Lower blood levels of isavuconazole in critically ill patients compared with other populations: possible need for therapeutic drug monitoring.

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 ±â€Š1.7) 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 ±â€Š2.26 mg/L. Significantly lower levels were observed in the ICU versus the non-ICU population: mean 2.02 ±â€Š1.22 versus 4.15 ±â€Š2.31 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.

Delafloxacin for the treatment of adult patients with community-acquired bacterial pneumonia.

INTRODUCTION: Delafloxacin is a novel fluoroquinolone with peculiar characteristics such as a weak acid character, frequent in vitro activity against methicillin-resistant Staphylococcus aureus (MRSA), and a low potential for resistance selection compared with other fluoroquinolones. AREAS COVERED: The present narrative review summarizes the available data on the use of delafloxacin for the treatment of community-acquired bacterial pneumonia (CABP). EXPERT OPINION: Delafloxacin is a novel fluoroquinolone with a unique profile and some interesting characteristics for the treatment of CABP, such as its marked activity against gram-positive bacteria, including MRSA, the possible use as monotherapy (owing to anti-Gram-negative and anti-atypical bacteria activity), the retained activity against many Gram-positive organisms resistant to other fluoroquinolones, and the availability of both oral and intravenous formulations. The results of the DEFINE-CABP phase-3 randomized controlled trial have shown noninferiority of delafloxacin vs. moxifloxacin for the treatment of CABP, thereby providing a further option for this indication. Against this background, future post-marketing experiences remain of crucial importance for further refining the place in therapy of delafloxacin in the real-life management algorithms of CABP, either as first-line option or step-down/outpatient treatment.

Current pharmacotherapy for methicillin-resistant Staphylococcus aureus (MRSA) pneumonia.

INTRODUCTION: Currently, several antibiotics are active against methicillin-resistant Staphylococcus aureus (MRSA) and can be used for the treatment of pneumonia. They show great variability in terms of antibiotic class, indication, pharmacodynamic/pharmacokinetic properties, type of available formulations, spectrum of activity against bacteria other than MRSA, and toxicity profile. AREAS COVERED: In this narrative review, the authors discuss the characteristics of currently available agents for the treatment of MRSA pneumonia. EXPERT OPINION: The availability of different agents with anti-MRSA activity, and approved for the treatment of pneumonia can allow a personalized approach for any given patient based on the severity of the disease, the setting of occurrence, the patient's baseline risk of toxicity and drug interactions, and the possibility of oral therapy whenever early discharge or outpatient treatment are possible. Although some gray areas still remain, like the lack of high certainty evidence on the efficacy of some old agents and on the precise role of companion agents with toxin inhibitory activity in the case of necrotizing pneumonia, the frequent availability of different treatment choices, each with peculiar characteristics, is already allowing an important step toward a precision medicine approach for the treatment of MRSA pneumonia.