List of Abbreviations
BD | asymptomatic bacteriuria |
|---|---|
ESBL | beta-lactam antibacterials: penicillins (J01C) |
GBS AB | group B streptococcus asymptomatic bacteriuria |
VITAL | vital and essential medicines |
UTI | urinary tract infection |
CFU | colony-forming unit |
CT | computed tomography |
MRI | magnetic resonance imaging |
AKI | acute kidney injury |
AGA | group B streptococcus |
GFR | glomerular filtration rate |
ESR | erythrocyte sedimentation rate |
CRP | C-reactive protein |
ultrasound | ultrasound examination |
CKD | chronic kidney disease |
Terms and Definitions
Asymptomatic bacteriuria – the presence of bacteria in a diagnostically significant titer in two consecutive microbiological (culture) examinations of midstream urine (taken no more than 14 days apart) obtained during urination, in the absence of clinical symptoms.
Urinary tract infection in pregnancy – symptomatic or asymptomatic infectious diseases of the urinary tract during pregnancy.
Acute kidney injury – a pathological condition developing as a result of a direct acute effect of renal and/or extrarenal damaging factors, lasting up to 7 days, and characterized by the rapid onset of signs of renal damage or dysfunction of varying severity.
Pyelonephritis – a nonspecific inflammatory process of the upper urinary tract with predominant involvement of the renal tubulointerstitium, most often of bacterial etiology.
Prolonged antibiotic therapy – continuous administration of antibacterial drugs throughout pregnancy following two ineffective courses of antibiotic therapy for a urinary infection.
Glomerular filtration rate (GFR) – the volume of blood plasma filtered in all renal glomeruli per minute. GFR is expressed in ml/min, is determined by renal plasma flow, filtration pressure, and filtration surface area, and depends on the mass of functioning nephrons. It is used as an integral indicator of the functional state of the kidneys and is standardized to body surface area.
Chronic kidney disease – kidney damage persisting for three or more months due to various etiological factors, based on the replacement of normal anatomical structures by fibrosis, leading to dysfunction.
Cystitis – inflammation of the urinary bladder, predominantly of bacterial etiology.
1. Brief information on the disease or condition
1.1 Definition of the disease or condition
Urinary tract infection (UTI) in pregnancy – an acute nonspecific infectious and inflammatory process characterized by simultaneous or sequential involvement of the urinary bladder, ureters, 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)
The main prerequisite for the development of UTI during pregnancy is progesterone-induced alteration of urodynamics.
The pathogenesis of UTI begins with the colonization of the vagina or urethra by uropathogens of the fecal flora, followed by their ascent through the urethra into the bladder. Smooth muscle relaxation and subsequent dilatation of the ureters and pelvicalyceal system contribute to increased urinary stasis and the penetration of bacteria from the bladder into the kidneys, leading to pyelonephritis. As the gestational age increases, the pressure exerted by the gravid uterus rises, resulting in elongation and lateroposition of the ureters. The negative effect is amplified under the conditions of pregnancy-induced immunosuppression [2,3, 23]. The ascending route of infection (which is predominant) is realized in this manner. The hematogenous route of infection occurs in cases of bacteremia and the direct entry of bacteria into the kidneys via the bloodstream. It is possible that some cases of pyelonephritis are associated with the seeding of bacteria from the lymphatic system.
In the postpartum period, the risk of developing pyelonephritis remains high, especially during the first 2–3 weeks after delivery (as long as upper urinary tract dilatation persists) [4]. In addition to the factors listed above, causative factors include the activation of pathogenic or opportunistic microflora against the background of a suppressed immune system; hormonal changes associated with lactation; and a history of bacterial vaginosis.
As in non-pregnant individuals, Escherichia coli is the most frequent causative agent of urinary tract infections in pregnant women (75–95%). Other pathogens include: Klebsiella spp. and Enterobacter spp. (3% each), Proteus spp. (2%), and gram-positive microorganisms, including group B streptococci (10%) [2]. Causative agents of pyelonephritis may also include Pseudomonas aeruginosa, Serratia spp., and Providencia spp., staphylococci, and fungi. Staphylococci typically reach the kidney via a hematogenous route and are the causative agents of purulent-inflammatory forms of pyelonephritis (carbuncle, renal abscess) even in the absence of urodynamic disorders, most commonly in patients with diabetes mellitus in the presence of a purulent infection focus in the body (infected wound, furuncle, carious tooth) [1,5,6,23].
1.3 Epidemiology of the Disease or Condition
Urinary tract infection is a frequent complication of pregnancy. Bacteriuria occurs with equal frequency during pregnancy and outside of it (2–7%), but the incidence of recurrent bacteriuria and pyelonephritis is higher in pregnant women [2].
Asymptomatic bacteriuria (AB) is most frequently diagnosed in the first trimester (up to 75% of cases) and less frequently in the second and third trimesters of pregnancy (25%) [6]. Risk factors for bacteriuria include a history of urinary tract infection, diabetes mellitus, and low socio-economic status [2,6,7,10]. Without treatment, 30–40% of pregnant women with AB develop symptomatic infection, including pyelonephritis [11,12]. Acute cystitis develops in 1–2% of pregnant women. The incidence of acute pyelonephritis is 15–39 cases per 10,000 population [1,5,13]. The frequency of complicated acute pyelonephritis reaches 35%.
The incidence of acute pyelonephritis is higher in young women; the recurrence rate within a year reaches 10%.
The frequency of acute pyelonephritis in pregnant women is 1–2%. Most cases of pyelonephritis occur in the second and third trimesters of pregnancy, when urinary stasis and hydronephrotic transformation of the kidneys are significantly pronounced [5]. In addition to bacteriuria, risk factors for pyelonephritis include young age (<20 years), first pregnancy, and smoking. When bacteriuria is eradicated, the risk of pyelonephritis is reduced by 70–80%.
