In vitro activity of telithromycin (HMR 3647) against 502 strains of anaerobic bacteria

Hannah M. Wexlerb,c,*, Eric Molitorisc, Denise Molitorisb and Sydney M. Finegolda,b,c,d

a Medical and b Research Services, VA Greater Los Angeles Healthcare System, Los Angeles, CA 90073; c Departments of Medicine and d Microbiology and Immunology, UCLA School of Medicine, Los Angeles, CA 90024, USA


    Abstract
 Top
 Abstract
 Introduction
 References
 
In a previous study, we compared HMR 3004 with azithromycin, clarithromycin, erythromycin and roxithromycin against 502 anaerobic bacteria using NCCLS-approved procedures. This report extends this study by reporting the activity of telithromycin (HMR 3647) against these strains. Telithromycin inhibited 10% of Bacteroides fragilis, 50% of other B. fragilis group organisms and 93% of other Bacteroides spp. Telithromycin inhibited all Porphyromonas spp. and 98% of Prevotella spp. Activity against Bilophila wadsworthia (85–96%) was excellent. Telithromycin was not active against the Fusobacterium mortiferum/varium group. Telithromycin inhibited 100% of Clostridium perfringens, 46–56% of Clostridium difficile and Clostridium ramosum and approximately 90% of non-spore-forming Gram-positive bacilli.


    Introduction
 Top
 Abstract
 Introduction
 References
 
This report describes the activity of telithromycin (HMR 3647) against 502 strains of anaerobic bacteria, extending a previous study comparing the activity of HMR 3004 against these organisms.1 All bacteria tested in this study were randomly selected recent clinical isolates from the Wadsworth Anaerobic Bacteriology Laboratory, VA Greater Los Angeles Healthcare System in West Los Angeles. Bacteria were identified according to established procedures.2 MICs were determined by the NCCLS-approved Wadsworth agar dilution technique using an inoculum of 105 cfu/spot, and Brucella base-laked blood agar.3 Plates were incubated in an anaerobic chamber (Anaerobe Systems, San Jose, CA, USA) for 48 h at 37°C. MICs were defined as the lowest concentration of antimicrobial resulting in a marked change in the appearance of growth as compared with the control plate, as described in the NCCLS protocol. Reference strains of Bacteroides fragilis (ATCC 25285) and Bacteroides thetaiotaomicron (ATCC 29741) were used as controls in each test. Telithromycin was obtained from Hoechst-Marion-Roussel R&D (Romainville, France).

Results of this study are listed in Table I. For the comparative values of the agents tested the reader is referred to a previously published report.1 Results are listed as per cent susceptible, intermediate and resistant using a breakpoint of 4 mg/L for inclusion in the intermediate category.

Both B. fragilis and other B. fragilis group species were very resistant to telithromycin (5% and 10% inhibited, respectively, at 4 mg/L). As reported previously, of the macrolides tested, clarithromycin was the most active against the B. fragilis group (84% of B. fragilis and 71% of other B. fragilis group species, respectively, inhibited at 4 mg/L); azithromycin, erythromycin and roxithromycin were considerably less effective, inhibiting 5–29% of other B. fragilis group species.

Telithromycin inhibited 92% of other Bacteroides spp. Telithromycin was very active against Campylobacter gracilis (formerly Bacteroides gracilis), an organism that may be involved in severe, deep-seated infections;4 only one of 13 strains had an MIC of 8 mg/L (this strain was also resistant to the other macrolides tested previously). Bilophila wadsworthia was the third most common anaerobe isolated in cases of perforated or gangrenous appendicitis.5 Telithromycin had good activity against B. wadsworthia (85% inhibited at 4 mg/L) in contrast to the other macrolides reported previously, except for HMR 3004, which had similar activity to telithromycin. The other macrolides inhibited 4–33% of strains of B. wadsworthia.1

Porphyromonas spp. were completely inhibited by telithromycin at 2 mg/L. Ninety-eight per cent of Prevotella spp. isolates were inhibited by telithromycin; as reported previously, azithromycin, clarithromycin and roxithromycin inhibited 81–93% of these strains at 2 mg/L. Telithromycin was somewhat active against Fusobacterium nucleatum (56% inhibited). Telithromycin was not active against the Fusobacterium mortiferum/varium group, and only slight to moderate activity (18–64%) was seen against other Fusobacterium species. Sutterella wadsworthensis,6 a Gram-negative anaerobe found in >10% of intraabdominal infections, was susceptible to telithromycin as well as to the other antimicrobials.

Telithromycin inhibited all Clostridium perfringens isolates at 4 mg/L and 46–56% of Clostridium difficile and Clostridium ramosum strains at 2 mg/L. Telithromycin was very active against Peptostreptococcus spp., inhibiting all strains at 2 mg/L; azithromycin, clarithromycin, erythromycin and roxithromycin, tested previously, were active against 66–83% of strains at 4 mg/L.1 Telithromycin inhibited approximately 90% of non-spore-forming Grampositive bacilli at 2 mg/L. The macrolides tested previously had very similar activity against these strains.

