Antibiotic Treatment In Children Research Articles

Outcomes of antibiotic treatment for respiratory infections in children an observational study in primary care

Background Antibiotic resistance is an increasing global threat, accelerated by both misuse and overuse of antibiotics. Most antibiotics to humans are prescribed in primary care, commonly for respiratory symptoms, and there is a need for research on the usage of and outcomes after antibiotic treatment to counteract antibiotic resistance. Objective To evaluate symptom duration, treatment length, and adverse events of antibiotic treatment in children. Design and Setting Observational study at four out-of-hours services and one paediatric emergency clinic in Norwegian emergency primary care. Subjects 266 children aged 0 to 6 years with fever or respiratory symptoms. Main Outcome Measures Duration of symptoms and absenteeism from kindergarten/school, treatment length, and reported adverse events. Results There were no differences in duration of symptoms, fever or absenteeism when comparing the groups prescribed (30.8%) and not prescribed (69.2%) antibiotics. This lack of difference remained when analysing the subgroup with otitis media. In the group prescribed antibiotics, 84.5% of parents reported giving antibiotics for 5-7 days, and 50.7% reported no difficulties. Adverse events of antibiotics were reported in 42.3% of the cases, the vast majority being gastrointestinal disturbances. Conclusion Children with fever or respiratory symptoms experience similar duration of symptoms and absenteeism regardless of antibiotic treatment. A substantial number of parents reported adverse events when the child received antibiotics. Several parents experienced additional difficulties with the treatment, some ending treatment within day 4. Trial Registration Number NCT02496559; Results.

2578. Trends in Pathogens and Antibiotic Treatment in Children with Cystic Fibrosis in 2018 and 2022: A Retrospective Multicenter Study

Abstract Background The new Cystic Fibrosis (CF) transmembrane conductance regulator modulator therapy combination (elexacaftor/tezacaftor/ivacaftor, ETI) has significantly improved the quality of life of children with CF and decreased the rate of pulmonary exacerbations (PEx). The focus of our study was to examine the infection characteristics of PEx in children with CF before the availability of ETI (2018) and following ETI approval and during emergence from COVID-19 (2022). Methods We conducted a multicenter (5 sites) retrospective review collecting data on children with CF over 12-month periods in 2018 and in 2022 who were hospitalized for PEx and treated with IV antibiotics. We analyzed the number of PEx, bacterial and fungal organisms identified by CF respiratory cultures and IV antibiotics used empirically at hospital admission. Results The number of hospitalizations for PEx decreased from 414 in 2018 to 163 in 2022. The most common organisms identified in all centers were Pseudomonas aeruginosa (Pa), Staphylococcus aureus (Sa) and Candida species, with no apparent overall difference in the relative percentages of pathogens isolated between 2018 and 2022 (figure 1), although fewer children were infected with methicillin-resistant S. aureus (MRSA) in 2022 (2.7%) than in 2018 (10%) (p=0.014). There was variability in the type of antipseudomonal agents and antistaphylococcal agents used empirically both within and between the different centers (figure 2). Conclusion Pathogens isolated from respiratory culture associated with PEx demonstrated similar rates of isolation of pathogens in the 2 time periods, consistent with historical CF pathogen isolation. The decreased number of PEx in 2022 compared to 2018 is consistent with the widespread use of ETI. The variability of usage antipseudomonal agents between centers and between years of data collection requires further investigation. Disclosures Andrea Hahn, MD, MS, TGV Dx: Advisor/Consultant Antonio C. Arrieta, MD, FIDSA, FPIDS, Astellas Pharma Global Development, Inc.: Advisor/Consultant|Astellas Pharma Global Development, Inc.: Grant/Research Support|Astellas Pharma Global Development, Inc.: Honoraria|Cumberland Pharmaceutical: Grant/Research Support|IDbyDNA: Advisor/Consultant|IDbyDNA: Grant/Research Support|Melinta: Grant/Research Support|Merck: Advisor/Consultant|Merck: Grant/Research Support|Nabriva: Grant/Research Support|Paratek Pharmaceuticals: Grant/Research Support|Pfizer, Inc: Advisor/Consultant|Pfizer, Inc: Grant/Research Support|Roche/Genentech: Grant/Research Support|The Medicine Company: Grant/Research Support

Shorter versus longer duration of antibiotic treatment in children with bacterial meningitis: a systematic review and meta-analysis.

