Devastating Community-Acquired Bacterial Meningitis Caused by Hypervirulent Klebsiella pneumoniae in an Immunocompetent Patient.
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ABSTRACT:
SUBMITTER: Oh H
PROVIDER: S-EPMC8242319 | biostudies-literature | 2021 Jul
REPOSITORIES: biostudies-literature
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Devastating Community-Acquired Bacterial Meningitis Caused by Hypervirulent <i>Klebsiella pneumoniae</i> in an Immunocompetent Patient.
Oh Hyunjoo H Heo Sang Taek ST Kim Misun M Kang Chul Hoo CH Yoo Jeong Rae JR
Journal of clinical neurology (Seoul, Korea) 20210701 3
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Project description:BackgroundCommunity-acquired bacterial meningitis due to Klebsiella pneumoniae has mainly been described in Southeast Asia and has a poor prognosis. Severe invasive infections caused by K. pneumoniae, including meningitis, are often due to hypervirulent strains (hvKP), which are characterized by capsular serotypes K1 and K2, a gene responsible for hypermucoviscosity, and the cluster for synthesis of the siderophore aerobactin.Case presentationA 55 year old man with a history of essential hypertension, benign prostate hyperplasia, hyperlipidemia, obstructive sleep apnea, and chronic alcoholism was admitted for meningitis due to Klebsiella pneumoniae with a wild-type susceptibility profile. Its genomic features were consistent with a capsular K2 strain belonging to clonal group 86 (CG86) displaying the large virulence of Klebsiella plasmid (pLVPK) with heavy metal resistance gene clusters, aerobactin, rmpA.ConclusionThis is the first case of community-acquired meningitis caused by a hypervirulent strain of hvKP ever reported in the Caribbean.
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Project description:Klebsiella pneumoniae (Kp) reference strain Kp52.145 is widely used in experimental Klebsiella pathophysiology. Since 1935, only one other strain of the same sublineage (sequence type ST66, capsular serotype K2) was isolated (AJ210, Australia). Here, we describe a community-acquired invasive infection caused by a ST66-K2 Kp strain in France. Four hypermucoviscous Kp isolates responsible for acute otitis media, meningitis, bacteraemia and bacteriuria, respectively, were obtained from a patient with a history of chronic alcoholism and diabetes mellitus, and infected with HIV. The isolates were characterized by phenotypic and genomic methods. The four genetically identical ST66-K2 isolates presented a full antimicrobial susceptibility profile, including to ampicillin, corresponding to a single strain (SB5881), which was more closely related to AJ210 (135 SNPs) than to Kp52.145 (388 SNPs). Colibactin and yersiniabactin gene clusters were present on the integrative and conjugative element ICEKp10 in the chromosome. The two plasmids from Kp52.145 were detected in SB5881. In addition to carrying genes for virulence factors RmpA, aerobactin and salmochelin, plasmid II has acquired in SB5881, the conjugation machinery gene cluster from plasmid I. We report the first case of community-acquired infection caused by a hypervirulent ST66-K2 Kp strain in Europe. This demonstrates the long-term persistence of the high-virulence and laboratory model ST66-K2 sublineage. The combination of a conjugative apparatus and major virulence genes on a single plasmid may contribute to the co-occurrence of hypervirulence and multidrug resistance in single Kp strains.
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Project description:Infections with hypervirulent Klebsiella pneumoniae (hvKp) commonly presents with primary liver infection, bacteremia, and metastatic abscesses. Here, we present 2 cases of severe community-acquired pulmonary infections by hvKp in patients in the Netherlands without recent travel history. Both bacterial isolates are closely related to an archetype ST23 hvKp reference isolate. Based on these findings, surveillance programs on hvKp may consider to include isolates from community-acquired pneumonia by K. pneumoniae.
