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. 1999 Nov;43(11):2801–2805. doi: 10.1128/aac.43.11.2801

Activities of Telithromycin (HMR 3647, RU 66647) Compared to Those of Erythromycin, Azithromycin, Clarithromycin, Roxithromycin, and Other Antimicrobial Agents against Unusual Anaerobes

Ellie J C Goldstein 1,2,*, Diane M Citron 1, C Vreni Merriam 1, Yumi Warren 1, Kerin Tyrrell 1
PMCID: PMC89565  PMID: 10543769

Abstract

The comparative activity of telithromycin (HMR 3647) against 419 human anaerobic isolates was determined by the agar dilution method. At concentrations of ≤0.5 μg/ml, telithromycin was active against Actinomyces israelii, Actinomyces odontolyticus, Bacteroides tectum, Bacteroides ureolyticus, Bacteroides gracilis (now Campylobacter gracilis), Porphyromonas spp. (including Porphyromonas gingivalis and Porphyromonas macacae), Prevotella intermedia, Prevotella heparinolytica, and almost all Peptostreptococcus species. Clostridia showed species and strain variability, often with a biphasic pattern. Fusobacterium species, except Fusobacterium russii, were relatively resistant.

Telithromycin (HMR 3647; RU 66647), a new ketolide, is a semisynthetic erythromycin A derivative characterized by a lack of l-cladinose and by having a 3-keto function. It has been demonstrated to be more active than macrolides against anaerobes (2, 6, 7) and erythromycin-A-resistant gram-positive cocci (efflux and inducible macrolides-lincosamides-streptogramin B) (3, 10, 12, 16).

Premarket in vitro testing focuses on the more typical bacterial pathogens, such as the Bacteroides fragilis group and Clostridium perfringens (2, 5, 6, 11). Previously, we reported telithromycin to be active against aerobic and anaerobic bite wound isolates (7). Since scant data exist on its activity against less-frequently isolated anaerobic pathogens, we determined telithromycin’s comparative activity against a plethora of unusual, anaerobic, pathogenic species encountered in human clinical infections.

Strains were identified by standard criteria (1, 4, 8, 9, 13, 15). B. fragilis ATCC 25285 and Bacteroides thetaiotaomicron ATCC 29741 were tested simultaneously as control strains. The numbers and species of isolates tested and their susceptibilities are given in Table 1.

TABLE 1.

In vitro activity of telithromycin (HMR 3647, RU 66647) and other agents against 419 unusual anaerobic pathogens

