Recommendation

A seven-day antibiotic regimen is recommended for all pregnant women with asymptomatic bacteriuria (ASB) to prevent persistent bacteriuria, preterm birth and low birth weight.

(Recommended)

 

Publication history

First published: December 2016

Updated: No update planned

Assessed as up-to-date: December 2016

 

Remarks

• This recommendation should be considered alongside the recommendation on ASB diagnosis
• Stakeholders may wish to consider context-specific ASB screening and treatment based on ASB and preterm birth prevalence, as it may not be appropriate in settings with low prevalence.
• Evidence on preterm birth is of low certainty and large multicentre trials are needed to confirm whether screening and antibiotic treatment reduces preterm birth and perinatal mortality in LMICs. Such trials should also aim to evaluate the effects of group B streptococcus (GBS) screening and treatment.
• Studies have shown that GBS bacteriuria is a sign of heavy GBS colonization, which may not be eradicated by antibiotic treatment. GBS bacteriuria is a risk factor for having an infant with early onset GBS disease. WHO recommends that pregnant women with GBS colonization receive intrapartum antibiotic administration to prevent early neonatal GBS infection (see WHO recommendations for prevention and treatment of maternal peripartum infections).
• Preterm birth indicators should be monitored with this intervention, as should changes in antimicrobial resistance.

 

Background

Defined as true bacteriuria in the absence of specific symptoms of acute urinary tract infection, ASB is common in pregnancy, with rates as high as 74% reported in some LMICs (1). Escherichia coli is associated with up to 80% of isolates (2). Other pathogens include Klebsiella species, Proteus mirabilis and group B streptococcus (GBS). While ASB in nonpregnant women is generally benign, in pregnant women obstruction to the flow of urine by the growing fetus and womb leads to stasis in the urinary tract and increases the likelihood of acute pyelonephritis. If untreated, up to 45% of pregnant women with ASB may develop this complication (3), which is associated with an increased risk of preterm birth.

 

Methods

The ANC recommendations are intended to inform the development of relevant health-care policies and clinical protocols. These recommendations were developed in accordance with the methods described in the WHO handbook for guideline development (4). In summary, the process included: identification of priority questions and outcomes, retrieval of evidence, assessment and synthesis of the evidence, formulation of recommendations, and planning for the implementation, dissemination, impact evaluation and updating of the guideline.

The quality of the scientific evidence underpinning the recommendations was graded using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) (5) and Confidence in the Evidence from Reviews of Qualitative research (GRADE-CERQual) (6) approaches, for quantitative and qualitative evidence, respectively. Up-to-date systematic reviews were used to prepare evidence profiles for priority questions. The DECIDE (Developing and Evaluating Communication Strategies to support Informed Decisions and Practice based on Evidence) (7) framework, an evidence-to-decision tool that includes intervention effects, values, resources, equity, acceptability and feasibility criteria, was used to guide the formulation and approval of recommendations by the Guideline Development Group (GDG) – an international group of experts assembled for the purpose of developing this guideline – at three Technical Consultations between October 2015 and March 2016.

To ensure that each recommendation is correctly understood and applied in practice, the context of all context-specific recommendations is clearly stated within each recommendation, and the contributing experts provided additional remarks where needed.

In accordance with WHO guideline development standards, these recommendations will be reviewed and updated following the identification of new evidence, with major reviews and updates at least every five years.

Further information on procedures for developing this recommendation are available here.

 

Recommendation question

For this recommendation, we aimed to answer the following question:

• For pregnant women with ASB (P), does a course of antibiotics (I) compared with no antibiotics (C) improve maternal and perinatal outcomes (O)? If so, what duration of treatment is the most effective?

 

Evidence summary

The evidence on the effects of antibiotics for ASB was derived from a Cochrane review that included 14 trials involving approximately 2000 women (8). Most trials were conducted in HICs between 1960 and 1987. Types of antibiotics included sulfonamides, ampicillin, nitrofurantoin and some antibiotics that are no longer recommended for use in pregnancy, such as tetracycline. Treatment duration between trials varied widely from a single dose, to continuous treatment throughout pregnancy. Bacteriuria was usually defined as at least one clean-catch, midstream or catheterized urine specimen with more than 100 000 bacteria/mL on culture, but other definitions were also used.

