title: Re-evaluation of in vitro activity of primycin against prevalent multiresistant bacteria.
abstract: With the increasing emergence of antibiotic resistances old antibiotics became a valuable source to find agents suitable to address this problem. More than 20 years after the last report, our purpose was to re-evaluate the in vitro antibacterial activity of the topical agent primycin against current important bacterial pathogens. Minimal inhibitory concentrations (MIC) and minimal bactericidal concentrations (MBC) of primycin were tested in comparison with agents widely applied topically, and with those of mupirocin and vancomycin, the topical and the non-topical gold-standard anti-MRSA agents. Primycin was ineffective (MIC>64 μg/ml) against all the Gram-negative isolates tested. On the other hand, all the tested Gram-positive isolates were susceptible with MIC90 values of 0.06 μg/ml for staphylococci and 0.5-1 μg/ml for enterococci, streptococci, and P. acnes isolates, including all the multiresistant strains. Against MRSA isolates primycin showed slightly higher activity than mupirocin, and inhibited the mupirocin-resistant strains also. MBC90 values ranged from 0.25 to 2 μg/ml for the investigated Gram-positive species. The bactericidal effect proved to be concentration-dependent in time-kill experiments. Spontaneous resistant mutants did not emerge in single-step mutation experiments and the resistance development was very slow by serial passaging. Passaged S. aureus strains showing increased primycin MIC values exhibited elevated vancomycin and daptomycin MIC values also. Though elucidation of the mechanisms behind warrants further investigations, these correlations can be related to development of vancomycin-intermediate phenotype. From the point of view of medical practice it is noteworthy that the increased primycin MIC values remained far below the concentration accessible by local application of the agent. These data make primycin a remarkable object of further investigations as well as a promising candidate for topical application against multiresistant Gram-positive pathogens.
authors.affiliation: PannonPharma Pharmaceutical Ltd, Pécsvárad, Hungary; Department of Medical Microbiology and Immunology, Medical School, University of Pécs, Pécs, Hungary.
authors.forename: Péter
authors.initials: P
authors.lastname: Feiszt
authors.affiliation: Department of Medical Microbiology and Immunology, Medical School, University of Pécs, Pécs, Hungary.
authors.forename: Gyula
authors.initials: G
authors.lastname: Mestyán
authors.affiliation: Department of Medical Microbiology and Immunology, Medical School, University of Pécs, Pécs, Hungary.
authors.forename: Monika
authors.initials: M
authors.lastname: Kerényi
authors.affiliation: Institute of Medical Microbiology, Faculty of Medicine, Semmelweis University, Budapest, Hungary.
authors.forename: Orsolya
authors.initials: O
authors.lastname: Dobay
authors.affiliation: Department of Medical Microbiology, Faculty of Medicine, University of Debrecen, Hungary.
authors.forename: Judit
authors.initials: J
authors.lastname: Szabó
authors.affiliation: Department of Medical Microbiology, Faculty of Medicine, University of Debrecen, Hungary.
authors.forename: Zsuzsanna
authors.initials: Z
authors.lastname: Dombrádi
authors.affiliation: Institute of Clinical Microbiology, Faculty of Medicine, University of Szeged, Szeged, Hungary.
authors.forename: Edit
authors.initials: E
authors.lastname: Urbán
authors.affiliation: Department of Medical Microbiology and Immunology, Medical School, University of Pécs, Pécs, Hungary; Institute for Veterinary Medical Research, Centre for Agricultural Sciences, Hungarian Academy of Sciences, Budapest, Hungary. Electronic address: levente.emody@aok.pte.hu.
authors.forename: Levente
authors.initials: L
authors.lastname: Emődy
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D024901:Drug Resistance, Multiple, Bacterial; D006090:Gram-Negative Bacteria / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000187:drug effects*; D006801:Humans; D018942:Macrolides / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D050296:Microbial Viability / Q000187:drug effects; D009154:Mutation; D012641:Selection, Genetic; D012692:Serial Passage
chemical_list: D000900:Anti-Bacterial Agents; D018942:Macrolides; C009041:primycin
keywords: MRSA; Primycin; Susceptibility; Time-kill; VISA; VRE