Question

What is the optimal treatment of urinary tract infections in pregnant women?

 

Is screening and treatment of asymptomatic bacteriuria in pregnant women recommended?

Recommendation

Nitrofurantoin (2 dd 100 mg) is the first choice and co-amoxiclav (3 dd 500/125 mg) is the second choice drug for the treatment of cystitis during pregnancy. Nitrofurantoin must not used in the last 30 days before delivery.

 

A 3rd generation cephalosporin (4 dd 1000 mg cefotaxime or 1 dd 2000 mg ceftriaxone) is the drug of first choice for the treatment of pyelonephritis during pregnancy.

 

The treatment duration of cystitis and pyelonephritis during pregnancy should be at least 5 days, and 10-14 days, respectively.

 

Antepartum pyelonephritis should be treated in a hospital setting and treatment should be started intravenously.

 

Screening and treatment of asymptomatic bacteriuria at 16-20 weeks gestation for better maternal and neonatal outcome is not recommended until new evidence is available. Exceptions are women with urinary tract anomalies and/or medical conditions including diabetes mellitus, renal transplant, sickle cell disease and neurological problems.

 

When Group B streptococcus (GBS) is present in the urine, which is a symptom of severe maternal GBS colonization, consultation with the gynaecologist is advised, because antibiotic prophylaxis during delivery is necessary.

Introduction

This guideline does not include individual introductions to each module. A general introduction can be found in the attachments under the heading 'related'.

Conclusions

Level 1

Antibiotic treatment of urinary tract infections during pregnancy results in reduction of new UTIs and pregnancy complications [(67) A1].

 

 

Level 2

Nitrofurantoin during the first trimester is not associated with increased risk of major malformations or other secondary adverse pregnancy outcomes. However, dispensing nitrofurantoin the last 30 days before delivery is associated with increased risk of neonatal jaundice (10.8%) compared with unexposed women (8.1%) [ (77) A2]

 

Level 3

In pregnant women suspected of having pyelonephritis empirical intravenous therapy requiring antepartum hospitalization results in good clinical outcome [(70) C, (71) D].

 

Level 1

A urine culture positive for group B streptococcus (GBS) is a sign of severe maternal GBS colonization, and consultation of a gynaecologist is advised, and in all cases administration of antibiotic prophylaxis during delivery is necessary [(76) A1; (78) A2].

Literature summary

Asymptomatic bacteriuria (ASB) is the presence of significant bacteriuria without the symptoms of a UTI. The prevalence of ASB is 2-10% in pregnant women. ASB during pregnancy can lead to serious complications for both mother and child. The incidence of ASB is similar in both pregnant and non-pregnant women (60). Pregnant women with ASB, however, develop pyelonephritis more often, probably due to the anatomic and physiologic changes that occur during pregnancy, which may facilitate bacterial growth and ascent of bacteria to the kidneys (61). If left untreated, 20-40% of pregnant women with ASB will develop pyelonephritis (60), (62), (63),  (64), (65).

 

Other possible adverse effects, such as preterm delivery and delivering a low birth weight infant, are less well established. Preterm delivery is the main cause of neonatal mortality and morbidity worldwide. The causal mechanisms remain unknown. One of the hypotheses is that endotoxins released by bacteria cause uterine contractions leading to preterm delivery.

UTIs, including pyelonephritis, are among the most common health problems during pregnancy. They occur in up to 20% of pregnancies in some disadvantaged populations (66). Pyelonephritis is an acute episode diagnosed in 1.4% of pregnant women. It can have serious complications of sepsis and acute respiratory and renal insufficiency, and death.

 

Choice of drug  

Antibiotic treatment in pregnancy is effective for the cure of UTIs and complications are rare (67). In a recent study, dispensing nitrofurantoin during the first trimester was not associated with increased risk of major malformations or other secondary adverse pregnancy outcomes when compared with the disease comparison group. However, dispensing nitrofurantoin the last 30 days before delivery was associated with increased risk of neonatal jaundice (103 of 959 [10.8%]) compared with unexposed women (10,336 of 127,507 [8.1%], OR 1.31, 95% CI 1.02-1.70) (77).

In view of the lack of teratogeniceffects described and the resistance percentages, the beta-lactam antibiotics are also a good choice for the treatment of a UTI during pregnancy. Nitrofurantoin (2 dd 100 mg) and co-amoxiclav (3dd 500/125 mg) are first-choice drugs for the treatment of cystitis during pregnancy in the guideline of the Dutch Society for Obstetrics and Gynaecology (NVOG). Nitrofurantoin must not used in the last days before delivery because of  neonatal polyneuropathy, and fetal anemia in the 3rd trimester in glucose-6 phosphate dehydrogenase (G6PD) deficient women is described (68). Both regimens are in line with national guidelines for non-pregnant women, and are effective and safe. In the most recent update, single-dose regimen antibiotics for the treatment of a symptomatic UTI may be less effective than the short-course regimens (4-7 day regimen) regarding cure rates, recurrences and pregnancy complications including preterm birth (67). Short-term relief of symptoms is achieved at a similar rate by a 3-day regimen and prolonged antibiotic therapy for cystitis; however, women with cystitis treated with antibiotics for 5 days (or longer) had better eradication of uropathogens (69).

