Journal of Antimicrobial Chemotherapy (2000) 46, 465-469
© 2000 The British Society for Antimicrobial Chemotherapy
Brief reports |
In vitro activity of an evernimicin derivative, SCH27899, against anaerobic bacteria and Propionibacterium acnes
Institute of Anaerobic Bacteriology, Gifu University School of Medicine, 40 Tsukasa-machi Gifu, 500-8705, Japan
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Abstract |
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The in vitro activity of SCH27899, a novel oligosaccharide antimicrobial agent, was compared with those of representatives of six classes of antimicrobial agents (piperacillin, clarithromycin, clindamycin, vancomycin, sitafloxacin and metronidazole) against clinical isolates of anaerobic bacteria and Propionibacterium acnes. Against Peptostreptococcus spp. and Clostridium difficile, SCH27899 was the most potent (MIC90 < 0.125 mg/L) of the agents examined. Besides these Gram-positive anaerobes, SCH27899 showed a moderate level of activity against Prevotella bivia, Prevotella intermedia and Porphyromonas spp. (MIC90
4 mg/L). |
Introduction |
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SCH27899 is a derivative of evernimicin, a novel oligosaccharide antimicrobial agent; it shows in vitro potency for Gram-positive bacteria and potentially relatively low nephrotoxicity. SCH27899 has potent activity for Gram-positive aerobic cocci.1–3 This agent has also been reported to be active against some Gram-negative bacteria, such as Moraxella catarrhalis,3 Legionella spp.4 and Borrelia burgdorferi.5 However, the antimicrobial activity of SCH27899 against anaerobic bacteria is unknown. The activity of SCH27899 for Gram-positive and Gram-negative obligate anaerobic bacteria was compared in vitro with that of six classes of antimicrobial agents. Propionibacterium acnes, some strains of which are aerotolerant or facultatively anaerobic, was included in the study.
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Materials and methods |
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Bacterial isolates
A total of 340 obligate anaerobic bacteria, isolated from clinical specimens between 1994 and 1997, was studied. Thirty-six strains of P. acnes, mainly isolated from specimens of pus, were also included in the study.
Antimicrobial agents
The following antimicrobial agents of known potency were used: SCH27899 (Schering-Plough K.K., Osaka, Japan), piperacillin (Toyama Chemical Co. Ltd, Tokyo, Japan), clarithromycin (Taisho Pharmaceutical Co. Ltd, Tokyo, Japan), clindamycin (Pharmacia & Upjohn, Tokyo, Japan), vancomycin (Shionogi & Co. Ltd, Osaka, Japan), sitafloxacin (DU-6859a) (Daiichi Pharmaceutical Co. Ltd, Tokyo, Japan) and metronidazole (Sigma, St Louis, MO, USA). Sitafloxacin is a new quinolone which has broad-spectrum, potent activity against both aerobic and anaerobic bacteria.6,7
Determination of MICs
MICs were determined by the NCCLS-recommended agar dilution technique8 using Brucella HK agar (Kyokuto Pharmaceutical, Tokyo, Japan) supplemented with 5% laked sheep blood. A final inoculum of 105 cfu/spot of test strains was incubated at 37°C in an anaerobic chamber (82% N2, 10% CO2, 8% H2) for 48 h. Bacteroides fragilis ATCC 25285 and Bacteroides fragilis GAI (Gifu Anaerobic Institute) 5562 were used as quality control strains.
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Results |
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MICs of piperacillin, clindamycin and metronidazole for the control strains were within one dilution step of the expected values described by the NCCLS.8 MICs of the seven tested agents for these two strains were stable (within one dilution step) throughout the study.
The MIC ranges, MIC50s and MIC90s of SCH27899 and other agents against recent clinical isolates are presented in Tables I and II
. Results for Gram-positive species are in Table I. SCH27899 was the most potent compound, showing excellent activity against all four species of Peptostreptococcus spp. (Peptostreptococcus anaerobius, Peptostreptococcus asaccharolyticus, Peptostreptococcus magnus, Peptostreptococcus micros) with an MIC90 of 0.06 mg/L. The activity of SCH27899 against these bacteria was comparable to or more potent than that of sitafloxacin. SCH27899 was also highly active against Clostridium spp. For Clostridium difficile, SCH27899 was the most active agent, followed by vancomycin, sitafloxacin and metronidazole; the MIC90 of SCH27899 was 0.125 mg/L, while that of the other three agents was 1 mg/L. On the other hand, all isolates of P. acnes were less susceptible to SCH27899 (MIC range >16 mg/L).
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Results for Gram-negative anaerobes, as shown in Table II
, SCH27899, indicated poor activity against B. fragilis, Bacteroides thetaiotaomicron, Fusobacterium nucleatum and Veillonella spp. MIC90s of SCH27899 were >16 mg/L and the activity of the agent was equal to that of vancomycin. However, SCH27899 showed moderate activity against Prevotella bivia, Prevotella intermedia and Porphyromonas spp., with an MIC90 of 4 mg/L. Overall, the basic spectrum of SCH27899 towards anaerobes was rather similar to that of vancomycin; SCH27899 was more active than vancomycin.
