Antibiotic Use In Infants Research Articles

Early Life Exposures as Risk Factors for Pediatric Eosinophilic Esophagitis

Few etiologic studies of eosinophilic esophagitis (EoE) have been conducted. Early life exposures have been shown to predispose to other allergic disease, but their role has not been assessed in EoE. The present study sought to explore early life exposures as possible risk factors for developing EoE in the pediatric population. This was a 2-phase case-control study conducted at the University of North Carolina. The first phase consisted of survey development for early life exposures via cognitive interview. In the second phase, a telephone-based questionnaire was administered to cases with EoE (n = 31) and 2 sets of controls, patients with gastroesophageal reflux disease, and siblings of nonsyndromic cleft lip/palate patients (n = 26 in each). Different controls were explored to identify controls reflective of the source population of the cases. Siblings of cleft lip/palate patients were identified as the more suitable control population. Odds ratios were calculated to evaluate the association between early life exposures and the development of pediatric EoE. Early life exposures were associated with increased odds of developing pediatric-onset EoE. Antibiotic use in infancy was associated with 6 times the odds of having EoE (95% confidence interval 1.7-20.8). Cesarean delivery, preterm birth, and formula-only or mixed (infant formula and breast milk) feeding also have trends toward increased odds for developing EoE. A number of early life exposures may be associated with the development of EoE. These are potentially modifiable risk factors that if confirmed would have implications for improved understanding of EoE pathogenesis and disease prevention.

42 Antibiotic Use in Infants in the First Year of Life in Five European Countries

Background and aimsIn view of antibiotic resistance problems and development of atopic diseases there is a need to improve the appropriateness of antibiotic use, especially in young children. Antibiotics are...

Environmental and demographic risk factors for egg allergy in a population‐based study of infants

Although egg allergy is the most common food allergy in infants and young children, risk factors for egg allergy remain largely unknown. This study examined the relationship between environmental and demographic factors and egg allergy in a population-based infant cohort. In a study of 5276 infants (HealthNuts), infants underwent skin prick testing (SPT) to egg white at 12months of age. Questionnaire data on relevant exposures were obtained. 699/873 (80%) infants eligible for oral food challenge (detectable wheal on SPT) attended for formal assessment of egg allergy status; 453 had confirmed egg allergy (positive challenge and SPT≥2mm). Associations between environmental and demographic factors and egg allergy were investigated using multivariable logistic regression. Children with older siblings and those with a pet dog at home were less likely to develop egg allergy by 1year of age (adjusted OR [aOR], 0.72; 95% CI, 0.62, 0.83 per sibling; and aOR, 0.72; 95% CI, 0.52, 0.99, respectively). Caesarean section delivery, antibiotic use in infancy, childcare attendance and maternal age were not associated with egg allergy. History of allergic disease in an immediate family member and having parents born in East Asia were strong risk factors for infantile egg allergy (aOR, 1.82; 95% CI, 1.40, 2.36; and aOR, 3.30; 95% CI, 2.45, 4.45, respectively). Exposure in the first year of life to siblings and dogs may decrease the risk of subsequent egg allergy. Infants with a family history of allergy and those with parents born in East Asia are at increased risk of egg allergy.

Interaction between IL13 genotype and environmental factors in the risk for allergic rhinitis in Korean children

The prevalence of allergic rhinitis (AR) is increasing worldwide. Allergic diseases develop in susceptible subjects when they are exposed to specific environmental factors. We analyzed changes in the prevalence of AR and identified genetic and environmental factors in early childhood that affect risk. We used the International Study of Asthma and Allergies in Childhood questionnaire to collect data on AR, allergies, and environmental exposures from 4554 elementary school students from 5 areas of Seoul, Korea, in 2008. We also obtained DNA from 1050 subjects from 1 area of Seoul for genotype analysis of IL13. We identified genetic and environmental factors during infancy and early childhood that increased the risk for current AR (resulting in a diagnosis of AR and AR symptoms in the past 12 months) in elementary school-aged children. These included allergic disease in parents and antibiotic use in infants, allergic disease in parents and exposure of infants to mold, and allergic disease in parents and moving an infant to a newly built house. The risk of current AR also increased in subjects with GA or AA at nucleotide 2044 in IL13 who had been exposed to mold in the home during infancy (adjusted odds ratio, 3.27; 95% CI, 1.75-6.11) compared with subjects who had GG at this position and had not been exposed to mold (adjusted odds ratio, 3.27; 95% CI, 1.75-6.11). The prevalence of AR is increasing in Korean children. Children with a family history of allergic disease and exposure to specific environmental risk factors during infancy are more likely to have AR. Children with GA or AA at IL13(+2044) are at increased risk for AR when exposed to mold in the home during the first year of life.

