Abstract: Surgical or radiological drainage is the treatment of choice for prostatic abscesses, in conjunction with appropriate antibiotics. Fungal prostatic abscesses are uncommon, and amphotericin or azoles are the usual agents used for treatment. To date, echinocandins have not been reported as agents of choice for fungal abscesses because of a concern regarding their large molecular size and high protein binding. We report a case of Candida glabrata prostatic abscess treated successfully using micafungin. Adequate intra-abscess concentrations of the drug were demonstrated.
Department of Internal Medicine/Section of Infectious Diseases, Yale University School of Medicine, The Anlyan Center, New Haven, CT.
Address correspondence and reprint requests to Shaili Gupta, MD, Department of Medicine/Section of Infectious Diseases, Yale University School of Medicine, The Anlyan Center, 300 Cedar Street, S169, New Haven, CT 06520-8022. E-mail: firstname.lastname@example.org.
Most prostatic abscesses occur in patients with diabetes, in immunocompromised patients, and in patients who may not have received appropriate therapy for acute prostatitis. Foreign bodies and urinary tract obstruction are other predisposing factors. Infection generally occurs by theascending route and is caused by common uropathogens.1 Infection with fungi, mycobacteria, and other granuloma-causingorganisms is uncommon. Among the fungi, Cryptococcal prostatic abscesses have been described in HIV-positive patients. The prostate is known to be a reservoir site for Cryptococcus species. Few cases of prostatic abscesses with Aspergillus, and with dimorphic fungi such as Blastomyces and Histoplasma, have been described. Among Candida spp., 2 cases each of C. tropicalis and C. albicans, and 1 case of C. glabrata have been described. The treatment of choice is transurethral resection and/or intravenous amphotericin B. Fluconazole hasbeen used for treatment of some deep-seated abscesses. To date, echinocandins have not been reported as agents ofchoice for prostatic abscesses. We describe a case of prostatic abscess caused by C. glabrata, successfully treated with micafungin.
A 73-year-old man was sent to the hospital from an extended care facility, with lethargy, chills, perineal pain, and tenesmus, which had progressively worsened over 2 days. He denied fevers, dysuria, abdominal pain, nausea, vomiting, diarrhea, cough, weight loss, and night sweats. His medical history included end-stage renal disease requiring peritoneal dialysis, insulin-dependent diabetes mellitus, hypertension, coronary artery disease, hypothyroidism, benign prostatic hypertrophy, and peripheral vascular disease requiring multiple revascularization surgeries. Ten months before admission, he had undergone extensive perineal resection and partial colectomy for Fournier gangrene. For 6 months before admission, the patient had been given systemic antibiotics for recurrent urinary tract infections with Escherichia coli and Candida glabrata. Until 2 months before admission, he had received urinary bladder irrigations with amphotericin B and neomycin/polymyxin B.
On admission, the patient's vital signs were stable, with temperature of 98.6°F, blood pressure of 140/80 mm Hg, pulse rate of 78 beats/min, and blood oxygen saturation of 97% on breathing air. Cardiopulmonary examination was unremarkable, and abdomen was soft, nontender, and distended with peritoneal dialysate. No groin lesions or skin rashes were noted. Rectal examination revealed an extremely tender enlarged prostate. Laboratory tests were notable for leukocytosis (18.6 cells per µL/mm3 with 89% granulocytes), hypokalemia (2.9 mEq/L), and hyperglycemia (269 mg/dL). Creatinine was elevated (5.5 mg/dL) as expected with his renal insufficiency. Electrolytes were repleted. Urine cultures grew E. coli and multidrug-resistant Proteus mirabilis, which were treated with intravenous ertapenem.
Computed tomographic scan of abdomen and pelvis with oral and intravenous contrast revealed a multiloculated prostatic collection, 6.0 × 4.5 cm in dimensions. Peritoneal dialysate and dialysis catheter were visualized; no other significant abnormalities were noted. Percutaneous radiologically guided catheterization of prostate was performed, and purulent fluid was obtained. Cultures of this fluid resulted in abundant growth of C. glabrata. Given his previous hospitalizations and nosocomial acquisition of C. glabrata urinary infection in the past, we predicted probable resistance to azole antifungals and, therefore, deferred using these for treatment. Later, this was confirmed when the isolate demonstrated minimal inhibitory concentrations (MICs) ≥256 µg/mL for fluconazole and ≥2 µg/mL for voriconazole. A long course of amphotericin B was relatively contraindicated in this patient to preserve his residual renal function and to avoid potential hyperkalemia.2
Due to concern of maintaining residual renal function, we recommended micafungin in addition to catheter-drainage to treat the prostatic abscess. The C. glabrata isolate was found to be susceptible to echinocandins, with an MIC of 0.06 µg/mL for caspofungin, which is therapeutically equivalent to micafungin.3 To determine tissue penetration of micafungin into the prostate, we measured levels of the drug in serum as well as abscess fluid. Micafungin level in serum was 1.28 µg/mL, and in abscess fluid, it was 0.43 µg/mL, well above the MIC for the isolate. The patient received micafungin 100 mg/d intravenously for 37 days. The patient was determined not to be a candidate for prostatectomy because of his underlying comorbidities. Several attempts at radiologically guided catheter-drainage failed because of multiple loculations in the abscess. Eventually, transurethral unroofing of the abscess was done with decortication of loculations, resulting in optimal drainage of abscess fluid via the urethra. Computed tomographic scan performed 45 days after admission showed complete resolution of the prostatic abscess.
