Evidence for short duration of antibiotic treatment for non-severe community acquired pneumonia (CAP) in children - are we there yet? A systematic review of randomised controlled trials.

Context: The ideal duration of antibiotic treatment for childhood community acquired pneumonia (CAP) has not yet been established. Objective: A literature search was conducted to evaluate the efficacy of shorter than 7 days duration of oral antibiotic treatment for childhood non-severe CAP. Data sources: A systematic literature search was performed using the PubMed database. The search was limited to randomised controlled trials (RCTs) conducted between January 1996 and May 2013 in children up to 18 years old. Search terms included pneumonia, treatment, duration, child, children, days, short, respiratory infection and non-severe (nonsevere). Study selection: Only RCTs of oral antibiotic treatment for non-severe CAP in children were included. Data extraction: Independent extraction of articles was done by 3 authors using a preformed questionnaire. Data synthesis: Eight articles meeting the selection criteria were identified: 7 from 2 developing countries (India and Pakistan), and 1 from a developed country (The Netherlands). Studies from developing countries used the World Health Organization clinical criteria for diagnosing CAP, which includes mainly tachypnoea. None of those studies included fever, chest radiography or any laboratory test in their case definition. The Dutch study case definition used laboratory tests and chest radiographies (x-rays) in addition to clinical criteria. Five articles concluded that 3 days of treatment are sufficient for non-severe childhood CAP, 2 articles found 5 days treatment to be sufficient, and one article found no difference between 3 days of amoxicillin treatment and placebo. Conclusions: The efficacy of short duration oral antibiotic treatment for non-severe CAP in children has not been established in developed countries. Current RCTs from developing countries used clinical criteria that may have failed to appropriately identify children with true bacterial pneumonia necessitating antibiotic treatment. More RCTs from developed countries with strict diagnostic criteria are needed to ascertain the efficacy of short duration oral antibiotic treatment for non-severe CAP in children.

Autosomal-recessive hypophosphatemic rickets is associated with an inactivation mutation in the ENPP1 gene.

Human disorders of phosphate (Pi) handling and hypophosphatemic rickets have been shown to result from mutations in PHEX, FGF23, and DMP1, presenting as X-linked recessive, autosomal-dominant, and autosomal-recessive patterns, respectively. We present the identification of an inactivating mutation in the ecto-nucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) gene causing autosomal-recessive hypophosphatemic rickets (ARHR) with phosphaturia by positional cloning. ENPP1 generates inorganic pyrophosphate (PPi), an essential physiologic inhibitor of calcification, and previously described inactivating mutations in this gene were shown to cause aberrant ectopic calcification disorders, whereas no aberrant calcifications were present in our patients. Our surprising result suggests a different pathway involved in the generation of ARHR and possible additional functions for ENPP1.