Matthew Bryan

Comparative Effectiveness of Intravenous vs Oral Antibiotics for Postdischarge Treatment of Acute Osteomyelitis in Children

IMPORTANCE 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. OBJECTIVE To compare the effectiveness and adverse outcomes of postdischarge antibiotic therapy administered via the PICC or the oral route. DESIGN, SETTING, AND PARTICIPANTS 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 childrens 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. INTERVENTIONS Postdischarge administration of antibiotics via the PICC or the oral route. MAIN OUTCOMES AND MEASURES The primary outcome was treatment failure. Secondary outcomes included adverse drug reaction, PICC line complication, and a composite of all 3 end points. RESULTS 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 (<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. CONCLUSIONS AND RELEVANCE 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.

Trajectories of symptoms and function in older adults with low back disorders.

Study Design. Prospective cohort study. Objective. To determine whether there are distinct trajectories of back pain and function among older adults and to identify characteristics that distinguish among patients with substantially different prognoses. Summary of Background Data. Although the differential diagnosis and course of low back pain among older adults may differ from middle-aged adults, there is little evidence. Better understanding variability in recovery among older adults may help target patients for more intensive clinical interventions, plan resource use, and design clinical studies of more homogeneous patient groups. Methods. Patients aged 65 years or older with a new episode of care for back pain were recruited at 3 geographically diverse sites. Patients completed pain intensity and Roland-Morris Disability measures at baseline and 3, 6, and 12 months later. We used latent class analysis to identify distinct trajectories of pain and function and then logistic regression to identify predictors of membership in the improving trajectories. Results. There were 3929 participants who completed outcome measures at every follow-up interval. Latent class analysis identified subgroups with low, intermediate, or high pain or disability scores who remained relatively stable over time. However, small subgroups showed dramatic improvement from baseline to 1 year (17% with major improvement in Roland score, pain intensity, or both). Shorter pain duration, higher patient confidence in improvement, and fewer comorbid conditions at baseline were each associated independently with favorable prognosis. Conclusion. Although most patients remained relatively stable over a year, latent class analysis identified small groups with major improvement in pain, function, or both. This technique may, therefore, be useful for studying back pain prognosis. Our results should help assemble more prognostically homogeneous groups for research, and the technique may help identify subgroups of patients with uniquely successful responses to investigational interventions. Level of Evidence: 3

Variability in Antibiotic Prescribing for Community-Acquired Pneumonia

This study explores clinical and sociodemographic factors associated with variability in prescribing practices for antibiotics for CAP in a retrospective cohort. BACKGROUND AND OBJECTIVES: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Association of Acute Kidney Injury With Concomitant Vancomycin and Piperacillin/Tazobactam Treatment Among Hospitalized Children

Importance &bgr;-Lactam antibiotics are often coadministered with intravenous (IV) vancomycin hydrochloride for children with suspected serious infections. For adults, the combination of IV vancomycin plus piperacillin sodium/tazobactam sodium is associated with a higher risk of acute kidney injury (AKI) compared with vancomycin plus 1 other &bgr;-lactam antibiotic. However, few studies have evaluated the safety of this combination for children. Objective To assess the risk of AKI in children during concomitant therapy with vancomycin and 1 antipseudomonal &bgr;-lactam antibiotic throughout the first week of hospitalization. Design, Setting, and Participants This retrospective cohort study focused on children hospitalized for 3 or more days who received IV vancomycin plus 1 other antipseudomonal &bgr;-lactam combination therapy at 1 of 6 large children’s hospitals from January 1, 2007, through December 31, 2012. The study used the Pediatric Health Information System Plus database, which contains administrative and laboratory data from 6 pediatric hospitals in the United States. Patients with underlying kidney disease or abnormal serum creatinine levels on hospital days 0 to 2 were among those excluded. Patients 6 months to 18 years of age who were admitted through the emergency department of the hospital were included. Data were collected from July 2015 to March 2016. Data analysis took place from April 2016 through July 2017. (Exact dates are not available because the data collection and analysis processes were iterative.) Main Outcomes and Measures The primary outcome was AKI on hospital days 3 to 7 and within 2 days of receiving combination therapy. Acute kidney injury was defined using KDIGO criteria and was based on changes in serum creatinine level from hospital days 0 to 2 through hospital days 3 to 7. Multiple logistic regression was performed using a discrete-time failure model to test the association between AKI and receipt of IV vancomycin plus piperacillin/tazobactam or vancomycin plus 1 other antipseudomonal &bgr;-lactam antibiotic. Results A total of 1915 hospitalized children who received combination therapy were identified. Of the 1915 patients, a total of 866 (45.2%) were female and 1049 (54.8%) were male, 1049 (54.8%) were identified as white in race/ethnicity, and the median (interquartile range) age was 5.6 (2.1-12.7) years. Among the cohort who received IV vancomycin plus 1 other antipseudomonal &bgr;-lactam antibiotic, 157 patients (8.2%) had antibiotic-associated AKI. This number included 117 of 1009 patients (11.7%) who received IV vancomycin plus piperacillin/tazobactam combination therapy. After adjustment for age, intensive care unit level of care, receipt of nephrotoxins, and hospital, IV vancomycin plus piperacillin/tazobactam combination therapy was associated with higher odds of AKI each hospital day compared with vancomycin plus 1 other antipseudomonal &bgr;-lactam antibiotic combination (adjusted odds ratio, 3.40; 95% CI, 2.26-5.14). Conclusions and Relevance Coadministration of IV vancomycin and piperacillin/tazobactam may increase the risk of AKI in hospitalized children. Pediatricians must be cognizant of the potential added risk of this combination therapy when making empirical antibiotic choices.

