title: In vitro and in vivo Pharmacodynamics of Colistin and Aztreonam Alone and in Combination against Multidrug-Resistant Pseudomonas aeruginosa.
abstract: BACKGROUND
  Reports of Pseudomonas aeruginosa with high antimicrobial resistance have steadily emerged, threatening the utility of a mainstay in antipseudomonal therapy. This study evaluated the antimicrobial activities of various combination therapies against P. aeruginosa with high antimicrobial resistance, including multidrug-resistant P. aeruginosa (MDRP) using an in vitro and in vivo study.
  
  
  METHODS
  We evaluated 24 combination therapies, including colistin, aztreonam, meropenem, ceftazidime, ciprofloxacin, amikacin, rifampicin, arbekacin and piperacillin against 15 MDRP isolates detected at Aichi Medical University Hospital with the break-point checkerboard method. Based on the results of the in vitro study, we evaluated antimicrobial activity against highly antimicrobial-resistant P. aeruginosa with an in vivo murine thigh infection model.
  
  
  RESULTS
  The combination regimens including colistin and aztreonam showed higher antimicrobial activity against the 15 MDRP isolates. In the in vivo study, the high-dose colistin monotherapy (16 mg/kg every 12 h) achieved greater log10 CFU changes than the normal-dose colistin regimen (8 mg/kg every 12 h) against 5 P. aeruginosa isolates, including 2 MDRP isolates (p < 0.05). Aztreonam monotherapy (400 mg every 8 h) yielded bacterial densities similar to untreated control mice for the MDRP isolate evaluated. The combination therapy with a higher dose of colistin had superior antimicrobial activity against 5 P. aeruginosa with colistin (MIC 0.5 μg/ml) and aztreonam (MIC ≥128 μg/ml) than colistin monotherapy.
  
  
  CONCLUSIONS
  The data suggest that the combination treatment of colistin and aztreonam could be the most useful for treating highly resistant P. aeruginosa with a higher susceptibility to colistin, including MDRP infections.
authors: Department of Clinical Infectious Diseases, Aichi Medical University Hospital, Nagakute, Japan.
authors: Yuka
authors: Y
authors: Yamagishi
authors: Mao
authors: M
authors: Hagihara
authors: Hideo
authors: H
authors: Kato
authors: Jun
authors: J
authors: Hirai
authors: Naoya
authors: N
authors: Nishiyama
authors: Yusuke
authors: Y
authors: Koizumi
authors: Daisuke
authors: D
authors: Sakanashi
authors: Hiroyuki
authors: H
authors: Suematsu
authors: Hazuki
authors: H
authors: Nakai
authors: Hiroshige
authors: H
authors: Mikamo
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage*; D001398:Aztreonam / Q000008:administration & dosage*; D003091:Colistin / Q000008:administration & dosage*; D024901:Drug Resistance, Multiple, Bacterial / Q000187:drug effects* / Q000502:physiology; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D051379:Mice; D008813:Mice, Inbred ICR; D011552:Pseudomonas Infections / Q000188:drug therapy / Q000473:pathology; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000302:isolation & purification / Q000502:physiology
chemical_list: D000900:Anti-Bacterial Agents; D001398:Aztreonam; D003091:Colistin