Dick Chung

The Changing Epidemiology of Vancomycin-Resistant Enterococcus (VRE) Bacteremia in Allogeneic Hematopoietic Stem Cell Transplant (HSCT) Recipients

The impact of the rising prevalence of vancomycin-resistant Enterococcus (VRE) prior to hematopoietic stem cell transplantation (HSCT) and changes in transplant techniques on risk of VREB (VRE bacteremia) early after HSCT is not known. This is a retrospective study of 247 adult patients who underwent allogeneic HSCT in the years 2008 and 2009 at the Memorial Sloan-Kettering Cancer Center. Sixty-eight of 247 (27.5%) patients were VRE colonized on pretransplant screening. VRE was the leading cause of bacteremia in the first 30 days after HSCT; 23 of 43 (53.5%) patients with positive blood cultures had VRE. Only 13 (57%) of the 23 patients with early VREB were colonized with VRE on pre-HSCT screening cultures. Mortality was directly attributable to VRE infection in 9% of patients with early VREB. VRE is emerging as the most common cause of preengraftment bacteremia in patients undergoing allogeneic HSCT, and is associated with substantial mortality. Pre-HSCT screening for VRE with stool cultures will not identify all patients who are at risk for VREB. The use of alternate agents with activity against Gram-positive bacteria for fever and neutropenia early after HSCT should be evaluated further in prospective studies.

Hepatic Safety of Voriconazole after Allogeneic Hematopoietic Stem Cell Transplantation

Voriconazole is increasingly used in allogeneic hematopoietic stem cell transplantation (HSCT) for prophylaxis and treatment of fungal infections. Hepatic dysfunction is common in patients undergoing HSCT and may have an impact on the clinical decision to institute voriconazole. We conducted a retrospective review of all adult and pediatric HSCT recipients who received >2 consecutive doses of voriconazole between January 2005 and February 2008. Clinical hepatotoxicity was defined as the subjective attribution of liver enzyme elevation (even a mild one) to hepatotoxicity because of voriconazole by the treating physician and leading to discontinuation of voriconazole. Biochemical hepatotoxicity was defined as an elevation in one or more liver enzymes to >3 times the upper limit of normal or >3 times the baseline value if abnormal at baseline. Liver enzymes assessed included aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and total bilirubin. Simple and multiple logistic regressions were used to define the risks for hepatic dysfunction. The Wilcoxon signed-rank test was used to assess the differences in liver function test values before, during, and after the use of voriconazole. Sixty-eight of 200 patients (34%) developed hepatotoxicity while on voriconazole. The median duration of voriconazole therapy was 72 days (range, 1-804 days). Biochemical hepatotoxicity occurred in 51 patients (75%); clinical hepatotoxicity, in 17 patients (25%). Thirty-five (51%) of the patients with hepatotoxicity required discontinuation of therapy. In simple logistic regression, acute graft-versus-host disease (GVHD) was a risk factor for hepatotoxicity, and receipt of a T-cell depleted allograft was protective. In multiple logistic regression, acute GVHD (P = .002) remained significant. There were no cases of liver failure or death attributed to voriconazole. In this cohort of patients undergoing allogeneic HSCT, the rate of hepatotoxicity while on voriconazole was 34%. In general, the hepatic dysfunction was mild and reversible. Voriconazole therapy with monitoring appears to be reasonably safe for use in HSCT recipients at high risk for invasive fungal infections.

Hematologic safety profile of linezolid in the early periengraftment period after allogeneic stem cell transplantation.

Vancomycin-resistant enterococci (VRE) are common pathogens of bloodstream infections in the peritransplantation period. Linezolid is approved by the FDA for treating VRE infections, but has been associated with low rates of hematologic toxicity in the general population; thus, there are concerns about its potential myelotoxicity in the allogeneic hematopoietic stem cell transplantation (HSCT) setting. We examined the impact of linezolid treatment on the times to neutrophil and platelet engraftment in 33 patients who underwent HSCT. In this retrospective case-controlled study conducted from 2000 through 2007, cases received > or = 7 consecutive days of linezolid therapy, starting before day +8 post-HSCT. Controls received > or = 7 consecutive days of vancomycin therapy before day +8 and were matched to cases by age and conditioning regimen. The cumulative incidence function was used to estimate the probabilities for the times to neutrophil and platelet engraftment. A competing-risk regression model was used to determine whether times to engraftment differed for cases and controls. A total of 33 cases were compared with 33 controls. The median duration of treatment after stem cell infusion was 14 days (range, 7 to 34 days) for linezolid and 16 days (range, 8 to 33 days) for vancomycin. The rates of neutrophil and platelet engraftment were similar between the cases and controls. After adjusting for baseline characteristics, no difference in the times to neutrophil or platelet engraftment was seen between the 2 groups. Our findings demonstrate no adverse effect on the times to neutrophil or platelet engraftment with linezolid use. Larger prospective studies are needed to fully determine the hematologic safety of linezolid in patients undergoing HSCT.