Antibiotic use in infants in the first year of life in five European countries

To assess in infants the number of illness episodes treated with antibiotics and prescription rates in five European countries. This study was embedded in a multicenter nutritional intervention study and was conducted in five European countries. Infants were followed until 1 year of age. Illness episodes and prescriptions of systemic antibiotics were recorded by the parents. Illness episodes were caused by upper respiratory tract infections (URTIs) in 55-64% and by otitis media (OM) in 2-6.8%. URTIs were statistically significant and more frequently treated with antibiotics in Italy (18.8%), and less frequently in Switzerland (1.4%). OM was statistically significant and less frequently treated with antibiotics in the Netherlands (55%) when compared to Italy (82%). The antibiotic prescription rate varied between countries, ranging from 0.2 to 1.3 prescriptions per infant per year. As the frequency of illness episodes did not differ between countries, other factors, such as physician's attitude, parental pressure or other socio-economic determinants, most likely play a role in antibiotic prescribing habits in the first year of life.

Etiological diagnosis reduces the use of antibiotics in infants with bronchiolitis

OBJECTIVE:Acute bronchiolitis is a leading cause of infant hospitalization and is most commonly caused by respiratory syncytial virus. Etiological tests are not required for its diagnosis, but the influence of viral screening on the therapeutic approach for acute bronchiolitis remains unclear.METHODS:A historical cohort was performed to assess the impact of viral screening on drug prescriptions. The study included infants up to one year of age who were hospitalized for bronchiolitis. Virus screening was performed using immunofluorescence assays in nasopharyngeal aspirates. The clinical data were obtained from the patients' medical records. Therapeutic changes were considered to be associated with viral screening when made within 24 hours of the release of the results.RESULTS:The frequency of prescriptions for beta agonists, corticosteroids and antibiotics was high at the time of admission and was similar among the 230 patients. The diagnosis of pneumonia and otitis was associated with the introduction of antibiotics but did not influence antibiotics maintenance after the results of the virus screening were obtained. Changes in the prescriptions were more frequent for the respiratory syncytial virus patients compared to patients who had negative viral screening results (p = 0.004), especially the discontinuation of antibiotics (p<0.001). The identification of respiratory syncytial virus was associated with the suspension of antibiotics (p = 0.003), even after adjusting for confounding variables (p = 0.004); however, it did not influence the suspension of beta-agonists or corticosteroids.CONCLUSION:The identification of respiratory syncytial virus in infants with bronchiolitis was independently associated with the discontinuation of antibiotics during hospitalization.

Current Resources for Evidence‐Based Practice January/February 2012

The Institute of Medicine Report on Clinical Preventive Services for Women: From Evidence to Policy As a central component of the Affordable Care Act (ACA), new health insurance plans will be required to cover preventive health services without cost sharing to plan members beginning on or after August 1, 2012. In response to this directive within the ACA, the United States Department of Health and Human Services (HHS) charged the Institute of Medicine (IOM) with conducting a comprehensive review of women’s preventive health services and recommending those services deemed necessary for the health of women in the United States (Gee et al, 2011).

Physicians' responsibility for antibiotic use in infants from periurban Lima, Peru.

