Chlorhexidine Resistance inMethicillin-Resi stant Staphylococcus aureus orJustanElevated MIC? AnInVitro andInVivoAssessment

MRSA isolates without NAB plasmids weremoresusceptible (0.25 and0.5,ug/ml) thanfourofeight MSSAthat wetested (range, 0.25 to2,ug/ml). Chlorhelidine MICswerehigher (4to8,ug/ml) forsevendistinct MRSA isolates withplasmids conveying resistance togentamicin andNAB(GNAB). Curing oftheGNABplasmid fromMRSA strains resulted inafall intheMIC(1to3.3,ug/ml), butnoconsistent fall inkilling bychlorhexidine wasobserved. Noeffect onthechlorhexidine MICorkilling wasobserved whenwe curedstrains ofmethicillin resistance. GNABplasmid transfer resulted inariseinthechlorhexidine MICfor thestrains butnoconsistent fall inkilling bychlorhexidine. Ethical approval wasgranted for10volunteers to eachhaveamethicillin-susceptible, GNAB-resistant, derived transcipient anditsGNAB-susceptible isogenic parent applied toseparate sites inaninvivo skintest; nosignificant difference wasseeninsurvival rates after theapplication ofchlorhexidine. Theseresults suggest thatchlorhexidine appears tobeaseffective asa hand-washing agentforMRSA isolates withorwithout NAB plasmids asitisforMSSAisolates. Nosocomial infection withmnethicillin-res istant Staphylococcus aureus (MRSA)hasbecomeamajor problem worldwide, andcertain MRSA strains- maypossess anepidemic potential (EMRSA), although itisunclear whatfactors are involved (7). Particular EMRSAisolates fromthesoutheast ofEngland (inthisreport theyaretermedEMRSA)and Australia (7,21)appear tobeverysimilar ifnotidentical and possess plasmids withgenescoding forresistance togentamicin, propamidine isethionate, andnucleic-acid binding (NAB)compounds (e.g., ethidium bromide) and,hence, are often termed GNAB plasmids (10). Guidelines (3)published previously tocontrol MRSAhave recommended theuseofantiseptics toreduce theMRSA loadonsuperficial colonized sites. Chlorhexidine, inparticular, hasbecomeacontroversial choice because ofreports ofelevated MICsforMRSA strains compared withthose for methicillin-susc eptible S.aureus (MSSA)strains. Brumfitt et al.(5)foundthat the. chlorhexidine MICforEMRSA (mean MIC,4.19p.g/ml) ishigher than that fornonisogenic MSSA (0.94 ,ug/ml), andMycock(14)reported similar findings, while this wasnotobserved byAl-Masaudi etal. (1). Haley etal.(12) failed toshowadifference between three MSSA andthree MRSA,all local American strains, inatest ofthe rateofkilling bychlorhexidine, buttheydidnotstate whether their strains wereresistant toGNAB. Others havepreferred toexamine isogenic isolates. Coleman etal.(6), ina studyofMRSA isolates inDublin,