OBJECTIVE: 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.

DESIGN: Prospective quasi-experimental study.

SETTING: Two intervention hospitals and one control hospital within a university health system from 2005 to 2009.

PATIENTS AND INTERVENTION: 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).

RESULTS: 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).

CONCLUSIONS: 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.

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.

<p>We used a survey to characterize contemporary infection prevention and antibiotic stewardship program practices across 64 healthcare facilities, and we compared these findings to those of a similar 2013 survey. Notable findings include decreased frequency of active surveillance for methicillin-resistant Staphylococcus aureus, frequent active surveillance for carbapenem-resistant Enterobacteriaceae, and increased support for antibiotic stewardship programs.</p>

<p><strong>Background: </strong>Biomarkers can facilitate safe antibiotic discontinuation in critically ill patients without bacterial infection.</p>

<p><strong>Methods: </strong>We tested the ability of a biomarker-based algorithm to reduce excess antibiotic administration in patients with systemic inflammatory response syndrome (SIRS) without bacterial infections (uninfected) in our pediatric intensive care unit (PICU). The algorithm suggested that PICU clinicians stop antibiotics if (1) C-reactive protein &lt;4 mg/dL and procalcitonin &lt;1 ng/mL at SIRS onset and (2) no evidence of bacterial infection by exam/testing by 48 hours. We evaluated excess broad-spectrum antibiotic use, defined as administration on days 3-9 after SIRS onset in uninfected children. Incidence rate ratios (IRRs) compared unadjusted excess length of therapy (LOT) in the 34 months before (Period 1) and 12 months after (Period 2) implementation of this algorithm, stratified by biomarker values. Segmented linear regression evaluated excess LOT among all uninfected episodes over time and between the periods.</p>

<p><strong>Results: </strong>We identified 457 eligible SIRS episodes without bacterial infection, 333 in Period 1 and 124 in Period 2. When both biomarkers were below the algorithm's cut-points (n = 48 Period 1, n = 31 Period 2), unadjusted excess LOT was lower in Period 2 (IRR, 0.53; 95% confidence interval, 0.30-0.93). Among all 457 uninfected episodes, there were no significant differences in LOT (coefficient 0.9, P = .99) between the periods on segmented regression.</p>

<p><strong>Conclusions: </strong>Implementation of a biomarker-based algorithm did not decrease overall antibiotic exposure among all uninfected patients in our PICU, although exposures were reduced in the subset of SIRS episodes where biomarkers were low.</p>

<p>In this multicenter study, we identified an increased risk of 30-day mortality among hospitalized children with carbapenem-resistant Enterobacteriaceae (CRE) isolated from clinical cultures compared with those with carbapenem-susceptible Enterobacteriaceae. We additionally report significant variation in antibiotic treatment for children with CRE infections with infrequent use of combination therapy.</p>

<p><strong>OBJECTIVES: </strong>Sepsis is associated with high early and total in-hospital mortality. Despite recent revisions in the diagnostic criteria for sepsis that sought to improve predictive validity for mortality, it remains difficult to identify patients at greatest risk of death. We compared the utility of nine biomarkers to predict mortality in subjects with clinically suspected bacterial sepsis.</p>

<p><strong>DESIGN: </strong>Cohort study.</p>

<p><strong>SETTING: </strong>The medical and surgical ICUs at an academic medical center.</p>

<p><strong>SUBJECTS: </strong>We enrolled 139 subjects who met two or more systemic inflammatory response syndrome (systemic inflammatory response syndrome) criteria and received new broad-spectrum antibacterial therapy.</p>

<p><strong>INTERVENTIONS: </strong>We assayed nine biomarkers (α-2 macroglobulin, C-reactive protein, ferritin, fibrinogen, haptoglobin, procalcitonin, serum amyloid A, serum amyloid P, and tissue plasminogen activator) at onset of suspected sepsis and 24, 48, and 72 hours thereafter. We compared biomarkers between groups based on both 14-day and total in-hospital mortality and evaluated the predictive validity of single and paired biomarkers via area under the receiver operating characteristic curve.</p>

<p><strong>MEASUREMENTS AND MAIN RESULTS: </strong>Fourteen-day mortality was 12.9%, and total in-hospital mortality was 29.5%. Serum amyloid P was significantly lower (4/4 timepoints) and tissue plasminogen activator significantly higher (3/4 timepoints) in the 14-day mortality group, and the same pattern held for total in-hospital mortality (Wilcoxon p ≤ 0.046 for all timepoints). Serum amyloid P and tissue plasminogen activator demonstrated the best individual predictive performance for mortality, and combinations of biomarkers including serum amyloid P and tissue plasminogen activator achieved greater predictive performance (area under the receiver operating characteristic curve &gt; 0.76 for 14-d and 0.74 for total mortality).</p>

