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Fournier’s gangrene caused by candida species as the primary organism
CASE REPORTS
FOURNIER’S GANGRENE CAUSED BY CANDIDA SPECIES AS THE PRIMARY ORGANISM KAZUYOSHI JOHNIN, MASAKI NAKATOH, TAKASHI KADOWAKI, MAYUMI KUSHIMA, SHUICHI KOIZUMI, AND YUSAKU OKADA
ABSTRACT Fournier’s gangrene is a rare entity caused by polymicrobial aerobic and anaerobic bacteria. We report a case of Fournier’s gangrene caused by Candida as the primary organism. A 65-year-old man presented with perineal soft-tissue infections. He underwent surgical debridement and suprapubic cystostomy with both antifungal and antimicrobial therapy. The histopathologic examination revealed necrotizing fasciitis with Candida species as the sole initial pathogen. The case suggests that primary fungal pathogens should be considered as a causative organism of Fournier’s gangrene. UROLOGY 56: 153xiii–153xv, 2000. © 2000, Elsevier Science Inc.
CASE REPORT A 65-year-old man came to our hospital with painful gross hematuria. He had had diabetes mellitus for 10 years without any treatment. He had no history of a urethral catheter insertion before presentation. He presented with erythema around the perineal area, with heat and tenderness, but no crepitus. Urinalysis demonstrated yeast-like fungi and Trichomonas, and urine culture yielded Candida species. Neither anaerobic nor aerobic bacteria could be detected by either urine examination. Laboratory data showed hyperglycemia of more than 500 mg/dL, severe signs of inflammation, and positive values with the CAND-TEC detection system (antigen titers of 1:4 or greater). A chest x-ray revealed a 6 ⫻ 5 ⫻ 4-cm tumor in his right lung mass, which proved to be an advanced lung neoplasm by additional examination. An ultrasound scan revealed scrotal skin thickening and swelling, with subcutaneous hyperechoic foci in the posterior scrotum and normal epididymis, spermatic cords, and testes, which indicated subcutaneous abscess and gas formation (Fig. 1A). Retrograde From the Departments of Urology and Internal Medicine, Uji Tokushukai Hospital, Kyoto; and Department of Urology, Shiga University of Medical Science, Shiga, Japan Address for correspondence: Kazuyoshi Johnin, M.D., Division of Urology, Osaka Medical Center and Research Institute for Maternal and Child Health, 840 Murodo-cho, Izumi, Osaka 5941101, Japan Submitted: September 29, 1999, accepted (with revisions): January 31, 2000 © 2000, ELSEVIER SCIENCE INC. ALL RIGHTS RESERVED
urethrography revealed periurethral extravasation and gas production around the bulbous urethra (Fig. 1B). Digital rectal examination demonstrated no evidence of perirectal or prostatic abscess. Since these typical findings indicated an early presentation of Fournier’s gangrene, we performed suprapubic cystostomy and surgical debridement. The bulbospongiosus muscles were dark colored and seemed to be necrotic but later proved to have no myonecrosis histologically. The Buck’s fascia seemed normal, but brown discharge flowed out after it was cut. We found a perforation on the posterior wall of the bulbous urethra. Judging from the clinical findings, such as urinary fungi and serum positive CAND-TEC values, we considered this infection to have been caused by both bacteria and fungi. We administered intravenous fluconazole at a dose of 300 mg/day for fungi until the serum CAND-TEC values decreased into the negative range. In addition, intravenous imipenem was given at a dose of 2.0 g/day for 7 days as antibiotic prophylaxis for probable bacterial infection. The final pathologic examination demonstrated Fournier’s gangrene, with budding yeast and pseudohyphae under periodic acid-Schiff stain (Fig. 2). Fungal cultures of the discharge yielded Candida species. In addition, we could not find either anaerobic or aerobic bacteria from either culture examination of the discharge. The wound quickly developed an excellent granulating bed after local debridement and wet-to-dry dressings with sterile saline or povidone-iodine until secondary closure. About 40 days later, we performed de0090-4295/00/$20.00 PII S0090-4295(00)00527-6 153xiii
FIGURE 1. (A) Ultrasound scan revealing scrotal skin thickening and swelling, with subcutaneous hyperechoic foci in the posterior scrotum, which suggested subcutaneous abscess and gas (arrowheads). (B) Retrograde urethrography revealed periurethral extravasation (arrowheads) and gas production around the bulbous urethra (arrowheads).
