Antimicrobial Resistance among Isolates Causing Invasive Pneumococcal Disease before and after Licensure of Heptavalent Conjugate Pneumococcal Vaccine

BACKGROUND: The impact of the pneumococcal conjugate vaccine (PCV-7) on antibiotic resistance among pneumococcal strains causing invasive pneumococcal disease (IPD) has varied in different locales in the United States. We assessed trends in IPD including trends for IPD caused by penicillin non-susceptible strains before and after licensure of PCV-7 and the impact of the 2008 susceptibility breakpoints for penicillin on the epidemiology of resistance. METHODOLOGY/PRINCIPAL FINDINGS: We performed a retrospective review of IPD cases at Morgan Stanley Children's Hospital of New York-Presbyterian, Columbia University Medical Center. Subjects were < or = 18 years of age with Streptococcus pneumoniae isolated from sterile body sites from January 1995-December 2006. The rate of IPD from 1995-1999 versus 2002-2006 significantly decreased from 4.1 (CI(95) 3.4, 4.8) to 1.7 (CI(95) 1.3, 2.2) per 1,000 admissions. Using the breakpoints in place during the study period, the proportion of penicillin non-susceptible strains increased from 27% to 49% in the pre- vs. post-PCV-7 era, respectively (p = 0.001), although the rate of IPD caused by non-susceptible strains did not change from 1995-1999 (1.1 per 1,000 admissions, CI(95) 0.8, 1.5) when compared with 2002-2006 (0.8 per 1,000 admissions, CI(95) 0.6, 1.2). In the multivariate logistic regression model controlling for the effects of age, strains causing IPD in the post-PCV-7 era were significantly more likely to be penicillin non-susceptible compared with strains in the pre-PCV-7 era (OR 2.46, CI(95) 1.37, 4.40). However, using the 2008 breakpoints for penicillin, only 8% of strains were non-susceptible in the post-PCV-7 era. CONCLUSIONS/SIGNIFICANCE: To date, there are few reports that document an increase in the relative proportion of penicillin non-susceptible strains of pneumococci causing IPD following the introduction of PCV-7. Active surveillance of pneumococcal serotypes and antibiotic resistance using the new penicillin breakpoints is imperative to assess potential changes in the epidemiology of IPD

Incidence, Risks, and Types of Infections in Pediatric Long-term Care Facilities

Importance: The population of infants, children, and adolescents cared for at pediatric long-term care facilities is increasing in complexity and size and thus consumes substantial health care resources. Infections are a significant cause of morbidity and mortality in this population, but few recent data describe their incidence and effects. Objectives: To describe the types of infections diagnosed in residents of pediatric long-term care facilities, calculate infection rates, and identify risk factors for respiratory tract infections (RTIs). Design, Setting, and Participants: This prospective cohort study, which was part of a larger trial called Keep It Clean for Kids, was conducted from September 1, 2012, to December 31, 2015, at 3 pediatric long-term care facilities in New York. Residents of the facilities who were 21 years or younger and either residents or admitted during the study period (n = 717) were enrolled in the study. Medical records were reviewed to identify infections diagnosed by site clinicians. Main Outcomes and Measures: Incidence of infections, such as RTIs; skin and soft-tissue infections; chronic comorbid conditions, including neurologic and respiratory disorders; and device use, including gastrostomy tubes and tracheostomies, was determined. Risk factors for RTIs were assessed by generalized linear mixed method regression modeling. Results: The 717 residents had a median (interquartile range) age at enrollment of 2.6 (0.4-9.1) years; 358 (49.9%) were male. Four hundred twenty-eight residents (59.7%) had feeding tubes and 215 (30.0%) had tracheostomies. Most chronic comorbid conditions were musculoskeletal or ambulation (532 residents [74.2%]), neurologic (505 [70.4%]), respiratory (361 [50.3%]), and gastrointestinal (230 [32.1%]) disorders, and 460 residents (64.2%) had 4 or more chronic comorbid conditions. Site clinicians diagnosed 2052 infections during the 3-year study period. Respiratory tract infections were most common and were diagnosed in 1291 residents (62.9%). The overall infection rate was 5.3 infections per 1000 resident-days, and RTI rates were 3.3 infections per 1000 resident-days. Overall infection rates and rates of RTI, skin and soft-tissue infection, urinary tract infection, and bloodstream infection varied among the 3 sites. In the multivariable model, younger age (incidence rate ratio [IRR], 1.05; 95% CI, 1.03-1.06), increased number of chronic comorbid conditions (IRR, 1.12; 95% CI, 1.06-1.19), and the use of feeding tubes (IRR, 1.34; 95% CI, 1.03-1.64) and tracheostomies (IRR, 1.40; 95% CI, 1.17-1.69) were associated with RTIs. Conclusions and Relevance: In this study, RTIs were the most common infections diagnosed, but modifiable risk factors for RTIs were not identified. Future work should focus on optimizing infection prevention and control strategies to reduce infections, particularly RTIs, in the pediatric long-term care population