The optimal duration of antibiotic treatment for the most common bacterial meningitis etiologies in the pediatric population, namely Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningitidis, is not well-established in the literature. Therefore, we aimed to perform an updated meta-analysis comparing shorter versus longer antibiotic treatment in children with meningitis. PubMed, EMBASE, and Cochrane databases were searched for randomized controlled trials (RCTs) that compared shorter (up to 7days) versus longer (10days or double the days of the equivalent short course) duration of antibiotic treatment in children with meningitis and reported the outcomes of treatment failure, death, neurologic sequelae, non-neurologic complications, hearing impairment, nosocomial infection, and relapse. Heterogeneity was examined with I2 statistics. RevMan 5.4.1 was used for statistical analysis and RoB-2 (Cochrane) for risk of bias assessment. Of 684 search results, 6 RCTs were included, with a cohort of 1333 children ages 3weeks to 15.5years, of whom 49.51% underwent a short antibiotic course. All RCTs included monotherapy with ceftriaxone, except one, which added vancomycin as well. No differences were found comparing the short and long duration of therapy concerning treatment failure, relapse, mortality, and neurologic complications at discharge and at follow-up. Conclusion: Because no statistically significant differences were found between groups for the analyzed outcomes, the results of this meta-analysis support shorter therapy. However, generalizing these results to complicated meningitis and infections caused by other pathogens should be made with caution.(PROSPERO identifier:CRD42022369843). What is Known: • Current recommendations on the duration of antibiotic therapy for bacterial meningitis are mostly based on clinical practice. • Defining an optimal duration of antibiotic therapy is essential for antimicrobial stewardship achievement, improving patient outcomes, and minimizing adverse effects. What is New: • There are no differences between shorter versus longer antibiotic treatment duration in regard to treatment failure, relapse, mortality, neurologic complications, and hearing impairment at discharge and at follow-up.

Biomarker-guided duration of antibiotic treatment in children hospitalised with confirmed or suspected bacterial infection: statistical analysis plan for the BATCH trial and PRECISE sub-study

IntroductionThe BATCH trial is a multi-centre randomised controlled trial to compare procalcitonin-guided management of severe bacterial infection in children with current management. PRECISE is a mechanistic sub-study embedded into the BATCH trial. This paper describes the statistical analysis plan for the BATCH trial and PRECISE sub-study.MethodsThe BATCH trial will assess the effectiveness of an additional procalcitonin test in children (aged 72 h to 18 years) hospitalised with suspected or confirmed bacterial infection to guide antimicrobial prescribing decisions. Participants will be enrolled in the trial from randomisation until day 28 follow-up. The co-primary outcomes are duration of intravenous antibiotic use and a composite safety outcome. Target sample size is 1942 patients, based on detecting a 1-day reduction in intravenous antibiotic use (90% power, two-sided) and on a non-inferiority margin of 5% risk difference in the composite safety outcome (90% power, one-sided), while allowing for up to 10% loss to follow-up.ResultsBaseline characteristics will be summarised overall, by trial arm, and by whether patients were recruited before or after the pause in recruitment due to the COVID-19 pandemic. In the primary analysis, duration of intravenous antibiotic use will be tested for superiority using Cox regression, and the composite safety outcome will be tested for non-inferiority using logistic regression. The intervention will be judged successful if it reduces the duration of intravenous antibiotic use without compromising safety. Secondary analyses will include sensitivity analyses, pre-specified subgroup analyses, and analysis of secondary outcomes. Two sub-studies, including PRECISE, involve additional pre-specified subgroup analyses. All analyses will be adjusted for the balancing factors used in the randomisation, namely centre and patient age.ConclusionWe describe the statistical analysis plan for the BATCH trial and PRECISE sub-study, including definitions of clinical outcomes, reporting guidelines, statistical principles, and analysis methods. The trial uses a design with co-primary superiority and non-inferiority endpoints. The analysis plan has been written prior to the completion of follow-up.Trial registrationBATCH: ISRCTN11369832, registered 20 September 2017, doi.org/10.1186/ISRCTN11369832.PRECISE: ISRCTN14945050, registered 17 December 2020, doi.org/10.1186/ISRCTN14945050.

Evaluating the utility of routine urine culture and antibiotic treatment in children with neurogenic bladder undergoing intradetrusor OnabotulinumtoxinA injection

OnabotulinumtoxinA is used as treatment for refractory idiopathic and neurogenic detrusor overactivity in children. Many patients perform intermittent self-catheterization and therefore have higher rates of asymptomatic bacteriuria, which may increase their risk of symptomatic urinary tract infection (UTI) following treatment. Multiple injections are often needed due to the short-term efficacy of onabotulinumtoxinA treatment, which may also increase the risk of UTI. We aim to evaluate whether a sterile urinary tract is necessary to decrease the risk of postoperative UTI in pediatric patients treated with onabotulinumtoxinA. A retrospective review of patients undergoing intradetrusor onabotulinumtoxinA injection from 2014 to 2021 was performed. Demographic data, clinical characteristics, antibiotic treatment and culture results were collected. A positive urine culture was defined as ≥ 103CFU/ml of uropathogenic bacteria. Our primary outcome was symptomatic UTI within 14 days of the procedure. 103 patients underwent 158 treatments with onabotulinumtoxinA. The incidence of postoperative UTI was 3.2%. The incidence of symptomatic postoperative UTI in patients with asymptomatic bacteriuria compared to those with sterile urine was not significantly different (3.8% vs 0%, p=0.57). Obtaining a preoperative urinalysis or urine culture did not affect the incidence of postoperative UTI (p=0.54). The number needed to treat with antibiotics to prevent one postoperative UTI was 27. The incidence of postoperative UTI was highest in patients with low-risk bladders (p=0.043). Prior history of multi-drug resistant UTI was a risk factor for postoperative UTI (p=0.048). For children undergoing onabotulinumtoxinA injection, there are no evidence-based recommendations regarding antibiotic prophylaxis and the need to screen for and treat asymptomatic bacteruria prior to treatment. Our study addresses this important clinical question, and shows no difference in the rate of postoperative UTI between patients with asymptomatic bacteriuria and those with sterile urine. Patients with a history of multi-drug resistant UTI are at increased risk of symptomatic postoperative UTI and may benefit from preoperative urine testing and treatment. Limitations of our retrospective study include its small sample size in the face of such a low incidence of our primary outcome. The risk of UTI following onabotulinumtoxinA injection in children is low. The presence of sterile urine at the time of surgery does not significantly decrease the risk of postoperative UTI. Routine treatment of asymptomatic bacteriuria prior to surgery results in a large number of patients receiving unnecessary antibiotics. As a result, we recommend against preoperative urine testing for most asymptomatic patients.

