This study aimed to assess and compare the clinical features of hvKP and cKP strains isolated from patients with pneumonia caused by K. pneumoniae and to investigate the effect of virulence factors and the K1 and K2 serotypes on mortality. This study is significant because, unlike other studies [10, 11], it compared hvKP and cKP considering all types of pneumonia caused by K. pneumoniae, including CAP, HCAP, and HAP. Our results demonstrated that the presence of virulence factors and the K1 and K2 serotypes did not affect mortality, whereas bacteremia, altered mental status, and respiratory rates >30 breaths/min were independent risk factors for mortality.
There were no significant risk factors associated with hvKP infection compared with cKP infection. Malignancy was associated with a significantly higher risk for cKP infection, which is consistent with the fact that hospitalized cancer patients are highly susceptible to cKP infection [7]. cKP is the primary strain of nosocomial infection, unlike hvKP, which is associated with CAP [7]. However, we found no significant difference between hvKP and cKP in CAP, HCAP, and HAP patients. In line with this finding, a study conducted in China revealed no difference between hvKP and cKP in HAP caused by K. pneumoniae [17].
Studies in Asia, Europe, and America showed that K1 and K2 have a close relationship with hvKP [5]. In our study, K1 and K2 serotypes were present in 61.5% of hvKP; this frequency was significantly higher than that of cKP. In two recent studies on VAP caused by K. pneumoniae, the prevalence rates of K1 and K2 serotypes in hvKP were 70.6% and 64.3%, respectively. Further, in bacteremic CAP, the prevalence rate of the K1 and K2 serotypes in hvKP was 53.1%, which was higher than that in cKP (46.9%) [10, 14, 18]. The prevalence of K1 and K2 is high in hvKP because strains of these serotypes are more resistant to phagocytosis and intracellular elimination by macrophages and neutrophils than are strains of other serotypes [19, 20]. In addition, a study on VAP reported that the number of virulence factors associated with hvKP is significantly higher than that associated with cKP [18].
In this study, the 30-day mortality in all patients with pneumonia due to K. pneumoniae was 23.1% (21/91). It was 14.3% (5/35) for CAP, 27.3% (6/22) for HCAP, 29.4% (10/34) for HAP, and 19.3% (11/57) for community-onset pneumonia (CAP and HCAP). The mortality associated with community-onset pneumonia caused by K. pneumoniae in this study was lower than that in Taiwan (CAP, 25.5%; HCAP, 34.1%; and community-onset pneumonia, 29.3%) [11]. However, in this study, the mortality due to K. pneumoniae-associated CAP was higher than the previous data (7.3%) due to total pathogens [2]. The mortality due to HAP was similar to the finding (25–58%) reported in a previous study [3].
There was no significant difference in mortality associated with the hvKP and cKP strains in our study. Moreover, the K1 and K2 serotypes and the virulence genes (rmpA, iutA, entB, ybtS, kfu, mrkD, and allS) were not independent risk factors for mortality. In univariate analysis, the unadjusted odds ratio (OR) of hvKP mortality was 0.6 (95% confidence interval [CI], 0.2–1.7). After adjustment for confounding variables in multivariate logistic regression analysis, the adjusted OR of hvKP was 0.8 (95% CI, 0.2–2.9) (data not shown). Therefore, hvKP was not associated with mortality. Similar results have been reported previously [10, 11, 14]. There was no significant difference in mortality between hvKP- and cKP-associated bloodstream infections [21, 22]. However, the pks gene cluster has been found to affect mortality in bloodstream infections caused by K. pneumoniae, and further studies on other virulence factors that affect mortality and on the relationships between virulence factors that contribute to mortality are warranted [23].
ASTs revealed no significant difference between the hvKP and cKP strains, except for susceptibility to ampicillin-sulbactam. In previous studies, resistance to third-generation cephalosporins in hvKP-associated VAP were 0–10% [18], 14.3% [24], and 30–40% [10]. In this study, the resistance rate of hvKP to cefotaxime was 29.2%. However, antibiotic resistance in hvKP may need monitoring as the prevalence of antibiotic-resistant-hvKP is increasing gradually, and early antibiotic administration is important for survival of pneumonia patients [25–27].
Our study had several limitations. First, it was a retrospective, single center study conducted in a small population. However, it is larger than the populations in previous studies on pneumonia due to K. pneumoniae [16, 17, 24]. Second, we could not evaluate all the risk factors that would be accessible in an observational study. Third, a standardized definition of hvKP has not yet been established. Although definitions of hvKP differ across studies, iuc and either rmpA or rmpA2 should be considered a key virulence factor of hvKP. In this study, of the 41 strains positive for iutA, 39 harbored rmpA. However, we did not analyze the presence of rmpA2 in two strains. Finally, we investigated only some virulence factors and tested none of the virulence factors in an animal study. We cannot exclude the possibility of inconsistencies between virulence experiments conducted by different groups.
In conclusion, to our knowledge, this is the first study comparing the influence of hvKp and cKP on the mortality in patients with pneumonia caused by K. pneumoniae. Our study is of value in investigating the relationship between bacterial virulence and the clinical outcome of pneumonia. We report that hvKP strains do not have a clinically significant effect on mortality in these patients. Future studies are required to confirm the interactions between related virulence factors and the role of other virulence factors in the clinical outcomes of pneumonia caused by K. pneumoniae.