THE JOURNAL OF INFECTIOUS DISEASES • VOL. 134, SUPPLEMENT © 1976 by the University of Chicago. All rights reserved.



AUGUST 1976

CLINICAL STUDIES: URINARY TRACT INFECTIONS Clinical Evaluation of Tobramycin in Urinary Tract Infections P. Altucci, G. F. Abbate, A. Gattoni, and V. Leonessa

From the First Faculty of Medicine, Institute of Medical Clinic, Naples University, Naples, Italy

Our previous results [1, 2], in agreement with those of Catalano et al. [3], have documented the high activity of tobramycin, the new aminoglycoside antibiotic produced by Streptomyces tenebrarius and formerly called nebramycin factor 6, in urinary tract infections for the most part due to coliform gram-negative bacilli and Pseudomonas; these results were obtained with use of a standard dosage of 50-100 mg three times daily (1.5-4 mg /kg ). Larger single doses of tobramycin have been reported to yield more effective serum concentrations of the drug than smaller doses given three times daily, and these concentrations are detectable for longer periods (8-12 hr after administration) [4]. Because of these findings and the greater convenience of a dosage regimen of two daily administrations of the drug, we have given two injections of tobramycin per day to patients in these clinical trials. Materials and Methods

Twenty-one patients were treated im with 80120 mg of tobramycin per day in two doses 12 hr apart (1.5-3 rug/kg per day) for seven to 15 days. The patients, whose ages ranged from 32 to 71 years, were affected by acute, asymptomatic, or chronic infections caused by gram-negative bacilli (table 1). The susceptibility of bacteria Please address requests for reprints to Prof. P. Altucci, First Faculty of Medicine, Institute of Medical Clinic, University of Naples, Piazza Miraglia, Naples, Italy.

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to tobramycin was tested through determination of MICs by the tube-dilution method. The evaluation of the therapeutic effect was based not only on clinical improvement or cure but also on the elimination or significant reduction of bacterial flora at the end of treatment; initial bacterial counts were generally at least 10 6 organisms/rnl. Urine cultures were also performed during therapy (days 2-5) and early after (days 12-15) and late after (day 15 and later) therapy. Hematologic studies, tests of hepatic and renal function, and urinalyses were performed before, during, and after treatment. All patients were closely observed for evidence of auditory or vestibular dysfunction. Results

Results of treatment with tobramycin are summarized in table 1; the infecting organisms, clinical diagnoses, and susceptibilities of the isolates to tobramycin are also specified. Fourteen of the 21 patients (67 % ) were cured, one patient improved, and three patients (14 % ) were treatment failures. Among these three patients, one had evidence of obstructive lesions, and two had evidence of bacteriologically active pyelonephritis without renal failure. At the end of treatment, three additional patients (14%) showed a substitution of the original pathogen by another organism, i.e., hemolytic Staphylococcus, which was less susceptible to tobramycin. Each of the patients also had diabetes with multiple vascular lesions. The dynamics of urine culture results in pa-

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Twenty-one patients with urinary tract infections due to Pseudomonas and coliform bacilli were treated with 80-120 mg of tobramycin per day in two daily doses. Of these patients, 14 (67%) were cured, one improved, three (14%) showed no improvement, and three (14%) showed a substitution of the original pathogen by another organism. Urine cultures demonstrated rapid sterilization in the cases in which patients responded well, and long-term sterility persisted in at least 50% of the subjects.

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Table 1.

Altucci et al.

Results of treatment with tobramycin of urinary tract infections in 21 patients. Clinical and bacteriological result t Duration of treatment (days)

Cure

Substitution by Improve- other ment pathogen Failure

(ug /rnl )

Pseudomonas (5)

Chronic urinary tract infection; pyelonephritis

0.::!5-4

1.7-3.0

7-tO

4

Indole-positive Proteus (4)

Acute or chronic urinary tract infection

0.50-4

1.7-3.0

10-12

3

0

0

Escherichia coli (10)

Acute or chronic urinary tract infection; pyelonephritis

0.25-4

1.5-3.0

7-15

6

0

2

Other coliform bacillit (2) Total (21)

Chronic urinary tract infection; pyelonephritis

0.50-4

1.8-3.0

8-11

Infecti ng agent (no. of cases)

MIC

0

1(5)

2

0

0

14(67)

0

3(14 )

3(14)

* Tobramycin was given in two daily doses. t Results are expressed as the number of cases (percentage). A patient was considered improved if the bacterial count was reduced to 10-tOo! organisms/ml, with clinical cure. The other pathogen involved in substitution was hemolytic Staphylococcus (1.5 X l O! organisms/ml); the patients infected with this organism were cured clinically. t Citrobacter or Enterobacter,

tients treated with tobramycin are shown in figure 1. Relatively rapid sterilization occurred in the cases responding well and promptly, whereas new pathogens were seen at about the time that therapy was stopped in patients who relapsed with infections due to different microorganisms. Figure 2 shows some peculiarities of the cases of urinary tract infection treated with tobramycin: the resistance of agents to other antibiotics (from a minimum of three to a maximum of eight), the number of preceding unsuccessful treatments (from two to five), and the results of long-term urine cultures. It is noteworthy that sterility persisted in 50% of cases (mainly acute uncomplicated infections), while 15 % had relapses with the same pathogen and 35 % were rein•_ _• cases respon

Clinical evaluation of tobramycin in urinary tract infections.

THE JOURNAL OF INFECTIOUS DISEASES • VOL. 134, SUPPLEMENT © 1976 by the University of Chicago. All rights reserved. • AUGUST 1976 CLINICAL STUDIES:...
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