Wilson, John

AbstractBackgroundRespiratory syncytial virus (RSV) infections may be fatal in immunocompromised patients. Aerosolized ribavirin is used for treatment, but it is very costly, teratogenic, and inconvenient. We aimed to assess the outcome of oral ribavirin treatment, with or without intravenous immunoglobulin (IVIG), for RSV infections in moderately to severely immunocompromised patients.MethodsMedical records of RSV polymerase chain reaction (PCR)‐positive patients during 2011–2013 were reviewed retrospectively. Eligible patients were moderately to severely immunocompromised and received oral ribavirin (600–800 mg twice daily) with or without IVIG (500 mg/kg q 48 h) as per protocol.ResultsOf 96 adults with PCR‐proven RSV infection, 34 were moderately to severely immunocompromised and received oral ribavirin treatment. The mean age was 56.2 years (range: 18–90); 21 were male. Underlying conditions were hematologic malignancy with or without hematopoietic stem cell transplant (n = 25), lung transplant (n = 3), or receipt of cytotoxic chemotherapy (n = 11). The presenting symptoms were cough (94%), fever (62%), and dyspnea (59%). The most common radiographic findings were patchy and nodular infiltrates and opacities. Of 34 patients, 31 were hospitalized, with 13 admitted to the intensive care unit and 6 required mechanical ventilation. The median absolute lymphocyte count on presentation was 480 cells/mm3. RSV pneumonia developed in 24 patients. The median initial duration of oral ribavirin treatment was 10 days (range: 4–11); 4 patients were re‐treated. Of 34 patients, 19 received a mean of 2.7 doses of IVIG. Two patients had adverse reactions to ribavirin (hemolytic anemia and lactic acidosis in 1 patient, and altered mental status in another). No patient died from RSV infection. Three patients died from complications of their underlying illness; all others recovered clinically.ConclusionsOral ribavirin with or without IVIG is a well‐tolerated treatment for RSV infection in moderately to severely immunocompromised hosts. Comparative prospective studies should ideally be performed to determine if oral ribavirin is the optimal therapy for RSV infection in this patient population.

The objective of this study is to characterize the outcomes of primary antifungal prophylaxis with voriconazole in patients receiving intensive chemotherapy for acute myelogenous leukemia (AML) or myelodysplastic syndromes (MDS). We conducted a single center, retrospective, cohort study of consecutive adult patients with AML or MDS at Mayo Clinic between January 1, 2006 and July 1, 2010. The study included patients undergoing induction or first relapse combination chemotherapy who received voriconazole 200 mg orally twice daily as prophylaxis during the neutropenic phase. Patient records were evaluated until 30 days after neutrophil recovery for development of invasive fungal infection (IFI) as defined per EORTC/MSG 2008 criteria with computed tomography scans independently reviewed by a radiologist. Therapeutic drug monitoring and reasons for voriconazole discontinuation were documented. Twenty four episodes of IFI were detected among 165 consecutive patients for an overall incidence of 145 per 1000 patients. The incidence of IFI was 24, 42, and 78 per 1000 patients for proven, probable, and possible infection, respectively. Four patients developed proven IFI (n = 2 Aspergillus spp., n = 2 Rhizopus spp.). Serum voriconazole trough concentrations were available in 39 patients, and no statistically significant difference in voriconazole trough level was observed between those with versus without an IFI. Voriconazole prophylaxis was discontinued in 81 patients due to suspected IFI (n = 24), fever of unknown origin (n = 19), adverse events (n = 23), and other causes (n = 17). Voriconazole as primary IFI prophylaxis is safe and may be beneficial in AML/MDS patients receiving intensive chemotherapy. Am. J. Hematol. 88:283–288, 2013. © 2013 Wiley Periodicals, Inc.

