Antibiotics in Paediatrics: A Boon or a Bane?

Antibiotics play an essential role in antimicrobial therapy. Among all the medications in children, the most commonly prescribed therapy is antibiotics and is currently the indispensable means to cure transmissible diseases. Several categories of antibiotics have been introduced into clinical practice to treat microbial infections. Reducing the unnecessary use of antibiotics is a global need and priority. This article aims to provide better knowledge and understanding of the impact of the early use of antibiotics. This article highlights the proper use of antibiotics in chil-dren, detailing how early and inappropriate use of antibiotics affect the gut microbiome during normal body development and consequently affect the metabolism due to diabetes mellitus, obe-sity, and recurrence of infections, such as UTI. Several new antibiotics in their development stage, newly marketed antibiotics, and some recalled and withdrawn from the market are also briefly discussed in this article. This study will help future researchers in exploring the latest information about antibiotics used in paediatrics.Copyright © 2023 Bentham Science Publishers.

X-Linked Inhibitor of Apoptosis (XIAP) deficiency presenting as hemophagocytic lymphohistiocytosis triggered by drug allergy

X-linked inhibitor of apoptosis (XIAP) deficiency is a primary immunodeficiency associated with recurrent hemophagocytic lymphohistiocytosis (HLH) episodes. The clinical phenotypes of XIAP deficiency vary, ranging from splenomegaly to life-threatening inflammation. We report a case of XIAP deficiency with unusual late-onset HLH presentation likely triggered by a drug allergy. A previously healthy adolescent boy presented to the hospital with fever and rash seven days after starting antibiotics for a neck abscess. Laboratory evaluation demonstrated cytopenias, elevated liver enzymes, and increased inflammatory markers. Initially, antibiotics were discontinued due to concern for drug rash. He continued to deteriorate clinically and became hypotensive. Additional testing revealed decreased NK cell function, as well as elevated ferritin, triglycerides, and soluble IL-2 receptor. SLAM-Associated Protein (SAP) and XIAP evaluation by flow cytometry demonstrated decreased XIAP expression. Subsequently, genetic testing revealed a known pathogenic mutation in BIRC4 (c.421_422del), confirming the diagnosis of XIAP deficiency.Copyright © 2023

Cardiac Magnetic Resonance Imaging for the Diagnosis of Infective Endocarditis in the COVID-19 Era

In the COVID-19 pandemic, to minimize aerosol-generating procedures, cardiac magnetic resonance imaging (CMR) was utilized at our institution as an alternative to transesophageal echocardiography (TEE) for diagnosing infective endocarditis (IE). This retrospective study evaluated the clinical utility of CMR for detecting IE among 14 patients growing typical microorganisms on blood cultures or meeting modified Duke Criteria. Seven cases were treated for IE. In 2 cases, CMR results were notable for possible leaflet vegetations and were clinically meaningful in guiding antibiotic therapy, obtaining further imaging, and/or pursuing surgical intervention. In 2 cases, vegetations were missed on CMR but detected on TEE. In 3 cases, CMR was non-diagnostic, but patients were treated empirically. There was no difference in antibiotic duration or outcomes over 1 year. CMR demonstrated mixed results in diagnosing valvular vegetations and guiding clinical decision-making. Further prospective controlled trials of CMR Vs TEE are warranted. © 2022 Elsevier Inc.

Reduced Antibiotic Duration Defaults in Outpatient Automated Dispensing Cabinets Change Antibiotic Prescribing Habits in a Tertiary VA Healthcare System

Background. Ten percent of adult, outpatient visits result in an antibiotic prescription (Rx). At the start of our intervention, our VA healthcare system consisted of 13 community-based outpatient clinics (CBOCs), 9 of which did not have an onsite pharmacy but utilized automated dispensing cabinets (ADCs) for prepackaged outpatient Rxs. ADC antibiotic orders are generated from electronic medical record (EMR) order sets. The stewardship team shortened the durations of 5 antibiotics in the ADC order sets to make them consistent with current literature and guidelines. We assessed the impact of these changes on antibiotic prescribing habits. Methods. We compared outpatient antibiotic Rx data between 10/1/2018-9/30/2019 (pre-intervention) and 10/1/19-9/30/20 (post-intervention) from 8 CBOCs with ADCs (1 closed during the pandemic). Amoxicillin-clavulanate 875/125mg (AMC), cephalexin 500mg (CPH), levofloxacin 500mg and 750mg (LEV 500 and LEV 750), and sulfamethoxazole-trimethoprim 800/160mg (SXT) prescription durations were all reduced by 3 days. Process metrics included days supplied/1000 prescriptions (DS/1000 Rx), median DS, and ADC utilization rates. We used Mann-Whitney U and correlation statistical analyses to assess differences and associations. Results. The DS/1000 Rx of antibiotics with a default duration change decreased in the post-intervention phase for CBOCs with ADCs (AMC, -25.4%;CPH, -21.1%;LEV 500, -18.9%;LEV 750, -28.0%;SXT, -27.4%). The median DS for these antibiotics all reduced by 3 days in concordance with new ADC prescriptions defaults (AMC, 10 vs 7 days, P< 0.001;CPH, 10 vs 7 days, P< 0.001;LEV 500, 8 vs 5 days, P< 0.001;LEV 750, 8 vs 5 days, P< 0.001;SXT 10 vs 7 days, P< 0.001). Due to COVID-19, 7/8 ADC CBOCs closed for in-person visits from 3/20/20-5/4/20. ADC utilization was inversely proportional to DS/1000 Rx for most antibiotics (R: -0.51 to -0.77) except SXT. Conclusion. EMR-driven reductions in ADC default Rx durations led to a corresponding decrease in overall outpatient antibiotic prescribing. Higher DS/1000 Rx were often associated with lower ADC utilization. Informatics-driven antibiotic interventions may be potential outpatient stewardship tools to increase guideline-concordant prescribing across multisite healthcare systems.

SYNTHESIS OF FUSED PYRIMIDINES DERIVATIVES AND MANNICH BASES AND ASSESS OF THEIR ANTIBACTERIAL ACTIVITY, LASER EFFICACY AND MOLECULAR DOCKING

Fused pyrimidines gain an increasing interest as being a precursor for biologically active new compounds. The fused pyrimidine derivatives (1-5) were prepared by condensation of the 1,8-diamine naphthalene with some medical compounds in the presence of ammonium chloride as a dehydration agent for the water molecule and toluene as a solvent. Mannich base compounds (6-10) were prepared by reacting pyrimidines (1-5) with formaldehyde and 4-methoxyaniline. A microwave method was used in preparing the compounds. The prepared compounds were characterized by physical methods, through melting points and color, as well as by spectroscopic methods such as FT-IR and 1H-NMR. The purity of the prepared compounds was evaluated using TLC. The bioactivity of these compounds was tested against two types of bacteria, i.e. Escherichia coli and Staphylococcus aureus. The results of bioactivity showed an antibacterial activity compared to the standard drugs Cephalexin and Amoxicillin. The stability of selected compounds was evaluated by laser irradiation for (10, 20, 30, 40) seconds, and was found to be stable and did not decompose with a 30 seconds exposure. On the other hand, their color was changed at 40 seconds of exposure. Molecular docking studies were conducted to examine how some of the synthesized compounds bind to the putative target, SARS COV2 RNA-dependent RNA polymerase. The study concluded that some of the prepared compounds showed promising antibacterial and antiviral bioactivities. Further in vitro and in vivo toxicological and pharmacological studies are required to evaluate the possibility of using these compounds as a medicine.