Clinical and Molecular Characteristics of Klebsiella pneumoniae Isolates Causing Bloodstream Infections in Japan: Occurrence of Hypervirulent Infections in Health Care

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ABSTRACT

Although hypervirulent Klebsiella pneumoniae (hvKp) has been associated with severe community-acquired infections that occur among relatively healthy individuals, information about hvKp infections in health care settings remains limited. Here, we systematically analyzed the clinical and molecular characteristics of K. pneumoniae isolates causing bloodstream infections in a cross-sectional study. Clinical characteristics of K. pneumoniae bloodstream infections from hospitals across Japan were analyzed by a review of the medical records. Whole-genome sequencing of the causative isolates was performed. Bacterial species were confirmed and hvKp were identified using whole-genome sequencing data. Clinical characteristics of hvKp infections were compared with those of non-hvKp infections by bivariate analyses. Of 140 cases of K. pneumoniae bloodstream infections, 26 cases (18.6%) were caused by various clones of hvKp defined by the carriage of cardinal virulence genes. Molecular identification revealed that 24 (17.1%) and 14 (10%) cases were caused by Klebsiella variicola and Klebsiella quasipneumoniae, respectively. Patients with hvKp infections had higher proportions of diabetes mellitus (risk ratio [RR], 1.75; 95% confidence interval [CI], 1.05 to 2.94), and their infections had significantly higher propensity to involve pneumonia (RR, 5.85; 95% CI, 1.39 to 24.6), liver abscess (RR, 5.85; 95% CI, 1.39 to 24.6), and disseminated infections (RR, 6.58; 95% CI, 1.16 to 37.4) than infections by other isolates. More than one-half of hvKp infections were health care associated or hospital acquired, and a probable event of health care-associated transmission of hvKp was documented. hvKp isolates, which are significantly associated with severe and disseminated infections, are frequently involved in health care-associated and hospital-acquired infections in Japan.

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The comprehensive antibiotic resistance database.

Andrew McArthur, Nicholas Waglechner, Fazmin Nizam … (2013)

The field of antibiotic drug discovery and the monitoring of new antibiotic resistance elements have yet to fully exploit the power of the genome revolution. Despite the fact that the first genomes sequenced of free living organisms were those of bacteria, there have been few specialized bioinformatic tools developed to mine the growing amount of genomic data associated with pathogens. In particular, there are few tools to study the genetics and genomics of antibiotic resistance and how it impacts bacterial populations, ecology, and the clinic. We have initiated development of such tools in the form of the Comprehensive Antibiotic Research Database (CARD; http://arpcard.mcmaster.ca). The CARD integrates disparate molecular and sequence data, provides a unique organizing principle in the form of the Antibiotic Resistance Ontology (ARO), and can quickly identify putative antibiotic resistance genes in new unannotated genome sequences. This unique platform provides an informatic tool that bridges antibiotic resistance concerns in health care, agriculture, and the environment.

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N. Friedman, Keith S. Kaye, Jason Stout … (2002)

Bloodstream infections occurring in persons residing in the community, regardless of whether those persons have been receiving health care in an outpatient facility, have traditionally been categorized as community-acquired infections. To develop a new classification scheme for bloodstream infections that distinguishes among community-acquired, health care-associated, and nosocomial infections. Prospective observational study. One academic medical center and two community hospitals. All adult patients admitted to the hospital with bloodstream infection. Demographic characteristics, living arrangements before hospitalization, comorbid medical conditions, factors predisposing to bloodstream infection, date of hospitalization, dates and number of positive blood cultures, results of microbiological susceptibility testing, dates of hospital discharge or death, and mortality rates at 3 to 6 months of follow-up. 504 patients with bloodstream infections were enrolled; 143 (28%) had community-acquired bloodstream infections, 186 (37%) had health care-associated bloodstream infections, and 175 (35%) had nosocomial bloodstream infections. Of the 186 patients with health care-associated bloodstream infection, 29 resided in a nursing home, 64 were receiving home health care, 78 were receiving intravenous or intravascular therapy at home or in a clinic, and 117 had been hospitalized in the 90 days before their bloodstream infection. Cancer was more common in patients with health care-associated or nosocomial bloodstream infection than in patients with community-acquired bloodstream infection. Intravascular devices were the most common source of health care-associated and nosocomial infections, and Staphylococcus aureus was the most frequent pathogen in these types of infections. Methicillin-resistant S. aureus occurred with similar frequency in the groups with health care-associated infection (52%) and nosocomial infection (61%) but was uncommon in the group with community-acquired bloodstream infection (14%) (P = 0.001). Mortality rate at follow-up was greater in patients with health care-associated infection (29% versus 16%; P = 0.019) or nosocomial infection (37% versus 16%; P < 0.001) than in patients with community-acquired infection. Health care-associated bloodstream infections are similar to nosocomial infections in terms of frequency of various comorbid conditions, source of infection, pathogens and their susceptibility patterns, and mortality rate at follow-up. A separate category for health care-associated bloodstream infections is justified, and this new category will have obvious implications for choices about empirical therapy and infection-control surveillance.

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Identification of biomarkers for the differentiation of hypervirulent Klebsiella pneumoniae from classical K. pneumoniae

James Johnson, Mark Miller, Ricardo M La Hoz … (2018)

Background . A hypervirulent Klebsiella pneumoniae (hvKp) pathotype is undergoing global dissemination. In contrast to the usual healthcare-associated epidemiology of classical K. pneumoniae (cKp) infections, hvKp causes tissue invasive infections in otherwise healthy individuals from the community, often involving multiple sites. An accurate test to identify hvKp strains is needed for improved patient care and epidemiologic studies. Methods and Results . To fill this knowledge gap, clinical criteria or random blood isolates from North American and United Kingdom strain collections were used to assemble hvKp-rich strain (N = 85) and cKp-rich (N = 90) cohorts respectively. The isolates were then assessed for multiple candidate biomarkers hypothesized to accurately differentiate the two cohorts. The genes peg-344 , iroB, iucA , p rmpA , and p rmpA2 all demonstrated >0.95 diagnostic accuracy for identifying strains in the hvKp-rich cohort. Next, to validate this epidemiological analysis all strains were assessed experimentally in a murine sepsis model. peg-344 , iroB, iucA , p rmpA , and p rmpA2 were all associated with a hazard ratio of >25 for severe illness or death, additionally supporting their utility for identifying hvKp strains. Quantitative siderophore production of ≥ 30 μg/mL also strongly predicted strains as members of the hvKp-rich cohort (accuracy 0.96) and exhibited a hazard ratio of 31.7 for severe illness or death. The string test, a widely used marker for hvKp strains, performed less well, achieving an accuracy of only 0.90. Lastly, using the most accurate biomarkers to define hvKp, prevalence studies were performed on two Western strain collections. Conclusions . These data strongly support the utility of several laboratory markers for identifying hvKp strains with a high degree of accuracy.