ABSTRACT QTc prolongation is a risk factor for development of torsades de pointes (TdP). Combination therapy with fluoroquinolones and azoles is used in patients with hematologic malignancies for prophylaxis and treatment of infection. Both drug classes are implicated as risk factors for QTc prolongation. The cumulative effect on and incidence of QTc prolongation for this combination have not been previously described. A retrospective chart review was performed with hospitalized inpatients from 1 September 2008 to 31 January 2010 comparing QTc interval data from electrocardiogram (ECG) assessment at baseline and after the initiation of combination therapy. Ninety-four patients were eligible for inclusion. The majority, 88 patients (93.6%), received quinolone therapy with levofloxacin. Fifty-three patients (56.4%) received voriconazole; 40 (42.6%) received fluconazole. The overall mean QTc change from baseline was 6.1 (95% confidence interval [CI], 0.2 to 11.9) ms. Twenty-one (22.3%) of the studied patients had clinically significant changes in the QTc while receiving combination fluoroquinolone-azole therapy. Statistically significant risk factors for clinically significant changes in QTc were hypokalemia ( P = 0.03) and a left-ventricular ejection fraction of <55% ( P = 0.02). Low magnesium ( P = 0.11), exposure to 2 or more drugs with the potential to prolong the QTc interval ( P = 0.17), and female sex ( P = 0.21) trended toward significance. Combination therapy with fluoroquinolone and azole antifungals is associated with increased QTc from baseline in hospitalized patients with hematologic malignancies. One in five patients had a clinically significant change in the QTc, warranting close monitoring and risk factor modification to prevent the possibility of further QTc prolongation and risk of TdP.

Purpose Multiple studies have found an association between the prompt initiation of empirically-appropriate antimicrobial therapy and improved patient outcomes. Such empiric-antimicrobial therapy is often broad; however, once the patient's infectious syndrome, microbiology, and susceptibilities are more defined, it is important to refine antimicrobial therapy. Despite the potential benefits of an “antimicrobial de-escalation” approach, it may be difficult to enforce in clinical practice. Mayo Clinic's Computer-Based Antimicrobial Monitoring System (CBAM) is a medical-informatics tool that was used to assist in this endeavor. This study evaluates the hypothesis that CBAM can enhance the de-escalation of vancomycin and broad-spectrum combination antimicrobial therapy. Methods Hospitalized patients at the Mayo Clinic were screened from January through June 2006 using rule-based algorithms incorporated by CBAM. Interventions were performed by physicians and pharmacists as pertinent. These patients were compared with a historical group of patients obtained by CBAM reporting capabilities. De-escalation rates and mean duration of antimicrobial therapy were compared between groups. Results Vancomycin de-escalation rates significantly improved from 33% to 68% with intervention ( P = 0.001). In addition, the average duration of therapy was decreased from 10.4 ± 7.3 days to 7.7 ± 2.4 days among patients who underwent vancomycin de-escalation per recommendation ( P = 0.014). Conclusions Utilizing the Mayo Clinic's CBAM system to identify potential patients for de-escalation is a unique approach and was successful at improving adherence to vancomycin de-escalation.

ABSTRACT The role of combination antibiotic therapy with a beta-lactam and a fluoroquinolone for bacteremia caused by gram-negative bacilli, to our knowledge, has not been previously described. Much of the previous study of combination therapy has included beta-lactams and aminoglycosides. We conducted a large retrospective cohort study to evaluate 28-day all-cause mortality in patients with monomicrobial bacteremia due to aerobic gram-negative bacilli who received either a combination of beta-lactams and fluoroquinolones or beta-lactam monotherapy. We enrolled adult patients admitted to Mayo Clinic hospitals from 1 January 2001 to 31 October 2006 in the study. After stratification of patients by Pitt bacteremia scores, we used Cox regression models to estimate the hazard ratios (HR) for 28-day all-cause mortality after adjusting for the propensity to receive combination therapy. We identified 398 and 304 unique patients with bacteremia caused by gram-negative bacilli who received single and combination antibiotic therapy, respectively. In less severely ill patients with Pitt bacteremia scores of <4, combination therapy was associated with lower 28-day mortality than single therapy (4.2% [9 of 214] versus 8.8% [28 of 319]; adjusted HR, 0.44; 95% confidence interval [CI], 0.20 to 0.98; P = 0.044). In critically ill patients with Pitt bacteremia scores of ≥4, there was no difference in 28-day mortality between combination and single therapy (25.6% [23 of 90] versus 27.8% [22 of 79]; adjusted HR, 0.87; 95% CI, 0.47 to 1.62; P = 0.660). These findings were consistent for 14-day all-cause mortality. In this large cohort, we found for the first time that combination therapy with beta-lactams and fluoroquinolones was associated with a reduction in 28-day all-cause mortality among less severely ill patients with bacteremia caused by gram-negative bacilli.