Genetic Determinants of Resistance among ESBL-Producing Enterobacteriaceae in Community and Hospital Settings in East, Central, and Southern Africa: A Systematic Review and Meta-Analysis of Prevalence.

Abstract

Background: The world prevalence of community and hospital-acquired extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae is increasing tremendously. Bacteria harboring ESBLs are currently the number one critical pathogens posing a major threat to human health.

Objective: To provide a summary of molecular evidence on the prevalence of ESBL-producing Enterobacteriaceae (ESBL-E) and associated genes at community and hospital settings in East, Central, and Southern African countries.

Methods: We conducted a systematic literature search on PubMed and Google Scholar databases for the available molecular studies on ESBL-E in hospitals and community settings in East, Central, and Sothern Africa (ECSA). Published studies in English language involving gene characterization of ESBLs from human samples in hospital and community settings were included in the review, inception to November 2019. A random effect meta-analysis was performed to estimate the prevalence of ESBL-E.

Results: A total of 27 studies involving molecular characterization of resistance genes from 20,225 ESBL-E isolates were included in the analysis. Seventy-four percent of all studies were hospital based, 15% were based in community settings, and others were done in both hospital and community settings. Of all the studies, 63% reported E. coli as the dominant isolate among ESBL-E recovered from clinical samples and Klebsiella pneumoniae was reported dominant isolates in 33% of all studies. A random pooled prevalence of ESBL-E was 38% (95% CI = 24-53%), highest in Congo, 92% (95% CI = 90-94%), and lowest in Zimbabwe, 14% (95% CI = 9-20%). Prevalence was higher in hospital settings 41% (95% CI = 23-58%) compared to community settings 34% (95% CI = 8-60%). ESBL genes detected from clinical isolates with ESBL-E phenotypes in ECSA were those of Ambler molecular class A [1] that belongs to both functional groups 2be and 2d of Bush and Jacob classification of 2010 [2]. Majority of studies (n = 22, 81.5%) reported predominance of blaCTX-M gene among isolates, particularly CTX-M-15. Predictors of ESBL-E included increased age, hospital admissions, previous use of antibiotics, and paramedical use of herbs.

Conclusion: Few studies have been conducted at a molecular level to understand the genetic basis of increased resistance among members of ESBL-E in ECSA. Limited molecular studies in the ECSA region leave a gap in estimating the burden and risk posed by the carriage of ESBL genes in these countries. We found a high prevalence of ESBL-E most carrying CTX-M enzyme in ECSA with a greater variation between countries. This could be an important call for combined (regional or global) efforts to combat the problem of antimicrobial resistance (AMR) in the region. Antibiotic use and hospital admission increased the carriage of ESBL-E, while poor people contributed little to the increase of AMR due to lack of access and failure to meet the cost of healthcare compared to high income individuals.