Organism (no. of isolates) and agent MIC (μg/ml)a
Organism (no. of isolates) and agent MIC (μg/ml)a
Range 50% 90% Range 50% 90%
Actinomyces species (16)b
 Telithromycin ≤0.015 ≤0.015 ≤0.015
 Erythromycin ≤0.015–0.03 0.03 0.03
 Azithromycin ≤0.015–0.06 0.03 0.06
 Clarithromycin ≤0.015 ≤0.015 ≤0.015
 Roxithromycin 0.03–0.06 0.06 0.06
 Clindamycin ≤0.015–0.5 0.06 0.25
 Penicillin G ≤0.015–0.5 0.06 0.25
 Amoxicillin-clavulanate 0.03–1 0.125 0.25
 Cefotaxime 0.03–0.5 0.25 0.5
 Metronidazole 1–>32 16 >32
 Trovafloxacin 0.5–4 2 4
Anaerobiospirillum spp. (16)c
 Telithromycin 0.5–8 2 8
 Erythromycin 1–16 4 16
 Azithromycin 0.125–1 0.5 1
 Clarithromycin 2–32 4 32
 Roxithromycin 4–>32 16 >32
 Clindamycin 8–>32 32 >32
 Penicillin G 0.06–1 0.06 0.5
 Amoxicillin-clavulanate 0.125–0.5 0.125 0.5
 Cefotaxime ≤0.015–0.06 ≤0.015 0.06
 Metronidazole 1–8 4 8
 Trovafloxacin 0.06–2 0.125 1
Bacteroides gracilis (11)
 Telithromycin 0.125–2 0.5 1
 Erythromycin 0.125–2 1 2
 Azithromycin 0.06–0.5 0.125 0.5
 Clarithromycin 0.25–2 1 1
 Roxithromycin 0.25–4 2 4
 Clindamycin 0.03–8 0.25 2
 Penicillin G ≤0.015–4 0.125 4
 Amoxicillin-clavulanate ≤0.015–2 0.5 2
 Cefotaxime ≤0.015–16 0.06 16
 Metronidazole 0.06–>32 0.5 >32
 Trovafloxacin ≤0.015–2 0.03 0.5
Bacteroides tectum (22)
 Telithromycin 0.125–0.5 0.25 0.5
 Erythromycin 0.25–1 0.5 0.5
 Azithromycin 0.5–2 1 2
 Clarithromycin 0.125 0.125 0.125
 Roxithromycin 0.5–1 1 1
 Clindamycin ≤0.015–0.125 ≤0.015 ≤0.015
 Penicillin G ≤0.015–32 0.03 16
 Amoxicillin-clavulanate 0.03–0.5 0.06 0.5
 Cefotaxime 0.03–16 0.06 8
 Metronidazole 0.125–2 0.5 0.5
 Trovafloxacin 0.03–0.125 0.06 0.125
Bacteroides ureolyticus (17)
 Telithromycin 0.125–2 0.5 1
 Erythromycin 0.125–2 0.25 2
 Azithromycin 0.06–0.25 0.06 0.25
 Clarithromycin 0.125–4 0.5 2
 Roxithromycin 0.125–4 0.5 2
 Clindamycin 0.03–0.5 0.06 0.25
 Penicillin G ≤0.015–1 ≤0.015 0.25
 Amoxicillin-clavulanate ≤0.015–1 ≤0.015 0.125
 Cefotaxime ≤0.015–0.25 ≤0.015 0.06
 Metronidazole 0.06–2 0.25 1
 Trovafloxacin ≤0.015–4 0.06 4
Bilophila wadsworthia (16)
 Telithromycin 0.5–4 2 4
 Erythromycin 4–32 16 32
 Azithromycin 1–16 4 16
 Clarithromycin 4–32 16 32
 Roxithromycin 16–>32 32 >32
 Clindamycin 0.25–2 0.5 2
 Penicillin G 2–16 4 8
 Amoxicillin-clavulanate 1–4 2 4
 Cefotaxime 4–>32 8 >32
 Metronidazole 0.125 0.125 0.125
 Trovafloxacin 0.125–>8 0.5 >8
Clostridium clostridioforme (11)
 Telithromycin 0.06–32 0.5 32
 Erythromycin 0.25–>32 16 >32
 Azithromycin 0.125–>32 16 >32
 Clarithromycin 0.125–>32 4 >32
 Roxithromycin 0.5–>32 32 >32
 Clindamycin ≤0.015–2 0.06 2
 Penicillin G 0.5–>32 1 16
 Amoxicillin-clavulanate 0.5–8 0.5 1
 Cefotaxime 8–>32 >32 >32
 Metronidazole 0.03–1 0.125 0.5
 Trovafloxacin 1–8 4 4
Clostridium difficile (14)
 Telithromycin 0.06–>32 0.25 >32
 Erythromycin 0.25–>32 0.5 >32
