Michael Y. Lin

Prior Antimicrobial Therapy and Risk for Hospital-Acquired Candida glabrata and Candida krusei Fungemia: a Case-Case-Control Study

ABSTRACT The incidence of infections caused by Candida glabrata and Candida krusei, which are generally more resistant to fluconazole than Candida albicans, is increasing in hospitalized patients. However, the extent to which prior exposure to specific antimicrobial agents increases the risk of subsequent C. glabrata or C. krusei candidemia has not been closely studied. A retrospective case-case-control study was performed at a university hospital. From 1998 to 2003, 60 patients were identified with hospital-acquired non-C. albicans candidemia (C. glabrata or C. krusei; case group 1). For comparison, 68 patients with C. albicans candidemia (case group 2) and a common control group of 121 patients without candidemia were studied. Models were adjusted for demographic and clinical risk factors, and the risk for candidemia associated with exposure to specific antimicrobial agents was assessed. After adjusting for both nonantimicrobial risk factors and receipt of other antimicrobial agents, piperacillin-tazobactam (odds ratio [OR], 4.15; 95% confidence interval [CI], 1.04 to 16.50) and vancomycin (OR, 6.48; CI, 2.20 to 19.13) were significant risk factors for C. glabrata or C. krusei candidemia. For C. albicans candidemia, no specific antibiotics remained a significant risk after adjusted analysis. Prior fluconazole use was not significantly associated with either C. albicans or non-C. albicans (C. glabrata or C. krusei) candidemia. In this single-center study, exposure to antibacterial agents, specifically vancomycin or piperacillin-tazobactam, but not fluconazole, was associated with subsequent hospital-acquired C. glabrata or C. krusei candidemia. Further studies are needed to prospectively analyze specific antimicrobial risks for nosocomial candidemia across multiple hospital centers.

Quality of traditional surveillance for public reporting of nosocomial bloodstream infection rates.

CONTEXT Central line-associated bloodstream infection (BSI) rates, determined by infection preventionists using the Centers for Disease Control and Prevention (CDC) surveillance definitions, are increasingly published to compare the quality of patient care delivered by hospitals. However, such comparisons are valid only if surveillance is performed consistently across institutions. OBJECTIVE To assess institutional variation in performance of traditional central line-associated BSI surveillance. DESIGN, SETTING, AND PARTICIPANTS We performed a retrospective cohort study of 20 intensive care units among 4 medical centers (2004-2007). Unit-specific central line-associated BSI rates were calculated for 12-month periods. Infection preventionists, blinded to study participation, performed routine prospective surveillance using CDC definitions. A computer algorithm reference standard was applied retrospectively using criteria that adapted the same CDC surveillance definitions. MAIN OUTCOME MEASURES Correlation of central line-associated BSI rates as determined by infection preventionist vs the computer algorithm reference standard. Variation in performance was assessed by testing for institution-dependent heterogeneity in a linear regression model. RESULTS Forty-one unit-periods among 20 intensive care units were analyzed, representing 241,518 patient-days and 165,963 central line-days. The median infection preventionist and computer algorithm central line-associated BSI rates were 3.3 (interquartile range [IQR], 2.0-4.5) and 9.0 (IQR, 6.3-11.3) infections per 1000 central line-days, respectively. Overall correlation between computer algorithm and infection preventionist rates was weak (ρ = 0.34), and when stratified by medical center, point estimates for institution-specific correlations ranged widely: medical center A: 0.83; 95% confidence interval (CI), 0.05 to 0.98; P = .04; medical center B: 0.76; 95% CI, 0.32 to 0.93; P = .003; medical center C: 0.50, 95% CI, -0.11 to 0.83; P = .10; and medical center D: 0.10; 95% CI -0.53 to 0.66; P = .77. Regression modeling demonstrated significant heterogeneity among medical centers in the relationship between computer algorithm and expected infection preventionist rates (P < .001). The medical center that had the lowest rate by traditional surveillance (2.4 infections per 1000 central line-days) had the highest rate by computer algorithm (12.6 infections per 1000 central line-days). CONCLUSIONS Institutional variability of infection preventionist rates relative to a computer algorithm reference standard suggests that there is significant variation in the application of standard central line-associated BSI surveillance definitions across medical centers. Variation in central line-associated BSI surveillance practice may complicate interinstitutional comparisons of publicly reported central line-associated BSI rates.

