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1.  Antibacterial Resistance Leadership Group: Open for Business 
The Antibacterial Resistance Leadership Group (ARLG) is tasked with prioritizing, designing, implementing, and conducting clinical studies to address antibacterial resistance. This article outlines clinical research resources and opportunities made available by ARLG and encourages submission of proposals that address antibacterial resistance.
Funded by the National Institute of Allergy and Infectious Diseases, the Antibacterial Resistance Leadership Group (ARLG) is tasked with developing a clinical research agenda and conducting clinical studies to address the growing public health threat of antibacterial resistance. The ARLG has identified 4 high-priority areas of research: infections caused by gram-negative bacteria, infections caused by gram-positive bacteria, antimicrobial stewardship and infection prevention, and diagnostics. The ARLG will be accepting proposals from the scientific community for clinical research that addresses 1 or more of these high-priority areas. These studies should have the potential to transform medical practice and be unlikely to occur without ARLG support. The purpose of this article is to make interested parties aware of clinical research opportunities made available by ARLG and to encourage submission of clinical research proposals that address the problem of antibacterial resistance.
PMCID: PMC4017892  PMID: 24610430
antibacterial resistance; ARLG; Leadership Group; clinical trials; clinical research
2.  Culture-inappropriate antibiotic therapy decreases quality of life improvement after sinus surgery 
Despite their widespread use, antibiotics have not been shown to improve chronic rhinosinusitis (CRS) outcomes. We aimed to determine whether culture-inappropriate postoperative antibiotic therapy was associated with less quality of life (QOL) improvement following functional endoscopic sinus surgery (FESS).
This retrospective cohort study recruited 376 adult CRS patients undergoing FESS between 10/1/2007 to 12/31/2011. Patient demographics, comorbidities and medications were collected at baseline. Trimethoprim-sulfamethoxazole and clindamycin were administered for 2 weeks postoperatively. The antibiotic appropriateness was determined based on bacterial resistance profile of organisms identified during intraoperative culture. The QOL outcome was defined as change of 22 item Sinonasal Outcome Test scores from preoperative visit to 1-, 3- and 6-month post-FESS. Clinically significant difference was defined as at least ½ SD of baseline QOL score in the reference group. Mixed-effects regression models were performed.
Seven percent of patients (n=27) had culture-inappropriate antibiotic therapy, and additional 5% (n=19) had culture-specific antibiotic adjustment. Compared to patients with culture-appropriate antibiotics, patients with culture-inappropriate antibiotics had significantly less improvement of QOL from baseline to postoperative 1-month and 3-month follow-up where the difference became clinically significant; patients with antibiotic adjustment had more QOL improvement from baseline to 1-month follow-up, but their QOL worsened at 3-month follow-up, and these changes were not clinically significant. However, all effects washed out at 6-month follow-up with no significant differences.
Culture-inappropriate postoperative antibiotic therapy decreased short-term QOL improvement to a clinically meaningful level after FESS. Culture guided selection of antibiotics may improve short-term FESS outcome.
PMCID: PMC4004654  PMID: 24415647
antibiotic therapy; quality of life; endoscopic sinus surgery; chronic rhinosinsitis; culture; the 22-question Sinonasal Outcome Test
3.  The Evolving Landscape of Healthcare-Associated Infections: Recent Advances in Prevention and a Road Map for Research 
This white paper identifies knowledge gaps and new challenges in healthcare epidemiology research, assesses the progress made toward addressing research priorities, provides the Society for Healthcare Epidemiology of America (SHEA) Research Committee’s recommendations for high-priority research topics, and proposes a road map for making progress toward these goals. It updates the 2010 SHEA Research Committee document, “Charting the Course for the Future of Science in Healthcare Epidemiology: Results of a Survey of the Membership of SHEA,” which called for a national approach to healthcare-associated infections (HAIs) and a prioritized research agenda. This paper highlights recent studies that have advanced our understanding of HAIs, the establishment of the SHEA Research Network as a collaborative infrastructure to address research questions, prevention initiatives at state and national levels, changes in reporting and payment requirements, and new patterns in antimicrobial resistance.
PMCID: PMC4226401  PMID: 24709716
4.  Clinical and Molecular Epidemiology of Escherichia coli Sequence Type 131 among Hospitalized Patients Colonized Intestinally with Fluoroquinolone-Resistant E. coli 
Antimicrobial Agents and Chemotherapy  2014;58(11):7003-7006.
This study examined molecular and epidemiologic factors associated with Escherichia coli sequence type 131 (ST131) among hospitalized patients colonized intestinally with fluoroquinolone (FQ)-resistant E. coli between 2002 and 2004. Among 86 patients, 21 (24%) were colonized with ST131. The proportion of ST131 isolates among colonizing isolates increased significantly over time, from 8% in 2002 to 50% in 2004 (P = 0.003). Furthermore, all 19 clonally related isolates were ST131. Future studies should identify potential transmissibility differences between ST131 and non-ST131 strains.
