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To the editor:
We have read with great interest the investigation by Ivanovska et al in which they compared the antibiotic formulations included on the WHO Essencial Medicines List for Children (EMLc) versus four pertinent International Formularies (-1- ). As a result, they identified nine clinically relevant additional formulations on the comparator lists which were not listed on the WHO EMLc.
We would like to mention another relevant formulation of great interest, which was not studied by the authors as it was not included on the lists they selected for the comparison study.
They found only one vancomycin formulation on the WHO EMLc (250mg powder for injection) and two additional formulations on the comparator lists (125mg and 250mg oral capsules). Neither the WHO EMLc nor the comparator lists had any reference about oral liquid formulations of vancomycin; they are commercially available only in a few countries. However, they are necessary to simplify and facilitate the proper oral administration of the drug to infants and young children to treat Clostridium Difficile (CD) Infection (CDI) disease in accordance with therapeutic guidelines.
CD has become the most common cause of health care-associated infections in US hospitals (-2- ). Since the discovery of CDI there has been an alarming increase in the incidence, severity, recurrence rate of the disease and mortality. The emergence of an epidemic hypervirulent strain of toxin –producing CD in r...
CD has become the most common cause of health care-associated infections in US hospitals (-2- ). Since the discovery of CDI there has been an alarming increase in the incidence, severity, recurrence rate of the disease and mortality. The emergence of an epidemic hypervirulent strain of toxin –producing CD in recent years is a matter of major concern due to it has been described as causing more severe disease. The US CDC estimated that almost half a million CD infections occurred in USA in 2011 and that they were associated with death in 29.000 patients that year (-2- ). In Europe, 175.000 cases were estimated in the same year (-3- ).
CDI is less common in children than in adults, but it is increasing (-4- ). According to international recommendations (-5- ) (-6- ), metronidazole is the initial recommended therapy for mild and moderate cases. For severe – severe complicated cases and recurrent episodes vancomycin is the drug of choice: 40mg/Kg/day divided in four doses (10mg/kg/dose). The use of oral metronidazole in severe CDI or life-threatening disease is strongly discouraged (-6- ). Fidaxomicin is a novel alternative antibiotic used for CDI treatment in adults (-7 - ).
Although oral vancomycin (in capsules) has potential contradictions with WHO rules, vancomycin is the recommended and preferred agent for severe disease and recurrent episodes, and it is the only drug approved by US FDA for CDI treatment in children (-5 - ).
In most countries there are no pharmaceutical products available on the market with oral liquid formulations to administer low amounts of vancomycin to infants (e.g. 55mg, 70mg) so every time we need to start a treatment we have to use compounded formulations usually prepared by the hospital pharmacy for each patient; or nurses have to obtain each dose by taking the intravenous injectable vial as a basis, from the dilution and fractionation of the existing injectable medicines for adults (500 mg/vial or 1000 mg/vial).
The WHO EMLc and International Formularies are used as a Model List by national Health Authorities for the selection and procurement of medicines, and they are especially taken into account in low and middle income countries to improve the availability of medicines.
Vancomycin oral liquid formulations (e.g. powder for oral liquid) simplify the dosing of low amounts of the drug, reduce medication errors and decrease the waste of medicines. They should be considered for evaluation to be listed, or somehow mentioned, on the WHO EMLc and International Formularies. These references will have an important influence to promote public (or private) pharmaceutical production, especially in low and middle income countries, with low cost, so that suitable formulations for infants and young children may be available to treat the severe and sometimes life threatening CDI cases.
Last month, on March 29th, the WHO launched a Global Initiative to reduce avoidable medication-associated harm in all countries by 50% over the next 5 years (- 8 - ).
A greater availability of age –appropriate formulations for neonates, infants and young children in all countries will help to achieve the goal globally.
Jorge Pisapia - Matías Lucero - Leonardo Giunta.
Clínica y Maternidad Suizo Argentina.
Department of Pharmacy.
SWISS MEDICAL GROUP. Buenos Aires. Argentina.
1 – Ivanovska V., Leufkens HG., Rademaker CMA. et al. Are age-appropriate antibiotic formulations missing from the WHO list of essential medicines for children? A comparison study. Arch Dis Child 2017; 102:352-356.
2 – Lessa FC., Mu Y., Bamberg WM., et al. Burden of Clostridium difficile infection in the United States. N Engl J Med 2015; 372(9):
3. - European Hospital and Healthcare Federation - HOPE (2013). Clostridium difficile infection in Europe - A CDI Europe Report. United Kingdom. https://www.doki.net/tarsasag/infektologia/upload/infektologia/document/... [05apr2017]
4. - Nylund CM., Goudie A., Garza JM. et al. Clostridium difficile Infection in hospitalized children in the United States. Arch Pediatr Adolesc Med 2011; 165(5):451-457.
5. - Schutze GE., Willoughby RE. Committee on Infectious Diseases. American Academy of Pediatrics. Clostridium difficile Infection in Infants and Children. Pediatrics 2013; 131(1):196-200.
6. - Debast SB., Bauer MP., Kuijper EJ. et al. European Society of Clinical Microbiology and Infectious Diseases (ESCMID): update of the treatment guidance document for Clostridium difficile infection (CDI). Clin Microbiol Infect 2014; 20 (Suppl 2):1-26.
7. European Medicines Agency EMA (Sept. /2016). Product information Dificlir- INN Fidaxomicin. United Kingdom. http://www.ema.europa.eu/docs/es_ES/document_library/EPAR_-_Product_Info...
8. – World Health Organization. WHO (29 march 2017). WHO launches global effort to halve medication-related errors in 5 years. Geneva/Bonn. http://www.who.int/mediacentre/news/releases/2017/medication-related-err... [05apr2017]