 Azithromycin 1–>32 2 >32
 Clarithromycin 0.125–>32 0.5 >32
 Roxithromycin 0.5–>32 2 >32
 Clindamycin 0.25–>32 0.5 >32
 Penicillin G 1–4 2 4
 Amoxicillin-clavulanate 0.5–1 1 1
 Cefotaxime >32 >32 >32
 Metronidazole 0.25–1 0.5 0.5
 Trovafloxacin 0.5–>8 1 >8
Clostridium innocuum (11)
 Telithromycin 0.06–>32 >32 >32
 Erythromycin 0.5–>32 >32 >32
 Azithromycin 0.125–>32 >32 >32
 Clarithromycin 0.25–>32 >32 >32
 Roxithromycin 1–>32 >32 >32
 Clindamycin 0.25–>32 0.5 >32
 Penicillin G 0.25–>32 0.5 0.5
 Amoxicillin-clavulanate 0.5–2 0.5 0.5
 Cefotaxime 8–16 8 16
 Metronidazole 0.5–2 0.5 1
 Trovafloxacin 0.25–>8 0.5 8
Clostridium ramosum (10)
 Telithromycin 0.03–>32 0.03 >32
 Erythromycin 0.5–>32 1 >32
 Azithromycin 0.125–>32 0.25 >32
 Clarithromycin 0.25–>32 0.5 >32
 Roxithromycin 1–>32 1 >32
 Clindamycin 0.25–4 2 2
 Penicillin G 0.06–1 0.06 1
 Amoxicillin-clavulanate 0.06–0.25 0.06 0.25
 Cefotaxime 1–4 1 2
 Metronidazole 1 1 1
 Trovafloxacin 0.25–8 0.5 2
Fusobacterium spp. group 1 (19)d
 Telithromycin ≤0.015–8 2 4
 Erythromycin 1–>32 8 32 90%
 Azithromycin 0.06–32 1 8
 Clarithromycin ≤0.015–32 8 32
 Roxithromycin 2–>32 16 >32
 Clindamycin ≤0.015–2 0.06 0.125
 Penicillin G ≤0.015–16 ≤0.015 2
 Amoxicillin-clavulanate ≤0.015–0.25 0.06 0.125
 Cefotaxime ≤0.015–>32 0.125 8
 Metronidazole 0.125–0.5 0.25 4
 Trovafloxacin 0.25–4 0.5 4
Fusobacterium spp. group 2 (12)e
 Telithromycin 2–>32 32 >32
 Erythromycin 8–>32 >32 >32
 Azithromycin 1–>32 16 32
 Clarithromycin 4–>32 >32 >32
 Roxithromycin 8–>32 >32 >32
 Clindamycin 0.06–8 1 8
 Penicillin G ≤0.015–>32 0.25 0.5
 Amoxicillin-clavulanate 0.125–>4 1 2
 Cefotaxime 0.25–>32 0.5 >32
 Metronidazole 0.125–1 0.5 1
 Trovafloxacin 1–>8 4 4
Fusobacterium russii (12)
 Telithromycin ≤0.015–32 0.5 16
 Erythromycin 1–>32 4 >32
 Azithromycin 0.03–32 0.25 32
 Clarithromycin 2–>32 4 >32
 Roxithromycin ≤0.015–>32 8 >32
 Clindamycin ≤0.015–0.125 0.03 0.06
 Penicillin G ≤0.015–0.06 0.03 0.06
 Amoxicillin-clavulanate ≤0.015–0.25 0.06 0.125
 Cefotaxime ≤0.015–0.25 0.06 0.25
 Metronidazole ≤0.015–0.25 0.125 0.25
 Trovafloxacin 0.5–4 4 4
Fusobacterium varium (17)
 Telithromycin 4–>32 >32 >32
 Erythromycin 32–>32 >32 >32
 Azithromycin 2–>32 32 >32
 Clarithromycin 32–>32 >32 >32
 Roxithromycin >32 >32 >32
 Clindamycin 0.06–16 4 16
 Penicillin G 0.03–>32 0.5 8
 Amoxicillin-clavulanate 0.125–4 2 4
 Cefotaxime 0.06–>32 16 >32
 Metronidazole 0.125–4 1 2
 Trovafloxacin 0.5–>8 4 >8
Peptostreptococcus  asaccharolyticus (11)
 Telithromycin 0.03–2 0.06 1
 Erythromycin 1–>32 4 >32
 Azithromycin 0.5–>32 4 >32
 Clarithromycin 0.5–>32 2 >32
 Roxithromycin 4–>32 8 >32
 Clindamycin ≤0.015–>32 0.06 >32
 Penicillin G ≤0.015–1 0.03 0.25
 Amoxicillin-clavulanate 0.03–1 0.03 0.125
 Cefotaxime 0.125–8 0.25 2
 Metronidazole 0.125–2 0.5 1
