Nosocomial urinary tract aspergilloma in an immunocompetent host: an unusual occurrence.

Fungal infections of the urinary tract are usually encountered following prolonged antibiotic use, instrumentation and indwelling urinary catheters. Candida is the most frequent causative fungus. However, infections with Aspergillus flavus have been reported previously in immune-compromised hosts. We, hereby, report a 32-year-old immunocompetent man diagnosed to have urinary tract infection caused by Aspergillus flavus following instrumentation for the removal of a ureteric stone. The infection was symptomatic, associated with abdominal pain and subsequent passage of fungal masses per urethra. Patient was treated successfully with a prolonged course of broad spectrum antifungal agent itraconazole.

What was known?

Candidal fungal infections of urinary tract following prolonged antibiotics, indwelling catheters and instrumentation are well known and symptoms vary from asymptomatic infections to fatal fungemia.

Urinary aspergillosis generally occurs in immunocompromised host and amphotericin B has been reported to be the treatment of choice for symptomatic infections.

Introduction

Fungal infections of the urinary tract are becoming increasingly becoming common due to overuse of antibiotics, urinary tract instrumentation or loss of immunocompetency in the host.[1] Most of the cases are a result of candidal infection.[1] Other rarer reported causes include Aspergillus or Cryptococcus. Fungal infections of the urinary tract tend to be symptomatic and also carry a significant risk of dissemination. We present an interesting case of an immunocompetent male who presented with nosocomially acquired aspegillus bezoars of the urinary tract, which were symptomatic and also favorably responded to oral antifungal therapy.

Case Report

A 32-year-old man of average built, visited a private hospital for surgical consult, with the complaints of recurrent, colicky abdominal pain of 6 months duration. On the basis of radiological investigations, he was diagnosed to have a right sided ureteric stone of 0.5 cm at the junction of upper 1/3rd and lower 2/3rd of the right ureter. He was also found to have significant bacteriuria with E. coli, for which he was treated with norfloxacin and amikacin. The ureteric stone was extracted by trans-urethral approach.

The removal of the stone led to subsidence of his symptoms. However, 3 weeks later, patient had recurrence of abdominal pain with low grade fever and malaise. He then presented to the department of surgery in our hospital. The pain was milder in intensity and accompanied by the passage of small, pinkish white soft balls per urethra during the process of urination. The pain subsided significantly following passage of these masses. The episodes of pain and subsequent passage of masses were intermittent, varying from twice a day to twice per week. His repeated urine cultures were sterile despite 2-3 neutrophils per high power field on microscopic examination. There were no signs of uretric obstruction, renal compromise or sepsis. He was reassured and prescribed antispasmodics with only temporary relief. He was then referred for dermatology opinion. The patient was asked to urinate in an open container to visualize the masses. On examination, these masses appeared fleshy, of variable size and shape, maximum being 2 cm in length and soft in consistency [Figure 1]. These masses were subjected to microscopic examination in 10% potassium hydroxide (KOH), fungal culture and histopathological examination. KOH examination revealed dense collection of septate hyaline hyphae with dichotomous branching at places [Figure 2]. For fungal culture, the specimen was inoculated on sabouraud dextrose agar (SDA) medium with antibiotics (chloramphenicol-0.4 gm/l, gentamicin-0.04 gm/l) and without cyclohexamide at 25°C. After 3-4 days, growth of colonies was observed which were green to grey in colour with a mat – like surface. Microscopically on lacto phenol cotton blue (LPCB) mount hyaline septate, relatively broad hyphae with long conidiophores were seen [Figure 3]. Vesicles were spherical, large with biseriate phialides bearing chains of conidia over most of the surface morphologically correlating with Aspergillus flavus. Histopathology too, was corroborative and revealed dense masses of interweaving septate filamentous hyphae.

