Background

Hospital-associated infections (HAIs) are associated with a considerable burden of disease and direct costs greater than $17 billion. The pathogens that cause the majority of serious HAIs are Enterococcus faecium, Staphylococcus aureus, Clostridium difficile, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species, referred as ESCKAPE. We aimed to determine the amount of funding the National Institute of Health (NIH) National Institute of Allergy and Infectious Diseases (NIAID) allocates to research on antimicrobial resistant pathogens, particularly ESCKAPE pathogens.

Methods

The NIH Research Portfolio Online Reporting Tools (RePORT) database was used to identify NIAID antimicrobial resistance research grants funded in 2007-2009 using the terms "antibiotic resistance," "antimicrobial resistance," and "hospital-associated infection."

Results

Funding for antimicrobial resistance grants has increased from 2007-2009. Antimicrobial resistance funding for bacterial pathogens has seen a smaller increase than non-bacterial pathogens. The total funding for all ESKCAPE pathogens was $ 22,005,943 in 2007, $ 30,810,153 in 2008 and $ 49,801,227 in 2009. S. aureus grants received $ 29,193,264 in FY2009, the highest funding amount of all the ESCKAPE pathogens. Based on 2009 funding data, approximately $1,565 of research money was spent per S. aureus related death and $750 of was spent per C. difficile related death.

Conclusions

Although the funding for ESCKAPE pathogens has increased from 2007 to 2009, funding levels for antimicrobial resistant bacteria-related grants is still lower than funding for antimicrobial resistant non-bacterial pathogens. Efforts may be needed to improve research funding for resistant-bacterial pathogens, particularly as their clinical burden increases.

Background

HIV patients are at increased risk of development of infections and infection-associated poor health outcomes. We aimed to 1) assess the prevalence of USA300 community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) among HIV-infected patients with S. aureus bloodstream infections and. 2) determine risk factors for infective endocarditis and in-hospital mortality among patients in this population.

Methods

All adult HIV-infected patients with documented S. aureus bacteremia admitted to the University of Maryland Medical Center between January 1, 2003 and December 31, 2005 were included. CA-MRSA was defined as a USA300 MRSA isolate with the MBQBLO spa-type motif and positive for both the arginine catabolic mobile element and Panton-Valentin Leukocidin. Risk factors for S. aureus-associated infective endocarditis and mortality were determined using logistic regression to calculate odds ratios (OR) and 95% confidence intervals (CI). Potential risk factors included demographic variables, comorbid illnesses, and intravenous drug use.

Results

Among 131 episodes of S. aureus bacteremia, 85 (66%) were MRSA of which 47 (54%) were CA-MRSA. Sixty-three patients (48%) developed endocarditis and 10 patients (8%) died in the hospital on the index admission Patients with CA-MRSA were significantly more likely to develop endocarditis (OR = 2.73, 95% CI = 1.30, 5.71). No other variables including comorbid conditions, current receipt of antiretroviral therapy, pre-culture severity of illness, or CD4 count were significantly associated with endocarditis and none were associated with in-hospital mortality.

Conclusions

CA-MRSA was significantly associated with an increased incidence of endocarditis in this cohort of HIV patients with MRSA bacteremia. In populations such as these, in which the prevalence of intravenous drug use and probability of endocarditis are both high, efforts must be made for early detection, which may improve treatment outcomes.

Background

The high prevalence of methicillin-resistant S. aureus (MRSA) has led clinicians to select antibiotics that have coverage against MRSA, usually vancomycin, for empiric therapy for suspected staphylococcal infections. Clinicians often continue vancomycin started empirically even when methicillin-susceptible S. aureus (MSSA) strains are identified by culture. However, vancomycin has been associated with poor outcomes such as nephrotoxicity, persistent bacteremia and treatment failure. The objective of this study was to compare the effectiveness of vancomycin versus the beta-lactam antibiotics nafcillin and cefazolin among patients with MSSA bacteremia. The outcome of interest for this study was 30-day in-hospital mortality.

