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In Vitro Activity of Quinolones and Other Antimicrobial Agents Against Anaerobic Bacteria

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In Vitro Activity of Quinolones and Other Antimicrobial Agents Against Anaerobic Bacteria SIS In Vitro Activity of Quinolones and Other Antimicrobial Agents Against Anaerobic Bacteria Carl Erik Nord From the Department of Immunology, Microbiology, Pathology, and Infectious Diseases, Huddinge University Hospital, Karolinska Institute, Stockholm, Sweden The in vitro activities of ciprofioxacin, lomefioxacin, ofioxacin, sparfioxacin, and DU-68S9a against peptostreptococci, Clostridium per/ringens, Clostridium difficile, Bacteroides jragilis, Porphyromonas, Downloaded fromhttps://academic.oup.com/cid/article/23/Supplement_1/S15/424437by gueston02October2021 Prevotella, and Fusobacterium were determined by an agar dilution method. These activities were compared with those of piperacillinltazobactam, cefoxitin, imipenem, clindamycin, and metronida­ zole. Imipenem, metronidazole, and DU-68S9a were the most active antimicrobial agents that were tested. The in vitro activity of DU-68S9a was superior to those of ciprofioxacin, lomefioxacin, ofioxacin, and sparfioxacin. The in vitro activity of older quinolones against anaerobic Three control strains (Bacteroides fragilis ATCC [American bacteria has been reported to be moderate or poor, while the Type Culture Collection] 25285, Bacteroides thetaiotaomicron newer quinolones are more active [1]. Antimicrobial agents ATCC 29741, and Clostridium peifringens ATCC 13124) were recommended for treatment of and prophylaxis for infections used for monitoring the antimicrobial susceptibility testing. due to anaerobic bacteria include metronidazole, clindamycin, The following antimicrobial agents were used in the study: ,B-lactam agents plus ,B-Iactamase inhibitors, cefoxitin, and imi­ ciprofioxacin (Bayer AG, Wuppertal, Germany), ofioxacin penem. The present investigation was undertaken to determine (Hoechst AG, Frankfurt, Germany), piperacillin and tazobac­ the in vitro activities of five quinolones-ciprofioxacin, 10- tam (Lederle-Praxis Biologicals, Pearl River, NY), cefoxitin mefioxacin, ofioxacin, sparfloxacin, and DU-6859a-against and imipenem (Merck, Sharp, & Dohme, West Point, PA), 320 anaerobic bacteria recently isolated from patients with in­ clindamycin (Upjohn, Kalamazoo, MI), metronidazole and fections. The activities were compared with those ofmetronida­ sparfloxacin (Rhone Poulenc Rorer, Antony Cedex, France), zole, clindamycin, piperacillinitazobactam, cefoxitin, and imi­ lomefioxacin (Searle, Chicago), and DU-6859a (Daiichi Phar­ penem. maceutical, Tokyo). The breakpoints of cefoxitin, imipenem, piperacillinltazo­ bactam, clindamycin, and metronidazole, which were outlined Materials and Methods by the National Committee for Clinical Laboratory Standards During 1995, 320 strains isolated from patients with intraab­ [3], were as follows: 32 mg/L, 8 mg/L, 64/4 mg/L, 4 mg/L, dominal and respiratory tract infections were submitted to the and 16 mg/L, respectively. The breakpoint of ciprofioxacin was Huddinge University Hospital, Karolinska Institute, Stock­ 2 mg/L, and the breakpoints of lomefioxacin, ofioxacin, and holm, for testing. All strains were identified on the basis of sparfloxacin (for aerobic bacteria) were 4 mg/L, 4 mg/L, and the requirements of the Manual of Clinical Microbiology [2]. 