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

Milena M. McLaughlin, M. R. Advincula, Michael Malczynski, Grace Barajas, Chao Qi, Marc H. Scheetz*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

79 Scopus citations

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.

Original languageEnglish (US)
Article number31
JournalBMC Infectious Diseases
Volume14
Issue number1
DOIs
StatePublished - Jan 15 2014

Funding

This study was supported in part by a grant from Midwestern University Chicago College of Pharmacy, Downers Grove, IL and the Society of Infectious Diseases Pharmacists.

Keywords

  • Galleria mellonella
  • Klebsiella pneumoniae producing carbapenemase Klebsiella pneumoniae
  • Mortality
  • Resistance
  • Virulence

ASJC Scopus subject areas

  • Infectious Diseases

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