Impact of Empiric Treatment for Vancomycin-Resistant Enterococcus in Colonized Patients Early after Allogeneic Hematopoietic Stem Cell Transplantation.

In recent years, vancomycin-resistant Enterococcus (VRE) colonization is being increasingly encountered in transplant recipients, and VRE has become one of the leading causes of bacteremia early after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Data are sparse on the effect of empiric VRE therapy for febrile, neutropenic allo-HSCT recipients colonized with VRE. All allo-HSCT recipients aged ≥18years who developed VRE bacteremia (VREB) between 2005 and 2014 were identified and categorized as to whether they received empiric or directed VRE therapy. There were 434 (33%) VRE-colonized and 872 (67%) non-VRE-colonized patients during the study period, and 172 of the 434 (40%) VRE-colonized patients received empiric therapy. There was no significant difference in incidence of VREB among colonized patients who did or did not receive empiric therapy (28 of 172 [16%] vs 55 of 262 [21%]; P = .22). There were 95 patients with VREB, of which the majority (83 of 95; 87%) was known to be VRE-colonized. Of the 95 VREB episodes, 29 (31%) were treated with empiric VRE therapy, whereas 66 (69%) were treated with directed therapy. No significant differences in clinical outcomes, including median duration of bacteremia (2 days vs 2 days; P = .39), recurrent VREB (3 of 29 [10%] vs 5 of 66 [8%]; P = .65), 30-day all-cause mortality (1 of 29 [3%] vs 4 of 66 [6%]; P = .62), or VRE-attributable mortality (1 of 29 [3%] vs 1 of 66 [2%]; P = .55), were observed between the empiric therapy and directed therapy groups. Kaplan-Meier curve analysis showed no significant difference in survival at 30days in allo-HSCT recipients with VREB who received empiric therapy and those who received directed therapy (97% vs 94%; P = .62). Based on our data, we recommend against empiric use of VRE-active agents for fever and neutropenia in VRE-colonized patients undergoing allo-HSCT.

Effect of daily chlorhexidine bathing on hospital-acquired infection.

BACKGROUND: Results of previous single-center, observational studies suggest that daily bathing of patients with chlorhexidine may prevent hospital-acquired bloodstream infections and the acquisition of multidrug-resistant organisms (MDROs). METHODS: We conducted a multicenter, cluster-randomized, nonblinded crossover trial to evaluate the effect of daily bathing with chlorhexidine-impregnated washcloths on the acquisition of MDROs and the incidence of hospital-acquired bloodstream infections. Nine intensive care and bone marrow transplantation units in six hospitals were randomly assigned to bathe patients either with no-rinse 2% chlorhexidine-impregnated washcloths or with nonantimicrobial washcloths for a 6-month period, exchanged for the alternate product during the subsequent 6 months. The incidence rates of acquisition of MDROs and the rates of hospital-acquired bloodstream infections were compared between the two periods by means of Poisson regression analysis. RESULTS: A total of 7727 patients were enrolled during the study. The overall rate of MDRO acquisition was 5.10 cases per 1000 patient-days with chlorhexidine bathing versus 6.60 cases per 1000 patient-days with nonantimicrobial washcloths (P=0.03), the equivalent of a 23% lower rate with chlorhexidine bathing. The overall rate of hospital-acquired bloodstream infections was 4.78 cases per 1000 patient-days with chlorhexidine bathing versus 6.60 cases per 1000 patient-days with nonantimicrobial washcloths (P=0.007), a 28% lower rate with chlorhexidine-impregnated washcloths. No serious skin reactions were noted during either study period. CONCLUSIONS: Daily bathing with chlorhexidine-impregnated washcloths significantly reduced the risks of acquisition of MDROs and development of hospital-acquired bloodstream infections. (Funded by the Centers for Disease Control and Prevention and Sage Products; ClinicalTrials.gov number, NCT00502476.).

Provider Differences in Use of Implanted Ports in Older Adults With Cancer.