PMCID: PMC4249391  PMID: 25199782
5.  The effect of diabetes mellitus on chronic rhinosinusitis and sinus surgery outcome 
Patients with diabetes mellitus (DM) are known to be liable to infection. However, the association between diabetes and chronic rhinosinusitis (CRS) has not been well studied. We sought to determine the effects of DM on CRS culture results and quality of life (QOL) after functional endoscopic sinus surgery (FESS).
We conducted a retrospective cohort study. Adult CRS patients undergoing FESS were recruited from 10/1/2007 to 12/31/2011. Patient demographics, comorbidities, medication use, Lund-Mackay CT scores were collected prior to FESS. Intraoperative culture was obtained. Preoperative and 1-, 3- and 6-month postoperative QOL was measured by the 22 item Sinonasal Outcome Test (SNOT-22) scores. A mixed effects model was performed for analysis.
Among the 376 CRS patients included, 19 patients (5.05%) had DM. Compared to non-DM patients, DM patients were significantly more likely to have Pseudomonas aeruginosa (26.32% versus 7.56%, p=0.004) and gram negative rods (26.32% vs. 8.96%, p= 0.013), but there were no significant difference in the prevalence of Staphylococcus aureus; DM patients were also significantly more likely to have nasal polyps and gastroesophageal reflux disease. Additionally, DM patients had significantly less improvement of postoperative SNOT-22 scores from baseline to 6-month follow-up than non-DM patients (adjusted mean=11.14, 95% CI (0.14, 22.15), p=0.047) after adjusting for all the other risk factors for CRS.
DM patients may be prone to gram negative bacterial sinus infections, and have significantly worse short-term postoperative QOL. Special postoperative care may need to be considered in CRS patients with DM
PMCID: PMC3975697  PMID: 24415555
chronic rhinosinsitis; diabetes mellitus; infection; quality of life; Pseudomonas aeruginosa
6.  The shared microbiota of humans and companion animals as evaluated from Staphylococcus carriage sites 
Microbiome  2015;3:2.
Staphylococcus aureus and other coagulase-positive staphylococci (CPS) colonize skin and mucous membrane sites and can cause skin and soft tissue infections (SSTIs) in humans and animals. Factors modulating methicillin-resistant S. aureus (MRSA) colonization and infection in humans remain unclear, including the role of the greater microbial community and environmental factors such as contact with companion animals. In the context of a parent study evaluating the households of outpatients with community MRSA SSTI, the objectives of this study were 1) to characterize the microbiota that colonizes typical coagulase-positive Staphylococcus spp. carriage sites in humans and their companion pets, 2) to analyze associations between Staphylococcus infection and carriage and the composition and diversity of microbial communities, and 3) to analyze factors that influence sharing of microbiota between pets and humans.
We enrolled 25 households containing 56 pets and 30 humans. Sampling locations were matched to anatomical sites cultured by the parent study for MRSA and other CPS. Bacterial microbiota were characterized by sequencing of 16S ribosomal RNA genes. Household membership was strongly associated with microbial communities, in both humans and pets. Pets were colonized with a greater relative abundance of Proteobacteria, whereas people were colonized with greater relative abundances of Firmicutes and Actinobacteria. We did not detect differences in microbiota associated with MRSA SSTI, or carriage of MRSA, S. aureus or CPS. Humans in households without pets were more similar to each other than humans in pet-owning households, suggesting that companion animals may play a role in microbial transfer. We examined changes in microbiota over a 3-month time period and found that pet staphylococcal carriage sites were more stable than human carriage sites.
We characterized and identified patterns of microbiota sharing and stability between humans and companion animals. While we did not detect associations with MRSA SSTI, or carriage of MRSA, S. aureus or CPS in this small sample size, larger studies are warranted to fully explore how microbial communities may be associated with and contribute to MRSA and/or CPS colonization, infection, and recurrence.
Electronic supplementary material
The online version of this article (doi:10.1186/s40168-014-0052-7) contains supplementary material, which is available to authorized users.
PMCID: PMC4335418  PMID: 25705378
16S rRNA; Methicillin-resistant Staphylococcus aureus (MRSA); Microbiome; Pet; Staphylococcus; Skin and soft tissue infection (SSTI)
7.  Adverse Events Associated with Prolonged Antibiotic Use 
The Infectious Diseases Society of America and US CDC recommend 60 days of ciprofloxacin, doxycycline or amoxicillin for anthrax prophylaxis. It is not possible to determine severe adverse drug event (ADE) risks from the few people thus far exposed to anthrax prophylaxis. This study’s objective was to estimate risks of severe ADEs associated with long-term ciprofloxacin, doxycycline and amoxicillin exposure using 3 large databases: one electronic medical record (General Practice Research Database) and two claims databases (UnitedHealthcare, HMO Research Network).
