ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, Nov. 1991, p. 2447-2449
Vol. 35, No. 11
0066-4804/91/112447-03$02.00/0 Copyright © 1991, American Society for Microbiology
Susceptibility of Anaerobic Bacteria Isolated from Intra-abdominal Infections to Ofloxacin and Interaction of Ofloxacin with Metronidazole ELLIE J. C. GOLDSTEIN* AND DIANE M. CITRON
R. M. Alden Research Laboratory, Santa Monica Hospital & Medical Center, Santa Monica, California 90404 Received 28 May 1991/Accepted 19 August 1991
The in vitro activities of ofloxacin alone and in combination with metronidazole against 177 anaerobic bacteria isolated from intra-abdominal infections, as determined by broth microdilution, showed that some Bacteroidesfragiis strains were susceptible and that most other B. fragiis group species strains were resistant to ofloxacin. Isolates of other anaerobic species and genera, including those causing female genital tract disease, were generally susceptible to ofloxacin. Ofloxacin in combination with metronidazole usually showed an additive or indifferent interaction but no antagonism.
Ofloxacin is a fluoroquinolone antimicrobial agent with a broad spectrum of activity against gram-positive and gramnegative aerobic bacteria (2, 4, 6, 8). Its activity against anaerobic bacteria is less well described (2, 4, 6, 8). Generally, ofloxacin, as well as the other fluoroquinolones such as norfloxacin and ciprofloxacin, is less active against anaerobic bacteria than against aerobes (4, 6). Ofloxacin is likely to be used for selective decontamination of the bowel in neutropenic patients (7, 11, 13) and in combination with other agents, especially metronidazole, in clinical settings involving mixed aerobic-anaerobic bacteria. It is therefore important to ascertain the in vitro activities of ofloxacin against a wide variety of common clinical anaerobic isolates, as well as the effect of its combination with metronidazole. We therefore explored its activity, using a broth microdilution and checkerboard assay. A total of 177 anaerobic bacteria, all recently isolated from intra-abdominal infections of patients hospitalized at Santa Monica Hospital Medical Center and St. John's Hospital & Health Center of Santa Monica, were studied (see Table 1). All isolates were identified by standard criteria (5, 10). Control strains Bacteroides fragilis ATCC 25285, Bacteroides thetaiotaomicron ATCC 29741, and Clostridium perfringens ATCC 13124 were included in each experiment. Standard laboratory powders were kindly supplied by R. W. Johnson Pharmaceutical Research Institute, Raritan, N.J. (ofloxacin), and G. D. Searle & Co., Chicago, Ill. (metronidazole). Antibiotic powders were reconstituted on the day of plate preparation according to the manufacturers' instructions. The concentrations of the drugs, prepared in serial twofold dilutions, were as follows: ofloxacin, 0.125 to 256 ,ug/ml; and metronidazole, 0.12 to 32 ,ug/ml. The microtiter plates were made by using the Quick Spense II system (Sandy Springs Instrument Co., Inc., Germantown, Md.) and stored at -70°C until used. For the synergy studies, a checkerboard pattern was used with the following drug concentrations: metronidazole, 0.03 to 1 ,ug/ml; and ofloxacin, 0.06 to 128 ,ugIml. Strains were taken from frozen stock cultures and transferred twice onto Prereduced Anaerobically Sterilized brucella blood agar (Anaerobe Systems, San Jose, Calif.) to *
Corresponding author.