BACKGROUND: Identifying unwarranted variation in health care can highlight opportunities to reduce harm. One often discretionary process in oncology is use of implanted ports to administer intravenous chemotherapy. While there are benefits, ports carry risks. This study's objective was to assess provider-driven variation in port use among cancer patients receiving chemotherapy. RESEARCH DESIGN: Retrospective assessment using population-based SEER-Medicare data to assess differences in port use across health care providers of older adults with cancer. Participants included over 18,000 patients ages 66 and older diagnosed with breast, colorectal, lung, or pancreatic cancer in 2005-2007, treated by approximately 2900 providers. We identified port use for patients receiving treatment from hospital outpatient facilities versus physicians' offices. Our main analysis assessed the likelihood of a patient receiving a port given port use by the provider's last patient. For a subset of high-use providers, we examined individual provider-level variation by estimating the risk-adjusted likelihood of insertion. RESULTS: Patients receiving chemotherapy in hospital outpatient facilities were significantly less likely to receive a port than those treated in physicians' offices, with adjusted odds ratios (AOR) varying from 0.50 to 0.75 across cancer sites. Implanting a port was associated with increased likelihood of port insertion in the provider's next patient (AOR varied from 1.71 to 2.25). Significant between-provider variation was found among providers with at least 10 patients. CONCLUSIONS: Our findings support the idea that there is provider-driven variation in the use of ports for chemotherapy administration. This variation highlights an opportunity to standardize practice and reduce unnecessary use.

IFN-γ release assays in the diagnosis of latent tuberculosis infection among immunocompromised adults.

Immunocompromised persons with latent tuberculosis infection (LTBI) are at increased risk for tuberculosis reactivation compared with the general population. The tuberculin skin test, the traditional assay for diagnosing LTBI, has reduced accuracy in immunocompromised patients. IFN-γ release assays (IGRAs) are in vitro blood tests that measure T-cell release of IFN-γ after stimulation with antigens unique to Mycobacterium tuberculosis. Here we review the data for the use of QuantiFERON-TB Gold In-Tube and T-SPOT.TB, the two currently available IGRAs, in immunocompromised adults, including persons infected with HIV, patients with immune-mediated inflammatory disorders, candidates for treatment with tumor necrosis factor-α inhibitors, patients receiving hemodialysis, solid-organ transplant recipients, and patients with cancer. On the basis of the available data, IGRAs have advantages over the tuberculin skin test in specific patient populations and in certain situations. Further studies are needed to more accurately define the usefulness of IGRAs in immunocompromised patients.

A pill for HIV prevention: déjà vu all over again?

Recent FDA approval of tenofovir-emtricitabine for prevention of human immunodeficiency virus (HIV) as a form of pre-exposure prophylaxis (PrEP) has led to concern about implementation of this strategy. Fifty years ago, a very similar national and international debate occurred when the oral contraceptive pill ("the Pill" or "OCP") was approved. Contentious issues included OCP safety, cost, and the potential impact on sexual behavior--many of the same concerns being voiced currently about PrEP. In this article, we review the social and medical history of OCP, drawing parallels with the current PrEP debate. We also explore the key areas where PrEP differs from its forbear: lower efficacy, presence of drug resistance, and a more circumscribed (and marginalized) target population. A thoughtful approach to PrEP implementation, bearing in mind the historical insights gained from the 1960s, might serve as well as we begin this new chapter in the control of the HIV epidemic.

Knowledge and use of pre-exposure prophylaxis among an online sample of young men who have sex with men in New York City.

Understanding prior knowledge and experience with pre-exposure prophylaxis (PrEP) among men who have sex with men (MSM) is critical to its implementation. In fall 2011, NYC MSM were recruited via banner advertisements on six popular dating websites and asked questions about their knowledge and use of PrEP (n = 329). Overall, 123 (38%) respondents reported knowledge of PrEP, of whom two (1.5%) reported PrEP use in the past 6 months. Knowledge of PrEP was associated with high educational attainment, gay identity and recent HIV testing, suggesting an uneven dissemination of information about PrEP and missed opportunities for education. To avoid disparities in use during scale-up, MSM should be provided with additional information about PrEP.

Sustained reduction of microbial burden on common hospital surfaces through introduction of copper.

The contribution of environmental surface contamination with pathogenic organisms to the development of health care-associated infections (HAI) has not been well defined. The microbial burden (MB) associated with commonly touched surfaces in intensive care units (ICUs) was determined by sampling six objects in 16 rooms in ICUs in three hospitals over 43 months. At month 23, copper-alloy surfaces, with inherent antimicrobial properties, were installed onto six monitored objects in 8 of 16 rooms, and the effect that this application had on the intrinsic MB present on the six objects was assessed. Census continued in rooms with and without copper for an additional 21 months. In concert with routine infection control practices, the average MB found for the six objects assessed in the clinical environment during the preintervention phase was 28 times higher (6,985 CFU/100 cm(2); n = 3,977 objects sampled) than levels proposed as benign immediately after terminal cleaning (<250 CFU/100 cm(2)). During the intervention phase, the MB was found to be significantly lower for both the control and copper-surfaced objects. Copper was found to cause a significant (83%) reduction in the average MB found on the objects (465 CFU/100 cm(2); n = 2714 objects) compared to the controls (2,674 CFU/100 cm(2); n = 2,831 objects [P < 0.0001]). The introduction of copper surfaces to objects formerly covered with plastic, wood, stainless steel, and other materials found in the patient care environment significantly reduced the overall MB on a continuous basis, thereby providing a potentially safer environment for hospital patients, health care workers (HCWs), and visitors.

