penicillin G, Glaxo, London, United Kingdom; ticarcillin,. Beecham Laboratories, London, United Kingdom; piper- acillin, Lederle Laboratories, Pearl River, N.Y.; ...
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, Jan. 1992, p. 195-197 0066-4804/92/010195-03$02.00/0 Copyright C 1992, American Society for Microbiology
Vol. 36, No. 1
In Vitro Susceptibilities of the Bacteroides fragilis Group to 14 Antimicrobial Agents in Korea KYUNGWON LEE,'* IN HO JANG,1 YOUNG JIN KIM,1 AND YUNSOP CHONG2 Yonsei University Wonju College of Medicine, Wonju,l and Yonsei University College of Medicine, Seoul,2 Korea Received 19 June 1991/Accepted 17 October 1991
The susceptibilities to 14 antimicrobial agents of 172 clinical isolates of the Bacteroides fragilis group from Korean patients during 1989 and 1990 were tested by an agar dilution method. All the isolates tested were susceptible to imipenem, chloramphenicol, and metronidazole. The rate of resistance to cefoxitin was 6%. Bacteroides fragilis group organisms are important anaerobic pathogens frequently isolated from intra-abdominal, pelvic, and soft tissue infections. Among the species of the group, B. fragilis causes serious anaerobic infections more often (4, 10). The changing patterns of susceptibilities of Bacteroides spp. have been noted by several investigators (2, 4, 9, 15) but, in general, anaerobic susceptibilities are not routinely tested. The selection of a therapeutic agent is, at best, based on published data. Frequent antimicrobial resistance of aerobic bacteria is a serious problem in Korea (3, 13); however, only a few studies have been done on the susceptibilities of anaerobic bacteria. The purpose of this study was to determine the current susceptibilities of members of the B. fragilis group isolated from Korean patients. (Part of this work was presented at the 91st General Meeting of the American Society for Microbiology [K. Lee, I. H. Jang, Y. J. Kim, and Y. Chong. 1991. Abstr. Annu. Meet. Am. Soc. Microbiol. 1991, C-136, p. 364].) Nonduplicated clinical isolates of the B. fragilis group were collected from January 1989 to May 1990 at two Korean medical centers: Severance Hospital, Seoul, and Wonju Christian Hospital, Wonju. Species identification was performed by established methods (12, 18) and with the ATB 32A system (API System SA, Montalieu Vercieu, France). Antimicrobial susceptibility testing of all the isolates was performed at Wonju Christian Hospital. The following numbers of isolates were used: B. fragilis, 113; B. thetaiotaomicron, 25; B. ovatus, 17; B. vulgatus, 11; and B. distasonis, 6. Standard antimicrobial powders were supplied as follows: penicillin G, Glaxo, London, United Kingdom; ticarcillin, Beecham Laboratories, London, United Kingdom; piperacillin, Lederle Laboratories, Pearl River, N.Y.; cefamandole, Eli Lilly & Co., Indianapolis, Ind.; cefoxitin, Merck Sharp & Dohme, West Point, Pa.; cefotaxime, Hoechst, Frankfurt, Germany; cefotetan, Yamanouchi, Tokyo, Japan; ceftazidime, Glaxo; ceftriaxone, Roche, Basel, Switzerland; imipenem, Merck Sharp & Dohme; chloramphenicol, Chong Kun Dang Co., Seoul, Korea; clindamycin, The Upjohn Co., Kalamazoo, Mich.; metronidazole, Shinkeeorug, Hong Kong; and tetracycline, Chong Kun Dang Co. Antimicrobial susceptibility testing was performed by an agar dilution method (18). Antimicrobial dilutions ranged from 256 to 0.063 ,ug/ml, except for imipenem, which was tested at 256 to 0.03 ,ug/ml. An inoculum of 105 CFU was applied to brucella agar supplemented with vitamin K, (10 *