purity and good growth. Inocula were prepared by suspending colonies in Anaerobe Broth MIC (Difco Laboratories, Detroit, Mich.) to achieve a 0.5 McFarland standard. The inocula were further diluted 1:50, and a 50-,ul aliquot was added to each well by using an automatic pipette (Rainin Instrument Co., Inc., Woburn, Mass.), giving a final volume of 100 ,ul and an inoculum concentration of approximately 106 CFU/ml. Colony counts were performed for selected isolates to verify the inoculum concentration. A National Committee for Clinical Laboratory Standardsrecommended (9) broth microdilution method with Anaerobe Broth MIC was used. The composition of the broth is the same as that of Wilkens-Chalgren agar without the agar. For peptostreptococci, 0.1% Tween 80 and, for some strains, 1% rabbit serum supplementation were added. For Peptostreptococcus micros, Porphyromonas spp., and some Prevotella spp., laked horse blood was added to a final concentration of 2%. All inoculation of bacteria was done in an anaerobic chamber. All plates were incubated at 37°C in an anaerobic chamber for 48 h and then read. The MIC was defined as the lowest antibiotic concentration to yield no visible turbidity. The effect of drug interaction was determined by calculating the fractional inhibitory concentration index (EFIC). Synergy was defined as a minimum EFIC of 4.0. Indifference or an additive effect was defined as an EFIC of 0.5 to 4.0. The susceptibilities of 177 clinical anaerobic bacterial isolates are summarized in Table 1. B. fragilis was the most susceptible member of the B. fragilis group, with an MIC for 90% of the strains tested of s4 g/ml. All B. thetaiotaomicron and Bacteroides ovatus isolates were resistant to ofloxacin (MIC, -8 ,ug/ml). All Fusobacterium nucleatum and Fusobacterium necrophorum and some Fusobacterium mortiferum and Fusobacterium varium strains, as well as C. perfringens, Eubacterium species, and most peptostreptococci, were also susceptible to ofloxacin. Some clostridia and peptostreptococci were resistant to ofloxacin. All isolates, with the exception of Gemella morbillorum, were susceptible to metronidazole. In the synergy studies, all isolates exhibited indifference to or an additive effect of the combination of ofloxacin and metronidazole except for some strains of C. perfringens which showed synergy. No antagonism was found. ensure
2447
2448
ANTIMICROB. AGENTS CHEMOTHER.
NOTES
TABLE 1. Susceptibilities of 177 strains of anaerobic bacteria to ofloxacin and metronidazole MIC (>Lg/ml)' Species
B. fragilis B. thetaiotaomicron B. distasonis B. vulgatus B. ovatus B. uniformis "Bacteroides" spp.c F. nucleatumiF. necrophorumd F. mortiferumiF. variume C. perfringens Clostridium spp.8 Eubacterium spp.h Peptostreptococcus spp.'
No.Ofloxacin strains tested Range 50%
11 14 10 12 12 10 17 15 19 10 17 10 20
1-8 8-256 2-64 1-16 16-32 2-64 0.25-8 1-4 2-64 0.5-1 0.5-256 0.25-4 0.125-16
2 16 2 4 16 8 2 2 4 1 2 1 0.5
FIC range"
Metronidazole
90%o
Range
50%o
90%o
Oflx
Met
4 16 8 8 32 16 4 2 16 1 8 2 8
0.5-2 1-4 0.25-2 0.25-2 1-2 0.25-2 0.06-4 0.03-0.5 0.125-2
1 1 1 0.5 1 0.5 1 0.25 0.5 4 0.5 0.5 0.5
2 2 2 2 2 1 2 0.5 1 8 2 1 2
0.5-1 0.5-1 0.5-1 0.5-1 0.25-1 0.5-1 0.25-1 0.25-1 0.5-1 0.25-1 0.25-1 0.25-1 0.25-1
0.5-1 0.5-1 1-1 0.5-1 0.5-1 1-1 0.5-1 0.5-1 0.5-1 0.25-0.5
0.25-8 0.03-2 s0.015-4 0.25->32
0.5-1 0.25-1
0.5-1
Index
1-2 1-2 1-2 1-2 0.75-2 1.5-2 1.25-2 0.75-2 1-2
0.25-0.5f 0.75-2 0.75-2 1.25-2
50%o and 90%o, MIC for 50 and 90%o of isolates, respectively. b FIC, fractional inhibitory concentration, calculated for each antibiotic at one-fourth of the MIC of the other antibiotic. Ofix, ofloxacin; Met, metronidazole. c Includes one Prevotella intermedia, six P. melaninogenica, four P. bivia, two P. buccae, two Porphyromonas asaccharolytica, one Bacteroides splanchnicus and one B. putredinis strains. d Includes seven F. nucleatum and eight F. necrophorum strains. Includes 8 F. mortiferum and 11 F. varium strains. f Based on three strains for which the MICs were within a calculable range. g Includes five C. ramosum, two C. butyricum, three Clostridium sp., and one each C. limosum, C. septicum, C. butyricum, C. bifermentans, C. difficile, C. paraputrificum, C. innocuum, and C. subterminale strains. h Includes four E. lentum, one E. limosum, and five Eubacterium sp. strains. i Includes six P. micros, four P. asaccharolyticus, three P. anaerobius, two P. magnus, and two P. prevotii strains and one anaerobic strain of G. morbillorum. a
