Detection of multiple hypervirulent Klebsiella pneumoniae strains in a New York City hospital through screening of virulence genes

Abstract

Objectives: The 'hypervirulent' variant of Klebsiella pneumoniae (hvKp) is a predominant cause of community-acquired pyogenic liver abscess in Asia, and is an emerging pathogen in Western countries. hvKp infections have demonstrated 'metastatic' dissemination in immunocompetent hosts, an unusual mode of infection associated with severe complications. Two cases alerted us to the possible presence of hvKp at our hospital, both involving elderly Hispanic males who presented with recurrent fever, bacteraemia, epigastric pain and liver abscesses/phlegmon, thus prompting an assessment of hvKp prevalence. Methods: A surveillance of K. pneumoniae blood, body fluid and wound isolates was conducted using real-time PCR to detect virulence-associated genes (uni-rmpA, iucA and peg344). Positive isolates were further characterized by wzi gene sequencing to determine capsular types (K-type) and by multilocus sequence typing and pulsed-field gel electrophoresis to determine strain relatedness. Results: Four-hundred and sixty-three K. pneumoniae isolates, derived from 412 blood, 21 body fluids and 30 abdominal wound specimens, were screened over a 3-year period. Isolates included 98 multidrugresistant strains. Eighteen isolates from 17 patients, including two from the index patient, screened positive for all three virulence genes. Sixteen of 18 positive isolates had K-types associated with hvKp, and isolates from different patients were unrelated strains, indicating likely community acquisition. Of 13 patients with significant morbidity, five died; eight patients had co-existing hepatobiliary disease, and six had diabetes mellitus. Conclusions: Multiple strains of hvKp are emerging in New York City and are associated with high mortality relative to multidrug-resistant and classical Klebsiella infections. Co-existing hepatobiliary disease appears to be a potential risk factor for these infections.

Genomic Characterization of Tissue Invasive Klebsiella pneumoniae Complex in a Hospital System with a Focus on Species Distribution and Hypervirulence

“…Furthermore, a comprehensive review of English language literature revealed only one previous report of K. quasipneumoniae isolated from liver, so our exclusive isolation of K. quasipneumoniae from liver specimens remains somewhat unexpected[54].We observed an isolation rate of 5.7% (n=2) for hvKp in our collection of sterile site specimens from Strong Memorial Hospital from between October 2018 and October 2019. This rate is consistent with the limited previous studies of the rate of hvKp in North American hospitals, with a rate of 8.2% found in Calgary, Alberta, Canada, rates of 7.9% and 3.9% in different hospitals in Houston, Texas, USA, and a rate of 3.7% in a New York City, New York, USA hospital[42,43,60]. Two of these studies, Periano et aland Chou et al, collected only blood isolates, while Parrott et al collected isolates from a variety of clinical specimens, predominantly blood.…”

“…Since its initial characterization, hvKp has become a leading cause of community acquired liver abscess, gram negative pneumonia and bacterial meningitis in Taiwan and is an emerging cause of necrotizing fasciitis [30][31][32][33][34][35][36][37][38][39]. HvKp has also been identified worldwide, [40] though there have been few systematic studies of hvKp in the United States [41][42][43].…”

“…Many of these virulence factors, including rmpA , rmpA2 , and aerobactin, are carried on non-conjugative plasmids, the prototype of which is pLVPK [49, 50]. Molecular definitions of hvKp have varied over time, though recent studies have identified the simultaneous presence of the aerobactin gene cluster ( iuc ) and rmpA or rmpA2 as a sensitive and specific marker for hvKp [43, 48]. It is generally believed that hvKp strains are K. pneumoniae sensu stricto, often of a single MLST, ST23.…”

Genomic surveillance for multidrug-resistant or hypervirulentKlebsiella pneumoniaeamong bloodstream isolates at a United States academic medical center

“…Case reports indicate that hvKp strains exist in the U.S., but their prevalence is unclear and has only been investigated in two surveillance studies (24,25). In this work, we determined the prevalence of hvKp at NMH by identifying isolates using diagnostic criteria of hvKp.…”

“…CC-BY-NC-ND 4.0 International license available under a (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made common in Asia, but little is known about their prevalence in the U.S. Case reports document the presence of hvKp infections and PLA in North America, but only a few surveillance studies have been performed (21,(24)(25)(26). hvKp strains frequently express a highly mucoid capsule, leading to a "hypermucoviscous" colony phenotype, and are considerably more virulent in mouse models than cKp strains (23).…”