In vitro activity of fosfomycin vs. extended-spectrum b-lactamase

Abstract number: P1174

Amin A., Khanna P., O'Sullivan C., Wareham D.

Objectives: Due to the increased isolation of ciprofloxacin resistant ESBL-producing Enterobacteriaceae from the urinary tract, alternative antibiotics are urgently required. Among currently available agents, fosfomycin trometamol may be a useful agent as it concentrates in the kidney and bladder. We set out to determine the in-vitro activity of fosfomycin against both community and hospital acquired urinary tract infection (UTI) isolates from the east London Region of the UK.

Methods: All isolates collected were screened for ESBL production using double disk synergy tests with cefpodoxime and cefpodoxime/clavulanate. Strains were identified to species level using a combination of chromogenic media and API 20E identification systems. Susceptibility to gentamicin, ampicillin, amoxicillin/ clavulanate, cephalexin, cefuroxime, ciprofloxacin, piperacillin/tazobactam, amikacin, trimethoprim, aztreonam, ceftazidime, nitrofurantion, minocycline, ampicillin/sulbactam, cefoxitin, trimethorpim/sulfamethoxazole, fosfomycin and imipenem were determined using the BSAC disc diffusion method. Minimum inhibitory concentrations (MIC) of fosfomycin were determined by agar dilution using isosensitest agar. All ESBLs were characterised by multiplex PCR for genes encoding CTXM3-like, CTXM14-like and SHV-like b-lactamases.

Results: 75 urinary isolates were tested, all of which were resistant to amoxicillin and cephalexin. 81.3% were also resistant to trimethoprim, 34.7% to nitrofurantoin, and 85.3% to ciprofloxacin, 74 out of 75 isolates (98.7%) were sensitive to fosfomycin, using the BSAC MIC breakpoint of 128 mg/L. MICs to fosfomycin ranged from 0.5–>128 mg/L, with an MIC50 of 16 and an MIC90 of 32 mg/L. CTXM3-like genes were detected in 82.5% of isolates, CTXM14-like genes in 12.3%, and SHV-like genes in 36.8%.

Conclusions: 98.7% of ESBL-producing urinary isolates tested in this study were sensitive to fosfomycin, with frequent resistance to other agents including ciprofloxacin. Fosfomycin is an oral agent which is known to be concentrated in the urine. It is not nephrotoxic, is considered safe in pregnancy, and is also active against Enterococcus species. This study suggests that fosfomycin may be a useful option in the treatment of urinary tract infections caused by multi-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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