Successful control of an outbreak of Klebsiella pneumoniae carbapenemase-producing K. pneumoniae at a long-term acute care hospital.

OBJECTIVE To determine the effect of a bundle of infection control interventions on the horizontal transmission of Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae during an outbreak. DESIGN Quasi-experimental study. Setting. Long-term acute care hospital. Intervention. On July 23, 2008, a bundled intervention was implemented: daily 2% chlorhexidine gluconate baths for patients, enhanced environmental cleaning, surveillance cultures at admission, serial point prevalence surveillance (PPS), isolation precautions, and training of personnel. Baseline PPS was performed before the intervention was implemented. Any gram-negative rod isolate suspected of KPC production underwent a modified Hodge test and, if results were positive, confirmatory polymerase chain reaction testing. Clinical cases were defined to occur for patients whose samples yielded KPC-positive gram-negative rods in clinical cultures. RESULTS Baseline PPS performed on June 17, 2008, showed a prevalence of colonization with KPC-producing isolates of 21% (8 of 39 patients screened). After implementation of the intervention, monthly PPS was performed 5 times, which showed prevalences of colonization with KPC-producing isolates of 12%, 5%, 3%, 0%, and 0% (P < .001). From January 1, 2008, until the intervention, 8 KPC-positive clinical cases--suspected to be due to horizontal transmission--were detected. From implementation of the intervention through December 31, 2008, only 2 KPC-positive clinical cases, both in August 2008, were detected. From January 1 through December 31, 2008, 8 patients were detected as carriers of KPC-producing isolates at admission to the institution, 4 patients before and 4 patients after the intervention. CONCLUSION A bundled intervention was successful in preventing horizontal spread of KPC-producing gram-negative rods in a long-term acute care hospital, despite ongoing admission of patients colonized with KPC producers.

The Importance of Long-term Acute Care Hospitals in the Regional Epidemiology of Klebsiella pneumoniae Carbapenemase–Producing Enterobacteriaceae

BACKGROUND In the United States, Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacteriaceae are increasingly detected in clinical infections; however, the colonization burden of these organisms among short-stay and long-term acute care hospitals is unknown. METHODS Short-stay acute care hospitals with adult intensive care units (ICUs) in the city of Chicago were recruited for 2 cross-sectional single-day point prevalence surveys (survey 1, July 2010-January 2011; survey 2, January-July 2011). In addition, all long-term acute care hospitals (LTACHs) in the Chicago region (Cook County) were recruited for a single-day point prevalence survey during January-May 2011. Swab specimens were collected from rectal, inguinal, or urine sites and tested for Enterobacteriaceae carrying blaKPC. RESULTS We surveyed 24 of 25 eligible short-stay acute care hospitals and 7 of 7 eligible LTACHs. Among LTACHs, 30.4% (119 of 391) of patients were colonized with KPC-producing Enterobacteriaceae, compared to 3.3% (30 of 910) of short-stay hospital ICU patients (prevalence ratio, 9.2; 95% confidence interval, 6.3-13.5). All surveyed LTACHs had patients harboring KPC (prevalence range, 10%-54%), versus 15 of 24 short-stay hospitals (prevalence range, 0%-29%). Several patient-level covariates present at the time of survey-LTACH facility type, mechanical ventilation, and length of stay-were independent risk factors for KPC-producing Enterobacteriaceae colonization. CONCLUSIONS We identified high colonization prevalence of KPC-producing Enterobacteriaceae among patients in LTACHs. Patients with chronic medical care needs in long-term care facilities may play an important role in the spread of these extremely drug-resistant pathogens.