1.4 Features of Coding the Disease or Condition
O23 Infections of urinary and genital tract in pregnancy
O23.0 Renal infections in pregnancy
O23.1 Bladder infections in pregnancy
O23.2 Urethral infections in pregnancy
O23.3 Infections of other parts of urinary tract in pregnancy
O23.4 Urinary tract infection in pregnancy, unspecified
O23.9 Other and unspecified infections of urinary and genital tract in pregnancy
O86.2 Urinary tract infection following delivery
O86.3 Other infections of genitourinary tract following delivery
1.5 Classification of the disease or condition
Classification of urinary tract infections (UTIs) in pregnant women [1]:
Asymptomatic bacteriuria
Cystitis – urinary frequency, urinary urgency, dysuria; elevated body temperature and pelvic pain may be present [1,17].
By the nature of morphological changes: [14].
catarrhal
ulcerofibrinous
Hemorrhagic
gangrenous
interstitial
Pyelonephritis: [14]
acute
chronic
By conditions of onset: (Urology Guidelines / Ed. by N.A. Lopatkin. – M.: Meditsina, 1998).
Primary acute pyelonephritis (uncomplicated) – pyelonephritis of an intact kidney (without developmental anomalies and visible urodynamic disorders of the upper urinary tract)
Secondary acute pyelonephritis (complicated) – pyelonephritis occurring against the background of diseases that impair urine passage: developmental anomalies of the kidneys and urinary tract; urolithiasis; ureteral strictures of various etiologies; Ormond's disease; vesicoureteral reflux and reflux nephropathy; bladder neck sclerosis; neurogenic bladder (especially of the hypotonic type); urinary tract tumors.
By localization: the process can be unilateral or bilateral.
Stages of acute pyelonephritis: [14]
serous inflammation,
purulent inflammation (apostematous pyelonephritis, renal carbuncle, renal abscess).
1.6 Clinical presentation of the disease or condition
Cystitis is a symptomatic infection of the bladder. Typical symptoms during pregnancy are the same as outside of it and include the sudden onset of dysuria and frequent urges to urinate [1,2,7]. Low-grade fever is occasionally noted. Fever and chills are not characteristic of cystitis. The presence of fever, chills, and flank pain may indicate pyelonephritis.
In the full-blown clinical picture of acute pyelonephritis, the following are noted: body temperature >38°C (sometimes with chills), fever, tenderness upon palpation in the renal area on the affected side, and a positive costovertebral angle tenderness sign (Pasternack's sign) on the affected side. The severity of symptoms can vary from moderate lumbar pain and low-grade fever to hectic fever and marked tenderness upon palpation in the renal area (in purulent pyelonephritis) [2,7,14].
Pregnant women with pyelonephritis have an increased risk of acute kidney injury (AKI), the clinical symptom of which is oliguria/anuria (a decrease in daily urine output to less than 5 ml/kg of body weight). The lack of timely diagnosis and correction of oliguria/anuria leads to the development of uremia [2,5].
2. Diagnostics, medical indications and contraindications for diagnostic methods
Diagnostic criteria
The diagnosis of UTI in pregnant women is established in the presence of any UTI symptoms and/or the detection of leukocyturia and/or bacterial growth in urine culture [2,16].
2.1 Complaints and Anamnesis
It is recommended to clarify the following when taking the medical history to verify the diagnosis of urinary infection in pregnant women: foci of chronic infection; renal and urinary tract anomalies; diseases capable of causing impaired urine passage from the kidneys; carbohydrate metabolism disorders and the degree of their correction; and immunodeficiency resulting from any disease or induced by medications [1,7].
GGR CLOC 5Grade of Recommendation C (Level of Evidence – 5).
Comments: If the patient has diseases that impair urine passage through the upper urinary tract (renal calculi, ureteral calculi, ureteral strictures), the impaired urine outflow from the upper urinary tract should be eliminated by placing an internal ureteral stent into the urinary tract or by performing percutaneous puncture nephrostomy under ultrasound guidance.
It is recommended to screen all pregnant women for dysuria and other lower urinary tract symptoms (LUTS) to establish a UTI diagnosis [7,17-21].
GGR CLOC 5Grade of Recommendation C (Level of Evidence – 5).
Comments: The development of dysuria – frequent painful urination of varying severity – is the main complaint in cystitis. Other complaints in acute cystitis include suprapubic pain, urinary frequency, voiding in small volumes, imperative urinary urges, and the presence of blood in the urine. Fever and chills are absent in cystitis. The presence of fever, chills, and flank pain should raise suspicion of pyelonephritis [1,2,21].
It is recommended in pregnant women with symptoms of acute pyelonephritis, prior to prescribing antibacterial therapy, to take a medical history indicating information on past inflammatory diseases of infectious etiology, the intake of antibacterial drugs and their efficacy, and to clarify the gestational age and the characteristics of its course in order to optimize treatment [1,7,18].
GSR CLOC 5Grade of Recommendation C (Level of Evidence – 5)
Comments: Data on previously used systemic antibacterial drugs can assist in prescribing empirical antibacterial therapy. The administration of safe medical treatment to pregnant women is directly related to the gestational age [7,13,22,23].
2.2 Physical Examination
It is recommended to perform palpation of the renal area to detect tenderness and muscle tension in the costovertebral angle in pregnant women presenting with dysuria, pain and/or urinary frequency, macrohematuria, suprapubic pain, or costovertebral angle tenderness [21,24].
Level CLevel 5Level of recommendation evidence C (reliability level of evidence – 5).
It is recommended to monitor diuresis to detect oliguria/anuria in pregnant women with suspected upper urinary tract infection, regardless of the presence of fever, in order to timely diagnose acute kidney injury [25–29].
GCR CLOE 5(Grade of Recommendation C, Level of Evidence – 5).
