Intrapulmonary disposition of amphotericin B after aerosolized delivery of amphotericin B lipid complex (Abelcet; ABLC) in lung transplant recipients.

BACKGROUND: Inhaled amphotericin preparations have been used for prophylaxis against invasive aspergillosis in lung transplant recipients. However, no published data exist regarding the pharmacokinetic profile of amphotericin B lipid complex in lung transplant recipients. METHODS: We prospectively determined the concentrations of amphotericin B in the epithelial lining fluid (ELF) and plasma after aerosolized nebulization (AeroEclipse), of amphotericin B lipid complex at 1 mg/kg every 24 hr for 4 days in 35 lung transplant recipients. One brochoalveolar lavage sample and a simultaneous blood sample were collected at various time points after the fourth dose from each subject. High-performance liquid chromatography and high-performance liquid chromatography-MS-MS were used to measure amphotericin B. RESULTS: Concentrations of amphotericin B in ELF (median, 25-75 IQR) were at 4 hr (n=5) 7.20 µg/mL (1.3-17.6), 24 hr (n=6) 8.26 µg/mL (3.9-82.7), 48 hr (n=5) 2.15 µg/mL (1.4-5.5), 72 hr (n=4) 1.25 µg/mL (0.75-5.5), 96 hr (n=6) 0.86 µg/mL (0.55-1.4), 120 hr (n=4) 1.04 µg/mL (0.44-1.6), 144 hr (n=1), 4.25 µg/mL, 168 hr (n=3) 1.14 µg/mL, and 192 hr (n=1) 1 µg/mL. The plasma concentration of the drug remained below 0.08 µg/mL at all time points. During the study, the side effects noted included wheezing, coughing, and 12% decline in forced expiratory volume in 1 sec. CONCLUSIONS: We conclude that administration through aerosolized nebulization of amphotericin B lipid complex every 24 hr for 4 days in lung transplant recipients achieved amphotericin B concentrations in ELF above minimum inhibitory concentration of the Aspergillus nearly at 168 hr after the last inhaled dose and is well tolerated.

Experience with immune monitoring in lung transplant recipients: correlation of low immune function with infection.

BACKGROUND: Lung transplants, in particular, have the highest rate of infections among solid organ transplant recipients. However, there is no existing objective measure to predict the development of infections. We report the correlation between Cylex ImmuKnow (ng/mL ATP) values and various infectious syndromes in a large prospective cohort of lung transplant recipients. METHODS: We followed up 175 lung transplants that developed 129 infectious episodes. Multiple logistic regression analysis was performed; generalized estimating equations were used to determine the odds ratio for infections. RESULTS: The median ImmuKnow values in cytomegalovirus disease (49.3 ng/mL ATP), viral infection (70 ng/mL ATP), and bacterial pneumonia (92 ng/mL ATP) were significantly different from stable state (174.8 ng/mL ATP). The median ImmuKnow values of fungal disease (85 ng/mL ATP) and tracheobronchitis (123 ng/mL ATP) had a tendency to be lower than stable state (P=0.10), whereas patients with fungal colonization had comparable ImmunKnow values (167 vs. 174.8 ng/mL ATP). Of the patients colonized with fungus who subsequently developed fungal disease within 100 days, the median value of ImmuKnow was significantly lower than in those who did not develop fungal disease (22.5 vs. 183.5 ng/mL ATP; P<0.0001). Generalized estimating equation regression analysis showed ImmuKnow values less than or equal to 100 ng/mL ATP to be an independent predictor of infections (odds ratio 2.81). CONCLUSIONS: Cylex ImmuKnow assay monitoring has the potential to identify the patients at risk of developing infection and those colonized with fungus that are at risk of developing disease.