Association between nasopharyngeal colonization with multiple pneumococcal serotypes and total pneumococcal colonization density in young Peruvian children.

OBJECTIVES: We examined the association of nasopharyngeal (NP) pneumococcal co-colonization (>1 pneumococcal serotype) and pneumococcal density in young Peruvian children enrolled in a prospective cohort study. METHODS: NP swabs collected monthly from children aged <3 years during both asymptomatic and acute respiratory illness (ARI) periods underwent culture-enriched microarray for pneumococcal detection and serotyping and lytA polymerase chain reaction for density assessment. We examined the serotypes commonly associated with co-colonization and the distribution of densities by co-colonization, age, current ARI, and other covariates. The association of co-colonization and pneumococcal density was assessed using a multivariable mixed-effects linear regression model, accounting for repeated measures and relevant covariates. RESULTS: A total of 27 children contributed 575 monthly NP samples. Pneumococcus was detected in 302 of 575 (53%) samples, and co-colonization was detected in 61 of these 302 (20%). The total densities were higher during ARI than non-ARI periods and lowest among the youngest children, increasing with age. In the multivariable analysis, there was no significant association between pneumococcal density and co-colonization (coefficient estimate 0.22, 95% confidence interval 0.11-0.55; reference: single-serotype detections). Serotypes 23B and 19F were detected significantly more frequently as single isolates. CONCLUSION: Pneumococcal co-colonization was common and not associated with increased pneumococcal density. Differential propensity for co-colonization was observed among individual serotypes.

Assessing the Impact of Acute Respiratory Illnesses on the Risk of Subsequent Respiratory Illness.

BACKGROUND: Whether acute respiratory illnesses (ARIs), often associated with virus detection, are associated with lower risk for subsequent ARI remains unclear. We assessed the association between symptomatic ARI and subsequent ARI in young children. METHODS: In a prospective cohort of Peruvian children <3 years, we examined the impact of index ARI on subsequent ARI risk. Index ARI were matched with ≤3 asymptomatic observations and followed over 28 days. We compared risk of subsequent ARI between groups using conditional logistic regression adjusting for several covariates, accounting for repeat observations from individual children. RESULTS: Among 983 index ARI, 339 (34%) had an ARI event during follow-up, compared with 876/2826 (31%) matched asymptomatic observations. We found no significant association of index ARI and subsequent ARI risk during follow-up overall (adjusted odds ratio [aOR], 1.10; 95% confidence interval [CI], .98-1.23) or when limited to index ARI with respiratory viruses detected (aOR, 1.03; 95% CI, .86-1.24). Similarly, when the outcome was limited to ARI in which viruses were detected, no significant association was seen (aOR, 1.05; 95% CI, .87-1.27). CONCLUSIONS: ARIs were not associated with short-term protection against subsequent ARI in these children. Additional longitudinal studies are needed to understand drivers of recurrent ARI in young children.

Nasopharyngeal Pneumococcal Density and Evolution of Acute Respiratory Illnesses in Young Children, Peru, 2009-2011.

We examined nasopharyngeal pneumococcal colonization density patterns surrounding acute respiratory illnesses (ARI) in young children in Peru. Pneumococcal densities were dynamic, gradually increasing leading up to an ARI, peaking during the ARI, and decreasing after the ARI. Rhinovirus co-infection was associated with higher pneumococcal densities.

Secondhand Smoke Exposure and Illness Severity among Children Hospitalized with Pneumonia.

OBJECTIVE: To assess the relationship between secondhand smoke (SHS) exposure and disease severity among children hospitalized with community-acquired pneumonia (CAP). STUDY DESIGN: Children hospitalized with clinical and radiographic CAP were enrolled between January 1, 2010, and June 30, 2012 at 3 hospitals in Tennessee and Utah as part of the Centers for Disease Control and Prevention's Etiology of Pneumonia in the Community study. Household SHS exposure was defined based on the number of smokers in the child's home. Outcomes included hospital length of stay, intensive care unit admission, and mechanical ventilation. Proportional hazards and logistic regression models were used to assess associations between SHS exposure and outcomes. All models were adjusted for age, sex, race/ethnicity, household education level, government insurance, comorbidities, enrollment site, year, and season. RESULTS: Of the 2219 children included in the study, SHS exposure was reported in 785 (35.4%), including 325 (14.8%) with ≥2 smokers in the home. Compared with nonexposed children, the children exposed to ≥2 smokers had longer length of stay (median, 70.4 hours vs 64.4 hours; adjusted hazard ratio, 0.85; 95% CI, 0.75-0.97) and were more likely to receive intensive care (25.2% vs 20.9%; aOR, 1.44; 95% CI, 1.05-1.96), but not mechanical ventilation. Outcomes in children exposed to only 1 household smoker were similar to those in nonexposed children. CONCLUSION: Children hospitalized with CAP from households with ≥2 smokers had a longer length of stay and were more likely to require intensive care compared with children from households with no smokers, suggesting that they experienced greater pneumonia severity.

