To the Editor—Infrequent and rare fungal infections represent special challenges with respect to infection prevention and control. The epidemiology of many of these infections is not well understood with regard to environmental reservoirs, modes of transmission, and ways to detect them. Because of their relative rarity, laboratory diagnosis of these potential pathogens is challenging. Specific identification requires expertise because most diagnoses of fungi, especially those that are filamentous, are morphology based and nonautomated. Antifungal susceptibility testing of these rare pathogens is challenging because reliable methodology and antifungal breakpoints are often not readily available. Quality-assured diagnosis requires confirmation of rare species in reference laboratories, posing problems with regard to transportation of microbiologically hazardous culture isolates. In addition, reference laboratory facilities are not available in all regions and countries, and sometimes international collaboration and shipment of materials are required for confirmation of diagnosis. Here, we relate 3 cases of unusual fungal infections to illustrate these points.

A 4-year-old male child with acute lymphoblastic leukemia and receiving chemotherapy developed blackish necrotic lesions on the back and forehead in September 2011. Histopathology from a lesion showed acutely angled branching fungal hyphae in the dermis, and Fusarium solani was isolated on culture. Antifungal susceptibility showed the following minimum inhibitory concentrations (MICs): amphotericin B 2 µg/mL, voriconazole 8 µg/mL, itraconazole 16 µg/m, posaconazole 16 µg/mL. The patient initially responded to antifungal therapy but had a relapse of similar skin lesions. He eventually responded to a combination of liposomal amphotericin B, which was given for 31 days (1 to 2.7 mg/kg/day, intravenously [IV]), and voriconazole for 71 days at 10 mg/kg/day, orally. The child survived and is well on follow-up (3 years).

A 22-year-old male with aplastic anemia underwent a haplo-identical stem cell transplantion from a brother in August 2013. He developed multiple erythematous papular skin lesions 18 days post transplantation and cellulitis of right big toe. A blood culture from the central line grew filamentous fungus after 4 days of incubation, identified as Fusarium spp. Antifungal susceptibility showed the following MICs: amphotericin B-1 µg/mL, voriconazole 4 µg/mL, itraconazole >16 µg/mL. The patient had acute graft rejection, hemorrhagic cystitis. He was treated with liposomal amphotericin B for 26 days (3 mg/kg/day, IV), voriconazole for 29 days (200 mg, orally, twice daily), and caspofungin for10 days (50 mg/day, IV). The patient died in September 2013.

A 75-year man with total colectomy developed Klebsiella bactermia on postoperative day 5, which initially responded to a course of meropenem and colistin. Antibiotics were changed to piperacillin-tazobactam, ciprofloxacin, and doxycyline when Ralstonia pickettii and Elizabethkingia meningoseptica were isolated from central-line tip on different occasions. Because the patient remained febrile, repeat blood cultures were taken, which grew Kodamaea ohmeri on several occasions while the patient was on fluconazole and then on caspofungin. Fungaemia persisted despite changing the central line. Treatment with conventional amphotericin B (IV) for 2 weeks cleared the fungus. The patient was discharged in stable condition.

Fusarium is a hyaline hyphomycetes fungus that may cause localized infections, such as keratitis and onychomycosis, and disseminated infections in immunocompromised hosts.Reference Nucci and Anaissie ^{1 ,} Reference Ho, Lee, Rosso and Montoya ² The natural habitat of Fusarium is said to be plants and soil.Reference Nucci and Anaissie ¹ Outbreaks of infections, such as keratitis due to contaminated lens solution, have been reported, as has the isolation of this fungus in hospital water systems.Reference Scheel, Hurst, Barreiros, Akiti, Nucci and Balajee ^{3 –} Reference Chang, Grant and O’Donnell ⁶ Unlike infection in a normal host, fusariosis in immunocompromised patients is typically invasive and disseminated.Reference Nucci and Anaissie ^{1 ,} Reference Ho, Lee, Rosso and Montoya ² Disseminated fusariosis has high mortality rates.Reference Nucci and Anaissie ¹ Predictors of poor outcome have been identified in various studies as persistent neutropenia and recent corticosteroid therapy.Reference Nucci and Anaissie ¹ There is no consensus on optimal management of fusariosis. Antifungals alone or in combination, together with other measures such as surgical intervention or colony-stimulating growth factors, have been used to treat such infections.Reference Nucci and Anaissie ¹

Kodamaea (Pichia) ohmeri, an uncommon fungus and formerly considered a contaminant, has recently been reported to cause fungemia, endocarditis, funguria, and peritonitis in immunocompromised patients.Reference Lee, Shin and Kim ^{7 –} Reference Chakrabarti, Rudramurthy and Kale ⁹ This yeast, previously known as Pichia ohmeri, is commonly used in the food industry for its fermentation properties in pickles.Reference Taj-Aldeen and Doiphode ⁸ Misidentification of this fungus as a Candida species is not unusual unless specific molecular methods are used (ie, DNA sequencing or matrix-assisted laser desorption/ionization–time of flight [MALDI-TOF]).Reference Chakrabarti, Rudramurthy and Kale ^{9 ,} Reference Ghosh, Paul and Sood ¹⁰

Prevention of infections due to rare fungi such as Fusarium and Kodamaea requires a multipronged strategy that includes the following elements: (1) attention to thorough environmental cleaning and disinfection, (2) surveillance of fungal infections through air and water microbiology especially in transplant units, (3) a high index of clinical suspicion especially in early phases when infections may still be localized (eg, onychomycosis in a case outlined above), (4) appropriate selection of prophylactic anti-fungal agents (eg, posaconazole in stem cell transplant recipients and voriconazole in patients with acute myeloblastic leukemia), (5) early diagnosis and appropriate empirical therapy in clinically suspected infections, and (6) availability of adequate laboratory diagnostic infrastructure for early recognition of these organisms in environmental and clinical samples. Furthermore, liaison with reference laboratories and specialists experienced in diagnosis and management of these infections is critical for optimizing outcome. In the cases outlined here, the Fusarium species were initially identified in the care-giving hospital by a laboratory technologist experienced in fungal diagnosis. Kodamaea was identified in the same center using the VITEK2 system (bioMerieux, Durham, NC). The fungal identifications were confirmed by India’s national reference laboratory for fungal infections, a World Health Organization Collaborating Center for Mycology. The cost of treatment, the need for prolonged intravenous antifungal therapy, the cost of prolonged hospital stay, and the cost of monitoring patients for optimal response, as well as side effects of treatment are major challenges on the path toward a successful outcome.