layed closure of the affected urethra without using a skin flap and graft. He urinated without a catheter 10 days after the second operation. He was transferred to another hospital to receive radiation therapy for the advanced lung cancer. He died of lung cancer 2 months later. COMMENT Fournier’s gangrene is infective necrotizing fasciitis of perineal, genital, or perianal regions due to 153xiv
synergistic polymicrobial aerobic and anaerobic bacteria. The infection begins adjacent to the area of the entry of the microorganism, whether urethral, rectal, or cutaneous in origin.1 In patients with Fournier’s syndrome from periurethral gland infection or urinary extravasation, the causative organisms probably represent a combination of normal urethral, rectal, and cutaneous flora.1 Normal male urethral flora, which consists of a mixture of aerobic and anaerobic organisms, cannot UROLOGY 56 (1), 2000
FIGURE 2. Pseudohyphae and blastospore were seen between necrotizing fasciitis (arrows). Periodic acidSchiff stain, original magnification ⫻40.
infect healthy people but can cause severe infections in patients with debilitating underlying diseases, such as immunocompromised states, chronic alcoholism, cancer, or diabetes mellitus.1 Candida species are indigenous human yeasts that colonize the skin and mucous membranes of normal people and produce infection only when the natural resistance is compromised.2 Superficial candidal genitourinary infection is more common than the others, including locally invasive, ascending, deeply invasive, or systemic infection. However, few reports of necrotizing fasciitis caused by a fungal microorganism exist. In particular, no Candida species were reported to be the single pathogen of Fournier’s gangrene. In addition to anaerobes, Candida albicans can induce gas-forming infections.1,3,4 The fermentation of glucose by bacteria or fungi that produce carbon dioxide has been considered the origin of gas formation. Humayun and Maliwan4 commented that C. albicans should be included in the etiologic diagnosis of gas-forming cellulitis of the genitalia, especially in diabetic patients. We did not palpate any crepitus around his perineal area, but ultrasound and radiography were very valuable in the early detection of gas in
UROLOGY 56 (1), 2000
the tissue. The CAND-TEC system, which detects protein antigens of Candida species for assessment of candidal antigenemia, was a beneficial tool in making the diagnosis of invasive or disseminated infection.5,6 Thus, we were able to detect early systemic candidiasis. Suits et al.5 suggested that the debilitated hospital patient with persistent candiduria should be evaluated for candidal antigenemia. The mortality rate of Fournier’s gangrene is still high (average approximately 20%, range 7% to 75%), because it is difficult to recognize patients with early-stage disease and few cutaneous manifestations of the underlying infection. Early diagnosis is the key to successful treatment. Aggressive hemodynamic stabilization, surgical debridement, and parenteral antibiotics are the primary treatment strategies, although it should be noted that powerful antimicrobial therapy can sometimes worsen the fungal infection. Clinically, candidal soft-tissue infection is similar to bacterial infection in both its indolent onset and good convalescence after appropriate treatment. The present case may suggest that fungal infections should be considered as a possible pathogen, when patients with debilitating underlying disease present with Fournier’s gangrene. REFERENCES 1. Paty R, and Smith AD: Gangrene and Fournier’s gangrene. Urol Clin North Am 19: 149 –162, 1992. 2. Braude AI: Candida, in Braude AI (Ed): Infectious Diseases and Medical Microbiology, 2nd ed. Philadelphia, WB Saunders, 1986, pp 571–577. 3. Wise GJ: Fungal infections of the urinary tract, in Walsh PC, Retik AB, Stamey TA, et al. (Eds): Campbell’s Urology, 6th ed. Philadelphia, WB Saunders, 1992, vol 1, pp 928 –950. 4. Humayun H, and Maliwan N: Emphysematous genital infection caused by Candida albicans. J Urol 128: 1049 –1050, 1982. 5. Suits T, Wise GJ, and Walters B: Candidal antigenemia: a prognostic determinant. J Urol 141: 1381–1384, 1989. 6. Fung JC, Donta ST, and Tilton RC: Candida detection system (CAND-TEC) to differentiate between Candida albicans colonization and disease. J Clin Microbiol 24: 542–547, 1986.
