Isavuconazole use and TDM in real-world pediatric practice.
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ABSTRACT:
SUBMITTER: Fernandez Ledesma B
PROVIDER: S-EPMC10720574 | biostudies-literature | 2023 Nov
REPOSITORIES: biostudies-literature
Publications
Isavuconazole use and TDM in real-world pediatric practice.
Fernández Ledesma Berta B Mendoza-Palomar Natalia N Melendo Pérez Susana S Fernández-Polo Aurora A Renedo Miró Berta B Pau Parra Alba A Luque Pardos Sonia S Grau Cerrato Santiago S Vima Bofarull Jaume J Martín-Gómez María Teresa MT Pujol Jover Montserrat M Benítez-Carbante Maria Isabel MI Díaz de Heredia Cristina C Soler-Palacin Pere P
Antimicrobial agents and chemotherapy 20231114 12
Isavuconazole (ISA) is approved for treating invasive aspergillosis and mucormycosis in adults, but its use in children remains off-label. We report on the use of ISA in real-world pediatric practice with 15 patients receiving ISA for treatment of invasive fungal infections. Therapeutic drug monitoring (TDM) was performed in all patients, with 52/111 (46.8%) C<sub>trough</sub> determinations out of range, thus supporting the need for TDM in children, especially those receiving extracorporeal mem ...[more]
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Project description:IntroductionCeftazidime-avibactam has proven activity against multidrug-resistant (MDR) bacteria in clinical trials and real-world studies. This study was conducted to describe the patterns of use of ceftazidime-avibactam (including indications and associated antibiotics), and the effectiveness and safety of ceftazidime-avibactam in real-world clinical practice.MethodsThis non-interventional medical chart review study was conducted in 11 countries across the European and Latin American (LATAM) regions. Consecutive patients treated in clinical practice with at least one dose of ceftazidime-avibactam for an approved indication per country label since 01 January 2018 (or launch date in the country if posterior) were enrolled. Effectiveness analyses were conducted in patients treated with ceftazidime-avibactam for at least 72 h.ResultsOf the 569 eligible patients enrolled, 516 (90.7%) were treated for at least 72 h (354 patients from Europe and 162 patients from LATAM); 390 patients (75.7%) had switched from another antibiotic line for Gram-negative coverage. Infection sources were intra-abdominal, urinary, respiratory, bloodstream infections, and other infections (approximately 20% each). K. pneumoniae was the most common microorganism identified in the latest microbiological evaluation before starting ceftazidime-avibactam (59.3%). Two-thirds of microorganisms tested for susceptibility were MDR, of which 89.3% were carbapenem-resistant. The common MDR mechanisms for K. pneumoniae were carbapenemase (33.9%), oxacillinase 48 (25.2%), extended-spectrum beta-lactamase (21.5%), or metallo-beta-lactamase (14.2%) production. Without prior patient exposure, 17 isolates (mostly K. pneumoniae) were resistant to ceftazidime-avibactam. Treatment success was achieved in 77.3% of patients overall (88.3% among patients with urinary infection), regardless of first or second treatment line. In-hospital mortality rate was 23.1%. Adverse events were reported for six of the 569 patients enrolled.ConclusionThis study provides important real-world evidence on treatment patterns, effectiveness, and safety of ceftazidime-avibactam in clinical practice through its recruitment in the European and LATAM regions. Ceftazidime-avibactam is one of the antibiotics to consider for treatment of MDR bacteria.Trial registrationClinicalTrials.gov identifier, NCT03923426.
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