Susan K. Seo

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.

Effect of antifungal therapy timing on mortality in cancer patients with candidemia.

ABSTRACT Prior studies have shown that delays in treatment are associated with increased mortality in patients with candidemia. The purpose of this study was to measure three separate time periods comprising the diagnosis and treatment of candidemia and to determine which one(s) is associated with hospital mortality. Patients with blood cultures positive for Candida spp. were identified. Subjects were excluded if no antifungal therapy was given or if there was preexisting antifungal therapy. Collected data included the time from blood culture collection to positivity (incubation period), the time from blood culture positivity to provider notification (provider notification period), and the time from provider notification to the first dose of antifungal given (antifungal initiation period). These times were assessed as predictors of inpatient mortality. A repeat analysis was done with adjustments for age, sex, race, underlying cancer, catheter removal, APACHE III score, acute renal failure, neutropenia, and non-Candida albicans species. A total of 106 episodes of candidemia were analyzed. The median incubation time was 32.1 h and was associated with mortality (univariate hazard ratio per hour, 1.025; P = 0.001). The median provider notification and antifungal initiation periods were 0.3 and 7.5 h, respectively, and were not associated with mortality. Adjusted analysis yielded similar results. For cancer patients with candidemia, the incubation period accounts for a significant amount of time, compared with the provider notification and antifungal initiation times, and is associated with in-hospital mortality. Strategies to shorten the incubation time, such as utilizing rapid molecularly based diagnostic methods, may help reduce in-hospital mortality.

Emergence of Daptomycin-Resistant VRE: Experience of a Single Institution

Recent surveillance from US hospitals shows that more than 99.5% of vancomycin-resistant enterococci (VRE) isolates remain susceptible to daptomycin. This report describes emergence of daptomycin-resistant VRE at a major cancer center. The percentage of patients with daptomycin-resistant VRE bacteremia increased from 3.4% in 2007 to 15.2% in 2009 ([Formula: see text]). Without susceptibility data, empiric daptomycin therapy for VRE infections should be used with caution.

Evaluation of postprescription review and feedback as a method of promoting rational antimicrobial use: A multicenter intervention

OBJECTIVEnTo evaluate the impact of postprescription review of broad-spectrum antimicrobial (study-ABX) agents on rates of antimicrobial use.nnnDESIGNnQuasi-experimental before-after study.nnnSETTINGnFive academic medical centers.nnnPATIENTSnAdults receiving at least 48 hours of study-ABX.nnnMETHODSnThe baseline, intervention, and follow-up periods were 6 months each in 2 units at each of 5 sites. Adults receiving at least 48 hours of study-ABX entered the cohort as case-patients. During the intervention, infectious-diseases physicians reviewed the cases after 48 hours of study-ABX. The provider was contacted with alternative recommendations if antimicrobial use was considered to be unjustified on the basis of predetermined criteria. Acceptance rates were assessed 48 hours later. The primary outcome measure was days of study-ABX per 1,000 study-patient-days in the baseline and intervention periods.nnnRESULTSnThere were 1,265 patients in the baseline period and 1,163 patients in the intervention period. Study-ABX use decreased significantly during the intervention period at 2 sites: from 574.4 to 533.8 study-ABX days/1,000 patient-days (incidence rate ratio [IRR], 0.93; 95% confidence interval [CI], 0.88-0.97; P = .002) at hospital B and from 615.6 to 514.4 study-ABX days/1,000 patient-days (IRR, 0.83; 95% CI, 0.79-0.88; P < .001) at hospital D. Both had established antimicrobial stewardship programs (ASP). Study-ABX use increased at 2 sites and stayed the same at 1 site. At all institutions combined, 390 of 1,429 (27.3%) study-ABX courses were assessed as unjustified; recommendations to modify or stop therapy were accepted for 260 (66.7%) of these courses.nnnCONCLUSIONSnPostprescription review of study-ABX decreased antimicrobial utilization in some of the study hospitals and may be more effective when performed as part of an established ASP.

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.

Esophageal Actinomycosis in a Fifty-Three-Year-Old Man with HIV: Case Report and Review of the Literature

Patients with advanced HIV infection commonly present with esophageal symptomatology most frequently due to Candida, cytomegalovirus, or herpes simplex virus. We present a case of a 53-year-old man with AIDS and prior esophageal candidiasis and oral aphthous ulcerations, who developed actinomycosis of the esophagus. This article aims to review clinical characteristics of this and seven previously reported cases occurring in HIV-infected patients. Esophageal actinomycosis is frequently preceded by other esophageal disease that likely results in breach of the mucosal barrier, allowing establishment of the infection. Health care providers should be aware of this rare entity, particularly in those with recurring symptoms, so that a timely diagnosis can be made.

