WHO recommendation on the method for diagnosing asymptomatic bacteriuria in pregnancy

WHO recommendation on the method for diagnosing asymptomatic bacteriuria in pregnancy

 

Recommendation

Midstream urine culture is the recommended method for diagnosing asymptomatic bacteriuria (ASB) in pregnancy. In settings where urine culture is not available, on-site midstream urine Gram staining is recommended over the use of dipstick tests as the method for diagnosing ASB in pregnancy.

(Context-specific recommendation)

 

Publication history

First published: December 2016

Updated: No update planned

Assessed as up-to-date: December 2016

 

Remarks

  • This recommendation should be considered alongside Recommendation on ASB treatment.
  • The GDG agreed that the higher resource costs associated with Gram stain testing might reduce the feasibility of this method in low-resource settings, in which case, dipstick tests may be used.
  • The GDG agreed that ASB is a priority research topic, given its association with preterm birth and the uncertainty around urine testing and treatment in settings with different levels of ASB prevalence. Specifically, studies are needed that compare on-site testing and treatment versus testing plus confirmation of test with treatment on confirmatory culture, to explore health and other relevant outcomes, including acceptability, feasibility and antimicrobial resistance. In addition, better on-site tests need to be developed to improve accuracy and feasibility of testing and to reduce overtreatment of ASB. Research is also needed to determine the prevalence of ASB at which targeted testing and treatment rather than universal testing and treatment might be effective.
  • Context-specific recommendation refers to: recommended only in the context of rigorous research/ recommended only with targeted monitoring and evaluation/ recommended only in other specific contexts.

 

 

Background

Asymptomatic bacteriuria (ASB) is a common urinary tract condition that is associated with an increased risk of urinary tract infections (cystitis and pyelonephritis) in pregnant women. Escherichia coli is associated with up to 80% of isolates; other pathogens include Klebsiella species, Proteus mirabilis and group B streptococcus (GBS) (1).

Methods for diagnosing ASB include midstream urine culture (the gold standard), Gram stain and urine dipstick tests. A urine culture can take up to seven days to get a result, with the threshold for diagnosis usually defined as the presence of 105 colony-forming units (cfu)/mL of a single organism (2). The Gram stain test uses colour stains (crystal violet and safrinin O) to exaggerate and distinguish between Gram-positive (purple) and Gram-negative (red) organisms on a prepared glass slide. Urine dipsticks test for nitrites, which are not found in normal urine, and leucocytes, which are identified by a reaction with leucocyte esterase, to identify the presence of bacteria and pus in the urine, respectively.

ASB is associated with an increased risk of preterm birth; once detected it is, therefore, usually actively managed with antibiotics.

 

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 (3). 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) (4) and Confidence in the Evidence from Reviews of Qualitative research (GRADE-CERQual) (5) 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) (6) 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 (P), what is the diagnostic value of Gram stain and dipstick on-site urine tests (I) compared with the reference standard (urine culture) (C) to detect ASB (O)?

 

 

Evidence summary

The evidence was derived from a test accuracy review of on-site urine tests conducted to support the ANC guideline (7). Four studies (1904 pregnant women) contributed data on urine Gram staining and eight studies (5690 pregnant women) contributed data on urine dipsticks. Most of the studies were conducted in LMICs. The average prevalence of ASB in the studies was 8%. A Gram stain was positive if one or more bacteria were detected per oilimmersed field, and a dipstick test was positive if it detected either nitrites or leucocytes. The reference standard used was urine culture with a threshold of 105 cfu/mL. However, the certainty of the evidence on the accuracy of both Gram stain tests and dipstick tests is very low, with pooled sensitivity and specificity of the Gram stain test estimated at 0.86 (95% CI: 0.80– 0.91) and 0.97 (95% CI: 0.93–0.99), respectively, and pooled sensitivity and specificity for urine dipsticks estimated at 0.73 (95% CI: 0.59–0.83) and 0.89 (95% CI: 0.79–0.94), respectively. A positive nitrite test alone on dipsticks was found to be less sensitive but more specific than when urine leucocytes were also considered.

 

Further information on evidence supporting this recommendation are available here.

 

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.

