28^th International Conference on Clinical Pediatrics April 15-16, 2020 London, UK

Fazal-e-Rabi Subhani is currently working as a Pedestrian at The Rotunda Hospital in Rotunda, Dublin, Ireland. He has done various publications and research works in the fields of infection.

Introduction: Vibrio cholerae is a highly diverse species. Whereas almost all cholera-causing strains fall in the serogroups O1 & O139, outbreaks of potentially fatal ‘cholera-like illnesses’ have been reported in estuarine environments in multiple parts of the world with lesser known non-O1/non-O139 serogroups. Phylogenetic studies suggest that all cholera-associated strains tend to cluster closely together in keeping with the concept that the outbreak of an epidemic illness requires the presence of an ‘epidemic genotype’ that comprises of multiple genes coming from a host of serogroups. Non-O1/non-O139 serogroups have been associated with gastroenteritis (either caused by faecal contamination of food & water, or eating raw or undercooked shellfish) and wound infections (caused by environmental exposure to contaminated water). Gastroenteritis/wound infection in turn can lead to septicaemia almost exclusively in immunocompromised patients or in patients with severe underlying liver disease. Method: A comprehensive search of PubMed & EMBASE from their inceptions to October 2019 was made using 3 search items: non-O1/non-O139 Vibrio cholerae, cholera outbreaks, & heat wave-associated vibriosis. The search items were combined using the Boolean operator. A further search was made of the United States Centres for Disease Control & Prevention (CDC) website, & ClinicalTrials.gov with no language restriction. Results: Mild gastroenteritis in immunocompetent patients often requires nothing more than fluid resuscitation (oral or intravenous depending upon the need). In severe diarrhoeal illnesses, however, empirical antibiotic therapy with doxycycline is known to reduce the duration of the illness & is therefore recommended pending susceptibility testing results. Alternatives include macrolides & fluoroquinolones. Wound infections even when mild require both debridement & empirical antibiotic therapy with tetracycline or macrolide for 5-7 days. Immunocompromised patients or those with severe underlying liver disease are at risk of developing septicaemia therefore mandating admission to intensive-care unit (ICU) & aggressive combination antibiotic therapy with either minocycline or doxycycline (100 mg orally twice daily), plus a third-generation cephalosporin (either cefotaxime 2 g IV 8 hourly or ceftriaxone 1 g ID once daily) for 1-2 weeks (or even longer) depending upon the response. Conclusion: In immunocompetent patients, diarrhoeal illness is often mild & self-limiting. Likewise, wound infections generally respond well to debridement & oral antibiotic therapy in immunocompetent patients. Immunocompromised patients or those with severe underlying liver disease, however, are at most risk of death and therefore require aggressive treatment in ICU settings. Given increasing rates of resistance to antibiotics, susceptibility testing should be performed to rationalize antibiotic selection in all cases. In resource-rich settings, non-O1/non-O139 Vibrio cholerae infections can be prevented by avoiding consumption of raw or undercooked shellfish. In resource-limited settings especially in the coastal areas, prevention will require avoidance of environmental exposure to contaminated water & cross-contamination of food by seafood. References: 1. Haley BJ, Choi SY, Grim CJ, et al. Genomic and phenotypic characterization of Vibrio cholerae non-O1 isolates from a US Gulf Coast cholera outbreak. PLoS One 2014; 9:e86264. 2. Crowe SJ, Newton AE, Gould LH, et al. Vibriosis, not cholera: toxigenic Vibrio cholerae non-O1, non-O139 infections in the United States, 1984-2014. Epidemiol Infect 2016; 144:3335. 3. Aydanian A, Tang L, Chen Y, et al. Genetic relatedness of selected clinical and environmental non-O1/O139 Vibrio cholerae. Int J Infect Dis 2015; 37:152. 4. Baker-Austin C, Trinanes JA, Salmenlinna S, et al. Heat Wave-Associated Vibriosis, Sweden and Finland, 2014. Emerg Infect Dis 2016; 22:1216.

