Epidemiology of Methicillin-Resistant Staphylococcus aureus Bacteremia in Children.

2017

pii: e2017018

2017 Jun

1098-4275

<p><strong>BACKGROUND: </strong>Methicillin-resistant Staphylococcus aureus (MRSA) bacteremia is associated with high rates of treatment failure in adults. The epidemiology, clinical outcomes, and risk factors for treatment failure associated with MRSA bacteremia in children are poorly understood.</p>

<p><strong>METHODS: </strong>Multicenter, retrospective cohort study of children ≤18 years hospitalized with MRSA bacteremia across 3 tertiary care children's hospitals from 2007 to 2014. Treatment failure was defined as persistent bacteremia &gt;3 days, recurrence of bacteremia within 30 days, or attributable 30-day mortality. Potential risk factors for treatment failure, including the site of infection, vancomycin trough concentration, critical illness, and need for source control, were collected via manual chart review and evaluated using multivariable logistic regression.</p>

<p><strong>RESULTS: </strong>Of 232 episodes of MRSA bacteremia, 72 (31%) experienced treatment failure and 23% developed complications, whereas 5 (2%) died within 30 days. Multivariable analysis of 174 children treated with vancomycin with steady-state vancomycin concentrations obtained found that catheter-related infections (odds ratio [OR], 0.36; 95% confidence interval [CI]: 0.13-0.94) and endovascular infections (OR, 4.35; 95% CI: 1.07-17.7) were associated with lower and higher odds of treatment failure, respectively, whereas a first vancomycin serum trough concentration &lt;10 μg/mL was not associated with treatment failure (OR, 1.34; 95% CI, 0.49-3.66). Each additional day of bacteremia was associated with a 50% (95% CI: 26%-79%) increased odds of bacteremia-related complications.</p>

<p><strong>CONCLUSIONS: </strong>Hospitalized children with MRSA bacteremia frequently suffered treatment failure and complications, but mortality was low. The odds of bacteremia-related complications increased with each additional day of bacteremia, emphasizing the importance of achieving rapid sterilization.</p>

10.1542/peds.2017-0183

Pediatrics

28562284

Variability in Antibiotic Prescribing for Community-Acquired Pneumonia.

2017

2017 Mar 07

1098-4275

<p><strong>BACKGROUND AND OBJECTIVES: </strong>Published guidelines recommend amoxicillin for most children with community-acquired pneumonia (CAP), yet macrolides and broad-spectrum antibiotics are more commonly prescribed. We aimed to determine the patient and clinician characteristics associated with the prescription of amoxicillin versus macrolide or broad-spectrum antibiotics for CAP.</p>

<p><strong>METHODS: </strong>Retrospective cohort study in an outpatient pediatric primary care network from July 1, 2009 to June 30, 2013. Patients prescribed amoxicillin, macrolides, or a broad-spectrum antibiotic (amoxicillin-clavulanic acid, cephalosporin, or fluoroquinolone) for CAP were included. Multivariable logistic regression models were implemented to identify predictors of antibiotic choice for CAP based on patient- and clinician-level characteristics, controlling for practice.</p>

<p><strong>RESULTS: </strong>Of 10 414 children, 4239 (40.7%) received amoxicillin, 4430 (42.5%) received macrolides and 1745 (16.8%) received broad-spectrum antibiotics. The factors associated with an increased odds of receipt of macrolides compared with amoxicillin included patient age ≥5 years (adjusted odds ratio [aOR]: 6.18; 95% confidence interval [CI]: 5.53-6.91), previous antibiotic receipt (aOR: 1.79; 95% CI: 1.56-2.04), and private insurance (aOR: 1.47; 95% CI: 1.28-1.70). The predicted probability of a child being prescribed a macrolide ranged significantly between 0.22 and 0.83 across clinics. The nonclinical characteristics associated with an increased odds of receipt of broad-spectrum antibiotics compared with amoxicillin included suburban practice (aOR: 7.50; 95% CI: 4.16-13.55) and private insurance (aOR: 1.42; 95% CI: 1.18-1.71).</p>

<p><strong>CONCLUSIONS: </strong>Antibiotic choice for CAP varied widely across practices. Factors unlikely related to the microbiologic etiology of CAP were significant drivers of antibiotic choice. Understanding drivers of off-guideline prescribing can inform targeted antimicrobial stewardship initiatives.</p>

10.1542/peds.2016-2331

Pediatrics

28270546

Intravenous Versus Oral Antibiotics for Postdischarge Treatment of Complicated Pneumonia.