To describe the use of antibiotics in Peruvian children under 1 year in a setting where they are available without a prescription. Data were analyzed from a cohort study between September 2006 and December 2007 of 1 023 children < 2 months old in periurban Lima, Peru, followed until they were 1 year old. Seven hundred seventy of 1 023 (75.3%) children took 2 085 courses of antibiotics. There were two courses per child per year (range 0-12). Higher rates of antibiotic use were found in children 3-6 months old (37.2%). Antibiotics were given to children for 8.2% of common colds, 58.6% of all pharyngitis, 66.0% of bronchitis, 40.7% of diarrheas, 22.8% of dermatitis, and 12.0% of bronchial obstructions. A physician's prescription was the most common reason for antibiotic use (90.8%). Medication use without a prescription was found in 6.9% of children, and in 63.9% of them it was preceded by a physician's prescription. Infants are often exposed to antibiotics in this setting. Overuse of antibiotics is common for diagnoses such as pharyngitis, bronchitis, bronchial obstruction, and diarrhea but is typically inappropriate (83.1% of courses) based on the most common etiologies for this age group. Interventions to improve the use of antibiotics should focus on physicians, since a physician's prescription was the most common reason for antibiotic use.

Infant antibiotic use and wheeze and asthma risk: a systematic review and meta-analysis

Our aim was to systematically review and meta-analyse longitudinal studies on antibiotic use and subsequent development of wheeze and/or asthma with regards to study quality, outcome measurement, reverse causation (RC; wheezing/asthma symptoms have caused prescription of antibiotics) and confounding by indication (CbI; respiratory tract infections leading to antibiotic use may be the underlying cause triggering asthma symptom development). English-language papers and studies published before November 1, 2010 with longitudinal observational design were included. Study quality was assessed using the Newcastle-Ottawa scale. We identified 21 longitudinal studies. The effect of antibiotic use on wheeze/asthma risk varied between studies. 18 studies were eligible for meta-analysis showing pooled OR 1.27 (95% CI 1.12-1.43) for wheeze/asthma. When we eliminated studies with possible RC and CbI, the pooled risk estimate in the nine remaining studies was attenuated to OR 1.12 (95% CI 0.98-1.26). Definition of wheeze/asthma and age at follow-up differed between studies. Three studies focused on wheeze/asthma beyond 5-6 yrs of age with the presence of active symptoms and/or medication (pooled OR 1.08, 95% CI 0.93-1.23; dominated by one study). RC and CbI lead to overestimation of the association between antibiotic use and subsequent development of wheeze/asthma. Association was weak when fully adjusted for these types of bias. Heterogeneity of disease definition between studies could affect the results.

Antibiotic use in infancy and symptoms of asthma, rhinoconjunctivitis, and eczema in children 6 and 7 years old: International Study of Asthma and Allergies in Childhood Phase III

Antibiotic use in infancy and symptoms of asthma, rhinoconjunctivitis, and eczema in children 6 and 7 years old: International Study of Asthma and Allergies in Childhood Phase III

Antibiotic use in infancy and symptoms of asthma, rhinoconjunctivitis, and eczema in children 6 and 7 years old: International Study of Asthma and Allergies in Childhood Phase III

Phase III of the International Study of Asthma and Allergies in Childhood measured the global prevalence of symptoms of asthma, rhinoconjunctivitis, and eczema in children. To investigate the associations between the use of antibiotics in the first year of life and symptoms of asthma, rhinoconjunctivitis, and eczema in children 6 and 7 years old. Parents or guardians of children 6 and 7 years old completed written questionnaires on current symptoms and possible risk factors. Prevalence odds ratios (ORs) were estimated by using logistic regression. A total of 193,412 children from 71 centers in 29 countries participated. Reported use of antibiotics in the first year of life was associated with an increased risk of current asthma symptoms (wheezing in the previous 12 months) with an OR (adjusted for sex, region of the world, language, and per capita gross national income) of 1.96 (95% CI, 1.85-2.07); this fell to 1.70 (1.60-1.80) when adjusted for other risk factors for asthma. Similar associations were observed for severe asthma symptoms (OR, 1.82; 95% CI, 1.67-1.98), and asthma ever (OR, 1.94; 95% CI, 1.83-2.06). Use of antibiotics in the first year of life was also associated, but less strongly, with increased risks of current symptoms of rhinoconjunctivitis (OR, 1.56; 95% CI, 1.46-1.66) and eczema (OR, 1.58; 95% CI, 1.33-1.51). There is an association between antibiotic use in the first year of life and current symptoms of asthma, rhinoconjunctivitis, and eczema in children 6 and 7 years old. Further research is required to determine whether the observed associations are causal or are a result of confounding by indication or reverse causation.

