The effect of a hospital-wide urine culture screening intervention on the incidence of extended-spectrum β-lactamase-producing Escherichia coli and Klebsiella species.

2013

1160-6

2013 Nov

1559-6834

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.

10.1086/673453

Infect Control Hosp Epidemiol

24113599

Impact of rapid diagnostics with antimicrobial stewardship support for children with positive blood cultures: A quasi-experimental study with time trend analysis.

2020

1-8

2020 Jun 23

1559-6834

<p><strong>OBJECTIVE: </strong>Evaluate the clinical impact of the implementation of VERIGENE gram-positive blood culture testing (BC-GP) coupled with antimicrobial stewardship result notification for children with positive blood cultures.</p>

<p><strong>DESIGN: </strong>Quasi-experimental study.</p>

<p><strong>SETTING: </strong>Quaternary children's hospital.</p>

<p><strong>PATIENTS: </strong>Hospitalized children aged 0-21 years with positive blood culture events 1 year before and 1 year after implementation of BC-GP testing.</p>

<p><strong>METHODS: </strong>The primary outcome was time to optimal antibiotic therapy for positive blood cultures, defined as receiving definitive therapy without unnecessary antibiotics (pathogens) or no antibiotics (contaminants). Secondary outcomes were time to effective therapy, time to definitive therapy, and time to stopping vancomycin, length of stay, and 30-day mortality. Time-to-therapy outcomes before and after the intervention were compared using Cox regression models and interrupted time series analyses, adjusting for patient characteristics and trends over time. Gram-negative events were included as a nonequivalent dependent variable.</p>

<p><strong>RESULTS: </strong>We included 264 preintervention events (191 gram-positive, 73 gram-negative) and 257 postintervention events (168 gram-positive, 89 gram-negative). The median age was 2.9 years (interquartile range, 0.3-10.1), and 418 pediatric patients (80.2%) had ≥1 complex chronic condition. For gram-positive isolates, implementation of BC-GP testing was associated with an immediate reduction in time to optimal therapy and time to stopping vancomycin for both analyses. BC-GP testing was associated with decreased time to definitive therapy in interrupted time series analysis but not Cox modeling. No such changes were observed for gram-negative isolates. No changes in time to effective therapy, length of stay, or mortality were associated with BC-GP.</p>

<p><strong>CONCLUSIONS: </strong>The implementation of BC-GP testing coupled with antimicrobial stewardship result notification was associated with decreased time to optimal therapy and time to stopping vancomycin for hospitalized children with gram-positive blood culture isolates.</p>

10.1017/ice.2020.191

Infect Control Hosp Epidemiol

32571440

Implementation of a Pragmatic Biomarker-Driven Algorithm to Guide Antibiotic Use in the Pediatric Intensive Care Unit: the Optimizing Antibiotic Strategies in Sepsis (OASIS) II Study.

2018

2018 Nov 22

2048-7207

<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>

10.1093/jpids/piy113

J Pediatric Infect Dis Soc

30476186

Increased 30-Day Mortality Associated With Carbapenem-Resistant Enterobacteriaceae in Children.

2018

ofy222

2018 Oct

2328-8957

<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>

10.1093/ofid/ofy222

Open Forum Infect Dis

30338267

Combined Biomarkers Predict Acute Mortality Among Critically Ill Patients With Suspected Sepsis.

2018

1106-1113

2018 Jul

1530-0293

<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>

10.1097/CCM.0000000000003137

Crit. Care Med.

29912095

Risk Factors for Colonization or Infection with Carbapenem-Resistant Enterobacteriaceae in Children: a Multicenter Study.

2017

2017 Oct 02

1098-6596

<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>

10.1128/AAC.01440-17

Antimicrob. Agents Chemother.

28971864

High fluoroquinolone MIC is associated with fluoroquinolone treatment failure in urinary tract infections caused by fluoroquinolone susceptible Escherichia coli.

2017

25

2017 Apr 08

1476-0711

<p><strong>BACKGROUND: </strong>Suboptimal clinical response to fluoroquinolone (FQ) therapy has been clearly documented in patients with Salmonella typhi infection with reduced FQ susceptibility. However, the clinical impact of reduced FQ susceptibility on other infections including E. coli urinary tract infections (UTIs) has never been evaluated.</p>

<p><strong>METHODS: </strong>We conducted a retrospective cohort study of female patients with fluoroquinolone susceptible E. coli (FQSEC) UTIs who received FQ therapy at outpatient services within University of Pennsylvania Health System, Philadelphia. Exposed patients were those with high MIC-FQSEC UTIs (the levofloxacin MIC&nbsp;&gt;&nbsp;0.12 but&nbsp;≤&nbsp;2&nbsp;mg/L) while unexposed patients were those with low MIC-FQSEC UTIs (the levofloxacin MIC&nbsp;≤&nbsp;0.12&nbsp;mg/L). The primary treatment outcome was treatment failure within 10&nbsp;weeks after initiation of FQ therapy.</p>

