ANTIMICROBICS AND INFECTIOUS DISEASES NEWSLETTER Editor-in-Chief Charles W. Stratton, Vanderbilt University School of Medicine Nashville, Tennessee Full editorial board appears on back cover Volume 18, Number 5 May 2000 Antibiotic Treatment in Cystic Fibrosis Part 2: Dose Optimization Johan W. Mouton, MD, PhD Medical Microbiologist Canisius Wilhelmina Hospital Ntjmegen, The Netherlands Daniel J. Touw, PharmD, PhD Hospital Pharmacist, Head Clinical Pharmacological and Toxicological Laboratory The Hague Hospitals Central Pharmacy The Hague, The Netherlands Alexander A.T.M.M. Vinks, PharmD, PhD Clinical Pharmacologist & Associate Director Pharmacology Research Centre Cincinnati, OH Alphons M. Horrevorts, MD, PhD Medical Microbiologist Canisius Wilhelmina Hospital Nijmegen, The Netherlands Harry G.M. Heijerman MD, PhD Pulmonary Physician Adult Cystic Fibrosis Centre Leyenburg Hospital The Hague, The Netherlands Address of correspondence: JW Mouton, MD PhD Streeklaboratorium Medische Microbiologic Canisius Wilhelmina Ziekenhuis Nijmegen Weg door Jonkerbos 100 6532 sz Nijmegen, The Netherlands Tel 00-3I-(0)24-3657514 Fax 00-31-(0)24-3657516 Email Mouton@cwz.nl In Part 1 of this paper, which appeared in the previous issue of this newsletter (Volume 18, No. 4), we discussed the clinical pharmacokinetics of antibiotics and the background of antimicrobial therapy in cystic fibrosis. This issue focuses on dosing and dose optimiza- tion in cystic fibrosis. Rationale for Pharmacokinetic Optimization of Antibiotic l’keatment in Cystic Fibrosis As in any treatment, the dosing regimen given to treat a pulmonary exacerbation in cystic fibrosis patients should be optimal: the dose or dosing regimen administered should have maximum efficacy minimum toxicity. In cystic fibrosis patients, two important issues play a role: the susceptibility of the micro-organisms (in particular, F! aeruginosa) causing the infection is relatively low (due to prolonged anti- microbial treatment), and the pharma- cokinetics and/or dosing regimens as discussed in Part 1 may be different for some antibiotics as compared to normal patients, especially if dosed per kg bodyweight. The relatively low sus- ceptibility of the microorganisms implies that relatively high doses are needed to achieve optimal efficacy. The altered pharmacokinetics for some drugs has led to the recognition that therapeutic drug monitoring in this patient group is of specific value. Therapeutic drug monitoring is a relatively young clinical discipline that integrates the determination of drug (serum) levels with the application of pharmacokinetic principles and phar- macodynamics with the purpose of optimizing dosage regimens in patients to improve outcomes. Recently, Ensom et al. discussed the value of therapeutic drug monitoring on patient outcomes. One of their conclusions was that drugs should be dosed individually to achieve predetermined target concentrations dependent on the disease state. Several studies have been performed evaluating the impact of pharmacokinetic optimi- zation, showing improved clinical out- come and positive impact on costs in various patient populations. However, in CF patients, such a study has not yet been performed, mainly because the endpoints of treatment (e.g., Lung func- tion tests, Schwachman score, quality of life score) are not clear. Although all have been used to evaluate therapy, few of the studies performed have the nec- essary power to demonstrate differences in efficacy between various antibiotic regimens. The important issue, however, is that antimicrobial therapy is one of the cornerstones in CF treatment, and that because of the difficulty of treat- ment which increases when the patients get older, therapy should be optimal and guided by using endpoints. In a recent study, it was demonstrated that there was a direct relationship between dosing regimen, susceptibility of p aeruginosa, and efficacy of tobramycin. One of the tools to achieve optimal zyxwvutsrqp In This Issue Antibiotic lkeatment in Cystic Fibrosis, Part 2 . . . . . . . . . . 33 Q-Fever Presenting with Intractable Diarrhea and Fever with Both Responding to Indomethaein . . . . . . . . . . . . . . . 38 Lawrence A. Cone, Saahill Saeed AIIXEX 18(5)33-40,200O 0 2001 Ekvier Science Inc. 1069-417X/00 (see frontmatter) 33