Background: Reports on metastatic or invasive infections by hypervirulent Klebsiella pneumoniae (hvKP) have increased recently. However, the effects of its virulence on clinical course and outcomes in pneumonia patients have rarely been addressed. We assessed and compared the clinical features of hvKp and classic K. pneumoniae (cKP) strains isolated from patients with pneumonia caused by K. pneumoniae. We also investigated the effects of virulence factors and the K. pneumoniae capsular serotypes K1 and K2 on mortality. Methods: In this retrospective study, we enrolled 91 patients diagnosed as having pneumonia caused by K. pneumoniae and obtained their demographic and clinical data from medical records. We evaluated genes for K1 and K2, antimicrobial susceptibility, and the virulence genes rmpA, iutA, entB, ybtS, kfu, mrkD, and allS. Strains that possessed rmpA and iutA were defined as hvKP (N=39), while the remaining were classified as cKP (N=52).Odds ratio (OR) for the risk factors associated with 30-day mortality was calculated using the binary logistic regression model. Results: The 30-day mortality in all patients was 23.1%; it was 17.9% (7/39) in the hvKP group and 26.9% (14/52) in the cKP group (P = 0.315). Bacteremia (OR = 38.1; 95% confidence interval [CI], 2.5–570.2), altered mental status (OR = 8.8; 95% CI, 1.7–45.0), and respiratory rate > 30 breaths/min (OR = 4.8; 95% CI, 1.2–20.0) were independent risk factors for 30-day mortality in all patients. Conclusions Our results suggest that hypervirulence determinants do not have a significant effect on 30-day mortality in patients with pneumonia caused by K. pneumoniae.

Hyperactivation of phosphoinositol 3-kinase (PI3K) has been suggested to be a potential mechanism for endoplasmic reticulum (ER) stress-enhanced airway hyperresponsiveness, and PI3K inhibitors have been examined as asthma therapeutics. However, the regulatory mechanism linking PI3K to ER stress and related pathological signals in asthma have not been defined. To elucidate these pathogenic pathways, we investigated the influence of a selective PI3Kδ inhibitor, IC87114, on airway inflammation in an ovalbumin/lipopolysaccharide (OVA/LPS)-induced asthma model. In OVA/LPS-induced asthmatic mice, the activity of PI3K, downstream phosphorylation of AKT and activation of nuclear factor-κB (NF-κB) were all significantly elevated; these effects were reversed by IC87114. IC87114 treatment also reduced the OVA/LPS-induced ER stress response by enhancing the intra-ER oxidative folding status through suppression of protein disulfide isomerase activity, ER-associated reactive oxygen species (ROS) accumulation and NOX4 activity. Furthermore, inositol-requiring enzyme-1α (IRE1α)-dependent degradation (RIDD) of IRE1α was reduced by IC87114, resulting in a decreased release of proinflammatory cytokines from bronchial epithelial cells. These results suggest that PI3Kδ may induce severe airway inflammation and hyperresponsiveness by activating NF-κB signaling through ER-associated ROS and RIDD–RIG-I activation. The PI3Kδ inhibitor IC87114 is a potential therapeutic agent against neutrophil-dominant asthma.