Maternal outcomes

The only maternal ANC guideline outcomes reported were infection outcomes. Low-certainty evidence suggests that antibiotics may reduce persistent bacteriuria (4 trials, 596 women; RR: 0.30, 95% CI: 0.18–0.53); however, the evidence on the effect on pyelonephritis is very uncertain.

Fetal and neonatal outcomes

Low-certainty evidence suggests that antibiotics for ASB may reduce low-birth-weight neonates (8 trials, 1437 neonates; RR: 0.64, 95% CI: 0.45–0.93) and preterm birth (2 trials, 142 women; RR: 0.27, 95% CI: 0.11–0.62). No other ANC guideline outcomes were reported.

Additional considerations

The GDG also evaluated evidence on treatment duration (single dose versus short-course [4–7 days]) from a related Cochrane review that included 13 trials involving 1622 women (9). Ten trials compared different durations of treatment with the same antibiotic, and the remaining three compared different durations of treatment with different drugs. A wide variety of antibiotics was used. The resulting pooled evidence on bacterial persistence (7 trials), recurrent ASB (8 trials) and pyelonephritis (2 trials) was judged as very uncertain. However, on sensitivity analysis including high-quality trials of amoxicillin and nitrofurantoin only, the high-certainty evidence indicates that bacterial persistence is reduced with a short course rather than a single dose (2 trials, 803 women; RR: 1.72, 95% CI: 1.27–2.33). High-certainty evidence from one large trial shows that a seven-day course of nitrofurantoin is more effective than a one-day treatment to reduce low birth weight (714 neonates; RR: 1.65, 95% CI: 1.06–2.57). Low-certainty evidence suggests that single-dose treatments may be associated with fewer side-effects (7 trials, 1460 women; RR: 0.70, 95% CI: 0.56–0.88).

The GDG also evaluated evidence on the test accuracy of urine Gram staining and dipstick testing.

Resources

Antibiotic costs vary. Amoxicillin and trimethoprim are much cheaper (potentially around US$ 1–2 for a week’s supply) than nitrofurantoin, which can cost about US$ 7–10 for a week’s supply of tablets (10). Repeated urine testing to check for clearance of

ASB has cost implications for laboratory and human resources, as well as for the affected women. The emergence of antimicrobial resistance is of concern and may limit the choice of antimicrobials (11).

Equity

Preterm birth is the leading cause of neonatal death worldwide, with most deaths occurring in LMICs; therefore, preventing preterm birth among disadvantaged populations might help to address inequalities.

Acceptability

In LMICs, some women hold the belief that pregnancy is a healthy condition and may not accept the use of antibiotics in this context (particularly if they have no symptoms) unless they have experienced a previous pregnancy complication (high confidence in the evidence) (12). Others view ANC as a source of knowledge, information and medical safety, and generally appreciate the interventions and advice they are offered (high confidence in the evidence). However, engagement may be limited if this type of intervention is not explained properly. In addition, where there are likely to be additional costs associated with treatment, women are less likely to engage (high confidence in the evidence).

Feasibility

A lack of resources in LMICs, both in terms of the availability of the medicines and testing, and the lack of suitably trained staff to provide relevant information and perform tests, may limit implementation (high confidence in the evidence)(13).

 

Further information and considerations related to this recommendation can be found in the WHO guidelines, available at:

http://apps.who.int/iris/bitstream/10665/250796/8/9789241549912-websupplement-eng.pdf?ua=1

 

