QTc prolongation during levofloxacin and triazole combination chemoprophylaxis: Prevalence and predisposing risk factors in a cohort of hematopoietic cell transplantation recipients.

BACKGROUND: QTc interval prolongation has been reported when combining fluoroquinolones and triazoles for chemoprophylaxis in cancer patients. Herein, we aimed to identify the prevalence and contributing factors to QTc prolongation in hematopoietic cell transplantation (HCT) recipients who received these agents during the neutropenic phase. METHODS: This is a retrospective medical chart review conducted at a university hospital in Lebanon from 2017 to 2020. It included all adult HCT inpatients on antimicrobial prophylaxis with fluoroquinolones and triazoles and whose baseline ECG monitoring done prior to chemoprophylaxis administration, then on day-3 and day-6 of therapy, were available. RESULTS: Overall, 68 HCT recipients met our inclusion criteria, of which 22% developed QTc prolongation. Based on bivariate analysis, female gender contributed to QTc prolongation (P = 0.001). There was a trend to QTc prolongation in patients with predisposing thyroid disease (P = 0.12), grade 2 vomiting and diarrhea (P = 0.16, P = 0.46, respectively), baseline hypokalemia (P = 0.18) and hypocalcemia (P = 0.3), hypomagnesemia on day-3 (P = 0.21) and day-6 hyponatremia (P = 0.36). Patients receiving two or more drugs with a known or probable risk of QTc prolongation (other than the fluoroquinolone/ triazole combination) were more prone to experience a prolonged QTc interval (P = 0.09). None of the patients that had QTc prolongation died or developed serious arrhythmias. CONCLUSION: The prevalence of QTc prolongation was 22% among HCT recipients on fluoroquinolone and triazole prophylaxis, yet we did not identify any independent risk factors for this issue. None of the patients that had QTc interval prolongation died or developed serious arrhythmias.

Once-daily aminoglycoside dosing: An update on current literature.

PURPOSE: The advantages and disadvantages of once-daily versus conventional dosing of aminoglycoside antibiotics are reviewed. SUMMARY: Although administration of multiple daily doses remains the standard method of aminoglycoside dosing, once-daily dosing may provide enhanced clinical efficacy and reduced toxicity in selected patient populations; demonstrated pharmacokinetic and pharmacodynamic advantages include enhanced postantibiotic effect and an increased likelihood of a high ratio of serum peak concentration to minimum inhibitory concentration. Published evidence identified in a MEDLINE search covering the period 1985-2014 indicates that once-daily high-dose aminoglycoside therapy generally provides clinical effectiveness equivalent or superior to that of multiple-daily dosing. The risk of nephrotoxicity appears to be comparable with once- and multiple-daily aminoglycoside dosing. Several nomograms have been developed to facilitate once-daily dosing; the Hartford nomogram (using a dose of 7 mg/kg) is the most extensively tested and generally considered the most reliable. However, although those nomograms are convenient to use and may reduce expenses, a daily dosing regimen determined by individualized pharmacokinetic monitoring is likely to be more effective for achieving specific serum concentrations and may be a preferable approach for some patients. Patients who are pregnant or have liver failure, severe renal insufficiency, serious illness, or nutritional deficiency are not appropriate candidates for once-daily dosing. CONCLUSION: Once-daily aminoglycoside dosing is an effective, well-established method to achieve therapeutic efficacy while limiting the risk of toxicity and simplifying the processes of dosing and monitoring.