title: Severity and outcome of HIV-associated Pneumocystis pneumonia containing Pneumocystis jirovecii dihydropteroate synthase gene mutations.
abstract: BACKGROUND
  The impact of Pneumocystis jirovecii (formerly P. carinii) dihydropteroate synthase (DHPS) gene mutations on morbidity and mortality of Pneumocystis pneumonia (PCP) in HIV-positive patients is unclear.
  
  
  OBJECTIVE
  To determine whether severity and outcome of HIV-associated PCP differs according to DHPS genotype.
  
  
  METHODS
  A prospective, observational study in a university-affiliated county hospital.
  
  
  METHODS
  The study included 197 patients with 215 microscopically confirmed PCP episodes and successfully sequenced DHPS genotypes; 175 (81%) episodes displayed mutant genotypes.
  
  
  METHODS
  All-cause mortality within 60 days.
  
  
  RESULTS
  The majority of patients (86%) with PCP containing Pneumocystis DHPS mutations survived. Although severity of PCP was comparable, there was a trend for more patients with mutant genotypes than patients with wild-type to require mechanical ventilation (14.3% versus 2.5%; P = 0.056) and to die (14.3% versus 7.5%, P = 0.31). Independent predictors of mortality at baseline were low serum albumin levels [odds ratio (OR), 4.62; 95% confidence interval (CI), 1.63-13.1; P = 0.004] and requiring intensive care within 72 h of hospitalization (OR, 5.06; 95% CI, 1.43-18.0; P = 0.012).
  
  
  CONCLUSIONS
  The majority of HIV-infected patients with PCP containing mutant Pneumocystis DHPS genotypes survived. Mortality was related primarily to the underlying severity of illness. However, a trend towards increased mortality in episodes of PCP containing mutant DHPS genotypes was observed and this warrants further study.
authors.affiliation: Positive Health Program and Division of Pulmonary and Critical Care Medicine, San Francisco General Hospital, University of California, San Francisco, California, USA. kristina.crothers@yale.edu
authors.forename: Kristina
authors.initials: K
authors.lastname: Crothers
authors.forename: Charles B
authors.initials: CB
authors.lastname: Beard
authors.forename: Joan
authors.initials: J
authors.lastname: Turner
authors.forename: Gena
authors.initials: G
authors.lastname: Groner
authors.forename: Melissa
authors.initials: M
authors.lastname: Fox
authors.forename: Alison
authors.initials: A
authors.lastname: Morris
authors.forename: Shary
authors.initials: S
authors.lastname: Eiser
authors.forename: Laurence
authors.initials: L
authors.lastname: Huang
mesh_terms: D017088:AIDS-Related Opportunistic Infections / Q000401:mortality / Q000821:virology*; D000328:Adult; D004094:Dihydropteroate Synthase / Q000235:genetics*; D005260:Female; D015658:HIV Infections / Q000401:mortality / Q000821:virology; D015497:HIV-1; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009154:Mutation; D016017:Odds Ratio; D045363:Pneumocystis carinii / Q000201:enzymology*; D011020:Pneumonia, Pneumocystis / Q000401:mortality* / Q000821:virology*; D011446:Prospective Studies
chemical_list: D004094:Dihydropteroate Synthase