In vitro activity of ceftazidime-avibactam, ceftolozane-tazobactam, and other comparable agents against clinically important Gram-negative bacilli: results from the 2017 Surveillance of Multicenter Antimicrobial Resistance in Taiwan (SMART)

Abstract

Objectives: We investigated the in vitro antimicrobial susceptibilities of clinically important Gram-negative bacteria (GNB) from 16 major teaching hospitals in Taiwan in 2017.

Materials and methods: Escherichia coli (n=686) and Klebsiella pneumoniae bloodstream isolates (n=673), non-typhoid Salmonella (NTS; n=221) from various sources, Shigella species (n=21) from fecal samples, and Neisseria gonorrhoeae (n=129) from the genitourinary tract were collected. Antibiotic minimum inhibitory concentrations (MICs) were determined using the broth microdilution method. Alleles encoding K. pneumoniae carbapenemases (KPCs), New Delhi metallo-β-lactamases (NDMs), Verona integron-encoded metallo-β-lactamase, imipenemase, _OXA-48-like, and mcr-1-5 genes were detected by molecular methods in Enterobacteriaceae isolates.

Results: Five (0.7%) E. coli isolates harbored mcr-1 alleles. Twenty-four (3.6%), seven (1.0%), four (0.6%), and one (0.15%) K. pneumoniae isolates contained bla _KPC, bla _OXA-48-like, mcr-1, and bla _NDM, respectively. Three (1.4%) NTS and no Shigella isolates harbored mcr-1 genes. Seventy-one (10.5%) K. pneumoniae isolates displayed non-susceptibility (NS) to carbapenem agent(s). Phenotypically extended-spectrum β-lactamase (ESBL)-producing K. pneumoniae isolates showed significantly higher rates of ertapenem, tigecycline, and ceftolozane-tazobactam (CLZ- TAZ) NS (40.2%, 16.3%, and 71%-80%, respectively) than E. coli isolates exhibiting ESBL phenotypes (5.4%, 0.7%, and 18%-28%, respectively). All phenotypically ESBL-producing E. coli isolates were ceftazidime-avibactam (CAZ-AVB) susceptible. Two (8.3%) KPC-producing K. pneumoniae isolates showed CAZ-AVB NS. Hospital-acquired K. pneumoniae isolates were significantly less susceptible to ertapenem and CLZ-TAZ than hospital-acquired E. coli isolates.

Conclusion: Third-generation cephalosporins remain the optimal choice for treating NTS, Shigella, and gonococcal infections in Taiwan. Hospital-acquired and phenotypically ESBL-producing K. pneumoniae are a heavy resistance burden in Taiwan.

Keywords: Enterobacteriaceae; Neisseria gonorrhoeae; avibactam; carbapenemase; ceftazidime; ceftolozane-tazobactam; extended-spectrum β-lactamases.

Figure 1

Comparison of (A) in vitro non-susceptibility to important antibiotics among overall, hospital-acquired, and community-acquired bloodstream Escherichia coli isolates, (B) Klebsiella pneumoniae isolates collected from 16 major teaching hospitals across Taiwan in 2017, and (C) in vitro non-susceptibility to important antibiotics between bloodstream Escherichia coli (n=148) and K. pneumoniae isolates (n=92) exhibiting the phenotype of extended-spectrum β-lactamase (unrelated to carbapenemase) production (ie, MDR phenotype). Abbreviations: CAZ–AVB, ceftazidime–avibactam; CLSI, Clinical and Laboratory Standards Institute 2018; CLZ–TAZ, ceftolozane–tazobactam; EUCAST, European Committee on Antimicrobial Susceptibility Testing; MDR, multidrug resistance.

Figure 2

Comparison of in vitro non-susceptibility to important antibiotics of hospital-acquired Escherichia coli (n=106) and Klebsiella pneumoniae bloodstream isolates (n=212) collected from 16 major teaching hospitals across Taiwan in 2017. Abbreviations: CAZ–AVB, ceftazidime–avibactam; CLSI, Clinical and Laboratory Standards Institute 2018; CLZ–TAZ, ceftolozane–tazobactam; EUCAST, European Committee on Antimicrobial Susceptibility Testing 2018.