TY - JOUR
T1 - 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
AU - Yoneda, Aki
AU - Thänert, Robert
AU - Burnham, Carey Ann D.
AU - Dantas, Gautam
N1 - Publisher Copyright:
© 2020 Elsevier Ltd
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/2
Y1 - 2020/2
N2 - 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.
AB - 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.
KW - Antibiotic combination
KW - Antibiotic resistance
KW - Clinical isolates
KW - MRSA
KW - Staphylococci
KW - Whole-genome sequencing
UR - http://www.scopus.com/inward/record.url?scp=85078025241&partnerID=8YFLogxK
U2 - 10.1016/j.ijantimicag.2019.105864
DO - 10.1016/j.ijantimicag.2019.105864
M3 - Article
C2 - 31870598
AN - SCOPUS:85078025241
VL - 55
JO - International Journal of Antimicrobial Agents
JF - International Journal of Antimicrobial Agents
SN - 0924-8579
IS - 2
M1 - 105864
ER -