<p><strong>CONCLUSIONS: </strong>Combined biomarkers predict risk for 14-day and total mortality among subjects with suspected sepsis. Serum amyloid P and tissue plasminogen activator demonstrated the best discriminatory ability in this cohort.</p>

<p>Carbapenem-resistant Enterobacteriaceae (CRE) are increasingly identified in children in the United States, but data on the epidemiology of CRE in this population are limited. The objectives of this study were to characterize risk factors for colonization or infection with CRE and describe the microbiologic characteristics of pediatric CRE isolates. We performed a multicenter matched case-control study from January 2011 to October 2015 at three tertiary care pediatric centers. Case patients were hospitalized children with CRE isolated from clinical cultures and were matched in a 2:1 ratio to control patients with carbapenem-susceptible Enterobacteriaceae (CSE). Risk factors for colonization or infection with CRE were then evaluated using multivariable conditional logistic regression. Additionally, we comprehensively reported the antimicrobial susceptibility pattern for CRE isolates. Sixty-three case patients were identified and matched to 126 control patients. On multivariable analysis, anti-pseudomonal antibiotic exposure within the previous 3 months (odds ratio [OR], 5.20; 95% confidence interval [CI], 1.71-15.9, P=0.004), prior surgery (OR, 6.30; 95% CI, 1.83-21.6, P=0.003), and mechanical ventilation (OR, 12.4; 95% CI, 1.26-122, P=0.031) were identified as risk factors for colonization or infection with CRE. Pediatric CRE isolates demonstrated relatively low rates of resistance to amikacin (5%) and ciprofloxacin (25%). Our findings support an important role for antibiotic stewardship interventions limiting the unnecessary use of anti-pseudomonal antibiotics as a strategy to prevent widespread emergence of CRE in children. Future studies should further characterize molecular determinants of antibiotic resistance among pediatric CRE isolates.</p>

<p>We characterized use of the carbapenems, polymyxins, and tigecycline in United States children's hospitals between 2010 and 2014. We found substantial variability in use across hospitals and overall decreased use over time. Most polymyxin and tigecycline use occurred in cystic fibrosis patients, and appendectomy was a common indication for carbapenem therapy.</p>

<p>Antibacterial resistance is increasing globally and has been recognized as a major public health threat. Antibacterial stewardship is the coordinated effort to improve the appropriate use of antibiotics with the aim to decrease selective pressure for multidrug-resistant organisms in order to preserve the utility of antibacterial agents. This article describes the activities of the Antibacterial Resistance Leadership Group (ARLG) in the area of antibacterial stewardship. To date, the ARLG has focused intensely on development of rapid diagnostic tests, which (when coupled with educational and institutional initiatives) will enable the robust stewardship that is needed to address the current crisis of antibacterial resistance. In addition to exploring the effectiveness of stewardship techniques in community hospitals, the ARLG has also developed strategy trials to assess the feasibility of reducing antibacterial usage while preserving patient outcome.</p>

<p><strong>BACKGROUND: </strong>Biomarkers that identify critically ill children with systemic inflammatory response syndrome (SIRS) at low risk for bacterial infection may help clinicians reduce unnecessary antibiotic use.</p>

<p><strong>METHODS: </strong>We conducted a prospective cohort study of children with SIRS and suspected infection admitted to a pediatric intensive care unit from January 5, 2012 to March 7, 2014. We enrolled patients upon initiation of new antibiotics (Time 0) and measured a panel of 8 serum biomarkers daily over 72 hours. Microbiology, imaging, and clinical data were reviewed to classify bacterial infections using Centers for Disease Control and Prevention definitions. We identified cut points of biomarker combinations to maximize the negative predictive value (NPV) and specificity for bacterial infection. Excess antibiotics were calculated as days of therapy beyond day 2 after SIRS onset in patients without bacterial infection.</p>

<p><strong>RESULTS: </strong>Infections were identified in 46 of 85 patients: bacterial (n = 22) and viral (24), whereas 39 patients had no infection identified. At Time 0, C-reactive protein (CRP) &lt;5 mg/dL plus serum amyloid A &lt;15.0 µg/mL had an NPV of 0.92 (95% confidence interval [CI], 0.79-1.0) and specificity of 0.54 (95% CI, 0.42-0.66) to identify patients without bacterial infection, whereas CRP &lt;4 mg/dL plus procalcitonin &lt;1.75 ng/mL had an NPV of 0.90 (95% CI, 0.79-1.0) and specificity of 0.43 (95% CI, 0.30-0.55). Patients without bacterial infection received a mean of 3.8 excess days of therapy.</p>

<p><strong>CONCLUSIONS: </strong>Early measurement of select biomarkers can identify children with SIRS in whom antibiotics might be safely discontinued when there is no other objective evidence of infection at 48 hours.</p>