James P. Steinberg

Liver-infiltrating lymphocytes in chronic human hepatitis C virus infection display an exhausted phenotype with high levels of PD-1 and low levels of CD127 expression.

ABSTRACT The majority of people infected with hepatitis C virus (HCV) fail to generate or maintain a T-cell response effective for viral clearance. Evidence from murine chronic viral infections shows that expression of the coinhibitory molecule PD-1 predicts CD8+ antiviral T-cell exhaustion and may contribute to inadequate pathogen control. To investigate whether human CD8+ T cells express PD-1 and demonstrate a dysfunctional phenotype during chronic HCV infection, peripheral and intrahepatic HCV-specific CD8+ T cells were examined. We found that in chronic HCV infection, peripheral HCV-specific T cells express high levels of PD-1 and that blockade of the PD-1/PD-L1 interaction led to an enhanced proliferative capacity. Importantly, intrahepatic HCV-specific T cells, in contrast to those in the periphery, express not only high levels of PD-1 but also decreased interleukin-7 receptor alpha (CD127), an exhausted phenotype that was HCV antigen specific and compartmentalized to the liver, the site of viral replication.

Clinical practice guidelines for antimicrobial prophylaxis in surgery

These guidelines were developed jointly by the American Society of Health-System Pharmacists (ASHP), the Infectious Diseases Society of America (IDSA), the Surgical Infection Society (SIS), and the Society for Healthcare Epidemiology of America (SHEA). This work represents an update to the previously published ASHP Therapeutic Guidelines on Antimicrobial Prophylaxis in Surgery, as well as guidelines from IDSA and SIS. The guidelines are intended to provide practitioners with a standardized approach to the rational, safe, and effective use of antimicrobial agents for the prevention of surgical-site infections (SSIs) based on currently available clinical evidence and emerging issues. Prophylaxis refers to the prevention of an infection and can be characterized as primary prophylaxis, secondary prophylaxis, or eradication. Primary prophylaxis refers to the prevention of an initial infection. Secondary prophylaxis refers to the prevention of recurrence or reactivation of a preexisting infection. Eradication refers to the elimination of a colonized organism to prevent the development of an infection. These guidelines focus on primary perioperative prophylaxis.

Timing of Antimicrobial Prophylaxis and the Risk of Surgical Site Infections Results From the Trial to Reduce Antimicrobial Prophylaxis Errors

Objective:The objective of this study is to determine the optimal timing for surgical antimicrobial prophylaxis (AMP). Summary Background Data:National AMP guidelines should be supported by evidence from large contemporary data sets. Methods:Twenty-nine hospitals prospectively obtained information on AMP from 4472 randomly selected cardiac, hip/knee arthroplasty, and hysterectomy cases. Surgical site infections (SSIs) were ascertained through routine surveillance, using National Nosocomial Infections Surveillance system methodology. The association between the prophylaxis timing and the occurrence of SSI was assessed using conditional logistic regression (conditioning on hospital). Results:One-hundred thirteen SSI were detected in 109 patients. SSI risk increased incrementally as the interval of time between antibiotic infusion and the incision increased (overall association between timing and infection risk P = 0.04). When antibiotics requiring long infusion times (vancomycin and fluoroquinolones) were excluded, the infection risk following administration of antibiotic within 30 minutes prior to incision was 1.6% compared with 2.4% associated with administration of antibiotic between 31 to 60 minutes prior to surgery (OR: 1.74; 95% confidence interval, 0.98–3.04). The infection risk increased as the time interval between preoperative antibiotic and incision increased or if the antibiotic was first infused after incision. Intraoperative redosing (performed in only 21% of long operations) appeared to reduce SSI risk in operations lasting more than 4 hours (OR of 3.08 with no redosing; 95% confidence interval 0.74–12.90), but only when the preoperative dose was given correctly. Conclusions:These data from a large multicenter collaborative study confirm and extend previous observations and show a consistent relationship between the timing of AMP and SSI risk with a trend toward lower risk occurring when AMP with cephalosporins and other antibiotics with short infusion times were given within 30 minutes prior to incision.

Subdural empyema and other suppurative complications of paranasal sinusitis

Suppurative intracranial infection, including meningitis, intracranial abscess, subdural empyema, epidural abscess, cavernous sinus thrombosis, and thrombosis of other dural sinuses, are uncommon sequelae of paranasal sinusitis. A high index of suspicion is necessary to identify these serious complications. We present a patient with subdural empyema in whom the diagnosis was delayed, followed by a discussion of suppurative complications of sinusitis. The case shows the rapid progression of subdural empyema, which represents a true neurosurgical emergency requiring prompt diagnosis and management.

