ArticleThe Journal of antimicrobial chemotherapy2026
Determinants of levofloxacin prophylaxis failure in high-risk haematology patients: a prospective study integrating resistant colonization and pharmacokinetic/pharmacodynamic target attainment.
Article in The Journal of antimicrobial chemotherapy, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
objectivesTo 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.
methodsThis 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.
resultsA 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.
conclusionsLevofloxacin 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.
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