24, 56].
GCR CLOE 5Grade of Recommendation C (Level of Evidence – 5)
Comments: this condition is life-threatening. The potential presence of nosocomial multiresistant strains is fundamentally hazardous.
Patients with persistent pronounced symptoms of pyelonephritis for 3 days or in case of disease relapse within 2 weeks are recommended to undergo repeated urine culture and antimicrobial susceptibility testing to determine the tactics of antibacterial therapy [15, 18, 27, 56].
GCR CLOE 5Grade of Recommendation C (Level of Evidence – 5)
In the absence of positive clinical and laboratory dynamics in the treatment of acute pyelonephritis, patients are recommended to undergo a repeated ultrasound of the kidneys and kidney CT in order to identify complicating factors and clarify the anatomical and functional state of the kidneys [18, 21].
Level of Recommendation CLevel of Evidence 4Level of Recommendation C (level of evidence – 4)
In the absence of anatomical and functional changes in the urinary tract in patients with persistent pronounced symptoms of pyelonephritis for 3 days or in case of disease relapse within 2 weeks, it is recommended to prescribe alternative therapy based on the results of microbiological (culture) urine tests for aerobic and facultatively anaerobic opportunistic microorganisms to eradicate the pathogen [15, 27, 56].
GCR CLOE 5Grade of Recommendation C (Level of Evidence – 5)
Comments: this may be due to the fact that the infectious agent was not sensitive to the antibiotic used.
In all patients with a relapse of the disease caused by the same uropathogen, it is recommended to rule out the presence of complicating factors to determine further treatment tactics [15, 16, 24, 27, 56].
GRL CLEL 5Guideline Recommendation Level C (Level of Evidence – 5)
3.3 Surgical treatment
The main principles of treatment are: timely restoration of urinary tract urodynamics, adequate empirical antimicrobial therapy, and elimination (if possible) of complicating factors (stones, catheters, drains, etc.)
In a severe condition of a patient with acute pyelonephritis (fever >38°, chills, shortness of breath, hypotension), emergency hospitalization is recommended for examination, identification of complicating factors, urinary tract drainage, and possible surgical treatment [15, 27, 28, 35, 36, 45, 56].
GRC CLeE 5Grade of Recommendation C (Level of Evidence – 5)
All patients with acute secondary pyelonephritis are recommended to undergo emergency kidney drainage: placement of an internal stent to restore urine passage [11, 15, 27, 28, 35, 36, 56].
GRC CLeE 5Grade of Recommendation C (Level of Evidence – 5)
Comments: This procedure is necessary as an emergency care to restore urine passage or as one of the main therapeutic measures in an extremely severe general condition of the patient and the impossibility of surgical treatment.
If stent placement is impossible in patients with acute secondary pyelonephritis, it is recommended to perform percutaneous puncture nephrostomy (PCPN) to enable long-term kidney drainage [35, 36].
GRC CLeE 5Grade of Recommendation C (Level of Evidence – 5)
Comments: this type of surgical intervention is often considered the method of choice in men due to the danger of transurethral manipulations. PCPNC, like internal stent placement, makes it possible to avoid open surgery in patients with acute calculous pyelonephritis, allows arresting the disease attack and, after some time (3–4 weeks) after adequate preoperative preparation, removing the stone using minimally invasive methods (extracorporeal shock wave lithotripsy or distant ureterolithotripsy, endoscopic, laparoscopic, and retroperitoneoscopic surgeries) [51].
It is recommended for all patients with acute secondary (complicated) pyelonephritis to start active antimicrobial therapy only after the elimination of urinary tract obstruction to increase treatment efficacy [15, 24, 27, 28, 56].
GDR CLE 5Grade of recommendation C (level of evidence – 5)
Comments: Data on antibacterial therapy for severe acute complicated pyelonephritis are presented in Appendix A3, Tables 3, 4. Conducting empirical treatment of complicated acute pyelonephritis with fluoroquinolones in patients staying in the urology department or who received drugs of this group over the past six months is not recommended.
It is recommended for all patients with complicated hospital-acquired urinary tract infection (UTI) in the presence of purulent pyelonephritis with the development of septic conditions to perform antibacterial treatment depending on the results of microbiological (culture) urine tests for aerobic and facultatively anaerobic opportunistic microorganisms to increase treatment efficacy and prevent relapses [15, 24, 27, 28, 56].