Our results show that ofloxacin is moderately active against some anaerobic bacteria, with variable activity against the different species. Most prior studies used a variety of inoculum densities and methods and have not identified many of their anaerobic isolates to species level, especially the B. fragilis group species, thereby giving less than optimal information (2, 4, 8). Our study showed variation in ofloxacin's activity against the B. fragilis group, with most B. fragilis strains being susceptible and Bacteroides distasonis, Bacteroides vulgatus, B. thetaiotaomicron, B. ovatus, and Bacteroides uniformis strains being resistant to ofloxacin. Isolates of the other species and genera were generally susceptible (MIC, .8 ,ug/ml) to ofloxacin. Because of this variability in the susceptibility patterns of anaerobes, it would be prudent to use a second agent, such as metronidazole, with activity against all B. fragilis group species when treating intra-abdominal infections with ofloxacin. No in vitro antagonism was demonstrated with this combination. This is similar to the effect Whiting et al. (12) found with ciprofloxacin and metronidazole. This lack of synergy may be related to the excellent activity of metronidazole against almost all anaerobic bacteria. Some studies have suggested that ofloxacin be used for selective decontamination of the gastrointestinal tract in neutropenic patients (1, 2, 7, 13). Even though ofloxacin exhibited moderate activity against many fecal anaerobic bacteria, several studies have noted that ofloxacin did not alter the anaerobic fecal flora in healthy volunteers (7, 11). This is consistent with our prior findings (3) for another fluoroquinolone (norfloxacin) with a marked inoculum effect against fecal anaerobic bacteria, causing the MIC to be even greater than the level attained in the feces. Edlund et al. (1) suggested an alternate mechanism due to binding of the quinolones to the feces, thereby decreasing the quinolones' effective local activity. van Saene et al. (11) found ofloxacin
to cause less
disturbance to the normal anaerobic bowel flora
(possibly because of the relatively greater activity of ciprofloxacin than of ofloxacin against anaerobes, as well as the lower absorption rate of ciprofloxacin than of ofloxacin), leading to higher fecal antibiotic levels. While the isolates studied were from intra-abdominal sources, some of these anaerobic species, including Prevotella intermedia, Prevotella melaninogenicus, Prevotella bivius, Porphyromonas asaccharolytica, and Peptostreptococcus species, are also causes of female genital tract infection. These isolates were generally susceptible to ofloxacin. This activity against anaerobic bacteria, coupled with the activity against aerobic bacteria, gonococci, and chlamydia, suggests that ofloxacin may be effective in treatment of female genital tract infections. We thank Judee H. Knight, Alice E. Goldstein, Margareta I. Ostovari, and Michael L. Corrado for various forms of assistance. This study was supported, in part, by a grant from the R. W. Johnson Pharmaceutical Research Institute, Raritan, N.J. REFERENCES 1. Edlund, C., L. Lindqvist, and C. E. Nord. 1988. Norfloxacin binds to human fecal material. Antimicrob. Agents Chemother. 32:1869-1874. 2. Fuchs, P. C. 1989. In vitro antimicrobial activity and susceptibility testing of ofloxacin: current status. Am. J. Med. 87(Suppl. 6C):10S-13S. 3. Goldstein, E. J. C., D. M. Citron, and M. L. Corrado. 1987. Effect of inoculum size on in vitro activity of norfloxacin against fecal anaerobic bacteria. Am. J. Med. 82(Suppl. 6B):84-87. 4. Grunberg, R. N., D. Felmingham, M. D. O'Hare, M. J. Robbins, K. Perry, R. A. Wall, and G. L. Ridgway. 1988. The comparative in-vitro activity of ofloxacin. J. Antimicrob. Chemother. 22(Suppl. C):9-19. 5. Holdeman, L. V., E. P. Cato, and W. E. C. Moore (ed.). 1977. Anaerobe laboratory manual, 4th ed. Virginia Polytechnic Institute and State University, Blacksburg. 6. King, A., K. Shannon, and I. Phillips. 1985. The in vitro
NOTES
VOL. 35, 1991
7.
