In vitro activity of temocillin against prevalent extended-spectrum beta-lactamases producing Enterobacteriaceae from Belgian intensive care units

Abstract

Temocillin is a narrow spectrum penicillin with high stability to most beta-lactamases including AmpC types and extended-spectrum types (ESBLs). We have analysed its in vitro activity against 652 clinical isolates of Enterobacteriaceae prospectively collected from patients hospitalised in intensive care units at seven different university hospitals in Belgium in 2005. Strains were screened for ESBL production using cefotaxime and ceftazidime screen agar plates and by double ESBL E-tests. The MIC of temocillin and of five comparators was determined using the E-test method. ESBLs were characterized at one central laboratory by isoelectric focusing, PCR for bla genes of the SHV, TEM, and CTX-M families, and by DNA sequencing. The prevalence of ESBL-producing Enterobacteriaceae averaged 11.8% and ranged between 3.0 and 29% in the different hospitals. Meropenem exhibited the highest in vitro activity overall (mode MIC 0.064 microg; MIC(90); 0.19 microg/ml), whereas ceftazidime (MIC(90) > 256 microg/ml) and ciprofloxacin (MIC(90) > 32 microg/ml) scored the worst. Temocillin was active against more than 90% of the isolates including most AmpC- and ESBL-producing isolates. These data indicate the well preserved activity of temocillin over the years against Enterobacteriaceae and show the wide variation in prevalence of ESBL-producing Enterobacteriaceae isolates in Belgian intensive care units. Prospective clinical studies are, however, needed to validate the usefulness of temocillin in the treatment of microbiologically documented infections caused by ESBL- and/or AmpC- overproducing nosocomial Enterobacteriaceae pathogens.

Continuous versus intermittent infusion of temocillin, a directed spectrum penicillin for intensive care patients with nosocomial pneumonia: stability, compatibility, population pharmacokinetic studies and breakpoint selection

“…25 On this basis, the Monte-Carlo simulations for temocillin, given at 2 g every 12 h, suggest a clinical breakpoint at an MIC of 16 mg/L (originally proposed as epidemiological cut-off ) 26 if using the median values, but at 8 mg/L to cover the 95% confidence interval. An ongoing survey of MIC distributions of temocillin towards Enterobacteriaceae based on data published over the last 25 years (data on file, available upon request) shows that about 90% of all isolates have MIC 8 mg/ L (confirmed by two recent independent surveys of ESBL-producing clinical isolates 9,27 ). The interest of administering b-lactams by CI has been repeatedly advocated, 1 but still needs support from both laboratory and clinical studies, which are presented here for temocillin.…”

AmpC β-Lactamases

“…Temocillin, a 6-␣-methoxy derivative of ticarcillin, is active in vitro against many AmpC-producing Enterobacteriaceae whether the enzyme is determined by chromosomal or plasmid genes and is also active against ESBL producers (108,187), but clinical experience is limited, and it is available in only a few countries. Amdinocillin is also effective in vitro against AmpCproducing E. coli strains but shows a marked inoculum effect unless clavulanic acid is present (43) and is also not available in the United States.…”

Activity of Temocillin against KPC-Producing Klebsiella pneumoniae and Escherichia coli

“…It is stable against hydrolysis by most ␤-lactamases, including extended-spectrum ␤-lactamases (ESBLs) and AmpC-type ␤-lactamases, with studies reporting MICs at which 90% of bacteria are inhibited (MIC 90 s) between 16 and 32 g/ml (3,4,8). Temocillin is thus drawing attention as a potential alternative to carbapenems in treatment of infections caused by the Enterobactericeae producing these broad-spectrum ␤-lactamases.…”