Review
Emerging opportunistic yeast infections

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Summary

A growing population of immunosuppressed patients has resulted in increasingly frequent diagnoses of invasive fungal infections, including those caused by unusual yeasts. The incidence of non-albicans species of Candida is increasing compared with that of Candida albicans, and several species, such as Candida glabrata and Candida krusei, may be resistant to azole antifungal therapy. Trichosporon species are the second most common cause of fungaemia in patients with haematological malignant disease and are characterised by resistance to amphotericin and echinocandins and poor prognosis. Rhodotorula species belong to the family Cryptococcaceae, and are a cause of catheter-related fungaemia, sepsis, and invasive disease in severely immunosuppressed patients. An increasing number of sporadic cases of invasive fungal infections by non-neoformans cryptococci have been reported in immunocompromised hosts, especially for patients with advanced HIV infection or cancer who are undergoing transplant. Other uncommon yeasts that can cause invasive disease in severely immunosuppressed patients include Geotrichum, Hansenula, Malassezia, and Saccharomyces. Host immune status is a crucial determinant of the type of invasive fungal infection a patient is at risk for. Diagnosis can be challenging and relies heavily on traditional cultures of blood and other sterile sites, although serum (1,3)-β-D-glucan testing might have an adjunctive role. Although rare yeasts are emerging as opportunistic human pathogens, diagnosis remains challenging and treatment suboptimal.

Introduction

Candida albicans is the predominant cause of invasive fungal infections from yeasts.1, 2 Nevertheless, the epidemiology of yeast infections is rapidly evolving and non-albicans Candida species and other rare yeasts have emerged as major opportunistic pathogens (panel). Horn and colleagues1 showed that prevalence of candidaemia caused by non-albicans Candida species was 54·4%. Other yeasts that are less common than candida have been associated with life-threatening infections in immunocompromised hosts.3, 4, 5, 6 Although the importance of these emerging opportunistic yeasts is recognised, little is known about present epidemiological traits of these pathogens. Indeed, these pathogens are frequently difficult to identify by phenotypic methods and show variable susceptibility profiles to antifungal drugs.7, 8 We address the epidemiological, diagnostic, and therapeutic aspects of emerging yeast infections.

Section snippets

Non-albicans Candida species

Although C albicans is the most common cause of invasive fungal infections in hospital settings, the growing number of new infections from non-albicans Candida species is increasingly recognised as a major source of infection. In most surveys and treatment studies in the USA, Candida glabrata is the second most common Candida species leading to invasive fungal infections. The ARTEMIS Global Antifungal Surveillance Program9 showed that C albicans was the most common (63–70%) candidal cause of

Multiple yeast infections

Patients at a high risk for fungal infection (eg, candida, aspergillus, and mucor) can have more than one occurrence concomitantly or successively. Use of antifungal agents selects for resistant pathogens, much the same as occurs in antibacterial resistance. Prolonged use of voriconazole for prophylaxis or treatment can result in breakthrough fungal infections such as mucormycosis.

Jensen and colleagues75 showed that mixed fungaemia occurred in 15 (3%) of 530 cases of fungaemia and C albicans

Role of host status

Host and pathogen interactions are crucial in pathogenesis of invasive fungal infections. Traditionally, severity and outcomes from fungal infections are attributed to the pathogen's capability to overcome host immune defence and inflict tissue damage. However, whether host immunity is impaired, uncontrolled, or hyper-reactive affects the severity and outcome of invasive mycosis.77, 78, 79

Phagocytic cells (neutrophils and mononuclear phagocytes) are the effector cells of the innate immunity.80

Diagnostic considerations

Diagnosis of emerging yeast infections depends largely on traditional microbiological culture and identification methods and histopathology. Yeast fungaemia, especially that caused by Candida species, can be detected with blood cultures, although supplementation of lipids is usually required for growth of Malassezia species.88 Growth of Candida species from blood or normally sterile sites nearly always represents true infection and should be treated as such. However, growth of Candida species

Controversies for treatment and prevention

Additional strategies to improve outcomes for patients with invasive fungal infections include use of immunomodulators and combination therapies. Adjunctive interferon γ might be indicated for refractory cryptococcosis.109 The role of interferon γ in invasive candidosis and other emerging yeast infections is undefined. Although combination therapy is well established for treatment of cryptococcal meningitis, its use in invasive candidosis is less clear. Combination therapy is recommended for

Conclusions

Non-albicans Candida species and other rare yeasts are emerging as key opportunistic pathogens. Early and specific diagnosis is crucial, and the decision to treat a patient with these unusual infections is often based on little clinical and microbiological information. Treatment decisions need careful consideration of the institutional epidemiological factors and the immune status of the population at risk.

Search strategy and selection criteria

We searched PubMed for articles published in English or Spanish between January, 1990, and March, 2010, with the terms “unusual yeasts”, “emerging fungal infections”, “non-albicans Candida”, “C. guilliermondii”, “C. krusei”, “C. parapsilosis”, “C. tropicalis”, “C. pseudotropicalis”, “C. lusitaniae”, “C. dubliniensis”, “C. glabrata”, “C. pelliculosa”, “C. kefyr”, “C. rugosa”, “C. famata”, “C. inconspicua”, “C. norvegensis”, “C. kefyr”, “C. orthopsilosis”, “C. metapsilosis”, “C. nivariensis

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