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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Paracoccidioidomycosis is a subacute or chronic systemic mycosis caused by Paracoccidioides brasiliensis, a soil saprophyte and thermally dimorphic fungus. The disease occurs mainly in rural workers in Latin America and is the most frequent endemic systemic mycosis in many countries of South America, where almost 10 million people are believed to be infected. Paracoccidioidomycosis should be regarded as a disease of travelers outside the endemic area. ⋯ The lungs are frequently involved, and the pulmonary clinical manifestations must be differentiated from many other infectious and noninfectious conditions. Diagnosis should be based on epidemiological, clinical, and microbiological data. Effective treatment regimens are available to control the fungal infection, but most patients develop fibrotic sequelae that may severely hamper respiratory and adrenal function and the patient's well-being.
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Fungal infections are among the most serious complications of lung transplantation. The 1-year cumulative incidence of invasive fungal infections in lung transplant recipients is 6 to 10%, which is higher than most other solid organ transplant recipients. ⋯ Most centers employ either universal or targeted antifungal prophylaxis in some form, but the agents, doses, durations, and monitoring strategies vary widely from one center to another. This review discusses the salient fungal organisms responsible for infection in lung transplant recipients and management strategies for prevention.
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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.