8. 9.
10.
activities of enoxacin and ofloxacin compared with that of ciprofloxacin. J. Antimicrob. Chemother. 15:551-558. Leigh, D. A., B. Walsh, K. Harris, P. Hancock, and G. Travers. 1988. Pharmacokinetics of ofloxacin and the effect on the faecal flora of healthy volunteers. J. Antimicrob. Chemother. 22(Suppl. C):115-125. Monk, J. P., and D. M. Campoli-Richards. 1987. Ofloxacin: a review of its antibacterial activity, pharmacokinetic properties and therapeutic use. Drugs 33:346-391. National Committee for Clinical Laboratory Standards. 1989. Methods for antimicrobial susceptibility testing of anaerobic bacteria, 2nd ed. Tentative standard (M11-T2). National Committee for Clinical Laboratory Standards, Villanova, Pa. Sutter, V. L., D. M. Citron, M. A. C. Edelstein, and S. M. Finegold. 1985. Wadsworth anaerobic bacteriology manual, 4th
2449
ed. Star Publishing Co., Belmont, Calif. van Saene, H. K. F., S. E. B. Lemmens, and J. J. M. van Saene. 1988. Gut decontamination by oral ofloxacin and ciprofloxacin in healthy volunteers. J. Antimicrob. Chemother. 22(Suppl. C):127-134. 12. Whiting, J. L., N. Cheng, and A. W. Chow. 1987. Interactions of ciprofloxacin with cindamycin, metronidazole, cefoxitin, cefotaxime, and mezlocillin against gram-positive and gram-negative anaerobic bacteria. Antimicrob. Agents Chemother. 31:13791382. 13. Winston, D. J., W. G. Ho, D. A. Bruckner, R. P. Gale, and R. E. Champlin. 1990. Ofloxacin versus vancomycin/polymyxin for prevention of infections in granulocytopenic patients. Am. J. Med. 88:36-42. 11.
Vol. 35, No. 11
0066-4804/91/112447-03$02.00/0 Copyright © 1991, American Society for Microbiology
Susceptibility of Anaerobic Bacteria Isolated from Intra-abdominal Infections to Ofloxacin and Interaction of Ofloxacin with Metronidazole ELLIE J. C. GOLDSTEIN* AND DIANE M. CITRON
R. M. Alden Research Laboratory, Santa Monica Hospital & Medical Center, Santa Monica, California 90404 Received 28 May 1991/Accepted 19 August 1991
The in vitro activities of ofloxacin alone and in combination with metronidazole against 177 anaerobic bacteria isolated from intra-abdominal infections, as determined by broth microdilution, showed that some Bacteroidesfragiis strains were susceptible and that most other B. fragiis group species strains were resistant to ofloxacin. Isolates of other anaerobic species and genera, including those causing female genital tract disease, were generally susceptible to ofloxacin. Ofloxacin in combination with metronidazole usually showed an additive or indifferent interaction but no antagonism.