Respiratory Viral Detections During Symptomatic and Asymptomatic Periods in Young Andean Children.

BACKGROUND: Viruses are commonly detected in children with acute respiratory illnesses (ARIs) and in asymptomatic children. Longitudinal studies of viral detections during asymptomatic periods surrounding ARI could facilitate interpretation of viral detections but are currently scant. METHODS: We used reverse transcription polymerase chain reaction to analyze respiratory samples from young Andean children for viruses during asymptomatic periods within 8-120 days of index ARI (cough or fever). We compared viral detections over time within children and explored reverse transcription polymerase chain reaction cycle thresholds (CTs) as surrogates for viral loads. RESULTS: At least 1 respiratory virus was detected in 367 (43%) of 859 samples collected during asymptomatic periods, with more frequent detections in periods with rhinorrhea (49%) than those without (34%, P < 0.001). Relative to index ARI with human rhinovirus (HRV), adenovirus (AdV), respiratory syncytial virus (RSV) and parainfluenza virus detected, the same viruses were also detected during 32, 22, 10 and 3% of asymptomatic periods, respectively. RSV was only detected 8-30 days after index RSV ARI, whereas HRV and AdV were detected throughout asymptomatic periods. Human metapneumovirus and influenza were rarely detected during asymptomatic periods (<3%). No significant differences were observed in the CT for HRV or AdV during asymptomatic periods relative to ARI. For RSV, CTs were significantly lower during ARI relative to the asymptomatic period (P = 0.03). CONCLUSIONS: These findings indicate that influenza, human metapneumovirus, parainfluenza virus and RSV detections in children with an ARI usually indicate a causal relationship. When HRV or AdV is detected during ARI, the causal relationship is less certain.

Incidence and Risk Factors for Respiratory Syncytial Virus and Human Metapneumovirus Infections among Children in the Remote Highlands of Peru.

INTRODUCTION: The disease burden and risk factors for respiratory syncytial virus (RSV) and human metapneumovirus (MPV) infections among children living in remote, rural areas remain unclear. MATERIALS AND METHODS: We conducted a prospective, household-based cohort study of children aged <3 years living in remote rural highland communities in San Marcos, Cajamarca, Peru. Acute respiratory illnesses (ARI), including lower respiratory tract infection (LRTI), were monitored through weekly household visits from March 2009 through September 2011. Nasal swabs collected during ARI/LRTI were tested for RSV, MPV, and other respiratory viruses using real-time RT-PCR. Incidence rates and rate ratios were calculated using mixed effects Poisson regression. RESULTS: Among 892 enrolled children, incidence rates of RSV and MPV ARI were 30 and 17 episodes per 100 child-years, respectively. The proportions of RSV and MPV ARI that presented as LRTI were 12.5% and 8.9%, respectively. Clinic visits for ARI and hospitalizations were significantly more frequent (all p values <0.05) among children with RSV (clinic 41% and hospital 5.3%) and MPV ARI (38% and 3.5%) when compared with other viral infections (23% and 0.7%) and infections without virus detected (24% and 0.6%). In multivariable analysis, risk factors for RSV detection included younger age (RR 1.02, 95% CI: 1.00-1.03), the presence of a smoker in the house (RR 1.63, 95% CI: 1.12-2.38), residing at higher altitudes (RR 1.93, 95% CI: 1.25-3.00 for 2nd compared to 1st quartile residents; RR 1.98, 95% CI: 1.26-3.13 for 3rd compared to 1st quartile residents). Having an unemployed household head was significantly associated with MPV risk (RR 2.11, 95% CI: 1.12-4.01). CONCLUSION: In rural high altitude communities in Peru, childhood ARI due to RSV or MPV were common and associated with higher morbidity than ARI due to other viruses or with no viral detections. The risk factors identified in this study may be considered for interventional studies to control infections by these viruses among young children from developing countries.

