Journal of Antimicrobial Chemotherapy (2001) 47, 675-680
© 2001 The British Society for Antimicrobial Chemotherapy
Brief report |
In vitro activity of linezolid and 11 other antimicrobials against 566 clinical isolates and comparison between NCCLS microdilution and Etest methods
a Service of Microbiology, Hospital de Bellvitge, Barcelona; b Department of Medical Microbiology, Fundación Jiménez Díaz, Avenida Reyes Católicos 2, 28040 Madrid, Spain
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Abstract |
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The in vitro activity of linezolid and 11 other antimicrobials was determined for 566 clinical isolates of Staphylococcus aureus, Staphylococcus epidermidis, Enterococcus spp., Streptococcus pyogenes, Streptococcus agalactiae, Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis, some of them resistant to several antibiotics, using a broth microdilution method and the Etest method. All Gram-positive organisms tested were inhibited by a concentration of
4 mg/L of linezolid, including methicillin-resistant staphylococci, vancomycin- and ampicillin-resistant enterococci, and penicillin-intermediate and -resistant pneumococci. MICs of linezolid by the Etest method were usually one to two dilution values lower than those obtained by microdilution. |
Introduction |
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Linezolid is an oxazolidinone that exhibits good activity against Gram-positive organisms.1,2 Linezolid is also active against some aerobic and anaerobic Gram-negative pathogens such as Pasteurella spp., Fusobacterium spp., Porphyromonas spp., Prevotella spp. and Bacteroides spp.3 Linezolid has been used effectively in the treatment of serious resistant Gram-positive bacterial infections, such as those produced by methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci.4
There have been some differences in the activity of linezolid against Gram-positive organisms, probably due to methodological variations5 or regional differences in susceptibility. This fact prompted us to determine the in vitro activity of linezolid and 11 other antimicrobials against 566 Gram-positive and -negative clinical isolates. We also compared linezolid MIC results obtained using National Committee for Clinical Laboratory Standards (NCCLS) microdilution methodology with those obtained using the Etest method.
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Materials and methods |
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Bacterial strains
A total of 566 clinical isolates from two tertiary centres in Spain were tested. The organisms included are shown in the Table.
Staphylococcus aureus ATCC 29213, Enterococcus faecalis ATCC 29212 and Streptococcus pneumoniae ATCC 49619 were used as controls.
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Antimicrobials
Linezolid, vancomycin, teicoplanin, gentamicin, penicillin G, ampicillin, co-amoxiclav, oxacillin, ciprofloxacin, erythromycin and clindamycin, provided by Pharmacia & Upjohn, Inc. (Kalamazoo, MI, USA), and clarithromycin, which was a gift from Abbott Laboratories (Chicago, IL, USA), were studied. Etest strips of linezolid and vancomycin were obtained from AB Biodisk (Solna, Sweden).
Antimicrobial susceptibility tests
Broth microdilution method.. MIC values were determined using the NCCLS method.6 For Streptococcus spp. and Haemophilus influenzae, the standard broth medium was supplemented with lysed horse blood. Isolates were categorized as susceptible based on NCCLS criteria, except for linezolid where we used the tentative breakpoint of 4 mg/L, as given previously by Johnson et al.5
Etest method.. The Etest was conducted according to the manufacturer's instructions. All organisms were tested using Mueller–Hinton agar (supplemented with 5% defibrinated sheep blood for streptococci). Both broth microdilution and Etest methods for linezolid and vancomycin were used for staphylococci and enterococci, and linezolid for streptococci.
ß-Lactamase testing
Isolates of H. influenzae and Moxarella catarrhalis were tested for ß-lactamase production using cefinase discs.
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Results |
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The MICs of linezolid and the other 11 antibiotics tested are summarized in the Table.
Linezolid was active against 100% of Gram-positive organisms tested. The activity of linezolid against S. aureus and Staphylococcus epidermidis was not influenced by oxacillin resistance. All Enterococcus spp. studied were inhibited by a concentration of 4 mg/L. The MIC50 and MIC90 of linezolid against S. pneumoniae were 0.5 and 1 mg/L, with no differences observed according to their penicillin susceptibility. All ß-haemolytic streptococci studied were inhibited by 2 mg/L linezolid. Vancomycin and teicoplanin were active against all Gram-positive organisms tested, except vancomycin-resistant Enterococcus spp., where only 30% of isolates were teicoplanin susceptible.
Rates of non-susceptibility in S. pneumoniae to clindamycin and clarithromycin varied from 11 to 59%. It is noteworthy that there were more clindamycin- and clarithromycin-resistant S. pneumoniae among the penicillin-intermediate strains than among the penicillin-resistant pneumococci. We found one penicillin-susceptible S. pneumoniae strain susceptible to clindamycin but resistant to clarithromycin, and one penicillin-intermediate S. pneumoniae strain susceptible to clindamycin but intermediate to clarithromycin (M efflux-based phenotype).
MICs of linezolid by the Etest method were usually one to two dilution values lower than those obtained by microdilution.
The most active antibiotics against H. influenzae were ciprofloxacin and co-amoxiclav, with 33% of H. influenzae isolates producing ß-lactamase. Two H. influenzae isolates (4.7%) were not susceptible to penicillin without production of ß-lactamase. All M. catarrhalis strains tested were susceptible to co-amoxiclav, and only one strain did not produce ß-lactamase.
