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