Klebsiella oxytoca is actually a complex of nine species— Klebsiella grimontii , Klebsiella huaxiensis , Klebsiella michiganensis , K. oxytoca , Klebsiella pasteurii , Klebsiella spallanzanii , and three unnamed novel species. Phenotypic tests can assign isolates to the complex, but precise species identification requires genome-based analysis.

Background: Klebsiella pneumoniae is the most common pathogen causing neonatal infections, leading to high mortality worldwide. Along with increasing antimicrobial use in neonates, carbapenem-resistant K. pneumoniae (CRKP) has emerged as a severe challenge for infection control and treatment. However, no comprehensive systematic review is available to describe the global epidemiology of neonatal CRKP infections. We therefore performed a systematic review of available data worldwide and combined a genome-based analysis to address the prevalence, clonal diversity, and carbapenem resistance genes of CRKP causing neonatal infections. Methods and findings: We performed a systematic review of studies reporting population-based neonatal infections caused by CRKP in combination with a genome-based analysis of all publicly available CRKP genomes with neonatal origins. We searched multiple databases (PubMed, Web of Science, Embase, Ovid MEDLINE, Cochrane, bioRxiv, and medRxiv) to identify studies that have reported data of neonatal CRKP infections up to June 30, 2022. We included studies addressing the prevalence of CRKP infections and colonization in neonates but excluded studies lacking the numbers of neonates, the geographical location, or independent data on Klebsiella or CRKP isolates. We used narrative synthesis for pooling data with JMP statistical software. We identified 8,558 articles and excluding those that did not meet inclusion criteria. We included 128 studies, none of which were preprints, comprising 127,583 neonates in 30 countries including 21 low- and middle-income countries (LMICs) for analysis. We found that bloodstream infection is the most common infection type in reported data. We estimated that the pooled global prevalence of CRKP infections in hospitalized neonates was 0.3% (95% confidence interval [CI], 0.2% to 0.3%). Based on 21 studies reporting patient outcomes, we found that the pooled mortality of neonatal CRKP infections was 22.9% (95% CI, 13.0% to 32.9%). A total of 535 neonatal CRKP genomes were identified from GenBank including Sequence Read Archive, of which 204 were not linked to any publications. We incorporated the 204 genomes with a literature review for understanding the species distribution, clonal diversity, and carbapenemase types. We identified 146 sequence types (STs) for neonatal CRKP strains and found that ST17, ST11, and ST15 were the 3 most common lineages. In particular, ST17 CRKP has been seen in neonates in 8 countries across 4 continents. The vast majority (75.3%) of the 1,592 neonatal CRKP strains available for analyzing carbapenemase have genes encoding metallo-β-lactamases and NDM (New Delhi metallo-β-lactamase) appeared to be the most common carbapenemase (64.3%). The main limitation of this study is the absence or scarcity of data from North America, South America, and Oceania. Conclusions: CRKP contributes to a considerable number of neonatal infections and leads to significant neonatal mortality. Neonatal CRKP strains are highly diverse, while ST17 is globally prevalent and merits early detection for treatment and prevention. The dominance of bla_NDM carbapenemase genes imposes challenges on therapeutic options in neonates and supports the continued inhibitor-related drug discovery.

Klebsiella oxytoca complex comprises nine closely related species causing human infections. We curated genomes labeled Klebsiella ( n = 14,256) in GenBank and identified 588 belonging to the complex, which were examined for precise species, sequence types, K- and O-antigen types, and virulence and antimicrobial resistance genes.

We performed whole-genome sequencing for 17 Enterobacter clinical strains and analyzed all available Enterobacter genomes and those of its closely related genera ( n = 3,389) from NCBI. The exact origins of plasmid-borne bla _CMH and bla _MIR genes are Enterobacter cloacae and Enterobacter roggenkampii , respectively, while plasmid-borne bla _ACT genes originated from multiple other Enterobacter species, including Enterobacter xiangfangensis , Enterobacter hoffmannii , Enterobacter asburiae , Enterobacter ludwigii , and Enterobacter kobei .

Carbapenem-resistant Klebsiella pneumoniae (CRKP) is a global challenge for human health. In health care settings, patients have frequent interactions with other patients and the environment, rendering challenges for untangling the introduction and transmission of CRKP.