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Discussion |
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TopAbstractIntroductionMaterials and methodsResultsDiscussionReferences |
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Infections by Gram-positive multi-resistant organisms are increasing worldwide and alternative therapies for these organisms are limited. Our data show good activity for linezolid against S. aureus and S. epidermidis, both oxacillin susceptible and resistant, as well as against vancomycin-susceptible and -resistant Enterococcus spp., which has been reported by others.2,5
Resistance in S. pneumoniae to several antibiotics, especially the ß-lactams and macrolides,7 sometimes makes it difficult to choose an alternative therapy. We found two macrolide-non-susceptible pneumococci (1.6%) of phenotype M strain. This phenotype has occasionally been found in Spain at frequencies of 0.5–3%.7 This is much lower than that found in the USA, where >40% of such strains are phenotype M.8 Linezolid can be administered both orally and parenterally, and may be a good alternative for treatment of such infections. Our data, as well as others reported previously,1 show good in vitro activity of this compound against penicillin-susceptible and non-susceptible S. pneumoniae. Its activity against Streptococcus pyogenes and Streptococcus agalactiae (100%) would make it an alternative treatment for conditions caused by these organisms, such as cellulitis and other soft-tissue infections.
One-third of H. influenzae in our study were ß-lactamase producing (BLP). Resistance to ampicillin by non-ß-lactamase production has been noted in several countries at rates no higher than 5%, and BLP co-amoxiclav-resistant strains (BLPACR) have recently been described.9 Two H. influenzae clinical isolates in our study were non-susceptible to penicillin without production of ß-lactamase. No BLPACR H. influenzae were detected in our study. Since 1992, >90% of clinical isolates of M. catarrhalis have been BLP strains.10 In our study, only one isolate of this microorganism was non-BLP.
Linezolid had a limited activity against H. influenzae (5% susceptible) and M. catarrhalis (47% susceptible) at the breakpoint stated. In our study, MICs of linezolid were lower according to the Etest method than microdilution against all organisms tested. Most differences were within one-fold dilution, which can be considered an experimental error, but it has also been described by others studying enterococci.5
In conclusion, linezolid has good in vitro activity against Gram-positive organisms and appears to be a promising agent for the treatment of corresponding infections. Its role in clinical practice must be addressed further in clinical trials.
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Acknowledgments |
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This work was supported by Pharmacia & Upjohn, Inc. (Kalamazoo, MI, USA).
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Notes |
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* Corresponding author. Tel: +34-91-544-7387; Fax: +34-91-549-4764; E-mail: fsoriano{at}fjd.es
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References |
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1 . Kearney, J. A., Barbadora, K., Mason, E. O., Wald, E. R. & Green, M. (1999). In vitro activities of the oxazolidinone compounds linezolid (PNU-100766) and eperzolid (PNU-100592) against middle ear isolates of Streptococcus pneumoniae. International Journal of Antimicrobial Agents 12, 141–4.[Web of Science][Medline]
2 . Patel, R., Rouse, M. S., Piper, K. E. & Steckelberg, J. M. (1999). In vitro activity of linezolid against vancomycin-resistant enterococci, methicillin-resistant Staphylococcus aureus and penicillin-resistant Streptococcus pneumoniae. Diagnostic Microbiology and Infectious Disease 34, 119–22.[Web of Science][Medline]
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Goldstein, E. J., Citron, D. M. & Merriam, C. V. (1999). Linezolid activity compared to those of selected macrolides and other agents against aerobic and anaerobic pathogens isolated from soft tissue bite infections in humans. Antimicrobial Agents and Chemotherapy 43, 1469–74.
4 . Chien, J. W., Kucia, M. L. & Salata, R. A. (2000). Use of linezolid, an oxazolidinone, in the treatment of multidrug-resistant grampositive bacterial infections. Clinical of Infectious Diseases 30, 146–51.[Web of Science][Medline]
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Johnson, A. P., Warner, M. & Livermore, D. M. (2000). Activity of linezolid against multi-resistant Gram-positive bacteria from diverse hospitals in the United Kingdom. Journal of Antimicrobial Chemotherapy 45, 225–30.
6 . National Committee for Clinical Laboratory Standards. (2000). Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow Aerobically—Fifth Edition: Approved Standard M7-A5. NCCLS, Wayne, PA.
7 . Liñares, J., Tubau, F. & Dominguez, M. A. (2000). Antibiotic resistance in S. pneumoniae in Spain: a overview in the 1900s. In Streptococcus pneumoniae. Molecular Biology and Mechanism of Disease, (Tomasz, A., Ed.), pp. 399–407. Mary Ann Lieber Inc., New York.
8 . Sutcliffe, J., Tait-Kamradt, A. & Wondrack, L. (1996). Streptococcus pneumoniae and Streptococcus pyogenes resistant to macrolides but sensitive to clindamycin: a common resistance pattern mediated by an efflux system. Antimicrobial Agents and Chemotherapy 40, 1817–24.[Abstract]
9 . Doern, G. V., Brueggemann, A. B., Pierce, G., Holley, H. P. J. & Rauch, A. (1997). Antibiotic resistance among clinical isolates of Haemophilus influenzae in the United States in 1994 and 1995 and detection of beta-lactamase-positive strains resistant to amoxicillin– clavulanate: results of a national multicenter surveillance study. Antimicrobial Agents and Chemotherapy 41, 292–7.[Abstract]
10 . Doern, G. V., Brueggemann, A. B., Pierce, G., Hogan, T., Holley, H. P. J. & Rauch, A. (1996). Prevalence of antimicrobial resistance among 723 outpatient clinical isolates of Moraxella catarrhalis in the United States in 1994 and 1995: results of a 30-center national surveillance study. Antimicrobial Agents and Chemotherapy 40, 2884–6.[Abstract]
Received 11 October 2000; returned 19 December 2000; revised 26 January 2001; accepted 6 February 2001
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