1023
Comparison of Bactericidal Activity of Five Antibiotics against Staphylococcus aureus Roger Baxter, John Chapman, and W. L. Drew
From Mount Zion Hospital and Medical Center, San Francisco. California
Osteomyelitis requires antibiotic therapy for an extended period, usually 4-6 weeks. An increasing number of patients with this disease are being treated as outpatients, using oral antibiotics. Several investigators have documented good success with various oral medications, but the literature lacks controlled comparisons of different oral antibiotics [1-5]. Serum bactericidal tests have been used as a measure of ongoing therapeutic efficacy for many years [6]. Their use is controversial in the management of the individual patient, and there are many problems in standardizing the test [7], but it is considered by many to be a useful prognostic indicator in endocarditis and osteomyelitis [8, 9]. The purpose of this study was to determine the relative serum bactericidal titer of five commonly used oral antibiotics against Staphylococcus aureus, the most common cause of osteomyelitis.
Subjects and Methods The 10volunteers were healthy men and women aged 25-62 years who had not taken antibiotics for at least I month. The antibiotics tested and doses used were dicloxacillin (Lederle Laboratories, Wayne, NJ), 1 g every 6 h; cephalexin (Keflex; Eli Lilly, Indianapolis), 1 g every 6 h; trimethoprim/sulfamethoxazole (TMP/SMZ, Bactrim; Roche Laboratories, Nutley NJ), I double strength (160 mg TMP and 800 mg SMZ) every 6 h; ciprofloxacin (Cipro; Miles, West Haven, CT), 750
Received 28 September 1989; revised 4 December 1989. Grant support: Miles Pharmaceuticals (West Haven, CT) and Upjohn (Kalamazoo, MI). All Volunteers signed a statement of informed consent, approved by the hospital institutional review board. Reprints and correspondence: Dr. Roger Baxter, Kaiser Permanente Medical Center, 280 W. MacArthur Blvd., Oakland, CA 94611. The Journal of Infectious Diseases 1990;161:1023-1025 © 1990 by The University of Chicago. All rights reserved. 0022-1899/90/6105-0036$01.00
mg every 12 h; and clindamycin (Cleocin; Upjohn, Kalamazoo, MI), 600 mg every 8 h. Patients were instructed to take medications on an empty stomach. Trough blood sampling was done 15-30 min before dose 5. Peak sampling was done 1 h after dose 5. The interval between antibiotic regimens was ~1 week. Laboratory Methods. Two clinical blood isolates of S. aureus were used. Both strains were sensitive by Kirby-Bauer disk diffusion testing to all antibiotics used in this study. One strain was sensitive to erythromycin and the other was resistant; both strains were resistant to penicillin and ampicillin and sensitive to oxacillin and tetracycline. Serum bactericidal titers (SBT) were determined using the microdilution method as described by Stratton and Reller [10-12], with dilution performed with a 50:50 ratio of pooled human serum and calcium- and magnesium-supplemented Mueller-Hinton broth. The bactericidal end point was defined as ~99.9% killing of the inoculum. All tests were performed in triplicate. The laboratory technician was blinded to the samples. Analysis. Statistical analysis was performed using repeated-measures analysis of variance and the Bonferroni test.
Results Mean peak SBT ranged from I :8.8 for cephalexin to
Comparison of Bactericidal Activity of Five Antibiotics against Staphylococcus aureus Roger Baxter, John Chapman, and W. L. Drew
From Mount Zion Hospital and Medical Center, San Francisco. California
Osteomyelitis requires antibiotic therapy for an extended period, usually 4-6 weeks. An increasing number of patients with this disease are being treated as outpatients, using oral antibiotics. Several investigators have documented good success with various oral medications, but the literature lacks controlled comparisons of different oral antibiotics [1-5]. Serum bactericidal tests have been used as a measure of ongoing therapeutic efficacy for many years [6]. Their use is controversial in the management of the individual patient, and there are many problems in standardizing the test [7], but it is considered by many to be a useful prognostic indicator in endocarditis and osteomyelitis [8, 9]. The purpose of this study was to determine the relative serum bactericidal titer of five commonly used oral antibiotics against Staphylococcus aureus, the most common cause of osteomyelitis.
Subjects and Methods The 10volunteers were healthy men and women aged 25-62 years who had not taken antibiotics for at least I month. The antibiotics tested and doses used were dicloxacillin (Lederle Laboratories, Wayne, NJ), 1 g every 6 h; cephalexin (Keflex; Eli Lilly, Indianapolis), 1 g every 6 h; trimethoprim/sulfamethoxazole (TMP/SMZ, Bactrim; Roche Laboratories, Nutley NJ), I double strength (160 mg TMP and 800 mg SMZ) every 6 h; ciprofloxacin (Cipro; Miles, West Haven, CT), 750
Received 28 September 1989; revised 4 December 1989. Grant support: Miles Pharmaceuticals (West Haven, CT) and Upjohn (Kalamazoo, MI). All Volunteers signed a statement of informed consent, approved by the hospital institutional review board. Reprints and correspondence: Dr. Roger Baxter, Kaiser Permanente Medical Center, 280 W. MacArthur Blvd., Oakland, CA 94611. The Journal of Infectious Diseases 1990;161:1023-1025 © 1990 by The University of Chicago. All rights reserved. 0022-1899/90/6105-0036$01.00
mg every 12 h; and clindamycin (Cleocin; Upjohn, Kalamazoo, MI), 600 mg every 8 h. Patients were instructed to take medications on an empty stomach. Trough blood sampling was done 15-30 min before dose 5. Peak sampling was done 1 h after dose 5. The interval between antibiotic regimens was ~1 week. Laboratory Methods. Two clinical blood isolates of S. aureus were used. Both strains were sensitive by Kirby-Bauer disk diffusion testing to all antibiotics used in this study. One strain was sensitive to erythromycin and the other was resistant; both strains were resistant to penicillin and ampicillin and sensitive to oxacillin and tetracycline. Serum bactericidal titers (SBT) were determined using the microdilution method as described by Stratton and Reller [10-12], with dilution performed with a 50:50 ratio of pooled human serum and calcium- and magnesium-supplemented Mueller-Hinton broth. The bactericidal end point was defined as ~99.9% killing of the inoculum. All tests were performed in triplicate. The laboratory technician was blinded to the samples. Analysis. Statistical analysis was performed using repeated-measures analysis of variance and the Bonferroni test.
Results Mean peak SBT ranged from I :8.8 for cephalexin to
