Molecular epidemiology of colonizing and disease-causing Klebsiella pneumoniae in paediatric patients

Abstract

Klebsiella pneumoniae causes a range of clinical disease in paediatric patients and is of increasing concern due to growing antibiotic resistance, yet little is known about the relative distribution of commensal and pathogens throughout the population structure of K. pneumoniae. We conducted a prospective, observational study of 92 isolates from Seattle Children's Hospital, including 49 disease isolates from blood and urine (13 and 36 isolates, respectively) and 43 colonization isolates from stool. Susceptibility to 20 antimicrobials was evaluated using disc diffusion, VITEK 2 and Etest. Strain relatedness was investigated using multilocus sequence typing (MLST). Demographic and clinical characteristics were largely similar between disease and colonization cohorts, with 85.7 and 74.4 % of disease and colonization cohort patients, respectively, having an underlying medical condition; the sole exception was a relative abundance of patients with urologic or renal abnormalities in the disease cohort, consistent with the predominance of urine specimens among the disease isolates. With regard to antibiotic susceptibility properties, no significant differences were noted between the disease and colonization cohorts. Using molecular analysis, 71 unique sequence types (STs) were distinguished, with novel MLST findings evident in both cohorts; 43 (46.7 %) isolates represented novel STs, including 22 with a novel allele sequence. Thirteen STs contained multiple isolates and all seven isolates with resistance to three or more antibiotic classes were within one of four multirepresentative STs. This study demonstrates that nearly half of paediatric Klebsiella isolates represent novel STs, with clustering of multidrug resistance within specific STs. These findings expand our understanding of the intersection of bacterial population structure, human colonization ecology and multidrug resistance in K. pneumoniae.

Fig. 1.

Resistance to antimicrobial classes among study isolates. Specific agents with resistance, by class: oxyimino-cephalosporin: ceftriaxone; β-lactam/β-lactamase inhibitor: piperacillin/tazobactam; aminoglycoside: gentamicin, amikacin, tobramycin; fluoroquinolone: ciprofloxacin, levofloxacin; folic acid inhibitor: trimethoprim/sulfamethoxazole.