The new aminoglycoside antibiotic, amikacin (formerly called BB-K8), was used to treat 12 episodes of urinary tract infection caused by hospital-acquired Proteus rettgeri strains. These bacteria were resistant in vitro to kanamycin and gentamicin, and infection persisted in most of the patients in spite of therapy with one of these agents. In all cases, the urinary tract infection was controlled or eradicated by therapy, although relapse or reinfection was frequently encountered in these patients with complicated urological problems. No toxicities attributable to the drug were encountered in the small group of patients.Amikacin (formerly called BB-K8) is a new gested that a reservoir of infection might exist in the semisynthetic aminoglycoside antibiotic with hospital, epidemiological studies failed to reveal a pharmacological properties similar to those of definite common source for the P. rettgeri organisms. the parent compound, kanamycin (3, 4, 7). The Therapy with amikacin was administered because antibacterial spectrum of amikacin is broader urological surgery was electively sceduled (cases 1, 3, than that of kanamycin, and includes many 4, 9) or because febrile clinical illness was present (the sthains of kanamycin, an .nincues many remaining cases). Most of the patients had received strains of kanamycin-or gentamicin-resistant other antimicrobial therapy without effect on the Enterobacteriaceae and Pseudomonas (2, 4-6, urinary infection before amikacin was started. One 8, 9). Animal studies have indicated that ami-patient (patient 1) received a second course of amikakacin is potentially nephrotoxic and ototoxic cin therapy after a relapse of infection and when an and that it may produce neuromuscular block-additional surgical procedure was required. ade (7).Specimens for culture were collected and processedThe following report summarizes the use of in the diagnostic bacteriology laboratories of the Ben intramuscular amikacin in 11 patients with 12 Taub General Hospital. Pretreatment urine cultures episodes of infection. All of thesepatientsh of all patients with urinary tract infection contained episodes ot infection. A of these patients had greater than 100,000 colonies/ml. Bacteria were idenurinary tract infections caused by a hospital tified by standard bacteriological methods, and disk strain of Proteus rettgeri resistant to kanamycin sensitivity testing was performed by the Bauer-Kirby and gentamicin, and one of the patients was method (1). bacteremic. Patients were carefully monitored The P. rettgeri strains isolated from the patients in for renal, vestibular, and auditory toxicity, and this series were resistant by Bauer-Kirby disk no evidence of toxicity to amikacin was de-susceptibility testing to all antibiotics routinely tected.

Acetohydroxamic acid (AHA) is a potent inhibitor of urease which prevents alkalinization of urine and stone formation in rats in the presence of infection caused by urease-producing bacteria. Because an antibacterial effect of AHA, and synergy between kanamycin and AHA have also been described, we studied the interaction between AHA and 12 antibiotics against 14 gram-negative bacteria. Synergy, sometimes to a striking degree, was found in 17% of interactions; however, antagonism was detected in 5%. Infecting organisms would need to be studied individually before the antibacterial effect of AHA and an antibiotic could be predicted.Acetohydroxamic acid (AHA) has been shown to be an effective inhibitor of bacterial urease in vitro (1, 2, 5, 5b). Administration of AHA to rats greatly reduced the degree of stone formation in urinary infections caused by Proteus mirabilis (5a). These data suggest that AHA may be useful in treating chronic urinary tract infections that are accompanied by urolithiasis.Studies of antibacterial synergy have been prompted by two sets of observations: (i) AHA has bacteriostatic effects against many pathogenic gram-negative bacteria (5b); (ii) synergy between hydroxamic acids and kanamycin for several strains of Proteus has previously been described (5). In the present paper we present data on the interaction between AHA and 12 commonly used antibiotics against 14 pathogenic gram-negative bacteria.MATERIALS AND METHODS Organisms. Fourteen gram-negative pathogenic bacteria that had been isolated from patients with urinary tract infections were selected from the Diagnostic Microbiology Laboratory, V.A. Hospital, Houston. These included the following: five strains of Proteus (two of morganii and one each of mi-abilis, rettgeri, and vulgaris