Differences in antimicrobial drug exposure in patients with various degrees of renal function based on recommendations from dosing references

STUDY OBJECTIVE: To calculate and compare 24-hour area under the unbound drug concentration-time curves (AUC(0-24)) of antimicrobials with dosing recommendations from six commonly used dosing references. INTERVENTION: Unbound plasma concentration-time profiles of 13 antimicrobial agents (4 penicillins, 3 cephalosporins, 2 carbapenems, aztreonam, 3 fluoroquinolones) were simulated at steady state using a one-compartment open model for a 70-kg adult based on pharmacokinetic parameters obtained from peer-reviewed literature. Simulations were performed at five levels of creatinine clearance (Cl(cr)). MEASUREMENTS AND MAIN RESULTS: Differences in AUC(0-24) for each antimicrobial agent were noted among the six references at each level of Cl(cr) as well as within references across the range of Cl(cr). In addition, up to 16-fold and 3-fold ranges in AUC(0-24) values were observed for beta-lactams and fluoroquinolones, respectively, in one reference based on dosing recommendations at a single level of Cl(cr) (due to more than one dose and/or dosing interval). CONCLUSION: Clinicians should be aware of differences among common references when selecting dosages of antimicrobial agents, especially for patients with moderate-to-severe renal impairment.