Development of an Antimicrobial Stewardship Intervention Using a Model of Actionable Feedback

We describe the development of an audit and feedback intervention to improve antibiotic prescribing in the neonatal intensive care unit (NICU) using a theoretical framework. Participants included attending physicians, neonatal fellows, pediatric residents, and nurse practitioners. The intervention was based on the “model of actionable feedback” which emphasizes that feedback should be timely, individualized, nonpunitive, and customized to be effective. We found that real-time feedback could not be provided for the parameters established in this study, as we had to collect and analyze numerous data elements to assess appropriate initiation and continuation of antibiotics and required longer intervals to examine trends in antibiotic use. We learned during focus groups that NICU clinicians strongly resisted assigning individual responsibility for antibiotic prescribing as they viewed this as a shared responsibility informed by each patient's laboratory data and clinical course. We were able to create a non-punitive atmosphere thanks to written informed consent from NICU attendings and assurance from leadership that prescribing practices would not be used to assess job performance. We provided customized, meaningful feedback integrating input from the participants. Adapting the principles of the “model of actionable feedback” to provide feedback for antimicrobial prescribing practices proved challenging in the NICU setting

Central line-associated blood stream infections in pediatric intensive care units: Longitudinal trends and compliance with bundle strategies.

BACKGROUND: Knowing the temporal trend central line-associated bloodstream infection (CLABSI) rates among U.S. pediatric intensive care units (PICUs), the current extent of central line bundle compliance, and the impact of compliance on rates is necessary to understand what has been accomplished and can be improved in CLABSI prevention. METHODS: This is a longitudinal study of PICUs in National Healthcare Safety Network hospitals and a cross-sectional survey of directors and managers of infection prevention and control departments regarding PICU CLABSI prevention practices, including self-reported compliance with elements of central line bundles. Associations between 2011-2012 PICU CLABSI rates and infection prevention practices were examined. RESULTS: Reported CLABSI rates decreased during the study period, from 5.8 per 1,000 line days in 2006 to 1.4 in 2011-2012 (P \u3c .001). Although 73% of PICUs had policies for all central line prevention practices, only 35% of those with policies reported ≥95% compliance. PICUs with ≥95% compliance with central line infection prevention policies had lower reported CLABSI rates, but this association was statistically insignificant. CONCLUSION: There was a nonsignificant trend in decreasing CLABSI rates as PICUs improved bundle policy compliance. Given that few PICUs reported full compliance with these policies, PICUs increasing their efforts to comply with these policies may help reduce CLABSI rates

Population pharmacokinetics of meropenem administered as a prolonged infusion in children with cystic fibrosis

OBJECTIVES: Meropenem is frequently used to treat pulmonary exacerbations in children with cystic fibrosis (CF) in the USA. Prolonged-infusion meropenem improves the time that free drug concentrations remain above the MIC (fT> MIC) in adults, but data in CF children are sparse. We describe the population pharmacokinetics, tolerability and treatment burden of prolonged-infusion meropenem in CF children. METHODS: Thirty children aged 6-17 years with a pulmonary exacerbation received 40 mg/kg meropenem every 8 h; each dose was administered as a 3 h infusion. Pharmacokinetics were determined using population methods in Pmetrics. Monte Carlo simulation was employed to compare 0.5 with 3 h infusions to estimate the probability of pharmacodynamic target attainment (PTA) at 40% fT> MIC. NCT#01429259. RESULTS: A two-compartment model fitted the data best with clearance and volume predicted by body weight. Clearance and volume of the central compartment were 0.41 ± 0.23 L/h/kg and 0.30 ± 0.17 L/kg, respectively. Half-life was 1.11 ± 0.38 h. At MICs of 1, 2 and 4 mg/L, PTAs for the 0.5 h infusion were 87.6%, 70.1% and 35.4%, respectively. The prolonged infusion increased PTAs to >99% for these MICs and achieved 82.8% at 8 mg/L. Of the 30 children, 18 (60%) completed treatment with prolonged infusion; 5 did so at home without any reported burden. Nine patients were changed to a 0.5 h infusion when discharged home. CONCLUSIONS: In these CF children, meropenem clearance was greater compared with published values from non-CF children. Prolonged infusion provided an exposure benefit against pathogens with MICs ≥1 mg/L, was well tolerated and was feasible to administer in the hospital and home settings, the latter depending on perception and family schedule

