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Importance: Acute respiratory tract infections account for the majority of antibiotic exposure in children, and broad-spectrum antibiotic prescribing for acute respiratory tract infections is increasing. It is not clear whether broad-spectrum treatment is associated with improved outcomes compared with narrow-spectrum treatment., Objective: To compare the effectiveness of broad-spectrum and narrow-spectrum antibiotic treatment for acute respiratory tract infections in children., Design, Setting, and Participants: A retrospective cohort study assessing clinical outcomes and a prospective cohort study assessing patient-centered outcomes of children between the ages of 6 months and 12 years diagnosed with an acute respiratory tract infection and prescribed an oral antibiotic between January 2015 and April 2016 in a network of 31 pediatric primary care practices in Pennsylvania and New Jersey. Stratified and propensity score-matched analyses to account for confounding by clinician and by patient-level characteristics, respectively, were implemented for both cohorts., Exposures: Broad-spectrum antibiotics vs narrow-spectrum antibiotics., Main Outcomes and Measures: In the retrospective cohort, the primary outcomes were treatment failure and adverse events 14 days after diagnosis. In the prospective cohort, the primary outcomes were quality of life, other patient-centered outcomes, and patient-reported adverse events., Results: Of 30 159 children in the retrospective cohort (19 179 with acute otitis media; 6746, group A streptococcal pharyngitis; and 4234, acute sinusitis), 4307 (14%) were prescribed broad-spectrum antibiotics including amoxicillin-clavulanate, cephalosporins, and macrolides. Broad-spectrum treatment was not associated with a lower rate of treatment failure (3.4% for broad-spectrum antibiotics vs 3.1% for narrow-spectrum antibiotics; risk difference for full matched analysis, 0.3% [95% CI, -0.4% to 0.9%]). Of 2472 children enrolled in the prospective cohort (1100 with acute otitis media; 705, group A streptococcal pharyngitis; and 667, acute sinusitis), 868 (35%) were prescribed broad-spectrum antibiotics. Broad-spectrum antibiotics were associated with a slightly worse child quality of life (score of 90.2 for broad-spectrum antibiotics vs 91.5 for narrow-spectrum antibiotics; score difference for full matched analysis, -1.4% [95% CI, -2.4% to -0.4%]) but not with other patient-centered outcomes. Broad-spectrum treatment was associated with a higher risk of adverse events documented by the clinician (3.7% for broad-spectrum antibiotics vs 2.7% for narrow-spectrum antibiotics; risk difference for full matched analysis, 1.1% [95% CI, 0.4% to 1.8%]) and reported by the patient (35.6% for broad-spectrum antibiotics vs 25.1% for narrow-spectrum antibiotics; risk difference for full matched analysis, 12.2% [95% CI, 7.3% to 17.2%])., Conclusions and Relevance: Among children with acute respiratory tract infections, broad-spectrum antibiotics were not associated with better clinical or patient-centered outcomes compared with narrow-spectrum antibiotics, and were associated with higher rates of adverse events. These data support the use of narrow-spectrum antibiotics for most children with acute respiratory tract infections.

Importance: 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., Objective: To assess the association between early-life antibiotic exposure and childhood weight gain., Design and Setting: 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., Participants: 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., Exposure: Systemic antibiotic use in the first 6 months of life., Main Outcomes and Measures: Weight, measured at preventive health visits from age 6 months through 7 years., Results: 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)., Conclusions and Relevance: 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.

Early onset neonatal sepsis is persistently associated with poor outcomes, and incites clinical practice based on the fear of missing a treatable infection in a timely fashion. Unnecessary exposure to antibiotics is also hazardous. Diagnostic dilemmas are discussed in this review, and suggestions offered for practical management while awaiting a more rapidly available 'gold standard' test; in an ideal world, this test would be 100% sensitive and 100% specific for the presence of organisms., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

We examined the impact of the Pediatric Infectious Diseases Society/Infectious Diseases Society of America guidelines that recommend ampicillin or amoxicillin for children hospitalized with community-acquired pneumonia. Prescribing of ampicillin/amoxicillin increased following guideline publication, but remains low. Cephalosporin and macrolide prescribing decreased but remains common. Further studies exploring outcomes of and reasons for compliance with guidelines are warranted.