Methods

This retrospective cohort study included all adult in-patients admitted to a tertiary-care facility between January 1, 2003 and June 30, 2007 who had a positive blood culture for MSSA and received nafcillin, cefazolin or vancomycin. Cox proportional hazard models were used to assess independent mortality hazards comparing nafcillin or cefazolin versus vancomycin. Similar methods were used to estimate the survival benefits of switching from vancomycin to nafcillin or cefazolin versus leaving patients on vancomycin. Each model included statistical adjustment using propensity scores which contained variables associated with an increased propensity to receive vancomycin.

Results

267 patients were included; 14% (38/267) received nafcillin or cefazolin, 51% (135/267) received both vancomycin and either nafcillin or cefazolin, and 35% (94/267) received vancomycin. Thirty (11%) died within 30 days. Those receiving nafcillin or cefazolin had 79% lower mortality hazards compared with those who received vancomycin alone (adjusted hazard ratio (HR): 0.21; 95% confidence interval (CI): 0.09, 0.47). Among the 122 patients who initially received vancomycin empirically, those who were switched to nafcillin or cefazolin (66/122) had 69% lower mortality hazards (adjusted HR: 0.31; 95% CI: 0.10, 0.95) compared to those who remained on vancomycin.

Conclusions

Receipt of nafcillin or cefazolin was protective against mortality compared to vancomycin even when therapy was altered after culture results identified MSSA. Convenience of vancomycin dosing may not outweigh the potential benefits of nafcillin or cefazolin in the treatment of MSSA bacteremia.

Background

Knowledge of seasonal trends in hospital-associated infection incidence may improve surveillance and help guide the design and evaluation of infection prevention interventions. We estimated seasonal variation in the frequencies of inpatient bloodstream infections (BSIs) caused by common bacterial pathogens and examined associations of monthly BSI frequencies with ambient outdoor temperature, precipitation, and humidity levels.

Methods

A database containing blood cultures from 132 U.S. hospitals collected between January 1999 and September 2006 was assembled. The database included monthly counts of inpatient blood cultures positive for several clinically important Gram-negative bacteria (Acinetobacter spp, Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa) and Gram-positive bacteria (Enterococcus spp and Staphylococcus aureus). Monthly mean temperature, total precipitation, and mean relative humidity in the postal ZIP codes of participating hospitals were obtained from national meteorological databases.

Results

A total of 211,697 inpatient BSIs were reported during 9,423 hospital-months. Adjusting for long-term trends, BSIs caused by each Gram-negative organism examined were more frequent in summer months compared with winter months, with increases ranging from 12.2% for E. coli (95% CI 9.2–15.4) to 51.8% for Acinetobacter (95% CI 41.1–63.2). Summer season was associated with 8.7% fewer Enterococcus BSIs (95% CI 11.0–5.8) and no significant change in S. aureus BSI frequency relative to winter. Independent of season, monthly humidity, monthly precipitation, and long-term trends, each 5.6°C (10°F) rise in mean monthly temperature corresponded to increases in Gram-negative bacterial BSI frequencies ranging between 3.5% for E. coli (95% CI 2.1–4.9) to 10.8% for Acinetobacter (95% CI 6.9–14.7). The same rise in mean monthly temperature corresponded to an increase of 2.2% in S. aureus BSI frequency (95% CI 1.3–3.2) but no significant change in Enterococcus BSI frequency.

Conclusions

Summer season and higher mean monthly outdoor temperature are associated with substantially increased frequency of BSIs, particularly among clinically important Gram-negative bacteria.

Accessory gene regulator (agr) dysfunction in Staphylococcus aureus has been associated with a longer duration of bacteremia. We aimed to assess the independent association between agr dysfunction in S. aureus bacteremia and 30-day in-hospital mortality. This retrospective cohort study included all adult inpatients with S. aureus bacteremia admitted between 1 January 2003 and 30 June 2007. Severity of illness prior to culture collection was measured using the modified acute physiology score (APS). agr dysfunction in S. aureus was identified semiquantitatively by using a δ-hemolysin production assay. Cox proportional hazard models were used to measure the association between agr dysfunction and 30-day in-hospital mortality, statistically adjusting for patient and pathogen characteristics. Among 814 patient admissions complicated by S. aureus bacteremia, 181 (22%) patients were infected with S. aureus isolates with agr dysfunction. Overall, 18% of patients with agr dysfunction in S. aureus died, compared to 12% of those with functional agr in S. aureus (P = 0.03). There was a trend toward higher mortality among patients with S. aureus with agr dysfunction (adjusted hazard ratio [HR], 1.34; 95% confidence interval [CI], 0.87 to 2.06). Among patients with the highest APS (scores of >28), agr dysfunction in S. aureus was significantly associated with mortality (adjusted HR, 1.82; 95% CI, 1.03 to 3.21). This is the first study to demonstrate an independent association between agr dysfunction and mortality among severely ill patients. The δ-hemolysin assay examining agr function may be a simple and inexpensive approach to predicting patient outcomes and potentially optimizing antibiotic therapy.

