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Background Isavuconazole is first-line treatment of invasive aspergillosis. Therapeutic drug monitoring (TDM) is deemed not necessary, since most patients reached therapeutic levels (>1 mg/L) in large studies. Low levels were reported in some critically ill patients admitted to the ICU. The aim was to compare isavuconazole levels between critically ill and non-critically ill patients. Materials and methods Retrospective analysis of data from all patients treated with standard-dose isavuconazole between 1 January 2019 and 26 October 2022 was performed. The following data were collected: TDM results from the first 30 days of therapy; ward of admission; demographic and clinical characteristics; continuous renal replacement therapy; extracorporeal membrane oxygenation; and co-administered drugs. Results Seventy-two patients (median age 65 years) and 188 TDM measurements (mean number of samples per patient 2.6 ± 1.7) were included; 33 (45.8%) were ICU patients (3 also had haematological disorders); 39 (54.2%) were non-ICU patients, of whom 31 had haematological disorders. In all patients, the mean isavuconazole blood level was 3.33 ± 2.26 mg/L. Significantly lower levels were observed in the ICU versus the non-ICU population: mean 2.02 ± 1.22 versus 4.15 ± 2.31 mg/L (P  < 0.001). Significantly higher rates of subtherapeutic levels were observed in ICU patients compared with the non-ICU population: all determinations <2 mg/L in 33.3% versus 7.7%, and all determinations <1 mg/L in 12.1% versus 0%, respectively. Predictors of lower isavuconazole levels were admission to the ICU, BMI > 25 kg/m2, bilirubin > 1.2 mg/dL and the absence of haematological disorder. Conclusions ICU patients had significantly lower isavuconazole blood levels compared to non-ICU population. The TDM of isavuconazole for efficacy should be performed in ICU. [ABSTRACT FROM AUTHOR]

Background Severely immunocompromised patients are at risk for prolonged or relapsed Coronavirus Disease 2019 (COVID-19), leading to increased morbidity and mortality. We aimed to evaluate efficacy and safety of combination treatment in immunocompromised COVID-19 patients. Methods We included all immunocompromised patients with prolonged/relapsed COVID-19 treated with combination therapy with 2 antivirals (remdesivir plus nirmatrelvir/ritonavir, or molnupiravir in case of renal failure) plus, if available, anti-spike monoclonal antibodies (mAbs), between February and October 2022. The main outcomes were virological response at day 14 (negative Severe Acute Respiratory Syndrome Coronavirus 2 [SARS-CoV-2] swab) and virological and clinical response (alive, asymptomatic, with negative SARS-CoV-2 swab) at day 30 and the last follow-up. Results Overall, 22 patients (Omicron variant in 17/18) were included: 18 received full combination of 2 antivirals and mAbs and 4 received 2 antivirals only; in 20 of 22 (91%) patients, 2 antivirals were nirmatrelvir/ritonavir plus remdesivir. Nineteen (86%) patients had hematological malignancy, and 15 (68%) had received anti-CD20 therapy. All were symptomatic; 8 (36%) required oxygen. Four patients received a second course of combination treatment. The response rate at day 14, day 30, and last follow-up was 75% (15/20 evaluable), 73% (16/22), and 82% (18/22), respectively. Day 14 and 30 response rates were significantly higher when combination therapy included mAbs. Higher number of vaccine doses was associated with better final outcome. Two patients (9%) developed severe side effects (bradycardia leading to remdesivir discontinuation and myocardial infarction). Conclusions Combination therapy including 2 antivirals (mainly remdesivir and nirmatrelvir/ritonavir) and mAbs was associated with high rate of virological and clinical response in immunocompromised patients with prolonged/relapsed COVID-19. [ABSTRACT FROM AUTHOR]

Background The objective of this study was to compare the clinical outcomes of patients receiving a short course (SC) vs a prolonged course (PC) of antifungal therapy for uncomplicated Candida bloodstream infections (BSIs). Methods All episodes of uncomplicated Candida BSI from September 1, 2018, to August 31, 2020, were reviewed. We compared the primary (all-cause 90-day mortality) and secondary study end points (1-year recurrent Candida BSI and all-cause 1-year mortality) among patients who underwent SC (5–11 days) or PC (12–24 days) therapy using propensity score analysis with the inverse probability of treatment weighting (IPTW) method. Results A total of 114 patients with uncomplicated Candida BSI were included: 35 (30.7%) were classified into the SC group (median [interquartile range {IQR}], 9 [7–11] days) and 79 (69.3%) into the PC group (median [IQR], 14 [14–16] days). Patients in the SC group compared with the PC group had a higher rate of hospitalization in the surgical ward (40.0% vs 19.0%; P =.02) or septic shock at the time of Candida BSI onset (11.4% vs 1.3%; P =.03). The risk of 90-day mortality was not different between the SC and PC groups (n = 8 [22.9%] vs 17 [21.5%], respectively; IPTW-adjusted subdistribution hazard ratio [sHR], 0.67; 95% CI, 0.31–1.47; P =.20). The risk for recurrent Candida BSI within 1 year of completing therapy (IPTW-adjusted sHR, 1.07; 95% CI, 0.20–5.80; P =.94) or for all-cause 1-year mortality (IPTW-adjusted HR, 0.72; 95% CI, 0.35–1.50; P =.38) did not differ between groups. Conclusions Receiving a short vs prolonged course of antifungal therapy did not affect mortality or BSI recurrence in patients with uncomplicated candidemia. [ABSTRACT FROM AUTHOR]