Antimicrobial Activity of Solithromycin (CEM-101), a Novel Fluoroketolide, Tested Against Isolates Collected in Europe during 2010 Surveillance

1136 DJ Biedenbach1, HS Sader1, RN Jones1, DJ Farrell1 1JMI Laboratories, North Liberty, Iowa, USA Objective: To evaluate the potency and spectrum of activity of solithromycin (SOL), a novel fluoroketolide, against a contemporary (2010) collection of European (EU) pathogens associated with community-acquired bacterial pneumonia (CABP) and acute bacterial skin and skin structure infections (ABSSSI), compared to erythromycin (ERY), azithromycin (AZI), clarithromycin (CLA), clindamycin (CLI) and telithromycin (TEL). Methods: A total of 6,378 isolates, collected from 41 medical centers (18 EU countries) in 2010 were included. Species/group (number of isolates) were: Staphylococcus aureus (SA; 2,539), coagulase-negative staphylococci (CoNS; 610), enterococci (ENT; 934), Streptococcus pneumoniae (SPN; 764), viridans group streptococci (VGS; 274) beta-haemolytic streptococci (BHS; 762) Haemophilus influenzae (HI; 326) and Moraxella catarrhalis , , (MCAT; 169). Consecutive isolates were susceptibility (S) tested by CLSI broth microdilution methods and results were interpreted by CLSI and EUCAST breakpoints. Results: SOL was eight-fold more active (MIC90, 0.25 mg/L) against SA compared toTEL (MIC90, 2 mg/L) with off-scale MIC90 values found for ERY (>4 mg/L) and CLI (>2 mg/L). SOL (MIC50/90, ≤0.03/>4 mg/L) had a comparable activity to TEL against CoNS (74.3% S). SOL was only moderately active against ENT (MIC50/90, 0.5/2 mg/L), but was two-fold more potent than TEL (MIC50/90, 1/4 mg/L). SOL demonstrated greater potency against E. faecalis (EF) (MIC50, 0.06 mg/L) compared to E. faecium (EFM; MIC50, 1 mg/L). SOL was very active against SPN (MIC90, ≤0.03 mg/L), VGS and BHS (MIC90, both ≤0.03 mg/L) with 100.0% of all streptococcal isolates inhibited at ≤0.5 mg/L. The tested SPN isolates were only 72.8, 75.1 and 82.5% S to penicillin (PEN), ERY and CLI, respectively. SOL was very active against MCAT (MIC90, 0.06 μg/ml) with lower activity against both beta-lactamase-positive and -negative HI isolates (MIC90, 2 μg/ml). SOL activity against HI was four-fold more active than ERY against MCAT. The EU collection sampled had 27.1% MRSA, 71.8% MR-CoNS, 1.2% vancomycin-resistant (VR)-EF, 18.1% VR-EFM, 22.3% PEN non-S VGS and 15.3% of HI were beta-lactamasepositive. Conclusions: SOL clearly exhibited greater potency than currently available macrolide agents, CLI and TEL (comparator ketolide), against contemporary (2010) EU pathogens commonly isolated in CABP or ABSSSI. This data supports clinical trial investigations of SOL for the treatment of these infections. Cumulative % occurrences at SOL MIC (mg/L): Organism (no.) ≤0.03 0.06 0.12 0.25 0.5 1 2 4 >4 SA (2,539) 61.4 88.3 89.8 90.0 90.1 90.2 90.2 90.3 100.0 CoNS (610) 52.6 71.0 73.6 74.1 74.3 74.4 74.6 75.3 100.0 ENT (934) 36.2 39.8 41.8 45.3 57.1 82.1 99.5 99.8 100.0 SPN (764) 91.4 94.2 96.6 99.5 100.0 -a VGS (274) 91.2 95.6 98.2 100.0 BHS (762) 94.5 97.0 98.7 99.6 100.0 HI (326) 0.3 0.3 0.9 1.8 19.0 83.7 98.2 98.2 100.0 MCAT (169) 20.7 95.3 100.0 a. = no occurrences; underlined value = MIC90.