title: Colistin hetero-resistance in multidrug-resistant Acinetobacter baumannii clinical isolates from the Western Pacific region in the SENTRY antimicrobial surveillance programme.
abstract: BACKGROUND
  Multidrug-resistant Acinetobacter baumannii has presented a global medical problem. Emergence of colistin resistance, including hetero-resistance, has been increasingly reported. This study examined the susceptibility to colistin of multidrug-resistant A. baumannii from the Western Pacific region.
  
  
  METHODS
  A total of 30 isolates were studied from 10 clinical centres in various countries. MICs were measured against 21 antibiotics by broth microdilution. Colistin population analysis profiles (PAPs) (0, 0.5, 1, 2, 3, 4, 5, 6, 8 and 10mg/L) were determined. Time-kill kinetics of colistin against 3 isolates (2 colistin-susceptible (one of which was colistin hetero-resistant) and 1 colistin-resistant) were studied over a wide range of concentrations and development of resistance was monitored by measurement of colistin PAPs after 24-h exposure.
  
  
  RESULTS
  All the isolates were highly multiresistant. Colistin MICs were 0.5-2mg/L except one isolate which had an MIC of 128mg/L. Seven isolates were colistin hetero-resistant with subpopulations growing at >2mg/L. For the 2 colistin-susceptible isolates examined, >3log killing was observed within 3h even at 0.5x MIC. Interestingly, >3log killing was also observed with the colistin-resistant isolate within 1h even at 0.5mg/L. Regrowth occurred at 24h for both colistin-susceptible and -resistant isolates. Emergence of resistance to colistin after 24-h exposure was confirmed by PAP.
  
  
  CONCLUSIONS
  Colistin was very active against A. baumannii based upon MICs and initial killing in time-kill studies. Hetero-resistance in this group of A. baumannii isolates was less common than in previous studies. Nevertheless, care is required with colistin monotherapy for A. baumannii infections.
authors.affiliation: Facility for Anti-infective Drug Development and Innovation, Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, Victoria, Australia.
authors.forename: Wing
authors.initials: W
authors.lastname: Yau
authors.forename: Roxanne J
authors.initials: RJ
authors.lastname: Owen
authors.forename: Anima
authors.initials: A
authors.lastname: Poudyal
authors.forename: Jan M
authors.initials: JM
authors.lastname: Bell
authors.forename: John D
authors.initials: JD
authors.lastname: Turnidge
authors.forename: Heidi H
authors.initials: HH
authors.lastname: Yu
authors.forename: Roger L
authors.initials: RL
authors.lastname: Nation
authors.forename: Jian
authors.initials: J
authors.lastname: Li
mesh_terms: D000151:Acinetobacter Infections / Q000276:immunology*; D040981:Acinetobacter baumannii / Q000187:drug effects* / Q000302:isolation & purification; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D003091:Colistin / Q000494:pharmacology*; D024901:Drug Resistance, Multiple, Bacterial; D006801:Humans; D008826:Microbial Sensitivity Tests; D050296:Microbial Viability; D014481:United States
chemical_list: D000900:Anti-Bacterial Agents; D003091:Colistin