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| |  Researchers Suggest Adjusting Doses of Antibiotics According to Bodyweight NEW YORK -- January 14, 2010 -- Doses of antibiotics and other antimicrobial agents should take into account the patient’s bodyweight, to maximise their potential effectiveness. The issues are discussed in a viewpoint in this week’s edition of The Lancet. “For most widely used antimicrobial agents, dosing recommendations in adults do not take into account adjustment to body size measures,” said authors Matthew E Falagas, MD, Alfa Institute of Biomedical Sciences, Athens, Greece, and Tufts University School of Medicine, Boston, Massacusetts, and Drosos Karageorgopoulos, MD, Alfa Institute of Biomedical Sciences. “Even when such recommendations are made for an agent, the degree of their application in routine clinical practice can be inadequate.” A hypothetical male patient with community-acquired pneumonia who weighs 90 kg and is 1.90 m tall has a calculated lean body mass twice that of a female patient who weighs 56 kg and is 1.50 m tall, even though they both have a body mass index of 24.9 kg/m˛, within the healthy weight range. However, according to present treatment guidelines, these patients would both receive the same dosage of antibiotics. As well as disparities of this kind, the obesity epidemic means there are many more patients with increased weight worldwide. Available data support the notion that antimicrobial agents, such as several beta-lactams, vancomycin, fluoroquinolones, macrolides, linezolid, sulphonamides, and fluconazole, which are approved as flat dosing regimens, should be given in higher doses to patients with large body size to better attain the drug’s pharmacodynamic targets. Moreover, specific antimicrobial agents have been approved for clinical use at dosages in adults that should be related to bodyweight. These agents are mainly those with a narrow therapeutic window (such as amino-glycosides, daptomycin, colistin, and amphotericin B), as well as agents given at high doses for specific indications (such as cotrimoxazole and metronidazole). “We believe that tailoring the dosing of antimicrobial agents in adults to the physical characteristics of individual patients could be an important way to achieve maximum effectiveness and safety of antimicrobial therapy,” the authors said. “This goal seems more important than ever, considering the increasing proportion of patients seen in clinical practice who have various risk factors for acquisition of infection or impaired immunological mechanisms for response to infection.” With respect to children, they added: “Considerations about appropriate antibiotic dosing for adult patients might also be necessary for children, as the proportion of children who are overweight increases in the general population. Even though a mg/kg antibiotic dosing strategy is routinely used in children, greater attention to pharmacokinetic and pharmacodynamic indices might be required for optimum dosing of some antimicrobial agents in paediatric patients. Careful use of antibiotics in children is also warranted, in view of the high rate of community-acquired infection by resistant pathogens reported in this population.” The authors discuss how doctors’ long-standing attitudes to antimicrobial drug prescribing will need to change in order for bodyweight-related dosing to take effect. Time-consuming and complicated mathematical formulas to work out the correct dose may not sit well with time constraints in general practice. “These difficulties could be overcome, however, with the use of novel technologies such as personal digital assistants or the aid of computerised pharmacy dosing systems... the routine dosing of antibiotics on a mg/kg basis in children suggests that similar strategies cannot be a far-fetched goal for adults,” the authors wrote. “We believe that the one-size-fits-all strategy for prescribing antimicrobial agents to adults is outdated in the era of increasing antimicrobial drug resistance,” they concluded. “The individual body size and composition characteristics of patients could substantially affect pharmacokinetic indices and clinical effectiveness of several antimicrobial agents. Appropriate studies are needed to provide guidance to clinicians on the common clinical question of how to achieve optimum effectiveness and safety of antimicrobial therapy for patients whose physical characteristics deviate from average.”
SOURCE: The Lancet
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