<p><strong>RESULTS: </strong>From May 2008 to April 2011, we enrolled 29 exposed patients and 246 unexposed patients. Two patients in each group experienced treatment failure; exposed vs. unexposed (6.9 vs. 0.8%; p&nbsp;=&nbsp;0.06). Risk difference and risk ratio (RR) for treatment failure were 0.06 [95% CI -0.03-0.15; exact-p&nbsp;=&nbsp;0.06] and 8.48 [95% CI 1.24-57.97; exact-p&nbsp;=&nbsp;0.06], respectively. After adjusting for underlying cerebrovascular disease, the RR was 7.12 (95% CI 1.20-42.10; MH-p&nbsp;=&nbsp;0.04).</p>

<p><strong>CONCLUSION: </strong>Our study demonstrated the negative impact of reduced FQ susceptibility on the treatment response to FQ therapy in FQSEC UTIs. This negative impact may be more intensified in other serious infections. Future studies in other clinical situations should be conducted to fill the gap of knowledge.</p>

10.1186/s12941-017-0202-4

Ann. Clin. Microbiol. Antimicrob.

28390438

Factors associated with persistent colonisation with methicillin-resistant Staphylococcus aureus.

2017

1-9

2017 Feb 21

1469-4409

<p>We conducted a prospective cohort study between 1 January 2010 and 31 December 2012 at five adult and paediatric academic medical centres to identify factors associated with persistent methicillin-resistant Staphylococcus aureus (MRSA) colonisation. Adults and children presenting to ambulatory settings with a MRSA skin and soft tissue infection (i.e. index cases), along with household members, performed self-sampling for MRSA colonisation every 2 weeks for 6 months. Clearance of colonisation was defined as two consecutive negative sampling periods. Subjects without clearance by the end of the study were considered persistently colonised and compared with those who cleared colonisation. Of 243 index cases, 48 (19·8%) had persistent colonisation and 110 (45·3%) cleared colonisation without recurrence. Persistent colonisation was associated with white race (odds ratio (OR), 4·90; 95% confidence interval (CI), 1·38-17·40), prior MRSA infection (OR 3·59; 95% CI 1·05-12·35), colonisation of multiple sites (OR 32·7; 95% CI 6·7-159·3). Conversely, subjects with persistent colonisation were less likely to have been treated with clindamycin (OR 0·28; 95% CI 0·08-0·99). Colonisation at multiple sites is a risk factor for persistent colonisation and may require more targeted decolonisation efforts. The specific effect of clindamycin on MRSA colonisation needs to be elucidated.</p>

10.1017/S0950268817000012

Epidemiol. Infect.

28219463

The Effect of Total Household Decolonization on Clearance of Colonization With Methicillin-Resistant Staphylococcus aureus.

2016

1-8

2016 Jul 28

1559-6834

<p>OBJECTIVE To determine the impact of total household decolonization with intranasal mupirocin and chlorhexidine gluconate body wash on recurrent methicillin-resistant Staphylococcus aureus (MRSA) infection among subjects with MRSA skin and soft-tissue infection. DESIGN Three-arm nonmasked randomized controlled trial. SETTING Five academic medical centers in Southeastern Pennsylvania. PARTICIPANTS Adults and children presenting to ambulatory care settings with community-onset MRSA skin and soft-tissue infection (ie, index cases) and their household members. INTERVENTION Enrolled households were randomized to 1 of 3 intervention groups: (1) education on routine hygiene measures, (2) education plus decolonization without reminders (intranasal mupirocin ointment twice daily for 7 days and chlorhexidine gluconate on the first and last day), or (3) education plus decolonization with reminders, where subjects received daily telephone call or text message reminders. MAIN OUTCOME MEASURES Owing to small numbers of recurrent infections, this analysis focused on time to clearance of colonization in the index case. RESULTS Of 223 households, 73 were randomized to education-only, 76 to decolonization without reminders, 74 to decolonization with reminders. There was no significant difference in time to clearance of colonization between the education-only and decolonization groups (log-rank P=.768). In secondary analyses, compliance with decolonization was associated with decreased time to clearance (P=.018). CONCLUSIONS Total household decolonization did not result in decreased time to clearance of MRSA colonization among adults and children with MRSA skin and soft-tissue infection. However, subjects who were compliant with the protocol had more rapid clearance Trial registration. ClinicalTrials.gov identifier: NCT00966446 Infect Control Hosp Epidemiol 2016;1-8.</p>

10.1017/ice.2016.138

Infect Control Hosp Epidemiol

27465112

A Pragmatic Biomarker-Driven Algorithm to Guide Antibiotic Use in the Pediatric Intensive Care Unit: The Optimizing Antibiotic Strategies in Sepsis (OASIS) Study.

2016

2016 May 4

2048-7207

<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>

10.1093/jpids/piw023

J Pediatric Infect Dis Soc

27147715