4 mg/L, respectively. Antimicrobial susceptibility testing was performed by an agar dilution method according to the National Committee for Clini­ cal Laboratory Standards [3]. The medium used was brucella Results agar supplemented with 5% laked blood agar, hemin, and vita­ min K. The inoculum was 105 cfu/roL, and the agar plates were The in vitro activities of the antimicrobial agents against incubated in anaerobic jars (GasPak, BBL Becton Dickinson anaerobic bacteria are shown in table 1. All peptostreptococcal Microbiology Systems, Cockeysville, MD) at 37°C for 48 strains were susceptible to piperacillinltazobactam, cefoxitin, hours. The MIC was defined as the lowest concentration of the imipenem, clindamycin, metronidazole, sparfloxacin, and DU- agent that inhibited growth. The appearance of a single colony 6859a, and some strains were resistant to lomefioxacin (50%), or a barely visible haze was disregarded. ciprofioxacin (10%), and ofioxacin (10%). The C. perfringens isolates were all susceptible to piperacillinltazobactam, cefoxi­ tin, imipenem, clindamycin, metronidazole, sparfioxacin, ci­ profioxacin, ofioxacin, and DU-6859a, and most ofthese strains Reprints or correspondence: Professor Carl Erik Nord, Department ofImmu­ (90%) were susceptible to lomefioxacin. All Clostridium diffi­ nology, Microbiology, Pathology, and Infectious Diseases, F88, Huddinge Uni­ cile strains were susceptible to piperacillinltazobactam, imi­ versity Hospital, S-141 86 Huddinge, Sweden. penem, metronidazole, and DU-6859a. Fifty percent of the Clinical Infectious Diseases 1996;23(Suppll):S15-8 difficile isolates were inhibited by 4 mg of clindamycinlL. © 1996 by The University of Chicago. All rights reserved. C. 1058-4838/96/2306-0004$02.00 All of these strains were resistant to cefoxitin, ciprofioxacin, S16 Nord CID 1996;23 (Suppll) Table 1. In vitro activities of quinolones and other antimicrobial agents against anaerobic bacteria isolated from human infections. MIC (mg/L) Species (no. of isolates)/antimicrobial agent Range MICso MIC90 Percentage resistant Peptostreptococci (50) Piperacillinltazobactam 0.016-2.0 0.125 0.25 0 Cefoxitin 0.064-8.0 1.0 4.0 0 Imipenem 0.016-0.064 0.032 0.064 0 Clindamycin 0.016-1.0 0.064 0.064 0 Downloaded fromhttps://academic.oup.com/cid/article/23/Supplement_1/S15/424437by gueston02October2021 Metronidazole 0.125-8.0 4.0 4.0 0 Ciprofioxacin 0.032-16.0 1.0 2.0 10 Lomefioxacin 2.0-8.0 4.0 8.0 50 Ofioxacin 0.125-8.0 2.0 8.0 10 Sparfioxacin 0.25-2.0 0.25 0.5 0 DU-6859a* 0.008-0.125 0.008 0.008 Clostridium perfringens (30) Piperacillinltazobactam 0.016-2.0 0.064 1.0 0 Cefoxitin 0.5-1.0 0.5 1.0 0 Imipenem 0.016-0.5 0.25 0.5 0 Clindamycin 0.008-1.0 0.125 1.0 0 Metronidazole 1.0-4.0 1.0 1.0 0 Ciprofioxacin 0.125-0.5 0.25 0.5 0 Lomefioxacin 1.0-4.0 1.0 4.0 10 Ofioxacin 0.5-2.0 1.0 2.0 0 Sparfioxacin 0.25-0.5 0.25 0.5 0 DU-6859a* 0.008-0.25 0.008 0.125 Clostridium difficile (50) Piperacillinitazobactam 0.125-8.0 4.0 4.0 0 