Jeffrey S. Gerber

Prevalence of Inappropriate Antibiotic Prescriptions Among US Ambulatory Care Visits, 2010-2011

IMPORTANCE The National Action Plan for Combating Antibiotic-Resistant Bacteria set a goal of reducing inappropriate outpatient antibiotic use by 50% by 2020, but the extent of inappropriate outpatient antibiotic use is unknown. OBJECTIVE To estimate the rates of outpatient oral antibiotic prescribing by age and diagnosis, and the estimated portions of antibiotic use that may be inappropriate in adults and children in the United States. DESIGN, SETTING, AND PARTICIPANTS Using the 2010-2011 National Ambulatory Medical Care Survey and National Hospital Ambulatory Medical Care Survey, annual numbers and population-adjusted rates with 95% confidence intervals of ambulatory visits with oral antibiotic prescriptions by age, region, and diagnosis in the United States were estimated. EXPOSURES Ambulatory care visits. MAIN OUTCOMES AND MEASURES Based on national guidelines and regional variation in prescribing, diagnosis-specific prevalence and rates of total and appropriate antibiotic prescriptions were determined. These rates were combined to calculate an estimate of the appropriate annual rate of antibiotic prescriptions per 1000 population. RESULTS Of the 184,032 sampled visits, 12.6% of visits (95% CI, 12.0%-13.3%) resulted in antibiotic prescriptions. Sinusitis was the single diagnosis associated with the most antibiotic prescriptions per 1000 population (56 antibiotic prescriptions [95% CI, 48-64]), followed by suppurative otitis media (47 antibiotic prescriptions [95% CI, 41-54]), and pharyngitis (43 antibiotic prescriptions [95% CI, 38-49]). Collectively, acute respiratory conditions per 1000 population led to 221 antibiotic prescriptions (95% CI, 198-245) annually, but only 111 antibiotic prescriptions were estimated to be appropriate for these conditions. Per 1000 population, among all conditions and ages combined in 2010-2011, an estimated 506 antibiotic prescriptions (95% CI, 458-554) were written annually, and, of these, 353 antibiotic prescriptions were estimated to be appropriate antibiotic prescriptions. CONCLUSIONS AND RELEVANCE In the United States in 2010-2011, there was an estimated annual antibiotic prescription rate per 1000 population of 506, but only an estimated 353 antibiotic prescriptions were likely appropriate, supporting the need for establishing a goal for outpatient antibiotic stewardship.

Vaccines and autism: a tale of shifting hypotheses.

Although child vaccination rates remain high, some parental concern persists that vaccines might cause autism. Three specific hypotheses have been proposed: (1) the combination measles-mumps-rubella vaccine causes autism by damaging the intestinal lining, which allows the entrance of encephalopathic proteins; (2) thimerosal, an ethylmercury-containing preservative in some vaccines, is toxic to the central nervous system; and (3) the simultaneous administration of multiple vaccines overwhelms or weakens the immune system. We will discuss the genesis of each of these theories and review the relevant epidemiological evidence.

Trends in the incidence of methicillin-resistant Staphylococcus aureus infection in children's hospitals in the United States.

BACKGROUND The incidence of and outcomes associated with methicillin-resistant Staphylococcus aureus (MRSA) infection in hospitalized children have been incompletely characterized. METHODS We performed a retrospective, observational study using the Pediatric Health Information System, a database of clinical and financial data from >40 freestanding US childrens hospitals. Using discharge coding data, we characterized S. aureus infections in children <18 years of age who were hospitalized during the period from 1 January 2002 through 31 December 2007. RESULTS During this 6-year study period, we identified 57,794 children with S. aureus infection, 29,309 (51%) of whom had MRSA infection. The median age of patients with S. aureus infection was 3.1 years (interquartile range, 0.8-11.2 years), and less than one-third of these patients had complex, chronic medical conditions. Over time, there was a significant increase in cases of MRSA infection (from 6.7 cases per 1000 admissions in 2002 to 21.1 cases per 1000 admissions in 2007; P = .02, by test for trend), whereas the incidence of methicillin-susceptible S. aureus infection remained stable (14.1 cases per 1000 patient-days in 2002 to 14.7 cases per 1000 patient-days in 2007; P = .85, by test for trend). Of the 38,123 patients whose type of infection was identified, 23,280 (61%) had skin and soft-tissue infections. The incidences of skin and soft-tissue infection, pneumonia, osteomyelitis, and bacteremia that were caused by S. aureus increased over time, and these increases were due exclusively to MRSA. The mortality rate for hospitalized children with MRSA infection was 1% (360 of 29,309 children). CONCLUSIONS There has been a recent increase in the number of hospitalized children with MRSA infection. This increase is largely driven by, but is not limited to, an increase in skin and soft-tissue infections. The mortality rate for hospitalized children with MRSA infection is low.

