title: Quantifying the clinical virulence of Klebsiella pneumoniae producing carbapenemase Klebsiella pneumoniae with a Galleria mellonella model and a pilot study to translate to patient outcomes.
abstract: BACKGROUND
  Previous studies may have overestimated morbidity and mortality due to Klebsiella pneumoniae producing carbapenemase (KPC) Klebsiella pneumoniae infections because of difficulties in modeling patient comorbidities. This pilot study sought to evaluate KPC virulence by combining clinical and Galleria mellonella models in patients with K. pneumoniae blood stream infections (BSIs).
  
  
  METHODS
  G. mellonella were inoculated using KPC(+) and KPC(-) isolates from these patients. Extent and rapidity of insect mortality was analyzed. Patients were stratified by KPC BSI status. Clinical outcomes of mortality and length of stay post-infection for survivors (LOS) were analyzed. Median virulence scores calculated from the insect studies were imputed in the clinical model.
  
  
  RESULTS
  The in-vivo model revealed greater mortality in KPC(-) isolates (p < 0.001). Fifteen patients with KPC(+) BSI were matched with 60 patients with KPC(-) BSI. Hospital mortality was greater in the KPC(+) group versus the KPC(-) group (OR 3.79, 95% CI 1.00 - 14.34). LOS was longer in the KPC(+) group (p < 0.01). Conversely the virulence score attenuated the association between KPC(+) status and mortality and LOS in the final translational models.
  
  
  CONCLUSIONS
  KPC(+) status was associated with decreased virulence in GM. Opposite findings were observed in patients. This pilot study demonstrates that measured virulence from GM may differ from human estimates of virulence.
authors.forename: Milena M
authors.initials: MM
authors.lastname: McLaughlin
authors.forename: M Renee
authors.initials: MR
authors.lastname: Advincula
authors.forename: Michael
authors.initials: M
authors.lastname: Malczynski
authors.forename: Grace
authors.initials: G
authors.lastname: Barajas
authors.forename: Chao
authors.initials: C
authors.lastname: Qi
authors.affiliation: Department of Pharmacy Practice, Midwestern University Chicago College of Pharmacy, 555 31st Street, Downers Grove, IL 60515, USA. mscheetz@nmh.org.
authors.forename: Marc H
authors.initials: MH
authors.lastname: Scheetz
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D016470:Bacteremia / Q000188:drug therapy / Q000382:microbiology* / Q000401:mortality; D001426:Bacterial Proteins / Q000378:metabolism*; D002641:Chicago / Q000453:epidemiology; D005260:Female; D054884:Host-Pathogen Interactions; D006801:Humans; D007709:Klebsiella; D007710:Klebsiella Infections / Q000188:drug therapy / Q000401:mortality*; D007711:Klebsiella pneumoniae / Q000201:enzymology / Q000472:pathogenicity*; D007814:Larva; D008297:Male; D008875:Middle Aged; D023421:Models, Animal; D009036:Moths; D010865:Pilot Projects; D011897:Random Allocation; D012189:Retrospective Studies; D014774:Virulence; D001618:beta-Lactamases / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D001618:beta-Lactamases; C063912:carbapenemase