2016

2016 Dec

1098-4275

<p><strong>BACKGROUND AND OBJECTIVES: </strong>Postdischarge treatment of complicated pneumonia includes antibiotics administered intravenously via a peripherally inserted central venous catheter (PICC) or orally. Antibiotics administered via PICC, although effective, may result in serious complications. We compared the effectiveness and treatment-related complications of postdischarge antibiotics delivered by these 2 routes.</p>

<p><strong>METHODS: </strong>This multicenter retrospective cohort study included children ≥2 months and &lt;18 years discharged with complicated pneumonia between 2009 and 2012. The main exposure was the route of postdischarge antibiotic administration, classified as PICC or oral. The primary outcome was treatment failure. Secondary outcomes included PICC complications, adverse drug reactions, other related revisits, and a composite of all 4 outcomes, termed "all related revisits."</p>

<p><strong>RESULTS: </strong>Among 2123 children, 281 (13.2%) received antibiotics via PICC. Treatment failure rates were 3.2% among PICC and 2.6% among oral antibiotic recipients and were not significantly different between the groups in across-hospital-matched analysis (matched odds ratio [OR], 1.26; 95% confidence interval [CI], 0.54 to 2.94). PICC complications occurred in 7.1%. Adverse drug reactions occurred in 0.6% of children; PICC antibiotic recipients had greater odds of adverse drug reaction in across hospital matched analysis (matched OR, 19.1; 95% CI, 4.2 to 87.3). The high rate of PICC complications and differences in adverse drug reactions contributed to higher odds of the composite outcome of all related revisits among PICC antibiotic recipients (matched OR, 4.71; 95% CI, 2.97 to 7.46).</p>

<p><strong>CONCLUSIONS: </strong>Treatment failure rates between PICC and oral antibiotics did not differ. Children with complicated pneumonia should preferentially receive oral antibiotics at discharge when effective oral options are available.</p>

10.1542/peds.2016-1692

Pediatrics

27940695

Intravenous Versus Oral Antibiotics for the Prevention of Treatment Failure in Children With Complicated Appendicitis: Has the Abandonment of Peripherally Inserted Catheters Been Justified?

2017

361-8

2017 Aug

1528-1140

<p><strong>OBJECTIVE: </strong>To compare treatment failure leading to hospital readmission in children with complicated appendicitis who received oral versus intravenous antibiotics after discharge.</p>

<p><strong>BACKGROUND: </strong>Antibiotics are often employed after discharge to prevent treatment failure in children with complicated appendicitis, although existing studies comparing intravenous and oral antibiotics for this purpose are limited.</p>

<p><strong>METHODS: </strong>We identified all patients aged 3 to 18 years undergoing appendectomy for complicated appendicitis, who received postdischarge antibiotics at 35 childrens hospitals from 2009 to 2012. Discharge codes were used to identify study subjects from the Pediatric Health Information System database, and chart review confirmed eligibility, treatment assignment, and outcomes. Exposure status was based on outpatient antibiotic therapy, and analysis used optimal and full matching methods to adjust for demographic and clinical characteristics. Treatment failure (defined as an organ-space infection) requiring inpatient readmission was the primary outcome. Secondary outcomes included revisits from any cause to either the inpatient or emergency department setting.</p>

<p><strong>RESULTS: </strong>In all, 4579 patients were included (median: 99/hospital), and utilization of intravenous antibiotics after discharge ranged from 0% to 91.7% across hospitals. In the matched analysis, the rate of treatment failure was significantly higher for the intravenous group than the oral group [odds ratio (OR) 1.74, 95% confidence interval (CI) 1.05-2.88; risk difference: 4.0%, 95% CI 0.4-7.6%], as was the rate of all-cause revisits (OR 2.11, 95% CI 1.44-3.11; risk difference: 9.4%, 95% CI 4.7-14.2%). The rate of peripherally inserted central catheter line complications was 3.2% in the intravenous group, and drug reactions were rare in both groups (intravenous: 0.7%, oral: 0.5%).</p>

<p><strong>CONCLUSIONS: </strong>Compared with oral antibiotics, use of intravenous antibiotics after discharge in children with complicated appendicitis was associated with higher rates of both treatment failure and all-cause hospital revisits.</p>

10.1097/SLA.0000000000001923

Ann. Surg.

27429024

Central Venous Catheter Retention and Mortality in Children With Candidemia: A Retrospective Cohort Analysis.

