Antibacterial Resistance Leadership Group ARLG

This study proposes to examine the pharmacokinetics (PK) of intravenous minocycline (Minocin®, for injection) in critically-ill patients with gram-negative infections in the Intensive Care Unit. Minocycline for injection was initially approved by the US FDA in the 1970s for a variety of infections, including those due to Acinetobacter spp. A new improved formulation that allows infusion using a smaller fluid volume that was recently approved by the US FDA. Minocycline has excellent activity against multi-drug resistant Acinetobacter baumannii complex, a growing world-wide problem, and has a known safety profile; however, there are little PK data in critically-ill patients. The study design will be a single dose PK study in approximately 50 ICU subjects who are receiving antimicrobial therapy for a gram-negative infection. Each patient would have ~4 blood sampled at varying time points over a 48 hr period following the single dose, The data would be analyzed using a population pharmacokinetic approach where drug and patient factors would be incorporated to identify factors associated with minocycline clearance. The objectives are: • To develop a population PK model for minocycline in critically-ill ICU patients with gram negative infections; • Assess patient and drug factors associated with minocycline pharmacokinetic properties in patients; • Provide dosage recommendations and adjustment, where needed, based on identifiable patient factors.