Ofloxacin is a fluoroquinolone antimicrobial agent with a broad spectrum of activity against gram-positive and gramnegative aerobic bacteria (2, 4, 6, 8). Its activity against anaerobic bacteria is less well described (2, 4, 6, 8). Generally, ofloxacin, as well as the other fluoroquinolones such as norfloxacin and ciprofloxacin, is less active against anaerobic bacteria than against aerobes (4, 6). Ofloxacin is likely to be used for selective decontamination of the bowel in neutropenic patients (7, 11, 13) and in combination with other agents, especially metronidazole, in clinical settings involving mixed aerobic-anaerobic bacteria. It is therefore important to ascertain the in vitro activities of ofloxacin against a wide variety of common clinical anaerobic isolates, as well as the effect of its combination with metronidazole. We therefore explored its activity, using a broth microdilution and checkerboard assay. A total of 177 anaerobic bacteria, all recently isolated from intra-abdominal infections of patients hospitalized at Santa Monica Hospital Medical Center and St. John's Hospital & Health Center of Santa Monica, were studied (see Table 1). All isolates were identified by standard criteria (5, 10). Control strains Bacteroides fragilis ATCC 25285, Bacteroides thetaiotaomicron ATCC 29741, and Clostridium perfringens ATCC 13124 were included in each experiment. Standard laboratory powders were kindly supplied by R. W. Johnson Pharmaceutical Research Institute, Raritan, N.J. (ofloxacin), and G. D. Searle & Co., Chicago, Ill. (metronidazole). Antibiotic powders were reconstituted on the day of plate preparation according to the manufacturers' instructions. The concentrations of the drugs, prepared in serial twofold dilutions, were as follows: ofloxacin, 0.125 to 256 ,ug/ml; and metronidazole, 0.12 to 32 ,ug/ml. The microtiter plates were made by using the Quick Spense II system (Sandy Springs Instrument Co., Inc., Germantown, Md.) and stored at -70°C until used. For the synergy studies, a checkerboard pattern was used with the following drug concentrations: metronidazole, 0.03 to 1 ,ug/ml; and ofloxacin, 0.06 to 128 ,ugIml. Strains were taken from frozen stock cultures and transferred twice onto Prereduced Anaerobically Sterilized brucella blood agar (Anaerobe Systems, San Jose, Calif.) to *
Corresponding author.
purity and good growth. Inocula were prepared by suspending colonies in Anaerobe Broth MIC (Difco Laboratories, Detroit, Mich.) to achieve a 0.5 McFarland standard. The inocula were further diluted 1:50, and a 50-,ul aliquot was added to each well by using an automatic pipette (Rainin Instrument Co., Inc., Woburn, Mass.), giving a final volume of 100 ,ul and an inoculum concentration of approximately 106 CFU/ml. Colony counts were performed for selected isolates to verify the inoculum concentration. A National Committee for Clinical Laboratory Standardsrecommended (9) broth microdilution method with Anaerobe Broth MIC was used. The composition of the broth is the same as that of Wilkens-Chalgren agar without the agar. For peptostreptococci, 0.1% Tween 80 and, for some strains, 1% rabbit serum supplementation were added. For Peptostreptococcus micros, Porphyromonas spp., and some Prevotella spp., laked horse blood was added to a final concentration of 2%. All inoculation of bacteria was done in an anaerobic chamber. All plates were incubated at 37°C in an anaerobic chamber for 48 h and then read. The MIC was defined as the lowest antibiotic concentration to yield no visible turbidity. The effect of drug interaction was determined by calculating the fractional inhibitory concentration index (EFIC). Synergy was defined as a minimum EFIC of 4.0. Indifference or an additive effect was defined as an EFIC of 0.5 to 4.0. The susceptibilities of 177 clinical anaerobic bacterial isolates are summarized in Table 1. B. fragilis was the most susceptible member of the B. fragilis group, with an MIC for 90% of the strains tested of s4 g/ml. All B. thetaiotaomicron and Bacteroides ovatus isolates were resistant to ofloxacin (MIC, -8 ,ug/ml). All Fusobacterium nucleatum and Fusobacterium necrophorum and some Fusobacterium mortiferum and Fusobacterium varium strains, as well as C. perfringens, Eubacterium species, and most peptostreptococci, were also susceptible to ofloxacin. Some clostridia and peptostreptococci were resistant to ofloxacin. All isolates, with the exception of Gemella morbillorum, were susceptible to metronidazole. In the synergy studies, all isolates exhibited indifference to or an additive effect of the combination of ofloxacin and metronidazole except for some strains of C. perfringens which showed synergy. No antagonism was found. ensure
2447
2448
ANTIMICROB. AGENTS CHEMOTHER.
NOTES
TABLE 1. Susceptibilities of 177 strains of anaerobic bacteria to ofloxacin and metronidazole MIC (>Lg/ml)' Species
B. fragilis B. thetaiotaomicron B. distasonis B. vulgatus B. ovatus B. uniformis "Bacteroides" spp.c F. nucleatumiF. necrophorumd F. mortiferumiF. variume C. perfringens Clostridium spp.8 Eubacterium spp.h Peptostreptococcus spp.'
