Journal of Antimicrobial Chemotherapy (2001) 47, 720
© 2001 The British Society for Antimicrobial Chemotherapy
Correspondence |
Pharmacokinetics of antibiotics in burns patients
Public Health Laboratory, Coventry and Warwickshire Hospital, Stoney Stanton Road, Coventry CV1 4FH, UK
Sir,
There are a paucity of data relating to the pharmacokinetics of many antibiotics in burns patients, so it was interesting to read the article by Sampol et al.1 They should be congratulated for undertaking such research. From their study of six patients they conclude that their results ‘demonstrate that it is not necessary to change the standard dosage of cefepime in burns patients’. I would like to suggest that whilst they might be correct, it is yet to be proven.
Burn patients share in common the presence of a burn and the accompanying physiological changes. However, the net effect on drug handling produces a highly heterogeneous population with patients spread over an extremely wide base. Thus, a common theme in many publications is the great variability in individual patient pharmacokinetic parameters.
When studying burns patients this heterogeneity must be taken into account. For example, although it is generally accepted that the dosage requirements for aminoglycosides in this patient group are substantially altered, there have been reports suggesting no difference.2–3 Presumably this relates to the population being sampled. Some burns patients do not require increased aminoglycoside dosage. The key is to encompass a wide range of patients in any study. Thus, in relation to the paper by Sampol et al.1 their sample population is neither sufficient in number or breadth to justify the dosage recommendation. Some burns patients have extremely high creatinine clearance values (in excess of 200 mL/min) but have not been represented in their study.
Small studies like this are nonetheless extremely worthwhile. Other centres need to be encouraged to undertake similar work, so data may then be pooled in an attempt to include large numbers of patients, in order to represent the extremes of drug handling. For this to succeed there needs to be agreement in advance over the various parameters to be measured, patient eligibility and target antibiotic levels. Many previous studies have been flawed for a variety of reasons. This includes measuring antibiotic levels within the first 48 h of injury, a time not only when sepsis is unlikely to occur but also, more importantly, when renal performance is impaired.4
How can a change in the way such studies are conducted be implemented? Ideally a working party should be set up to produce guidance on conducting future pharmacokinetic studies. To be successful their recommendations will need the support of both pharmaceutical companies and relevant medical journals.
It is 25 years since the alteration in aminoglycoside pharmacokinetics was first described. Despite this, there is little to support the current dosage recommendations for many other classes of antibiotic. To ensure the optimum therapy for every burns patient, standardization of pharmacokinetic studies needs to be introduced.
References
1
.
Sampol, E., Jacquet, A., Viggiano, M., Bernini, V., Manelli, J. C., Lacarelle, B. et al. (2000). Plasma, urine and skin pharmacokinetics of cefepime in burns patients. Journal of Antimicrobial Chemotherapy 46, 315–7.
2 . Zaske, D. E., Sawchuk, R. J., Gerding, D. N. & Strate, R. G. (1976). Increased dosage requirements of gentamicin in burns patients. Journal of Trauma 6, 824–8.
3
.
Polk, R. E., Mayhall, G. C., Smith, J., Hall, G., Kline, B. J., Swensson, E. et al. (1983). Gentamicin and tobramycin penetration into burn eschar: pharmacokinetics and microbiological effect. Archives of Surgery 118, 295–302.
4
.
Weinbren, M. J. (1999). Pharmacokinetics of antibiotics in burns patients. Journal of Antimicrobial Chemotherapy 44, 319–27.
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