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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.

bmc infectious diseases

Quantifying the clinical virulence of Klebsiella pneumoniae producing carbapenemase Klebsiella pneumoniae with a Galleria mellonellamodel and a pilot study to translate to patient outcomes