Treatment of Invasive Pulmonary Aspergillosis and Preventive and Empirical Therapy for Invasive Candidiasis in Adult Pulmonary and Critical Care Patients. An Official American Thoracic Society Clinical Practice Guideline

Abstract

Background: The incidence of invasive fungal infections is increasing in immune-competent and immune-compromised patients. An examination of the recent literature related to the treatment of fungal infections was performed to address two clinical questions. First, in patients with proven or probable invasive pulmonary aspergillosis, should combination therapy with a mold-active triazole plus echinocandin be administered vs. mold-active triazole monotherapy? Second, in critically ill patients at risk for invasive candidiasis who are non-neutropenic and are not transplant recipients, should systemic antifungal agents be administered either as prophylaxis or as empiric therapy?

Methods: A multidisciplinary panel reviewed the available data concerning the two questions. The evidence was evaluated, and recommendations were generated using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach.

Results: A conditional recommendation was made for patients with proven or probable invasive pulmonary aspergillosis to receive either initial combination therapy with a mold-active triazole plus an echinocandin or initial mold-active triazole monotherapy based on low-quality evidence. Further, a conditional weak recommendation was made against routine administration of prophylactic or empiric antifungal agents targeting Candida species for critically ill patients without neutropenia or a history of transplant based on low-quality evidence.

Conclusions: The recommendations presented in these Guidelines are the result of an analysis of currently available evidence. Additional research and new clinical data will prompt an update in the future.

Keywords: pulmonary aspergillosis; invasive candidiasis; therapeutics; echinocandins; triazoles.

Figure 1.

Flow diagram of literature selection and review for question 1.

Figure 2.

Meta-analysis of mortality following primary therapy in question 1. Events numbers for study by Upton and colleagues (19) were not reported in the published article and therefore we used the calculated RR to perform the meta-analysis. Studies by Upton and colleagues (19) and Raad and colleagues (17) reported 3 months mortality and Pagano and colleagues (16) reported 4 months mortality. RCT by Marr and colleagues (18) reported 3 months mortality. CI = confidence interval; RCT = randomized controlled trial; RR = relative risk.

Figure 3.

Meta-analysis of mortality following salvage therapy in question 1. CI = confidence interval; RR = relative risk.

Figure 4.

Flow diagram of literature selection and review for question 2. RCT = randomized controlled trial.

Figure 5.

Meta-analysis of mortality in question 2 according to strategy of therapy. CI = confidence interval; RR = relative risk.

Figure 6.

Meta-analysis of mortality in question 2 according to drug class. CI = confidence interval; RR = relative risk.