Penicillin: Dosage with a Retro-Look

3. February 2012
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Penicillin has for over 50 years been the most important antibiotic that is used on children. Every year, British children receive six million prescriptions of antibiotics for the treatment of bacterial infections, 4½ million of which being oral penicillins. Whether the dose however is high enough, according to researchers from King’s College London and University of London, is questionable, since dosage recommendations from the British National Formulatory for Children (BNFC) are based primarily on age groups, which largely ignore developments in body weight over recent decades.

Baby = one eighth of an adult?

Such is the declaration stated on a product from 2011 for Amoxil suspension for children under 40 kg body weight: 40 to 90 mg per kilogram per day for all indications. Other recommendations, for instance for amoxicillin and penicillin V, are based on age classes, whereby some additional weight-based recommendation indications exist. Frequently, the doses employed for children revolve around the motto: a big child corresponds to a half-adult, a small child corresponds to half a large child, and a baby is half a small child.

In order to understand the origin of current dosage recommendations, Paul Young and Mike Sharland examined the literature, on behalf of the Children’s Antibiotic Prescribing Research Network (iCAP), including historical archives belonging to the British Medical Association. Dosage recommendations among age classes were first proposed in the 1950s and are based on dosage studies. The references considered in it were the figures for average weight within each of the age classes. From 1963 onward, all antibiotics prescribed to children are supposed to have been dosed according to these age classes.
However, growth and weight have changed greatly since the development of these recommendations. While in 1963 the average weight for five year olds amounted to 18 kg, and for ten year olds 30 kg, the figures today are 21kg and 37 kilograms respectively. Children today show an average 20 percent higher body weight, according to a study in England from 2009. Underdoses are often the result.

Antibiotics error sources: From dosage to compliance

While adjustment processes are regularly undertaken for adult doses of penicillin, a review of recommendations for children remains overdue. There are for Germans as well some special problems in the prescription and dosing of oral antibiotics to children. Standardisations are not comparable with those of adults. Not only are antibiotics not approved for the treatment of children, but information on dosages of, for example penicillins or cephalosporins, are often only given in daily doses per milligram of body weight, where the specified range is often large.

The dosage has to be individually adjusted to the disease and its severity, current recommendations should be taken into account. Two to three daily intakes is often an option provided, which can mean a difference in efficacy, because the drug concentration in tissue is then differentiated. The frequency of administration also affects patient compliance. Additional sources of error exist where parents have to mix the antibiotic before it is ready to use.

In order to prevent the development of antibacterial resistance, not only are adjustments to the dosages of antibiotics by weight and individual factors in children necessary, but with adults as well dose adjustments are also lacking, say Greek scientists. Accordingly, current practice all too often lags well behind the findings from the area of molecular biology and the possibility of a therapy tailored to the patient.

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PD.Dr. Martin Dittmann
PD.Dr. Martin Dittmann

correct

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