1309. Adherence to Short-Term Antibiotic Therapy in Children – a Blinded, Prospective, Electronically-Monitored Study

Abstract Background Non-adherence to short-term antibiotic treatment in children can lead to treatment failure and development of drug resistance. To develop effective interventional programs reliable adherence data is needed, but previous studies are scarce and have mostly used parental self-reports. We aimed to determine true adherence rates of pediatric patients treated for acute infections with antibiotic suspensions. Secondary goals were to evaluate patient and treatment characteristics influencing adherence rates and whether the prescriber can predict adherence rates of patients. Methods A prospective, blinded, electronically monitored, observational study. Patients aged 2 months to 5 years diagnosed with an acute bacterial infection requiring short (5-10 days) oral antibiotic monotherapy were enrolled. Parents were told they received a new "childproof" cap for evaluation, but unknowingly were provided with an electronically monitored medication bottle recording every manipulation of the cap. At the end of treatment study purpose was disclosed and, if approved, cap data and patient and treatment information collected. Results 100 infants (49 boys, mean [range] age 1.87 years [0.2-5.1]) were included in the final analysis. Only 11 participants received all the recommended doses. Overall adherence (defined as administration of >75% of prescribed doses) was 62%, while timing adherence (administration of >75% of doses within ±20% of the prescribed interval) was only 21%. After applying a logistic regression model, the only factor significantly associated with non-adherence was being a single parent [OR=5.7 95%CI (1.07-30.3)]. Prescribers overestimated adherence, defining 49/62 (77.7%) participants as likely adherent. Patient/parent pairs that were predicted to be adherent were not more likely to be overall or timing adherent than those predicted to be non-adherent (31/47 vs. 6/16, p=0.77). Conclusion Adherence of children to short-term antimicrobial treatment for an acute infection is suboptimal, with only 62% showing good adherence and 21% with good adherence at proper timing intervals. Providers were unable to predict patient adherence. This data is important when considering recommended treatment durations and developing interventional programs to increase adherence. Disclosures All Authors: No reported disclosures.

488. Association between the Respiratory Microbiota and Response to Antibiotic Therapy in Children with Macrolide-resistant Mycoplasma pneumoniae Pneumonia