 

Additional considerations

  • A high level of accuracy in detecting ASB is important to avoid treating women unnecessarily, particularly in view of increasing antimicrobial resistance. Based on the uncertain evidence above, and assuming a prevalence of ASB of 9%, there would be 18 and 118 false-positive tests per 1000 women tested with Gram stain and dipstick tests, respectively. This suggests that, in settings where pregnant women are treated for ASB, dipstick diagnosis of ASB might lead to many women receiving unnecessary treatment.
  • Dipstick tests are multi-test strips that, in addition to testing for nitrites and leucocytes, may also include detection of urine protein and glucose. However, the accuracy of dipsticks to detect conditions associated with proteinuria (preeclampsia) and glycosuria (diabetes mellitus) is considered to be low.
  • Dipsticks are relatively low cost compared with the Gram stain test, as the latter requires trained staff and laboratory equipment and supplies (microscope, glass slides, reagents, Bunsen burner or slide warmer). Gram stain tests take longer to perform and to produce results than urine dipstick tests (10–30 minutes vs 60 seconds).
  • Preterm birth is the leading cause of neonatal death worldwide, with most deaths occurring in LMICs. Timely diagnosis and treatment of risk factors associated with preterm birth might therefore help to address health inequalities.
  • Qualitative evidence from a range of settings suggests that women view ANC as a source of knowledge, information and clinical expertise and that they generally appreciate the tests and advice they are offered (high confidence in the evidence) (8). However, engagement with ANC services may be limited if tests and procedures are not explained properly or when women feel their beliefs and traditions are being overlooked or ignored by healthcare professionals. In addition, if the Gram stain test is associated with long waiting times at ANC or having to return for test results, this may be less acceptable to women, as it might have additional cost and convenience implications for them (high confidence in the evidence).
  • Health professionals are likely to prefer the dipstick test as it is associated with less effort (no need to label samples for laboratory assessment, perform tests or schedule follow-up visits to provide the results) and might provide additional information pertaining to other conditions (pre-eclampsia and diabetes mellitus) (high confidence in the evidence).
  • Qualitative evidence indicates that, in some LMIC settings, the lack of diagnostic equipment at ANC facilities discourages women from attending, and that providers often do not have the diagnostic equipment, supplies or skills to perform tests (high confidence in the evidence) (9). Therefore, urine dipstick tests, which are cheaper and easy to perform, might be more feasible in low-resource settings.

 

Research implications

The GDG identified these research priorities related to this recommendation

  • What are the effects of on-site urine testing (dipsticks or Gram stain) with antibiotic treatment for ASB versus urine testing plus culture confirmation of urine test, followed by ASB treatment if indicated, on pregnancy and other relevant outcomes, including equity, acceptability, feasibility and antimicrobial resistance?
  • Can better on-site tests to diagnose ASB be developed to improve accuracy and feasibility of ASB testing and reduce overtreatment of ASB? What is the threshold prevalence of ASB at which targeted testing and treatment rather than universal testing and treatment might be a more effective strategy?

 

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

  1. Smaill FM, Vazquez JC. Antibiotics for asymptomatic bacteriuria in pregnancy. Cochrane Database Syst Rev. 2015;(8):CD000490.Sobhy S, Rogozinska E, Khan KS. Accuracy of onsite tests to detect anaemia in antenatal care: a systematic review. BJOG. 2016 (in press).
  2. Schmiemann G, Kniehl E, Gebhardt K, Matejczyk MM, Hummers-Pradier E. The diagnosis of urinary tract infection: a systematic review. Deutsches Ärzteblatt International. 2010;107(21):361–7. doi:10.3238/ arztebl.2010.0361
  3. 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).
  4. GRADE [website]. The GRADE Working Group; 2016 (http://gradeworkinggroup.org/, accessed 27 October 2016).
  5. GRADE-CERQual [website]. The GRADECERQual Project Group; 2016 (https://cerqual. org/, accessed 27 October 2016). 17. DECIDE [website].
  6. The DECIDE Project; 2016 (http://www.decide-collaboration.eu/, accessed 27 October 2016).
  7. Rogozinska E, Formina S, Zamora J, Mignini L, Khan KS. Accuracy of on-site tests to detect asymptomatic bacteriuria in pregnancy: a systematic review and meta-analysis. Obstet Gynecol. 2016;128(3):495–503. doi:10.1097/ AOG.0000000000001597.
  8. 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.
  9. 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 (in press).

 

Citation: WHO Reproductive Health Library. WHO recommendation on the method for diagnosing asymptomatic bacteriuria in pregnancy (December 2016). The WHO Reproductive Health Library; Geneva: World Health Organization.