In four patients with alkaline-encrusted cystitis, Corynebacterium group D2 was isolated from consecutive urine cultures and stones. Encrusted cystitis occurred in bladders harboring inflammatory or tumorous lesions in patients with chronic or recurrent urinary tract infections appearing after surgery or instrumentation. The urease activity of Corynebacterium group D2 and the neutralization of this enzyme by acetohydroxamic acid are shown. Clinical improvement, disappearance of struvite crystals, and decrease of the urine pH were obtained when these bacteria were eliminated from urine samples. Corynebacterium group D2 strains were highly resistant to many antimicrobial agents but were highly susceptible to norfloxacin and vancomycin when tested at two pHs (7.4 and 8.5).
The minimum dosage of antibiotics that reduced mortality in bacteraemic rats inoculated with two different Escherichia coli isolates was determined in an attempt to study the therapeutic importance of the inoculum effect. Low mortality rates (0-5%) at 48 h were obtained when antibiotics with minimal or no inoculum effect (ampicillin, cefuroxime, cefoxitin and gentamicin) were administered to yield serum levels 5 to 14 times the MIC, while antibiotics with a pronounced inoculum effect (piperacillin, cefotaxime and aztreonam) had to be administered to yield serum levels 57 to more than 1000 times the MIC determined with a standard (low) inoculum. All of the antibiotics with inoculum effect studied here are administered empirically in clinical practice at a higher dose than the microbiological and pharmacokinetic data would indicate (in order to reach peak serum concentrations exceeding the MICs of the pathogens by 4-10 times). Our experiment suggests that such high and empirical doses of antibiotics with inoculum effect may be justified.
The susceptibility in vitro of 28 Corynebacterium group D2 strains, mainly isolated from urine, to fifteen antimicrobial agents and acetohydroxamic acid (AHA) was determined at two pH values. The bactericidal activity of four antimicrobials and AHA was studied in three reference strains in broth at two pHs and with two inoculum sizes. The activity of norfloxacin and AHA, against one selected strain, in broth and human urine, was also determined. Vancomycin, ofloxacin and norfloxacin were the most active agents tested. Norfloxacin acted bactericidally in broth and in human urine but was not synergic with AHA.
The in vitro susceptibility of 30 Corynebacterium group D2 strains to nine antimicrobial agents was determined. Vancomycin and norfloxacin were the most active agents tested. All strains were resistant to ampicillin and cephalothin, all except one were resistant to gentamicin, and the activity of erythromycin, novobiocin, tetracycline, and rifampin varied.
Corynebacterium group D2 inoculated into normal human urine formed struvite crystals and an increase in pH and ammonium concentration after 24 h of incubation. Zinc disks dipped into a broth culture of this microorganism and inserted into the bladders of rats produced stones with a mean weight of 12.5 mg (ranging from 1 to 57.7 mg) after 12 days. Analysis of the infrared spectrum determined the stones to be composed of struvite. From these results its seems that stone formation by Corynebacterium group D2 may be possible both in vitro and in vivo, which may confirm a previous report involving these bacteria in human clinical encrusted cystitis.
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