No.Ofloxacin strains tested Range 50%
11 14 10 12 12 10 17 15 19 10 17 10 20
1-8 8-256 2-64 1-16 16-32 2-64 0.25-8 1-4 2-64 0.5-1 0.5-256 0.25-4 0.125-16
2 16 2 4 16 8 2 2 4 1 2 1 0.5
FIC range"
Metronidazole
90%o
Range
50%o
90%o
Oflx
Met
4 16 8 8 32 16 4 2 16 1 8 2 8
0.5-2 1-4 0.25-2 0.25-2 1-2 0.25-2 0.06-4 0.03-0.5 0.125-2
1 1 1 0.5 1 0.5 1 0.25 0.5 4 0.5 0.5 0.5
2 2 2 2 2 1 2 0.5 1 8 2 1 2
0.5-1 0.5-1 0.5-1 0.5-1 0.25-1 0.5-1 0.25-1 0.25-1 0.5-1 0.25-1 0.25-1 0.25-1 0.25-1
0.5-1 0.5-1 1-1 0.5-1 0.5-1 1-1 0.5-1 0.5-1 0.5-1 0.25-0.5
0.25-8 0.03-2 s0.015-4 0.25->32
0.5-1 0.25-1
0.5-1
Index
1-2 1-2 1-2 1-2 0.75-2 1.5-2 1.25-2 0.75-2 1-2
0.25-0.5f 0.75-2 0.75-2 1.25-2
50%o and 90%o, MIC for 50 and 90%o of isolates, respectively. b FIC, fractional inhibitory concentration, calculated for each antibiotic at one-fourth of the MIC of the other antibiotic. Ofix, ofloxacin; Met, metronidazole. c Includes one Prevotella intermedia, six P. melaninogenica, four P. bivia, two P. buccae, two Porphyromonas asaccharolytica, one Bacteroides splanchnicus and one B. putredinis strains. d Includes seven F. nucleatum and eight F. necrophorum strains. Includes 8 F. mortiferum and 11 F. varium strains. f Based on three strains for which the MICs were within a calculable range. g Includes five C. ramosum, two C. butyricum, three Clostridium sp., and one each C. limosum, C. septicum, C. butyricum, C. bifermentans, C. difficile, C. paraputrificum, C. innocuum, and C. subterminale strains. h Includes four E. lentum, one E. limosum, and five Eubacterium sp. strains. i Includes six P. micros, four P. asaccharolyticus, three P. anaerobius, two P. magnus, and two P. prevotii strains and one anaerobic strain of G. morbillorum. a
Our results show that ofloxacin is moderately active against some anaerobic bacteria, with variable activity against the different species. Most prior studies used a variety of inoculum densities and methods and have not identified many of their anaerobic isolates to species level, especially the B. fragilis group species, thereby giving less than optimal information (2, 4, 8). Our study showed variation in ofloxacin's activity against the B. fragilis group, with most B. fragilis strains being susceptible and Bacteroides distasonis, Bacteroides vulgatus, B. thetaiotaomicron, B. ovatus, and Bacteroides uniformis strains being resistant to ofloxacin. Isolates of the other species and genera were generally susceptible (MIC, .8 ,ug/ml) to ofloxacin. Because of this variability in the susceptibility patterns of anaerobes, it would be prudent to use a second agent, such as metronidazole, with activity against all B. fragilis group species when treating intra-abdominal infections with ofloxacin. No in vitro antagonism was demonstrated with this combination. This is similar to the effect Whiting et al. (12) found with ciprofloxacin and metronidazole. This lack of synergy may be related to the excellent activity of metronidazole against almost all anaerobic bacteria. Some studies have suggested that ofloxacin be used for selective decontamination of the gastrointestinal tract in neutropenic patients (1, 2, 7, 13). Even though ofloxacin exhibited moderate activity against many fecal anaerobic bacteria, several studies have noted that ofloxacin did not alter the anaerobic fecal flora in healthy volunteers (7, 11). This is consistent with our prior findings (3) for another fluoroquinolone (norfloxacin) with a marked inoculum effect against fecal anaerobic bacteria, causing the MIC to be even greater than the level attained in the feces. Edlund et al. (1) suggested an alternate mechanism due to binding of the quinolones to the feces, thereby decreasing the quinolones' effective local activity. van Saene et al. (11) found ofloxacin