Comments: Oliguria/anuria is one of the early criteria for acute kidney injury (AKI) in pregnancy associated with a high rate of maternal mortality (up to 14%), increased length of hospital stay, and higher treatment costs [28-31].
Timely diagnosis of oliguria (daily urine output decreasing below 5 ml/kg of body weight) or anuria (<100 ml of urine/day) in pyelonephritis prevents water-electrolyte balance disorders and the resulting uremic symptoms.
2.3 Laboratory Diagnostics
It is recommended that pregnant women with suspected UTI undergo a general (clinical) urine test [16-18,21,32].
GCR CLEL 5Grade of Recommendation C (Level of Evidence – 5).
Comments: A general (clinical) urine test makes it possible to detect an increased number of leukocytes and bacteria [16,21,32].
It is recommended that pregnant women with suspected UTI undergo microbiological (culture) urine testing for bacterial pathogens using automated inoculation to detect pathogen growth [20,21,32-34].
LE AQOE 3Level of Evidence A (reliability of evidence level – 3).
Comment: In clinical practice, a UTI diagnosis is generally established based on a single detection of bacteriuria with no more than two bacterial species, one of which is ≥105 CFU/ml in a midstream urine sample without follow-up microbiological testing. Asymptomatic bacteriuria is diagnosed by detecting the growth of no more than two bacterial species, one of which is ≥105 CFU/ml in two consecutive urine samples with the isolation of the same bacterial species upon repeated testing [35,36].
It is recommended to determine urine volume and test blood creatinine levels for the early diagnosis of AKI and stratification of its severity in acute pyelonephritis [2,18,29-31].
Level CLevel 5Level of recommendation evidence C (reliability level of evidence – 5).
Comment: Early diagnosis of AKI is based on assessing blood creatinine levels and urine volume. Urine volume is determined by measuring daily diuresis; normally, daily diuresis should exceed 500-800 ml.
Blood creatinine testing is an insensitive method for detecting early-stage AKI because creatinine levels rise only when the global functional capacity of the kidneys decreases by approximately half. Furthermore, due to creatinine kinetics, its concentration increases significantly (by more than a day) after a sudden drop in the glomerular filtration rate (GFR). The slowest rise in creatinine levels occurs in patients with pre-existing impaired renal function. Therefore, during the monitoring and treatment of a pregnant woman with pyelonephritis, in addition to assessing urine output volume, it is necessary to repeat the blood creatinine test.
It is recommended to collect urine from the renal pelvis in pregnant women with acute secondary pyelonephritis during ultrasound-guided percutaneous puncture nephrostomy for microbiological (culture) testing for bacterial pathogens [37-39].
GPP CLOE 4Grade of Recommendation C (Level of Evidence – 4).
It is recommended that pregnant women with acute pyelonephritis undergo a complete blood count (clinical blood test) and general biochemical blood test to assess the activity of the inflammatory process and the functional state of the kidneys [13,40-42].
GCR CLOE 3Grade of Recommendation C (Level of Evidence – 3).
Recommended nephron function testing via creatinine clearance (Rehberg's test) to assess renal filtration function in pregnant women with acute pyelonephritis with a history of chronic kidney disease (CKD) [38,43,44].
GCR CLOE 5Grade of Recommendation C (Level of Evidence – 5).
It is recommended to repeat the complete blood count (clinical blood test) and general (clinical) urine test no later than 48-72 hours from the start of antibacterial therapy in pregnant women with acute pyelonephritis to assess the efficacy of the prescribed empirical starting treatment [1,2,18,45].
GCR CLEL 5Grade of Recommendation C (Level of Evidence – 5).
It is recommended that pregnant women with UTI undergo microbiological (culture) urine testing for bacterial pathogens after completing the treatment course to monitor the efficacy of antibacterial therapy [32-34,41].
GCR CLEL 3Grade of Recommendation C (Level of Evidence – 3).
Comments: Follow-up testing should be performed 1-2 weeks after completing the course of antibacterial therapy [16,17].
2.4 Instrumental Diagnostics
It is recommended to perform a renal ultrasound (ultrasonography) to rule out upper urinary tract obstruction and calculi in pregnant women with acute pyelonephritis [46].
Level CLevel 5Level of recommendation evidence C (reliability level of evidence – 5).
Comments: Renal ultrasound makes it possible to detect destructive changes in the renal parenchyma and suspect obstruction in the presence of a clearly visualized calculus with an echonegative acoustic shadow in the projection of the upper third of the ureter and below.
It is recommended to perform magnetic resonance imaging (MRI) of the kidneys when the diagnosis cannot be clarified by ultrasound in pregnant women with pyelonephritis suspected of having a destructive process in the renal parenchyma [46,47].
GCR CLOE 5Grade of Recommendation C (Level of Evidence – 5).
It is recommended to evaluate the efficacy of ongoing therapy for acute pyelonephritis 48-72 hours after starting treatment, and to repeat renal ultrasound or renal MRI (if possible) in the absence of positive clinical and laboratory dynamics in pregnant women with acute pyelonephritis in order to identify complicating factors and clarify the anatomical and functional state of the kidneys [13,46].
GCR CLEL 5Grade of Recommendation C (Level of Evidence – 5).
2.5 Other Procedures
It is recommended for pregnant patients with UTI complications to have an appointment (examination, consultation) with a urologist for the timely correction of urodynamic disorders [23]1
GCR CLEL 5Grade of Recommendation C (Level of Evidence – 5).
1 Order of the Ministry of Health of the Russian Federation No. 1130n dated October 20, 2020. "On Approval of the Procedure for Providing Medical Care in the Field of 'Obstetrics and Gynecology (Excluding Assisted Reproductive Technologies)'"
3. Treatment, including drug and non-drug therapies, diet therapy, and pain management
3.1 Non-pharmacological treatments
It is recommended to consume sufficient fluids under the control of diuresis, as well as maintain a frequent urination regimen (bladder emptying every 3 hours) in pregnant women with UTI and restored urine flow to reduce the recurrence rate [48].
