In vitro activity of meropenem/piperacillin/tazobactam triple combination therapy against clinical isolates of Staphylococcus aureus, Staphylococcus epidermidis, Staphylococcus pseudintermedius and vancomycin-resistant Enterococcus spp.

Publisher: Elsevier Science Publishers Country of Publication: Netherlands NLM ID: 9111860 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1872-7913 (Electronic) Linking ISSN: 09248579 NLM ISO Abbreviation: Int J Antimicrob Agents Subsets: MEDLINE

Original Publication: Amsterdam : Elsevier Science Publishers, c1991-

Anti-Bacterial Agents/*therapeutic use ; Meropenem/*therapeutic use ; Piperacillin/*therapeutic use ; Staphylococcal Infections/*drug therapy ; Tazobactam/*therapeutic use ; Vancomycin-Resistant Enterococci/*drug effects; Drug Resistance, Multiple, Bacterial/genetics ; Drug Therapy, Combination ; Genome, Bacterial/genetics ; Genomics ; Humans ; Methicillin-Resistant Staphylococcus aureus/drug effects ; Methicillin-Resistant Staphylococcus aureus/genetics ; Microbial Sensitivity Tests ; Staphylococcus/drug effects ; Staphylococcus/genetics ; Staphylococcus epidermidis/drug effects ; Staphylococcus epidermidis/genetics ; Vancomycin-Resistant Enterococci/genetics ; Whole Genome Sequencing ; beta-Lactamase Inhibitors/therapeutic use

Objectives: To evaluate the activity of the reported synergistic and collaterally sensitive antibiotic combination, meropenem/piperacillin/tazobactam (ME/PI/TZ), against a panel of methicillin-resistant Staphylococcus aureus (MRSA) and other methicillin-resistant Staphylococcus species; and to investigate the relationship between ME/PI/TZ susceptibility and the genomic background of clinical isolates of MRSA.
Methods: ME/PI/TZ combination and single drug minimum inhibitory concentrations (MICs) were determined for 207 strains (including 121 MRSA, 4 methicillin-sensitive S. aureus [MSSA], 37 vancomycin-intermediate S. aureus [VISA], 6 ceftaroline non-susceptible MRSA, 29 coagulase-negative staphylococci [CoNS], 5 S. pseudointermedius and 5 vancomycin-resistant Enterococci [VRE]) by broth microdilution. Whole genomes of 168 S. aureus strains were sequenced, assembled, and comparatively analysed.
Results: USA300-SCCmec type IV isolates, clonal complex 8 (CC8)-MRSA isolates, including some VISA and ceftaroline (CPT)-intermediate strains, and all tested methicillin-resistant S. epidermidis isolates were highly susceptible to ME/PI/TZ. Isolates with elevated MICs (MICs of >16/16/16 mg/L) clustered with the USA100-SCCmec type II strain. Susceptibility of MRSA to ME/PI/TZ was correlated with susceptibility to ME. No obvious cross-resistance to CPT was observed among high-ME/PI/TZ MIC isolates.
Conclusions: The ME/PI/TZ combination is effective against a variety of clinical MRSA isolates, particularly of the USA300 lineage, which is expanding worldwide. ME/PI/TZ is also effective against drug-resistant CoNS and S. pseudintermedius clinical isolates.
(Copyright © 2020 Elsevier Ltd. All rights reserved.)

Keywords: Antibiotic combination; Antibiotic resistance; Clinical isolates; MRSA; Staphylococci; Whole-genome sequencing

0 (Anti-Bacterial Agents)
0 (beta-Lactamase Inhibitors)
FV9J3JU8B1 (Meropenem)
SE10G96M8W (Tazobactam)
X00B0D5O0E (Piperacillin)

Staphylococcus pseudintermedius

Date Created: 20191225 Date Completed: 20201116 Latest Revision: 20201116

20231215

10.1016/j.ijantimicag.2019.105864

31870598