Missed opportunities for tuberculosis screening in primary care.

OBJECTIVE: To assess how frequently pediatric practitioners perform latent tuberculosis infection (LTBI) screening according to guidelines. We hypothesized that screening occurs less frequently among children whose parents do not speak English as the primary language. STUDY DESIGN: We conducted a retrospective cohort study of patients attending well-child visits in an urban academic pediatric primary care clinic between April 1, 2012, and March 31, 2013. We assessed documentation of 3 LTBI screening components and tested the association between parent primary language and tuberculin skin test (TST) placement and documentation of results. RESULTS: During the study period, 387 of 9143 children (4%) had no documentation of screening question responses. Among the other 8756 children, 831 (10%) were identified as at high risk for LTBI. Of these, 514 (62%) did not have documented TST placement in the appropriate time frame. Thirty-nine of 213 children (18%) who had a TST placed did not have documented results. Multivariable regression showed that parent language was not associated with TST placement or documentation of results, but non-Hispanic Black children were more likely to not have a documented test result (aOR, 2.12; 95% CI, 1.07-4.19; P=.03) when adjusting for age, sex, parent primary language, insurance status, day of the week, and study year of TST placement. CONCLUSION: Parent primary language was not associated with LTBI testing. However, we found substantial gaps in TST placement and documentation of TST results among high-risk children, the latter of which was associated with race/ethnicity. Targeted quality improvement efforts should focus on developing processes to ensure complete screening in high-risk children.

Impact of home environment interventions on the risk of influenza-associated ARI in Andean children: observations from a prospective household-based cohort study.

BACKGROUND: The Respiratory Infections in Andean Peruvian Children (RESPIRA-PERU) study enrolled children who participated in a community-cluster randomized trial of improved stoves, solar water disinfection, and kitchen sinks (IHIP trial) and children from additional Andean households. We quantified the burden of influenza-associated acute respiratory illness (ARI) in this household-based cohort. METHODS: From May 2009 to September 2011, we conducted active weekly ARI surveillance in 892 children age <3 years, of whom 272 (30.5%) had participated in the IHIP trial. We collected nasal swabs during ARI, tested for influenza and other respiratory viruses by RT-PCR, and determined influenza incidence and risk factors using mixed-effects regression models. RESULTS: The overall incidence of influenza-associated ARI was 36.6/100 child-years; incidence of influenza A, B, and C was 20.5, 8.7, and 5.2/100 child-years, respectively. Influenza C was associated with fewer days of subjective fever (median 1 vs. 2) and malaise (median 0 vs. 2) compared to influenza A. Non-influenza ARI also resulted in fewer days of fever and malaise, and fewer healthcare visits than influenza A-associated ARI. Influenza incidence varied by calendar year (80% occurred in the 2010 season) and IHIP trial participation. Among households that participated in the IHIP trial, influenza-associated ARI incidence was significantly lower in intervention than in control households (RR 0.40, 95% CI: 0.20-0.82). CONCLUSIONS: Influenza burden is high among Andean children. ARI associated with influenza A and B had longer symptom duration and higher healthcare utilization than influenza C-associated ARI or non-influenza ARI. Environmental community interventions may reduce influenza morbidity.

A household-based study of acute viral respiratory illnesses in Andean children.

BACKGROUND: Few community studies have measured the incidence, severity and etiology of acute respiratory illness (ARI) among children living at high-altitude in remote rural settings. METHODS: We conducted active, household-based ARI surveillance among children aged <3 years in rural highland communities of San Marcos, Cajamarca, Peru from May 2009 through September 2011 (RESPIRA-PERU study). ARI (defined by fever or cough) were considered lower respiratory tract infections if tachypnea, wheezing, grunting, stridor or retractions were present. Nasal swabs collected during ARI episodes were tested for respiratory viruses by real-time, reverse-transcriptase polymerase chain reaction. ARI incidence was calculated using Poisson regression. RESULTS: During 755.1 child-years of observation among 892 children in 58 communities, 4475 ARI were observed, yielding an adjusted incidence of 6.2 ARI/child-year (95% confidence interval: 5.9-6.5). Families sought medical care for 24% of ARI, 4% were classified as lower respiratory tract infections and 1% led to hospitalization. Of 5 deaths among cohort children, 2 were attributed to ARI. One or more respiratory viruses were detected in 67% of 3957 samples collected. Virus-specific incidence rates per 100 child-years were: rhinovirus, 236; adenovirus, 73; parainfluenza virus, 46; influenza, 37; respiratory syncytial virus, 30 and human metapneumovirus, 17. Respiratory syncytial virus, metapneumovirus and parainfluenza virus 1-3 comprised a disproportionate share of lower respiratory tract infections compared with other etiologies. CONCLUSIONS: In this high-altitude rural setting with low-population density, ARI in young children were common, frequently severe and associated with a number of different respiratory viruses. Effective strategies for prevention and control of these infections are needed.

