1. Figure 1: Differential in MICs for common C. difficile ribotypes Introduction Clostridium difficile has been identified as the primary cause of nosocomial diarrhoea worldwide. C. difficile infection (CDI) is a significant cause of morbidity, particularly in elderly hospitalised patients, and a major burden on healthcare providers. CDI treatment remains limited with metronidazole and vancomycin the mainstay of treatment. Recent reports of reduced metronidazole efficacy in severe CDI cases and certain ribotypes plus increasing rates of relapse and re-infection warrants a need for alternative therapies. Surotomycin is a novel cyclic lipopeptide which has previously demonstrated potent bactericidal activity against C. difficile. This study aims to determine the susceptibilities of all C. difficile PCR ribotypes (including most common ribotypes), to surotomycin and comparator antimicrobials. The antimicrobials tested include those commonly used as treatments in UK, Europe and USA. Susceptibility of Clostridium difficile to Surotomycin and Therapeutic Comparators S. Copsey, S. Scotford*, S. Jones, C. Davis, M. Wootton, T. Morris, L. Chesnel, R.A. Howe Methods 580 C.difficile isolates representing all designated ribotypes including multiples of common types (001, 002, 014, 020, 027, 078 and 106) were tested. MICs were obtained using agar dilution according to CLSI guidelines for clindamycin (CLI), moxifloxacin (MOX), metronidazole (MET), rifaximin (RIF), tigecycline (TIG) and vancomycin (VAN). CLSI breakpoints (BP) were used to interpret MET, VAN, MOX & CLI. A EUCAST wild type epidemiological cut off (ECOFF) was used for TIG. A previously published putative BP of ≥32mg/L was used for RIF. There are no established BPs for fidaxomycin (FDX) due to no/little correlation between clinical BP/ECOFF and clinical efficacy. No BP has been determined for surotomycin (SUR) at this time. Conclusions Surotomycin displays good activity across all C. difficile ribotypes. Due to the well documented issues with current treatment options, it is likely that newer agents such as surotomycin will become an important part of CDI treatment in the future. Anaerobe Reference Unit, Public Health Wales, Cardiff, UK Email: selina.scotford@wales.nhs.uk P- 24 th ECCMID May 10 th – May 13 th, 2014 Barcelona, Spain Figure 3: Percentage resistance of C. difficile isolates to agents tested Table 1: Range and MIC 90 of all C. difficile isolates including common types b b Figure 2: Population density of C. difficile isolates to SUR, FDX, MET and VAN. Results Ribo SurotomycinMetronidazoleVancomycinRifaximinFidaxomicinMoxifloxacinClindamycinTigecycline BP/ ECOFF ** RangeMIC 90 BP (CLSI) RangeMIC 90 BP (CLSI) RangeMIC 90 BP*RangeMIC 90 BP/ ECOFF ** Range MIC 90 BP (CLSI) RangeMIC 90 BP (CLSI) RangeMIC 90 BP/ ECOFF ** RangeMIC 90 All (580) N/A0.03-20.25≥ 320.03-20.25≥ 160.12-41≥ 32 256 0.015N/A0.008-10.25≥ 8 0.12- >32 2≥ 8 0.06- >256 8≤ 0.250.03-20.12 001 N/A 0.03- 0.25 0.12≥ 320.12-10.5≥ 160.5-22≥ 32 0.004- 0.008 0.008N/A 0.008- 0.015 0.015≥ 80.12-3232≥ 81-2568≤ 0.25 0.06- 0.12 0.12 002 N/A 0.12- 0.5 0.25≥ 32 0.012- 0.25 0.25≥ 160.5-11≥ 32 0.004- 0.008 0.008N/A 0.015- 0.12 0.12≥ 80.5-22≥ 84-88≤ 0.250.06 014 N/A 0.06- 0.25 0.12≥ 32 0.03- 0.25 0.25≥ 160.5-10.5≥ 32 <0.002- 0.008 0.008N/A 0.03- 0.12 0.12≥ 81-88≥ 82-88≤ 0.25 0.06- 0.12 0.06 027 N/A 0.12- 0.5 0.5≥ 32 0.12- 2.0 2≥ 160.5-11≥ 32 0.008- 0.015 0.015N/A 0.12- 0.25 0.25≥ 81-1616≥ 84-88≤ 0.25 0.06- 0.12 0.12 MIC 90 and MIC ranges for the most common ribotypes are shown in the table 1, fig 1 All isolates were susceptible to MET and VAN For FDX all isolates were inhibited by 1 mg/L, with an MIC 90 of 0.25 mg/L The MIC 90 for SUR was 0.25 mg/L and all isolates were inhibited by 2 mg 10% (58) of isolates were resistant to MOX all belonged to the previously established resistant ribotypes 001, 027 and 106 41% of isolates were resistant to CLI with no particular ribotype implicated 0.9% (5) of isolates exhibited an MIC for TIG above the ECOFF of ≤ 0.25 mg/L 2.2% (13) of isolates were resistant to RIF using the putative breakpoint of ≥32 mg/L