The activity of mecillinam vs Enterobacteriaceae resistant to 3rd-generation cephalosporins in Bristol, UK

Abstract number: 1733_1156

Weston G., Bowker K., Noel A., MacGowan A., Howe R.

Objectives: Resistance in coliforms to 3rd generation cephalosporins (3GC) is an increasing problem both in hospitals and the community. Oral options for the treatment of these organisms is often limited due to resistance to multiple antimicrobial classes. Mecillinam, an amidinopenicillin that is available in Europe as the oral pro-drug pivmecillinam, is stable to many b-lactamases. We aim to establish the activity of mecillinam against Enterobacteriaceae resistant to 3GC.

Methods: Coliforms isolated from urine samples routinely submitted to North Bristol NHS Trust were screened for resistance to 3GC by disc testing with cefpodoxime on Isosensitest agar. Resistant isolates were identified using the BBL Crystal ID system. Further susceptibility testing was performed by agar dilution MIC using an inoculum of 104 cfu/spot on Mueller-Hinton agar. Phenotypic characterisation of 3GC resistance was determined from MICs for cefotaxime (CTX) and Ceftazidime (CAZ) with and without clavulanate at a fixed concentration of 2 mg/L.

MIC of mecillinam +/- clavulanate for ESBL-producing E. coli.

Results: 127 isolates were identified by screening of which 123 were confirmed as resistant to either CTX or CAZ by BSAC criteria. The majority of 3GC-resistant strains were E. coli 74/123 (60.2%), followed by Enterobacter spp. 16.2%, Klebsiella spp. 12.2%, and others 11.4%. Overall 98.4% of 3GC-resistant coliforms tested sensitive to mecillinam (BSAC breakpoint S≤64 mg/L). Of 30 strains that were multiply-resistant to 3GC, trimethoprim, nitrofurantoin, gentamicin, and ciprofloxacin, 96.7% tested sensitive to mecillinam. As shown in the figure, all 67 ESBL-producing E. coli tested sensitive to mecillinam with a 4-fold or greater decrease in MIC in the presence of clavulanate in most cases.

Conclusions: Mecillinam maintains good activity against Enterobacteriaceae resistant to 3GC. This includes prevalent strains of ESBL-producing E. coli. Oral formulations of mecillinam should be considered as possible agents for the treatment of uncomplicated urinary tract infections caused by such organisms.

Session Details

Date: 31/03/2007
Time: 00:00-00:00
Session name: European Society of Clinical Microbiology and Infectious Diseases
Location: ICC, Munich, Germany
Presentation type:
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