Effect of an outpatient antimicrobial stewardship intervention on broad-spectrum antibiotic prescribing by primary care pediatricians: a randomized trial.

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.

Antibiotics, pediatric dysbiosis, and disease.

Antibiotics are by far the most common medications prescribed for children. Recent epidemiological data suggests an association between early antibiotic use and disease phenotypes in adulthood. Antibiotic use during infancy induces imbalances in gut microbiota, called dysbiosis. The gut microbiomes responses to antibiotics and its potential link to disease development are especially complex to study in the changing infant gut. Here, we synthesize current knowledge linking antibiotics, dysbiosis, and disease and propose a framework for studying antibiotic-related dysbiosis in children. We recommend future studies into the microbiome-mediated effects of antibiotics focused on four types of dysbiosis: loss of keystone taxa, loss of diversity, shifts in metabolic capacity, and blooms of pathogens. Establishment of a large and diverse baseline cohort to define healthy infant microbiome development is essential to advancing diagnosis, interpretation, and eventual treatment of pediatric dysbiosis. This approach will also help provide evidence-based recommendations for antibiotic usage in infancy.

Variability in Antibiotic Use at Children's Hospitals

BACKGROUND: Variation in medical practice has identified opportunities for quality improvement in patient care. The degree of variation in the use of antibiotics in childrens hospitals is unknown. METHODS: We conducted a retrospective cohort study of 556 692 consecutive pediatric inpatient discharges from 40 freestanding childrens hospitals between January 1, 2008, and December 31, 2008. We used the Pediatric Health Information System to acquire data on antibiotic use and clinical diagnoses. RESULTS: Overall, 60% of the children received at least 1 antibiotic agent during their hospitalization, including >90% of patients who had surgery, underwent central venous catheter placement, had prolonged ventilation, or remained in the hospital for >14 days. Even after adjustment for both hospital- and patient-level demographic and clinical characteristics, antibiotic use varied substantially across hospitals, including both the proportion of children exposed to antibiotics (38%–72%) and the number of days children received antibiotics (368–601 antibiotic-days per 1000 patient-days). In general, hospitals that used more antibiotics also used a higher proportion of broad-spectrum antibiotics. CONCLUSIONS: Childrens hospitals vary substantially in their use of antibiotics to a degree unexplained by patient- or hospital-level factors typically associated with the need for antibiotic therapy, which reveals an opportunity to improve the use of these drugs.

Antibiotic Management of Staphylococcus aureus Infections in US Children's Hospitals, 1999–2008

OBJECTIVES: The objective of this study was to describe trends in antibiotic management for Staphylococcus aureus infections among hospitalized children from 1999 to 2008. METHODS: A retrospective study was conducted by using the Pediatric Health Information Systems database to describe antibiotic treatment of inpatients with S aureus infection at 25 childrens hospitals in the United States. Patients who were admitted from 1999 to 2008 with International Classification of Diseases, Ninth Revision, Clinical Modification codes for S aureus infection were included. Trends in the use of vancomycin, clindamycin, linezolid, trimethoprim-sulfamethoxazole, cefazolin, and oxacillin/nafcillin were examined for percentage use and days of therapy per 1000 patient-days. RESULTS: A total of 64813 patients had a discharge diagnosis for S aureus infection. The incidence of methicillin-resistant S aureus (MRSA) infections during this period increased 10-fold, from 2 to 21 cases per 1000 admissions, whereas the methicillin-susceptible S aureus infection rate remained stable. Among patients with S aureus infections, antibiotics that treat MRSA increased from 52% to 79% of cases, whereas those that treat only methicillin-susceptible S aureus declined from 66% to <30% of cases. Clindamycin showed the greatest increase, from 21% in 1999 to 63% in 2008. Similar trends were observed by using days of therapy per 1000 patient-days. CONCLUSIONS: Antibiotic prescribing patterns for the treatment of S aureus infections have changed significantly during the past decade, reflecting the emergence of community-associated MRSA. Clindamycin is now the most commonly prescribed antibiotic for S aureus infections among hospitalized children. The substantial use of clindamycin emphasizes the importance of continuous monitoring of local S aureus susceptibility patterns.