Surgical or radiologically guided drainage is the primary component of treatment of prostatic abscess. Amphotericin B remains the gold standard antifungal agent for most fungal abscesses. For sensitive Candida species, azole antifungals are a good option. Because of their small size molecules, the azoles can penetrate tissues well and attain high concentrations in deep tissues and abscess cavities. However, with the widespread use of fluconazole, azole-resistant Candida isolates are now being encountered. Recent results from the Global Antifungal Surveillance Study demonstrate the existence of cross-resistance between fluconazole and voriconazole, with the greatest emphasis on C. glabrata. Among 137,487 isolates of Candida spp. tested against voriconazole, less than 30% of fluconazole-resistant isolates of C. albicans, C. glabrata, C. tropicalis, and C. rugosa remained susceptible to voriconazole.4 Susceptibility of a Candida spp. to voriconazole was predicted by using fluconazole MICs ≤ 32 µg/mL to identify voriconazole-susceptible isolates and MICs ≥ 64 µg/mL to identify voriconazole resistance.5
Echinocandins have not been reported as therapeutic agents for fungal prostatic abscess. In fact, these newer antifungals have not been proven to eradicate fungi within abscesses in general. Echinocandins are large lipoprotein molecules with a relative molecular weight of approximately 1200 and with high protein binding and, therefore, are initially confined to the plasma compartment. The volume of distribution subsequently expands slowly to the extravascular space.6 Data exist regarding successful use of echinocandins in necrotizing pulmonary aspergillosis and aspergillomas, as well as in some cases of brain abscesses from Aspergillus.7,8 Survival is prolonged in such patients, but a moderate number of fungal elements may persist in tissues, partly because echinocandins are only fungistatic for Aspergillus spp.
For most Candida spp., echinocandins are highly fungicidal. Activity is less against C. parapsilosis and C. guilliermondii. The mean trough concentrations of echinocandins can be maintained over the MIC90 for clinically relevant Candida spp. when given in recommended doses. Tissue concentrations of these drugs have not been studied in human subjects with deep-seated fungal infections. Caspofungin tissue distribution has been quantitatively analyzed in rats.9 Tissues containing the highest amounts of drug were liver, kidney, lung, and spleen, with drug concentrations more than 4-fold the MIC90s. Therapeutic levels of micafungin have been achieved in lung, liver, spleen, and kidney of rabbits after long-term intravenous administration of 0.5 to 2 mg/kg.10 Similarly, multiple doses of 0.1 to 10 mg/kg per day of anidulafungin yielded therapeutic trough concentrations in lungs, liver, spleen, and kidney of rabbits, and a substantial accumulation in brain tissue was achieved at dosages ≥ 0.5 mg/kg per day.11
Micafungin efficacy has been found to be equal to that of fluconazole at 10% the dosage for therapy of deep-seated candidiasis in a cyclophosphamide-induced immunosuppressed mouse model, by inducing intraperitoneal abscess by C. albicans.12 The therapeutic effect of micafungin was similar to and superior to that of fluconazole at 24 hours and 8 days after the end of therapy, respectively. For invasive candidiasis and candidemia in humans, micafungin (100 mg/d) is as effective as, and causes fewer adverse events than, liposomal amphotericin (3 mg/kg per day).13 Efficacy is independent of the Candida spp., primary site of infection, neutropenic status, Acute Physiology and Chronic Health Evaluation II score, and catheter removal.
With the emergence of azole resistance among Candida spp. and the usual comorbidities of chronically ill patients who are more susceptible to fungal infections, echinocandins are rapidly emerging as antifungal agents of choice, given their efficacy against most Candida spp. and their relative safety compared with amphotericin. The major limiting factor for these drugs is their cost. Empiric use of these agents should be discouraged to avoid selection of fungal isolates resistant to yet another class of antifungal agents. For deep-seated fungal abscesses, the first-line treatment still is surgical drainage, along with an antifungal agent prudently chosen based on the susceptibility of the isolate, geographic and institutional prevalence of azole-resistant fungi, host factors, and cost-effectiveness. Based on the therapeutic success in our patient, echinocandins may be reasonably considered for deep-seated abscesses with susceptible Candida spp., when indicated.
The authors thank Dr Stephen C. Edberg, Director of Microbiology at Yale-New Haven Hospital, for testing echinocandin MIC for the Candida isolate, and Dr Michael G. Rinaldi of Fungus Testing Laboratory, University of Texas Health Science Center at San Antonio, for performing the micafungin assay for serum and tissue drug levels.
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