Search

BACKGROUND Recent antimicrobial resistance data are lacking from inpatient oncology settings to guide infection prophylaxis and treatment recommendations. We describe central line-associated bloodstream infection (CLABSI) pathogens and antimicrobial resistance patterns reported from oncology locations to the Centers for Disease Control and Prevention's National Healthcare Safety Network (NHSN). METHODS CLABSI data reported to NHSN from 2009 to 2012 from adult inpatient oncology locations were compared to data from nononcology adult locations within the same hospitals. Pathogen profile, antimicrobial resistance rates, and CLABSI incidence rates per 1000 central line-days were calculated. CLABSI incidence rates were compared using Poisson regression. RESULTS During 2009-2012, 4654 CLABSIs were reported to NHSN from 299 adult oncology units. The most common organisms causing CLABSI in oncology locations were coagulase-negative staphylococci (16.9%), Escherichia coli (11.8%), and Enterococcus faecium (11.4%). Fluoroquinolone resistance was more common among E. coli CLABSI in oncology than nononcology locations (56.5% vs 41.5% of isolates tested; P < .0001) and increased significantly from 2009-2010 to 2011-2012 (49.5% vs 60.4%; P = .01). Furthermore, rates of CLABSI were significantly higher in oncology compared to nononcology locations for fluoroquinolone-resistant E. coli (rate ratio, 7.37; 95% confidence interval [CI], 6.20-8.76) and vancomycin-resistant E. faecium (rate ratio, 2.27, 95% CI, 2.03-2.53). However, resistance rates for some organisms, such as Klebsiella species and Pseudomonas aeruginosa, were lower in oncology than in nononcology locations. CONCLUSIONS Antimicrobial-resistant E. coli and E. faecium have become significant pathogens in oncology. Practices for antimicrobial prophylaxis and empiric antimicrobial therapy should be regularly assessed in conjunction with contemporary antimicrobial resistance data.

Background. Histoplasmosis may complicate tumor necrosis factor (TNF)–α blocker therapy. Published case series provide limited guidance on disease management. We sought to determine the need for long-term antifungal therapy and the safety of resuming TNF-α blocker therapy after successful treatment of histoplasmosis. Methods. We conducted a multicenter retrospective review of 98 patients diagnosed with histoplasmosis between January 2000 and June 2011. Multivariate logistic regression was used to evaluate risk factors for severe disease. Results. The most commonly used biologic agent was infliximab (67.3%). Concomitant corticosteroid use (odds ratio [OR], 3.94 [95% confidence interval {CI}, 1.06–14.60]) and higher urine Histoplasma antigen levels (OR, 1.14 [95% CI, 1.03–1.25]) were found to be independent predictors of severe disease. Forty-six (47.4%) patients were initially treated with an amphotericin B formulation for a median duration of 2 weeks. Azole treatment was given for a median of 12 months. TNF-α blocker therapy was initially discontinued in 95 of 98 (96.9%) patients and later resumed in 25 of 74 (33.8%) patients at a median of 12 months (range, 1–69 months). The recurrence rate was 3.2% at a median follow-up period of 32 months. Of the 3 patients with recurrence, 2 had restarted TNF-α blocker therapy, 1 of whom died. Mortality rate was 3.2%. Conclusions. In this study, disease outcomes were generally favorable. Discontinuation of antifungal treatment after clinical response and an appropriate duration of therapy, probably at least 12 months, appears safe if pharmacologic immunosuppression has been held. Resumption of TNF-α blocker therapy also appears safe, assuming that the initial antifungal therapy was administered for 12 months.

Background Invasive candidiasis is the third most common bloodstream infection in the intensive care unit (ICU) and is associated with morbidity and mortality. Prophylaxis and preemptive therapy are attractive strategies for this setting. Methods We conducted a multicenter, randomized, double-blind, placebo-controlled trial of caspofungin as antifungal prophylaxis in 222 adults who were in the ICU for at least 3 days, were ventilated, received antibiotics, had a central line, and had 1 additional risk factor (parenteral nutrition, dialysis, surgery, pancreatitis, systemic steroids, or other immunosuppressants). Subjects' (1,3)-β-d-glucan levels were monitored twice weekly. The primary endpoint was the incidence of proven or probable invasive candidiasis by EORTC/MSG criteria in patients who did not have disease at baseline. Patients who had invasive candidiasis were allowed to break the blind and receive preemptive therapy with caspofungin. The preemptive approach analysis included patients all patients who received study drug, including those positive at baseline. Results The incidence of proven/probable invasive candidiasis in the placebo and caspofungin arms was 16.7% (14/84) and 9.8% (10/102), respectively, for prophylaxis (P = .14), and 30.4% (31/102) and 18.8% (22/117), respectively, for the preemptive approach (P = .04); however, this analysis included patients with baseline disease. There were no significant differences in the secondary endpoints of mortality, antifungal use, or length of stay. There were no safety differences. Conclusions Caspofungin was safe and tended to reduce the incidence of invasive candidiasis when used for prophylaxis, but the difference was not statistically significant. A preemptive therapy approach deserves further study. Clinical trials registration NCT00520234.

