Rare and Emerging Fungal Pulmonary Infections

Jay B. Varkey, MD; John R. Perfect, MD

Disclosures

Semin Respir Crit Care Med. 2008;29(2):121-131. 

In This Article

Abstract and Introduction

Abstract

The frequency and diversity of serious fungal infections are increasing. Persons who are severely immunocompromised are particularly vulnerable to infection from unusual molds and yeasts that are often found naturally in the environment. Clinical manifestations from these unusual fungal infections range from colonization of airways to chronic localized lesions to acute invasive or disseminated disease. When present, rare and emerging fungi are often isolated from the respiratory tract during a severely immunosup-pressed state, and diagnosis requires isolation and identification of the infecting organism. Histopathology is often required to differentiate tissue invasion from airway colonization. There are no diagnostic serologies, and radiological exams are not specific. Furthermore, many emerging opportunistic molds demonstrate in vitro resistance to the older azoles and amphotericin B. As a result, successful treatment may require adjunct surgical debridement and, when possible, reconstitution of the host immune system. Also, the newer triazoles such as voriconazole and posaconazole may be useful to treat some of these infections caused by rare and emerging molds.

Introduction

The human airway is continuously open to the nonsterile environment where fungal spores have the potential to reach lung tissue and produce disease. In the immunocompromised host, many fungi, including species of fungi typically considered nonpathogenic, have the potential to cause serious morbidity and mortality. Over the last several decades the advent of the human immunodeficiency virus (HIV) epidemic and the increasing use of immunosuppressive drugs for serious medical conditions have dramatically increased the number of persons who are severely immunocompromised. As a result, the incidence of invasive fungal infections of the lungs has risen substantially.[1] In addition, the range and diversity of fungi that cause disease have broadened. This is significant because, despite marked advances in antifungal therapy, infections caused by opportunistic fungal infections (rare and emerging) continue to be associated with high morbidity, high mortality, and poor patient outcomes. This results from a combination of drug-resistant strains, lack of robust clinical studies evaluating treatments, and severe underlying diseases in the patient.

Although Candida and Aspergillus species continue to be the fungal pathogens that most frequently cause invasive fungal disease in immunocompromised persons overall, infections due to previously uncommon hyaline and dematiaceous filamentous fungi are being reported with increasing frequency.[2,3] This article reviews a select group of hyaline molds, yeastlike fungi, and a diverse number of clinical diseases caused by dematiaceous fungi. The article also discusses the potential role of several new antifungal agents that may be useful to treat serious infections caused by rare and emerging fungal pathogens. However, despite progress made in developing new antifungal therapy, successful treatment of these unusual fungal infections remains rare and challenging. The first step is an accurate diagnosis, and in most cases, it will require obtaining specimens from lung tissue for culture and histopathology. Furthermore, for these rare fungi, we need expert mycology either from a visual identification or possibly from polymerase chain reaction (PCR) of tissue/cultures and sequencing information. With accurate diagnosis, rare fungal infections require treatments that may include adjunctive surgical debridement, reconstitution of the host immune system, and new and old antifungals singly or in combination, one case at a time.

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