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Project description:Hypervirulent K. pneumoniae (hvKp) is an evolving pathotype that is more virulent than classical K. pneumoniae (cKp). hvKp usually infects individuals from the community, who are often healthy. Infections are more common in the Asian Pacific Rim but are occurring globally. hvKp infection frequently presents at multiple sites or subsequently metastatically spreads, often requiring source control. hvKp has an increased ability to cause central nervous system infection and endophthalmitis, which require rapid recognition and site-specific treatment. The genetic factors that confer hvKp's hypervirulent phenotype are present on a large virulence plasmid and perhaps integrative conjugal elements. Increased capsule production and aerobactin production are established hvKp-specific virulence factors. Similar to cKp, hvKp strains are becoming increasingly resistant to antimicrobials via acquisition of mobile elements carrying resistance determinants, and new hvKp strains emerge when extensively drug-resistant cKp strains acquire hvKp-specific virulence determinants, resulting in nosocomial infection. Presently, clinical laboratories are unable to differentiate cKp from hvKp, but recently, several biomarkers and quantitative siderophore production have been shown to accurately predict hvKp strains, which could lead to the development of a diagnostic test for use by clinical laboratories for optimal patient care and for use in epidemiologic surveillance and research studies.
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Project description:We describe a case of endogenous endophthalmitis caused by sequence type 66-K2 hypervirulent Klebsiella pneumoniae in a diabetic patient with no travel history outside the United States. Genomic analysis showed the pathogen has remained highly conserved, retaining >98% genetic similarity to the original strain described in Indonesia in 1935.
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Project description:Klebsiella pneumoniae (K. pneumoniae) is one of the most common causes of bacterial meningitis worldwide. The purpose of this study was to investigate the clinical and microbiological characteristics of K. pneumoniae meningitis, as well as the association of antimicrobial resistance, virulence, and patient prognosis. The clinical data of patients with K. pneumoniae meningitis from 2014 to 2020 in a tertiary teaching hospital were retrospectively evaluated. Antimicrobial susceptibility profiles were performed by the agar dilution method and broth microdilution method. The isolates were detected for virulence-related genes, resistance genes, capsular serotypes, and molecular subtypes. A total of 36 individuals with K. pneumoniae meningitis were included in the study, accounting for 11.3% (36/318) of all cases of bacterial meningitis. Of the 36 available isolates, K1, K47, and K64 were tied for the most frequent serotype (7/36, 19.4%). MLST analysis classified the isolates into 14 distinct STs, with ST11 being the most common (14/36, 38.9%). Carbapenem resistance was found in 44.4% (16/36) of the isolates, while hypervirulent K. pneumoniae (HvKP) was found in 66.7% (24/36) of the isolates. The isolates of hypervirulent carbapenem-resistant K. pneumoniae (Hv-CRKP) were then confirmed to be 36.1% (13/36). Importantly, individuals with meningitis caused by Hv-CRKP had a statistically significant higher mortality than the other patients (92.3%, 12/13 vs. 56.5%, 13/23; P < 0.05). The high percentage and fatality of K. pneumoniae-caused meningitis, particularly in Hv-CRKP strains, should be of significant concern. More effective surveillance and treatment solutions will be required in future to avoid the spread of these life-threatening infections over the world.
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Project description:A patient in Japan with coronavirus disease and hypervirulent Klebsiella pneumoniae K2 sequence type 86 infection died of respiratory failure. Bacterial and fungal co-infections caused by region-endemic pathogens, including hypervirulent K. pneumoniae in eastern Asia, should be included in the differential diagnosis of coronavirus disease patients with acutely deteriorating condition.