153xv
FOURNIER’S GANGRENE CAUSED BY CANDIDA SPECIES AS THE PRIMARY ORGANISM KAZUYOSHI JOHNIN, MASAKI NAKATOH, TAKASHI KADOWAKI, MAYUMI KUSHIMA, SHUICHI KOIZUMI, AND YUSAKU OKADA
ABSTRACT Fournier’s gangrene is a rare entity caused by polymicrobial aerobic and anaerobic bacteria. We report a case of Fournier’s gangrene caused by Candida as the primary organism. A 65-year-old man presented with perineal soft-tissue infections. He underwent surgical debridement and suprapubic cystostomy with both antifungal and antimicrobial therapy. The histopathologic examination revealed necrotizing fasciitis with Candida species as the sole initial pathogen. The case suggests that primary fungal pathogens should be considered as a causative organism of Fournier’s gangrene. UROLOGY 56: 153xiii–153xv, 2000. © 2000, Elsevier Science Inc.
CASE REPORT A 65-year-old man came to our hospital with painful gross hematuria. He had had diabetes mellitus for 10 years without any treatment. He had no history of a urethral catheter insertion before presentation. He presented with erythema around the perineal area, with heat and tenderness, but no crepitus. Urinalysis demonstrated yeast-like fungi and Trichomonas, and urine culture yielded Candida species. Neither anaerobic nor aerobic bacteria could be detected by either urine examination. Laboratory data showed hyperglycemia of more than 500 mg/dL, severe signs of inflammation, and positive values with the CAND-TEC detection system (antigen titers of 1:4 or greater). A chest x-ray revealed a 6 ⫻ 5 ⫻ 4-cm tumor in his right lung mass, which proved to be an advanced lung neoplasm by additional examination. An ultrasound scan revealed scrotal skin thickening and swelling, with subcutaneous hyperechoic foci in the posterior scrotum and normal epididymis, spermatic cords, and testes, which indicated subcutaneous abscess and gas formation (Fig. 1A). Retrograde From the Departments of Urology and Internal Medicine, Uji Tokushukai Hospital, Kyoto; and Department of Urology, Shiga University of Medical Science, Shiga, Japan Address for correspondence: Kazuyoshi Johnin, M.D., Division of Urology, Osaka Medical Center and Research Institute for Maternal and Child Health, 840 Murodo-cho, Izumi, Osaka 5941101, Japan Submitted: September 29, 1999, accepted (with revisions): January 31, 2000 © 2000, ELSEVIER SCIENCE INC. ALL RIGHTS RESERVED
urethrography revealed periurethral extravasation and gas production around the bulbous urethra (Fig. 1B). Digital rectal examination demonstrated no evidence of perirectal or prostatic abscess. Since these typical findings indicated an early presentation of Fournier’s gangrene, we performed suprapubic cystostomy and surgical debridement. The bulbospongiosus muscles were dark colored and seemed to be necrotic but later proved to have no myonecrosis histologically. The Buck’s fascia seemed normal, but brown discharge flowed out after it was cut. We found a perforation on the posterior wall of the bulbous urethra. Judging from the clinical findings, such as urinary fungi and serum positive CAND-TEC values, we considered this infection to have been caused by both bacteria and fungi. We administered intravenous fluconazole at a dose of 300 mg/day for fungi until the serum CAND-TEC values decreased into the negative range. In addition, intravenous imipenem was given at a dose of 2.0 g/day for 7 days as antibiotic prophylaxis for probable bacterial infection. The final pathologic examination demonstrated Fournier’s gangrene, with budding yeast and pseudohyphae under periodic acid-Schiff stain (Fig. 2). Fungal cultures of the discharge yielded Candida species. In addition, we could not find either anaerobic or aerobic bacteria from either culture examination of the discharge. The wound quickly developed an excellent granulating bed after local debridement and wet-to-dry dressings with sterile saline or povidone-iodine until secondary closure. About 40 days later, we performed de0090-4295/00/$20.00 PII S0090-4295(00)00527-6 153xiii
FIGURE 1. (A) Ultrasound scan revealing scrotal skin thickening and swelling, with subcutaneous hyperechoic foci in the posterior scrotum, which suggested subcutaneous abscess and gas (arrowheads). (B) Retrograde urethrography revealed periurethral extravasation (arrowheads) and gas production around the bulbous urethra (arrowheads).