Serologic imprint of dengue virus in urban Haiti: characterization of humoral immunity to dengue in infants and young children.

Dengue is endemic to Haiti but not recognized as an important illness in the autochthonous population. To evaluate the prevalence of antibodies to dengue virus (DENV), serum samples from infants and young children 7-36 months of age (n = 166) were assayed by plaque reduction neutralization assays to each DENV serotype. Dengue virus serotype 1 had infected 40% of this study population, followed by serotype 2 (12%), serotype 3 (11%), and serotype 4 (2%). Fifty-three percent of infants and young children less than 12 months of age had already experienced DENV infection, and the seroprevalence of antibody to DENV increased to 65% by 36 months. Heterotypic antibody responses were an important component of the total dengue immunity profile.

Prevention of mother-to-child transmission of HIV in Haiti.

OBJECTIVES: To describe the effectiveness of a program designed to reduce the rate of mother-to-child transmission (MTCT) of HIV at the primary HIV testing and treatment center in Haiti between 1999 and 2004. METHODS: All pregnant, HIV-positive women who attended the major HIV testing and treatment clinic in Port-au-Prince, Haiti, between March 1999 and December 2004 were asked to participate in an MTCT prevention program. Of the 650 women who participated, 73.3% received zidovudine (AZT), 2.9% received nevirapine (NVP), and 10.1% received triple-drug therapy when it became available in 2003 and if clinical/laboratory indications were met. Approximately 13.8% received no antiretroviral medication. All participants received cotrimoxazole prophylaxis and infant formula for their children. Kaplan-Meier survival analysis and the log rank test were used to evaluate program impact on child survival. RESULTS: Complete data were available for 348 mother-infant pairs who completed the program to prevent MTCT of HIV. The rate of MTCT in the study was 9.2% (95% CI: 6.14-12.24), in contrast to the historical mother-to-child transmission rate of 27% in Haiti. HIV-positive infants were less likely to survive than HIV-negative infants at 18 months of follow-up (chi(2) = 19.06, P < .001, log rank test). Infant survival improved with early pediatric diagnosis and antiretroviral treatment. CONCLUSIONS: The MTCT prevention program described proved to be feasible and effective in reducing vertical HIV transmission in Haiti. The authors emphasize the need to expand testing, extend services to rural areas, and implement early HIV diagnosis to reduce infant mortality.

Prevention of mother-to-child transmission of HIV in Haiti

OBJECTIVES: To describe the effectiveness of a program designed to reduce the rate of mother-to-child transmission (MTCT) of HIV at the primary HIV testing and treatment center in Haiti between 1999 and 2004. METHODS: All pregnant, HIV-positive women who attended the major HIV testing and treatment clinic in Port-au-Prince, Haiti, between March 1999 and December 2004 were asked to participate in an MTCT prevention program. Of the 650 women who participated, 73.3% received zidovudine (AZT), 2.9% received nevirapine (NVP), and 10.1% received triple-drug therapy when it became available in 2003 and if clinical/laboratory indications were met. Approximately 13.8% received no antiretroviral medication. All participants received cotrimoxazole prophylaxis and infant formula for their children. Kaplan-Meier survival analysis and the log rank test were used to evaluate program impact on child survival. RESULTS: Complete data were available for 348 mother-infant pairs who completed the program to prevent MTCT of HIV. The rate of MTCT in the study was 9.2% (95% CI: 6.14-12.24), in contrast to the historical mother-to-child transmission rate of 27% in Haiti. HIV-positive infants were less likely to survive than HIV-negative infants at 18 months of follow-up (chi(2) = 19.06, P < .001, log rank test). Infant survival improved with early pediatric diagnosis and antiretroviral treatment. CONCLUSIONS: The MTCT prevention program described proved to be feasible and effective in reducing vertical HIV transmission in Haiti. The authors emphasize the need to expand testing, extend services to rural areas, and implement early HIV diagnosis to reduce infant mortality.