Multicenter observational study on factors and outcomes associated with various methicillin-resistant Staphylococcus aureus types in children with cystic fibrosis

Rationale: Methicillin-resistant Staphylococcus aureus (MRSA) prevalence continues to increase in patients with cystic fibrosis (CF) in the United States, reaching 26.5% in 2012. Approximately 30% of strains are SCCmec (staphylococcal cassette chromosome mec) IV type, frequently USA300, which in the general population have different genotypic and phenotypic features than SCCmec II type. Objectives: We hypothesized that risk factors for acquisition and outcomes in patients with CF differed for "health care-associated" (SCCmec II) versus "community-associated" (SCCmec IV)MRSAstrains. Methods: To determine the role of SCCmec type and Panton-Valentine leukocidin (PVL), MRSA isolates from patients not more than 18 years old at seven CF centers were typed and the association of potential risk factors and subsequent clinical course was assessed, using data provided by the CF Patient Registry. Measurements and Main Results: Participants with chronic MRSA (295) had typeable isolates and clinical data; 205 (69.5%) had SCCmec II PVL(-), 39 (13.2%) had SCCmec IV PVL(-), and 51 (17.3%) had SCCmec IVPVL(1) strains.SCCmec IV, comparedwith SCCmec II, increased during the study period, 1996-2010 (P = 0.03). SCCmec II was associated with Pseudomonas aeruginosa-positive cultures and three or more clinic visits in the 6 months preceding the first positive MRSA culture (adjusted odds ratio, 2.05; 95% confidence interval, 1.13-3.74; P = 0.019). Lung function and anthropometrics remained unchanged in the 6 months after initial MRSA detection compared with the 6 months prior. Although CF care increased for participants in both groups in the 6 months after MRSA detection, inhaled antibiotics were prescribed more frequently in those with SCCmec II strains and increased hospitalizations occurred in those with SCCmec IV PVL(-) strains compared with those with PVL(1) strains (adjusted difference, 34.10%; 95% confidence interval, 7.58-60.61; P = 0.012). Participants in both groups had an increase in CF care in the 2 years after MRSA detection compared with the 2 years prior. Conclusions: Increased exposure to CF clinics and P. aeruginosa may constitute risk factors for acquisition of SCCmec II MRSA strains. Clinical interventions increased 6 months and 2 years after initial MRSA detection regardless of SCCmec type

Measuring and improving respiratory outcomes in cystic fibrosis lung disease: Opportunities and challenges to therapy

Cystic fibrosis (CF) is a life-shortening disease with significant morbidity. Despite overall improvements in survival, patients with CF experience frequent pulmonary exacerbations and declining lung function, which often accelerates during adolescence. New treatments target steps in the pathogenesis of lung disease, such as the basic defect in CF (CF Transmembrane Conductance Regulator [CFTR]), pulmonary infections, inflammation, and mucociliary clearance. These treatments offer hope but also present challenges to patients, clinicians, and researchers. Comprehensive assessment of efficacy is critical to identify potentially beneficial treatments. Lung function and pulmonary exacerbation are the most commonly used outcome measures in CF clinical research. Other outcome measures under investigation include measures of CFTR function; biomarkers of infection, inflammation, lung injury and repair; and patient-reported outcomes. Molecular diagnostics may help elucidate the complex CF airway microbiome. As new treatments are developed for patients with CF, efforts should be made to balance treatment burden with quality of life. This review highlights emerging treatments, obstacles to optimizing outcomes, and key future directions for research

Outcomes and Treatment of Chronic Methicillin-Resistant Staphylococcus aureus Differs by Staphylococcal Cassette Chromosome mec (SCC mec ) Type in Children With Cystic Fibrosis

Methicillin-resistant Staphylococcus aureus (MRSA) infects ∼25% of patients with cystic fibrosis (CF) in the United States. We hypothesized that health-related outcomes differed between healthcare-associated (staphylococcal cassette chromosome mec [SCCmec] II) vs community-associated (SCCmec IV) MRSA strains in patients chronically infected with CF