a Sera & Vaccines Central Research Laboratory, Chelmska 30/34, 00-725 Warsaw; b Department of Internal Medicine, Warsaw University Medical School, Lindleya 1, 02-005 Warsaw, Poland
Sir,
Linezolid is one of the newer antibacterial agents with a spectrum of activity against Gram-positive bacteria. It is the first drug of a new class of antibiotics, the oxazolidinones, introduced recently to therapy. The aim of this study was to investigate the in vitro activity of linezolid against Gram-positive cocci isolated from patients suffering from various community- and hospital-acquired infections. Its activity was compared with glycopeptides and quinupristin/dalfopristin.
A total of 417 Gram-positive cocci selected from isolates collected in 2000 in 61 medical centres in Poland were included in the study. They were isolated from skin and soft tissue infections (33.3%), sputum and tracheobronchial fluids (23.2%), blood (23.2%), pharynx (6.2%), CSF (4.5%), urine (2.6%) and other sites (6.7%). The 106 isolates of Staphylococcus aureus included 72 methicillin-resistant isolates (MRSA), and 18 of the 21 isolates of coagulase-negative staphylococci (CNS) were methicillin resistant (MRCNS). Sixteen of 39 Enterococcus faecalis isolates were vancomycin resistant as were 20 of 47 Enterococcus faecium. Of the 144 Streptococcus pneumoniae isolates, 94 exhibited reduced susceptibility to penicillin. Fifty-six of 60 Streptococcus pyogenes isolates were erythromycin resistant. All isolates were identified by standard procedures. The antibiotics tested included linezolid (Pharmacia & Upjohn, Inc., Kalamazoo, MI, USA), vancomycin (Eli Lilly & Co., Indianapolis, IN, USA), teicoplanin (Marion Merrell, Denham, UK) and quinupristin/ dalfopristin (Rhone-Poulenc Rorer, Collegeville, PA, USA). Linezolid was tested in concentrations ranging from 0.12 to 16 mg/L, vancomycin and teicoplanin, 0.007 to 512 mg/L and quinupristin/dalfopristin, 0.12 to 32 mg/L. The oxacillin saltagar screening plate procedure was used for the detection of MRSA and high-concentration gentamicin and streptomycin agar tests were used for the detection of high-level aminoglycoside resistance (HLAR).1 Erythromycin resistance phenotypes were determined according to the method of Seppälä et al.2 MICs were determined by the agar dilution method for staphylococci and enterococci and by the broth microdilution method for pneumococci and S. pyogenes, according to NCCLS guidelines.1 Control strains used were S. aureus ATCC 29213, E. faecalis ATCC 29212, E. faecalis ATCC 51299, S. aureus ATCC 43300 and S. pneumoniae ATCC 49619.
The activities of linezolid and other antibiotics tested are shown in the Table. Linezolid inhibited all isolates at concentrations between 0.12 and 2 mg/L. It showed equally good activity against methicillin-susceptible and -resistant S. aureus and CNS with an MIC90 of 2 mg/L. The MIC90s of linezolid, vancomycin and teicoplanin for MRSA were the same (2 mg/L). Linezolid was also very active against MRCNS, including strains with MICs of teicoplanin of 4 mg/L. For all staphylococcal strains quinupristin/ dalfopristin were one- to two-fold dilutions lower than for linezolid. Recently, infections caused by multiresistant Enterococcus spp. have become a worldwide threat, and various novel compounds have been developed to eradicate them. In the present study, multiresistant E. faecalis and E. faecium with VanA, VanB and HLAR phenotypes were all inhibited by linezolid at concentrations of 0.52 mg/L and presented similar activities to quinupristin/dalfopristin against E. faecium. Our results were in agreement with the results of other in vitro studies3 and indicate that these new agents have the potential to become clinically valuable. However, quinupristin/dalfopristin is lacking activity against E. faecalis (MICs usually 1632 mg/L),4 which constitutes a serious therapeutic disadvantage.
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In the early 1990s there was an increase in erythromycin resistance among S. pyogenes in many countries including Poland. All clinical isolates of erythromycin-resistant S. pyogenes tested in this study were inhibited by linezolid at 0.121 mg/L.
This paper describes the results of the first study carried out in Poland to evaluate the in vitro activity of linezolid against multidrug-resistant Gram-positive cocci isolated from different specimens. The results are in agreement with previously reported data and demonstrate that the new streptogramin quinupristin/dalfopristin, and the oxazolidinone linezolid, have good activity in vitro against multidrug-resistant Gram-positive cocci.46 These drugs are promising therapeutic options in an era of rapidly growing antibiotic resistance.
Notes
* Corresponding author. Tel: +48-22-851-46-70; Fax: +48-22-841-29-49; E-mail: kazbunda{at}urania.il.waw.pl
References
1 . National Committee for Clinical Laboratory Standards. (2000). Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow AerobicallyFifth Edition: Approved Standard M7-A2. NCCLS, Villanova, PA.
2 . Seppälä, H., Nissinen, A., Yu, Q. & Huovinen, P. (1993). Three different phenotypes of erythromycin-resistant Streptococcus pyogenes in Finland. Journal of Antimicrobial Chemotherapy 32, 88591.[ISI][Medline]
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