Successful Treatment of Corynebacterium Urealyticum Encrusted Cystitis: a Case Report and Literature Review

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Le Infezioni in Medicina, n. 1, 56-58, 2007 Casi clinici Successful treatment of Corynebacterium urealyticum Case reports encrusted cystitis: a case report and literature review Terapia medica risolutiva della cistite crostosa da Corynebacterium urealyticum: descrizione di un caso e revisione della letteratura

Antonio Perciaccante, Maria Elena Pompeo, Flavia Fabi, Mario Venditti Servizio di Consulenze Internistico-Infettivologiche, III Clinica Medica, Dipartimento di Medicina Clinica, Policlinico Umberto I. Università di Roma “La Sapienza”, Rome, Italy

I INTRODUCTION toms, the patient underwent two additional percutaneous nephrostomy drainages with ncrusted cystitis is a very rare disease ureteral stenting and five cystoscopies in order characterized by a chronic inflammatory to remove the plaques. Analysis of these lesions Edisease of the bladder in patients with pre- showed struvite and carboapatite. Although disposing factors, caused by an urea-splitting urine analyses always showed pyuria and alka- bacterium [1-3]. Recently Corynebacterium spp. line pH (pH 7.5), several urine cultures were have been increasingly reported as the cause of negative for common microorganisms and this disease. Until now, as very few cases have acid-alcohol resistant bacilli. One month before been reported, clinical and microbiological in- admission, a Computerized Tomography (CT) dications for early diagnosis and optimal treat- scan showed no renal calcifications. From the ment are not well established. initial presentation of urinary symptoms he re- In the present article we report the case of a ceived multiple unsuccessful courses of antibi- Corynebacterium urealyticum encrusted cystitis otic therapy. These included a three-week in a immunosuppressed patient successfully course with ceftriaxone and a two-week course treated with teicoplanin and offer a review of with ciprofloxacin during the two months be- the medical literature on this topic. fore admission to our hospital. When we observed the patient, he still presented remark- able dysuria and urethral discomfort and the I CASE REPORT urine analysis showed pyuria and alkaline pH (pH 9). Two urine cultures on enriched media A 57-year-old man, with a 10-year history of with sheep blood agar yielded C. urealyticum af- systemic erythematosus lupus treated with cor- ter three days of incubation at 35°C. The isolate ticosteroids, presented a long period of dysuria proved resistant in vitro to ampicillin, second and urethral discomfort. Three years earlier he and third generation cephalosporins and fluo- had a lupoid obstructive uropathy with left hy- roquinolones. The patient was treated with te- dronephrosis, and following a percutaneous icoplanin 400 mg/die i.m. at domicile for 2 nephrostomy drainage with ureteral stenting, weeks. Five days after the beginning of this an- he began to complain of dysuria and strangury. tibiotic therapy, the urine analysis showed a pH Ultrasonography revealed hyperechogenic ma- 6 and disappearance of pyuria. Urine culture terials in the bladder and left hydronephrosis. did not show microbial growth. After one year Due to persistent and increasing urinary symp- no recurrence of symptoms was observed.