,ug/ml) and 5% laked sheep blood with a Steers replicator. Plates were incubated in an anaerobic chamber for 48 h at 37°C. The MIC was defined as the lowest concentration of an antimicrobial agent permitting no growth, one discrete colony, or a barely visible haze. Reference strain B. fragilis ATCC 25285 was used as a control with each species. ,-Lactamase activity was tested with a chromogenic cephalosporin, cefinase (BBL). The susceptibilities of the 172 isolates to the 14 drugs are shown in Table 1. 1-Lactamase production was detected in 92% of B. fragilis group organisms: B. fragilis, 89%; B. thetaiotaomicron, 100%; B. ovatus, 100%; B. vulgatus, 100%; and B. distasonis, 83%. The most active beta-lactam drug was imipenem. Imipenem had MICs for 50 and 90% of isolates (MIC50 and MIC9J, respectively) of 0.12 and 0.5 ,ug/ml, respectively, and we detected no resistance. Cefoxitin was the second most active, with an MIC50 and an MIC90 of 8 and 32 ,ug/ml, respectively, and an 6% resistance rate at the breakpoint. Piperacillin, ticarcillin, cefotetan, cefotaxime, and ceftriaxone were less active and had resistance rates of 21, 25, 28, 33, and 36%, respectively. More frequently, resistance was found to ceftazidime, cefamandole, penicillin G, and tetracycline. No isolates were found to be resistant to metronidazole or chloramphenicol. The MIC50 TABLE 1. Antimicrobial activities against B. fragilis group organisms Antimicrobial Antimicrobial MIC (,ug/ml) agent
Penicillin G Ticarcillin
Range
50%o
0.5->256 16 0.5->256 32 0.5->256 8 Piperacillin Cefamandole 8->256 64 Cefoxitin 2-128 8 Cefotaxime 0.5->256 8 Cefotetan 1->256 8 Ceftazidime 1->256 32 Ceftriaxone 0.25->256 8 0.12 256 >256 256 256 32 256 128 >256 256 0.5
% ~~~~~Resistanta
Breakpoint concnb
94 25 21 92 6 33
4 64 64
(j±g/ml)
16 32
0
32 32 16 32 8
4
0
16
>256 4 64
24 0 85
4 16 8
28 63 36
a At the breakpoint concentration. b Based on the criteria of the National Committee for Clinical Laboratory Standards (14): no anaerobic breakpoint for ceftazidime; aerobic breakpoint for ceftazidime, 16 ,ug/ml.
Corresponding author. 195
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ANTIMICROB. AGENTS CHEMOTHER.
NOTES TABLE 2. Rates of resistance of B. fragilis group species Species
(no. of isolates)
PEN
TIC
PIP
B. fragilis (113) B. thetaiotaomicron (25) B. ovatus (17) B. vulgatus (11) B. distasonis (6)
95 100 94 73 100
18 24 35 46 100
12 32 35 46 67
% Resistance" to the following antimicrobial agentb: CTT CAZ CFM FOX CTX
89 100 100 82 100
4 8 12 9 17
17 68 65 46 83
6 76 77 27 100
46 100 100 92 100
CRO
CLN
TET
14 92 71 64 67
18 32 35 27 68
84 84 88 82 100
At the breakpoint concentration. b PEN, penicillin G; TIC, ticarcillin; PIP, piperacillin; CFM, cefamandole; FOX, cefoxitin; CTX, cefotaxime; CTT, cefotetan; CAZ, ceftazidime; CRO, ceftriaxone; CLN, clindamycin; TET, tetracycline. a
and MIC9Q of clindamycin were 0.5 and >256 ,ug/ml, respectively, and the resistance rate was 24%. There was variability in resistance rates among the various species of the B. fragilis group for some drugs (Table 2). Among the various species in the group, B. fragilis was more often susceptible to the beta-lactam drugs, and B. distasonis was more often resistant. The results of this study indicate that there were marked differences in the in vitro activities of the currently available beta-lactam drugs against the B. fragilis group organisms. Imipenem was the most active beta-lactam drug and had similar activities against all species of the B. fragilis group. Cefoxitin was the second most active and showed some resistance variability by species, with B. distasonis most frequently displaying resistance (17%). These results are in agreement with those of published surveys (1, 5). P-Lactamases are produced by a majority of resistant isolates of the B. fragilis group (16, 21). In general, resistance to beta-lactam drugs in the B. fragilis group is the result of 1-lactamase inactivation of the drugs. The good activities of imipenem and cefoxitin are probably due to the resistance of