 Trovafloxacin 0.5–2 1 1
Peptostreptococcus magnus (13)
 Telithromycin 0.06 0.06 0.06
 Erythromycin 1–>32 4 >32
 Azithromycin 2–>32 4 >32
 Clarithromycin 0.5–>32 2 >32
 Roxithromycin 4–>32 8 >32
 Clindamycin 0.06–2 0.5 2
 Penicillin G ≤0.015–1 0.03 0.25
 Amoxicillin-clavulanate 0.03–1 0.03 0.125
 Cefotaxime 1–>32 8 >32
 Metronidazole 0.25–2 0.5 0.5
 Trovafloxacin 0.06–0.25 0.125 0.25
Peptostreptococcus micros (12)
 Telithromycin ≤0.015–0.03 ≤0.015 0.03
 Erythromycin 0.5–1 0.5 0.5
 Azithromycin 0.5–1 0.5 1
 Clarithromycin 0.6 0.5 0.5
 Roxithromycin 1 1 1
 Clindamycin 0.06–0.125 0.125 0.125
 Penicillin G ≤0.015–0.03 ≤0.015 0.03
 Amoxicillin-clavulanate 0.03–0.125 0.03 0.125
 Cefotaxime 0.25–0.5 0.25 0.5
 Metronidazole 0.03–0.25 0.25 0.25
 Trovafloxacin 0.03–0.125 0.06 0.06
Peptostreptococcus prevotii (9)
 Telithromycin ≤0.015–0.5 0.06
 Erythromycin 0.03–>32 >32
 Azithromycin 0.06–>32 32
 Clarithromycin ≤0.015–>32 >32
 Roxithromycin 0.03–>32 >32
 Clindamycin 0.030–32 1
 Penicillin G 0.03–0.06 0.03
 Amoxicillin-clavulanate ≤0.015–0.125 0.03
 Cefotaxime 0.06–4 0.25
 Metronidazole 0.125–1 0.5
 Trovafloxacin 0.25–1 0.25
Porphyromonas asaccharolytica (11)
 Telithromycin ≤0.015–>32 ≤0.015 32
 Erythromycin 0.03–32 0.03 32
 Azithromycin 0.125–>32 0.25 >32
 Clarithromycin ≤0.015–>32 0.06 >32
 Roxithromycin 0.03–4 0.06 4
 Clindamycin ≤0.015–>32 ≤0.015 >32
 Penicillin G ≤0.015 ≤0.015 ≤0.015
 Amoxicillin-clavulanate ≤0.015–0.03 ≤0.015 0.03
 Cefotaxime ≤0.015–0.25 0.03 0.25
 Metronidazole ≤0.015 ≤0.015 ≤0.015
 Trovafloxacin 0.03–0.25 0.25 0.25
Porphyromonas canoris (10)
 Telithromycin ≤0.015–0.125 0.06 0.125
 Erythromycin 0.03–0.25 0.06 0.125
 Azithromycin 0.125–0.5 0.25 0.25
 Clarithromycin 0.06–0.125 0.06 0.125
 Roxithromycin 0.06–0.25 0.125 0.125
 Clindamycin ≤0.015 ≤0.015 ≤0.015
 Penicillin G ≤0.015–0.03 ≤0.015 ≤0.015
 Amoxicillin-clavulanate ≤0.015–0.03 ≤0.015 0.03
 Cefotaxime 0.03–0.06 0.03 0.06
 Metronidazole ≤0.015–0.5 0.25 0.25
 Trovafloxacin 0.06–0.5 0.25 0.5
Porphyromonas gingivalis (13)
 Telithromycin ≤0.015–0.06 0.03 0.06
 Erythromycin 0.06–0.5 0.125 0.5
 Azithromycin 0.125–1 0.25 0.5
 Clarithromycin 0.06–0.125 0.06 0.125
 Roxithromycin 0.06–0.25 0.125 0.25
 Clindamycin ≤0.015 ≤0.015 ≤0.015
 Penicillin G ≤0.015–0.06 ≤0.015 0.03
 Amoxicillin-clavulanate ≤0.015–0.06 ≤0.015 0.06
 Cefotaxime ≤0.015–0.06 ≤0.015 0.06
 Metronidazole ≤0.015–0.03 ≤0.015 0.03
 Trovafloxacin 0.03–0.06 0.06 0.06
Porphyromonas macacae (13)
 Telithromycin 0.03–0.06 0.03 0.06
 Erythromycin 0.06–0.25 0.125 0.25
 Azithromycin 0.125–1 0.5 0.5
 Clarithromycin 0.06–0.125 0.125 0.125
 Roxithromycin 0.06–0.25 0.25 0.25
 Clindamycin ≤0.015–0.03 ≤0.015 ≤0.015
 Penicillin G ≤0.015–1 0.5 0.5
 Amoxicillin-clavulanate ≤0.015–0.06 ≤0.015 ≤0.015
 Cefotaxime ≤0.015–1 1 1
