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Antimicrobial Agents and Chemotherapy, June 1999, p. 1469-1474, Vol. 43, No. 6
0066-4804/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Linezolid Activity Compared to Those of Selected Macrolides and Other Agents against Aerobic and Anaerobic Pathogens Isolated from Soft Tissue Bite Infections in Humans

Ellie J. C. Goldstein,1,2,* Diane M. Citron,1 and C. Vreni Merriam1

R. M. Alden Research Laboratory, Santa Monica-UCLA Medical Center, Santa Monica, California 90404,1 and UCLA School of Medicine, Los Angeles, California 900242

Received 23 October 1998/Returned for modification 21 February 1999/Accepted 14 March 1999


    ABSTRACT
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Linezolid was tested against 420 aerobes and anaerobes, including 148 Pasteurella isolates, by an agar dilution method. Linezolid was active against all Pasteurella multocida subsp. multocida and P. multocida subsp. septica isolates and most Pasteurella canis, Pasteurella dagmatis, and Pasteurella stomatis isolates. The MIC was <= 2 µg/ml for staphylococci, streptococci, EF-4b, Weeksella zoohelcum, Fusobacterium nucleatum, other fusobacteria, Porphyromonas spp., Prevotella spp., peptostreptococci, and almost all Bacteroides tectum isolates.


    TEXT
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Approximately 5 million Americans are bitten annually by animals (2, 21, 23), and infectious complications result (3, 7, 15, 20) due to a wide variety of isolates (1, 4, 12, 17). Linezolid, (S)-N-[[3-[3-fluoro-4-(4-morpholinyl)phenyl]-2-oxo-5-oxazo-lidinyl]methyl]acetamide, a new oxazolidinone, is active against Streptococcus pyogenes, Staphylococcus aureus, and Staphylococcus epidermidis (5, 13, 14, 25), but limited information exists about its activity against anaerobes (24). It works by binding mRNA during the start of translation and therefore does not exhibit cross-resistance with currently available antimicrobial agents (5). Linezolid has shown activity in an animal model of skin and soft tissue infections (6) and is undergoing clinical trials for the therapy of skin and soft tissue infections. Scant data is available to evaluate its potential as therapy for cellulitis due to bite wounds, since the spectrum of bite wound isolates is varied and unique (3, 7, 8). We compared the susceptibilities of 420 recent bite wound isolates to linezolid, selected macrolides, and other agents.

The strains were isolated from bite wounds (Table 1) between 1990 and 1997 and were identified by standard criteria (11, 16, 17, 22). The sources (n) were dog bites (146), cat bites (208), human bites (23), and other (24). Seven American Type Culture Collection (ATCC) strains, 5 control strains, and 12 bovine respiratory strains (especially Pasteurella haemolytica) were included for comparative purposes.

                              
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  		TABLE 1.   In vitro activities of linezolid, azithromycin, clarithromycin, erythromycin, amoxicillin-clavulanate, vancomycin, teicoplanin, and clindamycin against 420 aerobic and anaerobic animal and human bite wound pathogens

Laboratory powders were supplied as follows: linezolid and clindamycin, Pharmacia & Upjohn Co., Kalamazoo, Mich.; azithromycin, Pfizer Inc., New York, N.Y.; clarithromycin, Abbott Laboratories, Abbott Park, Ill.; amoxicillin-clavulanate, SmithKline Beecham Pharmaceuticals, Philadelphia, Pa.; erythromycin and vancomycin, Eli Lilly & Co., Indianapolis, Ind.; and teicoplanin, Hoechst Marion Roussel, Cincinnati, Ohio.

Susceptibility testing was performed by use of National Committee for Clinical Laboratory Standards methods (18, 19). Brucella agar supplemented with hemin, vitamin K1, and 5% laked sheep blood was the basal medium used for anaerobic species and for Eikenella corrodens, Weeksella zoohelcum, and Capnocytophaga spp. Mueller-Hinton agar was used for staphylococci, and Mueller-Hinton agar supplemented with 5% sheep blood was used for the remainder of the organisms. Serial twofold dilutions of antimicrobial agents were reconstituted according to the manufacturers' instructions on the day of the test and added to the media at various concentrations.