 

In pregnant women suspected of having pyelonephritis empirical intravenous therapy requiring antepartum hospitalization should be started (70), (71). Although there are insufficient data to recommend a specific treatment regimen for pyelonephritis in pregnancy, a 3rd generation cephalosporin (4 dd 1000 mg cefotaxime or 1 dd 2000 mg ceftriaxone) is the drug of first choice for the treatment of a pyelonephritis during pregnancy, because no adverse effects have been described (72). Intravenous antimicrobial therapy should be continued until the woman is afebrile for 24-48 hours and symptoms have improved; afterward women can be treated with oral antibacterial therapy based on the culture results. The total treatment duration should be at least 10 days. Experts recommend that after completion of therapy a urine culture should be obtained to verify resolution of the bacteriuria (www.nvog.nl), (71), (73). The incidence of recurrent pyelonephritis is decreased in women treated with antimicrobial suppression during pregnancy. However, data on evidence and safety are lacking for prophylactic treatment for the duration of pregnancy (74).

 

Whenever a group B streptococcus (GBS) is found in the urine culture, this is a sign of maternal colonization with GBS. Intravenous antibiotic treatment of the mother during delivery reduces the number of neonatal infections with GBS (75). As far as GBS is concerned, in the NVOG guideline Prevention of Perinatal Group B Streptococcus Disease published in 1998, screening is not recommended; however, in the event of severe maternal GBS colonization (and therefore GBS in the urine) consultation with the gynaecologist is advised and in all cases administration of antibiotic prophylaxis during delivery is necessary (76).

Search and select

Databases were Pubmed and the Cochrane library.

 

Keywords: [urinary tract infection OR urosepsis OR pyelonephritis] AND pregnancy AND treatment

 

Limits: English, adults, humans, clinical trials, guideline, meta-analysis, RCT, review, last 10 years.

 

143 publication since Cochrane review

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Evidence tables

This guideline does not include evidence tables.

Considerations

Treatment of ASB is similar to that of cystitis (79), but it is currently recommended not to screen for ASB (www.nvog.nl). An RCT is currently being conducted to accumulate evidence for screening and treatment of ASB at 20 weeks gestation for better maternal and neonatal outcome, and cost-efficacy (trial number NTR3068).

Antibiotic treatment is effective in reducing the risk of pyelonephritis in pregnancy (65).

Due to the higher incidence of side effects of co-amoxiclav compared to nitrofurantoin, the Guideline committee recommends to use nitrofurantoin as the first and co-amoxiclav as the second choice empirical agent in pregnant women with a cystitis.

Women with urinary tract anomalies and medical conditions including diabetes mellitus, sickle cell disease and neurological problems are at increased risk for acquiring pyelonephritis in pregnancy. Therefore, experts recommend to culture the urine of these women at 16-20 weeks of gestation.

Authorization date and validity

Last review : 01-03-2013

Last authorization : 01-03-2013

This guideline was developed and approved by representatives of the professional medical societies, mentioned in the introduction and methods sections and therefore represents the current professional standard in 2013. The guideline contains general recommendations. It is possible that, in individual cases, these recommendations do not apply. Applicability of the guideline in clinical practice resorts to the responsibility of every individual practitioner. Facts or circumstances may occur, in which deviation of the guideline is justified, in order to provide optimal quality of care for the patient.

Initiative and authorization

Initiative : Stichting Werkgroep Antibioticabeleid

Authorized by:
  • Nederlandse Huisartsen Genootschap
  • Nederlandse Internisten Vereniging
  • Nederlandse Vereniging voor Medische microbiologie
  • Nederlandse Vereniging voor Obstetrie en Gynaecologie
  • Nederlandse Vereniging voor Urologie

General details

Development of this guideline was supported and financed by the SKMS (Kwaliteitsgelden Medisch Specialisten).

Scope and target group

The objective of these guidelines is to update clinicians with regard to important advances and controversies in the antibiotic treatment of patients with complicated urinary tract infections (UTIs).

 

The guidelines described here cover the empirical antimicrobial therapy of adult patients (for this guideline 12 years or older) with a complicated UTI admitted to a hospital (emergency room or ward) in the Netherlands. Uncomplicated UTIs are treated predominantly by the general practitioner. For the relevant guidelines, see the recently updated Standard for Urinary Tract Infections of the Dutch Society of General Practitioners (NHG). We have tried to adhere to this standard insofar as possible. Urethritis and epididymitis are not included in this guideline.