Importance: Antimicrobial stewardship programs have been effective for inpatients, often through prescribing audit and feedback. However, most antimicrobial use occurs in outpatients with acute respiratory tract infections (ARTIs)., Objective: To evaluate the effect of an antimicrobial stewardship intervention on antibiotic prescribing for pediatric outpatients., Design: Cluster randomized trial of outpatient antimicrobial stewardship comparing prescribing between intervention and control practices using a common electronic health record. After excluding children with chronic medical conditions, antibiotic allergies, and prior antibiotic use, we estimated prescribing rates for targeted ARTIs standardized for age, sex, race, and insurance from 20 months before the intervention to 12 months afterward (October 2008-June 2011)., Setting and Participants: A network of 25 pediatric primary care practices in Pennsylvania and New Jersey; 18 practices (162 clinicians) participated., Interventions: One 1-hour on-site clinician education session (June 2010) followed by 1 year of personalized, quarterly audit and feedback of prescribing for bacterial and viral ARTIs or usual practice., Main Outcomes and Measures: Rates of broad-spectrum (off-guideline) antibiotic prescribing for bacterial ARTIs and antibiotics for viral ARTIs for 1 year after the intervention., Results: Broad-spectrum antibiotic prescribing decreased from 26.8% to 14.3% (absolute difference, 12.5%) among intervention practices vs from 28.4% to 22.6% (absolute difference, 5.8%) in controls (difference of differences [DOD], 6.7%; P = .01 for differences in trajectories). Off-guideline prescribing for children with pneumonia decreased from 15.7% to 4.2% among intervention practices compared with 17.1% to 16.3% in controls (DOD, 10.7%; P < .001) and for acute sinusitis from 38.9% to 18.8% in intervention practices and from 40.0% to 33.9% in controls (DOD, 14.0%; P = .12). Off-guideline prescribing was uncommon at baseline and changed little for streptococcal pharyngitis (intervention, from 4.4% to 3.4%; control, from 5.6% to 3.5%; DOD, -1.1%; P = .82) and for viral infections (intervention, from 7.9% to 7.7%; control, from 6.4% to 4.5%; DOD, -1.7%; P = .93)., Conclusions and Relevance: In this large pediatric primary care network, clinician education coupled with audit and feedback, compared with usual practice, improved adherence to prescribing guidelines for common bacterial ARTIs, and the intervention did not affect antibiotic prescribing for viral infections. Future studies should examine the drivers of these effects, as well as the generalizability, sustainability, and clinical outcomes of outpatient antimicrobial stewardship., Trial Registration: clinicaltrials.gov Identifier: NCT01806103.

Objective: To determine whether racial differences exist in antibiotic prescribing among children treated by the same clinician., Methods: Retrospective cohort study of 1,296,517 encounters by 208,015 children to 222 clinicians in 25 practices in 2009. Clinical, antibiotic prescribing, and demographic data were obtained from a shared electronic health record. We estimated within-clinician associations between patient race (black versus nonblack) and (1) antibiotic prescribing or (2) acute respiratory tract infection diagnosis after adjusting for potential patient-level confounders., Results: Black children were less likely to receive an antibiotic prescription from the same clinician per acute visit (23.5% vs 29.0%, odds ratio [OR] 0.75; 95% confidence interval [CI]: 0.72-0.77) or per population (0.43 vs 0.67 prescriptions/child/year, incidence rate ratio 0.64; 95% CI 0.63-0.66), despite adjustment for age, gender, comorbid conditions, insurance, and stratification by practice. Black children were also less likely to receive diagnoses that justified antibiotic treatment, including acute otitis media (8.7% vs 10.7%, OR 0.79; 95% CI 0.75-0.82), acute sinusitis (3.6% vs 4.4%, OR 0.79; 95% CI 0.73-0.86), and group A streptococcal pharyngitis (2.3% vs 3.7%, OR 0.60; 95% CI 0.55-0.66). When an antibiotic was prescribed, black children were less likely to receive broad-spectrum antibiotics at any visit (34.0% vs 36.9%, OR 0.88; 95% CI 0.82-0.93) and for acute otitis media (31.7% vs 37.8%, OR 0.75; 95% CI 0.68-0.83)., Conclusions: When treated by the same clinician, black children received fewer antibiotic prescriptions, fewer acute respiratory tract infection diagnoses, and a lower proportion of broad-spectrum antibiotic prescriptions than nonblack children. Reasons for these differences warrant further study.