The present study aimed to determine the frequency of methicillin-resistant Staphylococcus aureus (MRSA)-positive clinical culture among hospitalized adults in different risk categories of a targeted MRSA active surveillance screening program and to assess the utility of screening in guiding empiric antibiotic therapy. We completed a prospective cohort study in which all adults admitted to non-intensive-care-unit locations who had no history of MRSA colonization or infection received targeted screening for MRSA colonization upon hospital admission. Anterior nares swab specimens were obtained from all high-risk patients, defined as those who self-reported admission to a health care facility within the previous 12 months or who had an active skin infection on admission. Data were analyzed for the subcohort of patients in whom an infection was suspected, determined by (i) receipt of antibiotics within 48 h of admission and/or (ii) the result of culture of a sample for clinical analysis (clinical culture) obtained within 48 h of admission. Overall, 29,978 patients were screened and 12,080 patients had suspected infections. A total of 46.4% were deemed to be at high risk on the basis of the definition presented above, and 11.1% of these were MRSA screening positive (colonized). Among the screening-positive patients, 23.8% had a sample positive for MRSA by clinical culture. Only 2.4% of patients deemed to be at high risk but found to be screening negative had a sample positive for MRSA by clinical culture, and 1.6% of patients deemed to be at low risk had a sample positive for MRSA by clinical culture. The risk of MRSA infection was far higher in those who were deemed to be at high risk and who were surveillance culture positive. Targeted MRSA active surveillance may be beneficial in guiding empiric anti-MRSA therapy.

Background

Appropriate empiric therapy, antibiotic therapy with in vitro activity to the infecting organism given prior to confirmed culture results, may improve Staphylococcus aureus outcomes. We aimed to measure the clinical impact of appropriate empiric antibiotic therapy on mortality, while statistically adjusting for comorbidities, severity of illness and presence of virulence factors in the infecting strain.

Methodology

We conducted a retrospective cohort study of adult patients admitted to a tertiary-care facility from January 1, 2003 to June 30, 2007, who had S. aureus bacteremia. Time to appropriate therapy was measured from blood culture collection to the receipt of antibiotics with in vitro activity to the infecting organism. Cox proportional hazard models were used to measure the association between receipt of appropriate empiric therapy and in-hospital mortality, statistically adjusting for patient and pathogen characteristics.

Principal Findings

Among 814 admissions, 537 (66%) received appropriate empiric therapy. Those who received appropriate empiric therapy had a higher hazard of 30-day in-hospital mortality (Hazard Ratio (HR): 1.52; 95% confidence interval (CI): 0.99, 2.34). A longer time to appropriate therapy was protective against mortality (HR: 0.79; 95% CI: 0.60, 1.03) except among the healthiest quartile of patients (HR: 1.44; 95% CI: 0.66, 3.15).

Conclusions/Significance

Appropriate empiric therapy was not associated with decreased mortality in patients with S. aureus bacteremia except in the least ill patients. Initial broad antibiotic selection may not be widely beneficial.

This 5-year study of 25,378 hospitalizations measured the utility of infection control documentation of prior methicillin-resistant Staphylococcus aureus (MRSA) colonization or infection for the optimization of empirical antibiotic therapy. Documented prior MRSA colonization or infection was predictive of subsequent MRSA infections (odds ratio, 4.05). Physicians appear to use this documentation when prescribing empirical therapy for suspected bacteremia.

Background

Severity of illness is an important confounder in infectious disease-outcome studies. However, it is unclear whether the time at which severity of illness is measured is important.