GGR CLOC 5Grade of Recommendation C (Level of Evidence – 5).
Comments: The volume of fluid intake should be 2000-2500 ml/day.
3.2 Pharmacological treatments
It is recommended that pregnant women with UTI be prescribed antibacterial therapy taking into account the susceptibility of the isolated pathogen to the antibacterial drug [1,2,11,23,34,49].
GCR ALOE 1Grade of Recommendation A (Level of Evidence – 1).
Comments: In pregnant women, UTIs are most frequently caused by Escherichia coli. Among oral drugs, fosfomycin** (powder or granules for oral solution) (95.6%) and #nitrofurantoin (100%) demonstrated maximum activity against Escherichia coli [2,49-53] (100 mg 3 times daily for 7 days) [2,23,54].
The susceptibility of Escherichia coli to oral 3rd-generation cephalosporins (cefixime) is >90%, which makes it possible to use them as drugs of choice in the empirical treatment of UTIs [2,11,47,55].
Among community-acquired UTIs, the susceptibility of Escherichia coli in the Russian population to amoxicillin+clavulanic acid** and ampicillin** is 66.8% and 47.5%, respectively [56]; therefore, pathogen-directed prescription of these drugs is possible after determining the susceptibility of the uropathogen to them [11,33,57]. The choice of the antimicrobial agent must also take into account safety during pregnancy (including the trimester of pregnancy) [58].
It is recommended to administer systemic antibacterial drugs parenterally to pregnant women with UTI presenting with fever, inability to take medications orally, inefficacy of prior therapy, or presence of risk factors for multiple drug resistance of the pathogen (recent antibacterial therapy, previous hospitalization, comorbid conditions) to improve treatment efficacy and prevent relapses [1,2,13,16-18,24].
GCR CLEL 5Grade of Recommendation C (Level of Evidence – 5).
Comments: Intravenous drugs for urinary tract infection in pregnant women include fosfomycin** (powder for solution for injection/infusion), 3rd-generation (cefotaxime**, ceftazidime**) and 4th-generation cephalosporins (cefepime**), as well as other cephalosporins and penems (J01DI). According to a Russian multicenter epidemiological study, resistance rates in pregnant women were generally slightly lower than in the adult non-pregnant subpopulation: Escherichia coli showed no resistance to nitrofurantoin, amikacin**, or meropenem**, and low rates of resistance to fosfomycin** (4.4%) and piperacillin+[tazobactam] (2.2%); the lowest resistance rates among all patient subpopulations analyzed in the study were observed for ceftazidime** and cefepime** (9.4% each); high resistance rates of E. coli were found to ampicillin** (52.5%), amoxicillin+[clavulanic acid]** (33.2%), cefotaxime** (21.6%), cefixime (22.7%), co-trimoxazole** (24.9%), and ciprofloxacin** (22.1%). The prevalence of ESBL production was 23.6%, demonstrating a statistically significant increase from 8.6% in this subpopulation over the past 5 years [56].
A repeat course of antibacterial therapy for 7 days is recommended in pregnant women with persistent ASB and a positive urine culture for bacterial pathogens after therapy (growth of the same bacterial species ≥105 CFU/mL) [11,17].
COR ALOE 1Class of recommendation A (level of evidence 1).
Long-term suppressive antibiotic therapy throughout pregnancy is recommended in pregnant women with persistent bacteriuria after two or more courses of therapy to suppress infection and prevent recurrences [17,38,58].
GCR CLEL 5Grade of Recommendation C (Level of Evidence – 5).
Comments: Long-term suppressive antibiotic therapy guided by susceptibility testing of aerobic and facultatively anaerobic microorganisms from urine culture is recommended up to 37 weeks of gestation.
Empirical antibacterial therapy guided by patient history is recommended before obtaining urine culture results for bacterial pathogens in pregnant women with acute pyelonephritis to improve treatment outcomes and prevent recurrences [5,17,38].
COR BLOE 3Class of recommendation B (level of evidence 3).
Comments: In acute pyelonephritis, treatment success directly depends on adequately selected empirical antibacterial therapy. Drug choice should be determined by: the spectrum and susceptibility of causative uropathogen strains; safety during pregnancy; UTI etiology (community-acquired or catheter-associated); epidemiological data on resistance rates of the most common causative uropathogens in community-acquired and catheter-associated UTIs; scope and duration of antimicrobial therapy during pregnancy; efficacy for specific indications in clinical trials; tolerability and adverse reactions.
Adjustment of antibacterial therapy is recommended in pregnant women after obtaining urine culture results for bacterial pathogens and antimicrobial susceptibility testing to improve treatment outcomes and prevent recurrences [11,17,38].
GCR CLEL 5Grade of Recommendation C (Level of Evidence – 5).
Oral administration of 2nd- or 3rd-generation cephalosporins or combinations of penicillins, including combinations with beta-lactamase inhibitors (amoxicillin+[clavulanic acid]**, if susceptibility is confirmed and there is no high risk of preterm delivery), is recommended in pregnant women with acute uncomplicated pyelonephritis for 7–10 days [11,17,38,59].
GCR CLEL 5Grade of Recommendation C (Level of Evidence – 5).
Administration of penicillin/beta-lactamase inhibitor combinations (amoxicillin+[clavulanic acid]**) is not recommended in pregnant women with acute uncomplicated pyelonephritis and a high risk of preterm delivery [11,60].
GCR CLEL 5Grade of Recommendation C (Level of Evidence – 5).
Antibacterial therapy with amoxicillin+[clavulanic acid]** is not recommended in cases of high risk of preterm delivery within the next 2 weeks due to the possible development of necrotizing enterocolitis in neonates. [11,60].
