First two cases of severe multifocal infections caused by Klebsiella pneumoniae in Switzerland: characterization of an atypical non-K1/K2-serotype strain causing liver abscess and endocarditis
Introduction
Klebsiella pneumoniae (Kp) causes a wide variety of community-acquired and nosocomial infections typically affecting immunocompromised hosts [1], [2]. However, the recent advent of hypervirulent (hv) strains led to the emergence of highly invasive community-acquired infections in previously healthy and immunocompetent people. Commonly, the invasive syndrome due to hvKp implies a clinical presentation of liver abscess with metastatic spread (e.g., involving eyes, lungs, central nervous system) and/or causative strains of hypermucoviscous (hmv) phenotype usually belonging to the K1 or K2 serotypes [3], [4].
The mucoviscosity-associated gene A (magA) in the serotype-specific region of the K1 capsule gene cluster and the regulator of mucoid phenotype A (rmpA) are two extensively studied genes associated with the overexpression of the capsular serotypes K1 and K2 in hvKp, respectively [5], [6]. The siderophore aerobactin (iucA) is another virulence determinant that has been associated to hvKp strains [7]. Additionally, there are several less characterized factors (e.g., porins, efflux pumps, iron transport systems, and genes involved in the allantoin metabolism) which have been linked to the hvKp invasive syndrome in at least one in vivo infection model [6].
In the past, hmv/hvKp isolates were widely reported in Asia [8], [9]. However, cases are now increasingly observed in North America [10], [11], whereas in Europe reports are still scarce and no cases have been reported so far in Switzerland [12], [13], [14], [15], [16], [17], [18]. Notably, while most of the patients with an hmv/hvKp invasive syndrome reported from outside Asia were of Asian descent, growing cases among non-Asians are now being observed [12], [18], [19]. We also note that only few whole genome sequencing (WGS) analyses have been performed on typical hvKp strains (i.e., hmv and/or of capsular type K1/K2) for molecular epidemiology and virulence analysis [20], [21], [22], [23].
In this work, we present the first Swiss case of invasive liver abscess syndrome due to an hvKp which occurred in a non-Asian patient and a rare case of liver abscess and endocarditis due to an atypical hypervirulent Kp. State of the art phenotypic and molecular analyses (including WGS) were implemented to characterize the causative pathogens, contributing to the growing knowledge of the potential virulence factors responsible for the invasiveness of these strains.
Section snippets
Antimicrobial susceptibility testing (AST) and β-lactamase screening
The MICs for several antibiotics were determined using the microdilution Sentitre™ GNX2F plate (Trek Diagnostic Systems, East Grinstead, UK) and interpreted in accordance with the 2016 European Committee on Antimicrobial Susceptibility Testing (EUCAST) criteria (version 6.0, 2016), except for doxycycline and minocycline for which the Clinical & Laboratory Standards Institute (CLSI) guidelines were used (M100-S26, 2016). The string test was performed to define the hmv phenotype [4]. β-Lactamase (
Case 1
A 45-year-old Eritrean man living in Switzerland for eight years (without travel history to Asia and/or comorbidity/predisposing factors for infection) was referred to a community-hospital with a 7-day history of cough, fever, chills, and conjunctivitis. At presentation he was febrile, with a conjunctival erythema in the left eye, and both raised inflammatory markers and liver function parameters. CT scan showed a 60 × 54 mm multi-loculated liver abscess and bilateral lung infiltrates. Empirical
Discussion
In this work, we described the first two cases of multifocal invasive infections due to K. pneumoniae in Switzerland. The first case consisted of an invasive liver syndrome caused by a classic hvKp (Kp1), confirming the continuous dissemination of such strains among patients of non-Asian descent in Europe [12], [13], [14], [15], [16], [17]. The second case was due to an atypical hvKp (Kp2) causing community-acquired liver abscess and endocarditis, to which we applied WGS and screened for less
Conclusions
Kp2 highlights the new genetic background of an atypical hypervirulent Kp not belonging to the classical hvKp strains [3]. The bacterial virulence factors found in Kp2 probably play a major role in the invasiveness of this isolate. However, the lack of deposited WGS data for other atypical hypervirulent Kp, and the small numbers of available WGS for hvKp, make a comparison of the genetic virulence backgrounds belonging to the two groups of strains difficult. Furthermore, future investigations
Funding
This work was supported by the Swiss National Science Foundation (SNSF) with grant No. 171259 (due to BBF) and grant No. 153377 (due to AE).