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Discussion |
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SCH27899 is highly active against Gram-positive aerobic bacteria.1–3 Generally, this agent is not active against Gram-negative aerobic bacteria, with some exceptions (M. catarrhalis and Legionella spp.).3,4 We found that the same general rules apply to anaerobic bacteria. The present study demonstrated that SCH27899 has potent activity against Gram-positive anaerobic cocci, and was also highly active against C. difficile and Clostridium perfringens. The antimicrobial activity of this agent for these bacteria was greater than that of vancomycin. From the results, it is suggested that SCH27899 has good clinical potential for treating infections caused by Gram-positive anaerobic cocci. In addition, vancomycin and metronidazole are the only agents that are currently effective for the treatment of C. difficile colitis. If oral administration of SCH27899 is possible, this agent may also be useful in the treatment of C. difficile colitis.
Of the antimicrobial agents examined, SCH27899 was the most effective against most of the Gram-positive species but, on the whole, had little activity against Gram-negative species. The basic spectrum of SCH27899 activity for anaerobic bacteria was similar to that of vancomycin. From experiments using a SCH27899-resistant mutant strain of Streptococcus pneumoniae, Adrian & Klugman suggested that SCH27899 acts by inhibiting protein synthesis.9 Vancomycin acts by inhibiting peptidoglycan synthesis. The similarity in basic spectra between SCH27899 and vancomycin does not, therefore, reflect their mechanisms of action. Vancomycin has a high molecular weight (1485.73) and is not active against Gram-negative bacteria because of the outer membrane barrier.10 SCH27899 also has a high molecular weight (1631.43), and so it is possible that outer membrane permeability affects the activity of SCH27899 for Gram-negative bacteria.
SCH27899 has potent activity against Gram-positive aerobic bacteria. In this study, it was also very active against Gram-positive anaerobic bacteria. It did not, however, show much activity against P. acnes. Further studies are required to clarify the mechanism of SCH27899 resistance in P. acnes.
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Notes |
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* Corresponding author. Tel: +81-58-267-2342; Fax: +81-58-265-9001; E-mail: kuni{at}cc.gifu-u.ac.jp
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References |
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1 . Nakashio, S., Iwasawa, H., Dun, F. Y., Kanemitsu, K. & Shimada, J. (1995). Everninomicin, a new oligosaccharide antibiotic: its antimicrobial activity, post-antibiotic effect and synergistic bactericidal activity. Drugs in Experimental Clinical Research 21, 7–16.
2 . Sato, Y., Kuga, A., Okamoto, R. & Inoue, M. (1998). In vitro antibacterial activity of SCH27899 (Ziracin) against Gram-positive cocci. In Program and Abstracts of the Thirty-Eighth Interscience Conference on Antimicrobial Agents and Chemotherapy, San Diego, CA, 1998. Abstract E-112, p. 202. American Society for Microbiology, Washington, DC.
3 . Jones, R. N., Marshall, S. A., Erwin, M. E. & the Quality Control Study Group. (1999). Antimicrobial activity and spectrum of SCH27899 (Ziracin) tested against gram-positive species including recommendations for routine susceptibility testing methods and quality control. Diagnostic Microbiology and Infectious Disease 34, 103–10.[Web of Science][Medline]
4 . Takemura, H., Ikejima, H., Kunishima, H., Terakubo, S., Kanemitsu, K., Yamamoto, H. et al. (1998). Evaluation of antimicrobial activities of SCH27899 (everninomycin, ziracin) for Legionella spp. In Program and Abstracts of the Thirty-Eighth Interscience Conference on Antimicrobial Agents and Chemotherapy, San Diego, CA, 1998. Abstract E-114, p. 203. American Society for Microbiology, Washington, DC.
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Dever, L. L., Torigian, C. V. & Barbour, A. G. (1999). In vitro activities of the everninomicin SCH27899 and other newer antimicrobial agents against Borrelia burgdorferi. Antimicrobial Agents and Chemotherapy 43, 1773–5.
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Sato, K., Hashino, K., Tanaka, M., Hayakawa, I. & Osada, Y. (1992). Antimicrobial activity of DU-6859, a new potent fluoroquinolone, against clinical isolates. Antimicrobial Agents and Chemotherapy 36, 1491–8.
7 . Kato, N., Kato, H., Tanaka-Bando, K., Watanabe, K. & Ueno, K. (1996). Comparison of in vitro activities of DU-6859a and other fluoroquinolones against Japanese isolates of anaerobic bacteria. Clinical Infectious Diseases 23, Suppl. 1. S31–5.
8 . National Committee for Clinical Laboratory Standards. (1997). Methods for Antimicrobial Susceptibility Testing of Anaerobic Bacteria—Fourth Edition: Approved Standard M11-4. NCCLS, Wayne, PA.
9 . Adrian, P. V. & Klugman, K. P. (1998). Ribosomal protein L16: the putative target site for evernimicin (SCH27899) action in Streptococcus pneumoniae. In Program and Abstracts of the Thirty-Eighth Interscience Conference on Antimicrobial Agents and Chemotherapy, San Diego, CA, 1998. Abstract C-110, p. 100. American Society for Microbiology, Washington, DC.
10 . Best, G. K., Best, N. H., Ferguson, D. V. & Durham, N. N. (1968). Adsorption of vancomycin by sensitive and resistant organisms. Biochemica et Biophysica Acta 165, 558–60.
Received 18 October 1999; returned 5 January 2000; revised 3 March 2000; accepted 10 April 2000
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