It should be noted that testing methods, especially the inclusion of CO2 in the atmosphere, can variably affect the activity of some macrolides because of a pH effect.7 Goldstein et al.8 tested telithromycin and other ketolide and macrolide compounds against organisms involved in bite wound infections by the standard NCCLS approved agar dilution method (as was done in this study). They found that telithromycin was active against Bacteroides tectus, Bacteroides forsythus, Peptostreptococcus, Prevotella and Porphyromonas spp. Five of 20 strains of Fusobacterium were resistant.8 In our study, telithromycin was also active against Porphyromonas, Prevotella (98%) and Peptostreptococcus spp. Ednie et al.9 tested 352 strains of anaerobes using Oxyrase and aerobic incubation for those strains not requiring CO2 and pH adjustment to a final pH of 7.1–7.2 and anaerobic incubation for those strains requiring CO2. The MIC ranges (approximately 0.5–>64 mg/L) for the B. fragilis group were similar to those seen in our study (2–>64 mg/L) as was the MIC90 (>64 mg/L), although the MIC50 (8 mg/L) was lower than ours (32 mg/L). Overall MIC50s and MIC90s were lower than found in this study. Edlund and co-workers10 studied 342 clinical isolates of anaerobic bacteria by the agar dilution method and found the following ranges: anaerobic cocci, 0.016–0.125 mg/L; C. difficile, 0.125–256 mg/L; B. fragilis, 0.032–16 mg/L; Bacteroides and Prevotella spp., 0.016–4.0 mg/L; and F. nucleatum, 0.016–8.0 mg/L.

In summary, telithromycin showed good activity against certain groups of anaerobes. Further study into the clinical utility of this agent for specific infections involving certain anaerobes merits investigation.


View this table:
[in this window]
[in a new window]
 
Table. Activity of telithromycin against various organismsa
 

    Acknowledgments
 
This work was supported in part by Hoechst-Marion-Roussel R&D, Romainville, France and in part by VA Medical Research Funds.


    Notes
 
* Correspondence address. Microbial Diseases Research Laboratory, Building 304, Room E3-224, VA Wadsworth Medical Center 691/151J, Los Angeles, CA 90073, USA. Tel: +1-310-268-3404; Fax: +1-310-268-4458. Back


    References
 Top
 Abstract
 Introduction
 References
 
1 . Wexler, H. M., Molitoris, E., Molitoris, D. & Finegold, S. M. (1999). In vitro activity of HMR 3004 (RU 64004) against 502 strains of anaerobic bacteria. Anaerobe 5, 65–8.[ISI]

2 . Summanen, P., Baron, E. J., Citron, D., Strong, C., Wexler, H. M. & Finegold, S. M. (1993). Wadsworth Anaerobic Bacteriology Manual, 5th edn. Star Publishing Company, Belmont, CA.

3 . National Committee for Clinical Laboratory Standards. (1997). Methods for Antimicrobial Susceptibility Testing of Anaerobic Bacteria: Fourth Edition—Approved Standard M11-A4. NCCLS, Wayne, PA.

4 . Vandamme, P., Daneshvar, M. I., Dewhirst, F. E., Paster, B. J., Kersters, K., Goossens H. et al. (1995). Chemotaxonomic analyses of Bacteroides gracilis and Bacteroides ureolyticus and reclassification of B. gracilis as Campylobacter gracilis comb. nov. International Journal of Systematic Bacteriology 45, 145–52.[Abstract]

5 . Bennion, R. S., Baron, E. J., Thompson, J. E., Downes, J., Summanen, P., Talan, D. A. et al. (1990). The bacteriology of gangrenous and perforated appendicitis—revisited. Annals of Surgery 211, 165–71.[ISI][Medline]

6 . Wexler, H. M., Reeves, D., Summanen, P. H., Molitoris, E., McTeague, M., Duncan, J. et al. (1996). Sutterella wadsworthensis gen. nov., sp. nov., bile-resistant microaerophilic Campylobacter gracilis-like clinical isolates. International Journal of Systematic Bacteriology 46, 252–8.[Abstract]

7 . Johnson, M. M., Hill, S. L. & Piddock, L. J. (1999). Effect of carbon dioxide on testing of susceptibilities of respiratory tract pathogens to macrolide and azalide antimicrobial agents. Antimicrobial Agents and Chemotherapy 43, 1862–5.[Abstract/Free Full Text]

8 . Goldstein, E. J., Citron, D. M., Gerardo, S. H., Hudspeth, M. & Merriam, C. V. (1998). Activities of HMR 3004 (RU 64004) and HMR 3647 (RU 66647) compared to those of erythromycin, azithromycin, clarithromycin, roxithromycin, and eight other antimicrobial agents against unusual aerobic and anaerobic human and animal bite pathogens isolated from skin and soft tissue infections in humans. Antimicrobial Agents and Chemotherapy 42, 1127–32.[Abstract/Free Full Text]

9 . Ednie, L. M., Jacobs, M. R. & Appelbaum, P. C. (1997). Comparative antianaerobic activities of the ketolides HMR 3647 (RU 66647) and HMR 3004 (RU 64004). Antimicrobial Agents and Chemotherapy 41, 2019–22.[Abstract]

10 . Edlund, C., Sillerstrom, E., Wahlund, E. & Nord, C. E. (1998). In vitro activity of HMR 3647 against anaerobic bacteria. Journal of Chemotherapy 10, 280–4.[ISI][Medline]

Received 4 May 2000; returned 30 August 2000; revised 16 October 2000; accepted 17 November 2000





This Article
Abstract
FREE Full Text (PDF)
Alert me when this article is cited
Alert me if a correction is posted
Services
Email this article to a friend
Similar articles in this journal
Similar articles in ISI Web of Science
Similar articles in PubMed
Alert me to new issues of the journal
Add to My Personal Archive
Download to citation manager
Search for citing articles in:
ISI Web of Science (3)
Disclaimer
Request Permissions
Google Scholar
Articles by Wexler, H. M.
Articles by Finegold, S. M.
PubMed
PubMed Citation
Articles by Wexler, H. M.
Articles by Finegold, S. M.