Abstract Background Along with the overuse of macrolides as the empirical treatment for M. pneumoniae infection, macrolide-resistant M. pneumoniae (MRMP) emerged up to 90 prevalence rate in Asian countries. We investigated whether respiratory microbiota at the beginning of hospitalization was associated with disease severity and response to antibiotic treatment in children with MRMP pneumonia. Methods Prospectively enrolled children aged < 18 years with community-acquired pneumonia caused by MRMP from 2017/4-2020/3 at Linkou Chang Gung Memorial Hospital. Oropharyngeal samplings were collected within 48 hours after admission. Total 66 children were included: 23 had not received macrolide or gave response to macrolide (defined as without effective treatment group); 43 needed doxycycline treatment (defined as doxycycline treatment group). Compared the oropharyngeal microbiota between groups using the 16S-rRNA-based sequencing. Patients who were administered antibiotics other than augmentin or Azithromax were excluded. The difference in microbial composition will be examined using microbial community analysis. Statistically significant species for each group were evaluated by the linear discriminant analysis of effect size analysis to identify differentially abundant biomarkers, comparing disease severity scores, CRP and febrile days lasting. Scheme of sample collection and analyses Augmentin with or without Azithromax was the most common antimicrobial agent used. If fever persisted under the impression of suspected MRMP infection, doxycycline was used following three days of Azithromax usage. Scheme of sample collection and analyses Correlation between microbiome and clinical feature. Results Doxycycline treatment group had longer duration of total febrile days (p< 0.001) and total hospitalization days (p=0.002). Without effective treatment group had higher microbial richness, different overall community composition (p< 0.01). The lowest respiratory alpha diversity had prolonged febrile days (p=0.032). Without effective treatment group had more abundant spices or genera. Classification of samples to detect patients with effective treatment or not based on these selected microbiota genera features achieved the ROC curve of 0.86. From the list of most relatively abundant species in MRMP patient without doxycycline, Fusobacterium periodonticum most negatively correlated with total febrile days and severity score. Clinical characteristics of patients enrolled in this study Data were shown as n (%) or mean ± standard deviation. N/A, not applicable. Taxonomic assignment of the all throat swab samples. Fraction of predominant microbiota with a relative abundance of at least 2% at the order level (A) and genus level (B) in all sample. Higher respiratory microbial diversity is associated with MRMP patients without effective treatment than MRMP patients who needed doxycycline treatment Microbial richness base on the different alpha-diversity index in MRMP patients without effective treatment (blue); MRMP patients with doxycycline treatment (red). (A)(B)The box represented the interquartile range (IQR, and the midline represented the median. Tukey’s honest significance test of ANOVA, p<0.05.) (C)Kaplan-Meier (KM) plot of febrile time by respiratory diversity. (D)Principal coordinates analysis (PCoA) for MRMP patients without effective treatment (blue), MRMP patients with doxycycline treatment (red) by Unweighted UniFrac distance. Significant differences were observed between MRMP patients without effective treatment and MRMP patients with doxycycline treatment. A PERMANOVA (α=0.05) with 999 random permutations, p = 0.001. Conclusion Respiratory dysbiosis was associated with persistent fever and disease severity in MRMP pneumonia. In our study, F. periodoticum negatively related to fever duration and disease severity. Compositional differences in the respiratory microbiome are associated with MRMP patients without effective treatment than MRMP patients who needed doxycycline treatment by LEfSE analysis LDA scores revealed differentially abundant bacteria in the respiratory microbiome of without effective treatment (blue) and doxycycline treatment (red) groups at genus level (A) and species level (B).The mean relative abundance of genera at right side. The mean relative abundance of genera at right side. (C) Receiver operating characteristic (ROC) curves of ASVs to predict MRMP patients without effective treatment or who needed doxycycline treatment. Pairwise Spearman rank correlation heat map of significantly different taxa in throat swabs at initial sampling and clinical severity score in MRMP patients without effective treatment/with doxycycline treatment The genus (A) and species (B) level. Genus and species were in rows; the correlation was indicated by color gradient. Disclosures All Authors: No reported disclosures.

Outcomes of Single-Dose Empirical Antibiotic Treatment in Children With Suspected Sepsis Implemented in the Emergency Department.

ObjectivesImplementing a single-dose empirical antibiotic (SDEA) strategy at the emergency department (ED) in children with suspected sepsis may improve outcomes. We aim to evaluate the outcomes of the SDEA strategy for children with suspected sepsis at the ED in a tertiary care center in Bangkok.MethodsChildren who met the predefined checklist screening criteria for suspected sepsis were administered single-dose intravenous cefotaxime 100 mg/kg, or meropenem 40 mg/kg if they were immunocompromised or recently hospitalized. The medical records of children diagnosed with sepsis and septic shock caused by bacterial or organ-associated bacterial infections before and after implementation of the SDEA strategy were reviewed.ResultsA total of 126 children with sepsis before and 127 after implementation of the SDEA strategy were included in the analysis. The time from hospital arrival to antibiotic initiation was significantly reduced after implementation of the SDEA strategy: median, 241 (110–363) minutes before versus 89 (62–132) minutes after (P < 0.001), with an increased number of patients starting antibiotics within 3 hours of hospital arrival: 42.1% vs 85.0% (P < 0.001). Comparing before and after SDEA implementation, children receiving SDEA had a shorter median duration of antibiotic therapy: 7 (5–13.3) versus 5 (3–7) days (P = 0.001), shorter length of hospital stay: 10 (6–16.3) versus 7 (4–11) days (P = 0.001), and fewer intensive care unit admissions: 30 (23.8%) versus 17 (13.4%; P = 0.036); however, mortality was not different: 3 (2.4%) in both groups. In multivariate analysis, SDEA strategy was the independent factor associated with reduced intensive care unit admission or death. Adherence to SDEA was 91.4%. Single-dose empirical antibiotic was retrospectively considered not necessary for 22 children (11.9%), mostly diagnosed with viral infections afterward.ConclusionsSingle-dose empirical antibiotic at the ED is an effective strategy to reduce the time from hospital arrival to antibiotic initiation and can help improve outcomes of sepsis in children.

Effectiveness of antibiotic treatment in children with Lyme neuroborreliosis - a retrospective study.

