ABSTRACT
Background. Coronavirus disease 2019 (COVID-19) associated pulmonary aspergillosis (CAPA) has emerged as a complication in critically ill COVID-19 patients. Corticosteroids are standard of care for COVID-19 patients. Prolonged corticosteroids have been associated with an increased risk of CAPA, but duration of use associated with this risk remains unknown. The objective of this study was to evaluate if the duration of corticosteroid therapy <= 10 days vs > 10 days affects the risk of developing CAPA. Methods. This single-center, retrospective, cohort study included patients >= 18 years old admitted to University Hospital between March 2020 and December 2021, diagnosed with severe COVID-19 pneumonia requiring mechanical ventilation, and who received at least 3 days of corticosteroid treatment. CAPA was defined according to 2020 European Confederation of Medical Mycology and the International Society for Human and Animal Mycology consensus guideline. Baseline characteristics, CAPA, and secondary outcomes were compared using appropriate bivariable analyses. Steroid duration was evaluated as an independent predictor of CAPA in a logistic regression model. Results. Final analysis included 278 patients (n=169 <= 10 days steroid duration;n=109 > 10 day steroid duration). Baseline characteristics were similar between groups, with the exception of acute kidney injury and solid organ transplantation. Median duration of steroids was 6 days in the <= 10 day group vs 18 days in the > 10 day group. In total, 20/278 (7.2%) patients developed CAPA. Patients treated with > 10 days of corticosteroid therapy had significantly higher incidence of CAPA (12% vs 4.1%;p = 0.0156) and duration was independently associated with CAPA (OR 3.25, 95% CI 1.03-10.24). Secondary outcomes including inpatient mortality (43.2% vs 77.1%;p < 0.0001), mechanical ventilation free days at 28 (1.5 vs 0;p < 0.0001) and secondary infections (28.4% vs 44.9% p = 0.0220) were all significantly worse for > 10 day corticosteroid cohort. Conclusion. Duration of corticosteroid treatment > 10 days in critically ill patients is associated with an increased risk of CAPA. Though patients may require corticosteroids for non-COVID-19 indications, clinicians should attempt to limit prolonged courses of corticosteroids in COVID-19 patients.
ABSTRACT
INTRODUCTION: Continuous renal replacement therapy (CRRT) augments a patient's volume of distribution and clearance leading to frequent subtherapeutic levels with intermittently dosed vancomycin. Continuous infusion (CI) vancomycin may offer an advantage in CRRT. Limited studies exist comparing intermittent infusion (II) and CI vancomycin. The purpose of this study was to determine if CI vancomycin in patients receiving CRRT results in more frequent therapeutic concentrations compared to II vancomycin. METHODS: This was a single-center, retrospective chart review of critically ill adult patients receiving CI or II vancomycin while on CRRT between January 1, 2017 and March 31, 2021. The primary outcome was frequency of therapeutic vancomycin concentration (15-25 mcg/mL) at 24 ± 6 hours. Secondary outcomes included percentage of patients therapeutic at first concentration, percentage of patients with subtherapeutic and supratherapeutic concentrations, and intensive care unit (ICU) and hospital mortality. RESULTS: A total of 268 patients were screened and 59 patients met inclusion criteria. Seventeen patients received CI vancomycin and 42 patients received II vancomycin. Baseline characteristics were similar with the exception of more COVID-19 patients, more frequent vasopressor therapy, a higher mean SOFA score, and higher BUN at CRRT initiation in the CI group. The total median loading dose was 1000 mg (IQR 1000-1750 mg) in the CI group and 2000 mg (IQR 1500-2000 mg) in the II group (p=0.003). The daily maintenance dose was 1250 mg (IQR 1250-1500 mg) in CI group and 1000 mg (IQR 1000-1000 mg) in the II group (p< 0.0001). Therapeutic concentration at 24 ± 6 hours was achieved in 52.9% of CI patients compared to 47.6% of II patients (p=0.78). Subtherapeutic concentrations occurred less frequently in the CI group (11.8% vs 42.9%, p=0.03) whereas supratherapeutic concentrations occurred more frequently in the CI group (35.3% vs 2.4%, p=0.0016). ICU and hospital mortality were higher in the CI group (88.2% vs 52.4%, p=0.02). CONCLUSION: CI vancomycin was associated with less subtherapeutic concentrations as compared to II vancomycin in patients receiving CRRT. However, there was no difference in frequency of therapeutic concentrations at 24 hours and CI was associated with more frequent supratherapeutic concentrations.