title: In vitro activity of solithromycin against erythromycin-resistant Streptococcus agalactiae.
abstract: The in vitro antibacterial activity of solithromycin (CEM-101) against macrolide-resistant isolates (n=62) of Streptococcus agalactiae (group B streptococcus [GBS]) was determined. Phenotypic characterization of macrolide-resistant strains was performed by double-disc diffusion testing. A multiplex PCR was used to identify the erm(B), erm(TR), and mef(A/E) genes, capsular genotypes, and alpha-like (Alp) protein genes from the GBS strains. Determination of MIC was carried out using the microdilution broth method. The Etest method was used for penicillin, azithromycin, clarithromycin, and erythromycin. Solithromycin had a MIC50 of ≤0.008 μg/ml and a MIC90 of 0.015 μg/ml against macrolide-susceptible S. agalactiae. These MICs were lower than those displayed by penicillin (MIC50 of 0.032 μg/ml and MIC90 of 0.047 μg/ml), the antibiotic agent of choice for prophylaxis and treatment of GBS infections. Against macrolide-resistant S. agalactiae, solithromycin had a MIC50 of 0.03 μg/ml and a MIC90 of 0.125 μg/ml. Against erm(B) strains, solithromycin had a MIC50 of 0.03 μg/ml and a MIC90 of 0.06 μg/ml, while against mef(A) strains, it had a MIC50 of 0.03 μg/ml and a MIC90 of 0.125 μg/ml. Most erythromycin-resistant GBS strains were of serotype V (64.5%) and associated significantly with alp2-3. Moreover, a statistically significant association was observed between the constitutive macrolide-lincosamide-streptogramin B resistance (cMLSB) phenotype and the erm(B) gene-carrying strains, the alp2-3 gene and the M phenotype, and the mef(A/E) gene and epsilon. Overall, our results show that solithromycin had lower or similar MICs than penicillin and potent activity against macrolide-resistant strains independent of their genotype or phenotype, representing a valid therapeutic alternative where β-lactams cannot be used.
authors.affiliation: Institute of Microbiology, Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Piccinelli
authors.forename: Prabhavathi
authors.initials: P
authors.lastname: Fernandes
authors.forename: Carlo
authors.initials: C
authors.lastname: Bonfanti
authors.forename: Francesca
authors.initials: F
authors.lastname: Caccuri
authors.forename: Arnaldo
authors.initials: A
authors.lastname: Caruso
authors.forename: Maria Antonia
authors.initials: MA
authors.lastname: De Francesco
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D052978:Disk Diffusion Antimicrobial Tests; D024881:Drug Resistance, Bacterial; D004917:Erythromycin / Q000494:pharmacology*; D005798:Genes, Bacterial / Q000235:genetics; D066298:In Vitro Techniques; D018942:Macrolides / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D060885:Multiplex Polymerase Chain Reaction; D013292:Streptococcus agalactiae / Q000187:drug effects* / Q000235:genetics; D014230:Triazoles / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D018942:Macrolides; D014230:Triazoles; D004917:Erythromycin; C547755:solithromycin