29 August 2021
WHO recommendation on antibiotics for asymptomatic bacteriuria
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
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:
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
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
References
Citation: WHO Reproductive Health Library. WHO recommendation on antibiotics for asymptomatic bacteriuria. (December 2016). The WHO Reproductive Health Library; Geneva: World Health Organization.
Even though the limited number of trials included in this review found oral, intramuscular and intravenous iron to increase maternal haemoglobin values, the data were not sufficient to ascertain the clinical significance of these findings. Hence, this review does not recommend any treatment for iron-deficiency anaemia in pregnant women.
Read ArticleVitamin D supplementation is not recommended for pregnant women to improve maternal and perinatal outcomes.
Read ArticleThe full intravenous or intramuscular magnesium sulfate regimens are recommended for the prevention and treatment of eclampsia.
Read Article