Implementation considerations

• The successful introduction of evidence-based policies related to antenatal care into national programmes and health care services depends on well-planned and participatory consensus-driven processes of adaptation and implementation. These processes may include the development or revision of national guidelines or protocols based on this recommendation.
• The recommendation should be adapted into locally-appropriate documents and tools that are able to meet the specific needs of each country and health service. Modifications to the recommendation, where necessary, should be justified in an explicit and transparent manner.
• An enabling environment should be created for the use of this recommendation, including changes in the behaviour of health care practitioners to enable the use of evidence-based practices.
• Local professional societies may play important roles in this process and an all-inclusive and participatory process should be encouraged.
• Antenatal care models with a minimum of eight contacts are recommended to reduce perinatal mortality and improve women’s experience of care. Taking this as a foundation, the GDG reviewed how ANC should be delivered in terms of both the timing and content of each of the ANC contacts, and arrived at a new model – the 2016 WHO ANC model – which replaces the previous four-visit focused ANC (FANC) model. For the purpose of developing this new ANC model, the ANC recommendations were mapped to the eight contacts based on the evidence supporting each recommendation and the optimal timing of delivery of the recommended interventions to achieve maximal impact.

 

Research implications

The GDG did not identify any priority question related to this recommendation.

 

Related links

WHO recommendations on antenatal care for a positive pregnancy experience

(2016) - full document and evidence tables

Managing Complications in Pregnancy and Childbirth: A guide for midwives and doctors

Pregnancy, Childbirth, Postpartum and Newborn Care: A guide for essential practice

WHO Programmes: Sexual and Reproductive health

Maternal Health

 

 

References

1. Rizvi M, Khan F, Shukla I, Malik A, Shaheen. Rising prevalence of antimicrobial resistance in urinary tract infections during pregnancy: necessity for exploring newer treatment options. J Lab Physicians. 2011;3(2):98–103. doi:10.4103/0974-2727.86842.
2. Smaill FM, Vazquez JC. Antibiotics for asymptomatic bacteriuria in pregnancy. Cochrane Database Syst Rev. 2015;(8):CD000490.
3. Wang E, Smaill F. Infection in pregnancy. In: Chalmers I, Enkin MW, Keirse MJNC, editors. Effective care in pregnancy and childbirth. Oxford: Oxford University Press; 1989:534–7
4. WHO handbook for guideline development, 2nd edition. Geneva: World Health Organization; 2014 (http://www.who.int/kms/handbook_2nd_ ed.pdf, accessed 6 October 2016).
5. GRADE [website]. The GRADE Working Group; 2016 (http://gradeworkinggroup.org/, accessed 27 October 2016).
6. GRADE-CERQual [website]. The GRADECERQual Project Group; 2016 (https://cerqual. org/, accessed 27 October 2016).
7. The DECIDE Project; 2016 (http://www.decide-collaboration.eu/, accessed 27 October 2016).
8. Smaill FM, Vazquez JC. Antibiotics for asymptomatic bacteriuria in pregnancy. Cochrane Database Syst Rev. 2015;(8):CD000490.
9. Joint Formulary Committee. Urinary tract infections. Chapter 5: Infection. In: British National Formulary (BNF) 72. London: BMJ Publishing Group Ltd and Royal Pharmaceutical Society; 2016.
10. Widmer M, Lopez I, Gülmezoglu AM, Mignini L, Roganti A. Duration of treatment for asymptomatic bacteriuria during pregnancy. Cochrane Database Syst Rev. 2015;(11):CD000491.
11. Rizvi M, Khan F, Shukla I, Malik A, Shaheen. Rising prevalence of antimicrobial resistance in urinary tract infections during pregnancy: necessity for exploring newer treatment options. J Lab Physicians. 2011;3(2):98–103. doi:10.4103/0974-2727.86842.
12. Downe S, Finlayson K, Tunçalp Ö, Gülmezoglu AM. Factors that influence the use of routine antenatal services by pregnant women: a qualitative evidence synthesis. Cochrane Database Syst Rev. 2016;(10):CD012392
13. Downe S, Finlayson K, Tunçalp Ö, Gülmezoglu AM. Factors that influence the provision of good quality routine antenatal care services by health staff: a qualitative evidence synthesis. Cochrane Database Syst Rev. 2016

 

Citation: WHO Reproductive Health Library. WHO recommendation on antibiotics for asymptomatic bacteriuria. (December 2016). The WHO Reproductive Health Library; Geneva: World Health Organization.