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Project description:BackgroundRecurrent bacterial meningitis has been found to occur in about 5% of meningitis cases.MethodsWe analyzed adults with recurrent episodes in a prospective nationwide cohort study of community-acquired bacterial meningitis.ResultsOf 2264 episodes of community-acquired bacterial meningitis between 2006 and 2018, 143 (6%) were identified as recurrent episodes in 123 patients. The median age was 57 years (interquartile range [IQR], 43-66), and 57 episodes (46%) occurred in men. The median duration between the first and the current episode was 5 years (IQR, 1-15). For 82 of 123 patients (67%), it was the first recurrent episode, 31 patients had 2-5 previous episodes (25%), 2 had 6-10 episodes (2%), and 2 had >10 episodes (2%). Predisposing factors were identified in 87 of 118 patients (74%) and most commonly consisted of ear or sinus infections (43 of 120, 36%) and cerebrospinal fluid leakage (37 of 116, 32%). The most common pathogens were Streptococcus pneumoniae (93 of 143, 65%) and Haemophilus influenzae (19 of 143, 13%). The outcome was unfavorable (Glasgow outcome scale score, <5) in 24 episodes with recurrent meningitis (17%) vs 810 for nonrecurrent meningitis patients (39%, P < .001). Six of 143 died (4%) vs 362 of 2095 patients (17%, P < .001).ConclusionsRecurrent meningitis occurs mainly in patients with ear or sinus infections and cerebrospinal fluid leakage. Predominant causative pathogens are S. pneumoniae and H. influenzae. The disease course is less severe, resulting in lower case fatality compared with nonrecurrent meningitis patients.
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Project description:Distinguishing hypervirulent (hvKp) from classical Klebsiella pneumoniae (cKp) strains is important for clinical care, surveillance, and research. Some combinations of iucA, iroB, peg-344, rmpA, and rmpA2 are most commonly used, but it is unclear what combination of genotypic or phenotypic markers (e.g., siderophore concentration, mucoviscosity) most accurately predicts the hypervirulent phenotype. Furthermore, acquisition of antimicrobial resistance may affect virulence and confound identification. Therefore, 49 K. pneumoniae strains that possessed some combinations of iucA, iroB, peg-344, rmpA, and rmpA2 and had acquired resistance were assembled and categorized as hypervirulent hvKp (hvKp) (N = 16) or cKp (N = 33) via a murine infection model. Biomarker number, siderophore production, mucoviscosity, virulence plasmid's Mash/Jaccard distances to the canonical pLVPK, and Kleborate virulence score were measured and evaluated to accurately differentiate these pathotypes. Both stepwise logistic regression and a CART model were used to determine which variable was most predictive of the strain cohorts. The biomarker count alone was the strongest predictor for both analyses. For logistic regression, the area under the curve for biomarker count was 0.962 (P = 0.004). The CART model generated the classification rule that a biomarker count = 5 would classify the strain as hvKP, resulting in a sensitivity for predicting hvKP of 94% (15/16), a specificity of 94% (31/33), and an overall accuracy of 94% (46/49). Although a count of ≥4 was 100% (16/16) sensitive for predicting hvKP, the specificity and accuracy decreased to 76% (25/33) and 84% (41/49), respectively. These findings can be used to inform the identification of hvKp.IMPORTANCEHypervirulent Klebsiella pneumoniae (hvKp) is a concerning pathogen that can cause life-threatening infections in otherwise healthy individuals. Importantly, although strains of hvKp have been acquiring antimicrobial resistance, the effect on virulence is unclear. Therefore, it is of critical importance to determine whether a given antimicrobial resistant K. pneumoniae isolate is hypervirulent. This report determined which combination of genotypic and phenotypic markers could most accurately identify hvKp strains with acquired resistance. Both logistic regression and a machine-learning prediction model demonstrated that biomarker count alone was the strongest predictor. The presence of all five of the biomarkers iucA, iroB, peg-344, rmpA, and rmpA2 was most accurate (94%); the presence of ≥4 of these biomarkers was most sensitive (100%). Accurately identifying hvKp is vital for surveillance and research, and the availability of biomarker data could alert the clinician that hvKp is a consideration, which, in turn, would assist in optimizing patient care.
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2024-07-17 | GSE243246 | GEO