Kinetics and dynamics of tobramycin action in patients with bacteriuria given single doses

Abstract

We studied the effect of a single intravenous dose of tobramycin on the rate of bacterial eradication from urine in 10 patients with bladder catheters. The catheter was replaced 4 to 6 h after the tobramycin dose. Pseudomonas aeruginosa was found in 7 of the 10 patients, while members of the family Enterobacteriaceae accounted for the remaining pathogens. The MIC for each bacterium was determined in both broth and urine. Tobramycin eradicated the bacteria from eight patients. Bacteriuria resolved in 21.8 18.0 h, and urine bactericidal activity persisted for 43.4 20.3 h after the dose of tobramycin. Most patients were recolonized by another bacterial species if use of Foley catheters was resumed on a continuous basis. Two patients required additional doses of tobramycin to eradicate the original pathogen. There were significant temporal relationships between the pharmacokinetics of tobramycin and the change in colony count of bacteria in urine.Urinary tract infections occur frequently in hospitalized patients with indwelling urinary catheters (14). A variety of approaches have been advocated for the management of such patients, including changing of the catheter and the administration of systemic antimicrobial agents for various lengths of time (3,4,7,14,17). Tobramycin is bactericidal against the majority of gram-negative bacilli, which are the pathogens most frequently encountered in urinary tract infections (9, 14). In addition, tobramycin exhibits a postantibiotic effect (PAE) against gram-negative bacilli, in which the bacteria remain inhibited for a substantial period of time following removal of tobramycin from the media in vitro (1, 2).The objectives of this study were (i) to determine the MICs and MBCs of tobramycin in urine against the isolated pathogens, (ii) to compare the relative activity of tobramycin in urine and broth, (iii) to determine the tobramycin concentration-time profile in serum and urine following a single dose of tobramycin, (iv) to assess the rate of bacterial eradication in urine following a single dose of tobramycin, and (v) to determine the presence of an in vivo PAE by measuring serial changes in bacterial colony counts in urine. MATERIALS AND METHODSPatients with short-term (less than 30 days) indwelling urinary catheters were eligible for participation in the study. Written informed consent was obtained from the patient or next of kin. Cultures of urine were aspirated from the port at the distal end of the indwelling catheter after the port surface was cleansed with an alcohol swab. In all patients, two or more consecutive cultures were positive for greater than 100,000 CFU of tobramycin-susceptible, gram-negative bacilli per ml within 48 h of entry into the study. Patients were specifically included when they were febrile, their urinalyses revealed numerous leukocytes, or culture of their urine grew * Corresponding author. t Present address:

European and Asian guidelines on management and prevention of catheter-associated urinary tract infections

“…Chronic antibiotic suppressive therapy is not effective and generally not recommended (A). Catheterised urine cannot be permanently sterilised [11,16,17,102,105,106] (IIa, III).…”