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The Activity of Mecillinam Vs Enterobacteriaceae Resistant to 3Rd Generation Cephalosporins in Bristol, UK

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The Activity of Mecillinam Vs Enterobacteriaceae Resistant to 3Rd Generation Cephalosporins in Bristol, UK The activity of mecillinam vs Enterobacteriaceae resistant to 3rd generation cephalosporins in Bristol, UK Welsh Antimicrobial Study Group Grŵp Astudio Wrthfiotegau Cymru G Weston1, KE Bowker1, A Noel1, AP MacGowan1, M Wootton2, TR Walsh2, RA Howe2 (1) BCARE, North Bristol NHS Trust, Bristol BS10 5NB (2) Welsh Antimicrobial Study Group, NPHS Wales, University Hospital of Wales, CF14 4XW Introduction Results Results Results Figure 1: Population Distributions of Mecillinam MICs for E. Figure 2: Population Distributions of MICs for ESBL- Resistance in coliforms to 3rd generation 127 isolates were identified by screening of which 123 were confirmed as resistant to CTX or coli (n=72), NON-E. coli Enterobacteriaceae (n=47) and multi- producing E. coli (n=67) against mecillinam or mecillinam + cephalosporins (3GC) is an increasing problem resistant strains (n=39) clavulanate CAZ by BSAC criteria. The majority of 3GC- both in hospitals and the community. Oral options MR Non-E. coli E. coli Mecalone Mec+Clav resistant strains were E. coli 60.2%, followed by for the treatment of these organisms is often 35 50 Enterobacter spp. 16.2%, Klebsiella spp. 12.2%, limited due to resistance to multiple antimicrobial 45 and others (Citrobacter spp., Morganella spp., 30 classes. Mecillinam, an amidinopenicillin that is 40 Pantoea spp., Serratia spp.) 11.4%. 25 available in Europe as the oral pro-drug 35 All isolates were susceptible to meropenem with s 20 30 e s pivmecillinam, is stable to many beta-lactamases. t e a t l a mecillinam the next most active agent with more l o 25 o s We aimed to establish the activity of mecillinam i s i 15 % than 95% of isolates susceptible (table). % against Enterobacteriaceae resistant to 3GC. 20 Although resistance rates to unrelated 10 15 antimicrobials was high, susceptibility to 10 mecillinam was maintained even in isolates 5 5 0 multiply-resistant to 3GC, trimethoprim, 0 0.06 0.12 0.25 0.5 1 2 4 8 16 32 64 nitrofurantoin, gentamicin, and ciprofloxacin 0.03 0.06 0.12 0.25 0.5 1 2 4 8 16 32 64 128 Methods MIC (mg/L) MIC(mg/L) (Figure 1). Coliforms isolated from urine samples routinely Conclusions submitted to North Bristol NHS Trust were screened for resistance to 3rd generation Susceptibilities of E. coli (n=72)and NON- E. coli Enterobacteriaceae (n=47) resistant to 3GC Mecillinam maintains good activity against cephalosporins (3GC) using a 10 g • cefpodoxime disc on Isosensitest agar. Resistant E. coli NON-E. coli Enterobacteriaceae resistant to 3GC. * * isolates were identified using the BBL Crystal ID MIC50 MIC90 %S MIC50 MIC90 %S system. Further susceptibility testing was •Mecillinam is active against prevalent strains of Meropenem 0.015 0.015 100 0.015 0.06 100 ESBL-producing E. coli. performed against a range of beta-lactam and un- Mecillinam 1 4 97.2** 2 8 95.6** related antimicrobials by agar dilution MIC using Ertapenem 0.12 0.5 95.5 0.12 1 83.0 The activity of mecillinam against ESBL- an inoculum of 104 cfu/spot on Mueller-Hinton • agar. Phenotypic characterisation of 3GC Cefepime 16 64 1.3 4 32 12.5 producing E. coli can be further enhanced by the resistance was determined from MICs for Ceftazidime 32 >128 1.4 >128 >128 4.3 addition of a beta-lactamase inhibitor such as clavulanate. Cefotaxime (CTX) and Ceftazidime (CAZ) with Cefotaxime 32 64 6.9 16 64 4.3 and without clavulanate at a fixed concentration Ciprofloxacin 128 >128 12.5 32 >128 27.7 of 2 mg/L. Strains were categorised as ESBL- •Oral formulations of mecillinam should be Gentamicin 16 128 33.3 32 128 29.8 considered as possible agents for the treatment of positive if they had a a CTX or CAZ MIC Trimethoprim 4 64 11.1** 64 128 27.7** >1mg/L which decreased ≥4-fold on addition of uncomplicated urinary tract infections caused ** ** rd clavulanate. Nitrofurantoin 64 128 45.8 64 128 40.4 byEnterobacteriaceae resistant to 3 generation cephalosporins. *-BSAC Breakpoints, ** - BSAC Urinary Breakpoints.
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