Background Febrile neutropenia (FN) is a common and serious complication in patients undergoing hematopoietic stem cell transplant (HSCT). Typically, broad-spectrum antibiotics (BSA) are promptly initiated with controversy on timing of de-escalation. ECIL 2013 guidelines suggest de-escalation after 72 hours if the patient is infection free and afebrile for at least 48 hours. Conversely, the 2011 IDSA recommends continuing BSA in patients who defervesce until absolute neutrophil count (ANC) recovery. In 2014, our center’s practice changed to early de-escalation and we sought to compare outcomes between the two practices. Methods We retrospectively analyzed patients who underwent a HSCT in 2013 and 2017 with an episode of FN and negative infectious work up. The standard care group (SCG) were continued on BSA until ANC recovery. The early de-escalation group (EDG) de-escalated to fluoroquinolone prophylaxis at least 24 hours prior to ANC recovery after the patient was fever free for 48 hours. The primary end-point was duration of BSA. Secondary endpoints included 30-day mortality, re-hospitalization and length of stay (LOS) from FN. Median values were compared with the Mann–Whitney test. Results Among 229 HSCT patients, 155 (68%) developed FN post-transplant and of those 97 (63%) were without infection (13 EDG and 84 SCG). Initial FN duration of BSA was less in the EDG (3.09 days vs. 4.69 days, P = 0.069). Total antibiotic free days to 30 day follow-up were similar (EDG 24.08 vs SCG 25.19, P = 0.81). Duration of neutropenia was less in the SCG with 7.99 days compared with 11.69 days in the EDG (P = 0.007), but duration of initial fever was less in the EDG (2.55 days vs. 3.33 days, P = 0.023). 30 day mortality was 0% in both groups. Rates of re-hospitalization within 30 days were approximately the same (7.1% vs. 7.6%). LOS from FN was not significantly different with 6.68 days in SCG and 7.75 days in EDG (P = 0.140). More new bacterial infections were identified within 30 days of FN in the SCG than the EDG (10.7% vs. 7.6%). Conclusion Early BSA de-escalation resulted in no significant difference in LOS from FN and fewer days of BSA with 30-day mortality and re-hospitalization rates similar. This data suggest de-escalating BSA prior to ANC recovery is likely safe and leads to less BSA exposure, but more multi-center data are needed. Disclosures All authors: No reported disclosures.

This document updates and expands the initial Infectious Diseases Society of America (IDSA) Fever and Neutropenia Guideline that was published in 1997 and first updated in 2002. It is intended as a guide for the use of antimicrobial agents in managing patients with cancer who experience chemotherapy-induced fever and neutropenia. Recent advances in antimicrobial drug development and technology, clinical trial results, and extensive clinical experience have informed the approaches and recommendations herein. Because the previous iteration of this guideline in 2002, we have a developed a clearer definition of which populations of patients with cancer may benefit most from antibiotic, antifungal, and antiviral prophylaxis. Furthermore, categorizing neutropenic patients as being at high risk or low risk for infection according to presenting signs and symptoms, underlying cancer, type of therapy, and medical comorbidities has become essential to the treatment algorithm. Risk stratification is a recommended starting point for managing patients with fever and neutropenia. In addition, earlier detection of invasive fungal infections has led to debate regarding optimal use of empirical or preemptive antifungal therapy, although algorithms are still evolving. What has not changed is the indication for immediate empirical antibiotic therapy. It remains true that all patients who present with fever and neutropenia should be treated swiftly and broadly with antibiotics to treat both gram-positive and gram-negative pathogens. Finally, we note that all Panel members are from institutions in the United States or Canada; thus, these guidelines were developed in the context of North American practices. Some recommendations may not be as applicable outside of North America, in areas where differences in available antibiotics, in the predominant pathogens, and/or in health care–associated economic conditions exist. Regardless of venue, clinical vigilance and immediate treatment are the universal keys to managing neutropenic patients with fever and/or infection.

