Impact of a cefepime shortage on dosing regimens and outcomes in hospitalized adults with febrile neutropenia.

BACKGROUND: Drug shortages may negatively impact outcomes in hospitalized patients. A cefepime dosing regimen of 1 gram every 6 hours (1 g q6h) has shown to provide similar exposures above target minimum inhibitory concentrations compared to the regimen of 2 g q8h approved by the United States Food and Drug Administration (FDA) for febrile neutropenia. Our objective was to determine if the dosing regimen of 1 g q6h amidst a cefepime shortage is an appropriate alternative for the treatment of febrile neutropenia. METHODS: A retrospective chart review of hospitalized patients who received cefepime for febrile neutropenia over a two-year period was performed. Patients were grouped based on cefepime dosing strategy: 2 g q8h vs. 1 g q6h. The primary objective was to compare time to defervescence after cefepime initiation. Secondary objectives included all-cause 30-day mortality, duration of antibiotic therapy, and inpatient length of stay. RESULTS: Seventy-five patients in each arm were included. There were no differences in baseline age or severity of illness between groups. There was no difference in the primary objective as median time to defervescence was similar between the 2 g q8h and 1 g q6h groups (69.0 vs. 65.3 h: p= 0.67). Additionally, no differences were found in the secondary objectives of all-cause 30-day mortality (10.7% vs. 9.3%: p = 0.79), duration of therapy (80.8 vs. 88.0 h: p = 0.34), or length of stay (9 vs. 7 days: p = 0.50). CONCLUSIONS: Our study identified no differences in clinical outcomes with cefepime 1 g q6h compared to the traditional FDA-approved 2 g q8h regimen for the treatment of febrile neutropenia.

Hematopoietic stem cell transplant-associated thrombotic microangiopathy: review of pharmacologic treatment options.

BACKGROUND: Transplant-associated thrombotic microangiopathy (TA-TMA) is a multifactorial disorder, which occurs as a result of treatment-related endothelial injury and underlying disease process after hematopoietic stem cell transplantation (HSCT). The reported incidence of TA-TMA after HSCT is 0% to 74% and has shown to be associated with mortality rate of up to 100%. TA-TMA is often diagnosed late in the disease progression, and therapeutic plasma exchange (TPE) has not been shown to produce a high response rate. STUDY DESIGN AND METHODS: All English-language articles describing pharmacologic treatments for TA-TMA were identified using Ovid in the Medline database (1966-May 2014). Search was limited to the HSCT population. RESULTS: Approximately 50% to 63% of patients with TA-TMA respond to withdrawal of the offending agent (calcineurin inhibitors) and TPE, and many will require additional treatment to better control the disease. Unfortunately, there is no established treatment strategy for TA-TMA. A number of pharmacologic agents that have been explored for the treatment of TA-TMA include rituximab, vincristine, defibrotide, pravastatin, and eculizumab. The overall response rates of these agents were similar (69%-80%); however, the differences in the treatment costs vary significantly between these agents. Defibrotide is an investigational agent in the United States; therefore, it is not readily available for use. CONCLUSION: Larger studies are warranted to validate the role of these pharmacologic agents in TA-TMA as upfront therapy and in TPE-refractory patients. Recently suggested predictive biomarkers for TA-TMA, such as neutrophil extracellular traps and circulating endothelial cells, deserve more attention in future studies.

Risk of posttransplant lymphoproliferative disorder associated with use of belatacept.

PURPOSE: Published evidence on a rare but serious malignancy associated with use of the first biological agent approved for long-term maintenance immunosuppression in renal transplant recipients is reviewed. SUMMARY: Belatacept (Nulojix, Bristol-Myers Squibb) is approved by the Food and Drug Administration for use in combination therapy to prevent renal graft rejection in patients who are Epstein-Barr virus seropositive. Belatacept appears to offer some advantages over calcineurin inhibitor-based regimens (e.g., no need for therapeutic drug monitoring), but its use poses a risk of posttransplant lymphoproliferative disorder (PTLD), a rapidly progressing and often lethal malignancy. The efficacy and safety of more-intensive and less-intensive belatacept regimens were established in two Phase III clinical trials, which found that rates of patient and graft survival were comparable to those in cyclosporine users; belatacept was shown to be superior in preserving renal function. The occurrence of PTLD, particularly PTLD involving the central nervous system, in 0-4% of belatacept-treated patients in clinical trials prompted postmarketing initiatives: (1) implementation of a risk evaluation and mitigation strategy (REMS) program to help ensure the safe and proper use of belatacept, (2) longitudinal studies to better define the risks and outcomes of belatacept therapy, and (3) a manufacturer-created patient registry to track belatacept use and encourage voluntary reporting of associated adverse events. CONCLUSION: Appropriate patient selection and adherence to REMS requirements, including patient counseling and facilitation of registry enrollment, are essential in mitigating the increased risk of PTLD associated with belatacept therapy.