Figure 1

Linear fleshy mass of fungus passed per urethra

Figure 2

Mass of septate hyaline hyphae with dichotomous branching on KOH microscopy

Figure 3

Greenish grey, hyaline septate relatively broad hyphae with long conidiophores seen on LPCB mount. Note: Large, spherical vesicles with biseriate phialides bearing chains of conidia characteristic of Aspergillus flavus

The patient underwent hematological investigations to rule out underlying diabetes, HIV or any other cause of immunodeficiency. His renal functions were within normal limits. Blood sample for bacterial and fungal cultures were sterile and X-ray chest did not reveal any focus of infection. He was started on oral itraconazole at a dose of 200 mg twice a day. Patient became afebrile and reported a feeling of well being within two weeks of therapy. The last fungal mass was passed 12 days after start of therapy but the treatment was continued for a period of three months. The patient has been well and asymptomatic for more than 6 months after discontinuation of therapy.

Discussion

Fungal infections of the urinary tract are increasing in incidence, mostly due to the increasing use of antibiotics, instrumentation and indwelling urinary catheters.[1] They may be symptomatic or may remain asymptomatic. A spectrum of clinical manifestations varying from asymptomatic colonization (most common), cystitis, pyelonephritis, renal infection, sepsis and fungemia have been reported.[1] There is a predilection for drainage structures rather than the renal parenchyma.[2] Funguria may become pathologic depending on host factors, thus the management depends on the patient's underlying health status. Candida is the most common fungus infecting the urinary tract.[1] However, other fungi may be involved depending on previous antifungal treatment and previous hospitalization.

Aspergillus is not a common cause of fungal urinary tract infections (UTI's). Primary aspergillus infection of the urinary tract is sufficiently rare, even more so in immunocompetent patients.[3] Bibler et al., reviewed 11 patients with aspergillomas of the renal system.[4] Ten of these were men and all had an underlying disease that predisposed to the fungal infection. In immunocompromised patients, varying manifestations in the form of aspergillus balls or bezoars,[35] ureteric obstruction,[4] ureteric colic, renal failure,[3] sepsis[3] or disseminated aspergillosis have been reported. Except for mild spasmodic pain and discomfort, our patient did not manifest any fever or severe constitutional symptoms. Disseminated aspergillosis in the form of pulmonary aspergillomas or prostatic involvement[6] has been reported even in immunocompetent patients. This can occur due to corticosteroid use or surgical intervention.[6] No signs of dissemination were seen in our patient. Visible passage of aspergillus balls in urine is an interesting and frightening symptom for the patient. This has rarely been reported previously in a patient with acute myelocytic leukemia.[7] To the best of our knowledge, our patient is the first immunocompetent host to develop aspergillus bezoars.

It is recommended that asymptomatic funguria in hospitalized patients may not be treated as treatment does not impact morbidity and mortality. It may be only a sickness indicator like bacteriuria in elderly.[8] Treatment is recommended only when funguria is symptomatic or in case where host factors increase the risk of fungemia.[1] Reduction of risk factors like removal of indwelling catheters and optimising antibiotic usage should be tried. In immunocompromised patients, a combined approach with topical and systemic antifungal agents and endourological access for extraction, lavage and debulking may be required.[9] However, in immunocompetent, surgical therapy is not necessary. Infact asymptomatic prostatic aspergillosis has been reported to disseminate after a routine transurethral resection procedure.[6] Aspergillosis is reported to behave more malignantly than candidiasis of urinary tract.[9] Treatment with amphotericin B has previously been recommended.[10] However, itraconazole treatment has proven effective even in amphotericin B resistant cases.[9] Our patient was healthy, immunocompetent and refused hospitalization; hence, we tried this as the first line therapy in our case with successful outcome.

The present case emphasizes the possibility of iatrogenic urinary fungal infection secondary to instrumentation in an otherwise immunocompetent patient. A high index of suspicion in such patients and careful investigations are needed to establish the diagnosis. Oral itraconazole may be recommended as a first line therapy.

What is new?

Iatrogenic fungal infection is a possibility secondary to invasive procedures even in an immunocompetent patients that should be confirmed on culture. Oral itraconazole should be used as first line of treatment.