Clinical Study of Voriconazole Combined with Caspofungin or Micafungin for Invasive Pulmonary Aspergillus in ICU Mechanical Ventilation Patients

Objective: To explore the clinical efficacy and safety of voriconazole combined with caspofungin or micafungin for invasive pulmonary aspergillus in ICU mechanical ventilation patients. Methods: This was a single center, retrospective, observational study of invasive pulmonary aspergillus patients admitted to the intensive care unit (ICU). Proven and probable invasive pulmonary aspergillus patients with invasive or noninvasive mechanical ventilation who received treatment of voriconazole or voriconazole combined with echinocandins (caspofungin or micafungin) were included in this study. Voriconazole was given with a loading dose of 400 mg IV every 12h for 2 doses, followed by 200mg every 12h. Caspofungin was given a single 70mg loading dose on day 1, followed by 50mg/day thereafter. Micafungin was given 100-200mg/day IV. The clinical efficacy, fungal clearance rate and adverse drug reactions were compared between the two groups. Results: A total of 92 invasive pulmonary aspergillus patients were included in the study. 45 patients received voriconazole treatment (voriconazole group) and 47 patients received voriconazole combined with echinocandins treatment (combined group). After treatment, the total effective rates were 82.98% (39/47) and 64.44% (29/45) in the combined and voriconazole groups, respectively. There were significant differences in the total effective rate between the combined and voriconazole groups (P<0.05). After treatment, the fungal clearance rates were 80.85% (38/47) and 53.33% (24/45) in the combined and voriconazole groups respectively; There were significant differences in fungal clearance rate between two groups (P<0.05). After treatment, the APACHE II scores, white blood cells and procalcitonin of the two groups were significantly lower than those before treatment, arterial oxygenation index of the two groups were significantly higher than those before treatment (P<0.05). Among them, the same change tendencies were observed in the combined group than those in the voriconazole group (P<0.05). The main adverse drug reactions in the combined and voriconazole groups were nausea and vomiting, skin rash and liver and kidney function damage The incidence rates were 12.77% and 13.33% in the combined and voriconazole groups, respectively, and there was no significant difference between two groups (P>0.05). Conclusion: Voriconazole combined with echinocandins (caspofungin or micafungin) therapy for invasive pulmonary aspergillus in ICU mechanical ventilation patients has significant clinical efficacy, high fungal clearance rate, and same drug safety.