Totally implantable venous access device placement by interventional radiologists: are prophylactic antibiotics necessary?

PURPOSE: To determine the rate of early infection for totally implantable venous access devices (TIVADs) placed without antibiotic prophylaxis. MATERIAL AND METHODS: A list of patients who underwent TIVAD placement in 2009 was obtained from the patient archiving and communication system (PACS). This list was cross-referenced to all patients who underwent TIVAD removal from January 1, 2009, through January 30, 2010, to identify TIVADs that were removed within 30 days of placement. Retrospective chart review was performed to record patient demographics, including age, sex, cancer diagnosis, and indication for removal. Concurrent antibiotic therapy, chemotherapy, and laboratory data before and within 30 days of placement were recorded. Central line-associated bloodstream infections (CLABSIs) were identified using U.S. Centers for Disease Control and Prevention (CDC) criteria. RESULTS: There were 1,183 ports placed and 13 removed. CLABSIs occurred in seven (0.6%) patients within 30 days of placement. At the time of TIVAD placement, 81 (7%) patients were receiving antibiotics incidental to the procedure. One patient who received an antibiotic the day of implantation developed a CLABSI. Chemotherapy was administered to 148 (13%) patients on the day of placement. CONCLUSIONS: The rate of early infection without antibiotic prophylaxis before TIVAD placement in the interventional radiology suite is < 1%. Based on these data, use of prophylactic antibiotics for TIVAD placement is not recommended.

Relapse versus reinfection: surveillance of Clostridium difficile infection.

Molecular typing was used to examine surveillance definitions for recurrent Clostridium difficile-associated diarrhea. Among 102 patients, 85 had a second episode within 8 weeks, 88% of which were relapses. Of 49 second episodes occurring after > 8 weeks, 65% were relapses. Categorization of a recurrent episode occurring after >8 weeks as a new infection may misrepresent the majority of episodes for surveillance.

Clinical practice guideline for the use of antimicrobial agents in neutropenic patients with cancer: 2010 Update by the Infectious Diseases Society of America.

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.

Clinical practice guideline for the use of antimicrobial agents in neutropenic patients with cancer: 2010 update by the infectious diseases society of america.

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.

The effect of HIV field-based testing on the proportion of notified partners who test for HIV in New York City.

HIV partner services can effectively reach populations with high HIV prevalence. However, located and notified sex and needle-sharing partners of persons infected with HIV often fail to test. Field testing may increase the proportion of notified partners who test for HIV. In 2008, New York City's health department incorporated field testing into partner services. After the introduction of field testing, the proportion of notified partners who tested for HIV rose from 52% to 76% (P<.001). HIV prevalence fell slightly among notified partners who accepted testing (12% to 9%, P=.82), but we identified more than double the number of new positives (11 vs 25). All positive and 97% of negative results were received by the person tested.

Excess mortality among injection drug users with AIDS, New York City (1999-2004).

We calculated proportions and trends in contributing causes of death among persons with AIDS (PWA) and a history of injection drug use (IDU) in New York City and compared the proportions with those among PWA with a transmission risk of high-risk heterosexual sex (HRH) and men who have sex with men (MSM). We included all 10,575 injection drug user, HRH, and MSM residents aged 13+ years with AIDS reported by September 30, 2006 , who died from 1999 through 2004. Accidental drug overdose was the most frequent contributing cause of death among IDUs (20.5%). Overdose prevention initiatives may greatly and immediately reduce deaths among PWA.

Rapidly growing mycobacteria infection in patients with cancer.