 Metronidazole ≤0.015–0.125 0.06 0.125
 Trovafloxacin 0.03–0.125 0.06 0.125
Porphyromonas spp. (11)f
 Telithromycin ≤0.015–0.125 0.03 0.03
 Erythromycin ≤0.015–0.5 0.06 0.06
 Azithromycin 0.125–1 0.25 0.5
 Clarithromycin 0.06–0.125 0.06 0.125
 Roxithromycin 0.03–0.25 0.125 0.25
 Clindamycin ≤0.015 ≤0.015 ≤0.015
 Penicillin G ≤0.015–4 ≤0.015 ≤0.015
 Amoxicillin-clavulanate ≤0.015–0.06 ≤0.015 ≤0.015
 Cefotaxime ≤0.015–0.5 ≤0.015 0.125
 Metronidazole ≤0.015–0.25 0.03 0.125
 Trovafloxacin 0.06–1 0.25 1
Prevotella bivia (21)
 Telithromycin ≤0.015–4 0.25 0.5
 Erythromycin 0.06–>32 1 2
 Azithromycin 0.25–>32 0.5 1
 Clarithromycin 0.06–>32 0.125 0.25
 Roxithromycin 0.125–>32 1 1
 Clindamycin ≤0.015–>32 ≤0.015 0.03
 Penicillin G 0.25–32 16 32
 Amoxicillin-clavulanate 0.06–4 0.5 4
 Cefotaxime 0.06–>32 8 >32
 Metronidazole 0.5–4 2 4
 Trovafloxacin 1–4 2 2
Prevotella buccae-oris group (22)g
 Telithromycin 0.125–8 0.25 1
 Erythromycin 0.5–8 1 2
 Azithromycin 0.125–4 0.5 1
 Clarithromycin 0.06–1 0.125 0.25
 Roxithromycin 0.25–8 0.5 2
 Clindamycin ≤0.015–0.125 ≤0.015 0.03
 Penicillin G 0.06–>32 8 >32
 Amoxicillin-clavulanate 0.125–2 0.25 1
 Cefotaxime 0.06–>32 2 >32
 Metronidazole 0.5–4 1 2
 Trovafloxacin 0.25–4 1 2
Prevotella heparinolytica (16)
 Telithromycin 0.06–0.5 0.25 0.5
 Erythromycin 0.25–0.5 0.25 0.25
 Azithromycin 0.5–1 0.5 1
 Clarithromycin 0.06–0.125 0.125 0.125
 Roxithromycin 0.25–0.5 0.5 0.5
 Clindamycin ≤0.015 ≤0.015 ≤0.015
 Penicillin G 0.06–0.25 0.06 0.125
 Amoxicillin-clavulanate 0.06–0.25 0.125 0.25
 Cefotaxime 0.06–0.25 0.125 0.125
 Metronidazole 0.06–1 0.5 1
 Trovafloxacin 0.125–0.25 0.125 0.25
Prevotella intermedia (11)
 Telithromycin ≤0.015–0.25 0.03 0.06
 Erythromycin 0.03–0.5 0.06 0.25
 Azithromycin 0.03–1 0.125 0.5
 Clarithromycin ≤0.015–0.125 ≤0.015 0.125
 Roxithromycin 0.03–1 0.125 0.25
 Clindamycin ≤0.015–0.03 ≤0.015 ≤0.015
 Penicillin G ≤0.015–18 0.03 4
 Amoxicillin-clavulanate 0.03–0.5 0.03 0.125
 Cefotaxime ≤0.015–4 0.125 1
 Metronidazole 0.03–1 0.5 1
 Trovafloxacin 0.06–1 0.5 1
Prevotella melaninogenica group (18)h
 Telithromycin 0.06–16 0.25 2
 Erythromycin 0.06–32 0.5 16
 Azithromycin 0.06–>32 0.5 32
 Clarithromycin 0.03–4 0.125 4
 Roxithromycin 0.125–16 0.5 8
 Clindamycin ≤0.015–32 ≤0.015 0.5
 Penicillin G ≤0.015–32 4 16
 Amoxicillin-clavulanate 0.03–2 0.125 2
 Cefotaxime 0.03–16 2 4
 Metronidazole 0.125–4 0.5 1
 Trovafloxacin 0.06–8 1 4
Veillonella spp. (24)
 Telithromycin 0.06–32 2 4
 Erythromycin 1–>32 16 >32
 Azithromycin 0.125–>32 4 >32
 Clarithromycin 1–>32 16 >32
 Roxithromycin 0.5–>32 >32 >32
 Clindamycin 0.03–>32 0.06 2
 Penicillin G ≤0.015–8 1 4
 Amoxicillin-clavulanate ≤0.015–>4 0.5 2
 Cefotaxime 0.06–8 4 8
 Metronidazole 0.25–2 1 2
 Trovafloxacin 0.125–>8 0.25 >8
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a