Antibiotic Resistance in Long-Term Acute Care Hospitals The Perfect Storm

OBJECTIVE To examine bacterial antibiotic resistance and antibiotic use patterns in long-term acute care hospitals (LTACHs) and to evaluate effects of antibiotic use and other hospital-level variables on the prevalence of antibiotic resistance. DESIGN Multihospital ecologic study. METHODS Antibiograms, antibiotic purchasing data, and demographic variables from 2002 and 2003 were obtained from 45 LTACHs. Multivariable regression models were constructed, controlling for other hospital-level variables, to evaluate the effects of antibiotic use on resistance for selected pathogens. Results of active surveillance in 2003 at one LTACH were available. RESULTS Among LTACHs, median prevalences of resistance for several antimicrobial-organism pairs were greater than the 90th percentile value for National Nosocomial Infections Surveillance system (NNIS) medical intensive care units (ICUs). The median prevalence of methicillin resistance among Staphylococcus aureus isolates was 84%. More than 60% of patients in one LTACH were infected or colonized with methicillin-resistant S. aureus and/or vancomycin-resistant Enterococcus at the time of admission. Antibiotic consumption in LTACHs was comparable to consumption in NNIS medical ICUs. In multivariable logistic regression modeling, the only significant association between antibiotic use and the prevalence of antibiotic resistance was for carbapenems and imipenem resistance among Pseudomonas aeruginosa isolates (odds ratio, 11.88 [95% confidence interval, 1.42-99.13]; P=.02). CONCLUSIONS The prevalence of antibiotic resistance among bacteria recovered from patients in LTACHs is extremely high. Although antibiotic use in LTACHs likely contributes to resistance prevalence for some antimicrobial-organism pairs, for the majority of such pairs, other variables, such as prior colonization with and horizontal transmission of antimicrobial-resistant pathogens, may be more important determinants. Further research on antibiotic resistance in LTACHs is needed, particularly with respect to determining optimal infection control practices in this environment.

Distribution of Pathogens in Central Line–Associated Bloodstream Infections among Patients with and without Neutropenia following Chemotherapy: Evidence for a Proposed Modification to the Current Surveillance Definition

OBJECTIVE Many bloodstream infections (BSIs) occurring in patients with febrile neutropenia following cytotoxic chemotherapy are due to translocation of intestinal microbiota. However, these infections meet the National Healthcare Safety Network (NHSN) definition of central line-associated BSIs (CLABSIs). We sought to determine the differences in the microbiology of NHSN-defined CLABSIs in patients with and without neutropenia and, using these data, to propose a modification of the CLABSI definition. DESIGN Retrospective review. SETTING Two large university hospitals over 18 months. METHODS All hospital-acquired BSIs occurring in patients with central venous catheters in place were classified using the NHSN CLABSI definition. Patients with postchemotherapy neutropenia (500 neutrophils/mm(3) or lower) at the time of blood culture were considered neutropenic. Pathogens overrepresented in the neutropenic group were identified to inform development of a modified CLABSI definition. RESULTS Organisms that were more commonly observed in the neutropenic group compared with the nonneutropenic group included Escherichia coli (22.7% vs 2.5%; P < .001) but not other Enterobacteriaceae, Enterococcus faecium (18.2% vs 6.1%; P = .002), and streptococci (18.2% vs 0%; P < .001). Application of a modified CLABSI definition (removing BSI with enterococci, streptococci, or E. coli) excluded 33 of 66 neutropenic CLABSIs and decreased the CLABSI rate in one study hospital with large transplant and oncology populations from 2.12 to 1.79 cases per 1,000 line-days. CONCLUSIONS Common gastrointestinal organisms were more common in the neutropenia group, suggesting that many BSIs meeting the NHSN criteria for CLABSI in the setting of neutropenia may represent translocation of gut organisms. These findings support modification of the NHSN CLABSI definition.

Prevalence of conditions associated with human immunodeficiency and hepatits virus infections among persons with haemophilia, 2001-2003

Summary.  Before the mid‐1980s, haemophilia often was unknowingly treated with contaminated plasma products, resulting in high rates of human immunodeficiency virus (HIV‐1), hepatitis C virus (HCV) and hepatitis B virus (HBV) infections. To estimate the impact of these infections, a new cohort was established. All HCV‐seropositive patients, age 13–88 years, at 52 comprehensive haemophilia treatment centres were eligible. Cross‐sectional data collected during April 2001 to January 2004 (median June 2002) were analysed. Plasma HIV‐1 and HCV RNA were quantified by polymerase chain reaction. Highly active antiretroviral therapy (HAART) was defined as use of at least three recommended medications. Among 2069 participants, 620 (30%) had HIV‐1. Of 1955 with known HBV status, 814 (42%) had resolved HBV and 90 (4.6%) were HBV carriers. Although 80% of the HIV‐1‐positive participants had ≥200 CD4+ cells μL−1, only 59% were on HAART. HIV‐1 RNA was undetectable in 23% of those not taking antiretroviral medications. Most (72%) participants had received no anti‐HCV therapy. HCV RNA was detected less frequently (59%) among participants treated with standard interferon plus ribavirin (P = 0.0001) and more frequently among HIV‐1‐positive than HIV‐1‐negative participants (85% vs. 70%, P < 0.0001). HIV‐1‐positive participants were more likely to have pancytopenia and subclinical hepatic abnormalities, as well as persistent jaundice, hepatomegaly, splenomegaly and ascites. HAART recipients did not differ from HIV‐negative participants in the prevalence of ascites. The clinical abnormalities were more prevalent with older age but were not confounded by HBV status or self‐reported alcohol consumption. Eleven participants presented with or previously had hepatocellular carcinoma or non‐Hodgkin lymphoma. Although prospective analysis is needed, our data reveal the scale of hepatic and haematological disease that is likely to manifest in the adult haemophilic population during the coming years unless most of them are successfully treated for HIV‐1, HCV or both.