GCR CLEL 5Grade of Recommendation C (Level of Evidence – 5).
Switching to oral therapy with the same antibiotic (or an agent from the same class) is recommended upon clinical improvement after 72 hours of parenteral antibacterial therapy for acute uncomplicated pyelonephritis to prevent adverse effects [17,38].
GCR CLOE 5Grade of Recommendation C (Level of Evidence – 5).
Administration of 2nd-, 3rd-, or 4th-generation cephalosporins is recommended if empirical initial therapy is ineffective after 48 hours to improve treatment outcomes and prevent recurrences [5,11,17,38,59].
GGR CLOC 5Grade of Recommendation C (Level of Evidence – 5).
Reserve carbapenem monotherapy is recommended in pregnant women with acute pyelonephritis suspected to be caused by multidrug-resistant nosocomial strains to improve treatment outcomes and prevent recurrences [17,24,59].
GGR CLOC 5Grade of Recommendation C (Level of Evidence – 5).
Comments: Meropenem** and ertapenem** are used to treat urinary tract infections in pregnant women. According to a Russian multicenter epidemiological study, susceptibility of all Enterobacterales was 100% to meropenem** and 99% to ertapenem** [56].
If there is a history or laboratory evidence of bacteriuria caused by Pseudomonas aeruginosa, it should be noted that ertapenem** has no antipseudomonal activity and is therefore not used.
Antibacterial therapy in pregnant women with secondary (obstructive) acute pyelonephritis is recommended to be administered alongside measures to restore urinary drainage from the upper urinary tract [5,61, 62].
COR BLOE 3Class of recommendation B (level of evidence 3)
Comment: To prevent serious complications of secondary (obstructive) pyelonephritis in pregnant women—such as bacteremia, sepsis, septic shock, renal and multiorgan failure—prompt relief of obstruction and restoration of urine flow are essential.
Dose adjustment of antibacterial drugs is recommended in pregnant women if glomerular filtration rate decreases below 30 mL/min to prevent adverse effects [27].
GGR CLOC 5Grade of Recommendation C (Level of Evidence – 5).
Comment: Management of pregnant patients with reduced glomerular filtration rate is carried out in consultation with a clinical pharmacologist.
A switch of antibacterial therapy based on urine culture results for bacterial pathogens is recommended in pregnant women with persistent severe UTI symptoms for 3 days in the absence of anatomic and functional abnormalities of the urinary tract, or in case of disease recurrence within 2 weeks, to eradicate pathogens and prevent relapses [13, 25].
COR CLOE 3Class of recommendation C (level of evidence 3).
Adjustment of antibacterial therapy based on urine culture results for bacterial pathogens is recommended in pregnant women with purulent pyelonephritis and development of sepsis to eradicate pathogens and prevent relapses [2, 28].
Level CLevel 5Level of recommendation evidence C (reliability level of evidence – 5).
Comment: Treatment strategy is agreed upon with a urologist.
Combination of antibacterial drugs with herbal medicinal products based on Centaurium erythraea herb + Levisticum officinale root + Rosmarinus officinalis leaves is recommended in pregnant women with UTIs for courses of 2 to 6 weeks to increase treatment efficacy and reduce the risk of recurrence [64,65].
Level CLevel 5Level of recommendation evidence C (reliability level of evidence – 5).
Comment: The use of herbal medicines in the comprehensive treatment of urinary tract infections improves treatment efficacy and reduces the risk of infection recurrence.
3.3 Surgical treatments
Emergency urinary stenting is recommended in pregnant women with UTI and impaired drainage from the upper urinary tract to restore urine flow [13, 63, 66-68].
COR CLOE 5Class of recommendation C (level of evidence 5).
Comments: This procedure is required as emergency management to restore urine flow or as one of the main therapeutic interventions in patients in critical general condition when surgical treatment is not feasible [66-68].
It is recommended that if urinary tract stenting is not feasible in pregnant women with acute secondary pyelonephritis, ultrasound-guided percutaneous puncture nephrostomy be performed to relieve upper urinary tract obstruction [69,70,71,72,74].
GCR BLOC 3Grade of Recommendation B (Level of Evidence 3)
It is recommended to perform open surgery for the radical elimination of the source of infection in pregnant women with acute pyelonephritis at the purulent inflammation stage if there is negative dynamics despite adequate antibacterial therapy and restored urine flow (functioning nephrostomy) [74].
LoE CGoR 4Level of evidence C (grade of recommendation – 4).
It is recommended during open surgery in pregnant women with acute pyelonephritis to restore urine flow by removing stones from the kidney and upper third of the ureter whenever possible [75].
Level of recommendation CLevel of evidence 5Level of recommendation C (level of evidence — 5).
It is recommended to perform radical nephrectomy in pregnant women with purulent destruction of more than 2/3 of the renal parenchyma, signs of renal vascular thrombosis, multiple coalescing renal carbuncles, purulent pyelonephritis of a non-functioning kidney, intoxication, toxic shock, or emphysematous pyelonephritis, if conservative therapy fails, to prevent complications [76].
GPP CLOE 4Strength of Recommendation C (Level of Evidence – 4)
4. Medical Rehabilitation and Sanatorium-Resort Treatment
Not applicable.
5. Prevention and Dispensary Observation
It is recommended that a pregnant patient be referred for a single microbiological (culture) urine test for aerobic and facultative anaerobic microorganisms at her first antenatal clinic visit to screen for asymptomatic bacteriuria [17,38].
GCR CLOE 5Grade of Recommendation C (Level of Evidence – 5).
Comment: Repeat screening is generally not indicated for low-risk women with UTI who tested negative initially. It is advisable to repeat microbiological urine testing for aerobic and facultative anaerobic microorganisms in women at high risk of infection (e.g., history of UTI, urinary tract anomalies, diabetes mellitus, etc.) [17,38].