Agar plates were inoculated with a Steers replicator (Craft Machine Inc., Chester, Pa.). The inoculum used for aerobes was 104 CFU per spot, and 105 CFU per spot was used for E. corrodens and anaerobes. Aerobic isolates were incubated at 35°C in an aerobic environment for 24 h and then examined. E. corrodens, W. zoohelcum, and streptococci were incubated in 5% CO2 for 48 h and then examined.

The control strains tested included S. aureus ATCC 29213, Enterococcus faecalis ATCC 29212, Escherichia coli ATCC 25922, Bacteroides fragilis ATCC 25285, and Eubacterium lentum ATCC 43055. In addition, P. haemolytica ATCC 33396, Pasteurella multocida subsp. gallicida ATCC 51689, P. multocida subsp. septica ATCC 51688, Pasteurella stomatis ATCC 43327, Pasteurella dagmatis ATCC 43325, Pasteurella canis ATCC 43326, and Neisseria canis ATCC 14687 were used.

The activities of linezolid and the other agents tested are shown in Table 1. The susceptibility of the control strains tested was within reference ranges. Linezolid was active against all P. multocida subsp. multocida and P. multocida subsp. septica isolates at <= 2 µg/ml. For P. canis isolates, the linezolid MIC at which 90% of the isolates were inhibited (MIC90) was 2 µg/ml. Almost all the other Pasteurella isolates were susceptible to <= 8 µg of linezolid per ml, except for 1 isolate of P. stomatis, for which the MIC was 16 µg/ml, and 4 of 16 other Pasteurella isolates (Table 1, footnote a). All P. haemolytica isolates were resistant (MIC, >32 µg/ml). Clindamycin was inactive against almost all Pasteurella isolates studied.

The staphylococci and streptococci studied were all susceptible to <= 2 µg of linezolid per ml. These results are similar to those reported by Jones et al. (13) and Jorgensen et al. (14). However, for many of our gram-negative aerobic bite wound pathogens, e.g., EF-4b, Moraxella catarrhalis, and other Moraxella species, the MIC of linezolid was >= 8 µg/ml, at the cusp of the proposed breakpoints (13). Zurenko et al. (25) studied 10 strains of M. catarrhalis and reported an MIC90 of 4 µg/ml and a range of 4 to 8 µg/ml. For E. corrodens, Neisseria weaveri, and other Neisseria species, the MIC90 was 16 µg/ml. For only one Neisseria isolate and one Haemophilus isolate was the MIC >= 32 µg/ml. The activity of the different macrolides was variable and consistent with that in prior reports (9, 10).

Vancomycin and teicoplanin were active against some of the unusual aerobic gram-negative bacilli and some of the Prevotella and Porphyromonas species. This result suggests that Gram stain characterization of these species may mask genetic relatedness to gram-positive species.

Yagi and Zurenko (24) studied a variety of common anaerobes encountered in general clinical infections, such as B. fragilis group members (MIC90, 8 µg/ml), but most of the isolates that they studied were different from our isolates. Zurenko et al. (25) studied 10 strains of B. fragilis and found a linezolid MIC90 of 4 µg/ml. All of our bite wound anaerobes were susceptible to <= 2 µg of linezolid per ml, with the exception of two Bacteroides tectum strains. For Fusobacterium nucleatum and other Fusobacterium species, the linezolid MIC was <= 1 µg/ml; this result was in sharp contrast to the absolute or relative resistance noted to all the macrolides tested. The activity of linezolid against F. nucleatum also compares favorably to that of the ketolides HMR 3004 and HMR 3647 (9). Linezolid was active against all Prevotella and Porphyromonas species at <= 2 µg/ml. Interestingly, many of the peptostreptococci were resistant to the macrolides but susceptible to clindamycin and to linezolid (MIC, <= 2 µg/ml). Yagi and Zurenko (24) and Jones et al. (13) also studied peptostreptococci and found all of them to be susceptible to <= 2 µg of linezolid per ml. The ketolides HMR 3004 and HMR 3647 were active at <= 0.5 µg/ml against a similar spectrum of bite wound pathogens (9).

