24

Nonbacterial Infections

of the Genitourinary Tract

Ryan N. Fogg and Jack H. Mydlo

Fungal Infections

The presence of fungal infections in genitourinary organs has become a common occurrence with the continuing increase in immunocompromised populations, and improved critical care of the elderly. A variety of fungi, either opportunistic or pathogens endemic to a specific region, cause human disease. Thus, a working knowledge of the common fungal infections, their clinical manifestations, and an awareness of at-risk populations is essential to early diagnosis and aggressive treatment.

Several types of patients are particularly vulnerable to fungal infections. Patients in immunocompromised states such as transplant patients, AIDS, diabetes, malignancies, chemotherapy, and premature infants are more susceptible to opportunistic infections and are vulnerable to endemic fungal dissemination and invasion. Malnutrition such as with chronic alcoholics makes the patients less able to fight systemic infection. Prolonged antibiotic use creates an environment ideal for opportunistic fungal overgrowth.Finally,patients with indwelling invasive catheters including intravenous catheters, particular in patients receiving total parental nutrition (TPN), as well as with indwelling urinary catheters are at increased risk of colonization, infection, and potential dissemination of fungal organisms.1 In the critical care setting, it is common for all three states to be present,accounting for their increased prevalence in this setting (Table 24.1).

Candidiasis

Candidiasis in the critical care setting comprises 10% of infections2 increasing with prolonged ICU stay. Candiduria is often seen in patients with prolonged indwelling catheters and antibiotic use exceeding 12–14 days,3 but its presence in the urine may represent colonization or active infection. The persistence of candiduria in populations at risk can disseminate into systemic invasive infections with mortality of 15–25%.4 Most patients with candiduria will be asymptomatic1, but some may present with frequency, urgency, dysuria, or hematuria.Active infections in the bladder typically cause mucosal edema, erythema, and white patches visible on cystoscopy, but may invade the bladder wall resulting in emphysematous cystitis and fungal balls or bezoars with resultant bladder obstruction or rupture.5 Infection can spread by local extension, perforation, or hematogenously. Invasion into the prostate results in prostatic abscesses and emphysematous prostatitis.6 In addition, epididymitis, while rare, has been reported.7 Candidemia in the ICU setting is most commonly caused by hematogenous dissemination of candiduria.8 Urologic manipulation of patients with candiduria has been demonstrated to cause candidemia. This is a serious sequela and must be aggressively treated as overall mortality approaches 40%.9 Dissemination can progress to renal involvement by hematogenous spread or as an ascending infection with

C.R. Chapple and W.D. Steers (eds.), Practical Urology: Essential Principles and Practice,	323
DOI: 10.1007/978-1-84882-034-0_24, © Springer-Verlag London Limited 2011

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	Table 24.1. risk factors for fungal infections		and fluorescence in situ hybridization (FISH).
	Prolonged urinary catheters		Local availability will determine the most appro-
			priate diagnostic method.
	central venous catheters		While Candida albicans has been the major
	total parental nutrition		organism of candidiasis, the emergence of non-
			albicans infections is becoming more prevalent.
	Malignancy
			Candida glabrata has emerged as a common
	HiV		cause of	candidiasis in				elderly	patients	with
			underlying malignancies, Candida tropicalis is
	solid organ transplantation
			found in leukemia patients with neutropenia,
	Broad spectrum antibiotics		and Candida parapsilosis is the most common
	diabetes mellitus		cause of candidiasis among neonates.9 This dis-
			tinction is important as culture sensitivities are
	chemotherapy		rarely performed in the hospital setting, and
	corticosteroids		each species has unique spectrum of antifungal
			sensitivities.
	neutropenia
	acute renal insufficiency		Aspergillosis
	Hemodialysis		Aspergilla is a ubiquitous fungus present in soil,
	Prematurity		vegetation, decaying vegetation, dust, spices, and
	severe pancreatitis		potted plants. In humans, Aspergillus fumigatus,
			A. flavus, and A. niger are opportunists causing
	gastrointestinal surgery
			disease in immunocompromised host.5,11
	ileal conduits		Infection typically begins in the respiratory tree,
			but may disseminate to extra pulmonary sites.
	alcohol abuse
			The most common genitourinary manifestation
	Malnutrition		is renal aspergillosis, occurring in 12% of dis-
	cirrhosis		seminated infections. Less common are pros-
			tatic, testicular, and adrenal involvement.12
	intravenous drug abuse		Renal infection may occur by hematogenous
			spread or ascending infection. Patients may
	resultant pyelonephritis, abscesses, papillary		present with hematuria, fevers, or flank pain due
			to obstructive uropathy.11 The sequelae of renal
	necrosis, renal failure, and obstructive uropathy
			aspergillosis		include			pyelonephritis,		renal
	by fungal bezoars. Patients may present with
			abscesses, papillary				necrosis, and obstruction
	fevers, colicky flank pain, and pyuria.5,10
			by fungus		balls	or	necrotic renal material
	The diagnosis of candidiasis can be demon-
			(Fig. 24.1). Diagnosis is by urine or tissue dem-
	strated in a number of ways. First, the patient
			onstration of microscopic birfurcate hyphae.13,14
	population should be considered. In patients
			Mortality is 40–90% necessitating prompt diag-
	with immunocompromise and significant risk
			nosis and systemic treatment. Prostatic asper-
	factors (See Table 24.1), especially in the ICU
			gillosis	presents		with		lower	urinary	tract
	setting, a low threshold must be maintained to
			symptoms and outlet obstruction and is typi-
	culture for Candida sp. Urine cultures are a
			cally diagnosed on histologic analysis of pros-
	mainstay of candiduria diagnosis, with colony
			tatic resection.Aspergillosis epididymo-orchitis
	counts greater than 10,000 generally considered
			has been reported requiring orchiectomy.5
	positive for an active infection.5 Blood cultures
	are an insensitive but specific measure of candi-
	demia.9 In addition to standard culture tech-		Cryptococcosis
	niques, a number of immunoassays are available
	and in development for diagnosis including the		Cryptococcus neoformans is an opportunistic
	latex agglutination assay, beta-glucan assay,		fungus found in bird excreta, soil, and decay-
	Enzyme-Linked ImmunoSorbentAssay (ELISA),		ing matter. Cryptococcosis occurs in							many

