Determinants of levofloxacin prophylaxis failure in high-risk haematology patients: a prospective study integrating resistant colonization and pharmacokinetic/pharmacodynamic target attainment
Journal of Antimicrobial Chemotherapy, cilt.81, sa.9, 2026 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Cilt numarası: 81 Sayı: 9
- Basım Tarihi: 2026
- Doi Numarası: 10.1093/jac/dkag284
- Dergi Adı: Journal of Antimicrobial Chemotherapy
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, CAB Abstracts, Chemical Abstracts Core, CINAHL, EMBASE, Environment Index, MEDLINE, Academic Search Ultimate (EBSCO), Biomedical Reference Collection: Corporate Edition (EBSCO), Health Research Premium Collection (ProQuest), Pharma Collection (ProQuest)
- Hacettepe Üniversitesi Adresli: Evet
Özet
Objectives: To evaluate the clinical and microbiological factors associated with the failure of levofloxacin prophylaxis in high-risk haematology patients, with a particular focus on the attainment of the pharmacokinetic/pharmacodynamic (PK/PD) target. Methods: This prospective case–control study evaluated adult high-risk haematology patients receiving levofloxacin prophylaxis (750 mg/day) during neutropenia. Analyses were performed at the episode level. Individual levofloxacin exposure was described using a population PK model, with the PK/PD target defined as fAUC0–24/MIC ≥80. Surveillance cultures were used to characterize Gram-negative bacterial (GNB) colonization and resistance profiles. Results: A total of 120 neutropenic episodes were analysed. Profound neutropenia was independently associated with prophylaxis failure (OR: 4.17; 95% CI: 1.70–10.2; P = 0.002], whereas achievement of fAUC/MIC ≥80 was independently associated with a reduced risk of failure (OR: 0.12; 95% CI: 0.02–0.62; P = 0.012). Receiver operating characteristic curve analysis identified fAUC/MIC ≥48.46 as the Youden-optimal cutoff (sensitivity 86.0%, specificity 38.3%; Youden J = 0.243). Achievement of this cutoff was also independently associated with a reduced risk of prophylaxis failure (OR: 0.26; 95% CI: 0.083–0.803; P = 0.019). Target non-attainment was strongly associated with levofloxacin-resistant GNB colonization, indicating that PK/PD failure was predominantly MIC driven. Conclusions: Levofloxacin prophylaxis failure appears to reflect an interplay between host factors and inadequate PK/PD target attainment, which was largely influenced by levofloxacin-resistant GNB colonization. The standard 750 mg dose was insufficient in a significant proportion of patients, supporting the need for prophylaxis strategies that integrate PK/PD targets and local resistance patterns.