Delay of Active Antimicrobial Therapy and Mortality among Patients with Bacteremia: Impact of Severe Neutropenia

ABSTRACT Increasing bacterial antimicrobial resistance has prompted physicians to choose broad-spectrum antimicrobials in order to reduce the likelihood of inactive empirical therapy. However, for bacteremic patients already receiving supportive care, it is unclear whether delay of active antimicrobial therapy significantly impacts patient outcomes. We performed a retrospective cohort study of patients with monomicrobial bloodstream infections at a large urban hospital in the United States from 2001 to 2006. We assessed the impact of delay of active antimicrobial therapy on mortality by using multivariable logistic regression modeling with and without propensity score methodology. We evaluated 1,523 episodes of monomicrobial bacterial bloodstream infections at our institution. Nine hundred eighty-three bacteremic episodes (64.5%) were treated with an active antimicrobial agent within 24 h of the index blood culture; the remaining 540 episodes (35.5%) were considered to have delay of active antimicrobial therapy. In adjusted analysis, among patients in the non-intensive-care-unit setting with an absolute neutrophil count (ANC) of <100 cells/μl, delay was associated with increased mortality (odds ratio [OR], 18.0; 95% confidence interval [CI], 2.84 to 114.5; P < 0.01); among intensive-care-unit patients with an ANC of <100 cells/μl, the effect of delay on mortality was nearly significant (OR, 5.56; 95% CI, 0.85 to 36.3; P = 0.07). However, for patients who were nonneutropenic (ANC, >500 cells/μl) or had ANCs of 100 to 500 cells/μl, delay was not associated with increased mortality. While the delay of active antimicrobial therapy was not significantly associated with higher mortality for most patients in this cohort, patients with severe neutropenia appeared to be vulnerable.

Transfer from High-Acuity Long-Term Care Facilities Is Associated with Carriage of Klebsiella pneumoniae Carbapenemase–Producing Enterobacteriaceae: A Multihospital Study

OBJECTIVE To determine whether transfer from a long-term care facility (LTCF) is a risk factor for colonization with Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacteriaceae upon acute care hospital admission. DESIGN Microbiologic survey and nested case-control study. SETTING Four hospitals in a metropolitan area (Chicago) with an early KPC epidemic. PATIENTS Hospitalized adults. METHODS Patients transferred from LTCFs were matched 1∶1 to patients admitted from the community by age (± 10 years), admitting clinical service, and admission date (± 2 weeks). Rectal swab specimens were collected within 3 days after admission and tested for KPC-producing Enterobacteriaceae. Demographic and clinical information was extracted from medical records. RESULTS One hundred eighty patients from LTCFs were matched to 180 community patients. KPC-producing Enterobacteriaceae colonization was detected in 15 (8.3%) of the LTCF patients and 0 (0%) of the community patients ([Formula: see text]). Prevalence of carriage differed by LTCF subtype: 2 of 135 (1.5%) patients from skilled nursing facilities without ventilator care (SNFs) were colonized upon admission, compared to 9 of 33 (27.3%) patients from skilled nursing facilities with ventilator care (VSNFs) and 4 of 12 (33.3%) patients from long-term acute care hospitals (LTACHs; [Formula: see text]). In a multivariable logistic regression model adjusted for a propensity score that predicted LTCF subtype, patients admitted from VSNFs or LTACHs had 7.0-fold greater odds of colonization (ie, odds ratio; 95% confidence interval, 1.3-42; [Formula: see text]) with KPC-producing Enterobacteriaceae than patients from an SNF. CONCLUSIONS Patients admitted to acute care hospitals from high-acuity LTCFs (ie, VSNFs and LTACHs) were more likely to be colonized with KPC-producing Enterobacteriaceae than were patients admitted from the community. Identification of healthcare facilities with a high prevalence of colonized patients presents an opportunity for focused interventions that may aid regional control efforts.

