Development of echinocandin-resistant Candida albicans candidemia following brief prophylactic exposure to micafungin therapy.

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.

Molecular Adsorbent Recirculating System (MARS(®)) removal of piperacillin/tazobactam in a patient with acetaminophen-induced acute liver failure.

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.