title: Is infection with hypermutable Pseudomonas aeruginosa clinically significant?
abstract: BACKGROUND
  Hypermutable Pseudomonas aeruginosa (HPA) with high mutation rate due to defects in the DNA mismatch repair genes are frequently isolated in the sputum of cystic fibrosis (CF) patients. These isolates tend to be multidrug resistant and may be better adapted to the CF lung environment. However, the clinical significance of this infection has not been determined.
  
  
  METHODS
  This prospective study enrolled patients with PA infection attending CF clinics in Jerusalem between 2010 and 2011. Mutation frequency of pseudomonas isolates was determined by quantification of colonies resistant to rifampicin.
  
  
  RESULTS
  Of the 73 patients enrolled, 22 (30%) were infected with HPA. Average mutation frequency was 2.95×10(-4) in HPA and 1×10(-7) in non-HPA. Pulmonary function tests, number of pulmonary exacerbations and the response to antibiotic therapy were similar between patients infected with HPA and non-HPA isolates. The only predictors for infection with HPA were resistance to multiple antimicrobial categories (OR=4.8, 95% CI: 1.8-12.4) and previous use of inhaled colistin (OR=8.1, 95% CI: 2-30). Resistant mutant subpopulation analysis was a poor screening test for identifying HPA isolates.
  
  
  CONCLUSIONS
  Infection with hypermutable strains represents the marked ability of PA to adapt to the lung environment, but was not associated with worse clinical outcome.
authors.affiliation: Pediatric Department, Shaare-Zedek Medical Center, Jerusalem, Israel.
authors.forename: Adi
authors.initials: A
authors.lastname: Auerbach
authors.affiliation: Pediatric Department, Cystic Fibrosis Center, Hadassah Hebrew University Medical Center, Jerusalem, Israel; Faculty of Medicine, Hebrew University Hadassah Medical School, Jerusalem, Israel.
authors.forename: Eitan
authors.initials: E
authors.lastname: Kerem
authors.affiliation: Microbiology Laboratory, Shaare-Zedek Medical Center, Jerusalem, Israel.
authors.forename: Marc Victor
authors.initials: MV
authors.lastname: Assous
authors.affiliation: Pediatric Department, Shaare-Zedek Medical Center, Jerusalem, Israel; Faculty of Medicine, Hebrew University Hadassah Medical School, Jerusalem, Israel.
authors.forename: Elie
authors.initials: E
authors.lastname: Picard
authors.affiliation: Pediatric Department, Shaare-Zedek Medical Center, Jerusalem, Israel; Faculty of Medicine, Hebrew University Hadassah Medical School, Jerusalem, Israel. Electronic address: mbarmeir@gmail.com.
authors.forename: Maskit
authors.initials: M
authors.lastname: Bar-Meir
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D002908:Chronic Disease; D003550:Cystic Fibrosis / Q000150:complications* / Q000382:microbiology; D004252:DNA Mutational Analysis; D004269:DNA, Bacterial / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007223:Infant; D008168:Lung / Q000382:microbiology*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011446:Prospective Studies; D011552:Pseudomonas Infections / Q000150:complications* / Q000382:microbiology; D011550:Pseudomonas aeruginosa / Q000235:genetics* / Q000302:isolation & purification; D013183:Sputum / Q000382:microbiology; D055815:Young Adult
chemical_list: D004269:DNA, Bacterial
keywords: Cystic fibrosis; Hypermutable; Pseudomonas aeruginosa