title: In vitro antibacterial activity of rifampicin in combination with imipenem, meropenem and doripenem against multidrug-resistant clinical isolates of Pseudomonas aeruginosa.
abstract: Multidrug-resistant Pseudomonas aeruginosa has emerged as one of the most important healthcare-associated pathogens. Colistin is regarded as the last-resort antibiotic for multidrug-resistant Gram-negative bacteria, but is associated with high rates of acute kidney injury. The aim of this in vitro study is to search for an alternative treatment to colistin for multidrug-resistant P. aeruginosa infections.
  
  
  
  Multidrug and carbapenem-resistant P. aeruginosa isolates were collected between January 2009 and December 2012 at MacKay Memorial Hospital. Minimal inhibitory concentrations (MICs) were determined for various antibiotic combinations. Carbapenemase-producing genes including bla VIM, other β-lactamase genes and porin mutations were screened by PCR and sequencing. The efficacy of carbapenems (imipenem, meropenem, doripenem) with or without rifampicin was correlated with the type of porin mutation (frameshift mutation, premature stop codon mutation) in multidrug-resistant P. aeruginosa isolates without carbapenemase-producing genes.
  
  
  
  Of the 71 multidrug-resistant clinical P. aeruginosa isolates, only six harboured the bla VIM gene. Imipenem, meropenem and doripenem were significantly more effective (reduced fold-change of MICs) when combined with rifampicin in bla VIM-negative isolates, especially in isolates with porin frameshift mutation.
  
  
  
  Imipenem + rifampicin combination has a low MIC against multidrug-resistant P. aeruginosa, especially in isolates with porin frameshift mutation. The imipenem + rifampicin combination may provide an alternative treatment to colistin for multidrug -resistant P. aeruginosa infections, especially for patients with renal insufficiency.
authors.affiliation: Division of Infectious Diseases, Department of Internal Medicine, MacKay Memorial Hospital, Taipei, Taiwan.|Department of Medical Research, MacKay Memorial Hospital, No. 92, Sec. 2, Zhongshan N. Road, Taipei, Taiwan.
authors.forename: Yi-Fan
authors.initials: YF
authors.lastname: Hu
authors.affiliation: Division of Infectious Diseases, Department of Internal Medicine, MacKay Memorial Hospital, Taipei, Taiwan. joeliu5929@hotmail.com.tw.|Department of Medical Research, MacKay Memorial Hospital, No. 92, Sec. 2, Zhongshan N. Road, Taipei, Taiwan. joeliu5929@hotmail.com.tw.|Department of Medicine, MacKay Medical College, New Taipei City, Taiwan. joeliu5929@hotmail.com.tw.|MacKay College of Medicine, Nursing and Management, Taipei, Taiwan. joeliu5929@hotmail.com.tw.|Infection Control Committee, MacKay Memorial Hospital, Taipei, Taiwan. joeliu5929@hotmail.com.tw.
authors.forename: Chang-Pan
authors.initials: CP
authors.lastname: Liu
authors.affiliation: Department of Medical Research, MacKay Memorial Hospital, No. 92, Sec. 2, Zhongshan N. Road, Taipei, Taiwan.
authors.forename: Nai-Yu
authors.initials: NY
authors.lastname: Wang
authors.affiliation: Department of Medical Research, MacKay Memorial Hospital, No. 92, Sec. 2, Zhongshan N. Road, Taipei, Taiwan. shihshou@gmail.com.|Department of Medicine, MacKay Medical College, New Taipei City, Taiwan. shihshou@gmail.com.|MacKay College of Medicine, Nursing and Management, Taipei, Taiwan. shihshou@gmail.com.|Infection Control Committee, MacKay Memorial Hospital, Taipei, Taiwan. shihshou@gmail.com.|Division of Gastroenterology, Department of Internal Medicine, MacKay Memorial Hospital, Taipei, Taiwan. shihshou@gmail.com.
authors.forename: Shou-Chuan
authors.initials: SC
authors.lastname: Shih
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000235:genetics; D015780:Carbapenems / Q000494:pharmacology; D003091:Colistin / Q000627:therapeutic use; D000077726:Doripenem; D024901:Drug Resistance, Multiple, Bacterial / Q000187:drug effects*; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D015378:Imipenem / Q000494:pharmacology; D008297:Male; D000077731:Meropenem; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D018272:Porins / Q000235:genetics; D011552:Pseudomonas Infections / Q000188:drug therapy / Q000382:microbiology*; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D012293:Rifampin / Q000494:pharmacology; D013624:Taiwan; D013845:Thienamycins / Q000494:pharmacology; D001618:beta-Lactamases / Q000235:genetics
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D015780:Carbapenems; D018272:Porins; D013845:Thienamycins; D015378:Imipenem; D000077726:Doripenem; D001618:beta-Lactamases; C063912:carbapenemase; D000077731:Meropenem; D012293:Rifampin; D003091:Colistin
keywords: Frameshift mutation; Imipenem; Porin mutation; Pseudomonas aeruginosa; Rifampicin