GDR CLE 5Grade of recommendation C (level of evidence – 5)
Open surgical treatment is recommended for patients with acute pyelonephritis in the stage of purulent inflammation, impossibility of kidney drainage by minimally invasive methods regardless of the cause, negative dynamics against the background of adequate antibacterial therapy, and a functioning nephrostomy to increase treatment efficacy [35-37, 53-55]
SOR CLOE 4Strength of Recommendation C (Level of Evidence – 4)
Comments: The scope of open surgery may include:
o lumbotomy;
o kidney revision;
o decapsulation of the kidney;
o opening of purulent foci;
o nephrotomy and nephrostomy
When performing open surgery in patients with acute pyelonephritis, it is recommended to remove calculi from the kidney and from the upper third of the ureter if possible (if this does not significantly increase the scope of the intervention) to increase treatment efficacy and prevent relapses [15, 27, 28, 35-37].
GCR CLOE 5Grade of Recommendation C (Level of Evidence – 5)
Nephrectomy (laparoscopic nephrectomy A16.28.004.001; robot-assisted nephrectomy A16.28.004.003) is recommended in the presence of purulent destruction of more than 2/3 of the renal parenchyma, signs of renal vessel thrombosis, multiple confluent renal carbuncles , purulent pyelonephritis of a non-functioning kidney, purulent pyelonephritis in a patient in extremely grave condition (due to purulent intoxication, toxic shock, decompensation of concomitant diseases), emphysematous pyelonephritis to eliminate the source of infection [15, 27, 28, 37, 56].
GCR CLOE 5Grade of Recommendation C (Level of Evidence – 5)
3.4. Diet therapy
Not provided
4. Medical Rehabilitation and Sanatorium-Resort Treatment
Methods of medical rehabilitation for patients with acute pyelonephritis are not provided.
5. Prevention and Dispensary Observation
It is recommended for patients to treat asymptomatic bacteriuria in risk groups for the prevention of acute pyelonephritis: pregnant women, patients with poorly controlled diabetes mellitus, patients before endourological interventions, in the presence of a nephrostomy drainage or an internal stent [15, 27, 28, 35].
GCR CLOE 5Grade of Recommendation C (Level of Evidence – 5)
It is recommended for patients to perform a microbiological (culture) urine test for aerobic and facultatively anaerobic opportunistic microorganisms in pregnant women 1-2 weeks after treatment and 1 time before childbirth for the purpose of preventing acute pyelonephritis [15, 27, 28, 63, 64].
GCR CLOE 5Grade of Recommendation C (Level of Evidence – 5)
6. Organization of Medical Care
Indications for elective hospitalization:
1. correction of all anatomical and functional disorders of the urinary tract;
2. removal of drains and catheters in the urinary tract;
3. treatment of concomitant diseases (diabetes mellitus, renal failure).
Indications for emergency hospitalization:
1. presence of complicating factors in anamnesis (urolithiasis, diabetes mellitus, urinary tract urodynamic disorders, presence of drains and catheters in the urinary tract);
2. severe condition of the patient (fever with chills, vomiting, tachycardia, shortness of breath).
Indications for discharging the patient from the hospital:
1. normalization of temperature;
2. normalization of complete blood count (absence of leukocytosis, lymphocytopenia, decrease in ESR);
3. decrease in the severity of leukocyturia;
4. absence of upper urinary tract urodynamic disorders.
7. Additional Information
The presence of risk factors in patients with urinary tract infection (renal failure, diabetes mellitus, immunosuppression) does not necessarily lead to generalization of the infectious process or rapid formation of purulent foci.
In diabetes mellitus, concomitant diabetic nephropathy and neuropathy causing urodynamic disorders exacerbate the course of UTI.
A decrease in the body's defense mechanisms and a decrease in granulocytes predispose to the persistence of pathogenic microorganisms.
In patients with diabetes mellitus, the formation of infectious interstitial nephritis with microabscesses, the development of acute renal failure, and often bacteremia are possible. The inflammatory process can progress unnoticed with the formation of renal and perinephric abscesses.
Papillary necrosis is more commonly observed in patients with acute pyelonephritis against the background of diabetes mellitus.
In patients with renal failure, the antibacterial activity of urine decreases.
In immunosuppression, there is a decrease in the barrier function of the uroepithelial layer and mucus.
Identification of patients in risk groups and their informing about the possibility of developing acute pyelonephritis should be carried out.
For patients with comorbid conditions, it is advisable to restrict the use of medicinal products with nephrotoxic action for the prevention of acute pyelonephritis.
