Marieke Pereboom

Prolongation of the QTc interval may result in Torsade de Pointes, a ventricular arrhythmia. Numerous risk factors for QTc interval prolongation have been described, including the use of certain drugs. In clinical practice, there is much debate about the management of the risks involved. In this study, we quantified the effect of these risk factors on the length of the QTc interval.

Purpose. Ciprofloxacin may prolong the QT interval and increase the risk of Torsade de Pointes (TdP). Intravenous administration of ciprofloxacin in patients with additional risks may elevate the risk of QTc interval prolongation. We prospectively assessed whether intravenous ciprofloxacin prolongs the QT interval in patients with additional co-morbidities and risk factors. We also reviewed the literature on the QT prolonging effect or TdP inducing effect of ciprofloxacin. Methods. ICU Patients who were treated with intravenous ciprofloxacin as part of their therapy were recruited. ECG was recorded within 60 min before start and in the last 30 min of 1 h infusion, or within 30 min after the end of ciprofloxacin infusion. QT interval was corrected for the heart rate using both Bazett’s and Fridericia’s formula. The changes were analyzed using the paired Student’s t-test. Results. Ten patients were included in the study (average age 74-y, 6 males). The average baseline QTc interval corrected with Bazett’s formula was 448 ms that was shortened during or after ciprofloxacin infusion by 3 ms and 2 ms based on Bazett’s (p=0.67) and Fridericia’s (p=0.68) formula, respectively. No observational study or cohort study thus far has shown that ciprofloxacin has a QT prolonging effect or increases the risk of TdP or (cardiovascular) mortality. Conclusion. Based on our results and the results of previous studies, it is unlikely that ciprofloxacin has a clinically relevant QT prolonging effect or an increased risk of TdP. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.

Intravitreal bevacizumab is frequently used off-label for the treatment of neovascular age-related macular degeneration, but there are concerns about the safety of intravitreal administered bevacizumab. It is suggested that repackaging bevacizumab in plastic syringes could affect the safety due to the unknown shelf life of the syringes. In this study, we analyzed the shelf life of the repackaged bevacizumab syringes, stored at 4 degrees C, at certain time intervals. Over the 32 days tested, bevacizumab concentration and the pH were stable. However, the number of particles in the repackaged bevacizumab syringes increased during storage at 4 degrees C and had exceeded the limits for intravitreal injections after 7 days. Since the number of particles seems to be the limitation of the shelf life of repackaged bevacizumab, it is necessary to quantify the number of particles in repackaged bevacizumab. Based on our results the maximum shelf life of repackaged bevacizumab should be 3 days.

Background. Fluconazole is recommended as first-line treatment in invasive candidiasis in children and infants. Although timely achievement of adequate exposure of fluconazole improves outcome, therapeutic drug monitoring is currently not recommended. Methods. We conducted a retrospective study of critically ill children treated with fluconazole from January 2007 to October 2013 and for whom fluconazole concentrations were available. We collected demographic, clinical, and treatment data through review of the medical records and determined the correlation of clinical variables with the fluconazole concentration. Additionally, we assessed the relation between the fluconazole concentration and the time to culture conversion in patients with proven invasive candidiasis. Results. In total, 99 pediatric patients met the inclusion criteria. The fluconazole concentration was considered subtherapeutic in 40% of the patients. Multiple linear regression analysis showed a significant, independent, and positive association of the fluconazole trough concentration with the fluconazole dose (P <.001), weight (P = .009), and the serum urea concentration (P = .003), and a significant, independent, and negative association with age (P = .004) and cancer as an underlying condition (P = .003). A higher fluconazole concentration was associated with a shorter time to culture conversion (hazard ratio = 1.076 [95% confidence interval, 1.017–1.138]; P = .011). Conclusions. The fluconazole concentration is not sufficient in pediatric cancer patients with the currently recommended dose regimen, and a higher fluconazole dose is required to achieve adequate drug exposure. Therapeutic drug monitoring of fluconazole can be a valuable tool to detect possible underexposure in critically ill children.