It is recommended to treat asymptomatic bacteriuria in pregnant patients to prevent urinary tract infections [18].
GGR CLOC 5Grade of Recommendation C (Level of Evidence – 5).
Comments: It should be kept in mind that 20%–40% of women with untreated asymptomatic bacteriuria may subsequently develop acute pyelonephritis during pregnancy.
It is recommended that patients diagnosed during the current pregnancy with asymptomatic bacteriuria caused by Group B Streptococcus (GBS ASB) receive intrapartum antibiotic prophylaxis, even if the bacteriuria has been successfully treated and follow-up microbiological (culture) urine tests for bacterial pathogens using automated plating are negative, in order to prevent early-onset neonatal group B streptococcal infection [18].
GCR CLOE 5Grade of Recommendation C (Level of Evidence – 5).
Comment: GBS ASB is a marker of vaginorectal colonization (the source of bacteriuria). Treatment of GBS asymptomatic bacteriuria does not lead to long-term eradication of the microorganism, and newborns of GBS-positive mothers remain at high risk for early-onset GBS-related infection [18].
It is recommended to perform a microbiological (culture) urine test for aerobic and facultative anaerobic microorganisms in pregnant women 1–2 weeks after treatment for ASB to enable timely diagnosis of recurrent acute pyelonephritis [18].
GCR CLOE 5Grade of Recommendation C (Level of Evidence – 5)
It is recommended to use local antibacterial therapy for bacterial vaginosis in pregnant women to prevent urinary tract infections [73].
GCP CLoE 4Grade of Recommendation C (Level of Evidence – 4).
6. Organization of Medical Care
Hospitalization in an inpatient facility is recommended for pregnant women with acute pyelonephritis for evaluation and treatment [4,29].
GCR CLOE 3Grade of Recommendation C (Level of Evidence – 3)
Indications for scheduled inpatient hospitalization:
correction of all anatomical and functional urinary tract abnormalities;
removal of urinary tract drains and catheters;
management of concomitant diseases (diabetes mellitus, renal failure).
Indications for emergency inpatient hospitalization:
history of complicating factors (urolithiasis, diabetes mellitus, urinary tract urodynamic disorders, presence of urinary tract drains and catheters);
severe patient condition (fever with chills, vomiting, tachycardia, shortness of breath).
Indications for discharging the patient from the hospital:
normalization of body temperature;
normalization of the complete blood count (absence of leukocytosis, lymphopenia, decreased ESR);
reduction in the degree of leukocyturia;
absence of upper urinary tract urodynamic disorders.
7. Additional Information
The presence of risk factors in pregnant women with urinary tract infections (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.
Pregnant women with diabetes mellitus may develop infectious interstitial nephritis with microabscesses, acute renal failure, and frequently bacteremia. The inflammatory process can progress insidiously, leading to renal and perinephric abscess formation.
Pregnant women with acute pyelonephritis and concurrent diabetes mellitus are more likely to experience papillary necrosis.
In pregnant women with renal failure, the antibacterial activity of urine is reduced.
In immunosuppression, there is a decrease in the barrier function of the uroepithelial layer and mucus.
Criteria for Evaluating the Quality of Medical Care
№ No. | Quality criterion | Performance |
|---|---|---|
1. | Complete (clinical) urinalysis performed in a pregnant woman with suspected urinary tract infection | Yes/No |
2. | Microbiological (culture) urine test for aerobic and facultative anaerobic microorganisms performed in a pregnant woman with a urinary tract infection | Yes/No |
3. | Renal ultrasound performed in a pregnant woman with acute pyelonephritis | Yes/No |
4. | Complete (clinical) and biochemical (general health) blood counts performed in a pregnant woman with acute pyelonephritis | Yes/No |
5. | Systemic antibacterial therapy administered to a pregnant woman with a urinary tract infection | Yes/No |
References
Show references
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Appendix A1. Working Group Composition
Natalia F. Kravchenko – Cand. Sc. (Med.), Senior Research Fellow at the 1st Department of Obstetric Pathology of Pregnancy, National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov of the Ministry of Health of Russia (Moscow). No conflict of interest.
Gevorg R. Kasyan – D. Sc. (Med.), Professor at the Department of Urology, A.I. Evdokimov Moscow State University of Medicine and Dentistry (Moscow). No conflict of interest.
Tatiana V. Kirsanova – Cand. Sc. (Med.), Senior Research Fellow at the Department of Reproductive Hematology and Clinical Hemostasiology, National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov of the Ministry of Health of Russia (Moscow). No conflict of interest.
Kristina A. Gladkova – Cand. Sc. (Med.), Head of the 1st Obstetric Department of Pregnancy Pathology, Senior Research Fellow at the Institute of Obstetrics, National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov of the Ministry of Health of Russia (Moscow). No conflict of interest.
Natalia E. Shabanova – Cand. Sc. (Med.), Associate Professor, Head of the Department of Clinical Pharmacology of Antimicrobial and Immunobiological Drugs, Institute of Microbiology, Antimicrobial Therapy and Epidemiology, National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov of the Ministry of Health of the Russian Federation (Moscow). No conflict of interest.
Leyla V. Adamyan – Academician of the Russian Academy of Sciences, Doctor of Medical Sciences, Professor, Honored Scientist, Head of the Department of Reproductive Surgery at A.I. Evdokimov Moscow State University of Medicine and Dentistry, Deputy Director for Research at the National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov of the Russian Ministry of Health (Moscow). No conflict of interest.
Natalya V. Artymuk – D.Sc. (Medicine), Professor, Head of the Professor G.A. Ushakov Department of Obstetrics and Gynecology, Kemerovo State Medical University of the Russian Ministry of Health, Chief Freelancer Specialist in Obstetrics and Gynecology of the Russian Ministry of Health in the Siberian Federal District (Kemerovo). No conflict of interest.