We include office visit, hospital admission and prescription data for 1/1/1999–6/30/2001. Exposure variable was oral antibiotic person-days (pds). Primary outcome was hospitalization during exposure with ADE diagnoses: anaphylaxis, phototoxicity, hepatotoxicity, nephrotoxicity, seizures, ventricular arrhythmia or infectious colitis.
We randomly sampled 999,773, 1,047,496 and 1,819,004 patients from Databases A, B and C respectively. 33,183 amoxicillin, 15,250 ciprofloxacin and 50,171 doxycycline prescriptions continued ≥30 days. ADE hospitalizations during long-term exposure were not observed in Database A. ADEs during long-term amoxicillin were seen only in Database C with 5 ADEs or 1.2(0.4–2.7) ADEs/100,000 pds exposure. Long-term ciprofloxacin showed 3 and 4 ADEs with 5.7(1.2–16.6) and 3.5(1.0–9.0) ADEs/100,000 pds in Databases B and C, respectively. Only Database B had ADEs during long-term doxycycline with 3 ADEs or 0.9(0.2–2.6) ADEs/100,000 pds. For most events, the incidence rate ratio, comparing >28 vs.1–28 pds exposure was <1, showing limited evidence for cumulative dose-related ADEs from long-term exposure.
Long-term amoxicillin, ciprofloxacin and doxycycline appears safe, supporting use of these medications if needed for large-scale post-exposure anthrax prophylaxis.
PMCID: PMC4269235  PMID: 18215001
Anti-infective agents; Anthrax prevention and control; Health services research; Databases; Bioterrorism
8.  The Effect of a Hospital-Wide Urine Culture Screening Intervention on the Incidence of Extended-Spectrum β-Lactamase-Producing Escherichia coli and Klebsiella Species 
Optimal strategies for limiting the transmission of extended-spectrum β-lactamase-producing Escherichia coli and Klebsiella spp (ESBL-EK) in the hospital setting remain unclear. The objective of this study was to evaluate the impact of a urine culture screening strategy on the incidence of ESBL-EK.
Prospective quasi-experimental study.
Two intervention hospitals and one control hospital within a university health system from 2005 to 2009.
All clinical urine cultures with E. coli or Klebsiella spp were screened for ESBL-EK. Patients determined to be colonized or infected with ESBL-EK were placed in a private room with contact precautions. The primary outcome of interest was nosocomial ESBL-EK incidence in nonurinary clinical cultures (cases occurring more than 48 hours after admission). Changes in monthly ESBL-EK incidence rates were evaluated with mixed-effects Poisson regression models, with adjustment for institution-level characteristics (eg, total admissions).
The overall incidence of ESBL-EK increased from 1.42/10,000 patient-days to 2.16/10,000 patient-days during the study period. The incidence of community-acquired ESBL-EK increased nearly 3-fold, from 0.33/10,000 patient-days to 0.92/10,000 patient-days (P < .001). On multivariable analysis, the intervention was not significantly associated with a reduction in nosocomial ESBL-EK incidence (incidence rate ratio, 1.38 [95% confidence interval, 0.83–2.31]; P =.21).
Universal screening of clinical urine cultures for ESBL-EK did not result in a reduction in nosocomial ESBL-EK incidence rates, most likely because of increases in importation of ESBL-EK cases from the community. Further studies are needed on elucidating optimal infection control interventions to limit spread of ESBL-producing organisms in the hospital setting.
PMCID: PMC3981746  PMID: 24113599
9.  Comparison of Prior Authorization and Prospective Audit with Feedback for Antimicrobial Stewardship 
Although prior authorization and prospective audit with feedback are both effective antimicrobial stewardship program (ASP) strategies, the relative impact of these approaches remains unclear. We compared these core ASP strategies at an academic medical center.
Quasi-experimental study.
We compared antimicrobial use during the 24 months before and after implementation of an ASP strategy change. The ASP used prior authorization alone during the preintervention period, June 2007 through May 2009. In June 2009, many antimicrobials were unrestricted and prospective audit was implemented for cefepime, piperacillin/tazobactam, and vancomycin, marking the start of the postintervention period, July 2009 through June 2011. All adult inpatients who received more than or equal to 1 dose of an antimicrobial were included. The primary end point was antimicrobial consumption in days of therapy per 1,000 patient-days (DOT/1,000-PD). Secondary end points included length of stay (LOS).
