In vitro activity of temocillin vs. extended-spectrum b-lactamase-producing Enterobacteriaceae from the UK

Abstract number: P1171

Khanna P., Wareham D.

Objectives: Temocillin is a semisynthetic pencillin derivative of ticarcillin. The methoxy group in the 6-a-position confers loss of activity against Gram-positive cocci and anaerobic Gram-negative bacilli but excellent activity against the Enterobacteriaceae family. This modification increases stability to b-lactamases, including AmpC and ESBLs. Owing to the increasing incidence of infections caused by multi-drug resistant Gram-negative bacteria and also because of the limited number of clinically active drugs available against such organisms, we aimed to determine the in vitro activity of temocillin versus clinical isolates prevalent in the UK.

Methods: Strains were identified using chromogenic media and API 20E. Susceptibility to gentamicin, ampicillin, amoxicillin/clavulanate, cefuroxime, ciprofloxacin, piperacillin/tazobactam, amikacin, trimethoprim, aztreonam, ceftazidime, nitrofurantion and imipenem was determined using the BSAC disc diffusion method. Eighty-one isolates of Enterobacteriaceae were screened for ESBL production by using double disk synergy test with cefpodoxime and cefpodoxime clavulanate. ESBLs were characterised by multiplex PCR for genes encoding CTXM3-like, CTXM-14 like and SHV-like b;-lactamases. Minimum inhibitory concentrations of Temocillin were determined by agar dilution using isosensitest agar.

Results: Eighty-one urinary isolates were tested. All isolates were resistant to cephalexin and ampicillin. 82.5% were also resistant to trimethoprim and 33.3% to nitrofurantoin, used commonly as first line agents for uncomplicated urinary tract infections. MICs to Temocillin ranged from 8–128 mg/L with an MIC50 of 8 and an MIC90 of 32 mg/L. The most common b-lactamases were CTX-M3 lilke (85.5%) followed by SHV-1 like (35.5%) and CTX-14 like (11.3%); 32.3% of isolates contained more that one ESBL. No difference in activity was seen versus strains exhibiting multi-drug resistance or the production of specific ESBLs.

Conclusions: Using the BSAC breakpoint of 32 mg/L for urinary isolates we found 93.9% of the isolates to be sensitive. Moreover, temocillin achieves urinary levels of 400–600 mg/L suggesting a considerable margin over the MICs. Thus we conclude that temocillin is a useful option for the growing number of infections, particularly of the urinary tract, that are caused by ESBL and cephalosporin resistant organisms.

Session Details

Date: 19/04/2008
Time: 00:00-00:00
Session name: 18th European Congress of Clinical Microbiology and Infectious Diseases
Location: Barcelona, Spain
Presentation type:
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