THE JOURNAL OF INFECTIOUS DISEASES • VOL. 134, SUPPLEMENT © 1976 by the University of Chicago. All rights reserved.
• AUGUST 1976
Comparison of Tobramycin and Gentamicin in the Treatment of Complicated Urinary Tract Infections From the Urology Section, Veterans Administration Hospital, and the Department of Surgery, University of Wisconsin School of Medicine, Madison, Wisconsin
PaulO. Madsen, Torben B. Kjaer, and Aage Mosegaard
Tobramycin is a new aminoglycoside antibiotic derived from the antibiotic complex nebramycin, which is produced by Streptomyces tenebrarius. Of the eight known active factors of nebramycin, tobramycin (factor 6) is the most active [1, 2]. The antibacterial activity of tobramycin is directed mainly against gram-negative organisms (especially Pseudomonas aeruginosa, indolepositive strains of Proteus, and Enterobacteriaceae) and Staphylococcus aureus [3-5]. The level of activity of tobramycin against gramnegative organisms, as measured by MIC, is approximately one and one-half to two times lower than that of gentamicin; the one exception is P. aeruginosa, against which tobramycin is two to five times more effective than gentamicin. In experiments with animals, tobramycin seems to be less toxic than gentamicin and neomycin [5, 6]. The efficacy and safety of tobramycin in the treatment of urinary tract infections in patients with impaired renal function have been supported in several publications [7, 8]. Please address requests for reprints to Dr. PaulO. Madsen, Urology Service, Veterans Administration Hospital, 2500 Overlook Terrace, Madison, Wisconsin 53705.
S150
In the present study, the safety and efficacy of two similar aminoglycoside antibiotics, tobramycin and gentamicin, were compared in the treatment of complicated urinary tract infections in a population of elderly male patients.
Materials and Methods
Seventy-five male patients (average age, 71 years) with complicated urinary .tract infections (due to obstruction of the lower urinary tract from benign hyperplasia, cancer of the prostate, or urethral strictures) were treated with tobramycin or gentamicin in a prospective, randomized study. The patients received 1 mg of drug/kg of body weight im every 8 hr for seven days. All patients had relatively normal renal function, as evidenced by a serum creatinine level of ::::; 1.5 mg/ 100 ml and/or a blood urea nitrogen level of :::;;:25 mg/ 100 rnl. The two groups of patients were comparable in terms of infecting microorganisms (table 1) and the pathology of the urinary tract. No patients had indwelling catheters. All microorganisms isolated from the urine were susceptible to gentamicin and tobramycin by the disk diffusion method using a 10-flg disk [9]. A zone of inhibi-
Downloaded from http://jid.oxfordjournals.org/ at University of Lethbridge on September 9, 2015
The efficacy and safety of intramuscular administration of either of the two aminoglycoside antibiotics tobramycin and gentamicin every 8 hr for seven days were compared in a prospective, randomized study of 75 elderly male patients with complicated urinary tract infections. All bacteria were sensitive to both antibiotics by the disk diffusion method. The two groups of patients (each receiving one of the two drugs) were comparable in terms of infecting microorganisms and underlying pathology of the urinary tract (mostly prostatic hyperplasia or carcinoma and urethral strictures). No patients had indwelling catheters. All patients had normal renal function (serum creatinine, :::;;: 1.5 mg/ 100 ml and/ or blood urea nitrogen, :::;;:25 mg/ 100 ml): In both groups 64% of the patients were cured of the infection, with cure defined as a negative urine culture result seven days after discontinuation of therapy. A statistically but not clinically significant increase in the level of serum creatinine in both groups of patients was noted after treatment.
Comparison of Tobramycin and Gentamicin
S151
Table 1. Distribution of bacteria isolated from urine of patients with complicated urinary tract infection who were treated with tobramycin or gentamicin.