In total, 55,336 patients were included (29,660 preintervention and 25,676 postintervention). During the preintervention period, both total systemic antimicrobial use (−9.75 DOT/1,000-PD per month) and broad-spectrum anti-gram-negative antimicrobial use (−4.00 DOT/1,000-PD) declined. After the introduction of prospective audit with feedback, however, both total antimicrobial use (+9.65 DOT/1,000-PD per month; P < .001) and broad-spectrum anti-gram-negative antimicrobial use (+4.80 DOT/1,000-PD per month; P < .001) increased significantly. Use of cefepime and piperacillin/tazobactam both significantly increased after the intervention (P = .03). Hospital LOS and LOS after first antimicrobial dose also significantly increased after the intervention (P = .016 and .004, respectively).
Significant increases in antimicrobial consumption and LOS were observed after the change in ASP strategy.
PMCID: PMC4198070  PMID: 25111916
10.  Impact of Antibiotic Use during Hospitalization on the Development of Gastrointestinal Colonization with Escherichia coli with Reduced Fluoroquinolone Susceptibility 
Infections due to fluoroquinolone-resistant Escherichia coli (FQREC) are associated with significant morbidity and mortality. Fluoroquinolone resistance likely arises at the level of gastrointestinal colonization. The objective of this study was to identify risk factors for the development of FQREC gastrointestinal tract colonization in hospitalized patients, including the impact of antibiotics prescribed during hospitalization.
A prospective cohort study was conducted from 2002 to 2004 within a university health system.
Hospitalized patients initially colonized with fluoroquinolone-susceptible E. coli were followed up with serial fecal sampling for new FQREC colonization or until hospital discharge or death. A Cox proportional hazards regression model was developed to identify risk factors for new FQREC colonization, with antibiotic exposure modeled as time-varying covariates.
Of 395 subjects, 73 (18.5%) became newly colonized with FQREC. Length of stay before sampling (hazard ratio [HR], 1.02 [95% confidence interval (CI), 1.1–1.03]; P = .003) and malignancy (HR, 0.37 [95% CI, 0.21–0.67]; P = .001) were significantly associated with the development of FQREC colonization. In addition, receipt of a first-generation cephalosporin (HR, 1.19 [95% CI, 1.10–1.29]; P < .001) or cefepime (HR, 1.05 [95% CI, 1.00–1.10]; P = .048) during hospitalization increased the risk of new FQREC colonization.
The acquisition of FQREC in the hospital setting is complex, and antimicrobial stewardship programs should take into account patterns of antibiotic use in implementing strategies to reduce the development of new FQREC colonization. Future studies are needed to identify risk factors for infection in hospitalized patients newly colonized with FQREC.
PMCID: PMC3979459  PMID: 24018924
11.  Public Reporting of Hospital-Acquired Infections Is Not Associated with Improved Processes or Outcomes 
Most US states have enacted or are considering legislation mandating hospitals to publicly report hospital-acquired infection (HAI) rates. We conducted a survey of infection control professionals and found that state-legislated public reporting of HAIs is not associated with perceived improvements in infection prevention program process measures or HAI rates.
PMCID: PMC3979462  PMID: 23838228
12.  Temporal Changes in Resistance Mechanisms in Colonizing Escherichia coli Isolates with Reduced Susceptibility to Fluoroquinolones 
The objective of this study was to characterize the temporal variability of fluoroquinolone resistance mechanisms among Escherichia coli colonizing the gastrointestinal tract of hospitalized patients. Patients with new fluoroquinolone-resistant E. coli (FQREC) colonization were followed with serial fecal sampling until discharge or death. Genetic mechanism(s) of resistance for all FQREC isolates were characterized, including mutations in gyrA and parC and efflux pump overexpression. Of 451 subjects, 73 (16.2%) became newly colonized with FQREC. There was significant variability in regard to temporal changes in resistance mechanisms and levofloxacin MICs among isolates from individual patients. Compared to patients with transient colonization, patients with persistent colonization were more likely to have a urinary catheter (P=0.04), diarrhea (P=0.04), and a longer duration of hospitalization (22 and 9.0 mean days, respectively; P=0.01) prior to sampling. Our data demonstrate the significant variability of resistance mechanisms in colonizing E. coli isolates among hospitalized patients.
PMCID: PMC3725193  PMID: 23719087
13.  Variations in Identification of Healthcare-Associated Infections 
Little is known about whether those performing healthcare-associated infection (HAI) surveillance vary in their interpretations of HAI definitions developed by the Centers for Disease Control and Prevention’s National Healthcare Safety Network (NHSN). Our primary objective was to characterize variations in these interpretations using clinical vignettes. We also describe predictors of variation in responses.
Cross-sectional study.
United States.
A sample of US-based members of the Society for Healthcare Epidemiology of America (SHEA) Research Network.
Respondents assessed whether each of 6 clinical vignettes met criteria for an NHSN-defined HAI. Individual- and institutional-level data were also gathered.
