Exposure to World Health Organization's AWaRe antibiotics and isolation of multidrug resistant bacteria: a systematic review and meta-analysis

Giorgia Sulis, Sena Sayood, Shashi Katukoori, Neha Bollam, Ige George, Lauren H. Yaeger, Miguel A. Chavez, Emmanuel Tetteh, Sindhu Yarrabelli, Celine Pulcini, Stephan Harbarth, Dominik Mertz, Mike Sharland, Lorenzo Moja, Benedikt Huttner, Sumanth Gandra

Research output: Contribution to journalReview articlepeer-review

48 Scopus citations


Background: Antibiotic use drives antibiotic resistance. Objectives: To systematically review the literature and estimate associations between prior exposure to antibiotics across World Health Organization's (WHO) AWaRe categories (Access, Watch, Reserve) and isolation of critical and high-priority multidrug resistant organisms (MDROs) on the WHO priority pathogen list. Data Sources: Embase, Ovid Medline, Scopus, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov (from inception to 20/08/2020). Study eligibility criteria: Case-control, cohort, or experimental studies that assessed the risk of infection/colonization with MDROs. Participants: Inpatients or outpatients of any age and sex. Interventions: Prior exposure to antibiotics that could be categorized into the AWaRe framework. Data analysis: Tailored design-specific checklists applied to each included study. For each antibiotic/class, crude odds ratios (ORs) were pooled through random-effects meta-analyses, both overall and by MDRO. Heterogeneity was examined. Results: We identified 349 eligible studies. All were observational, prone to bias due to design and lack of adjustment for confounding, and not primarily designed to compare associations across AWaRe categories. We found statistically significant associations between prior exposure to almost all antibiotics/classes across AWaRe categories and colonization/infection with any MDRO. We observed higher ORs for Watch and Reserve antibiotics than with Access antibiotics. First generation cephalosporins (Access) had the least association with any MDRO colonization/infection (58 studies; OR = 1.2 [95% CI: 1.0–1.4]), whereas strongest associations were estimated for linezolid (Reserve) (22 studies; OR = 2.6 [95% CI: 2.1–3.1]), followed by carbapenems (Watch) (237 studies; OR = 2.3 [95% CI: 2.1–2.5]). There was high heterogeneity for all antibiotic/MDRO associations. Conclusions: Optimising use of Access antibiotics is likely to reduce the selection of MDROs and global antibiotic resistance. Despite data limitations, our study offers a strong rationale for further adoption of AWaRe as an important tool to improve antibiotic use globally.

Original languageEnglish
Pages (from-to)1193-1202
Number of pages10
JournalClinical Microbiology and Infection
Issue number9
StatePublished - Sep 2022


  • AWaRe framework
  • Antibiotic exposure
  • Antibiotic stewardship
  • Critical priority pathogens
  • High-priority pathogens
  • Multidrug resistant organisms
  • Resistance selection


Dive into the research topics of 'Exposure to World Health Organization's AWaRe antibiotics and isolation of multidrug resistant bacteria: a systematic review and meta-analysis'. Together they form a unique fingerprint.

Cite this