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nonBactErial infEctions of tHE gEnitoUrinary tract

a

b

Figure 24.1. renal aspergillosis. (a) coronal non-contrast ct images of left hydronephrosis and pyelonephritis in 64-year- old male with renal aspergillosis after lung transplant.

(b) intraoperative retrograde pyelogram of same patient during stent placement with multiple filling defects.

immunocompromised states but particularly in the AIDS population. Beginning as a pulmonary infection, it can disseminate typically to the nervous system and beyond. Caseating adrenal necrosis with resulting insufficiency has been reported.15 Renal involvement may be as high as 50% in disseminated cryptococcosis, causing a granulomatous pyelonephritis or renal abscesses with flank pain, fevers, hematuria, or pyuria on presentation. Prostatic involvement may be present in as many as one quarter of disseminated infections. Patients may be asymptomatic, present with prostatism or outlet obstruction and examination may mimic prostatitis or neoplasm.11,16 Particularly in the AIDS era, the prostate has become a reservoir of infection even after the disseminated infection has been cleared, thus becoming a source of future systemic infections.17 Penile lesions may occur in cryptococcosis, presenting as ulcers, pseudotumors, or necrotizing infections. Cryptococcal infections can be diagnosed by India ink stain, methenamine silver stain, as well as by serum antigen titers and latex agglutination tests.11

Blastomycosis

Blastostomyces dermatitidis is a fungus endemic to the Mississippi,Missouri and Ohio river basins, as well as moist soil near Lake Michigan. It begins as a self-limited pulmonary infection, but in immunocompromised populations it can disseminate into a systemic infections with genitourinary involvement reported in approximately 20% of patients. Most commonly, the prostate, epididymis, and testes are involved.18 Clinical manifestations range from asymptomatic infection to epididymo-orchitis, irritative voiding symptoms, urinary retention, and prostatic abscesses.19 Conjugal transmission from infected prostatic and spermatic secretions has been reported.20 Diagnosis can be made by demonstration of the fungi in tissue, semen or urine by culture, serum blastomyces A antigen, and ELISA.5

Coccidioidomycosis

Coccidioides immitis is indigenous to the arid desert regions of western USA and Mexico, preferring hot, dry soil with high saline content.

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		Practical Urology: EssEntial PrinciPlEs and PracticE
The primary infection is pulmonary and mild,		Radiographic Findings
but rarely disseminated infections occur.
Patients at risk for systemic infections include		The radiographic findings associated with fun-
those with immunocompromised states, chil-		gal infections of the genitourinary tract differ
dren younger than 5 years, and adults greater		based on the organ of involvement, but overall
than 50 years old. Postmortem analysis of		have broad similarities that will be present
patients with disseminating infections revealed		despite the specific organism. Adrenal necrosis
renal involvement in 35–60% of patients,		will appear heterogeneous and may present with
17–22% with adrenal infections, 4.6–6% with		enlargement, or calcification on CT scan. Renal
prostatic infections, 6% with retroperitoneal		abscesses may be present in the cortex or in the
involvement,and 1–5% with scrotal infections.21		perinephric space seen best by contrast CT, MRI,
Additionally, systemic allergic reactions can		or ultrasound. Fungus balls or sloughed papilla
occur due to the high antigenicity, causing cuta-		may be present at any point along the course of
neous manifestations similar to erythema		the upper tracts and bladder and typically
nodosum.11 Renal coccidioidomycosis presents		appear as filling defects with or without hydro-
as graunlomas or microabscesses and may		nephrosis on intravenous pyelogram (IVP), CT,
radiographically resemble tuberculosis with		and ultrasound. Prostatic abscesses will be well
renal calcifications, infundibular stenosis or		visualized by CT or by transrectal ultrasound.
“moth-eaten” calices.22 Prostatic infections can		Scrotal abscesses and epididymo-orchitis are
present with hematuria, pyuria, and bladder		well demonstrated by scrotal ultrasound. Overall,
outlet obstruction, and examination demon-		the radiographic findings associated with fungal
strates a tender indurated prostate.23 Scrotal		infections may be nonspecific and difficult to
manifestations can include abscesses, sinus		distinguish from bacterial infections or malig-
tracts, and epididymal graunlomas.21 Diagnosis		nancy, but must be combined with a low thresh-
can be made by culture of secretions, urine or		old of suspicion in those populations at risk, and
tissue, as well as by coccidioidal compliment		with the variety of laboratory tests available
fixation antibody titers, and latex agglutination		diagnose the specific causative organisms.5,10
studies.5,24,25

