title: Investigation and Treatment of Fusidic Acid Resistance Among Methicillin-Resistant Staphylococcal Isolates from Egypt.
abstract: Methicillin resistance among staphylococci isolated from patients in northern Egypt has escalated alarmingly in the past decade. Data about the prevalence of fusidic acid (FA) resistance in Egyptian clinical isolates are limited. This work investigates the prevalence and mechanism of FA resistance among 81 methicillin-resistant staphylococcal isolates from major hospitals of Alexandria, Egypt. Some combinations for treating infections due to resistant isolates were studied. Twenty-six isolates (32.1%) were FA resistant (minimum inhibitory concentrations [MICs] = 2-1,024 μg/ml), and fusB and fusC genes coding for FA resistance were detected in 30.77% and 34.62% of the FA-resistant strains, respectively. One highly resistant isolate, S502 (MIC = 1,024 μg/ml), possessed both genes. Plasmid curing resulted in fusB loss and MIC decrease by 16-64 folds. Conjugation caused acquisition of FA resistance among susceptible isolates. Serial passages in subinhibitory FA concentrations produced mutants with increased MIC by 4-32 folds. The combination of FA with rifampin, gentamicin, or ampicillin/sulbactam, in a subinhibitory concentration, was synergistic against the isolates, including serial passage mutants, decreasing number of survivors by an average of 2-4 logs. A relatively moderate rate of FA resistance was detected in Alexandria hospitals. Combination therapy with gentamicin, rifampin, or ampicillin/sulbactam is crucial to preserve the effectiveness of FA.
authors.affiliation: 1 Department of Microbiology, Faculty of Pharmacy, Alexandria University , Alexandria, Egypt .
authors.forename: Alaa
authors.initials: A
authors.lastname: Abouelfetouh
authors.affiliation: 1 Department of Microbiology, Faculty of Pharmacy, Alexandria University , Alexandria, Egypt .
authors.forename: Mervat
authors.initials: M
authors.lastname: Kassem
authors.affiliation: 2 Department of Microbiology, Faculty of Pharmacy, Damanhour University , Damanhour, Egypt .
authors.forename: Marwa
authors.initials: M
authors.lastname: Naguib
authors.affiliation: 1 Department of Microbiology, Faculty of Pharmacy, Alexandria University , Alexandria, Egypt .
authors.forename: Moustafa
authors.initials: M
authors.lastname: El-Nakeeb
mesh_terms: D000667:Ampicillin / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism; D003227:Conjugation, Genetic; D004338:Drug Combinations; D024901:Drug Resistance, Multiple, Bacterial / Q000235:genetics; D004357:Drug Synergism; D004534:Egypt / Q000453:epidemiology; D005672:Fusidic Acid / Q000494:pharmacology*; D015964:Gene Expression Regulation, Bacterial; D005839:Gentamicins / Q000494:pharmacology; D006801:Humans; D008712:Methicillin / Q000494:pharmacology*; D016106:Methicillin Resistance / Q000235:genetics*; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development / Q000378:metabolism; D008826:Microbial Sensitivity Tests; D010957:Plasmids / Q000737:chemistry / Q000378:metabolism; D012293:Rifampin / Q000494:pharmacology; D013203:Staphylococcal Infections / Q000188:drug therapy / Q000453:epidemiology / Q000382:microbiology; D013407:Sulbactam / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D004338:Drug Combinations; C492443:FusB protein, Staphylococcus aureus; D005839:Gentamicins; D005672:Fusidic Acid; D000667:Ampicillin; D008712:Methicillin; D013407:Sulbactam; D012293:Rifampin
keywords: conjugation; mechanisms of antibiotic resistance fusB and fusC; plasmid curing antibiotic combinations