Background The empiric initial antibiotic regimen (IAR) for treatment of febrile neutropenia (FN) relies on a knowledge of epidemiology and susceptibility patterns of bacterial bloodstream infections (BSI), especially in high-risk patient populations, i.e., those receiving chemotherapy for hematologic malignancies (HM) or undergoing hematopoietic stem cell transplant (HCT). As the last US national survey of BSI epidemiology in cancer patients was published in 2003, we sought to update these data focusing exclusively on high-risk patients with attention to IARs used and their concordance with susceptibilities of isolated bloodstream pathogens. Methods A prospective ongoing survey among 14 high-volume US cancer centers submitting clinical and microbiologic data from consecutive HM patients with BSI during first FN after cytotoxic chemotherapy or HCT. Concordance between antibiotic and BSI was determined by investigator (AZ, AF) interpretation of susceptibility reports provided by each center compared with IAR used, for single organism bacteremias only. Results Among 294 FN bacteremic episodes (93 HCT), there were 336 bacterial pathogens (48.5% Gram negative [GN] 46.5% Gram positive [GP] and 6% anaerobes), with 88% monomicrobial episodes. E. coli and viridans group Streptococci (VGS) were the most commonly isolated GN and GP, respectively, each accounting for nearly 25% of total organisms identified. IARs included cefepime 61%, piperacillin–tazobactam 24%, and meropenem 8%. Isolates were nonsusceptible to the IAR in 38/227 (17%) of FN episodes. Antibiotic mismatch was more likely to occur with a non-VGS GP (37%) vs. GN (13%) or VGS (2%) P < 0.001. Conclusion This is the first US national survey of high-risk BSI in FN. Although mismatch between BSI and IAR occurs in 17% of FN bacteremia episodes, this is driven primarily by non-VGS GP isolates such as CoNS and MRSA. Currently used IARs, comprised primarily of cefepime and piperacillin–tazobactam, generally provide reliable coverage for GN isolates across the United States (87%) but careful tracking of this rate is essential to identify further erosion of coverage in the current era of antimicrobial resistance. Disclosures A. Zimmer, Merck: Investigator, Research grant. A. G. Freifeld, Merck: Investigator, Research grant. S. Pergam, Merck: Consultant, Consulting fee; Chimerix: Consultant, Consulting fee. K. V. Rolston, Merck: Investigator, Research grant; JMI Laboratories: Investigator, Research grant; Shionogi (Japan): Investigator, Research grant. S. Shoham, Merck: Investigator and Scientific Advisor, Consulting fee and Grant recipient; Astellas: Investigator, Grant recipient; Shionogi (Japan): Investigator, Grant recipient; Gilead: Investigator, Grant recipient; Shire: Investigator, Grant recipient. T. J. Walsh, Merck: Grant Investigator, Research grant; Atellas: Consultant, Grant Investigator and Scientific Advisor, Consulting fee and Research grant; Gilead: Scientific Advisor, Consulting fee; Allergan: Grant Investigator and Scientific Advisor, Consulting fee and Research grant; Scynexis: Grant Investigator, Research grant; Amplyx: Grant Investigator, Research grant; Shionogi: Scientific Advisor, Consulting fee. J. A. Young, GSK: Investigator, The University of Minnesota is reimbursed for contract costs associated with conducting clinical trials of vaccine. I receive no personal financial benefit.. J. Meza, Merck: Investigator, Research grant. Y. Zhang, Merck: Investigator, Research grant.

Background The incidence and epidemiology of invasive fungal infections (IFIs), a leading cause of death among hematopoeitic stem cell transplant (HSCT) recipients, are derived mainly from single-institution retrospective studies. Methods The Transplant Associated Infections Surveillance Network, a network of 23 US transplant centers, prospectively enrolled HSCT recipients with proven and probable IFIs occurring between March 2001 and March 2006. We collected denominator data on all HSCTs preformed at each site and clinical, diagnostic, and outcome information for each IFI case. To estimate trends in IFI, we calculated the 12-month cumulative incidence among 9 sequential subcohorts. Results We identified 983 IFIs among 875 HSCT recipients. The median age of the patients was 49 years; 60% were male. Invasive aspergillosis (43%), invasive candidiasis (28%), and zygomycosis (8%) were the most common IFIs. Fifty-nine percent and 61% of IFIs were recognized within 60 days of neutropenia and graft-versus-host disease, respectively. Median onset of candidiasis and aspergillosis after HSCT was 61 days and 99 days, respectively. Within a cohort of 16,200 HSCT recipients who received their first transplants between March 2001 and September 2005 and were followed up through March 2006, we identified 718 IFIs in 639 persons. Twelve-month cumulative incidences, based on the first IFI, were 7.7 cases per 100 transplants for matched unrelated allogeneic, 8.1 cases per 100 transplants for mismatched-related allogeneic, 5.8 cases per 100 transplants for matched-related allogeneic, and 1.2 cases per 100 transplants for autologous HSCT. Conclusions In this national prospective surveillance study of IFIs in HSCT recipients, the cumulative incidence was highest for aspergillosis, followed by candidiasis. Understanding the epidemiologic trends and burden of IFIs may lead to improved management strategies and study design.

Although West Nile fever is mild in the vast majority of infected persons, there is growing evidence that the disease may be more severe in the immunocompromised population. We describe 3 recipients of kidney or pancreas transplants who developed West Nile fever, 2 of whom had meningoencephalitis. As is the norm when treating serious infections in transplant recipients, a reduction of immunosuppression was pursued for these patients. Despite the severe nature of the disease in 2 patients, all recovered from the disease. The time course of neurologic recovery in the 2 patients with meningoencephalitis is highlighted. We also review the literature on West Nile fever in organ transplant recipients. In areas where West Nile virus is endemic, one must have a high index of suspicion for the illness when dealing with fever in transplant recipients.