Associations of Doctor-Diagnosed Asthma with Immigration Status, Age at Immigration, and Length of Residence in the United States in a Sample of Mexican American School Children in Chicago

Among Mexican Americans in the United States, children who were born in the US had higher rates of asthma than their Mexico-born peers. The purpose of this study was to examine the associations of doctor-diagnosed asthma with immigration-related variables and to investigate whether these associations could be explained by factors that may change with migration. We surveyed parents of 2,023 school children of Mexican descent and examined the associations of asthma with nativity, age at immigration, and length of residence in the US after adjusting for potential confounding variables. In multivariate analyses, US-born children had a 2.42-fold (95% confidence interval [CI]: 1.52-3.83) increased odds of asthma compared with their Mexico-born peers. Mexico-born participants who moved to the US before 2 years of age were almost twice as likely to experience asthma compared with Mexico-born children who moved to the US >or=2 years of age. In addition, Mexico-born participants who lived in the US for 10 years or more were 2.37 times more likely to have asthma than Mexico-born students who lived in the US for less than 10 years. These associations were not explained by a wide variety of factors such as place of residence in infancy; exposure to animals/pets; history of infections, Tylenol use, and antibiotic use in infancy; breastfeeding; exposure to environmental tobacco smoke; daycare attendance and number of siblings; and language use. Our findings point to the effects of nativity, age at immigration, and duration of residence in the US on the risk of asthma in Mexican American children, suggesting that potentially modifiable factors that change with migration may be linked with the disease. The findings of this study should stimulate further research to explain factors that may be responsible for the observed differentials in the risk of asthma among Mexican Americans.

Associations of Doctor-Diagnosed Asthma with Immigration Status, Age at Immigration, and Length of Residence in the United States in a Sample of Mexican American School Children in Chicago

Objectives. Among Mexican Americans in the United States, children who were born in the US had higher rates of asthma than their Mexico-born peers. The purpose of this study was to examine the associations of doctor-diagnosed asthma with immigration-related variables and to investigate whether these associations could be explained by factors that may change with migration. Methods. We surveyed parents of 2,023 school children of Mexican descent and examined the associations of asthma with nativity, age at immigration, and length of residence in the US after adjusting for potential confounding variables. Results. In multivariate analyses, US-born children had a 2.42-fold (95% confidence interval [CI]: 1.52–3.83) increased odds of asthma compared with their Mexico-born peers. Mexico-born participants who moved to the US before 2 years of age were almost twice as likely to experience asthma compared with Mexico-born children who moved to the US ≥2 years of age. In addition, Mexico-born participants who lived in the US for 10 years or more were 2.37 times more likely to have asthma than Mexico-born students who lived in the US for less than 10 years. These associations were not explained by a wide variety of factors such as place of residence in infancy; exposure to animals/pets; history of infections, Tylenol use, and antibiotic use in infancy; breastfeeding; exposure to environmental tobacco smoke; daycare attendance and number of siblings; and language use. Conclusions. Our findings point to the effects of nativity, age at immigration, and duration of residence in the US on the risk of asthma in Mexican American children, suggesting that potentially modifiable factors that change with migration may be linked with the disease. The findings of this study should stimulate further research to explain factors that may be responsible for the observed differentials in the risk of asthma among Mexican Americans.

Prophylactic systemic antibiotics to reduce morbidity and mortality in neonates with central venous catheters