The Guidelines give a general therapy advice for all UTI with systemic symptoms because, at first presentation of a patient, it is not always possible to differentiate between an acute prostatitis, pyelonephritis or urosepsis. In addition, this differentiation has no consequences for the choice of empirical antimicrobial therapy. Apart from these general guidelines, we give specific advice for certain groups of patients separately.

Samenstelling werkgroep

Preparation of the guideline text was carried out by a multidisciplinary committee consisting of experts, delegated from the professional societies for infectious diseases (VIZ), medical microbiology (NVMM), hospital pharmacists (NVZA), urology (NVU), gynaecology (NVO), nephrology (NFN) and general practice (NHG). After consultation with the members of these professional societies, the definitive guideline was drawn up by the delegates and approved by the board of SWAB.

 

  • Dr. S.E. Geerlings (coordinator, SWAB), Internal Medicine/Infectious Diseases specialist, Department of Internal Medicine, Division of Infectious Diseases, Academic Medical Center, Amsterdam
  • Dr. C. van Nieuwkoop (VIZ, NIV), Internal Medicine, Emergency Medicine and Infectious Diseases specialist, Department of Internal Medicine, Hagaziekenhuis, the Hague
  • E. van Haarst (NVU), Urologist, Department of Urology, St. Lucas Andreas Hospital, Amsterdam
  • Dr. M. van Buren (NFN), Internal Medicine and Nephrology specialist, Department of Internal Medicine, Hagaziekenhuis, the Hague
  • Dr. B.J. Knottnerus (NHG), General Practitioner, Department General Practice, Academic Medical Center, Amsterdam
  • Dr. E. E. Stobberingh (NVMM), Medical microbiologist, Lab Medical Microbiology, Maastricht Univerisity Medical Center, Maastricht
  • Prof. dr. C.J. de Groot (NVOG), Gynaecologist, Department of Obstetrics and Gynaecology, Vrije Universiteit Medical Center, Amsterdam
  • Prof. dr. J.M. Prins (SWAB), Internal Medicine/Infectious Diseases specialist, Department of Internal Medicine, Division of Infectious Diseases, Academic Medical Center, Amsterdam

 

The Guideline committee would also like to thank Frederique Bemelman (nephrologist) for her comments on the chapter about renal transplantation and Albert Vollaard (infectious disease specialist) for his comments on the subchapter about methenamine.

Declaration of interest

The SWAB employs strict guidelines with regard to potential conflicts of interests as described in the SWAB Format for Guideline Development (www.swab.nl). Members of the preparatory committee reported the following potential conflicts of interest:

 

SE Geerlings: for the RCTs mentioned in the reference numbers 84 en 168 (Beerepoot et al.): Ref 84: Cranberry capsules and placebo capsules for this trial were delivered by Springfield Nutraceuticals, Oud Beijerland, The Netherlands. Ref 168: Chr Hansen A/S, Denmark has the patents for Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14 and donated the placebo capsules for this trial.

E v Haarst: has received speaker fees on a national urological symposium from GlaxoSmithKline, the manufacturer of amoxicillin-clavulanic acid.

Other authors: no potential conflicts of interest declared.

Patient involvement

This guideline does not include patient involvement.

Method of development

Evidence based

Implementation

This guideline does not include an implementation strategy.

Methods and proces

This guideline was drawn up according to the recommendations for evidence-based development of guidelines (6), (Evidence-Based Richtlijn-Ontwikkeling (EBRO) and Appraisal of Guidelines Research and Evaluation (AGREE), www.agreecollaboration.org). The guidelines are derived from a review of literature based on the 9 key questions concerning the treatment of UTI. Studies were assigned a degree of evidential value according to the handbook of the Dutch Institute for Healthcare Improvement (Centraal Begeleidingsorgaan/Kwaliteitsinstituut voor de gezondheidszorg, CBO) (CBO. Evidence-based Richtlijnontwikkeling, handleiding voor werkgroepleden. Utrecht: CBO; 2007). Conclusions were drawn, completed with the specific level of evidence, according to the grading system adopted by SWAB (Table 1 and 2). The only exception concerns Nethmap, an annual report from which the resistance surveillance data were used. The Guideline committee cannot give Nethmap a level of evidence and decided to use an asterix (*), but is of the opinion that the results can be given substantial weight, since the surveillance data described in Nethmap cover 30% of the Dutch population. Subsequently, specific recommendations were formulated.

In order to develop recommendations for the optimal treatment of UTI, the literature was searched for the key questions. For each question a literature search was performed in the PubMed database (January 1966 to January 2012) as well as in the Cochrane Register of Controlled Trials (CENTRAL). For resistance surveillance data NethMap 2011 was used, and for the interpretation of susceptibility test results, in addition, reports of the European Committee on Antimicrobial Susceptibility Testing (EUCAST) were used. When scientific verification could not be found, the guideline text was formulated on the basis of the opinions and experiences of the members of the Guideline committee.

Search strategy

Searches are available upon request. Please contact the Richtlijnendatabase.