2015

2015 Aug 16

2048-7207

<p><strong>BACKGROUND: </strong>Candidemia causes significant morbidity and mortality among children. Removal of a central venous catheter (CVC) is often recommended for adults with candidemia to reduce persistent and metastatic infection. Pediatric-specific data on the impact of CVC retention are limited.</p>

<p><strong>METHODS: </strong>A retrospective cohort study of inpatients &lt;19 years with candidemia at the Children's Hospital of Philadelphia between 2000 and 2012 was performed. The final cohort included patients that had a CVC in place at time of blood culture and retained their CVC at least 1 day beyond the blood culture being positive. A structured data collection instrument was used to retrieve patient data. A discrete time failure model, adjusting for age and the complexity of clinical care before onset of candidemia, was used to assess the association of CVC retention and 30-day all-cause mortality.</p>

<p><strong>RESULTS: </strong>Two hundred eighty-five patients with candidemia and a CVC in place at the time of blood culture were identified. Among these 285 patients, 30 (10%) died within 30 days. Central venous catheter retention was associated with a significant increased risk of death on a given day (odds ratio, 2.50; 95% confidence interval, 1.06-5.91).</p>

<p><strong>CONCLUSIONS: </strong>Retention of a CVC was associated with an increased risk of death after adjusting for age and complexity of care at candidemia onset. Although there is likely persistence of unmeasured confounding, given the strong association between catheter retention and death, our data suggest that early CVC removal should be strongly considered.</p>

10.1093/jpids/piv048

J Pediatric Infect Dis Soc

26407279

Comparative effectiveness of fungicidal vs. fungistatic therapies for the treatment of paediatric candidaemia.

2016

173-8

2016 Mar

1439-0507

<p>Adult data suggest that echinocandins for treatment of candidaemia are associated with decreased mortality, attributed to their fungicidal activity. There are limited data comparing antifungals in children. We compared 30-day all-cause mortality among paediatric candidaemia patients treated with fungicidal vs. fungistatic agents. All inpatients (&gt;6 months and &lt;19 years of age) with candidaemia between 2000 and 2012 at The Children's Hospital of Philadelphia were retrospectively identified. Definitive therapy with fungicidal (amphotericin B and caspofungin) agents was compared with fungistatic (fluconazole) agents. A propensity score model generated the inverse probability of receiving a fungicidal agent, which was included in a weighted logistic regression model. Among 203 children meeting inclusion criteria, 151 (74.4%) and 52 (25.6%) received a fungicidal and fungistatic agent, respectively. Overall, 18 (8.9%) patients died within 30 days. There was no statistically significant difference in mortality between patients started on a fungicidal or fungistatic agent (OR: 2.19, 95% CI: 0.42-11.48). In a propensity score-weighted model, definitive therapy with a fungicidal agent did not result in a significant decrease in mortality. These data suggest that both agents can be considered definitive therapy for paediatric candidaemia. The results should be interpreted with caution given the small sample size. Larger cohort studies are needed.</p>

10.1111/myc.12449

Mycoses

26692326

Antibiotic Exposure During the First 6 Months of Life and Weight Gain During Childhood.

2016

1258-65

2016 Mar 22-29

1538-3598

<p><strong>IMPORTANCE: </strong>Early-life antibiotic exposure has been associated with increased adiposity in animal models, mediated through the gut microbiome. Infant antibiotic exposure is common and often inappropriate. Studies of the association between infant antibiotics and childhood weight gain have reported inconsistent results.</p>

<p><strong>OBJECTIVE: </strong>To assess the association between early-life antibiotic exposure and childhood weight gain.</p>

<p><strong>DESIGN AND SETTING: </strong>Retrospective, longitudinal study of singleton births and matched longitudinal study of twin pairs conducted in a network of 30 pediatric primary care practices serving more than 200,000 children of diverse racial and socioeconomic backgrounds across Pennsylvania, New Jersey, and Delaware.</p>

<p><strong>PARTICIPANTS: </strong>Children born between November 1, 2001, and December 31, 2011, at 35 weeks' gestational age or older, with birth weight of 2000 g or more and in the fifth percentile or higher for gestational age, and who had a preventive health visit within 14 days of life and at least 2 additional visits in the first year of life. Children with complex chronic conditions and those who received long-term antibiotics or multiple systemic corticosteroid prescriptions were excluded. We included 38,522 singleton children and 92 twins (46 matched pairs) discordant in antibiotic exposure. Final date of follow-up was December 31, 2012.</p>

<p><strong>EXPOSURE: </strong>Systemic antibiotic use in the first 6 months of life.</p>