Diagnostic and surgical interventions on the urinary system carry a certain risk of developing UTI and acute pyelonephritis, especially in elderly patients with multiple comorbid conditions. Indications for manipulations in this category of patients must be sufficiently well-founded [15, 16, 22, 24, 27].
To prevent acute pyelonephritis, patients with severe somatic diseases must strictly follow the indications for the use of immunosuppressants [7, 15, 16, 22, 24, 27].
Criteria for Evaluating the Quality of Medical Care
№ No. | Quality criterion | Performance |
|---|---|---|
1. | Complete blood count (CBC) performed during initial diagnosis | yes/no |
2. | Urinalysis performed at the initial diagnosis stage | yes/no |
3. | Microbiological (culture) urine test for aerobic and facultatively anaerobic opportunistic pathogens, determination of microbial susceptibility to antimicrobial chemotherapeutic agents | yes/no |
4. | Ultrasound examination of the kidneys performed in patients with a complicated course of acute pyelonephritis | yes/no |
5. | General biochemical blood test performed (blood creatinine level test, blood glucose level test, serum C-reactive protein level test) | yes/no |
6. | Antibacterial drug therapy administered in the presence of indications and absence of contraindications | yes/no |
References
Show references
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Appendix A1. Working Group Composition
Zaitsev Andrey Vladimirovich – MD, Professor, Department of Urology, A.I. Evdokimov Moscow State University of Medicine and Dentistry.
Kasyan Gevorg Rudikovich – MD, Professor, Department of Urology, A.I. Evdokimov Moscow State University of Medicine and Dentistry.
Spivak Leonid Grigoryevich – MD, Professor, Institute of Urology and Human Reproductive Health, I.M. Sechenov First Moscow State Medical University (Sechenov University).
Kharchilava Revaz Revazovich – PhD, Director of the Praxi Medica Training and Simulation Center, I.M. Sechenov First Moscow State Medical University (Sechenov University).
Conflict of interest: All Working Group members have confirmed the absence of financial support / conflicts of interest that need to be disclosed.
Appendix A2. Methodology for Developing Clinical Guidelines
Target audience for these clinical guidelines: specialists with higher medical education in the following specialties:
1. Urology
2. Therapy
3. General practice (family medicine)
4. Obstetrics and gynecology.
5. Surgery
In these clinical guidelines, all data are ranked by level of reliability (evidence) depending on the quantity and quality of studies on the issue.
Table 1. Level of Evidence (LoE) grading scale 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 method control or individual randomized clinical trials and systematic reviews of studies of any design, except for randomized clinical 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 | There is only a rationale for the mechanism of action or expert opinion |
Table 2. Level of Evidence (LoE) grading scale for prevention, treatment, and rehabilitation methods (preventive, therapeutic, and rehabilitative interventions)
LoE | Definitions |
|---|---|
1 | Systematic review of RCTs with meta-analysis |
2 | Individual RCTs and systematic reviews of studies of any design, except for RCTs using meta-analysis |
3 | Non-randomized comparative studies, including cohort studies |
4 | Non-comparative studies, case reports or case series, case-control studies |
5 | There is only a rationale for the mechanism of action of the intervention (preclinical studies) or expert opinion |
Table 3. Grade of Recommendation (GoR) scale 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 are of low methodological quality, and their conclusions on the outcomes of interest are inconsistent) |
Appendix A3. Reference Materials
References to regulatory acts
1. Order of the Russian Ministry of Health No. 907n dated November 12, 2012, "On approval of the rules for the provision of medical care to the adult population in the field of urology".
2. Tables for antibacterial therapy of acute pyelonephritis (drugs, dosing, course duration)
Table 1 – Antibacterial therapy for acute uncomplicated mild-to-moderate pyelonephritis
Antibiotic | Daily dose | Duration of treatment course, days |
|---|---|---|
Ciprofloxacin** | 500 mg 2 times/day | 7–10 |
Levofloxacin** | 500 mg 1 time/day | 7–10 |
Alternative drugs (equivalent clinical but not microbiological efficacy compared to fluoroquinolones) | ||
Cefixime | 400 mg 1 time/day | 10 |
Note. ** – the drug is included in the VLDN list (Vital and Essential Drugs).
