Seminars in respiratory and critical care medicine
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Semin Respir Crit Care Med · Dec 2011
ReviewAntifungal PK/PD considerations in fungal pulmonary infections.
Pharmacokinetic/pharmacodynamic (PK/PD) studies examine the relationships of drug pharmacokinetic properties, in vitro drug potency, and treatment efficacy. Study results are integral to the design of optimal dosing strategies, prevention of toxicity, development and interpretation of susceptibility break points, and prevention and recognition of drug resistance. These principles are increasingly utilized to optimize therapy for pulmonary fungal pathogens such as ASPERGILLUS species, although they have been underutilized for other difficult-to-treat fungal pathogens. Understanding the design and implementation of PK/PD studies facilitates more effective utilization of the available antifungal agents to improve outcomes for many of these life-threatening infections.
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Semin Respir Crit Care Med · Dec 2011
ReviewAllergic bronchopulmonary aspergillosis and related allergic syndromes.
While allergic bronchopulmonary aspergillosis (ABPA) is well recognized as a fungal complication of asthma, severe asthma with fungal sensitization (SAFS) is not. In ABPA the total immunoglobulin E (IgE) is usually >1,000 IU/mL, whereas in SAFS it is <1,000 IU/mL, and either skin prick tests or fungus-specific IgE tests are positive. ABPA may present with any severity of asthma, and occasionally with no asthma or cystic fibrosis, the other common underlying disease. ⋯ Complications of ABPA include bronchiectasis, typically central in distribution, and chronic pulmonary aspergillosis. Most patients with ABPA and SAFS can be stabilized for long periods with inhaled corticosteroids and itraconazole or another antifungal agent. Novel immunotherapies are on the horizon.
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Fungal pneumonia is increasingly common, particularly in highly immunosuppressed patients, such as solid organ or hematopoietic stem cell transplant recipients, and the diagnosis is evolving. Although standard techniques such as microscopy and culture remain the mainstays of diagnosis, relatively recent advances in serological and molecular testing are important additions to the field. This article reviews the laboratory tools used to diagnose fungal respiratory disease.
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Pulmonary histoplasmosis is an important cause of morbidity in the United States. Several outbreaks of acute pulmonary histoplasmosis have been linked to potentially preventable environmental exposures. Progressive disseminated histoplasmosis, which is seen frequently in the growing population of immunocompromised hosts, often presents with prominent pulmonary manifestations and is more commonly encountered in hospitalized patients than acute, subacute, or chronic pulmonary histoplasmosis. ⋯ Posaconazole exhibits promise as a salvage agent. Antifungal prophylaxis is not routinely recommended for at-risk populations. Measures to minimize environmental contamination may reduce the risk of epidemic-type acute pulmonary histoplasmosis related to high-risk exposures.
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Semin Respir Crit Care Med · Dec 2011
ReviewPneumonia and lung infections due to emerging and unusual fungal pathogens.
Invasive mold infections affecting the lungs are increasing in incidence and diversity. Severely immunocompromised patients are particularly vulnerable to infection from unusual, normally nonpathogenic fungi that are found naturally in the environment. Certain fungi such as Scedosporium and the dematiaceous fungi also cause lung disease in hosts without overt immune compromise. ⋯ Many rare molds and yeasts demonstrate reduced in vitro susceptibility to antifungal agents. Although amphotericin B formulations remain clinically useful for many of these infections, voriconazole and posaconazole are more effective for some of these difficult-to-treat pathogens. Surgical resection of diseased tissue and support of the host immune system are often required to optimize outcomes.