layed closure of the affected urethra without using a skin flap and graft. He urinated without a catheter 10 days after the second operation. He was transferred to another hospital to receive radiation therapy for the advanced lung cancer. He died of lung cancer 2 months later. COMMENT Fournier’s gangrene is infective necrotizing fasciitis of perineal, genital, or perianal regions due to 153xiv
synergistic polymicrobial aerobic and anaerobic bacteria. The infection begins adjacent to the area of the entry of the microorganism, whether urethral, rectal, or cutaneous in origin.1 In patients with Fournier’s syndrome from periurethral gland infection or urinary extravasation, the causative organisms probably represent a combination of normal urethral, rectal, and cutaneous flora.1 Normal male urethral flora, which consists of a mixture of aerobic and anaerobic organisms, cannot UROLOGY 56 (1), 2000
FIGURE 2. Pseudohyphae and blastospore were seen between necrotizing fasciitis (arrows). Periodic acidSchiff stain, original magnification ⫻40.
infect healthy people but can cause severe infections in patients with debilitating underlying diseases, such as immunocompromised states, chronic alcoholism, cancer, or diabetes mellitus.1 Candida species are indigenous human yeasts that colonize the skin and mucous membranes of normal people and produce infection only when the natural resistance is compromised.2 Superficial candidal genitourinary infection is more common than the others, including locally invasive, ascending, deeply invasive, or systemic infection. However, few reports of necrotizing fasciitis caused by a fungal microorganism exist. In particular, no Candida species were reported to be the single pathogen of Fournier’s gangrene. In addition to anaerobes, Candida albicans can induce gas-forming infections.1,3,4 The fermentation of glucose by bacteria or fungi that produce carbon dioxide has been considered the origin of gas formation. Humayun and Maliwan4 commented that C. albicans should be included in the etiologic diagnosis of gas-forming cellulitis of the genitalia, especially in diabetic patients. We did not palpate any crepitus around his perineal area, but ultrasound and radiography were very valuable in the early detection of gas in
UROLOGY 56 (1), 2000
the tissue. The CAND-TEC system, which detects protein antigens of Candida species for assessment of candidal antigenemia, was a beneficial tool in making the diagnosis of invasive or disseminated infection.5,6 Thus, we were able to detect early systemic candidiasis. Suits et al.5 suggested that the debilitated hospital patient with persistent candiduria should be evaluated for candidal antigenemia. The mortality rate of Fournier’s gangrene is still high (average approximately 20%, range 7% to 75%), because it is difficult to recognize patients with early-stage disease and few cutaneous manifestations of the underlying infection. Early diagnosis is the key to successful treatment. Aggressive hemodynamic stabilization, surgical debridement, and parenteral antibiotics are the primary treatment strategies, although it should be noted that powerful antimicrobial therapy can sometimes worsen the fungal infection. Clinically, candidal soft-tissue infection is similar to bacterial infection in both its indolent onset and good convalescence after appropriate treatment. The present case may suggest that fungal infections should be considered as a possible pathogen, when patients with debilitating underlying disease present with Fournier’s gangrene. REFERENCES 1. Paty R, and Smith AD: Gangrene and Fournier’s gangrene. Urol Clin North Am 19: 149 –162, 1992. 2. Braude AI: Candida, in Braude AI (Ed): Infectious Diseases and Medical Microbiology, 2nd ed. Philadelphia, WB Saunders, 1986, pp 571–577. 3. Wise GJ: Fungal infections of the urinary tract, in Walsh PC, Retik AB, Stamey TA, et al. (Eds): Campbell’s Urology, 6th ed. Philadelphia, WB Saunders, 1992, vol 1, pp 928 –950. 4. Humayun H, and Maliwan N: Emphysematous genital infection caused by Candida albicans. J Urol 128: 1049 –1050, 1982. 5. Suits T, Wise GJ, and Walters B: Candidal antigenemia: a prognostic determinant. J Urol 141: 1381–1384, 1989. 6. Fung JC, Donta ST, and Tilton RC: Candida detection system (CAND-TEC) to differentiate between Candida albicans colonization and disease. J Clin Microbiol 24: 542–547, 1986.
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