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 7 days) versus longer (10 days 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 3 weeks to 15.5 years, 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.

Shorter versus longer-course of antibiotic therapy for urinary tract infections in pediatric population: an updated meta-analysis.

Urinary tract infections (UTI) affect between 3% to 7.5% of the febrile pediatric population each year, being one of the most common bacterial infections in pediatrics. Nevertheless, there is no consensus in the medical literature regarding the duration of per oral (p.o.) antibiotic therapy for UTI among these patients. Therefore, our meta-analysis aims to assess the most effective therapy length in this scenario. PubMed, Cochrane, and Embase were searched for randomized controlled trials (RCTs) comparing short (≤ 5 days) with long-course (≥ 7 days) per os (p.o.) antibiotic therapy for children with UTI. Statistical analysis was performed using R Studio version 4.2.1, heterogeneity was assessed with I2 statistics, and the risk of bias was evaluated using the RoB-2 tool. Risk Ratios (RR) with p < 0.05 were considered statistically significant. Seventeen studies involving 1666 pediatric patients were included. Of these, 890 patients (53.4%) were randomized to receive short-course therapy. Patients undergoing short-course therapy showed higher treatment failure rates (RR 1.61; 95% CI 1.15-2.27; p = 0.006). Furthermore, there were no statistically significant differences between groups regarding reinfection (RR 0.73; 95% CI 0.47-1.13; p = 0156) and relapse rates (RR 1.47; 95% CI 0.8-2.71; p = 0.270).  Conclusion: In summary, our results suggest that long-course p.o. antibiotic therapy is associated with a lower rate of treatment failure when compared to short-course p.o. antibiotic therapy. There was no statistical difference between both courses regarding reinfection and relapse rates within 15 months.    PROSPERO identifier: CRD42023456745. What is Known: • Urinary tract infections (UTIs) are common in children, affecting around 7.5% of those under 18. • The optimal duration of antibiotic treatment for pediatric UTIs has been a subject of debate. What is New: • Short-course therapy (5 or fewer days) was associated with a significantly higher failure rate when compared to long-course therapy. • There was no significant difference in reinfection and relapse rates within 15 months between short and long-course therapy.

Shorter versus longer duration of Amoxicillin-based treatment for pediatric patients with community-acquired pneumonia: a systematic review and meta-analysis.

Streptococcus pneumoniae is the most common typical bacterial cause of pneumonia among children. The World Health Organization (WHO) recommends a 5-day Amoxicillin-based empiric treatment. However, longer treatments are frequently used. This study aimed to compare shorter and longer Amoxicillin regimens for children with uncomplicated community-acquired pneumonia (CAP). A search of PubMed, EMBASE, and Cochrane Central was conducted to identify randomized controlled trials (RCTs) comparing 5-day and 10-day courses of Amoxicillin for the treatment of CAP in children older than 6 months in an outpatient setting. Studies involving overlapping populations, lower-than-standard antibiotic doses, and hospitalized patients were excluded. The outcome of interest was clinical cure. Statistical analysis was performed using RevMan 5.4. Heterogeneity was assessed using the Cochran Q test and I2 statistics. Two independent authors conducted the critical appraisal of the included studies according to the RoB-2 tool for assessing the risk of bias in randomized trials, and disagreements were resolved by consensus. We used the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) tool to evaluate the certainty of evidence of our results. Three RCTs and 789 children aged from 6 months to 10 years were included, of whom 385 (48.8%) underwent a 5-day regimen. Amoxicillin-based therapy was used in 774 (98%) patients. No differences were found between 5-day and 10-day therapy regarding clinical cure (RR 1.01; 95% CI 0.98-1.05; p = 0.49; I2 = 0%). Subgroup analysis of children aged 6-71 months showed no difference in the rates of the same outcome (RR 1.01; 95% CI 0.98-1.05; p = 0.38; I2 = 0%). The GRADE tool suggested moderate certainty of evidence. CONCLUSION: These findings suggest that a short course of Amoxicillin (5 days) is just as effective as a longer course (10 days) for uncomplicated CAP in children under 10 years old. Nevertheless, generalizations should be made with caution considering the socioeconomic settings of the studies included.PROSPERO Identifier: CRD42022328519. WHAT IS KNOWN: • In the outpatient setting, a few international guidelines recommend a 10-day Amoxicillin course as first-line treatment for community-acquired pneumonia (CAP). • Recent trials have shown that shorter courses of Amoxicillin may be as effective as 10-day regimens in uncomplicated pneumonia. WHAT IS NEW: • When comparing 5-day to 10-day Amoxicillin regimens, evidence suggests no significant difference in clinical cure rates for uncomplicated CAP in outpatient settings. • Generalizations should be made with caution considering the socioeconomic context of the population within the included studies.

Adolescent Hepatitis C: Prevalence, Impact, and Management Challenges.

The prevalence of Hepatitis C virus infection (HCV), a leading cause of chronic liver disease worldwide, is rising in the United States (US) and other high-income countries, especially among youth and young adults. This surge in cases is closely associated with the opioid crisis and intravenous drug use (IVDU). However, its prevalence and impact on the adolescent population have not been thoroughly studied and therefore is poorly understood. The pediatric population tends to have milder liver disease and progression when compared to adults; however, there is a risk of developing liver cirrhosis, in addition to facing decreased quality of life and stigmatization from the disease. The recent approval of direct-acting antiviral (DAA) regimens for all HCV genotypes and age greater than 3 years has revolutionized its management. Therapy has shifted from the prolonged interferon-based regimens, to shorter duration, once daily oral pills that are highly effective, curative and with fewer side effects. Therapy is now indicated for all adolescents with hepatitis C virus infection, regardless of stage of liver disease, recent IVDU, or coinfection with HIV, therefore eliminating a lifetime risk of chronic liver disease, cirrhosis and hepatocarcinoma. Nonetheless, adolescents are rarely tested or treated for hepatitis C infection, and very few adolescents complete therapy. Implementation of point of care (POC) testing of high-risk youth at drug treatment centers or other juvenile facilities may be a good strategy to increase testing, diagnosis and therapy. This review article aims to educate pediatricians and other primary care providers to help decrease the existing knowledge gap on the subject.

Environmental Influences Measured by Epigenetic Clock and Vulnerability Components at Birth Impact Clinical ASD Heterogeneity.

Although Autism Spectrum Disorders (ASD) is recognized as being heavily influenced by genetic factors, the role of epigenetic and environmental factors is still being established. This study aimed to identify ASD vulnerability components based on familial history and intrauterine environmental stress exposure, explore possible vulnerability subgroups, access DNA methylation age acceleration (AA) as a proxy of stress exposure during life, and evaluate the association of ASD vulnerability components and AA to phenotypic severity measures. Principal Component Analysis (PCA) was used to search the vulnerability components from 67 mothers of autistic children. We found that PC1 had a higher correlation with psychosocial stress (maternal stress, maternal education, and social class), and PC2 had a higher correlation with biological factors (psychiatric family history and gestational complications). Comparing the methylome between above and below PC1 average subgroups we found 11,879 statistically significant differentially methylated probes (DMPs, p < 0.05). DMPs CpG sites were enriched in variably methylated regions (VMRs), most showing environmental and genetic influences. Hypermethylated probes presented higher rates in different regulatory regions associated with functional SNPs, indicating that the subgroups may have different affected regulatory regions and their liability to disease explained by common variations. Vulnerability components score moderated by epigenetic clock AA was associated with Vineland Total score (p = 0.0036, adjR2 = 0.31), suggesting risk factors with stress burden can influence ASD phenotype.