BACKGROUND: Rapidly growing mycobacteria (RGM) have been associated with various clinical syndromes in immunocompetent and immunocompromised hosts. The risk factors and outcomes of RGM infection in patients with cancer have not been clearly defined. METHODS: Data were derived from 2 distinct sources. Demographic and clinical data were collected for all patients with cancer at Memorial Sloan-Kettering Cancer Center with a culture positive for RGM from January 1999 through December 2008. We also reviewed the literature for studies describing RGM infection in patients with cancer. RESULTS: During the 10-year period, 28 patients with cancer at Memorial Sloan-Kettering Cancer Center had cultures positive for RGM. Most cases occurred in patients with solid tumors and were confined to the lung. A review of the literature identified 313 additional patients with cancer and RGM infection. Combining our series data with cases from the literature, we defined 3 distinct syndromes: pulmonary disease, which occurred in 158 patients (47%); bloodstream infection, occurring in 151 patients (45%); and disseminated infection involving at least 1 end organ, affecting 26 persons (8%). The syndromes differed by age of onset, underlying cancer, main RGM species, and outcome. Persons with bloodstream infection typically were young and had an excellent outcome; those with disseminated infection were older, had pronounced immunosuppression, and had a very poor prognosis. CONCLUSIONS: RGM infections in patients with cancer comprise 3 distinct disorders with different risk factors, predominant mycobacterial species, and prognoses. In turn, the approach to management, including number and duration of antimycobacterial drugs, may be fundamentally different for various patients with cancer who receive a diagnosis of RGM infection.

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.

Nosocomial infections in patients with cancer.

Nosocomial infections are those that become evident 48 h or more after a patient is admitted for treatment in a hospital or in another health-care setting. These infections cause substantial morbidity and mortality in patients who are immunosuppressed. Over the past few decades, understanding of host vulnerability has improved and more rigorous management and infection-control practices have been adopted for treating susceptible populations. Despite efforts, outbreaks continue to occur. In this Review, we outline current knowledge of the incidence and microbiology of various nosocomial infections in patients with cancer-a large, immunosuppressed population.

The effect of daily bathing with chlorhexidine on the acquisition of methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus, and healthcare-associated bloodstream infections: results of a quasi-experimental multicenter trial.

OBJECTIVE: Spread of multidrug-resistant organisms within the intensive care unit (ICU) results in substantial morbidity and mortality. Novel strategies are needed to reduce transmission. This study sought to determine if the use of daily chlorhexidine bathing would decrease the incidence of colonization and bloodstream infections (BSI) because of methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE) among ICU patients. DESIGN, SETTING, AND PATIENTS: Six ICUs at four academic centers measured the incidence of MRSA and VRE colonization and BSI during a period of bathing with routine soap for 6 months and then compared results with a 6-month period where all admitted patients received daily bathing with a chlorhexidine solution. Changes in incidence were evaluated by Poisson and segmented regression modeling. INTERVENTIONS: Daily bathing with a chlorhexidine-containing solution. MEASUREMENTS AND MAIN RESULTS: Acquisition of MRSA decreased 32% (5.04 vs. 3.44 cases/1000 patient days, p = 0.046) and acquisition of VREdecreased 50% (4.35 vs. 2.19 cases/1000 patient days, p = 0.008) following the introduction of daily chlorhexidine bathing. Segmented regression analysis demonstrated significant reductions in VRE bacteremia (p = 0.02) following the introduction of chlorhexidine bathing. VRE-colonized patients bathed with chlorhexidine had a lower risk of developing VRE bacteremia (relative risk 3.35; 95% confidence interval 1.13-9.87; p = 0.035), suggesting that reductions in the level of colonization led to the observed reductions in BSI. CONCLUSION: We conclude that daily chlorhexidine bathing among ICU patients may reduce the acquisition of MRSA and VRE. The approach is simple to implement and inexpensive and may be an important adjunctive intervention to barrier precautions to reduce acquisition of VRE and MRSA and the subsequent development of healthcare-associated BSI.

Recognizing therapeutic failure.

Cases are presented that raise the issue of how to recognize treatment failure, including radiologic, serologic, and/or clinical definitions with special attention to assessment when available information is conflicting or ambiguous. Just as the diagnosis of invasive aspergillus (IA) remains difficult to secure for many patients, so too is the assessment of a patient for possible treatment failure. Specifically the absence of a sensitive surrogate marker to monitor response leaves clinicians with several insensitive, non-specific and often conflicting pieces of information. For example, CT evidence of response is well-described to lag at least a week behind patient improvement and so this modality cannot be relied upon to assess daily or even weekly patient response. The clinical assessment of the patient is complicated by the presence or absence of neutropenia since patients may appear to worsen as their neutropenia recovers; conversely, patients with advanced infection may exhibit only subtle signs of IA if profoundly immunosuppressed. Finally, IA does not respond to any antifungal quickly; thus the clinician must patiently wait longer than is typical for a bacterial infection to determine whether the response is slow or simply not present. Assessment of a patient with IA for treatment failure is a complicated determination that requires the clinician to synthesize incomplete and often conflicting information. Further adding to the difficulty are the morbidity and mortality of the disease and the relative lack of effectiveness of the available antifungal agents.