Microbial Drug Resistance, 2019. 26(3), 0-, DOI: https://doi.org/10.1089/mdr.2019.0079

SHV hyperproduction as a mechanism for piperacillin–tazobactam resistance in extended-spectrum cephalosporin-susceptible Klebsiella pneumoniae

Mi Seon Han, Kwang Seung Park;Jeong Ho Jeon; Joon Kee Lee;Jung Hun Lee;Eun Hwa Choi;Sang Hee Lee

Abstract

This study aimed to determine the mechanism of resistance to piperacillin–tazobactam (TZP) in Klebsiella pneumoniae bloodstream isolates that are susceptible to extended-spectrum cephalosporins (ESCs). Antibiotic susceptibility was determined for K. pneumoniae isolated from children with bacteremia. The beta-lactamase genes were detected using a large-scale bla detection method (LARGE-SCALEblaFinder) and confirmed by sequencing analysis. The isolates were further characterized by b-lactamase activity assays and multilocus sequence typing. Among the 300 bloodstream isolates of K. pneumoniae, 11 (3.7%) were TZP resistant but ESC susceptible. The TZP minimum inhibitory concentrations (MICs) of the isolates ranged from 128/4 to > 2,048/4 mg/L. Avibactam markedly inhibited piperacillin resistance, reducing the MICs to the range of ≤ 1 to 8 mg/L. Among the 11 isolates, four hyperproduced SHV-1 and two hyperproduced SHV-11, exhibiting 77- to 496-fold higher b-lactamase activity compared with the SHV-1- and SHV-11-producing reference strains that are susceptible to TZP. OXA-1 was coproduced in three isolates, and the remaining two isolates produced TEM-30. Transformants with recombinant plasmids carrying the b-lactamase genes demonstrated an increase in MICs of TZP. The TZP-resistant and ESC-susceptible isolates were not epidemiologically related. Hyperproduction of SHV-1 and SHV-11 represents a novel mechanism for reducing TZP activity in K. pneumoniae isolates resistant to ESCs. Continuous monitoring and investigation of TZP-resistant isolates are needed in the current era of high TZP consumption.

• DOI: https://doi.org/10.1089/mdr.2019.0079
• ISBN or ISSN: 1076-6294

• 본 연구는 질병관리본부 연구개발과제연구비를 지원받아 수행되었습니다.
• This research was supported by a fund by Research of Korea Centers for Disease Control and Prevention.