Linezolid appears to be more active than the macrolides tested against staphylococci, peptostreptococci, and fusobacteria isolated from human and animal bite wounds and merits further clinical evaluation.


    ACKNOWLEDGMENTS

We thank Judee H. Knight, Alice E. Goldstein, and David Talan for various forms of assistance.

This study was funded in part by an educational grant from Pharmacia & Upjohn Co.


    FOOTNOTES

* Corresponding author. Mailing address: 2021 Santa Monica Blvd., Suite 640E, Santa Monica, CA 90404. Phone: (310) 315-1511. Fax: (310) 315-3662. E-mail: EJCGMD{at}aol.com.


    REFERENCES
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References

1. Alexander, C. J., D. M. Citron, S. H. Gerardo, M. C. Claros, D. Talan, and E. J. C. Goldstein. 1997. Characterization of saccharolytic Bacteroides and Prevotella isolates from infected dog and cat bite wounds in humans. J. Clin. Microbiol. 35:406-411[Abstract].
2. Anonymous. 30 May 1997. Dog bites have increased 37%, p. A-3. The Outlook, Santa Monica, Calif.
3. Brook, I. 1987. Microbiology of human and animal bite wounds in children. Pediatr. Infect. Dis. J. 6:29-32[Medline].
4. Citron, D. M., M. C. Claros, S. H. Gerardo, F. Abrahamian, D. A. Talan, and E. J. C. Goldstein. 1996. Frequency of Porphyromonas species isolated from infected dog and cat bite wounds in humans and their characterization by biochemical tests and AP-PCR fingerprinting. Clin. Infect. Dis. 23(Suppl. 1):78-82.
5. Dresser, L. D., and M. J. Rybak. 1998. The pharmacologic and bacteriologic properties of oxazolidinones, a new class of synthetic antimicrobials. Pharmacotherapy 18:456-462[Medline].
6. Ford, C. W., J. C. Hamel, D. M. Wilson, J. K. Moerman, D. Stapert, R. J. Yancey, D. K. Hutchinson, M. R. Barbachyn, and S. J. Brickner. 1996. In vivo activities of U-100592 and U-100766, novel oxazolidinone antimicrobial agents, against experimental bacterial infections. Antimicrob. Agents Chemother. 40:1508-1513[Abstract].
7. Goldstein, E. J. C. 1991. Bite wounds and infection. Clin. Infect. Dis. 14:633-640.
8. Goldstein, E. J. C., D. M. Citron, B. Wield, U. Blachman, V. L. Sutter, T. A. Miller, and S. M. Finegold. 1978. Bacteriology of human and animal bite wounds. J. Clin. Microbiol. 8:667-672[Abstract/Free Full Text].
9. Goldstein, E. J. C., D. M. Citron, S. H. Gerardo, M. Hudspeth, and C. V. Merriam. 1998. Activities of HMR 3004 (RU-64004) and HMR 3647 (RU-66647) compared to those of erythromycin, azithromycin, roxithromycin, and eight other antimicrobial agents against unusual aerobic and anaerobic human and animal pathogens isolated from skin and soft tissue infections in humans. Antimicrob. Agents Chemother. 42:1127-1132[Abstract/Free Full Text].
10. Goldstein, E. J. C., D. M. Citron, M. Hudspeth, S. H. Gerardo, and C. V. Merriam. 1998. Trovafloxacin compared to levofloxacin, ofloxacin, ciprofloxacin, azithromycin and clarithromycin against unusual aerobic and anaerobic human and animal bite wound pathogens. J. Antimicrob. Chemother. 41:391-396[Abstract/Free Full Text].
11. Holdeman, L. V., and W. E. C. Moore. 1977. Anaerobic laboratory manual, 4th ed. Virginia Polytechnic Institute and State University, Blacksburg.
