title: Evaluation of the in vitro activities of ceftobiprole and comparators in staphylococcal colony or microtitre plate biofilm assays.
abstract: The aim of this study was to evaluate the in vitro efficacy of ceftobiprole and comparator antibiotics, either alone or in combination, in staphylococcal MBEC™ (minimum biofilm eradication concentration) and colony biofilm assays at dilutions of the maximum free-drug plasma concentration attained during clinical use (fCmax). Staphylococci tested included meticillin-susceptible and meticillin-resistant Staphylococcus aureus (n=6) and Staphylococcus epidermidis (n=2). Relative to no-drug controls, after 7 days of exposure ceftobiprole concentrations from 1/4 fCmax to fCmax generally decreased CFUs in MBEC or colony biofilms of S. aureus isolates by ca. 1.5log10 to ≥2.5log10. Gentamicin reduced colony biofilm CFUs by ≥1.4log10 at these concentrations with gentamicin-susceptible isolates. Following 7 days of exposure, vancomycin and rifampicin were ineffective as single agents or in combination in the colony model, but yielded CFU decreases from 0 to 5log10 in the MBEC model. Treatment of biofilms with rifampicin for 7 days yielded rifampicin-resistant mutants, and the selection of rifampicin resistance was inhibited by co-treatment with ceftobiprole. Thus, ceftobiprole alone or in combination demonstrated promising activity against biofilms of meticillin-susceptible and -resistant staphylococci at clinically relevant concentrations. In contrast, vancomycin and rifampicin, two agents used clinically for the treatment of biofilm infections, tested separately or together gave inconsistent results and generally had little impact on cell viability.
authors.affiliation: Janssen Research & Development, 1000 Route 202, Raritan, NJ 08869, USA. Electronic address: DAbbanat@its.jnj.com.
authors.forename: Darren
authors.initials: D
authors.lastname: Abbanat
authors.affiliation: Janssen Research & Development, 1000 Route 202, Raritan, NJ 08869, USA.
authors.forename: Wenchi
authors.initials: W
authors.lastname: Shang
authors.affiliation: Janssen Research & Development, 1000 Route 202, Raritan, NJ 08869, USA.
authors.forename: Karen
authors.initials: K
authors.lastname: Amsler
authors.affiliation: Janssen Research & Development, 1000 Route 202, Raritan, NJ 08869, USA.
authors.forename: Colleen
authors.initials: C
authors.lastname: Santoro
authors.affiliation: Janssen Research & Development, 1000 Route 202, Raritan, NJ 08869, USA.
authors.forename: Ellen
authors.initials: E
authors.lastname: Baum
authors.affiliation: Janssen Research & Development, 1000 Route 202, Raritan, NJ 08869, USA.
authors.forename: Steven
authors.initials: S
authors.lastname: Crespo-Carbone
authors.affiliation: Janssen Research & Development, 1000 Route 202, Raritan, NJ 08869, USA.
authors.forename: A Simon
authors.initials: AS
authors.lastname: Lynch
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D018441:Biofilms / Q000187:drug effects*; D002511:Cephalosporins / Q000494:pharmacology*; D015169:Colony Count, Microbial; D006801:Humans; D008826:Microbial Sensitivity Tests; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000254:growth & development / Q000502:physiology; D013212:Staphylococcus epidermidis / Q000187:drug effects* / Q000254:growth & development / Q000502:physiology; D013997:Time Factors
chemical_list: D000900:Anti-Bacterial Agents; D002511:Cephalosporins; C443755:ceftobiprole
keywords: Antibiotic resistance; Biofilm; Ceftobiprole; Staphylococcus