Treatment of encrusted cystitis caused by Corynebacterium group D2 with norfloxacin, ciprofloxacin, and teicoplanin in an experimental model in rats

Abstract

Oral doses of norfloxacin (80 mg/kg of body weight per day) and ciprofloxacin (25 and 80 mg/kg/day) and intramuscular doses of teicoplanin (5 mg/kg/day), all administered once a day for 10 days, were evaluated as a means of preventing encrusted cystitis caused by Corynebacterium group D2. Zinc disks dipped into a 24-h broth culture of these microorganisms were inserted into the bladders of female Wistar rats, and treatment was started 14 days after bacterial challenge. The appearanee of encrusted cystitis was directly related to a documented urinary tract infection by these coryneforms (71.7 and 0% for rats with positive and negative urine cultures, respectively). All rats that died between days 18 to 43 after bacterial challenge presented very severe encrusted cystitis, which was prevented by teicoplanin and high doses of ciprofloxacin. Rats surviving up to day 44 after bacterial challenge were sacrificed; they presented a lower incidence of encrusted cystitis which was also less severe, with teicoplanin and a high dose of ciprofloxacin being more active in reducing the rate of positive cultures (78.8 and 65.7% reduction, respectively). All antibiotics and doses used were active in vivo at preventing encrusted cystitis by Corynebacterium group D2, but the best therapeutic effect was obtained with teicoplanin.Corynebacterium group D2 (CGD2) was involved in cases of human encrusted cystitis in 1985 (16). Since then, several other cases of this disease have been reported (4, 12, 13); the infections were described as severe and very difficult to treat. Such difficulty is mainly due to the underlying conditions suffered by the patients, the multiple antibiotic resistance of CGD2, and the presence of foreign bodies within the bladder, such as indwelling catheters and struvite (ammonium magnesium phosphate) stones induced by the high levels of urease produced by CGD2 (14). Most infections have been treated with antibiotics active in vitro against the pathogen and with the endoscopic resection of the stones encrusted in the bladder mucosa (13,16).Although the in vitro susceptibility of CGD2 is well known (1,5,10,19), there are neither human nor animal controlled therapeutic trials using different antibiotics for treating encrusted cystitis caused by this microorganism. The aim of this study was to evaluate the in vivo activity of three antimicrobial agents active in vitro against CGD2 in an experimental model of encrusted cystitis in rats.( Animal model. Female Wistar rats weighing 180 to 200 g were used in all experiments. Rats were anesthetized with ether, the abdomen hair was shaved, and then the abdominal wall was thoroughly swabbed with povidone iodine. A small suprapubic incision was made at the abdominal wall, the bladder was exposed and opened, and a 6-mm-diameter zinc disk that had been dipped into a 24-h broth culture of CGD2 was immediately inserted. Disks treated in this fashion carried ca. 105 microorganisms each. A polypropylene suture (6-0 Surgilene) was used to close the incision of the bladder, and a s...

Microbiological and clinical features of Corynebacterium urealyticum: urinary tract stones and genomics as the Rosetta Stone

“…Strong adherence to uroepithelial cells has been demonstrated [27], and in bladder biopsies the organism has been seen completely embedded within the mucosa [5,8]. C. urealyticum could also reach the renal pelvis through a nephrostomy catheter [7] or by an ascendant route [66].…”

“…The urease leads to hyperammoniuria and alkalinization of the urine, which causes hypersaturation with struvite and calcium phosphate with consequent crystallization of struvite and apatite. These types of urinary stone have been experimentally reproduced in vitro [67,68] and in vivo [66,67]. In the same experimental model, it was shown that bladder instillation of C. urealyticum can produce both encrusted cystitis and pyelitis [66].…”

The lifestyle of Corynebacterium urealyticum derived from its complete genome sequence established by pyrosequencing

“…Encrusted cystitis may require endoscopic resectioning of encrustations and antibiotic therapy for permanent cure (Funke et al, 1997;van Hooland et al, 2005). The majority of C. urealyticum strains are, however, highly resistant to a large number of antibiotics, including ␤-lactams, aminoglycosides, and macrolides (García-Rodriguez et al, 1991;Soriano et al, 1995;Martínez-Martínez et al, 1998), although the glycopeptides vancomycin and teicoplanin remain universally active against these isolates (Soriano et al, 1991(Soriano et al, , 1998Lagrou et al, 1998). It has been suggested that the appearance of multiresistant C. urealyticum strains is favored by the use of antibiotics in hospital settings and that these strains are likely to be acquired by inpatients directly from the bacterial flora present in the hospital environment (Garcia-Bravo et al, 1996).…”

Successful treatment of encrusted cystitis: A case report and review of literature

“…As the calcification contains a large number of bacteria and limits the role of antibiotics, local treatment with cystoscopic or surgical removal of the mucosal encrustations is required (especially when the calcification is thick and cannot be dissolved by urine acidification therapy)[ 29 ]. Because the calcification is attached to the mucosa, it may be difficult to completely scrape out at one time.…”