50% and 90%, MICs at which 50 and 90% of the isolates are inhibited, respectively. 

b

Actinomyces odontolyticus (10) and Actinomyces israelii (6). 

c

Anaerobiospirillum thomasii (13) and Anaerobiospirillum succiniciproducens (3). 

d

Fusobacterium gonidiaformans (1), Fusobacterium naviforme (8), Fusobacterium necrophorum (8), Fusobacterium nucleatum (1), and Fusobacterium nucleatum subsp. animalis (1). 

e

Fusobacterium mortiferum (2), Fusobacterium necrogenes (3), and Fusobacterium ulcerans (7). 

f

Porphyromonas cangingivalis (4), Porphyromonas cansulci (2), Porphyromonas circumdentaria (2), and Porphyromonas levii (3). 

g

Prevotella buccae (20) and Prevotella oris (2). 

h

Prevotella melaninogenica (12), Prevotella denticola (2), and Prevotella loescheii (4). 

Standard laboratory powders were supplied as follows: telithromycin (HMR 3647), cefotaxime, and roxithromycin, Hoechst Marion Roussel, Romanville, France; trovafloxacin and azithromycin, Pfizer, Inc., New York, N.Y.; clarithromycin, Abbott Laboratories, Abbott Park, Ill.; clindamycin, Pharmacia Upjohn Co., Kalamazoo, Mich.; metronidazole, Searle Research & Development, Skokie, Ill.; amoxicillin-clavulanate, SmithKline Beecham Pharmaceuticals, Philadelphia, Pa.; erythromycin, Eli Lilly & Co., Indianapolis, Ind.; and penicillin G, Sigma Chemical Co., St. Louis, Mo.

Susceptibility testing was performed according to National Committee for Clinical Laboratory Standards standards (14). Brucella agar supplemented with hemin, vitamin K1, and 5% laked sheep blood was the basal medium used. For Bilophila wadsworthia, the medium was also supplemented with pyruvate. Antimicrobial agents were reconstituted according to the manufacturers’ instructions. Serial twofold dilutions of antimicrobial agents were prepared on the day of the test and were added to the medium in various concentrations. Agar plates were inoculated (105 CFU per spot) with a Steers replicator (Craft Machine, Inc., Chester, Pa.).

Telithromycin MICs of <1 μg/ml were seen against many genera and species. There were marked interspecies and intraspecies differences in the susceptibilities of less-commonly identified anaerobes to telithromycin.

Actinomyces spp. had telithromycin MICs of ≤0.015 μg/ml and were generally susceptible to the other agents tested with the exception of trovafloxacin which had a MIC at which 90% of isolates were inhibited (MIC90) of 4 μg/ml. Almost all (42 of 45) Peptostreptococcus species had telithromycin MIC90s of ≤0.06 μg/ml (the exceptions were 2 of the 11 Peptostreptococcus asaccharolyticus isolates and 1 of the 9 Peptostreptococcus prevotii isolates). All 14 of the 45 Peptostreptococcus isolates that were resistant to one or more macrolides had telithromycin MICs of ≤1 μg/ml.

Telithromycin had MIC90s of ≤1 μg/ml for Bacteroides species, including Bacteroides tectum, Bacteroides ureolyticus, and Campylobacter gracilis. Penicillin had a MIC of 4 μg/ml for 3 of 10 C. gracilis isolates. All Porphyromonas species—Porphyromonas canoris, Porphyromonas gingivalis, and Porphyromonas macacae—were susceptible to <0.125 μg of telithromycin per ml except for 2 of 11 Porphyromonas asaccharolytica strains tested which were resistant (≥32 μg/ml) to telithromycin and consequently influenced the MIC90 curve for that species.

