SIGNIFICANCE OF BETA-LACTAMASE ON POLYMICROBIAL URINARY TRACT INFECTION

Abstract

Clinical efficacies of 15 antimicrobial agents, ampicillin, carbenicillin, carindacillin, piperacillin, cefazolin, cefoxitin, cefmetazole, cefamandole, ceftizoxime, cefotaxime, cefinenoxime, latamoxef, gentamicin, amikacin and pipemidic acid on 2218 patients with complicated urinary tract infections were studied. All patients had pyuria of 5 or more WBCs per hpf, bacteriuria of 10⁴ or more bacteria per ml of urine and underlying urinary disease.
Overall clinical efficacy of the treatment was evaluated by the criteria proposed by the UTI Committee in Japan as excellent, moderate or poor based on the combination of changes in pyuria and bacteriuria. Excellent plus moderate responses were obtained in 53.2% of the 1597 patients with monomicrobial infections and in 36.9% of the 621 patients with polymicrobial infections. This difference was statistically significant. The difference of clinical efficacies between patients with monomicrobial infections and those with polymicrobial infections was especially significant in patients treated with penicillins and cephems of the first generation.
Bacteriological responses to the treatment were determined in sensitive, intermediate and resistant groups. Bacteriological response was defined as eradicated if bacteria identical to the original strain were not isolated after treatment, and as persisted if bacteria identical to the original strain were isolated after treatment regardless of bacterial count. Bacterial eradication rate of penicillin sensitive strains(MIC:≤12.5μg/ml) was significantly lower in patients with polymicrobial infections than in those with monomicrobial infections. But no significant differences were observed between patients with monomicrobial and polymicrobial infections treated with the other antibiotics in the bacterial eradication rates.
The responses to antibiotics of single and mixed culture of Escherichia coli and β-lactamase producing Staphylococcus epidermidis were studied in an in vitro system by use of biophotometer. When ampicillin was added to achieve a concentration of 25μg per ml (4 MIC for both strains), rapid lysis of E. coli and delayed lysis of S. epidermidis occurred, growth of both organismus was suppressed for the whole 24 hour period of observation. When the mixture of the two organismus was exposed to a similar concentration of ampicillin, rapid lysis was again observed, but growth resumed after several hours. The MIC of both organismus which were fully grown in the broth were determined again, but the susceptibility of the organismus to ampicillin was not different from that of the original strains, and it was observed that the concentration of ampicillin was rapidly reduced in the broth of the mixture. When the mixture of the two organismus was exposed to amoxicillin, similar results were obtained. But when the mixture was exposed to cefotaxime or ampicillin with clavulanic acid, growth of both organismus was suppressed throughout the 24 hour period of observation.
In conclusion, β-lactamase production by another organismus in the mixture, was considered one possible reason why fully susceptible bacteria, which would normally be eradicated when present as the single infecting organism, frequently persisted when present in mixed infection.