Background Carbapenem-resistant Klebsiella pneumoniae (CRKP) is a threat to public health in India because of its high dissemination, mortality, and limited treatment options. Its genomic variability is reflected in the diversity of sequence types, virulence factors, and antimicrobial resistance (AMR) mechanisms. This study aims to characterize the clonal relationships and genetic mechanisms of resistance and virulence in CRKP isolates in India. Materials and Methods We characterized 344 retrospective K. pneumoniae clinical isolates collected from 8 centers across India collected in 2013–2019. Susceptibility to antibiotics was tested with VITEK 2. Capsular types, multilocus sequence type, virulence genes, AMR determinants, plasmid replicon types, and a single-nucleotide polymorphism phylogeny were inferred from their whole genome sequences. Results Phylogenetic analysis of the 325 Klebsiella isolates that passed quality control revealed 3 groups: K. pneumoniae sensu stricto (n = 307), K. quasipneumoniae (n = 17), and K. variicola (n = 1). Sequencing and capsular diversity analysis of the 307 K. pneumoniae sensu stricto isolates revealed 28 sequence types, 26 K-locus types, and 11 O-locus types, with ST231, KL51, and O1V2 being predominant. blaOXA-48-like and blaNDM-1/5 were present in 73.2% and 24.4% of isolates, respectively. The major plasmid replicon types associated with carbapenase genes were IncF (51.0%) and Col group (35.0%). Conclusion Our study documents for the first time the genetic diversity of K and O antigens circulating in India. The results demonstrate the practical applicability of genomic surveillance and its utility in tracking the population dynamics of CRKP. It alerts us to the urgency for longitudinal surveillance of these transmissible lineages.

Background Klebsiella pneumoniae is a World Health Organization high-priority antibiotic-resistant pathogen. However, little is known about Klebsiella lineages circulating in Nigeria. Methods We performed whole-genome sequencing (WGS) of 141 Klebsiella isolated between 2016 and 2018 from clinical specimens at 3 antimicrobial-resistance (AMR) sentinel surveillance tertiary hospitals in southwestern Nigeria. We conducted in silico multilocus sequence typing; AMR gene, virulence gene, plasmid, and K and O loci profiling; as well as phylogenetic analyses, using publicly available tools and Nextflow pipelines. Results Phylogenetic analysis revealed that the majority of the 134 K. pneumoniae and 5 K. quasipneumoniae isolates from Nigeria characterized are closely related to globally disseminated multidrug-resistant clones. Of the 39 K. pneumoniae sequence types (STs) identified, the most common were ST307 (15%), ST5241 (12%), ST15 (~9%), and ST25 (~6%). ST5241, 1 of 10 novel STs detected, is a single locus variant of ST636 carrying dfrA14, tetD, qnrS, and oqxAB resistance genes. The extended-spectrum β-lactamase (ESBL) gene blaCTX_M-15 was seen in 72% of K. pneumoniae genomes, while 8% encoded a carbapenemase. No isolate carried a combination of carbapenemase-producing genes. Four likely outbreak clusters from 1 facility, within STs 17, 25, 307, and 5241, were ESBL but not carbapenemase-bearing clones. Conclusions This study uncovered known and novel K. pneumoniae lineages circulating in 3 hospitals in Southwest Nigeria that include multidrug-resistant ESBL producers. Carbapenemase-producing isolates remain uncommon. WGS retrospectively identified outbreak clusters, pointing to the value of genomic approaches in AMR surveillance for improving infection prevention and control in Nigerian hospitals.

BackgroundAcinetobacter baumannii are of major human health importance because they cause life-threatening nosocomial infections and often are highly resistant to antimicrobials. Specific multidrug-resistant A. baumannii lineages are implicated in hospital outbreaks globally. We retrospectively investigated a suspected outbreak of carbapenem-resistant A. baumannii (CRAB) colonizing patients in an intensive care unit (ICU) of a tertiary hospital in Southwest Nigeria where genomic surveillance of Acinetobacter has hitherto not been conducted.MethodsA prospective observational study was conducted among all patients admitted to the ICU between August 2017 and June 2018. Acinetobacter species were isolated from rectal swabs and verified phenotypically with the Biomerieux Vitek 2 system. Whole genome sequencing (WGS) was performed on the Illumina platform to characterize isolates from a suspected outbreak during the study period. Phylogenetic analysis, multilocus sequence typing, and antimicrobial resistance gene prediction were carried out in silico.ResultsAcinetobacter isolates belonging to the A. baumannii complex were recovered from 20 (18.5%) ICU patients. Single nucleotide polymorphism (SNP) analysis and epidemiological information revealed a putative outbreak clone comprising seven CRAB strains belonging to the globally disseminated international clone (IC) 2. These isolates had ≤2 SNP differences, identical antimicrobial resistance and virulence genes, and were all ST1114/1841.ConclusionWe report a carbapenem-resistant IC2 A. baumannii clone causing an outbreak in an ICU in Nigeria. The study findings underscore the need to strengthen the capacity to detect A. baumannii in human clinical samples in Nigeria and assess which interventions can effectively mitigate CRAB transmission in Nigerian hospital settings.

Background Salmonellosis causes significant morbidity and mortality in Africa. Information on lineages of invasive Salmonella circulating in Nigeria is sparse. Methods Salmonella enterica isolated from blood (n = 60) and cerebrospinal fluid (CSF, n = 3) between 2016 and 2020 from five tertiary hospitals in southwest Nigeria were antimicrobial susceptibility-tested and Illumina-sequenced. Genomes were analysed using publicly-available bioinformatic tools. Results Isolates and sequence types (STs) from blood were S. Typhi [ST1, n = 1 and ST2, n = 43] and invasive non-typhoidal Salmonella (iNTS) (S. Enteritidis [ST11, n = 7], S. Durham [ST10, n = 2], S. Rissen [ST8756, n = 2], S. Chester [ST2063, n = 1], S. Dublin [ST10, n = 1], S. Infantis [ST603, n = 1], S. Telelkebir [ST8757, n = 1] and S. Typhimurium [ST313, n = 1]). S. Typhi ST2 (n = 2) and S. Adabraka ST8757 (n = 1) were recovered from CSF. Most S. Typhi belonged to genotype 3.1.1 (n = 44), carried an IncY plasmid, had several antibiotic resistance genes (ARGs) including blaTEM-1 (n = 38), aph(6)-Id (n = 32), tet(A) (n = 33), sul2 (n = 32), dfrA14 (n = 30) as well as quinolone resistance-conferring gyrA_S83Y single-nucleotide polymorphisms (n = 37). All S. Enteritidis harboured aph(3”)-Ib, blaTEM-1, catA1, dfrA7, sul1, sul2, tet(B) genes, and a single ARG, qnrB19, was detected in S. Telelkebir. Typhoidal toxins cdtB, pltA and pltB were detected in S. Typhi, Rissen, Chester, and Telelkebir. Conclusion Most invasive salmonelloses in southwest Nigeria are vaccine-preventable infections due to multidrug-resistant, West African dominant S. Typhi lineage 3.1.1. Invasive NTS serovars, including some harbouring typhoidal toxin or resistance genes, represented a third of the isolates emphasizing the need for better diagnosis and surveillance.

In this Supplement, we detail outputs of the National Institute for Health Research Global Health Research Unit on Genomic Surveillance of Antimicrobial Resistance project, covering practical implementation of whole-genome sequencing across our consortium, which consists of laboratories in Colombia, India, Nigeria, and the Philippines.