Are low-income and middle-income countries being neglected in genomic surveillance of the emergence and spread of multidrug-resistant Enterobacterales?
Authors: Dennis Nurjadi, Sébastien Boutin, Thirumalaisamy P Velavan
Journal: The Lancet Microbe (2024)

In their Comment, Fábio Parra Sellera and colleagues1Sellera FP Lincopan N Fuentes-Castillo D Stehling EG Furlan JPR Rapid evolution of pan-beta-lactam resistance in Enterobacterales co-producing KPC and NDM: insights from global genomic analysis after the COVID-19 pandemic.Lancet Microbe. 2024; (published online Feb 14)https://doi.org/10.1016/S2666-5247(24)00018-1Summary Full Text Full Text PDF PubMed Scopus (0) Google Scholar highlighted a disturbing global trend towards the evolution and spread of pan-β-lactam-resistant Enterobacterales, revealing that 249 (0·7%) of 35 761 strains, extracted from genomic surveillance data, showed dual carbapenemase production, specifically attributed to Klebsiella pneumoniae co-producing New Delhi metallo-β-lactamase (NDM) and Klebsiella pneumoniae carbapenemase (KPC). Similar rates were observed in Italy (0·8%)2Bianco G Boattini M Comini S et al.Occurrence of multi-carbapenemases producers among carbapenemase-producing Enterobacterales and in vitro activity of combinations including cefiderocol, ceftazidime-avibactam, meropenem-vaborbactam, and aztreonam in the COVID-19 era.Eur J Clin Microbiol Infect Dis. 2022; 41: 573-580Crossref PubMed Scopus (13) Google Scholar and the USA (0·4%).3Ham DC Mahon G Bhaurla SK et al.Gram-negative bacteria harboring multiple carbapenemase genes, United States, 2012–2019.Emerg Infect Dis. 2021; 27: 2475-2479Crossref PubMed Scopus (8) Google Scholar Although genomes obtained from 21 countries were analysed by Sellera and colleagues, the data were predominantly from high-income regions in Europe, Asia, and the Americas, raising concerns about the under-representation of genomic surveillance data in low-income and middle-income countries (LMICs) in the Association of Southeast Asian Nations (ASEAN) and Africa (appendix p 2). A recent study by Pham and colleagues4Pham MH Hoi LT Beale MA et al.Evidence of widespread endemic populations of highly multidrug resistant Klebsiella pneumoniae in hospital settings in Hanoi, Vietnam: a prospective cohort study.Lancet Microbe. 2023; 4: e255-e263Summary Full Text Full Text PDF PubMed Scopus (0) Google Scholar revealed a more alarming trend in Viet Nam, where 47% of circulating K pneumoniae strains were double carbapenemase producers (mainly co-producing NDM-1 and KPC-2). Unpublished data from our study conducted in Viet Nam are consistent with this trend, showing that 29% of K pneumoniae strains co-produced NDM-1 and KPC-2 (12%) or NDM-4 and OXA-181 (17%). This substantially increased proportion of dual carbapenemase producers in carbapenem-resistant K pneumoniae highlights the inadequate representation of genomic surveillance in LMICs and challenges the findings that are over-represented in high-income countries. The global expansion of dual carbapenemase producers might be driven by countries in the ASEAN, such as Viet Nam, Cambodia, Laos, the Philippines, Thailand, and Indonesia. Although these regions are acknowledged as hot spots for multidrug-resistant bacteria, widespread implementation of genomic surveillance for antimicrobial resistance is hampered owing to infrastructural challenges5Jauneikaite E Baker KS Nunn JG et al.Genomics for antimicrobial resistance surveillance to support infection prevention and control in health-care facilities.Lancet Microbe. 2023; 4: e1040-e1046Summary Full Text Full Text PDF PubMed Scopus (0) Google Scholar, thus making these regions potentially inadequate contributors to this alarming trend. The evolutionary trajectory of multidrug-resistant Enterobacterales is likely to be shaped by antibiotic consumption; in LMICs, humans and livestock show the highest levels of antibiotic usage, which influences the development of multidrug resistance.6Browne AJ Chipeta MG Haines-Woodhouse G et al.Global antibiotic consumption and usage in humans, 2000–18: a spatial modelling study.Lancet Planet Health. 2021; 5: e893-e904Summary Full Text Full Text PDF PubMed Google Scholar This process results in contaminated wastewater, which affects food crops, water, soil, and ecosystems, promoting the occurrence of antibiotic-resistant bacteria and emergence of antibiotic resistance genes. Many LMICs do not have mandatory measures in place to monitor and eliminate antibiotic-resistant bacteria and antibiotic resistance genes during wastewater treatment. Bridging this gap is essential for the development of effective global strategies to combat antimicrobial resistance within the One Health framework. Although we acknowledge and agree with the viewpoints of Sellera and colleagues1Sellera FP Lincopan N Fuentes-Castillo D Stehling EG Furlan JPR Rapid evolution of pan-beta-lactam resistance in Enterobacterales co-producing KPC and NDM: insights from global genomic analysis after the COVID-19 pandemic.Lancet Microbe. 2024; (published online Feb 14)https://doi.org/10.1016/S2666-5247(24)00018-1Summary Full Text Full Text PDF PubMed Scopus (0) Google Scholar regarding the importance of improving genomic surveillance capacity, the mismatch between the hot spots of origin and the availability of genomic data underscores the limitations of genomic surveillance that is predominantly focused on high-income and middle-income countries. Therefore, a more comprehensive and integrative strategy should be built to develop and expand genomic surveillance capacity, particularly in LMICs, to identify the origin; in the absence of such a strategy, undetected outbreaks could lead to the spatial and temporal spread of new multidrug-resistant bacteria and compromise infection prevention and control measures. DN has received speaker's honoraria from Shionogi outside the scope of this work. SB and TPV declare no competing interests. DN and TPV are members of the PAN ASEAN Coalition for Epidemic and Outbreak Preparedness (DAAD-PACE-UP Project ID: 57592343). Download .pdf (.32 MB) Help with pdf files Supplementary appendix Rapid evolution of pan-β-lactam resistance in Enterobacterales co-producing KPC and NDM: insights from global genomic analysis after the COVID-19 pandemicEnterobacterales co-producing Klebsiella pneumoniae carbapenemase (KPC) and New Delhi metallo-β-lactamase (NDM) enzymes are rapidly emerging worldwide.1–5 In some countries, this emergence has been linked to the empirical use of antimicrobials for potential bacterial infections associated with COVID-19 during the pandemic period.1,3–6 Concurrently, Latin American and Caribbean countries reported the occurrence and rapid dissemination of carbapenemase combinations, predominantly associated with KPC and NDM, to PAHO/WHO, triggering the issuance of an epidemiological alert. Full-Text PDF Open Access