BackgroundLyme neuroborreliosis (LNB) is a tick-borne infection caused by the spirochete Borrelia burgdorferi sensu lato complex with various neurological manifestations. The recommended treatment for LNB in Swedish children has been intravenous ceftriaxone 50–100 mg/kg × 1 (< 8 years of age) or oral doxycycline 4 mg/kg × 1 (≥ 8 years of age) for 10–14 days. Studies on adult LNB patients have shown equal efficacy for ceftriaxone and doxycycline, but no such studies have been conducted on pediatric LNB patients. The aim of this study is to retrospectively evaluate clinical outcome in children with LNB who have received intravenous ceftriaxone or oral doxycycline.ResultsClinical and laboratory data from three previously conducted prospective studies on children with LNB (1998–2014) were retrospectively analyzed. A total of 321 children (1–19 years of age), who received antibiotic treatment for definite LNB or possible LNB, were included. Clinical outcome at the 2-month follow-up (recovery/non-recovery) was evaluated using Chi2 test and logistic multivariate regression analysis. Out of 321 LNB patients, 194 children (60%) had received ceftriaxone and 127 children (40%) had received doxycycline. When comparing clinical outcome between treatment groups, no difference was found (p = 0,217). Results did not change when incorporating relevant clinical and laboratory data into the logistic multivariate regression analysis.ConclusionIn this large retrospective study, no difference in clinical outcome was found, independent of age, when comparing children who received ceftriaxone with those who received doxycycline, supporting an equal effectiveness for treatment of LNB pediatric patients. However, future randomized comparative treatment studies are warranted for evaluation of efficacy of antibiotic treatment in pediatric LNB patients.

Implications of Broad Spectrum Antibiotic Treatment in Children with Acute Upper Respiratory Tract infection. A Clinical Study

Aims and objectives: The aims and objectives of current study were to identify the proper spectrum of different broad spectrum antibiotics in children for acute upper respiratory infections. Methodology: Total 200 children patients with acute upper respiratory tract infections like acute sinusitis, acute bronchitis, pharyngitis, otitis media, laryngitis, and tracheitis were reported. Different antibiotics such as quinolones, amoxicillin, co-amoxiclav, azithromycin and clarithromycin were prescribed. Results: All individual reported their medical conditions and predominate symptoms were fever, cough, sore throat and wheezing. Broad spectrum antibiotics were prescribed to the all children patients regarding to their culture sensitivity test. These agents, Amoxicillin, Clamoxin, third generation Cephalosporin, Ciprofloxacin, Levofloxacin, Cefixime were given to all children according to their sensitivity spectrum. Conclusion: More incidences of acute upper respiratory infections with empyema being caused by bacteria have been documented. Microorganisms S. pneumonia and H. influenza were found in a large number of samples.

Biomarker-guided duration of Antibiotic Treatment in Children Hospitalised with confirmed or suspected bacterial infection (BATCH): protocol for a randomised controlled trial

IntroductionProcalcitonin (PCT) is a biomarker more specific for bacterial infection and responds quicker than other commonly used biomarkers such as C reactive protein, but is not routinely used in the...

Rapid Increase of Oral Bacteria in Nasopharyngeal Microbiota After Antibiotic Treatment in Children With Invasive Pneumococcal Disease.

IntroductionAntibiotics are commonly prescribed to young children for treating bacterial infections such as invasive pneumococcal disease (IPD) caused by Streptococcus pneumoniae. Despite the obvious benefits of antibiotics, little is known about their possible side effects on children’s nasopharyngeal microbiota. In other ecological niches, antibiotics have been described to perturb the balanced microbiota with short- and long-term effects on children’s health. The present study aims to evaluate and compare the nasopharyngeal microbiota of children with IPD and different degree of antibiotic exposure.MethodsWe investigated differences in nasopharyngeal microbiota of two groups of children <18 years with IPD: children not exposed to antibiotics before sample collection (n=27) compared to children previously exposed (n=54). Epidemiological/clinical data were collected from subjects, and microbiota was characterized by Illumina sequencing of V3-V4 amplicons of the 16S rRNA gene.ResultsMain epidemiological/clinical factors were similar across groups. Antibiotic-exposed patients were treated during a median of 4 days (IQR: 3–6) with at least one beta-lactam (100.0%). Higher bacterial richness and diversity were found in the group exposed to antibiotics. Different streptococcal amplicon sequence variants (ASVs) were differentially abundant across groups: antibiotic use was associated to lower relative abundances of Streptococcus ASV2 and Streptococcus ASV11 (phylogenetically close to S. pneumoniae), and higher relative abundances of Streptococcus ASV3 and Streptococcus ASV12 (phylogenetically close to viridans group streptococci). ASVs assigned to typical bacteria from the oral cavity, including Veillonella, Alloprevotella, Porphyromonas, Granulicatella, or Capnocytophaga, were associated to the antibiotic-exposed group. Common nosocomial genera such as Staphylococcus, Acinetobacter, and Pseudomonas were also enriched in the group exposed to antibiotics.ConclusionOur results point toward a reduction of S. pneumoniae abundance on the nasopharynx of children with IPD after antibiotic treatment and a short-term repopulation of this altered niche by oral and nosocomial bacteria. Future research studies will have to evaluate the clinical implications of these findings and if these populations would benefit from the probiotic/prebiotic administration or even from the improvement on oral hygiene practices frequently neglected among hospitalized children.

Changes in Antibiotic Treatment for Children With Lyme Meningitis 2015-2020.