Surveys were distributed to 143 SHEA Research Network members from 126 hospitals. In total, 113 responses were obtained, representing at least 61 unique hospitals (30 respondents did not identify a hospital); 79.2% (84 of 106 nonmissing responses) were infection preventionists, and 79.4% (81 of 102 nonmissing responses) worked at academic hospitals. Among the 6 vignettes, the proportion of respondents correctly characterizing the vignettes was as low as 27.3%. Combining all 6 vignettes, the mean percentage of correct responses was 61.1% (95% confidence interval, 57.7%–63.8%). Percentage of correct responses was associated with presence of a clinical background (ie, nursing or physician degrees) but not with hospital size or infection prevention and control department characteristics.
Substantial heterogeneity exists in the application of HAI definitions in this survey of infection preventionists and hospital epidemiologists. Our data suggest a need to better clarify these definitions, especially when comparing HAI rates across institutions.
PMCID: PMC3981741  PMID: 23739071
14.  Defining Relatedness in Studies of Transmission of Antimicrobial-Resistant Organisms: Variability in Definitions across Studies and Impact of Different Approaches on Study Conclusions 
Comparison of studies evaluating patient-to-patient transmission of organisms is difficult, given the lack of standardized criteria. We used fluoroquinolone-resistant Escherichia coli (FQREC) as a model to characterize variability in definitions of relatedness across studies and to evaluate the resultant impact on study conclusions.
Narrative review and cohort study.
The narrative review compared relatedness criteria across studies of FQREC. Additionally, an existing database was used to compare relatedness of isolates on the basis of molecular criteria alone versus molecular plus clinical criteria with different temporal cutoffs (hospitalization overlap of ≥ 1 day or allowance for nonoverlap of hospitalization dates of ≤7 days or ≤30 days).
Forty-six articles met narrative review inclusion criteria. Sixteen studies exclusively utilized molecular criteria to define relatedness. Thirty studies included molecular and clinical criteria. Of these, 6 included temporal data (ie, time period of isolate identification), 10 included patient location, and 14 included proximity and temporal criteria. For the database analysis, 353 patients were colonized with FQREC. There were 2 main clusters containing 48 and 17 related isolates within 49 pulsed-field gel electrophoresis types. Among the clusters, 18.4% of isolates were related by molecular criteria. Incorporating clinical criteria, fewer isolates were considered related: 5.7% of isolates using 30-day criteria, 3.1% using 7-day criteria, and 1.4% using 1-day overlap.
There is considerable variability in definitions of relatedness of FQREC. Utilizing molecular criteria alone to define relatedness overestimates transmission compared with definitions including clinical criteria. Standard definitions of relatedness in studies of antimicrobial-resistant organisms are needed.
PMCID: PMC3983273  PMID: 23221191
15.  Prior Vancomycin Use Is a Risk Factor for Reduced Vancomycin Susceptibility in Methicillin-Susceptible but Not Methicillin-Resistant Staphylococcus aureus Bacteremia 
Staphylococcus aureus is a cause of community- and healthcare-acquired infections and is associated with substantial morbidity, mortality, and costs. Vancomycin minimum inhibitory concentrations (MICs) among S. aureus have increased, and reduced vancomycin susceptibility (RVS) may be associated with treatment failure. We aimed to identify clinical risk factors for RVS in S. aureus bacteremia.
Academic tertiary care medical center and affiliated urban community hospital.
Cases were patients with RVS S. aureus isolates (defined as vancomycin E-test MIC >1.0 μg/mL). Controls were patients with non-RVS S. aureus isolates.
Of 392 subjects, 134 (34.2%) had RVS. Fifty-eight of 202 patients (28.7%) with methicillin-susceptible S. aureus (MSSA) isolates had RVS, and 76 of 190 patients (40.0%) with methicillin-resistant S. aureus (MRSA) isolates had RVS (P =.02). In unadjusted analyses, prior vancomycin use was associated with RVS (odds ratio [OR], 2.08; 95% confidence interval [CI], 1.00–4.32; P =.046). In stratified analyses, there was significant effect modification by methicillin susceptibility on the association between vancomycin use and RVS (P = .04). In multivariable analyses, after hospital of admission and prior levofloxacin use were controlled for, the association between vancomycin use and RVS was significant for patients with MSSA infection (adjusted OR, 4.02; 95% CI, 1.11–14.50) but not MRSA infection (adjusted OR, 0.87; 95% CI, 0.36–2.13).
A substantial proportion of patients with S. aureus bacteremia had RVS. The association between prior vancomycin use and RVS was significant for patients with MSSA infection but not MRSA infection, suggesting a complex relationship between the clinical and molecular epidemiology of RVS in S. aureus.
PMCID: PMC3983274  PMID: 22227985
16.  Risk Factors for Gastrointestinal Tract Colonization with Extended-Spectrum β-Lactamase (ESBL)–Producing Escherichia coli and Klebsiella Species in Hospitalized Patients 
We describe the prevalence of and risk factors for colonization with extended-spectrum β-lactamase (ESBL)–producing Escherichia coli and Klebsiella species (ESBL-EK) in hospitalized patients. The prevalence of colonization with ESBL-EK was 2.6%. Colonization was associated with cirrhosis, longer duration of hospital stay prior to surveillance, and prior exposure to clindamycin or meropenem.