<p><strong>MAIN OUTCOMES AND MEASURES: </strong>Weight, measured at preventive health visits from age 6 months through 7 years.</p>

<p><strong>RESULTS: </strong>Of 38,522 singleton children (50% female; mean birth weight, 3.4 kg), 5287 (14%) were exposed to antibiotics during the first 6 months of life (at a mean age of 4.3 months). Antibiotic exposure was not significantly associated with rate of weight change (0.7%; 95% CI, -0.1% to 1.5%; P = .07, equivalent to approximately 0.05 kg; 95% CI, -0.004 to 0.11 kg of added weight gain between age 2 years and 5 years). Among 92 twins (38% female; mean birth weight, 2.8 kg), the 46 twins who were exposed to antibiotics during the first 6 months of life received them at a mean age of 4.5 months. Antibiotic exposure was not significantly associated with a weight difference (-0.09 kg; 95% CI, -0.26 to 0.08 kg; P = .30).</p>

<p><strong>CONCLUSIONS AND RELEVANCE: </strong>Exposure to antibiotics within the first 6 months of life compared with no exposure was not associated with a statistically significant difference in weight gain through age 7 years. There are many reasons to limit antibiotic exposure in young, healthy children, but weight gain is likely not one of them.</p>

10.1001/jama.2016.2395

JAMA

27002447

Comparative effectiveness of intravenous vs oral antibiotics for postdischarge treatment of acute osteomyelitis in children.

2015

120-8

02/2015

2168-6211

<p><strong>IMPORTANCE: </strong>Postdischarge treatment of acute osteomyelitis in children requires weeks of antibiotic therapy, which can be administered orally or intravenously via a peripherally inserted central catheter (PICC). The catheters carry a risk for serious complications, but limited evidence exists on the effectiveness of oral therapy.</p>

<p><strong>OBJECTIVE: </strong>To compare the effectiveness and adverse outcomes of postdischarge antibiotic therapy administered via the PICC or the oral route.</p>

<p><strong>DESIGN, SETTING, AND PARTICIPANTS: </strong>We performed a retrospective cohort study comparing PICC and oral therapy for the treatment of acute osteomyelitis. Among children hospitalized from January 1, 2009, through December 31, 2012, at 36 participating children's hospitals, we used discharge codes to identify potentially eligible participants. Results of medical record review confirmed eligibility and defined treatment group allocation and study outcomes. We used within- and across-hospital propensity score-based full matching to adjust for confounding by indication.</p>

<p><strong>INTERVENTIONS: </strong>Postdischarge administration of antibiotics via the PICC or the oral route.</p>

<p><strong>MAIN OUTCOMES AND MEASURES: </strong>The primary outcome was treatment failure. Secondary outcomes included adverse drug reaction, PICC line complication, and a composite of all 3 end points.</p>

<p><strong>RESULTS: </strong>Among 2060 children and adolescents (hereinafter referred to as children) with osteomyelitis, 1005 received oral antibiotics at discharge, whereas 1055 received PICC-administered antibiotics. The proportion of children treated via the PICC route varied across hospitals from 0 to 100%. In the across-hospital (risk difference, 0.3% [95% CI, -0.1% to 2.5%]) and within-hospital (risk difference, 0.6% [95% CI, -0.2% to 3.0%]) matched analyses, children treated with antibiotics via the oral route (reference group) did not experience more treatment failures than those treated with antibiotics via the PICC route. Rates of adverse drug reaction were low (&lt;4% in both groups) but slightly greater in the PICC group in across-hospital (risk difference, 1.7% [95% CI, 0.1%-3.3%]) and within-hospital (risk difference, 2.1% [95% CI, 0.3%-3.8%]) matched analyses. Among the children in the PICC group, 158 (15.0%) had a PICC complication that required an emergency department visit (n = 96), a rehospitalization (n = 38), or both (n = 24). As a result, the PICC group had a much higher risk of requiring a return visit to the emergency department or for hospitalization for any adverse outcome in across-hospital (risk difference, 14.6% [95% CI, 11.3%-17.9%]) and within-hospital (risk difference, 14.0% [95% CI, 10.5%-17.6%]) matched analyses.</p>

<p><strong>CONCLUSIONS AND RELEVANCE: </strong>Given the magnitude and seriousness of PICC complications, clinicians should reconsider the practice of treating otherwise healthy children with acute osteomyelitis with prolonged intravenous antibiotics after hospital discharge when an equally effective oral alternative exists.</p>

10.1001/jamapediatrics.2014.2822

JAMA Pediatr

25506733