222 unique episodes of K. pneumoniae BSIs were identified, of which 103 (46%) episodes were community-onset. Since community-onset infection is one of the hallmarks of HVKp infections, we compared clinical manifestations of community-onset BSIs with those of hospital-onset BSIs (Table 1). Comparing to hospital-onset BSIs, patients with community-onset BSIs were older (72.6 v. 64.4) and biliary tract diseases were more often observed as underlying disease (34.0% v. 14.3%). Five patients (4.9%) with community-onset BSIs had no underlying disease, whereas all patients with hospital-onset BSIs had underlying diseases. Most notably, liver abscess was observed only in patients with community-onset BSIs. No significant difference was observed in antibacterial treatments in both patient cohorts, and the 30-day survival was comparable (82.3% v. 84.6%).
Analyses of isolated strains from these K. pneumoniae infections revealed several distinct characters with community-onset BSIs. Hypermucoviscosity phenotype was more often observed in community-onset BSIs than in hospital-onset BSIs (14.6% v. 5.0%). When the expression of rmpA gene, which is associated with the production of capsules [14], was determined in 133 strains, the gene was preferentially expressed in strains isolated from patients with community-onset BSIs than with hospital-onset BSIs (21.2% v. 6.2%). In terms of antimicrobial resistance, ESBL-producing K. pneumoniae was detected in 1.9% and 18.5% of patients with community-onset and hospital-onset BSIs, respectively. Resistance to carbapenems was observed in only one case of hospital-onset BSI.
Since liver abscess formation is uniformly associated with HV K. pneumoniae infections, we checked the medical records to identify patients in whom abdominal computed tomography (CT) scans were performed. We looked for cases with abdominal CT scans available and excluded cases examined with abdominal echograms, since abdominal CT scan is the most reliable method to detect liver abscesses caused by K. pneumoniae [15,16]. Among our patient cohort, 127 (57.2%) patients received abdominal CT scans irrespective of contrast-enhancement within seven days after the onset of K. pneumoniae BSIs. Abdominal CT scans were preferentially performed in patients aged 65 or older (odds ratio (OR), 1.98; 95% confidence interval (CI), 1.12-3.51) or in cases of community-onset BSIs (OR, 2.70; 95% CI, 1.55-4.70) by univariate analyses.
We found 10 cases of liver abscesses in patients checked by abdominal CT scans. Among these cases we found a case complicated by endophthalmitis and another case with vertebral osteomyelitis and epidural abscess. In the former case, onset of K. pneumoniae BSI and the endophthalmitis was at the same time. However, in the second case, lower back pain has developed after the onset of K. pneumonae BSI, and the vertebral osteomyelitis and epidural abscess was diagnosed after three weeks from the onset of BSI by magnetic resonance imaging.
When cases with and without liver abscesses were compared, several differences in clinical manifestations and bacterial characteristics were found (Table 2). All cases of liver abscesses were observed in community-onset BSIs, which contrast to cases without liver abscesses in which 53% of BSI episodes were community-onset. Thirty-day mortality was not significantly different between cases with and without liver abscesses (30% v. 18%). Absence of any underlying disease was more often identified in cases with liver abscesses than in cases without liver abscesses (20% v. 3%). In terms of bacterial characteristics, K1 capsular serotype and hypermucoviscosity phenotype were more often observed in isolates from patients with liver abscesses than in isolates from patients without liver abscesses (50% v. 6% and 50% v. 10%, respectively).
Based on these observations, we performed multivariate analyses to identify risk factors for liver abscess formation (Table 3). When adjusted by age, sex, and underlying diseases, community-onset BSIs (p=0.0005), K1 capsular serotype (p=0.0003), and hypermucoviscosity phenotype (p=0.01) were identified as independent risk factors for liver abscess formation. Next, we evaluated whether these risk factors could be used as scores to identify cases with liver abscess formation. Each risk factor was given one point, so that the total scores would be from zero to three points (Table 3). To determine the cut-off value for the identification of cases with liver abscesses, we performed receiver operating characteristic (ROC) curve analysis (Figure 1). The area under ROC was 0.90, indicating that the analysis was highly accurate. The sensitivity and specificity for each score were shown in Table 4. The score of >2 points provided maximal Youden’s index with a sensitivity and specificity of 0.70 and 0.94, respectively.