Pharmacokinetics of beta-lactam antibiotics in patients with intra-abdominal disease: a structured review.

Background and Purpose: The objective of this structured review was to analyze critically the findings of pharmacokinetic studies of beta-lactam antibiotics in patients with intra-abdominal disease; that is, intra-abdominal infection (IAI) or previous abdominal surgery and determine the requirements for dosage modification in this population. Methods: Data were identified by structured review of PUBMED from February 1983 to February 2011. All 1.4 articles reviewed described the pharmacokinetics of beta-lactam antibiotics in patients with intra-abdominal disease. Results: Antibiotic classes included carbapenems, penicillins, cephalosporins, and monobactams. Possible physiological changes in these patients include development of abscesses, perforation, or ischemia of the bowel as well as intra-abdominal hypertension. These disorders may cause changes in antibiotic pharmacokinetics, including increased volume of distribution and faster drug clearance, both resulting in lower antibiotic concentrations. High inter-individual pharmacokinetic variability was common to each of the studies. Conclusion: Most of the available data demonstrate that drug volume of distribution can be increased significantly in the presence of intra-abdominal disease. Drug clearance is likely to vary in line with renal or hepatic function. Thus, dose optimization is important to prevent development of antibiotic resistance or therapeutic failure. However, further research is necessary to determine the clinical outcome of individualized dosing on the basis of pharmacokinetic/pharmacodynamic studies.