title: High-Dose Ampicillin-Sulbactam Combinations Combat Polymyxin-Resistant Acinetobacter baumannii in a Hollow-Fiber Infection Model.
abstract: Acinetobacter baumanniiis emerging with resistance to polymyxins. In 24-h time-kill experiments, high-dose ampicillin-sulbactam in combination with meropenem and polymyxin B achieved additivity or synergy against 108CFU/ml of two clinicalA. baumanniiisolates resistant to all three drugs (maximum reductions, 1.6 and 3.1 logs). In a 14-day hollow-fiber infection model, high-dose ampicillin-sulbactam (8/4 g every 8 h, respectively) in combination with meropenem (2 g every 8 h) and polymyxin B (1.43 mg/kg of body weight every 12 h with loading dose) resulted in rapid (96 h) eradication ofA. baumannii.
authors.affiliation: Laboratory for Antimicrobial Dynamics, NYS Center of Excellence in Bioinformatics & Life Sciences, Buffalo, New York, USA.|School of Pharmacy and Pharmaceutical Sciences, University at Buffalo, New York, USA.|California Northstate University College of Pharmacy, Elk Grove, California, USA.
authors.forename: Justin R
authors.initials: JR
authors.lastname: Lenhard
authors.affiliation: Laboratory for Antimicrobial Dynamics, NYS Center of Excellence in Bioinformatics & Life Sciences, Buffalo, New York, USA.|School of Pharmacy and Pharmaceutical Sciences, University at Buffalo, New York, USA.
authors.forename: Nicholas M
authors.initials: NM
authors.lastname: Smith
authors.affiliation: Laboratory for Antimicrobial Dynamics, NYS Center of Excellence in Bioinformatics & Life Sciences, Buffalo, New York, USA.|School of Pharmacy and Pharmaceutical Sciences, University at Buffalo, New York, USA.
authors.forename: Zackery P
authors.initials: ZP
authors.lastname: Bulman
authors.affiliation: Center for Pharmacometrics and Systems Pharmacology, College of Pharmacy, University of Florida, Orlando, Florida, USA.
authors.forename: Xun
authors.initials: X
authors.lastname: Tao
authors.affiliation: Division of Infectious Diseases and Tropical Medicine, Department of Medicine, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand.
authors.forename: Visanu
authors.initials: V
authors.lastname: Thamlikitkul
authors.affiliation: Catholic University of Daegu, Hayang, South Korea.
authors.forename: Beom S
authors.initials: BS
authors.lastname: Shin
authors.affiliation: Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia.
authors.forename: Roger L
authors.initials: RL
authors.lastname: Nation
authors.affiliation: Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia.
authors.forename: Jian
authors.initials: J
authors.lastname: Li
authors.affiliation: Center for Pharmacometrics and Systems Pharmacology, College of Pharmacy, University of Florida, Orlando, Florida, USA.
authors.forename: Jürgen B
authors.initials: JB
authors.lastname: Bulitta
authors.affiliation: Laboratory for Antimicrobial Dynamics, NYS Center of Excellence in Bioinformatics & Life Sciences, Buffalo, New York, USA btsuji@buffalo.edu.|School of Pharmacy and Pharmaceutical Sciences, University at Buffalo, New York, USA.
authors.forename: Brian T
authors.initials: BT
authors.lastname: Tsuji
mesh_terms: D000151:Acinetobacter Infections / Q000188:drug therapy / Q000382:microbiology; D040981:Acinetobacter baumannii / Q000187:drug effects* / Q000254:growth & development; D000667:Ampicillin / Q000097:blood / Q000493:pharmacokinetics; D000900:Anti-Bacterial Agents / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001682:Biological Availability; D015992:Body Mass Index; D004334:Drug Administration Schedule; D004338:Drug Combinations; D054796:Drug Dosage Calculations; D024901:Drug Resistance, Multiple, Bacterial; D004357:Drug Synergism; D006801:Humans; D000077731:Meropenem; D008826:Microbial Sensitivity Tests; D015233:Models, Statistical; D011112:Polymyxin B / Q000097:blood / Q000493:pharmacokinetics*; D013407:Sulbactam / Q000097:blood / Q000493:pharmacokinetics; D013845:Thienamycins / Q000097:blood / Q000493:pharmacokinetics*
chemical_list: D000900:Anti-Bacterial Agents; D004338:Drug Combinations; D013845:Thienamycins; C035444:sultamicillin; D000667:Ampicillin; D000077731:Meropenem; D011112:Polymyxin B; D013407:Sulbactam
keywords: Acinetobacter; antibiotic resistance; antimicrobial combinations; meropenem; polymyxins; sulbactam; synergism