title: Combination therapy for carbapenem-resistant Gram-negative bacteria.
abstract: The emergence of resistant to carbapenems Gram-negative bacteria (CR GNB) has severely challenged antimicrobial therapy. Many CR GNB isolates are only susceptible to polymyxins; however, therapy with polymyxins and other potentially active antibiotics presents some drawbacks, which have discouraged their use in monotherapy. In this context, along with strong pre-clinical evidence of benefit in combining antimicrobials against CR GNB, the clinical use of combination therapy has been raised as an interesting strategy to overcome these potential limitations of a single agent. Polymyxins, tigecycline and even carbapenems are usually the cornerstone agents in combination schemes. Optimization of the probability to attain the pharmacokinetic/pharmacodynamic targets by both cornerstone drug and adjuvant drug is of paramount importance to achieve better clinical and microbiological outcomes. Clinical evidence of the major drugs utilized in combination schemes and how they should be prescribed considering pharmacokinetic/pharmacodynamic characteristics against CR GNB will be reviewed in this article.
authors.affiliation: Infectious Diseases Service, Hospital de Clínicas de Porto Alegre, 2350 Ramiro Barcelos St, Porto Alegre, 90.035-903, Brazil.
authors.forename: Alexandre P
authors.initials: AP
authors.lastname: Zavascki
authors.forename: Jurgen B
authors.initials: JB
authors.lastname: Bulitta
authors.forename: Cornelia B
authors.initials: CB
authors.lastname: Landersdorfer
mesh_terms: D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D015780:Carbapenems / Q000493:pharmacokinetics / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D054796:Drug Dosage Calculations; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D006090:Gram-Negative Bacteria / Q000187:drug effects / Q000502:physiology; D016905:Gram-Negative Bacterial Infections / Q000188:drug therapy* / Q000382:microbiology; D006801:Humans; D008911:Minocycline / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D011113:Polymyxins / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000078304:Tigecycline; D018440:beta-Lactam Resistance / Q000502:physiology
chemical_list: D000900:Anti-Bacterial Agents; D015780:Carbapenems; D011113:Polymyxins; D000078304:Tigecycline; D008911:Minocycline