Gentamicin (n 37)
=
Tobramycin (n=38)*
16
19
Escherichia Klebsiella-Enterobacter Proteus Pseudomonas Staphylococcus
without
5
5
6 7 3
4 7
5
organisms.
tion of ~ 14 mm was considered to be evidence of susceptibility. Urine cultures with colony counts were done before treatment, on the third and seventh day of treatment, and one week after discontinuation of treatment. Specimens of urine were collected by the midstream clean-catch technique. Complete blood counts, blood urea nitrogen levels, and serum creatinine levels were determined within 48 hr before initiation of treatment and again on the last day of treatment. The therapeutic results were defined according to the urine culture results as follows: cure, negative culture one week after treatment; persistence, > 10 5 colonies of the original organisms/rnl of urine during treatment; relapse, negative culture during therapy and > 10 5 colonies of the original organism/rnl of urine one week after therapy; reinfection, > 10 5 colonies of an organism different from that originally isolated/ml of urine one week after therapy; and superinfection, > 10 5 colonies of a different organism/ml of urine during therapy. Microorganisms were identified
Both antibiotics were well tolerated by all patients; there were no detectable adverse clinical reactions. The bacteriological results are presented in table 2. In our patients the therapeutic results would be expected to be poor. Both antibiotics, however, cleared practically all urine cultures of infecting bacteria, and about two-thirds of the patients in both groups were cured by our criterion. The effect of the two drugs on renal function is outlined in table 3. A statistically but not clinically significant increase was noted in the serum creatinine values after tobramycin treatment and Table 2. Results of treatment of complicated urinary tract infections with 1 mg of gentamicin (37 patients) or tobramycin (38 patients)/kg of body weight im every 8 hr for seven days. No. of patients with
Time of culture, therapy
Negative culture
Relapse or persistence
Reinfection or superinfection
(% )
(% )
(% )
Day 3 of treatment Gentamicin Tobramycin
86 95
a
8
6 5
End of therapy Gentamicin Tobramycin
89 89
5.5 3
5.5 8
One week after therapy Gentamicin Tobramycin
64 64
19 17
17 19
Table 3. Blood urea nitrogen (BUN) and serum creatinine values before and after treatment of patients with 1 mg of gentamicin (n = 36) or tobramycin (n = 36)jkg of body weight im every 8 hr for seven days. BUN value Drug
Before
Creatinine value After
Before
After
Tobramycin
17.1 ± 1.0 (9-27)
17.3 ± 1.2 (9-33)
1.20 ± 0.04 (0.9-1.9)
1.26 ± 0.05 (0.8-2.1 )
Gentamicin
16.6 ± 0.6 (9-22)
19.9 ± 1.3 (11-33 )
1.17 ± 0.04 (0.6-1.7)
1.30 ± 0.05 (0.6-2.1)
NOTE. Values given are mean ± SE (range) number of mg/IOO rnl. The change in BUN value from before treatment to after treatment was not significant for tobramycin but was significant for gentamicin (P
• AUGUST 1976
Comparison of Tobramycin and Gentamicin in the Treatment of Complicated Urinary Tract Infections From the Urology Section, Veterans Administration Hospital, and the Department of Surgery, University of Wisconsin School of Medicine, Madison, Wisconsin
PaulO. Madsen, Torben B. Kjaer, and Aage Mosegaard
Tobramycin is a new aminoglycoside antibiotic derived from the antibiotic complex nebramycin, which is produced by Streptomyces tenebrarius. Of the eight known active factors of nebramycin, tobramycin (factor 6) is the most active [1, 2]. The antibacterial activity of tobramycin is directed mainly against gram-negative organisms (especially Pseudomonas aeruginosa, indolepositive strains of Proteus, and Enterobacteriaceae) and Staphylococcus aureus [3-5]. The level of activity of tobramycin against gramnegative organisms, as measured by MIC, is approximately one and one-half to two times lower than that of gentamicin; the one exception is P. aeruginosa, against which tobramycin is two to five times more effective than gentamicin. In experiments with animals, tobramycin seems to be less toxic than gentamicin and neomycin [5, 6]. The efficacy and safety of tobramycin in the treatment of urinary tract infections in patients with impaired renal function have been supported in several publications [7, 8]. Please address requests for reprints to Dr. PaulO. Madsen, Urology Service, Veterans Administration Hospital, 2500 Overlook Terrace, Madison, Wisconsin 53705.
S150
In the present study, the safety and efficacy of two similar aminoglycoside antibiotics, tobramycin and gentamicin, were compared in the treatment of complicated urinary tract infections in a population of elderly male patients.
