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Open Access Highly Accessed Research article

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 McLaughlin12, M Renee Advincula3, Michael Malczynski2, Grace Barajas4, Chao Qi25 and Marc H Scheetz12*

Author Affiliations

1 Department of Pharmacy Practice, Midwestern University Chicago College of Pharmacy, 555 31st Street, Downers Grove, IL 60515, USA

2 Northwestern Memorial Hospital, 251 E Huron St, Chicago, IL 60611, USA

3 Midwestern University, Chicago College of Pharmacy, 555 31st Street, Downers Grove, IL 60515, USA

4 Jesse Brown VA Medical Center, 820 S Damen Ave, Chicago, IL 60612, USA

5 Northwestern University, 710 N Lake Shore Dr, Chicago, IL 60611, USA

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BMC Infectious Diseases 2014, 14:31  doi:10.1186/1471-2334-14-31

Published: 15 January 2014

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.

Keywords:
Klebsiella pneumoniae producing carbapenemase Klebsiella pneumoniae; Galleria mellonella; Virulence; Mortality; Resistance