PMCID: PMC3983276  PMID: 23143363
17.  The Effect of Staphylococcal Cassette Chromosome mec (SCCmec) Type on Clinical Outcomes in Methicillin-Resistant Staphylococcus aureus Bacteremia 
The Journal of infection  2012;66(1):41-47.
The impact of staphylococcal cassette chromosome mec (SCCmec) type on mortality in methicillin-resistant Staphylococcus aureus (MRSA) infections remains unclear. The objective of this study was to determine the association between SCCmec type and mortality in MRSA bacteremia.
A cohort study of patients who were hospitalized with MRSA bacteremia was conducted within a university health system. A multivariable logistic regression model was developed to evaluate the association of SCCmec type with 30-day in-hospital mortality.
Thirty-four of a total of 184 patients with MRSA bacteremia died, resulting in a mortality rate of 18.5%. Adjusted risk factors for 30-day mortality included APRDRG Risk of Mortality score (odds ratio [OR], 5.33; 95% confidence interval [CI], 2.28-12.4; P<0.001), white blood cell count (OR, 1.09; 95% CI, 1.03-1.15; P=0.002), and malignancy (OR, 3.25; 95% CI, 1.17-9.02; P=0.02). On multivariable analyses, SCCmec II was not significantly associated with mortality in patients with MRSA bacteremia (OR, 1.85; 95% CI, 0.69-4.92; P=0.22).
Mortality in MRSA bacteremia was independent of SCCmec type. SCCmec type II is most likely a marker for disease severity rather than a direct mediator of mortality. Further research is needed to elucidate the factors associated with poor clinical outcomes in MRSA infections.
PMCID: PMC3518704  PMID: 22960078
methicillin-resistant; Staphylococcus aureus; outcomes; bacteremia
18.  Risk Factors for Efflux Pump Overexpression in Fluoroquinolone-Resistant Escherichia coli 
The Journal of Infectious Diseases  2012;206(10):1597-1603.
Background. We conducted a case-control study to identify risk factors for efflux overexpression, an important mechanism of fluoroquinolone resistance, among patients with fluoroquinolone-resistant Escherichia coli (FQREC) gastrointestinal tract colonization.
Methods. Three annual fecal surveillance surveys were performed hospital-wide, and all patients colonized with FQREC (levofloxacin minimum inhibitory concentration, ≥8 μg/mL) were included in the study. Cases and controls were defined on the basis of overexpression of the AcrAB efflux pump, as measured by the organic solvent tolerance (OST) assay. A multivariable logistic regression model was developed to identify risk factors for OST positivity among patients with FQREC colonization.
Results. Eighty-nine patients were colonized with FQREC: 44 (49.4%) and 45 (50.6%) patients had isolates that were OST-positive and OST-negative, respectively. On multivariable analyses, location on the surgical service was significantly associated with recovery of an OST-positive isolate (odds ratio, 7.36; 95% confidence interval, 1.82–29.7; P = .005). Furthermore, patients who had received a first-generation cephalosporin in the 30 days prior to sampling were less likely to have an OST-positive isolate (odds ratio, 0.20; 95% confidence interval, .04–.94; P = .04).
Conclusions. Among phenotypically identical FQREC isolates, different factors may drive the emergence of different resistance mechanisms. Further studies are needed to elucidate the relationship between antimicrobial use and specific resistance mechanisms.
PMCID: PMC3475638  PMID: 22966123
19.  Reduced vancomycin susceptibility and staphylococcal cassette chromosome mec (SCCmec) type distribution in methicillin-resistant Staphylococcus aureus bacteraemia 
Journal of Antimicrobial Chemotherapy  2012;67(10):2346-2349.
Recent epidemiological evidence suggests that genotypic and phenotypic characteristics that have typically distinguished community-associated methicillin-resistant Staphylococcus aureus (MRSA) and healthcare-associated MRSA strains may be evolving. The objective of this study was to examine the association between reduced vancomycin susceptibility (RVS) and staphylococcal cassette chromosome mec (SCCmec) type in MRSA bloodstream isolates.
A cohort study of patients who were hospitalized from 2007 to 2009 with S. aureus bacteraemia was conducted within a university health system. Bivariable analyses were conducted to determine the association between RVS and SCCmec type, as well as other microbiological characteristics including Panton–Valentine leucocidin, accessory gene regulator (agr) dysfunction and vancomycin heteroresistance.