Table 2 – Antibacterial therapy for severe acute uncomplicated pyelonephritis
Antibiotic | Daily dose | Duration of treatment course, days |
|---|---|---|
Initial parenteral therapy | ||
Ertapenem** | IV, IM 1 g 1 time/day | 7–10 |
Imipenem + cilastatin** | IV 500 mg 4 times/day | 7–10 |
Meropenem** | IV 500 mg – 1 g 3 times/day | 7–10 |
Piperacillin + [tazobactam] | IV 4 g + 0.5 g 3 times/day | 7–10 |
± Amikacin** | IV up to 15 mg/kg 1 time/day | – |
Alternative therapy (for known susceptibility and if ESBL < 10%) | ||
Ceftazidime** | IV, IM 2 g 3 times/day | 14 |
Cefotaxime** | IV, IM 2 g 3 times/day | 14 |
Ceftriaxone** | IV, IM 1–2 g 2 times/day | 14 |
Cefepime** | IV, IM 2 g 2 times/day | 14 |
± Amikacin** | IV up to 15 mg/kg 1 time/day | – |
Only if pathogen susceptibility is known and ESBL < 10% | ||
Levofloxacin** | IV 500 mg 1–2 times/day | 7–10 |
Ciprofloxacin** | IV 400 mg 2 times/day | 7–10 |
± Amikacin** | IV up to 15 mg/kg 1 time/day | – |
Note. ** – the drug is included in the VLDN list (Vital and Essential Drugs).
+ – combination therapy is possible
Table 3 – Antibacterial therapy for acute complicated pyelonephritis (initial empiric treatment), including in the presence of neutropenia and septicemia
Antibiotic | Daily dose | Duration of treatment course, days |
|---|---|---|
Initial parenteral therapy | ||
Ceftazidime** | IV, IM 2 g 3 times/day | 7-14 |
Cefotaxime** | IV, IM 2 g 3 times/day | 7-14 |
Ceftriaxone** | IV, IM 1–2 g 1 time/day | 7-14 |
± Amikacin** | IV up to 15 mg/kg 1 time/day | – |
Ertapenem** | IV, IM 1 g 1 time/day | 7–10 |
In case of inefficacy of initial empiric treatment | ||
Imipenem + cilastatin** | IV 500 mg 4 times/day | 10-14 |
Meropenem** | IV 500 mg – 1 g 3 times/day | 10-14 |
Piperacillin + [tazobactam] | IV 4 g + 0.5 g q8h | 7–14 |
Cefepime** | IV, IM 2 g 2 times/day | 14 |
Gentamicin** | IV 3–5 mg/kg q24h | 7 |
Netilmicin | IV 4–6 mg/kg q24h | 7 |
Note: ** – the drug is included in the VLDN (VITAL) list.
+ – combination therapy is possible
Table 4 – Antibacterial therapy for severe acute complicated pyelonephritis complicated by sepsis
Antibiotic | Daily dose | Duration of treatment course, days |
|---|---|---|
Cefotaxime** | IV, IM 2 g 3 times/day | 7-14 |
Ceftazidime** | IV, IM 2 g 3 times/day | 7-14 |
Ceftriaxone** | IV, IM 1–2 g 1 time/day | 7-14 |
Cefepime** | IV, IM 2 g q8–12h | 14 |
Piperacillin + [tazobactam] | IV 4 g + 0.5 g q8h | 7–14 |
Ceftolozane + [tazobactam]** | IV 1.5 g q8h | 7-10 |
Ceftazidime + [avibactam]** | IV 2000 mg ceftazidime + 500 mg avibactam q8h | 7-10 |
Ertapenem** | IV, IM 1 g 1 time/day | 10–14 |
Imipenem + cilastatin** | IV 500 mg 4 times/day | 10-14 |
Meropenem** | IV 500 mg – 1 g 3 times/day | 10-14 |
Gentamicin ** | IV 3–5 mg/kg q24h | 7-10 |
Amikacin** | IV up to 15 mg/kg 1 time/day | 7-10 |
Note. ** – the drug is included in the VLDN (VITAL) list.
Appendix B. Physician Action Algorithms
Appendix C. Patient Information
Acute pyelonephritis is an infectious and inflammatory disease of the kidney caused by various microorganisms entering it via the bloodstream or along the lumen of the urinary tract. The disease manifests with loin pain, fever, chills, nausea, vomiting, and urinary disturbances. You will be provided with information on measures to prevent relapses of pyelonephritis, the risks of self-medication with antibiotics, the need for regular blood pressure monitoring, and the action plan in case of a disease exacerbation. In case of acute pyelonephritis, medical consultation and examination are mandatory. Progressive disease may lead to a decrease or complete loss of renal function, as well as the development of sepsis and life-threatening conditions.
Appendix G. Assessment Scales, Questionnaires, and Other Evaluation Tools
Not applicable.