Empiric antifungal coverage is indicated in patients with graft-versus-host disease (GVHD) following a stem cell transplant (SCT) who are febrile and neutropenic for extended periods of time. Empiric antifungal coverage is indicated for patients with hematologic malignancies who have persistent fever and neutropenia as well as patients who have GVHD following SCT. Although the prophylactic use of antifungals is a cornerstone of the care for such patients, the selection of the particular antifungal is at the discretion of the clinician. We report a patient case whose surveillance blood cultures obtained 14 days after the switch from voriconazole to micafungin were positive for the growth of Candida albicans. Clinicians prescribing echinocandin therapy for antifungal prophylaxis must be aware of the risks of echinocandin resistance and possible breakthrough candidemia with C. albicans.
The objective of this study was to illustrate the pharmacokinetic removal of piperacillin/tazobactam in an anuric patient on Molecular Adsorbent Recirculating System (MARS(®)). The patient was a 32-year-old woman who presented to a medical intensive care unit with acute liver failure secondary to an acetaminophen overdose. While awaiting transplant, she was started on MARS therapy as a bridge to liver transplant and empirically started on piperacillin/tazobactam therapy. MARS is an extracorporeal hemofiltration device, which incorporates a continuous venovenous hemofiltration (CVVHD) machine linked to an albumin-enriched dialysate filter to normalize excess electrolytes, metabolic waste, and protein-bound toxins. In addition to protein-bound waste, MARS removes water-soluble, low molecular-weight molecules. The patient received piperacillin/tazobactam 4.5 g infused intravenously over 3 h. A steep decline in serum levels occurred between hours 4 and 6 while MARS continued and no antibiotic was infused. The elimination rate constant (k(e)) for the removal of piperacillin in this patent was 0.453 h(-1) and the half-life (λ) was 1.53 h. The k(e) was 2.9-fold higher than with CVVHD alone and the λ was 3.7-fold shorter. Low levels of piperacillin are achieved during MARS therapy, but in the treatment of more resistant organisms, such as Pseudomonas aeruginosa, these low levels may not be adequate to achieve bactericidal activity. Drug levels following a standard infusion of 30 min would likely be even lower. Formalized pharmacokinetic studies of piperacillin/tazobactam removal in patients on MARS therapy are necessary to make clear dosing recommendations.
Vancomycin is a glycopeptide antibiotic used in the treatment of gram-positive infections including methicillin-resistant Staphylococcus aureus (MRSA). The most common adverse reaction to vancomycin is red man syndrome, which is a histaminergic reaction causing a rash on the upper torso, neck, and face after rapid infusion of the drug. Less commonly, vancomycin has been associated with thrombocytopenia. The etiology is believed to be the induction of drug-dependent antibodies, which in turn cause immune-mediated destruction of platelets. We describe a 41-year-old man who received two courses of vancomycin for the treatment of MRSA pneumonia and then experienced a decline in platelet count to a nadir of 15 x 10³/mm³. Vancomycin was discontinued, doxycycline was started, and the patient's platelet count rebounded over the next 6 days. The patient was readmitted to the hospital 2 months later for MRSA bacteremia and was rechallenged with vancomycin. He again experienced a decline in platelet count. Vancomycin was discontinued, and daptomycin was started. The patient's platelet count rebounded to normal levels over the next 5 days. Although the patient experienced acute thrombocytopenia after vancomycin exposure, no bleeding complications occurred, and the patient's platelet count rebounded to normal after the discontinuation of vancomycin. The patient had no other known risk factors for the development of rapid thrombocytopenia. Use of the Naranjo adverse drug reaction probability scale indicated a definite relationship (score of 9) between the patient's development of thrombocytopenia and vancomycin therapy. Although vancomycin was the presumed cause of thrombocytopenia in this patient, no drug-dependent antibody was isolated from blood samples collected after both exposures to vancomycin (analyzed by using a screening assay to identify drug-dependent antibodies to vancomycin [developed by the BloodCenter of Wisconsin]). Although the evidence supporting vancomycin induction of antibody-mediated destruction of platelets was lacking, further studies delineating alternate mechanisms of platelet destruction are warranted. Therefore, even in the absence of a positive antibody test, vancomycin should still be considered in the differential diagnosis as a cause of drug-induced thrombocytopenia.
Background Voriconazole is an azole antifungal utilized for prophylaxis and treatment of invasive fungal infections in hematologic patients. Previous studies have revealed decreased efficacy and increased toxicity with subtherapeutic <1 mcg/mL and supratherapeutic > 4 mcg/mL levels. A voriconazole dose modification guideline was introduced in July 2014 based on a retrospective analysis. Objective The primary objective was to evaluate the voriconazole dose modification guideline. Secondary objectives were to identify patient-specific characteristics that contribute to inadequate levels, adverse effects, and breakthrough invasive fungal infections. Methods This prospective study included 128 patients with 250 admissions who received voriconazole from July 2014 to February 2016. Eligible adult patients receiving voriconazole for prophylaxis or treatment with at least one trough level, drawn appropriately, were included. Demographics, adverse effects, and breakthrough invasive fungal infections were documented. Results Voriconazole use was categorized as: new start, new start with loading dose, or continuation of home therapy. The median initial levels were 1.5, 3.5, and 1.7 mcg/mL with 62% (73/119), 55% (6/11), and 60% (72/120) within the therapeutic range, respectively. Using the voriconazole dose modification guideline, 80% were within goal by the second dose adjustment. Age ≤ 30 and BMI ≤ 25 kg/m had higher rates of subtherapeutic levels in the new start cohorts ( p = 0.024 and p = 0.009). Approximately 7.6% of patients experienced an adverse effect with neurologic/psychological being the most common. A total of 8.5% of patients had a possible, probable or proven breakthrough invasive fungal infections while on voriconazole. Conclusion Using the voriconazole dose modification guideline, the number of patients that reached therapeutic range improved from 36% to 80% by the second dose adjustment ( p = 0.007). This voriconazole dose modification guideline can be utilized to help dose and adjust voriconazole in order to achieve therapeutic levels.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.