1 Department of Microbiology & Infection Control, London Health Sciences Centre; 2 University of Western Ontario, London, Ontario, Canada
Received 18 January 2002; returned 17 July 2002; revised 28 August 2002; accepted 10 September 2002
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Abstract |
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Methods: Susceptibilities to three new antibiotics and oxacillin, vancomycin, clindamycin and erythromycin were determined by the agar dilution method, as described by the NCCLS.
Results: Resistance to linezolid was not observed in any isolates, although MIC90 values varied between species. Fifteen of 658 (2.3%) isolates were resistant to quinupristin/dalfopristin, but <1% of the clinically most important isolates of Staphylococcus epidermidis, Staphylococcus haemolyticus and Staphylococcus hominis demonstrated resistance to this agent. Susceptibility to clindamycin correlated with susceptibility to quinupristin/dalfopristin; however, resistance to clindamycin did not predict quinupristin/dalfopristin resistance. Telithromycin was the least active of the new agents tested, showing activity similar to that of clindamycin. Susceptibility and resistance to clindamycin were predictive of susceptibility and resistance to telithromycin.
Conclusion: Clindamycin susceptibility can be used as a surrogate marker for susceptibility to quinupristin/dalfopristin and telithromycin. Quinupristin/dalfopristin and linezolid show good activity against both mecA-positive and -negative CNS.
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Introduction |
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The purpose of this study was to determine the in vitro activity of three new antimicrobials, linezolid, quinupristin/dalfopristin and telithromycin, against a collection of speciated CNS. For the purpose of comparison, the MICs of clindamycin, erythromycin, oxacillin and vancomycin were determined.
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Materials and methods |
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Thirteen species were represented amongst the isolates: Staphylococcus auricularis (five), Staphylococcus capitis (29), Staphylococcus caprae (34), Staphylococcus cohnii (31), Staphylococcus epidermidis (186), Staphylococcus haemolyticus (39), Staphylococcus hominis (76), Staphylococcus lugdunensis (51), Staphylococcus saprophyticus (38), Staphylococcus schleiferi (45), Staphylococcus simulans (39), Staphylococcus warneri (43) and Staphylococcus xylosus (42). In addition to susceptibilities to linezolid, quinupristin/dalfopristin and telithromycin, MICs of erythromycin, clindamycin, oxacillin and vancomycin were determined. Linezolid, and quinupristin/dalfopristin and telithromycin reference powders were kindly provided by Pharmacia & Upjohn, Inc. (Kalamazoo, MI, USA) and Aventis Pharma (Bridgewater, NJ, USA), respectively. All other reference antibiotic powders were obtained from Sigma Chemical Co. (Indianapolis, IN, USA). Agar dilution MIC testing was carried out by the procedures advocated by the NCCLS.7 In addition to test isolates, the NCCLS-recommended control strains Staphylococcus aureus ATCC 29213, Enterococcus faecalis ATCC 29212 and Enterococcus faecium ATCC 19434 were included with each test batch.
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Results |
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Linezolid demonstrated good activity against all CNS and resistance to it was not observed. S. caprae was most susceptible with an MIC90 of 1 mg/L. S. capitis, S. hominis, S. lugdunensis, S. haemolyticus, S. simulans and S. warneri had MIC90s of 2 mg/L. All the remaining species had an MIC90 of 4 mg/L. Resistance to oxacillin, clindamycin or any other agent did not affect susceptibility to linezolid.
The activity of telithromycin against CNS was similar to that of clindamycin. Susceptibility and resistance to clindamycin were predictive of telithromycin MICs of <2 or >4 g/L. Of 522 clindamycin-susceptible isolates, 98.1% had MICs of <2 g/L, and of 136 clindamycin-resistant strains, 123 (90.4%) had MICs of telithromycin > 4 g/L. Overall, activity of telithromycin against CNS was better than that of erythromycin, with resistance rates of 34.6% for erythromycin and 20.2% for telithromycin.
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Discussion |
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Marked increases in multidrug-resistant Gram-positive bacteria have compromised the selection of agents available for therapy.4 Emergence of vancomycin-resistant enterococci raised the concern that this resistance could be transferred to staphylococci, and recently a vancomycin-resistant S. aureus was isolated from a patient with a catheter exit-site infection.9 New classes of antibiotics with novel mechanisms of action are highly desirable. Quinupristin/dalfopristin, linezolid, and to certain extent telithromycin, are such antibiotics.
Quinupristin/dalfopristin had good activity against most species of CNS regardless of the presence of the mecA gene. More than 97% of isolates had MICs of <4 g/L. Amongst the three most commonly occurring species, S. epidermidis, S. haemolyticus and S. hominis, resistance rates were <1.0%. Overall susceptibility results of this study are similar to those published previously.1012 However, species-specific rates of resistance in the present study differed significantly from those reported from Taiwan.10
Susceptibility to clindamycin was found to be predictive of susceptibility to quinupristin/dalfopristin; a similar correlation has been reported for S. aureus.13 Quinupristin/dalfopristin, unlike other macrolides and lincosamides, is bactericidal and has a prolonged post-antibiotic effect, so that the potential for development of resistance is low.14 Its use is complicated by a number of drug incompatibilities and its metabolism by the P450 cytochromes leads to numerous drug interactions. Resistance to quinupristin/dalfopristin has already been reported, both in E. faecium and staphylococci. Several mechanisms of resistance have been identified.15
Linezolid, along with vancomycin, was the most active agent against the CNS isolates, both mecA positive and negative. A report from Taiwan documented non-susceptibility to linezolid in 2% of CNS isolates from that country.10 Although clinical data are lacking, linezolid may prove to be a useful agent in treating CNS infections owing to its excellent oral bioavailability. There have been reports of reversible myelosuppression with longer-term use of linezolid, and further experience is needed on the use of this agent in infections requiring long-term therapy (such as prosthetic valve endocarditis or orthopaedic device infections).16
In our study, telithromycin showed superior activity against mecA-positive and -negative CNS when compared with erythromycin. This observation has also been reported previously.1719 Activity was, however, no better than that of clindamycin. In the present study, susceptibility and resistance to clindamycin were predictive of susceptibility and resistance to telithromycin. A similar correlation was noted by Jamijian et al.20 between clindamycin and another ketolide (RU-64004).
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Acknowledgements |
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Footnotes |
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References |
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