Effect of Nebulized Amphotericin B in Critically ill Patients With Respiratory Candida spp. De-colonization: A Retrospective Analysis

The potential relationship among airway Candida spp. de-colonization, nebulized amphotericin B (NAB), and occurrence of ventilator-associated pneumonia (VAP) in patients who are critically ill has not been fully investigated, especially concerning effects on survival. In this observational, retrospective, cohort study in a 22-bed central intensive care unit, we included patients aged >18 years who required mechanical ventilation (MV) for >48 h, with at least two consecutive positive Candida spp. test results. Patients were categorized into NAB and no NAB (control) groups. Propensity matching at 1:1 was performed according to strict standards, and multiple Cox proportional hazard model and multivariate analyses were performed to evaluate the effects of NAB treatment. Throughout an 8-year study period, 526 patients had received MV and had positive respiratory tract Candida spp. cultures. Of these, we included 275 patients and excluded 251 patients. In total, we successfully matched 110 patients from the two groups (each group, n = 55; total population median age, 64 years; Acute Physiology and Chronic Health Evaluation II [APACHE II] score, 25.5; sequential organ failure assessment score, 9). The Candida spp. de-colonization rate was 69.1% in patients treated with NAB. VAP incidence did not differ significantly between the NAB (10.91%) and control (16.36%) groups (P = 0.405). Pseudomonas aeruginosa-related VAP rates differed significantly between the NAB (10.91%) and control (25.45%) groups (P = 0.048). Five (9.1%) patients in the NAB group died during hospitalization compared with 17 (30.9%) controls (P = 0.014). At 28 days, 9 (16.4%) and 16 (29.1%) deaths occurred in the NAB and control groups, respectively, (P = 0.088). The cumulative 90-day mortality rate differed significantly between the two groups (23.6 vs. 43.6%, P = 0.015). Multivariate logistic regression analyses indicated a decreased 90-day mortality in the NAB group (adjusted odds ratio 0.413; 95% confidence interval 0.210–0.812; P = 0.01). In subgroup analyses, the NAB-associated decreased risk of death at 90 days was consistent across subgroups of patients with a Candida score of 2, younger age (<64 years), a higher APACHE II score (≥25), fewer Candida sites (<2), or MV at admission. NAB treatment contributed to Candida spp. airway de-colonization, was associated with a reduced risk of P. aeruginosa-related VAP, and improved 90-day mortality in patients critically ill with Candida spp. tracheobronchial colonization who had received MV for >2 days. NAB may be an alternative treatment option for critically ill patients with VAP.