Septic Pulmonary Emboli and Bacteremia Associated with Deep Tissue Infections Caused by Community-Acquired Methicillin-Resistant Staphylococcus aureus

ABSTRACT We report four adult patients who presented with septic pulmonary emboli and community-acquired methicillin-resistant Staphylococcus aureus bacteremia associated with deep tissue infections, such as pyomyositis, osteomyelitis, and prostatic abscess. The patients lacked evidence of right-sided endocarditis or thrombophlebitis. This association, previously described in children, may also be important in adults.

Formulation of a model for automating infection surveillance: algorithmic detection of central-line associated bloodstream infection

OBJECTIVE To formulate a model for translating manual infection control surveillance methods to automated, algorithmic approaches. DESIGN We propose a model for creating electronic surveillance algorithms by translating existing manual surveillance practices into automated electronic methods. Our model suggests that three dimensions of expert knowledge be consulted: clinical, surveillance, and informatics. Once collected, knowledge should be applied through a process of conceptualization, synthesis, programming, and testing. RESULTS We applied our framework to central vascular catheter associated bloodstream infection surveillance, a major healthcare performance outcome measure. We found that despite major barriers such as differences in availability of structured data, in types of databases used and in semantic representation of clinical terms, bloodstream infection detection algorithms could be deployed at four very diverse medical centers. CONCLUSIONS We present a framework that translates existing practice-manual infection detection-to an automated process for surveillance. Our experience details barriers and solutions discovered during development of electronic surveillance for central vascular catheter associated bloodstream infections at four hospitals in a variety of data environments. Moving electronic surveillance to the next level-availability at a majority of acute care hospitals nationwide-would be hastened by the incorporation of necessary data elements, vocabularies and standards into commercially available electronic health records.

Long-Term Serologic Follow-Up of Isolated Hepatitis B Core Antibody in HIV-Infected and HIV-Uninfected Women

BACKGROUND Isolated antibody to hepatitis B core antigen (anti-HBc) is a common serologic finding in persons infected with human immunodeficiency virus (HIV), but the outcome and clinical significance are uncertain. METHODS We performed repeated hepatitis B virus (HBV) serologic tests on women who participated in the Womens Interagency HIV Study and who had isolated anti-HBc at study entry. RESULTS Repeated serologic tests were performed for 322 women (282 HIV-infected and 40 HIV-uninfected) at a median of 7.5 years after study entry. Seventy-one percent of women retained isolated anti-HBc serologic status, 20% acquired antibody to hepatitis B surface antigen (anti-HBs), and 2% acquired hepatitis B surface antigen (HBsAg). In unadjusted analysis, increasing age, injection drug use, and hepatitis C viremia were negatively associated with acquisition of anti-HBs. For HIV-infected women, predictors of acquisition of anti-HBs were an increase in CD4 cell count and the use of highly active antiretroviral therapy (HAART). Receipt of drugs with activity against HBV and self-reported HBV vaccination did not predict anti-HBs acquisition. In the multivariable regression model, HAART use remained a significant predictor of anti-HBs acquisition, whereas women with hepatitis C viremia were more likely to retain isolated anti-HBc serologic status. CONCLUSIONS Isolated anti-HBc status remained stable over time for the majority of women, especially women with chronic hepatitis C virus infection. Development of anti-HBs was predicted by HAART use and an increase in CD4 cell count. We conclude that a proportion of HIV-infected women with isolated anti-HBc have prior natural HBV infection with anti-HBs that is at an undetectable level because of immune dysfunction. Isolated anti-HBc in the presence of chronic hepatitis C virus infection may be attributable to a different phenomenon, such as dysfunctional antibody production.

Data Requirements for Electronic Surveillance of Healthcare-Associated Infections

Electronic surveillance for healthcare-associated infections (HAIs) is increasingly widespread. This is driven by multiple factors: a greater burden on hospitals to provide surveillance data to state and national agencies, financial pressures to be more efficient with HAI surveillance, the desire for more objective comparisons between healthcare facilities, and the increasing amount of patient data available electronically. Optimal implementation of electronic surveillance requires that specific information be available to the surveillance systems. This white paper reviews different approaches to electronic surveillance, discusses the specific data elements required for performing surveillance, and considers important issues of data validation.