Intravenous Versus Oral Antibiotics for Postdischarge Treatment of Complicated Pneumonia.

BACKGROUND AND OBJECTIVES: 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. METHODS: This multicenter retrospective cohort study included children ≥2 months and <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.” RESULTS: 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). CONCLUSIONS: 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.

Epidemiology of Methicillin-Resistant Staphylococcus aureus Bacteremia in Children

This multicenter retrospective cohort study evaluates the clinical epidemiology and outcomes of children with MRSA bacteremia and determines risk factors for treatment failure. BACKGROUND: 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. METHODS: 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 >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. RESULTS: 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 <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. CONCLUSIONS: 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.

Association of Broad- vs Narrow-Spectrum Antibiotics With Treatment Failure, Adverse Events, and Quality of Life in Children With Acute Respiratory Tract Infections

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.

Predicting Subsequent High-Frequency, Low-Acuity Utilization of the Pediatric Emergency Department

OBJECTIVE To derive and test a predictive model for high-frequency (4 or more visits per year), low-acuity (emergency severity index 4 or 5) utilization of the pediatric emergency department. METHODS The study sample used 3 years of data (2012-2014) from a single tertiary-care childrens hospital for patients <21 years of age. Utilization in 2013 defined the index visit; prior utilization was drawn from 2012; and 2014 was used for outcome measurement. Candidate predictor variables were those that would be available at the time of triage. Data were split into derivation and test sets randomly; variables with a significant univariate association in the derivation set were included for multivariable modeling. The final model from the derivation set was then tested in the validation set, with calculation of a receiver operating characteristic curve. RESULTS There were 90,972 visits in 2013, of which 61,430 were first (index) visits. A total of 590 (1%) had 4 or more triage level 4 or 5 visits in the following year (2014). The final model included site of primary care, age, acuity, previous utilization, race, and insurance, and had an area under the receiver operating characteristic curve of 0.84. CONCLUSIONS Data available to the emergency department provider at the time of initial visit triage can predict utilization for low-acuity complaints in the subsequent year. Future work should focus on validation and refinement of the model in additional settings, and electronic calculation of risk status for targeted intervention to improve appropriate utilization of health care services.

Associations Between Relative Value Units and Patient-Reported Back Pain and Disability:

Objective: To describe associations between health care utilization measures and patient-reported outcomes (PROs). Method: Primary data were collected from patients ≥65 years with low back pain visits from 2011 to 2013. Six PROs of pain and functionality were collected 12 and 24 months after the index visits and total and spine-specific relative value units (RVUs) from electronic health records were tabulated over 1 year. We calculated correlation coefficients between RVUs and 12- and 24-month PROs and conducted linear regressions with each 12- and 24-month PRO as the outcome variables and RVUs as predictors of interest. Results: We observed very weak correlations between worse PROs at 12 and 24 months and greater 12-month utilization. In regression analyses, we observed slight associations between greater utilization and worse 12- and 24-month PROs. Discussion: We found that 12-month health care utilization is not strongly associated with PROs at 12 or 24 months.

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

Objective: To compare treatment failure leading to hospital readmission in children with complicated appendicitis who received oral versus intravenous antibiotics after discharge. Background: 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. Methods: 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. Results: 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%). Conclusions: 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.