the drugs to ,B-lactamases (6, 7, 17, 19, 20). The rates of resistance to piperacillin, ticarcillin, and cefotetan were slightly higher than those observed in other studies (2, 5). Cefotetan, ceftriaxone, and cefotaxime showed the highest variations in activities against the species of the B. fragilis group. The cefotetan resistance rate was lowest with B. fragilis (6%) and highest with B. distasonis (100%). As expected, to ceftazidime, cefamandole, penicillin G, and tetracycline the rates of resistance were higher, and these drugs should not be considered for the treatment of infections involving organisms of the B. fragilis group. Chloramphenicol and metronidazole were the most active non-beta-lactam drugs, and to these no resistant isolates were found. The rate of resistance to clindamycin, 24%, was similar to those found by Betriu et al. (1) and Finegold and Wexler (11) but was higher than those found in other studies (2, 5, 8). Clindamycin displayed poor activity against the non-B. fragilis species of the B. fragilis group. These results emphasize the usefulness of periodic susceptibility studies of anaerobic bacteria in each country and the need for further investigations to demonstrate changes in susceptibility patterns. This work was supported in part by grants from Samil Pharmacy and Trading Co. REFERENCES 1. Betriu, C., E. Campos, C. Cabronero, C. Rodriguez-Avial, and J. J. Picazo. 1990. Susceptibilities of species of the Bacteroides fragilis group to 10 antimicrobial agents. Antimicrob. Agents Chemother. 34:671-673.
2. Bourgault, A.-M., G. K. Harding, J. A. Smith, G. B. Horsman, T. J. Marrie, and F. Lamothe. 1986. Survey of anaerobic susceptibility patterns in Canada. Antimicrob. Agents Chemother. 30:798-801. 3. Chong, Y. 1989. Trend of antimicrobial agent resistance of bacteria isolated from clinical materials. Korean J. Infect. Dis. 12:51-55. 4. Cuchural, G. J., Jr., F. P. Tally, N. V. Jacobus, K. Aldridge, T. Cleary, S. M. Finegold, G. Hill, P. Iannini, J. P. O'Keefe, C. Pierson, D. Crook, T. Russo, and D. Hecht. 1988. Susceptibility of the Bacteroides fragilis group in the United States: analysis by site of isolation. Antimicrob. Agents Chemother. 32:717722. 5. Cuchural, G. J., Jr., F. P. Tally, N. V. Jacobus, T. Cleary, S. M. Finegold, G. Hill, P. Iannini, J. P. O'Keefe, and C. Pierson. 1990. Comparative activities of newer beta-lactam agents against members of the Bacteroides fragilis group. Antimicrob. Agents Chemother. 34:479-480. 6. Cuchural, G. J., Jr., F. P. Tally, N. V. Jacobus, P. K. Marsh, and J. W. Mayhew. 1983. Cefoxitin inactivation by Bacteroides fragilis. Antimicrob. Agents Chemother. 24:936-940. 7. Darland, G., and J. Birnbaum. 1977. Cefoxitin resistance to beta-lactamase: a major factor for susceptibility of Bacteroides fragilis to the antibiotic. Antimicrob. Agents Chemother. 11: 725-734. 8. Dubreuil, L., J. Devos, C. Neut, and C. Romond. 1984. Susceptibility of anaerobic bacteria from several French hospitals to three major antibiotics. Antimicrob. Agents Chemother. 25:
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fragilis. Antimicrob. Agents Chemother. 22:579-584. 18. Sutter, V. L., D. M. Citron, M. A. C. Edelstein, and S. M. Finegold. 1985. Wadsworth anaerobic bacteriology manual, 4th ed. Star Publishing Co., Belmont, Calif. 19. Tally, F. P., J. P. O'Keefe, N. M. Sullivan, and S, L. Gorbach. 1979. Inactivation of cephalosporins by Bacteroides. Antimi-
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crob. Agents Chemother. 16:565-571. 20. Wexler, H. M., and S. M. Finegold. 1985. In vitro activity of imipenem against anaerobic bacteria. Rev. Infect. Dis. 7(Suppl. 3):417-425. 21. Wexler, H. M., and S. M. Finegold. 1987. Antimicrobial resistance in Bacteroides. J. Antimicrob. Chemother. 19:143-146.
