Clinical and genomic characterization of Klebsiella pneumoniae infections in Dhaka, Bangladesh

Abstract

Background: Klebsiella pneumoniae (Kpn), a WHO priority pathogen with high rates of antimicrobial resistance (AMR), has emerged as a leading cause of hospital acquired pneumonia and neonatal sepsis.

Objective: We aimed to define the clinical characteristics of a cohort of patients with Kpn infection in Dhaka, Bangladesh and to perform phenotypic and genetic characterization of the associated isolates.

Methods: We retrospectively extracted clinical data about patients at Dhaka Medical College Hospital from whom Klebsiella spp was isolated from a clinical specimen collected between February and September 2022. We used standard microbiologic techniques to evaluate AMR and whole-genome sequencing (WGS) to assess dominant lineages, common capsular (K) and O-polysaccharide (O) antigen types, and AMR and virulence genes.

Results: Ninety-eight patients were included, with diagnoses of pneumonia (38/98, 39 %), wound infection (29/98, 31 %), urinary tract infection (29/98, 31 %) and bacteremia (2/98, 2 %). We tested isolates for susceptibility to eight classes of antibiotics. Of the 98 isolates, 41 % were multidrug resistant (MDR), 15 % were extensively drug resistant (XDR), and 16 % were pan-drug resistant (PDR). Three isolates (3 %) were resistant to polymyxin B. Outcome data were available for 46 patients; 4 patients (8 %) died from infections caused by PDR (n = 2), XDR (n = 1), and MDR isolates (n = 1). WGS revealed a high degree of genomic diversity, with multiple sequence types (STs), O-types and K-types represented; ST16:K81:OL101 and ST43:K30:O1 were the most prevalent.

Conclusion: Our findings suggest alarming levels of AMR among Kpn isolates in Bangladesh and a critical need for improved treatment modalities and vaccine development.

Keywords: Antimicrobial resistance; Bacterial virulence; Klebsiella pneumoniae; Sequence types.

Fig. 1.. AMR patterns of Klebsiella isolates.

A. Antimicrobial susceptibility testing results by disk diffusion for the 16 tested antibiotics. B. Number of non-MDR, MDR, XDR, and PDR isolates by isolate source. C. Number of HAI and CAI, indicated by non-MDR, MDR, XDR, and PDR classification.

Fig. 2.. Phylogenetic tree representing the 86 Kpn isolates.

Midpoint-rooted phylogenetic tree of 86 Kpn isolates with O- and K- antigen types and phenotypic AMR. O and K antigen types are indicated by circles and diamonds, respectively. The phenotypic AMR categories of the respective isolates are indicated by squares in the outermost column.

Fig. 3.. Resistance and virulence characteristics of Kpn isolates.

A. Proportion of total carbapenemase genes found across all isolates. B. Comparison of the Kleborate resistance (x-axis) and virulence (y-axis) scores, with four ST:K:O combinations highlighted. Resistance and virulence scores are integer values, but jitter was used in the plot to distinguish isolates.