Cefepime/tazobactam compared with other tazobactam combinations against problem Gram-negative bacteria.
Int J Antimicrob Agents
; 57(5): 106318, 2021 May.
Article
in English
| MEDLINE | ID: covidwho-1131354
ABSTRACT
OBJECTIVES:
Piperacillin/tazobactam has long been a broad-spectrum 'workhorse' antibiotic; however, it is compromised by resistance. One response is to re-partner tazobactam with cefepime, which is easier to protect, being less ß-lactamase labile, and to use a high-dose and prolonged infusion. On this basis, Wockhardt are developing cefepime/tazobactam (WCK 4282) as a 2+2 g q8h combination with a 90-min infusion.METHODS:
The activity of cc cefepime/tazobactam was assessed, with other tazobactam combinations as comparators, against 1632 Enterobacterales, 745 Pseudomonas aeruginosa and 450 other non-fermenters, as submitted to the UK National Reference Laboratory. These were categorised by carbapenemase-gene detection and interpretive reading of phenotypes, with MICs determined by British Society for Antimicrobial Chemotherapy agar dilution.RESULTS:
Although higher breakpoints may be justifiable, based on the pharmacodynamics, the results were reviewed against current cefepime criteria. On this basis, cefepime/tazobactam was broadly active against Enterobacterales with AmpC enzymes and extended-spectrum ß-lactamases (ESBLs), even when they had ertapenem resistance, suggesting porin loss. At 8+8 mg/L, activity extended to > 90% of Enterobacterales with OXA-48 and KPC carbapenemases, although the MICs for KPC producers belonging to the international Klebsiella pneumoniae ST258 lineage were higher; metallo-ß-lactamase producers remained resistant. Cefepime/tazobactam was less active than ceftolozane/tazobactam against Pseudomonas aeruginosa with AmpC de-repression or high-level efflux but achieved wider antipseudomonal coverage than piperacillin/tazobactam. Activity against other non-fermenters was species-specific.CONCLUSION:
Overall, cefepime/tazobactam had a spectrum exceeding those of piperacillin/tazobactam and ceftolozane/tazobactam and resembling or exceeding that of carbapenems. Used as a 'new-combination of old-agents' it has genuine potential to be 'carbapenem-sparing'.Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Cephalosporins
/
Cefepime
/
Piperacillin, Tazobactam Drug Combination
/
Tazobactam
/
Gram-Negative Bacteria
/
Anti-Bacterial Agents
Type of study:
Diagnostic study
Limits:
Humans
Language:
English
Journal:
Int J Antimicrob Agents
Year:
2021
Document Type:
Article
Affiliation country:
J.ijantimicag.2021.106318
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