Although ceftriaxone has been the first-line treatment of Lyme meningitis, the 2020 Infectious Disease Society of America, American College of Rheumatology, and American Academy of Neurology guideline recommends either doxycycline or ceftriaxone. Our objective was to explore recent trends in enteral antibiotic treatment of children with Lyme meningitis. Using International Classification of Diseases, 10th Revision codes for case identification, we performed a multicenter retrospective study of patients ≤21 years of age presenting to a pediatric hospital contributing to the Pediatric Health Information System who were diagnosed with Lyme meningitis from 2015 to 2020. Our primary outcome was treatment with parenteral antibiotics, defined by either a procedure code for indwelling catheter placement or >7 days of inpatient parenteral Lyme disease-specific therapy. To examine trends over the study period, we used a generalized estimating equation, with parenteral antibiotics as the dependent variable and study year as the independent variable, adjusted for patient age, sex, race, ethnicity, and insurance status clustered by hospital. We identified 239 patients with Lyme meningitis treated at 24 participating centers. Overall, 48 (20.0%) were treated with parenteral antibiotics, with a declining rate over the study period (43.8% in 2015 to 8.9% in 2020). After adjustment, the odds of treatment with a parenteral antibiotic decreased over the study period (adjusted odds ratio 0.57; 95% confidence interval 0.41-0.80). Parenteral antibiotic treatment of children with Lyme meningitis has been on the decline in advance of the published clinical guideline. Carefully designed comparative effectiveness studies are needed to examine the effect of oral versus parenteral treatment regimens on clinical outcomes.

Reasonable application of antibiotics in pediatric acute rhinosinusitis

The incidence of upper respiratory tract infection in children is extremely high, and some of them are prone to develop to acute rhinosinusitis. Antibiotics are the first-line medication to alleviate bacterial infections. However, due to the lack of practical and accurate objective indicators for the diagnosis of acute rhinosinusitis, it is difficult to distinguish the acute bacterial rhinosinusitis subgroup, leading to the overuse of antibiotics. In recent years, the form of antibiotic resistance has become more severe, and the application conditions of antibiotics have become more stringent. In addition, the physiological conditions of children are different from adults. Chinese and foreign studies are controversial about the rational application of antibiotics in children with acute rhinosinusitis. The relevant researches of antibiotic treatment in children with acute rhinosinusitis are now reviewed, with a view to providing clinical reference for the rational use of antibiotics in this group of people.

Tanzanian primary healthcare workers\u2019 experiences of antibiotic prescription and understanding of antibiotic resistance in common childhood infections: a qualitative phenomenographic study

BackgroundAntibiotic resistance is a threat to global child health. Primary healthcare workers play a key role in antibiotic stewardship in the community, but few studies in low-income countries have described their experiences of initiating antibiotic treatment in children. Thus, the present study aimed to describe primary healthcare workers’ experiences of antibiotic prescription for children under 5 years of age and their conceptions of antibiotic resistance in Northern Tanzania.MethodsA qualitative study involving individual in-depth interviews with 20 prescribing primary healthcare workers in Moshi urban and rural districts, Northern Tanzania, was performed in 2019. Interviews were transcribed verbatim, translated from Kiswahili into English and analysed according to the phenomenographic approach.FindingsFour conceptual themes emerged during the analysis; conceptions in relation to the prescriber, the mother and child, other healthcare actors and in relation to outcome. The healthcare workers relied mainly on clinical examination and medical history provided by the mother to determine the need for antibiotics. Confidence in giving advice concerning non-antibiotic treatment varied among the participants and expectations of antibiotic treatment were perceived to be common among the mothers. Antibiotic resistance was mainly perceived as a problem for the individual patient who was misusing the antibiotics.ConclusionsTo increase rational antibiotic prescription, an awareness needs to be raised among Tanzanian primary healthcare workers of the threat of antibiotic resistance, not only to a few individuals, but to public health. Guidelines on childhood illnesses should be updated with advice concerning symptomatic treatment when antibiotics are not necessary, to support rational prescribing practices and promote trust in the clinician and mother relationship.

Duration of amoxicillin-clavulanate for protracted bacterial bronchitis in children (DACS): a multi-centre, double blind, randomised controlled trial