Methods

We used a retrospective cohort of adult patients with 328 episodes of Gram-negative bacteremia to assess the impact of the time of measurement of severity of illness on the association between empiric antimicrobial therapy and in-hospital mortality. Using a modified Acute Physiology Score (APS), severity of illness was measured at: 1) hospital admission and 2) 24 hours prior to collection of the first positive blood culture. Multivariate logistic regression was used to estimate the impact of adjusting for APS on the relationship between empiric therapy (the exposure) and in-hospital mortality (the outcome).

Results

The mean [standard deviation] APS increased during the hospital stay [19.2 (11.6) vs. 24.2 (13.6); p < 0.01]. When examining the association between empiric therapy and in-hospital mortality, there was a trend towards a decreased impact of appropriate therapy on in-hospital mortality controlling for APS. The unadjusted odds ratio (OR) for the association between appropriate therapy and in-hospital mortality was 0.83 (95% CI: 0.51-1.34). After controlling for APS at admission, this was attenuated (OR 0.94; 95% CI 0.57-1.55) and when change in APS was also included in the model the association was further attenuated (OR 0.99; 95% CI 0.58-1.69).

Conclusions

The magnitude of the association between appropriate antimicrobial therapy and in-hospital mortality among patients with Gram-negative bacteremia was sensitive to the timing of adjustment for severity of illness.

Background

Previous studies have suggested that informatics tools, such as automated alert and decision support systems, may increase the efficiency and quality of infection control surveillance. However, little is known about the cost effectiveness of these tools.

Methods

We focus on two types of economic analyses that have utility in assessing infection control interventions, cost-effectiveness analysis and business-case analysis, and review the available literature on the economics of computerized infection control surveillance systems.

Results

Previous studies on the effectiveness of computerized infection control surveillance have been limited to assessments of whether these tools increase the sensitivity and specify of surveillance over traditional methods. Furthermore, we identified only two studies, which assessed the costs associated with computerized infection control surveillance. Thus, it remains unknown whether computerized infection control surveillance systems are cost effective and whether use of these systems improves patient outcomes.

Conclusions

The existing data are insufficient to allow for a summary conclusion on the cost effectiveness of infection control surveillance technology. All future studies of computerized infection control surveillance systems should aim to collect outcomes and economic data to inform decision-making and assist hospitals with completing business-cases analyses.

Background

It is unclear whether appropriate empiric antimicrobial therapy improves outcomes in patients with bacteremia due to Escherichia coli or Klebsiella. The objective of this study is to assess the impact of appropriate empiric antimicrobial therapy on in-hospital mortality and post-infection length of stay in patients with Escherichia coli or Klebsiella bacteremia while adjusting for important confounding variables.

Methods

We performed a retrospective cohort study of adult patients with a positive blood culture for E. coli or Klebsiella between January 1, 2001 and June 8, 2005 and compared in-hospital mortality and post-infection length of stay between subjects who received appropriate and inappropriate empiric antimicrobial therapy. Empiric therapy was defined as the receipt of an antimicrobial agent between 8 hours before and 24 hours after the index blood culture was drawn and was considered appropriate if it included antimicrobials to which the specific isolate displayed in vitro susceptibility. Data were collected electronically and through chart review. Survival analysis was used to statistically assess the association between empiric antimicrobial therapy and outcome (mortality or length of stay). Multivariable Cox proportional hazards models were used to calculate hazard ratios (HR) and 95% confidence intervals (CI).

Results

Among 416 episodes of bacteremia, 305 (73.3%) patients received appropriate empiric antimicrobial therapy. Seventy-one (17%) patients died before discharge from the hospital. The receipt of appropriate antimicrobial agents was more common in hospital survivors than in those who died (p = 0.04). After controlling for confounding variables, there was no association between the receipt of appropriate empiric antimicrobial therapy and in-hospital mortality (HR, 1.03; 95% CI, 0.60 to 1.78). The median post-infection length of stay was 7 days. The receipt of appropriate antimicrobial agents was not associated with shortened post-infection length of stay, even after controlling for confounding (HR, 1.11; 95% CI 0.86 to 1.44).

Conclusion

Appropriate empiric antimicrobial therapy for E. coli and Klebsiella bacteremia is not associated with lower in-hospital mortality or shortened post-infection length of stay. This suggests that the choice of empiric antimicrobial agents may not improve outcomes and also provides data to support a randomized trial to test the hypothesis that use (and overuse) of broad-spectrum antibiotics prior to the availability of culture results is not warranted.