Prevalence of Measles Antibody Among Young Adult Healthcare Workers in a Cancer Hospital: 1980s Versus 1998–1999

Despite the 1989 Advisory Committee on Immunization Practices recommendation of a second dose of vaccine, measles seropositivity rates had declined for adult healthcare workers in their 20s hired at a cancer hospital between 1998 and 1999 compared with those of the same age hired between 1983 and 1988. Continued monitoring will be important as individuals born after 1989 enter the workforce.

Impact of peri-transplant vancomycin and fluoroquinolone administration on rates of bacteremia in allogeneic hematopoietic stem cell transplant (HSCT) recipients: A 12-year single institution study

BACKGROUNDnWe analyzed the effect of peri-transplant prophylaxis on the epidemiology of bacteremia in a 12-year contemporary cohort of allogeneic HSCT recipients at our center.nnnMETHODSnThis was an observational study of 1052 consecutive adult HSCT from 2000 to 2011. Formal prophylaxis with vancomycin only, fluoroquinolone (FQ) only, or vancomycinxa0+xa0FQ was implemented in 2006. The cumulative incidence of day 100 bacteremia was compared between the Early Period (2000-2005) and the Recent Period (2006-2011). Predictors for pre-engraftment bacteremia were analyzed with Cox-proportional hazard models in a subcohort of 821 HSCT who received myeloablative or reduced intensity conditioning (MA/RIC).nnnRESULTSnThe incidence of bacteremia decreased in the Recent Period (32% vs 27%; Pxa0=xa00.002), whereas the rates of resistance in gram-negative rods (GNR) and vancomycin-resistant enterococci (VRE) were similar between the two Periods (P values are not statistically significant.) In multivariate analyses, prophylaxis with vancomycin only or vancomycinxa0+xa0FQ was protective (HRxa0=xa00.5; CIxa0=xa00.30-0.72) and (HRxa0=xa00.3; CIxa0=xa00.12-0.52, Pxa0<xa00.01). Vancomycin or vancomycinxa0+xa0FQ eliminated viridans streptococcal bacteremia (VSB); vancomycinxa0+xa0FQ decreased GNR bacteremia (HRxa0=xa00.35; CIxa0=xa00.15-0.85).nnnCONCLUSIONSnVancomycin-based prophylaxis peri-transplant in MA/RIC HSCT was associated with elimination of VSB and may be considered at centers with high incidence of this infection.

Atypical presentation of Legionella pneumonia among patients with underlying cancer: A fifteen-year review

BACKGROUNDnImmunocompromised patients, especially those receiving treatment with corticosteroids and cytotoxic chemotherapy are at increased risk for developing Legionella pneumonia.nnnOBJECTIVEnThe aim of this study was to determine clinical and radiographic characteristics of pulmonary infection due to Legionella in persons undergoing treatment for cancer and stem cell transplant (SCT) recipients.nnnMETHODSnRetrospective review of Legionella cases at MSKCC over a fifteen-year study period from January 1999 and December 2013. Cases were identified by review of microbiology records.nnnRESULTSnDuring the study period, 40 cases of Legionella infection were identified; nine among these were due to non-pneumophila species. Most cases occurred during the summer. The majority [8/9, (89%)] of patients with non-pneumophila infection had underlying hematologic malignancy, compared to 18/31 (58%) with Legionella pneumophila infections. Radiographic findings were varied-nodular infiltrates mimicking invasive fungal infection were seen only among patients with hematologic malignancy and hematopoietic stem cell transplant (SCT) recipients and were frequently associated with non-pneumophila infections (50% vs 16%; Pxa0=xa00.0594). All cases of nodular Legionella pneumonia were found incidentally or had an indolent clinical course.nnnCONCLUSIONSnLegionella should be considered in the differential diagnosis of nodular lung lesions in immunocompromised patients, especially those with hematologic malignancy and SCT recipients. Most cases of nodular disease due to Legionella are associated with non-pneumophila infections.

Antimicrobial Stewardship: Considerations for a Cancer Center

Since the discovery of penicillin, unbridled enthusiasm for antibiotics has led to their extensive application in medicine, animal care, and agriculture. Injudicious antimicrobial use has also contributed to the emergence and spread of multidrug-resistant bacteria, creating a situation in which there are few or no treatment options for infections due to these organisms. There is increasing awareness that antimicrobial resistance adversely impacts patient safety and public health. In essence, effective antimicrobial stewardship entails the optimal selection, dose, and duration of an antibiotic, resulting in the cure of an infection with minimal toxicity to the patient and minimal impact on selective pressure. A detailed discussion on this important issue is presented in this chapter.