12. Holst, E., J. Rollof, L. Larsson, and J. P. Nielsen. 1992. Characterization and distribution of Pasteurella species recovered from infected humans. J. Clin. Microbiol. 30:2984-2987[Abstract/Free Full Text].
13. Jones, R. N., D. M. Johnson, and M. E. Erwin. 1996. In vitro antimicrobial activities and spectra of U-100592 and U-100766, two novel fluorinated oxazolidinones. Antimicrob. Agents Chemother. 40:720-726[Abstract].
14. Jorgensen, J. H., M. L. McElmeel, and C. W. Trippy. 1997. In vitro activities of the oxazolidinone antibiotics U-100592 and U-100766 against Staphylococcus aureus and coagulase-negative Staphylococcus species. Antimicrob. Agents Chemother. 41:465-467[Abstract].
15. Levin, J. M., and D. A. Talan. 1990. Erythromycin failure with subsequent Pasteurella multocida meningitis and septic arthritis in a cat bite victim. Ann. Emerg. Med. 19:1458-1461[Medline].
16. Murray, P. R., E. J. Baron, M. A. Pfaller, F. C. Tenover, and R. H. Yolken (ed.). 1995. Manual of clinical microbiology, 6th ed. American Society for Microbiology, Washington, D.C.
17. Mutters, R., P. Ihm, S. Pohl, W. Frederiksen, and W. Mannheim. 1985. Reclassification of the genus Pasteurella Trevisan 1887 on the basis of deoxyribonucleic acid homology, with proposals for the new species Pasteurella dagmatis, Pasteurella canis, Pasteurella stomatis, Pasteurella anatis, and Pasteurella langaa. Int. J. Syst. Bacteriol. 35:309-322.
18. National Committee for Clinical Laboratory Standards. 1998. Methods for antimicrobial susceptibility testing of anaerobic bacteria, 4th ed. Approved standard. NCCLS publication no. M11-A4. National Committee for Clinical Laboratory Standards, Villanova, Pa.
19. National Committee for Clinical Laboratory Standards. 1998. Method for dilution antimicrobial susceptibility testing for bacteria that grow aerobically, 4th ed. Approved standard. NCCLS publication no. M7-A4. National Committee for Clinical Laboratory Standards, Villanova, Pa.
20. Orton, D. W. 1984. Pasteurella multocida: bilateral septic knee joint prosthesis from a distant cat bite. Ann. Emerg. Med. 13:1065-1067[Medline].
21. Sachs, J. J., M. Kresnow, and B. Houston. 1996. Dog bites: how big a problem? Injury Prev. 2:52-54[Abstract].
22. Summanen, P., E. J. Baron, D. M. Citron, C. A. Strong, H. M. Wexler, and S. M. Finegold. 1993. Wadsworth anaerobic bacteriology manual, 5th ed. Star Publishing Co., Belmont, Calif.
23. Talan, D. A., D. M. Citron, F. A. Abrahamian, G. J. Moran, E. J. C. Goldstein, and the Emergency Medicine Animal Bite Infection Study Group. 1999. The bacteriology and management of dog and cat bite wound infections presenting to emergency departments. N. Engl. J. Med. 340:85-92[Abstract/Free Full Text].
24. Yagi, B. H., and G. E. Zurenko. 1997. In vitro activity of linezolid and eperezolid, two novel oxazolidinone antimicrobial agents, against anaerobic bacteria. Anaerobe 3:301-306. [Medline]
25. Zurenko, G. E., B. H. Yagi, R. A. Schaadt, J. W. Allison, J. O. Kilburn, S. E. Glickman, D. K. Hutchinson, M. R. Barbachyn, and S. J. Brickner. 1996. In vitro activities of U-100592 and U-100766, novel oxazolidinone antibacterial agents. Antimicrob. Agents Chemother. 40:839-845[Abstract].

Antimicrobial Agents and Chemotherapy, June 1999, p. 1469-1474, Vol. 43, No. 6
0066-4804/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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