Purpose: Antibiotics are frequently prescribed for acute nonspecific respiratory infections (ARIs), presumably to avoid small risks of progression to serious bacterial illness. However, even low risks of associated adverse drug events could result in many such events at the population level. Our objective was to assess the risks and benefits of antibiotic use in a cohort of patients with ARIs, comparing outcomes of patients who were prescribed antibiotics with outcomes of patients not receiving antibiotics., Methods: We used a June 1986 to August 2006 cohort of adult patients with ARI visits from a UK primary care database. Exposure was an antibiotic prescribed with the visit. Primary outcomes were hospitalization within 15 days for (1) severe adverse drug events (hypersensitivity, diarrhea, seizure, arrhythmia, hepatic or renal failure), and (2) community-acquired pneumonia., Results: The cohort included 1,531,019 visits with an ARI diagnosis; prescriptions for antibiotics were given in 65% of cases. The adjusted risk difference for treated vs untreated patients per 100,000 visits was 1.07 fewer adverse events (95% CI, -4.52 to 2.38; P = .54) and 8.16 fewer pneumonia hospitalizations (95% CI, -13.24 to -3.08; P = .002). The number needed to treat to prevent 1 hospitalization for pneumonia was 12,255., Conclusions: Compared with patients with ARI who were not treated with antibiotics, patients who were treated with antibiotics were not at increased risk of severe adverse drug events and had a small decreased risk of pneumonia hospitalization. This small benefit from antibiotics for a common ambulatory diagnosis creates persistent tension; at the societal level, physicians are compelled to reduce antibiotic prescribing, thus minimizing future resistance, whereas at the encounter level, they are compelled to optimize the benefit-risk balance for that patient.

The objective was to evaluate the effect of separate interventions on antimicrobial prescribing for uncomplicated upper respiratory tract infections. The authors conducted a quasi-experimental pre-post study with concurrent control groups for each intervention. Academic detailing led to a significant reduction in unnecessary antibiotic prescribing. However, there was no significant change in antibiotic prescribing in response to educational mailings to providers or to provider involvement in patient mailings. Organizations that seek to reduce inappropriate use of antibiotics should use proven approaches, even when they are more expensive.

Aim: To examine the prevalence of antimicrobial-resistant Salmonella in chicken meat and correlate with isolates from ill humans., Methods: We isolated Salmonella from raw chicken purchased from a randomly selected sample of retail outlets in central Pennsylvania during 2006-2007. Salmonella isolates from meat were compared, using pulsed-field gel electrophoresis, to isolates in the PulseNet database of Salmonella recovered from humans., Results: Of 378 chicken meat samples, 84 (22%) contained Salmonella. Twenty-six (31%) of the Salmonella isolates were resistant to > or = 3 antimicrobials and 18 (21%) were resistant to ceftiofur. All ceftiofur-resistant isolates exhibited reduced susceptibility (minimum inhibitory concentration >2 microg/mL) to ceftriaxone and carried a bla(CMY) gene, as detected by polymerase chain reaction. Among the 28 Salmonella serovar Typhimurium isolates, 20 (71.4%) were resistant to > or = 3 antimicrobials and 12 (42.9%) were resistant to ceftiofur. One ceftiofur-resistant Salmonella serovar Typhimurium poultry isolate exhibited a rare pulsed-field gel electrophoresis pattern indistinguishable from a human isolate in PulseNet; both isolates carried the bla(CMY-2) gene., Conclusions: These data demonstrate the presence of multidrug-resistant Salmonella in poultry meat, including bla(CMY) plasmid-mediated genes that confer resistance to both ceftiofur, used in poultry, and ceftriaxone, used for treating salmonellosis in humans. This study illustrates the potential for molecular subtyping databases to identify related Salmonella isolates from meat and ill humans, and suggests that chicken could be a source for multidrug-resistant salmonellosis in humans.

Objectives: Early transition from intravenous to oral antimicrobial therapy for acute osteomyelitis in children has been suggested as a safe and effective alternative to traditional prolonged intravenous therapy via central venous catheter, but no studies have directly compared these 2 treatment modalities. We sought to compare the effectiveness of early transition from intravenous to oral antimicrobial therapy versus prolonged intravenous antimicrobial therapy for the treatment of children with acute osteomyelitis., Methods: We conducted a retrospective cohort study of children aged 2 months to 17 years diagnosed with acute osteomyelitis between 2000 and 2005 at 29 freestanding children's hospitals in the United States to confirm the extent of variation in the use of early transition to oral therapy. We used propensity scores to adjust for potential differences between children treated with prolonged intravenous therapy and logistic regression to model the association of outcome (treatment failure rates within 6 months of diagnosis) and difference in the mode of therapy within hospitals and across hospitals., Results: Of the 1969 children who met inclusion criteria, 1021 received prolonged intravenous therapy and 948 received oral therapy. The use of prolonged intravenous therapy varied significantly across hospitals (10%-95%). The treatment failure rate was 5% (54 of 1021) in the prolonged intravenous therapy group and 4% (38 of 948) in the oral therapy group. There was no significant association between treatment failure and the mode of antimicrobial therapy. Thirty-five (3.4%) children in the prolonged intravenous therapy group were readmitted for a catheter-associated complication., Conclusions: Treatment of acute osteomyelitis with early transition to oral therapy is not associated with a higher risk of treatment failures and avoids the risks of prolonged intravenous therapy through central venous catheters.