Prevotella species were susceptible, with telithromycin MIC90s as follows: Prevotella bivia, 0.5 μg/ml; Prevotella oris-buccae group, 1 μg/ml; Prevotella heparinolytica, 0.5 μg/ml; Prevotella intermedia, 0.06 μg/ml; and Prevotella melaninogenica, 2 μg/ml. Occasional strains from several genera were more resistant, which influenced the MIC ranges and occasionally the MIC90s. For example, telithromycin had a MIC of 2 μg/ml for two strains of P. melaninogenica but had a MIC of ≤0.5 μg/ml for 10 P. melaninogenica strains; telithromycin had a MIC of >1 μg/ml for 3 of 22 P. oris-buccae group isolates, while 18 P. oris-buccae group isolates were susceptible to ≤0.5 μg of telithromycin per ml.

Telithromycin had a MIC50 of 2 μg/ml and a MIC90 of 4 μg/ml for both B. wadsworthia and Veillonella species. Telithromycin was more active on a weight basis than the other macrolides against Veillonella species and B. wadsworthia. Penicillin MICs for B. wadsworthia ranged from 2 to 16 μg/ml, and 4 of 16 isolates were resistant to trovafloxacin (MIC, >8 μg/ml). Anaerobiospirillum species were also in this intermediate group, with MICs ranging from 2 to 8 μg of telithromycin per ml; all isolates were resistant to clindamycin and also had metronidazole MICs of 1 to 8 μg/ml. Azithromycin was the most active macrolide against Anaerobiospirillum spp. (MICs ranging from 0.125 to 1 μg/ml).

The Clostridium species tested were generally susceptible to telithromycin at concentrations of ≤0.5 μg/ml, but in each species there seemed to be a biphasic pattern between very susceptible isolates and resistant strains. Clostridium clostridioforme tended to be more resistant, with penicillin MICs of >16 μg/ml for 2 of 11 isolates, and relative resistance to telithromycin was seen in 4 of 11 strains (MICs, >8 μg/ml), but all isolates were susceptible to clindamycin (MIC, <2 μg/ml). Clostridium innocuum had 7 of 13 strains with telithromycin MICs of >32 μg/ml and similar sensitivity to macrolides, including one strain that was also resistant to penicillin (MIC, >32 μg/ml). Seven of 10 Clostridium ramosum isolates were susceptible to telithromycin (MIC, ≤0.03 μg/ml) and other macrolides; none were resistant to clindamycin.

The fusobacteria were problematic for telithromycin and the macrolides. Fusobacterium ulcerans and Fusobacterium varium tend to be resistant to the agents (MIC90, >16 μg/ml), while 9 of 12 Fusobacterium russii isolates tended to be susceptible (MIC, ≤1 μg/ml). The other Fusobacterium species did not show any distinct trends.

Several differences exist between our study and those of others, including the variety of isolates studied, the agar media used, and the inoculum employed. Jones and Biedenbach (11) reported that the MIC of telithromycin for B. fragilis group species (no data shown and agar used not elucidated) was >8 μg/ml. Boswell et al. (2) used an inoculum of 104 CFU/ml and Wilkins Chalgren media supplemented with 50 mg of 1-(4-nitrophenyl)-glycerol per liter in order to study 53 strains of B. fragilis (telithromycin MIC90, 2 μg/ml), 10 strains of C. perfringens and Clostridium difficile (telithromycin MIC90s, 0.06 and 1 μg/ml, respectively), and 20 strains of Peptostreptococcus species (telithromycin MIC90, 0.008 μg/ml). Ednie et al. (6) studied a larger variety of anaerobes using Oxyrase supplementation and did identify many isolates to species level; most of their isolates were of species different than those tested in our study. When the same species were tested, the resulting MIC90 results were similar for P. bivia, P. intermedia, and peptostreptococci in both studies. In all studies so far, the peptostreptococci have been uniformly susceptible to telithromycin (MIC90s, ≤0.06 μg/ml) (2, 5, 6, 7). Our isolates of P. melaninogenica were slightly more resistant to telithromycin than those reported by Ednie et al. (6) (MIC90 of 2 μg/ml versus 0.25 μg/ml, respectively).

Since clinicians must rely on published studies to help guide both empirical therapy and specific therapy in situations that involve commonly and less-commonly isolated or identified anaerobes in mixed infections (2, 5, 11), our study suggests that telithromycin (HMR 3647) has in vitro activity against unusual anaerobes and merits further evaluation.

Acknowledgments

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

This study was funded, in part, by an educational grant from Hoechst Marion Roussel, Romanville, France.

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