A population-based investigation of invasive vancomycin-resistant enterococcus infection in metropolitan Atlanta, Georgia, and predictors of mortality

BACKGROUND Vancomycin-resistant Enterococcus organisms (VRE) have emerged as common nosocomial pathogens, but few population-based data are available on the impact of invasive VRE infections. METHODS We assessed the incidence of invasive VRE infections and predictors of mortality among patients identified during prospective, population-based surveillance performed in the metropolitan statistical area (MSA) of Atlanta, Georgia. RESULTS From July 1997 through June 2000, a total of 192 patients who resided in the Atlanta MSA developed an invasive VRE infection, for a rate of 1.57 cases per 100,000 person-years. The incidence of invasive VRE disease significantly increased from 0.91 cases per 100,000 person-years during the first year of the study to 1.73 cases per 100,000 person-years during the third year of the study (P<.001). Rates of invasive VRE infection were significantly higher among African American patients than white patients (2.59 vs 0.70 cases per 100,000 person-years; P<.001). Blood was the most common sterile site from which VRE was recovered (161 [83%] of 193 isolates), followed by deep surgical sites (17 [9%]), peritoneal fluid (10 [5%]), pleural fluid (3 [2%]), and cerebrospinal fluid (1 [0.5%]). In multivariate analysis, a Charlson comorbidity index of 5 or greater, previous receipt of antibiotic therapy, having 2 or more sets of blood cultures positive for VRE, and receipt of central parenteral nutrition were independent predictors of mortality, whereas receipt of an antibiotic with in vitro activity against the VRE isolate was associated with a decreased risk of mortality. Molecular typing revealed 38 different pulsed-field gel electrophoresis patterns, but the 2 most common pulsed-field gel electrophoresis types were found at 3 Emory University-affiliated hospitals. CONCLUSIONS The incidence of invasive VRE infection significantly increased in the Atlanta MSA during the 3-year study period, with significant racial disparities detected. Receipt of an antimicrobial agent with in vitro activity against VRE was associated with a lower mortality rate. Molecular typing results demonstrated polyclonal emergence of VRE in Atlanta.

Evidence-Based Design of Healthcare Facilities: Opportunities for Research and Practice in Infection Prevention

Affiliations: 1. SimTigrate Design Lab, School of Architecture, Georgia Institute of Technology, Atlanta, Georgia; 2. Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia; 3. Health Systems Institute, Georgia Institute of Technology, Atlanta, Georgia; 4. School of Industrial Design, Georgia Institute of Technology, Atlanta, Georgia; 5. Agency for Healthcare Research and Quality, Rockville, Maryland; 6. RTI International, Washington, DC. Received October 2, 2012; accepted November 21, 2012; electronically published April 9, 2013. 2013 by The Society for Healthcare Epidemiology of America. All rights reserved. 0899-823X/2013/3405-0011

The Role of Facility Design in Preventing the Transmission of Healthcare-Associated Infections: Background and Conceptual Framework

15.00. DOI: 10.1086/670220 Evidence-based design (EBD) of healthcare facilities is an emerging field that has the potential to significantly reduce the burden of healthcare-associated infections (HAIs). There is a growing body of evidence demonstrating that the built environment of healthcare settings—their layout, materials, equipment, and furnishings—plays a key role in facilitating or preventing transmission of pathogens. The infection prevention community can be an important partner in further developing this evidence base by advocating for and including healthcare facility design in its research agenda. At the same time, the EBD of the built environment has the promise of providing an additional set of tools for infection prevention. A relatively new discipline, EBD has deep roots in environmental psychology, architecture, medicine, and other sciences. It postulates that the design of the built environment fundamentally impacts patient, provider, and organizational outcomes (ie, decreased infection rates, length of stay, falls, use of analgesics, and operating costs) while improving patient and caregiver experience and satisfaction. Similar to evidence-based medicine, EBD uses the best available evidence to inform decision making and includes measurement of outcomes. EBD of healthcare facilities gained prominence in the early 2000s with the publication of the Institute of Medicine’s report Crossing the Quality Chasm, a growing research evidence base, and the initiation of the largest hospital construction program in US history. After a decade of closing hospitals, the US began spending more than