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I DISCUSSION The successful isolation and culture of C. urealyticum can be difficult because this microor- Alkaline encrusted cystitis is a chronic inflam- ganism requires culturing for 48-72 hours at 37° matory disease of the bladder, first described in C on enriched media with sheep blood agar or 1914 by Francois [1]. Presently, Corynebacterium 5% carbon dioxide [1]. This may explain delays urealyticum, a urea-splitting bacterium, is re- in the diagnosis of encrusted cystitis or pyelitis, ported as the principal aetiological agent of en- as it was in the present case. In other circum- crusted cystitis and pyelitis. This microorgan- stances the organism may be considered as a ism is a commensal bacterium of the skin and contaminant. causes urinary infection only when it is trans- Ultrasonography is a useful diagnostic tool for ported into the urinary tract [2]. encrusted cystitis, because it shows thickening In the last twenty years, an increasing number and calcified lesions on the bladder’s mucosa of cases of alkaline encrusted cystitis and [2]. CT appears to be an optimal technique to pyelitis caused by C. urealyticum have been de- diagnose encrustation, particularly in the upper scribed. We think that this increase in reports urinary tract [6]. Cystoscopy plays an impor- may be related to the increase in the use of uro- tant diagnostic and therapeutic role in en- logical endoscopic procedures and immuno- crusted cystitis, because it permits the direct vi- suppressive therapy, that are predisposing fac- sualization and removal of the encrusted tors for these infections. Moreover, these infec- plaques [6]. tions may well have been previously undiag- Another matter of interest is the peculiar multi- nosed due to the difficulties in identifying C. ple antibiotic resistance of C. urealyticum. Since urealyticum. its first description as Corynebacterium group In all cases of encrusted cystitis reported in the D2, it proved resistant to ampicillin, literature, the patients underwent a previous cephalosporins and aminoglycosides [7]. Sus- urological procedure [2-6]. These procedures ceptibility to fluoroquinolones is variable and can favour transport of C. urealyticum, which is resistance was reported higher than 50% [3]. In a commensal skin microorganism, into the uri- particular norfloxacin, moxifloxacin and nary tract. The interval between urological pro- ciprofloxacin were not in vitro active in 76%, cedure and diagnosis of encrusted cystitis or 53% and 60% of cases, respectively [8]. pyelitis ranges from a few days to 3 years [3]. Glycopeptides are the current antibiotics of Other reported predisposing factors are neuro- choice for treatment of encrusted diseases. All logical bladder dysfunction and malakoplakia strains of C. urealyticum are susceptible in vitro [1, 2]. to vancomycin and teicoplanin and these drugs The encrustations are due to urease produced showed efficacy in an experimental rat model by microorganisms. The bacterial urease hy- of encrusted cystitis regardless of the urine pH drolyzes urea and releases ammonia, inducing [8]. alkalinization of urine, which causes hypersat- Overall only 4 cases of encrusted cystitis and 2 uration with ammonium, magnesium and cases with encrusted pyelitis treated with te- phosphate (struvite). Precipitation of these icoplanin have been reported in the medical lit- crystals results in bladder wall encrustations. erature, and all were cured, as was our patient. Encrusted cystitis and pyelitis are chronic dis- In conclusion, encrusted cystitis is a rare diseases with long-lasting symptoms. Symptoms ease that can cause considerable discomfort and such as dysuria, urethral discomfort, soprapu- substantial morbidity with ascending pyelitis bic or lumbar pain with gross haematuria are and renal failure: alkaline urine and initial neg- considerable and much more frequent than ative cultures should prompt suspicion for fever, that is reported in 25-50% of the patients early diagnosis and effective therapy [9, 10]. [3]. Eventually, renal failure may complicate Optimal treatment requires removal of en- encrusted cystitis and pyelitis, making the crusted lesions and medical therapy with gly- prognosis worse [3]. copeptides. We propose teicoplanin as the an- Medical history, clinical context and urine tibiotic of choice in patients with encrusted cys- analysis associated with radiological findings titis, due to the chance of outpatient therapy. are the basic elements for the diagnosis of encrusted cystitis or pyelitis. Urine analysis always shows leukocyturia, haematuria, alkaline Key words: Encrusted cystitis, Corynebacterium pH and triple phosphate crystals (2). urealyticum, Teicoplanin

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SUMMARY

Encrusted cystitis is a very rare chronic inflamma- systemic erythematosus lupus with a long history of tory disease of the bladder characterized by precip- dysuria and suprapubic pain who underwent per- itation and incrustation of phosphate and ammo- cutaneous nephrostomy drainage with urethral nium-magnesium salts on the vescical mucosa, stenting for lupoid obstructive uropathy. Before the caused by urinary infection due to urolithic mi- diagnosis of encrusted cystitis by Corynebacterium croorganisms. Corynebacterium urealyticum or urealyticum was established, the patient underwent Corynebacterium group D2, a multiple antibiotic-re- five cystoscopies to remove the plaques and multi- sistant urea-splitting bacterium, is the most fre- ple unsuccessful antibiotic treatment courses. Even- quently incriminated aetiology. tually the infection was definitively cured after a We report a case of a 57-year-old man affected by two-week course with intramuscular teicoplanin.

RIASSUNTO

L’encrusted cystitis è una rara malattia infiammatoria di stent ureterale a causa di un’uropatia ostruttiva lu- cronica della vescica caratterizzata da precipitati di sali poide. di fosfato, ammonio e magnesio sulla mucosa della ve- Prima di porre diagnosi di encrusted cystitis ed isolare scica, causata da un’infezione dovuta a microorganismi il Corynebacterium urealyticum, il paziente era stato urealitici. L’agente eziologico più frequentemente iso- sottoposto a cinque interventi per via cistoscopia, al fine lato è Corynebacterium urealyticum o Corynebac- di rimuovere i precipitati presenti sulla mucosa vesci- terium di gruppo D2, un batterio caratterizzato da an- cole, e a ripetuti cicli di terapia con vari antibiotici. tibioticoresistenza multipla. Una volta posta la diagnosi di encrusted cystitis, il pa- Noi riportiamo il caso di un uomo di 57 anni affetto da ziente è stato trattato per 2 settimane con teicoplanina Lupus Eritematoso Sistemico che presentava una lunga per via intramuscolare con risoluzione della sintomato- storia di disuria e dolore sovrapubico e che era stato sot- logia, negativizzazione dell’esame colturale e scomparsa toposto a drenaggio per via nefrostomica e ad inserzione dei precipitati.

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