Cefoxitin 64.0-128.0 64.0 128.0 100 Imipenem 8.0 8.0 8.0 0 Clindamycin 0.5-128.0 4.0 8.0 50 Metronidazole 0.125-0.25 0.125 0.25 0 Ciprofioxacin 4.0-16.0 8.0 16.0 100 Lomefioxacin 4.0-32.0 16.0 32.0 100 Ofioxacin 4.0-16.0 8.0 16.0 100 Sparfioxacin 0.5-8.0 4.0 8.0 80 DU-6859a* 0.125-0.25 0.125 0.25 Bacteroides fragilis (100) Piperacillinitazobactam 0.064-64.0 4.0 32.0 0 Cefoxitin 2.0-32.0 8.0 16.0 0 Imipenem 0.064-0.25 0.064 0.125 0 Clindamycin 0.016-8.0 0.5 2.0 5 Metronidazole 0.25-2.0 0.5 1.0 0 Ciprofioxacin 2.0-32.0 4.0 8.0 90 Lomefioxacin 2.0-32.0 8.0 16.0 90 Ofioxacin 2.0-16.0 4.0 8.0 90 Sparfioxacin 0.25-16.0 2.0 2.0 10 DU-6859a* 0.008-0.5 0.008 0.25 Prevotella and Porphyromonas (50) Piperacillinltazobactam 0.064-4.0 1.0 4.0 0 Cefoxitin 0.125-1.0 0.5 1.0 0 Imipenem 0.016-0.25 0.032 0.032 0 Clindamycin 0.016-0.25 0.016 0.016 0 Metronidazole 0.064-4.0 1.0 1.0 0 Ciprofioxacin 0.016-16.0 1.0 8.0 10 Lomefioxacin 4.0-16.0 4.0 8.0 50 Ofioxacin 1.0-16.0 4.0 8.0 50 Sparfioxacin 1.0-8.0 2.0 4.0 10 DU-6859a* 0.008-0.25 0.016 0.25 eID 1996;23 (Suppll) Quinolone Activity Against Anaerobic Bacteria S17 Table 1. (Continued) MIC (mg/L) Species (no. of isolates)/antimicrobial agent Range MICso MIC90 Percentage resistant Fusobacterium (40) Piperacillinltazobactam 0.032-1.0 0.064 0.064 0 Cefoxitin 0.064-16.0 0.5 0.5 0 Imipenem 0.008-0.064 0.032 0.064 0 Clindamycin 0.016 0.016 0.016 0 Downloaded fromhttps://academic.oup.com/cid/article/23/Supplement_1/S15/424437by gueston02October2021 Metronidazole 0.25-4.0 4.0 4.0 0 Ciprofloxacin 0.016-16.0 1.0 2.0 10 Lomefloxacin 4.0-8.0 4.0 8.0 50 Ofloxacin 1.0-16.0 2.0 8.0 50 Sparfloxacin 0.5-2.0 1.0 2.0 0 DU-6859a* 0.008-0.25 0.008 0.032 * Data for this agent were obtained from Daiichi Pharmaceutical, Tokyo. lomefioxacin, and ofioxacin, while 80% of the strains were be prolonged to avoid relapses because of the marked tendency resistant to sparfioxacin. for anaerobes to cause tissue necrosis, abscess formation, and The B. fragilis strains were susceptible to piperacillinltazo­ septic thrombophlebitis. Agents commonly used in the treat­ bactam (100%), cefoxitin (100%), imipenem (100%), clinda­ ment of infections due to anaerobic bacteria are nitroimidaz­ mycin (95%), metronidazole (100%), and DU-6859a (100%). oles, carbapenems, and combinations of ,B-lactam drugs with Ten percent of the strains were susceptible to ciprofioxacin, ,B-lactamase inhibitors [4]. lomefioxacin, and ofioxacin, while 10% of the strains were The third-generation quinolones are used for treatment of resistant to sparfioxacin (table 1). All Prevotella and Porphyro­ many different human infections, such as respiratory tract in­ monas strains were susceptible to piperacillinltazobactam, cef­ fections, urinary tract infections, sexually transmitted diseases, oxitin, imipenem, clindamycin, metronidazole, and DU-6859a; diarrheal diseases, and osteomyelitis [5]. However, so far, most the MIC90 values of ciprofioxacin, lomefioxacin, ofioxacin, and clinically used quinolones have minor activities against anaero­ sparfioxacin were 8.0 mg/L, 8.0 mglL, 8.0 mg/L, and 4.0 mg/L, bic bacteria. On the other hand, it has been shown that three respectively.
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