Protracted bacterial bronchitis (PBB) is a leading cause of chronic wet cough in children. The current standard treatment in European and American guidelines is 2 weeks of antibiotics, but the optimal duration of therapy is unknown. We describe the first randomised controlled trial to assess the duration of antibiotic treatment in children with chronic wet cough and suspected PBB. We hypothesise that 4 weeks of amoxicillin-clavulanate is superior to 2 weeks for improving clinical outcomes. Our parallel, double-blind, placebo-controlled, randomised controlled trial was completed in four Australian hospitals. Children aged 2 months to 19 years with chronic (>4 weeks duration) wet cough, and suspected PBB were randomly assigned (1:1) using permuted block randomisation (stratified by age and site) to 4 weeks of amoxicillin-clavulanate (25-35 mg/kg twice daily oral suspension; 4-week group) or 2 weeks of amoxicillin-clavulanate followed by 2 weeks of placebo (2-week group). The children, caregivers, all the study coordinators, and investigators were masked to treatment assignment until data analysis was completed. The primary outcome was clinical cure (cough resolution) by day 28. Secondary outcomes were recurrence of PBB at 6 months, time to next exacerbation, change in Parent-proxy Cough-Specific Quality-of-Life (PC-QoL) score from baseline to day 28 and from day 28 to 7 months, adverse events, nasal swab bacteriology, and antimicrobial resistance. Analyses followed the intention-to-treat principle. This trial is complete and registered with Australian/New Zealand Registry, ACTRN12616001725459. Between March 8, 2017, and Sept 30, 2019, 106 children were randomly assigned (52 in the 4-week group, median age 2·2 years [IQR 1·3-4·1]; 54 in the 2-week group, median age 1·7 years [1·2-3·8]) with 90 children completing the 4-week treatment. By day 28, the primary endpoint of clinical cure in the 4-week group (32 [62%] of 52 patients) was not significantly different to the 2-week group (38 [70%] of 54 patients; adjusted relative risk 0·87 [95% CI 0·60 to 1·28]; p=0·49). Time to next wet cough exacerbation was significantly longer in the 4-week group than the 2-week group (median 150 days [IQR 38-181] vs 36 days [15-181]; adjusted hazard ratio 0·47 [0·25 to 0·90]; p=0·02). The rate of recurrence of PBB at 6 months was 17 (53%) of 32 patients in the 4-week group vs 28 (74%) of 38 patients in the 2-week group, but the difference between the groups was not significant (adjusted odds ratio 0·39 [0·14 to 1·04]; p=0·07). PC-QoL significantly improved from baseline to day 28 in both groups, but there was no significant difference between them (mean difference in change -0·2 [95% CI -1·0 to 0·6]; p=0·64). From day 28 to 7 months, median PC-QoL remained stable in both groups with no difference in change between them. Data on respiratory pathogens and antimicrobial resistance (paired swabs available for 48 children) were similar between groups. Adverse events occurred in 13 (25%) children in the 2-week group and ten (19%) in the 4-week group (p=0·57). A 4-week course of amoxicillin-clavulanate for treating children with chronic wet cough and suspected PBB confers little advantage compared with a 2-week course in achieving clinical cure by 28 days. However, as a 4-week duration led to a longer cough-free period, identifying children who would benefit from a longer antibiotic course is a priority. Queensland Children's Hospital Foundation.

Dynamic Changes in Microbiome Composition Following Mare's Milk Intake for Prevention of Collateral Antibiotic Effect.

IntroductionProbiotics and prebiotics are widely used for recovery of the human gut microbiome after antibiotic treatment. High antibiotic usage is especially common in children with developing microbiome. We hypothesized that dry Mare’s milk, which is rich in biologically active substances without containing live bacteria, could be used as a prebiotic in promoting microbial diversity following antibiotic treatment in children. The present pilot study aims to determine the impacts of dry Mare’s milk on the diversity of gut bacterial communities when administered during antibiotic treatment and throughout the subsequent recovery phase.MethodsSix children aged 4 to 5 years and diagnosed with bilateral bronchopneumonia were prescribed cephalosporin antibiotics. During the 60 days of the study, three children consumed dry Mare’s milk whereas the other three did not. Fecal samples were collected daily during antibiotic therapy and every 5 days after antibiotic therapy. Total DNA was isolated and taxonomic composition of gut microbiota was analyzed by 16S rRNA amplicon sequencing. To assess the immune status of the gut, stool samples were analyzed by bead-based multiplex assays.ResultsMare’s milk treatment seems to prevent the bloom of Mollicutes, while preventing the loss of Coriobacteriales. Immunological analysis of the stool reveals an effect of Mare’s milk on local immune parameters under the present conditions.

The effect of nebulized antibiotics in children with tracheostomy

IntroductionChildren with tracheostomy have an increased risk of bacterial colonization and infection of the lower respiratory tracts. This study aimed to investigate the effects of nebulized antibiotics on the bacterial load, the need for oral antibiotics, the number of hospitalizations, and the length of stay in the intensive care unit in tracheotomised children with persistent colonization. MethodsChildren with tracheostomy and persistent bacterial colonization who were started on nebulized antibiotic therapy after a lower respiratory tract infection were included in the study. Nebulized gentamicin or colistin were used according to the results of the tracheal aspirate cultures. Demographic and clinic characteristics were recorded from one year prior until one year after initiation of nebulized antibiotic treatment. ResultsNebulized antibiotic treatment was initiated in 22 patients. Nebulized gentamicin was administered to 14 patients (63.6%) and colistin to 8 patients (36.4%). The median duration of treatment was 3 months (range 2–5 months). Following nebulized antibiotic treatment, median number of hospitalizations decreased from 2 (range 1.0–3.5) to 1 (range 0.0–1.5) (p = 0.04). The median length of stay in the intensive care unit reduced significantly from 89.5 days (range 43.0–82.5) to 25 days (range 7.75–62.75) after starting nebulized antibiotics (p = 0.028). Following nebulized antibiotic treatment median bacterial colony count also decreased (from 105 CFU/ml (range 105-106) to 6 × 104 CFU/ml (range 104-105); p = 0.003). There were no significant side effects during nebulized antibiotic therapy. ConclusionsThe use of nebulized antibiotics reduced the number of hospitalizations, length of stay in the intensive care unit, and bacterial load in tracheotomised children with persistent airway colonization without significant side effects. The use of nebulized antibiotics showed a statistically significant decrease in the measures studied. Use of nebulized antibiotics may help to decrease the health care burden of these children, families and health care system. Further studies are needed to determine the indications and optimal duration of long-term nebulized antibiotic treatment in children with tracheostomy.

