Abstract
The recent emergence of multidrug-resistant (MDR) Klebsiella pneumoniae with hypervirulent traits causing severe infections and considerable mortality is a global cause for concern. The challenges posed by these hypermucoviscous strains of K. pneumoniae with regard to their optimal treatment, management, and control policies are yet to be answered. We studied a series of extensively drug-resistant (XDR) and hypervirulent K. pneumoniae ST5235 isolates with resistance to carbapenems and polymyxins causing neonatal sepsis in a tertiary care hospital in India. A total of 9 K. pneumoniae isolates from 9 cases of neonatal sepsis were studied with respect to their clinical relevance, antimicrobial susceptibility profile, presence of extended spectrum β lactamase (ESBL) production, and responsible genes, carbapenemases (classes A, B, and D), and aminoglycoside-resistant genes. Hypervirulence genes encoding hypermucoid nature, iron uptake, and siderophores were detected by multiplex PCR. The plasmid profile was studied by replicon typing. Isolates were typed by multilocus sequence typing (MLST) and enterobacterial repetitive intergenic consensus (ERIC) PCR to study the sequence types (STs) and clonal relation, respectively. The neonates in the studied cases had history of pre-maturity or low birth weight with maternal complications. All the cases were empirically treated with piperacillin–tazobactam and amikacin followed by imipenem/meropenem and vancomycin and polymyxin B as a last resort. However, all the neonates finally succumbed to the condition (100%). The studied isolates were XDR including resistance to polymyxins harboring multiple ESBL genes and carbapenemase genes (blaNDM and blaOXA−48). Hypervirulence genes were present in various combinations with rmpA/A2 genes present in all the isolates. IncFI plasmids were detected in these isolates. All belonged to ST5235. In ERIC PCR, 6 different clusters were seen. The study highlighted the emergence and burden of XDR hypervirulent isolates of K. pneumoniae causing neonatal sepsis in a tertiary care hospital.
Highlights
Drug resistance in Klebsiella pneumoniae is ever increasing with adoption of several evolutionary routes by this “World Health Organization (WHO) critical priority pathogen” [1]
In majority of the cases (6, 66.6%), the mode of delivery was by lower-segment Cesarean section (LSCS)
All the cases were empirically treated with piperacillin– tazobactam and amikacin followed by imipenem/meropenem and vancomycin
Summary
Drug resistance in Klebsiella pneumoniae is ever increasing with adoption of several evolutionary routes by this “World Health Organization (WHO) critical priority pathogen” [1]. Evolving gradually from multidrug-resistant (MDR) to extensively drugresistant (XDR), K. pneumoniae isolates had not exhibited simultaneous drug resistance and hypervirulence for long until recently with the emergence of carbapenem-resistant hypervirulent K. pneumoniae (CR-hvKP) [2]. The primary reason for this delayed emergence has been the successive convergence of two distinct traits of drug resistance and virulence through recombination of several plasmids, resulting in MDR-virulent strains [3]. Prevalent and diverse convergent MDR-virulent strains of K. pneumoniae have already been reported from the South Asian region including India [6]. The first report on CR-hvKP in sepsis from the subcontinent came in 2018 followed by a single case of neonatal sepsis recently [7, 8]. We report a series of neonatal sepsis due to CR-hvKP along with simultaneous resistance to polymyxins causing high mortality from a tertiary care center
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