Fazal-e-Rabi Subhani is currently working as a Pedestrian at The Rotunda Hospital in Rotunda, Dublin, Ireland. His main works are into the field of pediatrics and he has published many articles for the same.

Hemodynamically significant patent ductus arteriosus (PDA) in preterm infants is known to be associated with greater mortality and substantial morbidity in the form of pulmonary oedema/haemorrhage, bronchopulmonary dysplasia (BPD) and potential end-organ ischaemic injury. Considerable practice variability exists regarding different PDA management approaches from supportive care alone to pharmacological closure to surgical ligation. Method: A comprehensive search of PubMed & EMBASE from their inceptions to October 2019 was made using 3 search items: patent ductus arteriosus, preterm infants, & management approaches. The search items were combined using the Boolean operator. A further search was made of the Cochrane Central Register of Controlled Trials, & ClinicalTrials.gov with no language restriction. Results: Literature review suggests that the most appropriate management approach is a step-wise strategy beginning with supportive care provided to all preterm infants including a neutral thermal environment, moderate fluid restriction (110-130 mL/kg/day) & adequate respiratory support (target SpO2 90-95%, PaCO2 55-65 mmHg, pH 7.3-7.4, & haematocrit above 35%). The next step is pharmacological closure attempted in infants who remain ventilator-dependent after one week. It is done in the form a course of non-selective COX inhibitors therapy (indomethacin, ibuprofen), or paracetamol. Latter is generally considered if COX inhibitor therapy is considered contraindicated (untreated infection, NEC, active bleeding, thrombocytopenia, significant renal impairment, concomitant congenital heart disease like pulmonary atresia, severe tetralogy of Fallot, severe coarctation of aorta). An echocardiogram is performed 1-2 days after completion of drug course. If it shows PDA closure, a positive response to therapy is confirmed. Unfortunately, a significant proportion of infants fail to respond to the initial course as evidenced by visualization of persistent PDA on follow-up echocardiogram & infants remaining ventilator-dependent. Limited date suggests that a second course of COX inhibitor is associated with 40% rate of ductal closure in such instances. Infants who fail to respond to even the second course & remain ventilator-dependent on maximum settings are unlikely to respond to drug treatment & therefore no further medical therapy is considered appropriate in such instances. Although rarely necessary in real life, surgical ligation should be considered in these cases. Conclusion: Head-to-head comparison of different drugs used to attempt pharmacological closure of PDA (indomethacin, ibuprofen, & paracetamol) is particularly tricky due to variations of criteria used to define hemodynamically significant PDA and multiple treatment protocols used with variations in dosing & route of administration (enteral vs IV bolus vs IV continuous) across different studies. A recent meta-analysis however concluded that high-dose oral ibuprofen was the most efficacious regimen for pharmacological closure of PDA. Because surgical ligation has become increasingly uncommon & published data is observational, it remains uncertain whether infants who fail pharmacological closure are more severely compromised to begin with, or in fact surgical intervention contributes to increased morbidity & mortality seen in such cases. References: 1. Mitra S, Florez ID, Tamayo ME, et al. Association of Placebo, Indomethacin, Ibuprofen, and Acetaminophen With Closure of Hemodynamically Significant Patent Ductus Arteriosus in Preterm Infants: A Systematic Review and Meta-analysis. JAMA 2018; 319:1221. 2. Dang D, Wang D, Zhang C, et al. Comparison of oral paracetamol versus ibuprofen in premature infants with patent ductus arteriosus: a randomized controlled trial. PLoS One 2013; 8:e77888. 3. Ohlsson A, Walia R, Shah SS. Ibuprofen for the treatment of patent ductus arteriosus in preterm or low birth weight (or both) infants. Cochrane Database Syst Rev 2015; :CD003481. 4. Terrin G, Conte F, Oncel MY, et al. Paracetamol for the treatment of patent ductus arteriosus in preterm neonates: a systematic review and meta-analysis. Arch Dis Child Fetal Neonatal Ed 2016; 101:F127.