Prevention of mother-to-child transmission of HIV in Haiti / Prevención de la transmisión del VIH de madre a hijo en Haití

OBJECTIVES: To describe the effectiveness of a program designed to reduce the rate of mother-to-child transmission (MTCT) of HIV at the primary HIV testing and treatment center in Haiti between 1999 and 2004. METHODS: All pregnant, HIV-positive women who attended the major HIV testing and treatment clinic in Port-au-Prince, Haiti, between March 1999 and December 2004 were asked to participate in an MTCT prevention program. Of the 650 women who participated, 73.3 percent received zidovudine (AZT), 2.9 percent received nevirapine (NVP), and 10.1 percent received triple-drug therapy when it became available in 2003 and if clinical/laboratory indications were met. Approximately 13.8 percent received no antiretroviral medication. All participants received cotrimoxazole prophylaxis and infant formula for their children. Kaplan-Meier survival analysis and the log rank test were used to evaluate program impact on child survival. RESULTS: Complete data were available for 348 mother-infant pairs who completed the program to prevent MTCT of HIV. The rate of MTCT in the study was 9.2 percent (95 percent CI: 6.14-12.24), in contrast to the historical mother-to-child transmission rate of 27 percent in Haiti. HIV-positive infants were less likely to survive than HIV-negative infants at 18 months of follow-up (χ2 = 19.06, P < .001, log rank test). Infant survival improved with early pediatric diagnosis and antiretroviral treatment. CONCLUSIONS: The MTCT prevention program described proved to be feasible and effective in reducing vertical HIV transmission in Haiti. The authors emphasize the need to expand testing, extend services to rural areas, and implement early HIV diagnosis to reduce infant mortality.

OBJETIVOS: Describir la eficacia de un programa diseñado para reducir la tasa de transmisión del VIH de madre a hijo (TMH) en el principal centro de diagnóstico y tratamiento de esa infección en Haití entre 1999 y 2004. MÉTODOS: Se invitó a participar en un programa para la prevención de la TMH a todas las embarazadas positivas al VIH que asistían a la clínica principal de diagnóstico y tratamiento de la infección por el VIH en Puerto Príncipe, Haití, entre marzo de 1999 y diciembre de 2004. De las 650 mujeres que participaron, 73,3 por ciento recibieron zidovudina (AZT), 2,9 por ciento nervirapine (NVP) y 10,1 por ciento tripleterapia cuando esta se hizo disponible en 2003 y cumplían los indicadores clínicos y de laboratorio requeridos. Aproximadamente 13,8 por ciento no recibió medicamentos antirretrovirales. Todas las participantes recibieron el tratamiento profiláctico con cotrimoxazole y fórmula infantil para sus hijos. Para evaluar el impacto del programa sobre la supervivencia infantil se aplicó el análisis de supervivencia de Kaplan-Meier y la prueba de rangos logarítmicos. RESULTADOS: Se obtuvieron los datos completos de 348 parejas madre-hijo que terminaron el programa de prevención de la TMH del VIH. La tasa de TMH en el estudio fue de 9,2 por ciento (intervalo de confianza de 95 por ciento: 6,14 a 12,24), frente a una tasa de TMH histórica en Haití de 27 por ciento. A los 18 meses de seguimiento, los niños positivos al VIH presentaron una menor probabilidad de supervivencia que los negativos (χ2 = 19,06; P < 0,001; prueba de rangos logarítmicos). La supervivencia de los niños aumentó con el diagnóstico y el tratamiento antirretroviral pediátricos tempranos. CONCLUSIONES: El programa de prevención de la TMH descrito demostró su factibilidad y eficacia para reducir la transmisión vertical del VIH en Haití. Los autores sub rayan la necesidad de extender el tamizaje y los servicios a áreas rurales, así como de implementar el diagnóstico temprano del VIH para reducir la mortalidad infantil

Improving outcomes in infants of HIV-infected women in a developing country setting.

