title: Emergence of resistance among USA300 methicillin-resistant Staphylococcus aureus isolates causing invasive disease in the United States.
abstract: USA300 methicillin-resistant Staphylococcus aureus (MRSA) isolates are usually resistant only to oxacillin, erythromycin, and, increasingly, levofloxacin. Of these, oxacillin and levofloxacin resistances are chromosomally encoded. Plasmid-mediated clindamycin, mupirocin, and/or tetracycline resistance has been observed among USA300 isolates, but these descriptions were limited to specific patient populations or isolated occurrences. We examined the antimicrobial susceptibilities of invasive MRSA isolates from a national surveillance population in order to identify USA300 isolates with unusual, possibly emerging, plasmid-mediated antimicrobial resistance. DNA from these isolates was assayed for the presence of resistance determinants and the presence of a pSK41-like conjugative plasmid. Of 823 USA300 isolates, 72 (9%) were tetracycline resistant; 69 of these were doxycycline susceptible and tetK positive, and 3 were doxycycline resistant and tetM positive. Fifty-one (6.2%) isolates were clindamycin resistant and ermC positive; 22 (2.7%) isolates were high-level mupirocin resistant (mupA positive); 5 (0.6%) isolates were trimethoprim-sulfamethoxazole (TMP-SMZ) resistant, of which 4 were dfrA positive; and 7 (0.9%) isolates were gentamicin resistant and aac6'-aph2'' positive. Isolates with pSK41-like plasmids (n = 24) were positive for mupA (n = 19), dfrA (n = 6), aac6'-aph2'' (n = 6), tetM (n = 2), and ermC (n = 8); 20 pSK41-positive isolates were positive for two or more resistance genes. Conjugative transfer of resistance was demonstrated between four gentamicin- and mupirocin-resistant and three gentamicin- and TMP-SMZ-resistant USA300 isolates; transconjugants harbored a single pSK41-like plasmid, which was PCR positive for aac6'-aph2'' and either mupA and/or dfrA. USA300 and USA100 isolates from the same state with identical resistance profiles contained pSK41-like plasmids with indistinguishable restriction and Southern blot profiles, suggesting horizontal plasmid transfer between USA100 and USA300 isolates.
authors.affiliation: Division of Healthcare Quality Promotion (G-08), Centers for Disease Control and Prevention, 1600 Clifton Rd. NE, Atlanta, GA 30333, USA. lkm1@cdc.gov
authors.forename: Linda K
authors.initials: LK
authors.lastname: McDougal
authors.forename: Gregory E
authors.initials: GE
authors.lastname: Fosheim
authors.forename: Ainsley
authors.initials: A
authors.lastname: Nicholson
authors.forename: Sandra N
authors.initials: SN
authors.lastname: Bulens
authors.forename: Brandi M
authors.initials: BM
authors.lastname: Limbago
authors.forename: Julia E S
authors.initials: JE
authors.lastname: Shearer
authors.forename: Anne O
authors.initials: AO
authors.lastname: Summers
authors.forename: Jean B
authors.initials: JB
authors.lastname: Patel
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002981:Clindamycin / Q000494:pharmacology; D004318:Doxycycline / Q000494:pharmacology; D018432:Drug Resistance, Multiple; D005839:Gentamicins / Q000494:pharmacology; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects* / Q000235:genetics; D008826:Microbial Sensitivity Tests; D016712:Mupirocin / Q000494:pharmacology; D010957:Plasmids / Q000235:genetics; D016133:Polymerase Chain Reaction; D013752:Tetracycline / Q000494:pharmacology; D015662:Trimethoprim, Sulfamethoxazole Drug Combination / Q000494:pharmacology; D014481:United States
chemical_list: D000900:Anti-Bacterial Agents; D005839:Gentamicins; D002981:Clindamycin; D015662:Trimethoprim, Sulfamethoxazole Drug Combination; D016712:Mupirocin; D013752:Tetracycline; D004318:Doxycycline