Materials and Methods
Seventy-five male patients (average age, 71 years) with complicated urinary .tract infections (due to obstruction of the lower urinary tract from benign hyperplasia, cancer of the prostate, or urethral strictures) were treated with tobramycin or gentamicin in a prospective, randomized study. The patients received 1 mg of drug/kg of body weight im every 8 hr for seven days. All patients had relatively normal renal function, as evidenced by a serum creatinine level of ::::; 1.5 mg/ 100 ml and/or a blood urea nitrogen level of :::;;:25 mg/ 100 rnl. The two groups of patients were comparable in terms of infecting microorganisms (table 1) and the pathology of the urinary tract. No patients had indwelling catheters. All microorganisms isolated from the urine were susceptible to gentamicin and tobramycin by the disk diffusion method using a 10-flg disk [9]. A zone of inhibi-
Downloaded from http://jid.oxfordjournals.org/ at University of Lethbridge on September 9, 2015
The efficacy and safety of intramuscular administration of either of the two aminoglycoside antibiotics tobramycin and gentamicin every 8 hr for seven days were compared in a prospective, randomized study of 75 elderly male patients with complicated urinary tract infections. All bacteria were sensitive to both antibiotics by the disk diffusion method. The two groups of patients (each receiving one of the two drugs) were comparable in terms of infecting microorganisms and underlying pathology of the urinary tract (mostly prostatic hyperplasia or carcinoma and urethral strictures). No patients had indwelling catheters. All patients had normal renal function (serum creatinine, :::;;: 1.5 mg/ 100 ml and/ or blood urea nitrogen, :::;;:25 mg/ 100 ml): In both groups 64% of the patients were cured of the infection, with cure defined as a negative urine culture result seven days after discontinuation of therapy. A statistically but not clinically significant increase in the level of serum creatinine in both groups of patients was noted after treatment.
Comparison of Tobramycin and Gentamicin
S151
Table 1. Distribution of bacteria isolated from urine of patients with complicated urinary tract infection who were treated with tobramycin or gentamicin.
Gentamicin (n 37)
=
Tobramycin (n=38)*
16
19
Escherichia Klebsiella-Enterobacter Proteus Pseudomonas Staphylococcus
without
5
5
6 7 3
4 7
5
organisms.
tion of ~ 14 mm was considered to be evidence of susceptibility. Urine cultures with colony counts were done before treatment, on the third and seventh day of treatment, and one week after discontinuation of treatment. Specimens of urine were collected by the midstream clean-catch technique. Complete blood counts, blood urea nitrogen levels, and serum creatinine levels were determined within 48 hr before initiation of treatment and again on the last day of treatment. The therapeutic results were defined according to the urine culture results as follows: cure, negative culture one week after treatment; persistence, > 10 5 colonies of the original organisms/rnl of urine during treatment; relapse, negative culture during therapy and > 10 5 colonies of the original organism/rnl of urine one week after therapy; reinfection, > 10 5 colonies of an organism different from that originally isolated/ml of urine one week after therapy; and superinfection, > 10 5 colonies of a different organism/ml of urine during therapy. Microorganisms were identified
Both antibiotics were well tolerated by all patients; there were no detectable adverse clinical reactions. The bacteriological results are presented in table 2. In our patients the therapeutic results would be expected to be poor. Both antibiotics, however, cleared practically all urine cultures of infecting bacteria, and about two-thirds of the patients in both groups were cured by our criterion. The effect of the two drugs on renal function is outlined in table 3. A statistically but not clinically significant increase was noted in the serum creatinine values after tobramycin treatment and Table 2. Results of treatment of complicated urinary tract infections with 1 mg of gentamicin (37 patients) or tobramycin (38 patients)/kg of body weight im every 8 hr for seven days. No. of patients with
Time of culture, therapy
Negative culture
Relapse or persistence
Reinfection or superinfection
(% )
(% )
(% )
Day 3 of treatment Gentamicin Tobramycin
86 95
a
8
6 5
End of therapy Gentamicin Tobramycin
89 89
5.5 3
5.5 8
One week after therapy Gentamicin Tobramycin
64 64
19 17
17 19
Table 3. Blood urea nitrogen (BUN) and serum creatinine values before and after treatment of patients with 1 mg of gentamicin (n = 36) or tobramycin (n = 36)jkg of body weight im every 8 hr for seven days. BUN value Drug
Before
Creatinine value After
Before
After
Tobramycin
17.1 ± 1.0 (9-27)
17.3 ± 1.2 (9-33)
1.20 ± 0.04 (0.9-1.9)
1.26 ± 0.05 (0.8-2.1 )
Gentamicin
16.6 ± 0.6 (9-22)
19.9 ± 1.3 (11-33 )
1.17 ± 0.04 (0.6-1.7)
1.30 ± 0.05 (0.6-2.1)
NOTE. Values given are mean ± SE (range) number of mg/IOO rnl. The change in BUN value from before treatment to after treatment was not significant for tobramycin but was significant for gentamicin (P