Competing interests
None declared.
Ethical approval
Written informed consent was obtained from all individual participants included in the study.
Author contribution
Conception and design (BBF and AE); acquisition of data (BBF, VD, NB); analysis of data (BBF, VD, AE); drafting the work (BBF, VD, NB, AE); critical revision of the work (all authors); final approval of the manuscript (all authors).
Acknowledgments
We thank Prof. Stephen L. Leib (Director of the Institute for Infectious Diseases) for providing the laboratory space and equipment to perform this study. We also thank Prof. Andri Rauch and the colleagues of Department of Pneumology for providing us clinical data about the patients.
References (40)
- et al.
Klebsiella pneumoniae liver abscess: a new invasive syndrome
Lancet Infect Dis
(2012) - et al.
Klebsiella pneumoniae liver abscesses in a public hospital in Queens, New York
Travel Med Infect Dis
(2008) - et al.
Endogenous endophthalmitis as a first clinical manifestation of Klebsiella sepsis: the importance of an early diagnosis
Arch Soc Esp Oftalmol
(2011) - et al.
Emergence of Klebsiella pneumoniae co-producing NDM-1, OXA-48, CTX-M-15, CMY-16, QnrA and ArmA in Switzerland
Int J Antimicrob Agents
(2014) - et al.
Oxford nanopore MinIONsequencing and genome assembly
Genom Proteom Bioinform
(2016) - et al.
Identification of Klebsiella pneumoniae genes uniquely expressed in a strain virulent using a murine model of bacterial pneumonia
Microb Pathog
(2007) - et al.
Comparison of prevalence of virulence factors for Klebsiella pneumoniae liver abscesses between isolates with capsular K1/K2 and non-K1/K2 serotypes
Diagn Microbiol Infect Dis
(2008) - et al.
Sequencing and analysis of the large virulence plasmid pLVPK of Klebsiella pneumoniae CG43
Gene
(2004) - et al.
Characteristics of bacteremia between community-acquired and nosocomial Klebsiella pneumoniae infection: risk factor for mortality and the impact of capsular serotypes as a herald for community-acquired infection
Arch Intern Med
(2002) - et al.
Klebsiella spp. as nosocomial pathogens: epidemiology, taxonomy, typing methods, and pathogenicity factors
Clin Microbiol Rev
(1998)
Hypervirulent (hypermucoviscous) Klebsiella pneumoniae: a new and dangerous breed
Virulence
Association between rmpA and magA genes and clinical syndromes caused by Klebsiella pneumoniae in Taiwan
Clin Infect Dis
Klebsiella pneumoniae: going on the offense with a strong defense
Microbiol Mol Biol Rev
Aerobactin mediates virulence and accounts for increased siderophore production under iron-limiting conditions by hypervirulent (hypermucoviscous) Klebsiella pneumoniae
Infect Immun
Hypermucoviscosity: an extremely sticky phenotype of Klebsiella pneumoniae associated with emerging destructive tissue abscess syndrome
Clin Infect Dis
High prevalence of hypervirulent Klebsiella pneumoniae infection in China: geographic distribution, clinical characteristics and antimicrobial resistance
Antimicrob Agents Chemother
Prevalence of hypervirulent Klebsiella pneumoniae associated genes rmpA and magA in two tertiary hospitals in Houston, Texas USA
J Med Microbiol
Emerging severe and fatal infections due to Klebsiella pneumoniae in two university hospitals in France
J Clin Microbiol
Hepatic abscess due to Klebsiella pneumoniae in an Asian immigrant
Enferm Infecc Microbiol Clin
Endogenous endophthalmitis complicating Klebsiella pneumoniae liver abscess in Europe: case report
Int Ophthalmol
Cited by (0)
- 1
Equal contribution.