Radical treatment for blastomycosis following unsuccessful liposomal amphotericin.

Pulmonary blastomycosis is a respiratory disease that is caused by the fungus Blastomyces spp, which is acquired through inhalation of the fungal spores. Blastomycosis is relatively uncommon, with yearly incidence rate of 1-2 cases per 100 000 people. Blastomycosis is a disease that is endemic to the midwest and southern regions of the USA, most commonly affecting immunocompromised patients. About 50% of patients are asymptomatic, but for those who progress to acute respiratory distress syndrome (ARDS) mortality can be as high as 80%. Patients with severe blastomycosis are initially treated with intravenous amphotericin B, followed by long-term itraconazole maintenance therapy. In this Grand Round, we present the case of an immunocompetent 35-year-old man diagnosed with chronic pulmonary blastomycosis who had a poor response to 10 days of intravenous liposomal amphotericin B (L-AmB). He was endotracheally intubated and eventually cannulated for extracorporeal membrane oxygenation (ECMO), due to worsening respiratory function. L-AmB was replaced with a continuous infusion of intravenous amphotericin B deoxycholate (AmB-d). He improved significantly and was decannulated from ECMO on day 9 of AmBd continuous infusion and extubated on day 12 Although L-AmB is considered first-line treatment for blastomycosis, mortality remains high for patients with ARDS associated with blastomycosis. This case highlights the importance of considering AmB-d continuous infusions for patients with severe blastomycosis who might have poor clinical responses to L-AmB.

Variable pharmacokinetics of extended interval tobramycin or gentamicin among critically ill patients undergoing continuous venovenous hemofiltration.

BACKGROUND/AIMS: Aminoglycosides are a major weapon against serious Gram-negative rod infections, yet aminoglycoside usage is limited by the risk of nephrotoxicity. The risk of toxicity is reduced by extended-interval dosing of aminoglycosides, defined as 5 - 7 mg/kg given intravenously in intervals of 24 hours or greater based on serum drug concentrations. In critically ill patients undergoing continuous venovenous hemofiltration, there are few published reports of the pharmacokinetics of extended-interval dosing of aminoglycosides. METHODS: We evaluated the pharmacokinetics of extended-interval dosing of gentamicin and tobramycin in 9 critically ill patients on continuous venovenous hemofiltration at Dartmouth-Hitchcock Medical Center between April 2007 and September 2011. RESULTS: Aminoglycoside elimination half-life values were highly variable (median 7 hours, range 3 - 26 hours) and did not correlate with total body weight or estimated creatinine clearance derived from the dose of continuous venovenous hemofiltration. Five of 9 patients cleared infection, but only 4 patients survived to hospital discharge, 2 of whom were dialysis-dependent. CONCLUSION: Extended interval aminoglycoside dosing during continuous venovenous hemofiltration yields unpredictable half-lives and drug levels among high-risk critically ill patients. Close monitoring of serum aminoglycoside levels is required.