Histoplasmosis

Histoplasma capsulatum has worldwide distribution with a predilection for the Mississippi and Ohio river valleys in soil infused with bird and bat excrement. Infection begins as a mild respiratory infection that can disseminate in the face of immunosuppression with spread to the liver, spleen, bone marrow, reticuloendothelial system, and genitourinary tract. Patients with disseminated infections may present with fever, cough, chest pain, weight loss, hepatosplenomegaly, and lymphadenopathy.26 Genitourinary manifestations occur most commonly in the adrenal glands, with additional sites including the kidneys, testes, and prostate.27 Adrenal involvement may result in insufficiency.28 Patients may also present with renal abscesses, penile ulcers, prostatitis with prostatic abscess, or epididymitis. Diagnosis is made by demonstration of the organism in culture or tissue, Wright-Giemsa-stained blood smears, as well as by serum antigen levels, complement fixation, or immunodiffusion.11

Treatment

Treatment of fungal infections of the genitourinary tract depends upon the specific organism in question as well as the site of infection (Table 24.2). Thus, treatment must be considered on an individual basis and typically with the assistance of the infectious disease specialists. Despite this, several important principles exist. Three classes of antifungal agents are available and include: Amphotericin B, generally considered the gold standard for disseminated fungal infections and may be administered parentally or by bladder irrigation; Fluconazole which may be given intravenously or orally though its effectiveness varies among organisms; and Caspofungin, an effective broad spectrum antifungal. Medication regimens may require different lengths and routes of administration. For example, disseminated infection generally requires systemic intravenous administration, and prostatic infection often requires extended periods of antifungal treatment spanning weeks to months. Antifungal infections often need to be combined with surgical

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Table 24.2. treatment agents (adapted from Bartlett29)
Pathogen	Infection	Agent	Dose	Duration
antifungals
candidaa	Urinaryb	fluconazole	200 mg iV or Po	7–14 days
		amphotericin Bc	0.3–0.5 mg/kg/day iV
			50 mg in il sterile water at	5 days
			42 cc/h bladder irrigation
	systemic	fluconazole	400–800 mg iV × 1 then Po	2 weeksd
	infections
		amphotericin B	0.7–1 mg/kg/day iV
		caspofungin	70 mg iV daily then 50 mg
			iV daily
aspergillosise		amphotericin B	1–1.5 mg/kg/day iV	at least 10 weeks
		Voriconazole	6 mg/kg q 12 h × 1 day then
			4 mg/kg iV q 12 h then
			200 mg Po Bid
cryptococcus		amphotericin	0.7 mg/kg/day iV	2 weeks then
		B + flucytosine then	100 mg/kg/day
		fluconazole	400 mg Po daily	for 8 more weeks
Blastomycosis		itraconazole	200 mg Po Bid	6–12 months
		amphotericin B	0.7–1 mg/kg/day	6–12 weeks
coccidioidomycosis		itraconazole	200 mg Po Bid	at least 1 year
		fluconazole	400–800 mg daily
		amphotericin B	0.5–0.7 mg/kg/day iV
Histoplasmosis		itraconazole	200 mg Po Bid	6–8 months
		amphotericin B	0.7–1 mg/kg/day iV	10–12 weeks
tuberculosis		isoniazid	5 mg/kg Po daily	6–9 months
		+ Pyrazinamide	15–30 mg/kg Po daily
		+ rifampin	10 mg/kg Po daily
		+ Ethambutolf	15–25 mg/kg Po daily
		+ Vitamin B6	50 mg Po daily
schistosomiasis		Praziquantel	20 mg/kg Po Bid	1 day
filariasis		albendazole	400 mg Po x 1
		+ ivermectin	150 mg/kg x1
		diethylcarbamazineg	2 mg/kg Po tid	2 weeks
onchocerciasis		ivermectin	150 mg/kg × 1	semiannual ×
				2 years,
				then yearly

aagents and doses listed are for Candida albicans. other candida species will require consultation with infectious disease specialists for local sensitivities.

bisolated asymptomatic candiduria does not generally require treatment.

cdosages are for amphotericin B deoxycholate. alternative formulations will require alternative dosage regimens. dtreatment is for 2 weeks after the patient is afebrile and blood cultures are negative.

eitraconazole or caspofungin can be used as alternative agents. fcan discontinue ethambutol after 2 months if sensitivities permit.

gPatients with high microfilarial counts may have significant side effects and causes the mazzotti reaction in onchocerciasis.