Study Objective: We seek to determine the impact of emergency department (ED) crowding on delays in antibiotic administration for patients with community-acquired pneumonia., Methods: We performed a retrospective cohort study of adult patients admitted with community-acquired pneumonia from January 1, 2003, to April 31, 2005, at a single, urban academic ED. The main outcome was a delay (>4 hours from arrival) or nonreceipt of antibiotics in the ED. Eight ED crowding measures were assigned at triage. Multivariable regression and bootstrapping were used to test the adjusted impact of ED crowding measures of delayed (or no) antibiotics. Predicted probabilities were then calculated to assess the magnitude of the impact of ED crowding on the probability of delayed (or no) antibiotics., Results: In 694 patients, 44% (95% confidence interval [CI] 40% to 48%) received antibiotics within 4 hours and 92% (95% CI 90% to 94%) received antibiotics in the ED. Increasing levels of ED crowding were associated with delayed (or no) antibiotics, including waiting room number (odds ratio [OR] 1.05 for each additional waiting room patient [95% CI 1.01 to 1.10]) and recent ED length of stay for admitted patients (OR 1.14 for each additional hour [95% CI 1.04 to 1.25]). When the waiting room and recent length of stay were both at the lowest quartiles (ie, not crowded), the predicted probability of delayed (or no) antibiotics within 4 hours was 31% (95% CI 21% to 42%); when both were at the highest quartiles, the predicted probability was 72% (95% CI 61% to 81%)., Conclusion: ED crowding is associated with delayed and nonreceipt of antibiotics in the ED for patients admitted with community-acquired pneumonia.

Background: Antibiotics within four hours of arrival for patients with pneumonia and percutaneous intervention (PCI) within two hours for patients with acute myocardial infarction (AMI) are standard measures of emergency department (ED) quality., Objectives: To assess the institutional-level association between measures of ED crowding and process measures for pneumonia and AMI., Methods: The authors used summary data from 24 academic hospitals in the University Health Consortium. Analysis included the 2004 ED cycle time survey and performance data from January to December 2004 regarding the Joint Commission for Accreditation of Healthcare Organizations' PN-5b (initial antibiotic administration within four hours) for pneumonia and AMI-8a (PCI received within 120 minutes). Spearman correlation coefficients were used to determine associations between crowding and performance measures., Results: Across all institutions, 59% (range 43%-77%) of pneumonia patients received antibiotics within four hours, and 57% (range 22%-95%) of AMI patients received PCI within two hours. An increase in overall ED length of stay (-0.44, p = 0.04) and for admitted patients (-0.37, p = 0.08) was associated with a decrease in the proportion of pneumonia patients receiving antibiotics within four hours. An increase in chest x-ray turnaround time (-0.83, p < 0.001) and an increase in the left-without-being-seen rate (-0.51, p = 0.01) were also associated with a decrease in the proportion of pneumonia patients receiving antibiotics within four hours. No measures of crowding exhibited an association with time to PCI for AMI patients., Conclusions: Administrative measures of ED crowding showed an association with poorer performance on pneumonia quality of care measures but not with AMI quality of care measures. Hospitals might consider improving ED throughput, reducing boarding times for admitted patients, and reducing chest x-ray turnaround times to improve pneumonia care.

Antibiotics are increasingly prescribed in the peripartum period, for both maternal and fetal indications. Their effective use undoubtedly reduces the incidence of specific invasive infections in the newborn, such as group B streptococcal septicaemia. However, the total burden of infectious neonatal disease may not be reduced, particularly if broad-spectrum agents are used, as the pattern of infections has been shown to alter to allow dominance of previously uncommon organisms. This area has been relatively understudied, and there are almost no studies of long-term outcome. Recent findings suggest that such long-term data should be sought. First, there is evidence that organisms initially colonising the gut at birth may establish chronic persistence in many children, in contrast to prompt clearance if first encountered in later infancy, childhood or adulthood. Second, there is a rapidly advancing basic scientific data showing that individual members of the gut flora specifically induce gene activation within the host, modulating mucosal and systemic immune function and having an additional impact on metabolic programming. We thus review the published data on the impact of perinatal antibiotic regimens upon composition of the flora and later health outcomes in young children and summarise the recent scientific findings on the potential importance of gut flora composition on immune tolerance and metabolism.