Review and analysis of the overlapping threats of carbapenem and polymyxin resistant E. coli and Klebsiella in Africa.

BACKGROUND: Carbapenem-resistant Enterobacterales are among the most serious antimicrobial resistance (AMR) threats. Emerging resistance to polymyxins raises the specter of untreatable infections. These resistant organisms have spread globally but, as indicated in WHO reports, the surveillance needed to identify and track them is insufficient, particularly in less resourced countries. This study employs comprehensive search strategies with data extraction, meta-analysis and mapping to help address gaps in the understanding of the risks of carbapenem and polymyxin resistance in the nations of Africa. METHODS: Three comprehensive Boolean searches were constructed and utilized to query scientific and medical databases as well as grey literature sources through the end of 2019. Search results were screened to exclude irrelevant results and remaining studies were examined for relevant information regarding carbapenem and/or polymyxin(s) susceptibility and/or resistance amongst E. coli and Klebsiella isolates from humans. Such data and study characteristics were extracted and coded, and the resulting data was analyzed and geographically mapped. RESULTS: Our analysis yielded 1341 reports documenting carbapenem resistance in 40 of 54 nations. Resistance among E. coli was estimated as high (> 5%) in 3, moderate (1-5%) in 8 and low (< 1%) in 14 nations with at least 100 representative isolates from 2010 to 2019, while present in 9 others with insufficient isolates to support estimates. Carbapenem resistance was generally higher among Klebsiella: high in 10 nations, moderate in 6, low in 6, and present in 11 with insufficient isolates for estimates. While much less information was available concerning polymyxins, we found 341 reports from 33 of 54 nations, documenting resistance in 23. Resistance among E. coli was high in 2 nations, moderate in 1 and low in 6, while present in 10 with insufficient isolates for estimates. Among Klebsiella, resistance was low in 8 nations and present in 8 with insufficient isolates for estimates. The most widespread associated genotypes were, for carbapenems, blaOXA-48, blaNDM-1 and blaOXA-181 and, for polymyxins, mcr-1, mgrB, and phoPQ/pmrAB. Overlapping carbapenem and polymyxin resistance was documented in 23 nations. CONCLUSIONS: While numerous data gaps remain, these data show that significant carbapenem resistance is widespread in Africa and polymyxin resistance is also widely distributed, indicating the need to support robust AMR surveillance, antimicrobial stewardship and infection control in a manner that also addresses broader animal and environmental health dimensions.

Carbapenem and colistin resistance in Enterobacteriaceae in Southeast Asia: Review and mapping of emerging and overlapping challenges.

Carbapenem-resistant Enterobacteriaceae infections have spread globally, leaving polymyxins, including colistin, as 'last-resort treatments'. Emerging colistin resistance raises the spectre of untreatable infections. Despite this threat, data remain limited for much of the world, including Southeast Asia where only 3 of 11 nations submitted data on carbapenem and colistin resistance for recent World Health Organization (WHO) reports. To improve our understanding of the challenge, we utilised broad strategies to search for and analyse data on carbapenem and colistin resistance among Escherichia coli and Klebsiella in Southeast Asia. We found 258 studies containing 526 unique reports and document carbapenem-resistant E. coli and Klebsiella in 8 and 9 of 11 nations, respectively. We estimated carbapenem resistance proportions through meta-analysis of extracted data for nations with ≥100 representative isolates. Estimated resistance among Klebsiella was high (>5%) in four nations (Indonesia, Philippines, Thailand and Vietnam), moderate (1-5%) in two nations (Malaysia and Singapore) and low (<1%) in two nations (Cambodia and Brunei). For E. coli, resistance was generally lower but was high in two of seven nations with ≥100 isolates (Indonesia and Myanmar). The most common carbapenemases were NDM metallo-ß-lactamases and OXA ß-lactamases. Despite sparse data, polymyxin resistance was documented in 8 of 11 nations, with mcr-1 being the predominant genotype. Widespread presence of carbapenem and polymyxin resistance, including their overlap in eight nations, represents a continuing risk and increases the threat of infections resistant to both classes. These findings, and remaining data gaps, highlight the urgent need for sufficiently-resourced robust antimicrobial resistance surveillance.

Review and mapping of carbapenem-resistant Enterobacteriaceae in Africa: Using diverse data to inform surveillance gaps.

Carbapenem-resistant Enterobacteriaceae (CRE) are among the most difficult to treat emerging multidrug-resistant organisms. Major limitations exist in surveillance needed to address CRE, particularly in areas with inadequate resources. We utilised optimised strategies to search for data on carbapenem susceptibility of Klebsiella spp. and Escherichia coli from the World Health Organization (WHO) Africa Region. Core data elements were extracted for meta-analysis and mapping. Despite sparse data in existing reviews, 180 documents including 314 reports on susceptibility of E. coli and/or Klebsiella were located, providing information on 31 (66%) of 47 nations. Carbapenem-resistant E. coli or Klebsiella were identified in 22 (71%) of these 31 countries. Crude resistance proportions were estimated for nations with >100 representative isolates. Median resistance among E. coli was <1% in 11 (61%) of 18 nations meeting criteria, 1-5% in 6 nations (33%) and >5% in 1 nation (6%). For Klebsiella spp., corresponding figures were <1% in 10 (67%) of 15 nations, 1-5% in 3 nations (20%) and >5% in 2 nations (13%). Comprehensive, customised search strategies with analysis and mapping of defined data elements provide an enhanced view of carbapenem-resistant E. coli and Klebsiella in Africa. These CRE are widely distributed and are generally present at low to moderate levels. Whilst use of diverse and largely clinically derived data has limitations and cannot substitute for surveillance, it can enhance situational awareness. The approaches utilised can support improved risk understanding and prioritisation and may be applied to other micro-organisms and areas where surveillance remains inadequate.