BACKGROUND: Since 1999 GHESKIO, a large voluntary counseling and HIV testing center in Port-au-Prince, Haiti, has had an ongoing collaboration with the Haitian Ministry of Health to reduce the rate of mother to child HIV transmission. There are limited data on the ability to administer complex regimens for reducing mother to child transmission and on risk factors for continued transmission and infant mortality within programmatic settings in developing countries. METHODS AND FINDINGS: We analyzed data from 551 infants born to HIV-infected mothers seen at GHESKIO, between 1999 and 2005. HIV-infected mothers and their infants were given "short-course" monotherapy with antiretrovirals for prophylaxis; and, since 2003, highly active antiretroviral therapy (HAART) when clinical or laboratory indications were met. Infected women seen in the pre-treatment era had 27% transmission rates, falling to 10% in this cohort of 551 infants, and to only 1.9% in infants of women on HAART. Mortality rate after HAART introduction (0.12 per year of follow-up [0.08-0.16]) was significantly lower than the period before the availability of such therapy (0.23 [0.16-0.30], P<0.0001). The effects of maternal health, infant feeding, completeness of prophylaxis, and birth weight on mortality and transmission were determined using univariate and multivariate analysis. Infant HIV-1 infection and low birth weight were associated with infant mortality in less than 15 month olds in multivariate analysis. CONCLUSIONS: Our findings demonstrate success in prevention of mother-to-child HIV transmission and mortality in a highly resource constrained setting. Elements contributing to programmatic success include provision of HAART in the context of a comprehensive program with pre and postnatal care for both mother and infant.

Contribution of bacterial sepsis to morbidity in infants born to HIV-infected Haitian mothers.

BACKGROUND: Haiti is a country with a heavy burden of HIV infection in childbearing women. Previous studies have shown that early infant deaths are common in children of HIV-infected women. This study was designed to define the rates of and risk factors for systemic bacterial and mycobacterial infection in such children and to identify the causative agents. METHODS: A cohort of 120 children born to HIV-infected mothers between May 2001 and December 2003 were prospectively observed to 15 months of age. They received comprehensive pediatric care at the GHESKIO Centers. Children were assigned to being HIV-infected by serology, RNA detection, and/or defining clinical illnesses. Blood cultures were obtained before giving antibiotics in children who were febrile or chronically ill. Blood cultures also were obtained at selected visits on well children. RESULTS: The mortality rate in the first 15 months was high, 22 of 106 (207/1,000 live births) in these children. Sixteen (70%) deaths were within 6 months of birth. Fourty-eight blood cultures had clinically significant organisms of which 38 were Staphylococcus aureus. Blood cultures were more likely to be positive in symptomatic and in HIV-infected children. CONCLUSIONS: Despite perinatal HIV treatment, mortality in children born to HIV-infected mothers remained high. Bacteremia, particularly with Staphylococcus aureus, is a partial explanation for excess illness.

Differences in antibiotic prescribing patterns for children younger than five years in the three major outpatient settings.

OBJECTIVES: To perform a comprehensive analysis of the use of antibiotics in three major sites for outpatient care: private office-based clinics, emergency departments (ED), and hospital-based clinics. STUDY DESIGN: Data from the National Ambulatory Medical Care Survey (NAMCS) and National Hospital Ambulatory Medical Care Survey (NHAMCS) were used to determine visit rates and antibiotic prescribing patterns for the three major outpatient care settings from 1994 to 2000 for children <5 years of age. RESULTS: Antibiotic prescription rates declined from 1405 to 1088 per 1000 children over the study years (P=.032) [correction]. Significant declines in antibiotic prescriptions were noted in both the office-based setting and ED: 1119 to 841 (P=.049) in the office-based setting and 237 to 198 antibiotic prescriptions per 1000 children in the ED (P=.003) [correction]. Sites of care differed markedly with white children receiving 82.5%, 14.3%, and 3.2% of antibiotics in the office-based settings, ED, and hospital-based clinics, respectively, compared with 60%, 31%, and 9% for black children (P<.001). However, total visits, visits resulting in a diagnosis of otitis media, and antibiotic prescribing rates were similar for white and black children during the latter study years. CONCLUSIONS: There has been a decline in antibiotic prescribing in children <5 years of age, which was most notable in office-based and emergency department settings.