Activity of linezolid against levofloxacin-resistant Streptococcus pneumoniae, methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci in Hong Kong

P. L. Ho*,, T. K. Ng, R. W. H. Yung, T. L. Que, Eric K. T. Yip, C. W. S. Tse and K. Y. Yuen

Antimicrobial Resistance Study Group, Center of Infection, Faculty of Medicine, The University of Hong Kong, Pokfulam Road, Pokfulam, Hong Kong

Sir,

Worldwide, antimicrobial resistance among the Grampositive cocci is increasing. In South East Asia, multidrug resistance among Staphylococcus aureus and Streptococcus pneumoniae is particularly problematic. At present, vancomycin-resistant enterococci (VRE) are uncommon in this region, but clusters have been reported.1 Our previous study and those of others showed that susceptibility of drug-resistant Gram-positive cocci to new antimicrobial agents, even in the pre-marketing stage in South East Asia can differ from those in the Western hemisphere.2,3 The present study was therefore conducted to examine the in vitro antibacterial activities of linezolid against recent clinical isolates of enterococcus, S. aureus and S. pneumoniae collected from all over Hong Kong.

Isolates of S. aureus and S. pneumoniae were recovered from clinical specimens of in-patients in the participating laboratories (A to E) between 1 January 2000 and 31 March 2001. These laboratories provide a microbiology service to hospitals serving about half of the population in Hong Kong. All isolates were selected at random and were believed to be clinically significant, using local criteria. Only one isolate from each patient was included. The specimen source of the S. pneumoniae isolates was either respiratory tract (n = 117) or blood (n = 3). The numbers of S. pneumoniae isolates from each laboratory were: 29 (A), 23 (B), 15 (C), 27 (D) and 26 (E). The source of the S. aureus isolates was blood (n = 120) or other sterile body fluids (n = 40). Each of the laboratories A to D contributed 40 S. aureus strains (20 methicillin susceptible and 20 methicillin resistant). Eleven genotypically characterized clinical isolates of VRE obtained from five hospitals between November 1997 and February 2001 were also included. Three were vancomycin-resistant Enterococcus faecalis (all vanA) and eight were vancomycin-resistant Enterococcus faecium (four vanA and four vanB).

The Etest (AB Biodisk, Solna, Sweden) was used to determine the MIC of the antimicrobial agents. The following antimicrobial agents were used: cefotaxime, clindamycin, erythromycin, fusidic acid, levofloxacin, linezolid, penicillin, trimethoprim–sulfamethazole and vancomycin. S. aureus susceptibility to methicillin was determined by the oxacillin–salt agar screening test.4 All the MIC results were interpreted according to NCCLS criteria.4 For linezolid, the following tentative breakpoints were used: enterococcus (<=2 mg/L, susceptible; 4 mg/L, intermediate; >8 mg/L, resistant); S. pneumoniae (<=2 mg/L, susceptible) and S. aureus (<=4 mg/L, susceptible).

The TableGo shows a comparison of in vitro activities of linezolid and reference drugs against clinical isolates of S. pneumoniae, S. aureus and VRE. Linezolid was active against the entire S. pneumoniae and S. aureus collection over a narrow range (1–2 mg/L). Activity was the same irrespective of susceptibility to ß-lactams or other drugs. All 14 levofloxacin-resistant S. pneumoniae were susceptible to linezolid. Four vancomycin-resistant E. faecium had an intermediate linezolid MIC of 4 mg/L. The remaining three vancomycin-resistant E. faecium and three vancomycin-resistant E. faecalis were inhibited by 2 mg/L of linezolid.


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Table. Antibacterial activity of linezolid and reference drugs against clinical isolates of S. pneumoniae, S. aureus and VRE
 
In agreement with other studies,5 we demonstrated that the penicillin non-susceptible S. pneumoniae, methicillin-resistant S. aureus and VRE isolates are inhibited by low concentrations of linezolid. Importantly, activity of linezolid was the same against isolates susceptible or resistant to levofloxacin. This finding is encouraging given that fluoroquinolone-resistant S. pneumoniae are often multiply resistant to penicillin and other antimicrobial agents.3 In South East Asia, drug-resistant S. pneumoniae is highly prevalent.6 The in vitro activity of linezolid indicates that it might be a potentially useful drug for therapy of drug-resistant S. pneumoniae. However, available clinical data on the role of linezolid in drug-resistant S. pneumoniae are limited. For S. pneumoniae infection, the drug is currently only licensed for therapy of infections caused by penicillin-susceptible strains. Similar to a recent study from Taiwan,2 all methicillin-resistant S. aureus isolates were inhibited by linezolid at 2 mg/L. While only one of 100 vancomycin-resistant E. faecium in the Taiwan study had a linezolid MIC of 4 mg/L, the same level of reduced susceptibility was found in four of seven vancomycin-resistant E. faecium in this study. In summary, our results indicate that linezolid may prove useful in the treatment of infections caused by drug-resistant Gram-positive bacteria such as fluoroquinolone-resistant S. pneumoniae, but close monitoring of the susceptibility of vancomycin-resistant E. faecium to this agent will be needed.

Acknowledgements

This study was supported in part by a research grant from Pharmacia (Hong Kong).

Notes

* Corresponding author. Tel: +852-2855-4892; Fax: +852-2855-1241; E-mail: plho{at}hkucc.hku.hk Back

References

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3 . Ho, P. L., Que, T. L., Tsang, D. N., Ng, T. K., Chow, K. H. & Seto, W. H. (1999). Emergence of fluoroquinolone resistance among multiply resistant strains of Streptococcus pneumoniae in Hong Kong. Antimicrobial Agents and Chemotherapy 43, 1310–3.[Abstract/Free Full Text]

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