to cause less
disturbance to the normal anaerobic bowel flora
(possibly because of the relatively greater activity of ciprofloxacin than of ofloxacin against anaerobes, as well as the lower absorption rate of ciprofloxacin than of ofloxacin), leading to higher fecal antibiotic levels. While the isolates studied were from intra-abdominal sources, some of these anaerobic species, including Prevotella intermedia, Prevotella melaninogenicus, Prevotella bivius, Porphyromonas asaccharolytica, and Peptostreptococcus species, are also causes of female genital tract infection. These isolates were generally susceptible to ofloxacin. This activity against anaerobic bacteria, coupled with the activity against aerobic bacteria, gonococci, and chlamydia, suggests that ofloxacin may be effective in treatment of female genital tract infections. We thank Judee H. Knight, Alice E. Goldstein, Margareta I. Ostovari, and Michael L. Corrado for various forms of assistance. This study was supported, in part, by a grant from the R. W. Johnson Pharmaceutical Research Institute, Raritan, N.J. REFERENCES 1. Edlund, C., L. Lindqvist, and C. E. Nord. 1988. Norfloxacin binds to human fecal material. Antimicrob. Agents Chemother. 32:1869-1874. 2. Fuchs, P. C. 1989. In vitro antimicrobial activity and susceptibility testing of ofloxacin: current status. Am. J. Med. 87(Suppl. 6C):10S-13S. 3. Goldstein, E. J. C., D. M. Citron, and M. L. Corrado. 1987. Effect of inoculum size on in vitro activity of norfloxacin against fecal anaerobic bacteria. Am. J. Med. 82(Suppl. 6B):84-87. 4. Grunberg, R. N., D. Felmingham, M. D. O'Hare, M. J. Robbins, K. Perry, R. A. Wall, and G. L. Ridgway. 1988. The comparative in-vitro activity of ofloxacin. J. Antimicrob. Chemother. 22(Suppl. C):9-19. 5. Holdeman, L. V., E. P. Cato, and W. E. C. Moore (ed.). 1977. Anaerobe laboratory manual, 4th ed. Virginia Polytechnic Institute and State University, Blacksburg. 6. King, A., K. Shannon, and I. Phillips. 1985. The in vitro
NOTES
VOL. 35, 1991
7.
8. 9.
10.
activities of enoxacin and ofloxacin compared with that of ciprofloxacin. J. Antimicrob. Chemother. 15:551-558. Leigh, D. A., B. Walsh, K. Harris, P. Hancock, and G. Travers. 1988. Pharmacokinetics of ofloxacin and the effect on the faecal flora of healthy volunteers. J. Antimicrob. Chemother. 22(Suppl. C):115-125. Monk, J. P., and D. M. Campoli-Richards. 1987. Ofloxacin: a review of its antibacterial activity, pharmacokinetic properties and therapeutic use. Drugs 33:346-391. National Committee for Clinical Laboratory Standards. 1989. Methods for antimicrobial susceptibility testing of anaerobic bacteria, 2nd ed. Tentative standard (M11-T2). National Committee for Clinical Laboratory Standards, Villanova, Pa. Sutter, V. L., D. M. Citron, M. A. C. Edelstein, and S. M. Finegold. 1985. Wadsworth anaerobic bacteriology manual, 4th
2449
ed. Star Publishing Co., Belmont, Calif. van Saene, H. K. F., S. E. B. Lemmens, and J. J. M. van Saene. 1988. Gut decontamination by oral ofloxacin and ciprofloxacin in healthy volunteers. J. Antimicrob. Chemother. 22(Suppl. C):127-134. 12. Whiting, J. L., N. Cheng, and A. W. Chow. 1987. Interactions of ciprofloxacin with cindamycin, metronidazole, cefoxitin, cefotaxime, and mezlocillin against gram-positive and gram-negative anaerobic bacteria. Antimicrob. Agents Chemother. 31:13791382. 13. Winston, D. J., W. G. Ho, D. A. Bruckner, R. P. Gale, and R. E. Champlin. 1990. Ofloxacin versus vancomycin/polymyxin for prevention of infections in granulocytopenic patients. Am. J. Med. 88:36-42. 11.