Igor I. Baranov – Doctor of Medical Sciences, Professor, Head of the Department of Scientific and Educational Programs at the National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov of the Russian Ministry of Health (Moscow). No conflict of interest.
Bashmakova Nadezhda Vasilievna – MD, PhD, Professor, Chief Researcher, Ural Research Institute of Maternal and Infant Care of the Russian Ministry of Health, Chief Freelance Specialist of the Russian Ministry of Health in Obstetrics and Gynecology in the Ural Federal District (Yekaterinburg). No conflict of interest.
Vitaly F. Bezhenar – Doctor of Medical Sciences, Professor, Head of the Department of Obstetrics, Gynecology and Reproductology at the First Pavlov State Medical University of St. Petersburg of the Russian Ministry of Health, Chief freelance specialist in obstetrics and gynecology of the Russian Ministry of Health in the Northwestern Federal District (St. Petersburg). No conflict of interest.
Tatyana E. Belokrinitskaya – D.Sc. (Medicine), Professor, Head of the Department of Obstetrics and Gynecology, Faculty of Advanced Training and Professional Retraining, Chita State Medical Academy of the Russian Ministry of Health, Honored Doctor of the Russian Federation, Chief Freelancer Specialist in Obstetrics and Gynecology of the Russian Ministry of Health in the Far Eastern Federal District (Chita). No conflict of interest.
Natalia V. Dolgushina – Doctor of Medical Sciences, Professor, Deputy Director – Head of the Department of Scientific Activity Organization at the National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov of the Russian Ministry of Health (Moscow). No conflict of interest.
Andrey V. Zaytsev – Doctor of Medical Sciences, Professor at the Department of Urology, A.I. Evdokimov Moscow State University of Medicine and Dentistry (Moscow). No conflict of interest.
Natalia E. Kan – Professor, Doctor of Medical Sciences, Deputy General Director, Director of the Institute of Obstetrics at the National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov of the Ministry of Health of the Russian Federation. No conflict of interest.
Vladimir A. Klimov – Candidate of Medical Sciences, Chief freelance specialist in obstetrics of the Russian Ministry of Health, Head of the Medical Care Organization Service at the National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov. No conflict of interest.
Irina I. Kukarskaya – Doctor of Medical Sciences, Professor, Chief freelance specialist in obstetrics and gynecology of the Department of Health of the Tyumen Region, Chief Medical Officer of the Tyumen Perinatal Center, Head of the Department of Obstetrics and Gynecology of the Faculty of Advanced Training and Professional Retraining of Tyumen State Medical University (Tyumen). No conflict of interest.
Victoria A. Krutova – MD, Professor, Chief Physician of the Clinic, Vice-Rector for Clinical Work, Kuban State University of the Russian Ministry of Health, Chief freelance specialist in obstetrics and gynecology of the Russian Ministry of Health in the Southern Federal District (Krasnodar). No conflict of interest.
Anna I. Malyshkina – Doctor of Medical Sciences, Professor, Director of the V.N. Gorodkov Ivanovo Research Institute of Motherhood and Childhood of the Russian Ministry of Health, Chief freelance specialist in obstetrics and gynecology of the Russian Ministry of Health in the Central Federal District (Ivanovo). No conflict of interest.
Anton V. Mikhaylov – Doctor of Medical Sciences, Chief Medical Officer of Maternity Hospital No. 17 of St. Petersburg, Chief Obstetrician-Gynecologist of the Health Committee of the Government of St. Petersburg, Professor at the Departments of Obstetrics and Gynecology of the Mechnikov North-Western State Medical University and Obstetrics, Gynecology and Perinatology of the Pavlov First Saint Petersburg State Medical University (St. Petersburg). No conflict of interest.
Olenev Anton Sergeevich – PhD in Medical Sciences, Associate Professor, Chief Freelance Specialist in Obstetrics and Gynecology of the Moscow Healthcare Department, Head of the Perinatal Center, City Clinical Hospital No. 24 (Moscow). No conflict of interest.
Tatiana V. Priputnevich – Corresponding Member of the Russian Academy of Sciences, Doctor of Medical Sciences, Associate Professor, Director of the Institute of Microbiology, Antimicrobial Therapy and Epidemiology at the National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov of the Russian Ministry of Health (Moscow). No conflict of interest.
Viktor E. Radzinsky – Honored Scientist of the Russian Federation, Doctor of Medical Sciences, Professor, Corresponding Member of the Russian Academy of Sciences, Head of the Department of Obstetrics and Gynecology with the Course of Perinatology at the Peoples' Friendship University of Russia of the Ministry of Education of Russia (Moscow). No conflict of interest.
Viktoria A. Sakalo – Obstetrician-Gynecologist at the 1st Department of Obstetric Pathology of Pregnancy, National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov of the Russian Ministry of Health (Moscow). No conflict of interest.
Vladimir N. Serov – Academician of the Russian Academy of Sciences, Doctor of Medical Sciences, Professor, Honored Scientist of the RF, President of the Russian Society of Obstetricians and Gynecologists, Chief Researcher at the National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov of the Russian Ministry of Health (Moscow). No conflict of interest.
Lyubov A. Sinyakova – Doctor of Medical Sciences, Professor, Department of Urology and Surgical Andrology, Russian Medical Academy of Continuous Professional Education of the Russian Ministry of Health (Moscow). No conflict of interest.
Ildar F. Fatkullin – D.Sc. (Medicine), Professor, Head of the Prof. V.S. Gruздеv Department of Obstetrics and Gynecology, Kazan State Medical University, Chief freelance specialist of the Russian Ministry of Health in obstetrics and gynecology in the Volga Federal District (Kazan). No conflict of interest.