The use of central venous catheters is recognised as a risk factor for nosocomial infection. Prophylactic antibiotics may be effective in preventing catheter-related blood stream infection in newborns but may also have the undesirable effect of promoting the emergence of resistant strains of micro-organisms. To determine the effect of prophylactic antibiotics on mortality and morbidity in neonates with central venous catheters. Searches were done of the Cochrane Neonatal Review Group Specialised Register, MEDLINE from 1950 to April 2007, CINAHL from 1982 to April 2007, and the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 2 2007). Previous reviews (including cross references) were also searched. Randomised controlled trials or quasi-randomised controlled trials of adequate quality in which either individual newborn infants or clusters of infants were randomised to receive prophylactic antibiotics (not including antifungals) versus placebo or no treatment. Infants must have had central venous catheters, been full term infants less than 28 days old or preterm infants up to 44 weeks (postmenstrual) corrected age. Criteria and methods used to assess the methodological quality of the trials: standard methods of the Cochrane Collaboration and its Neonatal Review Group were used. The review authors extracted data independently. Attempts were made to contact study investigators for additional information as required. Three small studies have been included in this review. Prophylactic antibiotics in neonates with central venous catheters had no effect on overall mortality (typical RR 0.68, 95% confidence interval 0.31, 1.51). Prophylactic antibiotics in neonates with central venous catheters decreased the rate of proven bacterial sepsis (typical RR 0.38, 95% confidence interval 0.18, 0.82). Prophylactic antibiotics in neonates with central venous catheters decreased the rate of suspected or proven bacterial septicaemia (typical RR 0.40, 95% confidence interval 0.20, 0.78). No resistant organisms colonising infants were identified in any of the studies. No pooled data were available for other important outcome measures such as chronic lung disease or neurodevelopmental outcome. Prophylactic systemic antibiotics in neonates with a central venous catheter reduces the rate of proven or suspected septicaemia. However, this may not be clinically important in the face of no significant difference in overall mortality and the lack of data on long-term neurodevelopmental outcome. Furthermore, there is a lack of data pertaining to the potentially significant disadvantages of this approach such as the selection of resistant organisms. The routine use of prophylactic antibiotics in infants with central venous catheters in neonatal units cannot currently be recommended.

A Historical Perspective on Pharmacological Studies of Gentamicin for Therapy of Neonatal Meningitis

Address correspondence to: George H. McCracken, Jr., MD, UT Southwestern Medical Center, Dallas, Department of Pediatrics, Division of Infectious Diseases, 5323 Harry Hines Blvd., F3-202, Dallas, TX 75390-9063, email: george.mccracken@utsouthwestern.edu © 2006 Pediatric Pharmacy Advocacy Group ABBREVIATIONS CSF, cerebral spinal fluid; IL-1β, interleukin-1 beta; LPS, lipopolysaccharide; MIC, minimal inhibitory concentration; PPRU, Pediatric Pharmacology Research Unit Much of my early career in Pediatric Infectious Disease was devoted to defining the optimal management of neonatal meningitis caused by Gram negative enteric bacteria. To accomplish this required an understanding of clinical pharmacology of antibiotics in newborn infants, an area rarely explored in the period before the late 1960s when I started my investigative career. Indeed, in 1968 Dr. Harry Shirkey, a pharmacist-turned-pediatrician, lamented the fact that infants and children were often denied use of many drugs because of the lack of data on their pharmacokinetics, safety and efficacy.1 He termed these patients “therapeutic orphans” and encouraged the development of active programs of clinical pharmacology and drug testing in pediatric patients, especially in infants and young children. It was in this setting that I launched my investigations of the clinical pharmacology of antibiotics in newborn and young infants, particularly as they pertained to treatment of bacterial meningitis. Now, 38 years later, I am thrilled to receive the Sumner J. Yaffe Lifetime Achievement Award in Pediatric Pharmacology and Therapeutics from the Pediatric Pharmacy Advocacy Group in recognition of these and other studies that helped to clarify the safe and effective use of antibiotics in infants and children. I am honored to receive this award named for Dr. Yaffe, who was as instrumental as anyone in promoting the critical impor-

Report looks into effects of antibiotic use in infancy on teeth

Report looks into effects of antibiotic use in infancy on teeth

Pregnancy and childbirth‐related factors associated with recurrent antibiotic use in infants

To determine the reasons for the possible overuse of antibiotics by investigating whether family-related medical, behavioural, emotional, and social risk factors during the mother's pregnancy and childbirth are associated with subsequent recurrent antibiotic therapy of infants. Subject selection was based on stratified randomized cluster sampling. A total of 1443 women (91%) and their spouses expecting their first child gave informed consent to participate and 1287 infants were born. The parents of 817/1025 infants (80%) reported the number of courses of antibiotic therapy the child had received at the ages of 9 and 18 mo. The outcome measure was the number of courses of antibiotic therapy (none/1-5/=6) given during the first 18 mo of life. The explanatory variables included family-related factors during the pregnancy and immediately after childbirth. In the final multivariate stepwise analysis, parents' long-term illnesses were associated with recurrent antibiotic medication. Parents with long-term illnesses need special guidance and support from the beginning of the mother's pregnancy in order to minimize the subsequent risk for recurrent antibiotic therapy of their infants. Preventive healthcare workers should be aware of the effects of these factors on parental guidance.

