Emergence of New Delhi Metallo-β-Lactamase (NDM-5) in Klebsiella quasipneumoniae from Neonates in a Nigerian Hospital

Abstract

Outbreaks of infection occur more often than they are reported in most developing countries, largely due to poor diagnostic services. A Klebsiella species bacteremia outbreak in a newborn unit with high mortality was recently encountered at a location being surveilled for childhood bacteremia. These surveillance efforts offered the opportunity to determine the cause of this neonatal outbreak. In this report, we present the whole-genome sequences of New Delhi metallo-β-lactamase (NDM-5)-containing Klebsiella quasipneumoniae subsp. similipneumoniae bloodstream isolates from a neonatal bacteremia outbreak at a tertiary hospital in Nigeria and as part of the largest collection of K. pneumoniae bloodstream isolates from children in Africa. Comparative analysis of the genetic environment surrounding the NDM-5 genes revealed nearly perfect sequence identity to bla_NDM-5-bearing IncX3-type plasmids from other members of the EnterobacteriaceaeIMPORTANCE Carbapenem-resistant Klebsiella pneumoniae is of global health importance, yet there is a paucity of genome-based studies in Africa. Here we report fatal blood-borne NDM-5-producing K. quasipneumoniae subsp. similipneumoniae infections from Nigeria, Africa. New Delhi metallo-β-lactamase (NDM)-producing Klebsiella spp. are responsible for high mortality and morbidity, with the NDM-5 variant showing elevated carbapenem resistance. The prevalence of NDM-5 in Klebsiella has been limited primarily to K. pneumoniae, with only one isolate being collected from Africa. During an outbreak of sepsis in a teaching hospital in Nigeria, five NDM-5-producing K. quasipneumoniae subsp. similipneumoniae sequence type 476 isolates were identified. Given the increased resistance profile of these strains, this study highlights the emerging threat of bla_NDM-5 dissemination in hospital environments. The observation of these NDM-5-producing isolates in Africa stresses the urgency to improve monitoring and clinical practices to reduce or prevent the further spread of resistance.

Keywords: ESBL; Enterobacteriaceae; Klebsiella; New Delhi metallo-β-lactamase (NDM-5); Nigeria; antimicrobial resistance; bacteria; carbapenemase; neonate.

FIG 1

Phylogenetic analysis of K. quasipneumoniae subsp. similipneumoniae isolates. The resulting tree was rooted with type strain K. quasipneumoniae subsp. similipneumoniae 07A044 (GenBank accession no. NZ_CBZR010000000) and annotated with genotypes of resistance to common carbapenemases. The isolates discussed in this study are highlighted. The predicted sequence type (ST), isolation year, and geographical origin are displayed. Novel STs are indicated by “new.” The numbers at the nodes represent >50% bootstrap support. The scale bar represents the number of nucleotide substitutions per site.

FIG 2

Linear comparison of the genetic environment of the bla_NDM-5 region found on IncX3 plasmids from members of the Enterobacteriaceae. E. coli plasmid pEC14_35 (GenBank accession no. JN935899) represents the prototypical IncX3 plasmid that lacks known antibiotic resistance determinants. Group A represents the sequence from E. coli plasmid pNDM5-NJ-IncX3 (GenBank accession no. KX447767). Group B consists of two sequences (GenBank accession no. NEWC01000014.1 and NEWB01000014.1), both from K. quasipneumoniae. Group C has 3 members: sequences with GenBank accession no. CP027204 and MF547511 from E. coli and the sequence with GenBank accession no. CP028536 from Enterobacter hormaechei. Group D represents the sequence with GenBank accession no. KY041843 from E. coli plasmid pZHDC40. Group E contains 37 examples consisting of sequences with GenBank accession no. CP019073, CP021692, CP021738, CP024825, CP025948, CP026577, CP028577, CP028705, CP029245, KF220657, KT824791, KU167608, KU167609, KX023261, KX507346, KX960109, MF547507, MF547508, MF547509, MF547510, MF679143, MG252891, MG545911, MG825368, MG825382, MG825384, and MH094148 from E. coli; CM007781 and MTKV01000083 from Salmonella enterica subsp. enterica serovar Typhimurium; CP024820 from Citrobacter freundii; CP014006, KF220657, KU761328, MH161191, and MH341575 from K. pneumoniae; CP022351 and CP023188 from Klebsiella michiganensis; and MG833406 from Klebsiella oxytoca. Group F represents the sequence with GenBank accession no. KY435936 from E. coli plasmid pNDM5_WCHEC0215. Group G represents the sequence with GenBank accession no. MG591703 from E. coli plasmid pNDM-EC36. Group H represents the sequence with GenBank accession no. MH107030 from K. pneumoniae plasmid pTBCZNDM01. Group I represents the sequence with GenBank accession no. MH349095 from E. coli plasmid pMTC948. Group J contains 5 examples (from this study), sequences with GenBank accession no. NZ_NFXE01000097 (G4582), CP034133 (G4584), NZ_NFXD01000099 (G4593), NZ_NFXB01000102 (G4601), and NZ_NFWY01000105 (G4612), all from K. quasipneumoniae subsp. similipneumoniae. Arrows indicate protein-coding genes (CDSs) drawn to scale and colored as follows: salmon for factors involved in plasmid replication, yellow for factors involved in plasmid maintenance and mobility, red for antibiotic resistance determinants, blue for mobile elements, green for other known proteins, and gray for unknown proteins. Homologous CDSs between adjacent groups are joined vertically by colored lines.