Khodzhayeva Zulfiya Sagdullayevna – MD, Professor, Deputy Director for Scientific Work, Institute of Obstetrics, National Medical Research Center for Obstetrics, Gynecology and Perinatology Named after Academician V.I. Kulakov of the Russian Ministry of Health (Moscow). No conflict of interest.
Roman G. Shmakov – Doctor of Medical Sciences, Professor of the RAS, Director of the V.I. Krasnopolsky Moscow Regional Research Institute of Obstetrics and Gynecology, Professor at the G.M. Savelieva Department of Obstetrics and Gynecology, Pediatric Faculty, Pirogov Russian National Research Medical University. No conflict of interest.
Taras V. Shatylko. – Candidate of Medical Sciences, Urologist at the Andrology and Urology Department, National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov of the Russian Ministry of Health (Moscow). No conflict of interest.
Appendix A2. Methodology for Developing Clinical Guidelines
Target audience for these clinical guidelines:
obstetrician-gynecologists
urologists
students; residents, postgraduate students, obstetricians-gynecologists, urologists
lecturers, researchers
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 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 assessing levels of reliable evidence (LRE) for prevention, treatment, and rehabilitation methods (preventive, therapeutic, rehabilitation interventions)
LoE | Transcript |
|---|---|
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 |
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
Related documents
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Order of the Ministry of Health of the Russian Federation No. 1130n dated October 20, 2020. "On approval of the Procedure for the provision of medical care in the field of obstetrics and gynecology (excluding the use of assisted reproductive technologies)"
Order of the Russian Ministry of Health No. 907n dated November 12, 2012, "On Approval of the Procedure for Providing Medical Care to the Adult Population in the Profile 'Urology'."
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American College of Obstetricians and Gynecologists. ACOG Practice Bulletin No. 91: Treatment of urinary tract infections in nonpregnant women. Obstet Gynecol. 2008;111(3):785–94. doi: http://dx.doi.org/ 10.1097/AOG.0b013e318169f6ef. PubMed.
Table 1 – Antibacterial therapy for urinary tract infections (UTIs) in pregnant women
Drug | Daily dose | Duration of course of treatment, days |
|---|---|---|
Amoxicillin + Clavulanic acid** J01CR02 | Oral: 1000 mg (875 mg + 125 mg) every 12 hours or 625 mg (500 mg + 125 mg) every 8 hours IV: 1200 mg (1000 mg + 200 mg) every 8 hours | 7-10 |
Ampicillin+[Sulbactam]** J01CR01 | IV 1500 mg (1000 mg + 500 mg) every 6 hours | 7-10 |
Cefuroxime** J01DC02 | IV: 750 mg every 8 hours | 7-10 |
Cefixime J01DD08 | Oral: 400 mg every 24 hours | 7-10 |
Ceftriaxone** J01DD04 | IV 1-2 g every 24 hours | 7-10 |
Cefoperazone J01DD12 | IV 1-2 g every 12 hours | 7-10 |
Cefotaxime** J01DD01 | IV 2000 mg every 12 hours (contraindicated for formulations containing lidocaine as a diluent) | 7-10 |
Cefepime** J01DE01 | IV 500 mg-1000 mg every 12 hours | 7-10 |
Fosfomycin** (for cystitis) J01XX01 | Oral 3000 mg single dose | 1 |
Table 2 – Regimens for parenteral empiric systemic antibacterial therapy of pyelonephritis in pregnancy
Drug | Dose, interval |
|---|---|
Fosfomycin** J.01.X.X.01 | IV 2000-4000 mg every 6-8 hours |
Amoxicillin + Clavulanic acid** J.01.D.C.02 | IV 1200 mg every 8 hours |
Ampicillin + [Sulbactam]** J.01.C.R | IV 1500 mg every 6 hours |
Cefuroxime** J.01.D.C.02 | IV 750 mg every 8 hours |
Ceftriaxone** J.01.D.D.04 | IV 2000 mg every 24 hours |
Cefotaxime** J.01.D.D.01 | Intravenous 1000–2000 mg every 8 hours |
Cefoperazone + [Sulbactam]** J.01.D.D.62 | Intravenous 2000–4000 every 12 hours |
Cefepime** J.01.D.E.01 | Intravenous 1000 mg every 12 hours |
Severe pyelonephritis caused by hospital-acquired multiresistant strains | |
Meropenem** J.01.D.H.02 | Intravenous 500 mg every 8 hours |
Ertapenem** J.01.D.H.03 | Intravenous 1000 mg every 24 hours |
Imipenem + [Cilastatin]** J.01.D.H.51 | Intravenous 500 every 6 hours or 1000 mg every 8 hours |
Doses are indicated for patients with normal renal function.
Appendix B. Physician Action Algorithms
Appendix C. Patient Information
Urinary tract infection in pregnant women is an infectious and inflammatory disease of the urinary tract caused by various microorganisms entering it via the bloodstream or through the urinary tract lumen. The disease manifests with lumbar pain, fever, chills, nausea and vomiting, as well as urination disorders. In addition, the disease may be asymptomatic. Pregnant women need to be screened in the first trimester of pregnancy to monitor bacteria in the urine. It is necessary to collect a urine sample correctly, minimizing bacterial contamination from the vagina. For optimal urine collection, it is advisable to pre-clean the perineum, spread the labia, and collect a midstream urine sample. If bacteria are present in the urine or urination disorders occur in a pregnant woman, consultation and examination by a physician is mandatory. You will be provided with information on possible measures to prevent relapses, the dangers of uncontrolled antibacterial therapy, the need for regular blood pressure monitoring, and the course of action in case of disease exacerbation. As a result of the progressive course of the disease, premature birth, neonatal infectious diseases, decreased or complete loss of renal function, as well as the development of a septic condition and life-threatening complications are possible.
Appendix G. Assessment Scales, Questionnaires, and Other Evaluation Tools
Not applicable.