Antimicrobial Resistance and Molecular Analysis of Staphylococcus aureus in Staphylococcal Scalded Skin Syndrome among Children in Korea.

BackgroundStaphylococcal scalded skin syndrome (SSSS) is a skin disease characterized by blistering and desquamation caused by exfoliative toxins (ETs) of Staphylococcus aureus (S. aureus). Although many countries show predominance of methicillin-susceptible S. aureus (MSSA), cases of methicillin-resistant S. aureus (MRSA) have been reported.MethodsTwenty-six children aged <15 years diagnosed with SSSS from January 2010 to December 2017 from three hospitals were included. S. aureus isolates from cases were analyzed for multilocus sequence types and ETs. Medical records were reviewed for clinical characteristics, treatment, and antimicrobial susceptibility patterns of S. aureus.ResultsAmong the 26 cases, mean age was 2.3 years. According to skin manifestations patients were classified as generalized (n = 10, 38.5%), intermediate (n = 11, 42.3%), and abortive (n = 5, 19.2%). Among all cases, 96.2% (25/26) were due to MRSA and the macrolide-resistance rate was 92.3% (24/26). ST89 (n = 21, 80.8%) was the most prevalent clone, followed by single clones of ST1, ST5, ST72, ST121, and ST1507. The eta gene was detected in one (3.8%) isolate which was MSSA. The etb gene was detected in 14 (53.8%) isolates, all of which were ST89. Nafcillin or first-generation cephalosporin was most commonly prescribed (n=20, 76.9%). Vancomycin was administered in four patients (15.4%) and clindamycin in nine patients (34.6%). Among MRSA cases, there was no difference in duration of treatment when comparing the use of antimicrobials to which the causative bacteria were susceptible or non-susceptible (9.75 vs. 8.07 days, P > 0.05).ConclusionS. aureus isolated from children with SSSS in Korea demonstrated a high prevalence of methicillin-resistant ST89 clones that harbored the etb gene. The predominance of MRSA suggests that antibiotics to which MRSA are susceptible may be considered for empirical antibiotic treatment in children with SSSS in Korea. Further studies on the role and effectiveness of systemic antibiotics in SSSS are warranted.

1357. Urinary Symptom Management in Children with Neuropathic Bladder Presenting to the Emergency Department

BackgroundChildren with neuropathic bladders are at high risk for developing urinary tract infections (UTIs). The accurate diagnosis of UTI is complicated by altered sensation and the ubiquity of bacterial colonization. As a result, overdiagnosis and overtreatment for presumed UTIs is common. The objective of this study is to estimate potential overdiagnosis and unnecessary antibiotic treatment in children with neuropathic bladder presenting to the Emergency Department (ED) with urinary symptoms.MethodsRetrospective cohort study of patients with neuropathic bladder presenting to the Children’s National Hospital ED between October 2008 and December 2019. Chart review was used to determine presenting symptoms, urinary evaluation, and antibiotic treatment. We used the validated urinary symptoms questionnaire (USQNB-IC) to categorize ED visits as ‘evaluation warranted’ if the patient presented with at least one of the actionable symptoms on the USQNB-IC. We used the Spina Bifida Association’s (SBA) published definitions for UTI to determine which patients warranted presumptive antibiotic treatment.ResultsThere were 211 visits by 82 patients (43% female), with a mean of 4.6 visits per patient (IQR 6). Mean age at ED visit was 5.2 years (SD 4.2 years). The most common presenting symptoms were fever (57%), emesis (32%), abdominal pain (24%), foul-smelling urine (11%), and cloudy urine (8%). Of the total visits, 122 (58%) had a urinary evaluation and 31% were treated with antibiotics. Sixteen ED visits (8%) resulted in a urinary evaluation that was not warranted. Of the 122 ED visits with urinary evaluation, 32 patients (26%) did not meet SBA criteria for UTI but were treated empirically with antibiotics.Table 1: Urinary evaluation in children with neuropathic bladder seen in CNH ED between October 2008 and December 2019. Table 2: UTI treatment in children with neuropathic bladder seen in CNH ED between October 2008 and December 2019. ConclusionMost children with neuropathic bladder presenting to the ED were appropriately evaluated and treated for presumed UTI. One-quarter of evaluated children received empiric antibiotics despite not meeting SBA criteria for UTI, indicating this may be a target for educational initiatives to promote antibiotic stewardship. Further research is needed to generate and validate clinical guidelines for emergency department providers to limit unnecessary testing and antibiotic therapy in this population.Disclosures All Authors: No reported disclosures