A total of 188 patients with MRSA bacteraemia were identified: 116 (61.7%) and 72 (38.3%) patients had infections due to healthcare-associated MRSA and community-associated MRSA, respectively. As defined by a vancomycin Etest MIC > 1.0 mg/L, the prevalence of RVS was 40.4%. Isolates with RVS were significantly more likely to be associated with SCCmec II compared with isolates without RVS (74.7% and 47.3%, respectively, P < 0.001), but not with Panton–Valentine leucocidin (P = 0.10), agr dysfunction (P = 0.19) or healthcare-associated infection (P = 0.36).
The results of our study demonstrate important microbiological characteristics among MRSA isolates characterized by RVS, including a significant association between SCCmec II and elevated vancomycin MIC. It is clear that the clinical and molecular epidemiology of MRSA is evolving, and further understanding of factors determining virulence will be important for the elucidation of optimal treatment approaches for associated infections.
PMCID: PMC3444231  PMID: 22761330
MRSA; virulence factors; antimicrobial resistance; epidemiology
20.  Surveillance Definitions of Infections in Long-Term Care Facilities: Revisiting the McGeer Criteria 
(See the commentary by Moro, on pages 978–980.)
Infection surveillance definitions for long-term care facilities (ie, the McGeer Criteria) have not been updated since 1991. An expert consensus panel modified these definitions on the basis of a structured review of the literature. Significant changes were made to the criteria defining urinary tract and respiratory tract infections. New definitions were added for norovirus gastroenteritis and Clostridum difficile infections.
PMCID: PMC3538836  PMID: 22961014
21.  Does Nonpayment for Hospital-Acquired Catheter-Associated Urinary Tract Infections Lead to Overtesting and Increased Antimicrobial Prescribing? 
This retrospective cohort study of 39 US hospitals found that Centers for Medicare & Medicaid Services nonpayment for hospital-acquired catheter-associated urinary tract infections (UTIs) has not led to overtesting for UTI on admission or to increased antimicrobial prescribing.
Background. On 1 October 2008, in an effort to stimulate efforts to prevent catheter-associated urinary tract infection (CAUTI), the Centers for Medicare & Medicaid Services (CMS) implemented a policy of not reimbursing hospitals for hospital-acquired CAUTI. Since any urinary tract infection present on admission would not fall under this initiative, concerns have been raised that the policy may encourage more testing for and treatment of asymptomatic bacteriuria.
Methods. We conducted a retrospective multicenter cohort study with time series analysis of all adults admitted to the hospital 16 months before and 16 months after policy implementation among participating Society for Healthcare Epidemiology of America Research Network hospitals. Our outcomes were frequency of urine culture on admission and antimicrobial use.
Results. A total of 39 hospitals from 22 states submitted data on 2 362 742 admissions. In 35 hospitals affected by the CMS policy, the median frequency of urine culture performance did not change after CMS policy implementation (19.2% during the prepolicy period vs 19.3% during the postpolicy period). The rate of change in urine culture performance increased minimally during the prepolicy period (0.5% per month) and decreased slightly during the postpolicy period (–0.25% per month; P < .001). In the subset of 10 hospitals providing antimicrobial use data, the median frequency of fluoroquinolone antimicrobial use did not change substantially (14.6% during the prepolicy period vs 14.0% during the postpolicy period). The rate of change in fluoroquinolone use increased during the prepolicy period (1.26% per month) and decreased during the postpolicy period (–0.60% per month; P < .001).
Conclusions. We found no evidence that CMS nonpayment policy resulted in overtesting to screen for and document a diagnosis of urinary tract infection as present on admission.
PMCID: PMC3657518  PMID: 22700826
22.  Effect of Accessibility of Influenza Vaccination on the Rate of Childcare Staff Vaccination 
We assessed the impact of free on-site influenza vaccination on childcare staff vaccination prevalence using 2 before-and-after studies. Vaccination was offered during the 2003–2004 and 2006–2007 influenza seasons. Staff vaccination prevalence was higher in each intervention season compared to the prior, nonintervention season. No baseline characteristics were associated with receipt of vaccination.
PMCID: PMC3697428  PMID: 18419374
23.  Potential for pet animals to harbor methicillin-resistant Staphylococcus aureus (MRSA) when residing with human MRSA patients 
Zoonoses and Public Health  2012;59(4):286-293.
