title: Can Pharmacokinetic and Pharmacodynamic Principles Be Applied to the Treatment of Multidrug-Resistant Acinetobacter?
abstract: OBJECTIVE
  To discuss treatment options that can be used for treatment of Acinetobac/erinfections.
  
  
  METHODS
  A MEDLINE search (1966-November 2010) was conducted to identify English-language literature on pharmacotherapy of Acinetobacter and the bibliographies of pertinent articles. Programs and abstracts from infectious diseases meetings were also searched. Search terms included Acinetobacter, multidrug resistance, pharmacokinetics, pharmacodynamics, Monte Carlo simulation, nosocomial pneumonia, carbapenems, polymyxins, sulbactam, aminoglycosides, tetracyclines, tigecycline, rifampin, and fluoroquinolones.
  
  
  METHODS
  All articles were critically evaluated and all pertinent information was included in this review.
  
  
  RESULTS
  Multidrug resistant (MDR) Acinetobacter, defined as resistance to 3 or more antimicrobial classes, has increased over the past decade. The incidence of carbapenem-resistant Acinetobacter is also increasing, leading to an increased use of dose optimization techniques and/or alternative antimicrobials, which is driven by local susceptibility patterns. However, Acinetobacter infections that are resistant to all commercially available antibiotics have been reported. General principles are available to guide dose optimization of aminoglycosides, β-lactams, fluoroquinolones, and tigecycline for infections due to gram-negative pathogens. Unfortunately, data specific to patients with Acinetobacter infections are limited. Recent pharmacokinetic-pharmacodynamic information has shed light on colistin dosing. The dilemma with colistin is its concentration-dependent killing, which makes once-daily dosing seem like an attractive option, but its short postantibiotic effect limits a clinician's ability to extend the dosing interval. Localized delivery of antimicrobials is also an attractive option due to the ability to increase drug concentration at the infection site while minimizing systemic adverse events, but more data are needed regarding this approach.
  
  
  CONCLUSIONS
  Increased reliance on dosage optimization, combination therapy, and localized delivery of antimicrobials are methods to pursue positive clinical outcomes in MDR Acinetobacter infections since novel antimicrobials will not be available for several years. Well-designed clinical trials with MDR Acinetobacter are needed to define the best treatment options for these patients.
authors.affiliation: Travis W Cooper PharmD BCPS, Clinical Pharmacy Specialist, Infectious Disease, Parkland Health & Hospital System; Clinical Assistant Professor, University of Texas Southwestern Medical School, Dallas, Texas.
authors.forename: Travis W
authors.initials: TW
authors.lastname: Cooper
authors.affiliation: Steven E Pass PharmD FCCM FCCP BCPS, Associate Professor, Texas Tech University Health Sciences Center, School of Pharmacy, Dallas.
authors.forename: Steven E
authors.initials: SE
authors.lastname: Pass
authors.affiliation: Sara D Brouse PharmD FCCP BCPS, Associate Professor, Texas Tech University Health Sciences Center, School of Pharmacy.
authors.forename: Sara D
authors.initials: SD
authors.lastname: Brouse
authors.affiliation: Ronald G Hall II PharmD MSCS BCPS, Associate Professor and Program Director, Dose Optimization and Outcomes Research (DOOR) Program, Texas Tech University Health Sciences Center, School of Pharmacy Ronald.hall@ttuhsc.edu.
authors.forename: Ronald G
authors.initials: RG
authors.lastname: Hall
mesh_terms: D000617:Aminoglycosides / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D003428:Cross Infection / Q000188:drug therapy; D024901:Drug Resistance, Multiple, Bacterial; D004359:Drug Therapy, Combination; D024841:Fluoroquinolones / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D011113:Polymyxins / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D013754:Tetracyclines / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D047090:beta-Lactams / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D024841:Fluoroquinolones; D011113:Polymyxins; D013754:Tetracyclines; D047090:beta-Lactams