Antimicrobial Stewardship Programs in Freestanding Children’s Hospitals

BACKGROUND AND OBJECTIVE: Single-center evaluations of pediatric antimicrobial stewardship programs (ASPs) suggest that ASPs are effective in reducing and improving antibiotic prescribing, but studies are limited. Our objective was to compare antibiotic prescribing rates in a group of pediatric hospitals with formalized ASPs (ASP+) to a group of concurrent control hospitals without formalized stewardship programs (ASP−). METHODS: We evaluated the impact of ASPs on antibiotic prescribing over time measured by days of therapy/1000 patient-days in a group of 31 freestanding children’s hospitals (9 ASP+, 22 ASP−). We compared differences in average antibiotic use for all ASP+ and ASP− hospitals from 2004 to 2012 before and after release of 2007 Infectious Diseases Society of America guidelines for developing ASPs. Antibiotic use was compared for both all antibacterials and for a select subset (vancomycin, carbapenems, linezolid). For each ASP+ hospital, we determined differences in the average monthly changes in antibiotic use before and after the program was started by using interrupted time series via dynamic regression. RESULTS: In aggregate, as compared with those years preceding the guidelines, there was a larger decline in average antibiotic use in ASP+ hospitals than in ASP− hospitals from 2007 to 2012, the years after the release of Infectious Diseases Society of America guidelines (11% vs 8%, P = .04). When examined individually, relative to preimplementation trends, 8 of 9 ASP+ hospitals revealed declines in antibiotic use, with an average monthly decline in days of therapy/1000 patient-days of 5.7%. For the select subset of antibiotics, the average monthly decline was 8.2%. CONCLUSIONS: Formalized ASPs in children’s hospitals are effective in reducing antibiotic prescribing.

Prevalence and Characteristics of Antimicrobial Stewardship Programs at Freestanding Children's Hospitals in the United States

BACKGROUND AND OBJECTIVE Antimicrobial stewardship programs (ASPs) are a mechanism to ensure the appropriate use of antimicrobials. The extent to which ASPs are formally implemented in freestanding childrens hospitals is unknown. The objective of this study was to determine the prevalence and characteristics of ASPs in freestanding childrens hospitals. METHODS We conducted an electronic survey of 42 freestanding childrens hospitals that are members of the Childrens Hospital Association to determine the presence and characteristics of their ASPs. For hospitals without an ASP, we determined whether stewardship strategies were in place and whether there were barriers to implementing a formal ASP. RESULTS We received responses from 38 (91%) of 42. Among responding institutions, 16 (38%) had a formal ASP, and 15 (36%) were in the process of implementing a program. Most ASPs (13 [81%] of 16) were started after 2007. The median number of full-time equivalents dedicated to ASPs was 0.63 (range, 0.1-1.8). The most common antimicrobials monitored by ASPs were linezolid, vancomycin, and carbapenems. Many hospitals without a formal ASP were performing stewardship activities, including elements of prospective audit and feedback (9 [41%] of 22), formulary restriction (9 [41%] of 22), and use of clinical guidelines (17 [77%] of 22). Antimicrobial outcomes were more likely to be monitored by hospitals with ASPs (100% vs 68%; P = .01), although only 1 program provided support for a data analyst. CONCLUSIONS Most freestanding childrens hospitals have implemented or are developing an ASP. These programs differ in structure and function, and more data are needed to identify program characteristics that have the greatest impact.

Racial Differences in Antibiotic Prescribing by Primary Care Pediatricians

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.