No abstract

Effective antimicrobial exposure is essential to treat infections and prevent antimicrobial resistance, both being major public health problems in low and middle income countries (LMIC). Delivery of drug concentrations to the target site is governed by dose and pharmacokinetic processes (absorption, distribution, metabolism and excretion). However, specific data on the pharmacokinetics of antimicrobials in children living in LMIC settings are scarce. Additionally, there are significant logistical constraints to therapeutic drug monitoring that further emphasize the importance of understanding pharmacokinetics and dosing in LMIC. Both malnutrition and diarrheal disease reduce the extent of enteral absorption. Multiple antiretrovirals and antimycobacterial agents, commonly used by children in low resource settings, have potential interactions with other antimicrobials. Hypoalbuminemia, which may be the result of malnutrition, nephrotic syndrome or liver failure, increases the unbound concentrations of protein bound drugs that may therefore be eliminated faster. Kidney function develops rapidly during the first years of life and different inflammatory processes commonly augment renal clearance in febrile children, potentially resulting in subtherapeutic drug concentrations if doses are not adapted. Using a narrative review approach, we outline the effects of growth, maturation and comorbidities on maturational and disease specific effects on pharmacokinetics in children in LMIC.

Background: In December 2019, a local outbreak of pneumonia presented in Wuhan (China), and quickly identified to be caused by a novel coronavirus, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). The disease caused by SARS-CoV-2 was named COVID-19 and was soon declared as pandemic because of the millions of infections and thousands of deaths worldwide. Children infected with SARS-CoV-2 usually develop asymptomatic or mild disease compared to adults. They are also more likely to have atypical and non-specific clinical manifestations than adults. Methods: A literature search was performed in PubMed and Scopus to summarize the extrapulmonary manifestations of SARS-CoV-2 infection in children since the beginning of the pandemic. Peer-reviewed papers in English were retrieved using the following keywords and combinations: ‘pediatric’, ‘child’, ‘infant’, ‘neonate’, ‘novel coronavirus’, ‘SARS-CoV-2’, ‘COVID 19’ and ‘gastrointestinal’, ‘renal’, ‘cardiac’, ‘dermatologic’ or ‘ophthalmologic’. We included published case series and case reports providing clinical symptoms and signs in SARS-CoV2 pediatric patients. Results: Although fever and symptoms of upper respiratory infection are the most frequently presented, a variety of other atypical presentations has also been reported. The clinical spectrum includes dermatological, ophthalmological, neurological, cardiovascular, renal, reproductive, and gastrointestinal presentations. In addition, a rare multi-inflammatory syndrome associated with SARS-CoV-2 infection has been reported in children, often leading to shock requiring inotropic support and mechanical ventilation. Conclusions: Clinicians need to be aware of the wider range of extrapulmonary atypical manifestations of SARS-CoV-2 infection in children, so that appropriate testing, treatment, and public health measures can be implemented rapidly.