Effect of Linezolid on Hematologic Recovery in Newly Diagnosed Acute Myeloid Leukemia Patients Following Induction Chemotherapy.

OBJECTIVE: Assess the effects of linezolid on hematologic outcomes in newly diagnosed patients with acute myeloid leukemia (AML) following induction chemotherapy. DESIGN: Single-center, retrospective, observational, cohort study. SETTING: Large, tertiary care academic medical center. PATIENTS: A total of 225 patients ≥ 18 years admitted between December 2010 and 2013 with newly diagnosed AML were assessed for inclusion. Patients were identified through the use of ICD-9 codes and chemotherapy ordered via the computerized physician order entry system. Sixty-eight patients met inclusion criteria and were grouped into two arms based on antimicrobial treatment: LZD group (linezolid plus gram-negative antimicrobial, n=21) or control group (vancomycin or daptomycin plus gram-negative antimicrobial, n=47). INTERVENTIONS: The LZD group received linezolid ≥ 72 hours. The control group received vancomycin or daptomycin ≥ 72 hours. If patients switched extended gram-positive therapy, they were included in the LZD group as long as they had received ≥ 72 hours of linezolid. MEASUREMENTS/RESULTS: The primary end point of time to neutrophil recovery was not statistically different (28 days for LZD group vs 26 days for control group; p=0.675). The preplanned subgroup analysis of patients who received ≥ 14 days of linezolid demonstrated statistically similar median times to neutrophil recovery (29 days for LZD group vs 26 days for control group; p=0.487). Total duration of extended gram-positive antimicrobial therapy was significantly longer in the LZD group (27 days vs 16 days; p<0.001). Secondary end points not found to be statistically significant included platelet count at time of neutrophil recovery, duration of neutropenia, and length of hospital stay. CONCLUSIONS: There were no significant differences in hematologic outcomes in newly diagnosed AML patients who received linezolid for extended gram-positive antimicrobial coverage following induction chemotherapy. This study provides new insight with a primary focus on the effects of hematologic outcomes when using linezolid in a well-defined acute leukemia population. Further study is warranted with larger populations to assess the potential adverse effects linezolid may have in patients with acute leukemia.

Long-term treatment with temozolomide in malignant glioma.

Six months of maintenance temozolomide (TMZ) following concurrent TMZ chemotherapy and radiation therapy has become the standard of care in the treatment of glioblastoma. In addition, TMZ has also been used to treat other forms of glioma although less evidence of efficacy exists. TMZ administration longer than 6months is common in clinical practice, but it is unusual for the drug to be administered longer than 1 to 2years. We report five patients who received long-term treatment with TMZ chemotherapy at normal dosing levels. One of these patients was diagnosed with glioblastoma, two with anaplastic astrocytoma, one with gliosarcoma, and one with oligo-astrocytoma. The length of treatment in our group of patients ranged from 45 to 85 cycles of TMZ. Common Terminology Criteria for Adverse Events (CTCAE) developed by The National Cancer Institute was used to classify toxicity. Two patients experienced no toxicity per CTCAE guidelines. One patient experienced grade I thrombocytopenia, one developed grade I leukopenia, and one experienced both grade I thrombocytopenia and grade I nausea, all which resolved with either withholding TMZ for 1month or supportive treatment. Our report provides evidence that long-term TMZ chemotherapy is a therapeutic option when appropriately monitored.

The reversal of inhibitors in congenital hemophilia.

Hemophilias A and B are heritable bleeding disorders characterized by deficient baseline levels of factor VIII (fVIII) and factor IX (fIX), respectively. Standard treatment for acute bleeding events and for prophylaxis in patients with severe disease consists of recombinant fVIII and fIX infusions. The development of alloantibodies, or inhibitors, is a serious complication of congenital hemophilia that may impair the effectiveness of fVIII and fIX, leading to increased morbidity and cost of therapy. When inhibitors are present, bypassing agents such as recombinant activated factor VII and factor eight inhibitor bypass agent are available for treatment of bleeding events. Although usually effective, they are costly treatments. Immune-modulatory therapy may reverse inhibitors, allowing fVIII and fIX to be used again. Immune tolerance induction is the chief treatment option to decrease inhibitor levels, but about 20-30% of patients fail this treatment. Alternatively, multiple immune-modulating agents have been tried with limited success. Rituximab, an anti-CD20 monoclonal antibody, is one therapy that has been successful in reducing inhibitor titers in multiple case reports. Although current evidence is limited and questions regarding its use and place in therapy still exist, this agent shows promise for the future.

Emergency pharmacist impact on health care-associated pneumonia empiric therapy.

PURPOSE: Health care-associated pneumonia (HCAP) is a serious infection dependent on proper treatment that often presents in the emergency department (ED) and deviation from treatment guidelines appears to be high. This study was conducted to evaluate the impact of emergency medicine pharmacists (EPhs) on adherence of empiric antibiotic therapy to guideline recommendations. METHODS: A retrospective chart review of adult patients with HCAP who presented to an academic medical center ED from September 1, 2008 to June 30, 2010 was conducted. The control group included those patients with HCAP who presented to the ED outside of the EPhs' hours (23:00-13:00), and the treatment group consisted of those patients who presented during the EPhs' hours (13:00-23:00). RESULTS: The 81 patients presenting inside the EPhs' hours were significantly more likely to receive guideline adherent empiric antibiotics than the 70 patients presenting outside the EPhs' hours (49.38% vs 25.7%, P = .005). Also, patients in the treatment group received antibiotics in a shorter amount of time (11.37 vs 15.56 hours, P = .272) and at more appropriate doses (85.2% vs 77.1%, P = .29) although these outcomes were not statistically significant. CONCLUSION: The presence of the EPh significantly increased the likelihood of at-risk patients receiving empiric antimicrobial therapy consistent with guideline recommendations.