Pregnancy and childbirth-related factors associated with recurrent antibiotic use in infants

Pregnancy and childbirth-related factors associated with recurrent antibiotic use in infants

An oral introduction of intestinal bacteria prevents the development of a long‐term Th2‐skewed immunological memory induced by neonatal antibiotic treatment in mice

Recent epidemiological studies indicate that antibiotic use in infancy may be associated with an increased risk of developing atopy. Our previous work on animals demonstrated that kanamycin use during infancy promotes a shift in the Th1/Th2 balance towards a Th2-dominant immunity. The first purpose of this study is to clarify whether or not the supplementation of intestinal bacteria can reverse such a Th2-skewed response induced by neonatal antibiotic use. The second objective is to elucidate the contribution of genetic factors to antibiotic-induced immune-deviation. BALB/c or C57BL/6 mice at 3 weeks of age were orally administered 600 microg/day of kanamycin sulphate for seven consecutive days. Thereafter, the mice were inoculated with one type of intestinal bacterial species: Enterococcus faecalis, Lactobacillus acidophilus or Bacteroides vulgatus. Blood samples were collected 10 weeks after the cessation of kanamycin treatment, and the effect of the kanamycin treatment on Th1/Th2 balance was evaluated based on in vivo antibody levels. A kanamycin-induced elevation of the serum IgE levels was reversed by the supplementation with Enterococcus faecalis, and to a lesser extent by that with Lactobacillus acidophilus. The IgE/IgG2a ratio in the mice supplemented with Enterococcus faecalis significantly decreased in comparison with that in the kanamycin-treated mice without any bacterial supplementation, while such a ratio was enhanced in the mice inoculated with Bacteroides vulgatus. No antibiotic-induced Th2-skewed response was seen in C57BL/6 mice that are genetically biased towards Th1-dominant immunity. These results suggest that adequate probiotic intervention after antibiotic treatment may improve the intestinal ecosystem, and thereby prevent the Th2-shifted immunity induced by neonatal antibiotic use. In addition, the difference of genetic backgrounds also contributes to such an antibiotic-induced Th2-skewed response.

Antibiotic use during infancy promotes a shift in the TH1/TH2 balance toward TH2-dominant immunity in mice

Background: Recent epidemiologic studies indicate that antibiotic use in infancy may be associated with an increased risk of development of atopy; however, its precise mechanism remains to be elucidated. Objective: The purpose of this study is to clarify whether one such antibiotic, kanamycin, affects the TH1/TH2 balance. Methods: BALB/c mice at 3 and 52 weeks of age were orally administered 600 mg/d kanamycin sulfate for 7 consecutive days. Blood samples were collected on weeks 0, 10, 18, and 26 after the cessation of kanamycin treatment, and the effect of the kanamycin treatment on the TH1/TH2 balance was evaluated on the basis of both the in vivo antibody levels and the in vitro splenocyte cytokine secretion pattern. Results: The administration of kanamycin increased the serum levels of total IgG1 and IgE while decreasing the serum IgG2a levels. Moreover, when spleen cells were stimulated with immobilized anti-CD3 antibody in vitro, such kanamycin treatment enhanced the in vitro IL-4 secretion while reducing the in vitro IFN-γ secretion. The basal IL-12 p70 secretion levels of splenic dendritic cells in the kanamycin-treated mice were lower than those in the control mice, although no significant difference was seen in IL-12 p40 levels between either group of mice. Conclusion: These results suggested that antibiotic use during infancy may indeed quantitatively disturb, qualitatively disturb, or both the intestinal microflora and thereby prevent postnatal TH1 cell maturation, thus resulting in a TH2-polarized immune deviation. (J Allergy Clin Immunol 2001;107:153-9.)