Colonization by methicillin-resistant Staphylococcus aureus (MRSA) may be persistent in people, and is horizontally transmissible. The scientific literature suggests that domestic pets may also participate in cross-transmission of MRSA within households. The objectives of this study were to evaluate the prevalence of and risk factors for MRSA carriage by pets residing in households with an MRSA-infected person. From 66 households in which an MRSA infected patient resided, we screened 47 dogs and 52 cats using a swab protocol. Isolates from pets and humans were genotyped using two techniques, and compared for concordance. Human participants completed a 22-question survey of demographic and epidemiologic data relevant to staphylococcal transmission. Eleven of 99 pets (11.5%) representing 9 (13.6%) of households were MRSA-positive, but in only 6 of these households were the human and animal-source strains genetically concordant. Human infection by strain USA 100 was significantly associated with pet carriage [OR = 11.4 (95% C.I. 1.7, 76.9); p=0.013]. Yet, for each day of delay in sampling the pet after the person’s MRSA diagnosis, the odds of isolating any type of MRSA from the pet decreased by 13.9% [(95% C.I. 2.6%, 23.8%); p=0.017)]. It may be concluded that pets can harbor pandemic strains of MRSA while residing in a household with an infected person. However, the source of MRSA to the pet cannot always be attributed to the human patient. Moreover, the rapid attrition of the odds of obtaining a positive culture from pets over time suggests that MRSA carriage may be fleeting.
PMCID: PMC3326176  PMID: 22233337
Pets; Staphylococcus; MRSA; zoonosis; Bacterial Typing Techniques
24.  Risk Factors for Infection or Colonization with CTX-M Extended-Spectrum-β-Lactamase-Positive Escherichia coli 
Antimicrobial Agents and Chemotherapy  2012;56(11):5575-5580.
There has been a significant increase in the prevalence of Enterobacteriaceae that produce CTX-M-type extended-spectrum β-lactamases. The objective of this study was to evaluate risk factors for infection or colonization with CTX-M-positive Escherichia coli. A case-control study was conducted within a university system from 1 January 2007 to 31 December 2008. All patients with clinical cultures with E. coli demonstrating resistance to extended-spectrum cephalosporins were included. Case patients were designated as those with cultures positive for CTX-M-positive E. coli, and control patients were designated as those with non-CTX-M-producing E. coli. Multivariable logistic regression analyses were performed to evaluate risk factors for CTX-M-positive isolates. A total of 83 (56.8%) of a total of 146 patients had cultures with CTX-M-positive E. coli. On multivariable analyses, there was a significant association between infection or colonization with CTX-M-type β-lactamase-positive E. coli and receipt of piperacillin-tazobactam in the 30 days prior to the culture date (odds ratio [OR], 7.36; 95% confidence interval [CI], 1.61 to 33.8; P = 0.01) and a urinary culture source (OR, 0.36; 95% CI, 0.17 to 0.77; P = 0.008). The rates of resistance to fluoroquinolones were significantly higher in isolates from case patients than in isolates from control patients (90.4 and 50.8%, respectively; P < 0.001). We found that nonurinary sources of clinical cultures and the recent use of piperacillin-tazobactam conferred an increased risk of colonization or infection with CTX-M-positive E. coli. Future studies will need to focus on outcomes associated with infections due to CTX-M-positive E. coli, as well as infection control strategies to limit the spread of these increasingly common organisms.
PMCID: PMC3486585  PMID: 22890772
25.  Effect of Reduced Vancomycin Susceptibility on Clinical and Economic Outcomes in Staphylococcus aureus Bacteremia 
Antimicrobial Agents and Chemotherapy  2012;56(10):5164-5170.
Reduced vancomycin susceptibility (RVS) may lead to poor clinical outcomes in Staphylococcus aureus bacteremia. The objective of this study was to evaluate the clinical and economic impact of RVS in patients with bacteremia due to S. aureus. A cohort study of patients who were hospitalized from December 2007 to May 2009 with S. aureus bacteremia was conducted within a university health system. Multivariable logistic regression and zero-truncated negative binomial regression models were developed to evaluate the association of RVS with 30-day in-hospital mortality, length of stay, and hospital charges. One hundred thirty-four (34.2%) of a total of 392 patients had bacteremia due to S. aureus with RVS as defined by a vancomycin Etest MIC of >1.0 μg/ml. Adjusted risk factors for 30-day in-hospital mortality included the all patient refined-diagnosis related group (APRDRG) risk-of-mortality score (odds ratio [OR], 7.11; 95% confidence interval [CI], 3.04 to 16.6), neutropenia (OR, 13.4; 95% CI, 2.46 to 73.1), white blood cell count (OR, 1.05; 95% CI, 1.01 to 1.09), immunosuppression (OR, 6.31; 95% CI, 1.74 to 22.9), and intensive care unit location (OR, 3.51; 95% CI, 1.65 to 7.49). In multivariable analyses, RVS was significantly associated with increased mortality in patients with S. aureus bacteremia as a result of methicillin-susceptible (OR, 3.90; 95% CI, 1.07 to 14.2) but not methicillin-resistant (OR, 0.53; 95% CI, 0.19 to 1.46) isolates. RVS was associated with greater 30-day in-hospital mortality in patients with bacteremia due to methicillin-susceptible S. aureus but not methicillin-resistant S. aureus. Further research is needed to identify optimal treatment strategies to reduce mortality associated with RVS in S. aureus bacteremia.
PMCID: PMC3457402  PMID: 22825122

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