Community-acquired hypervirulent Klebsiella pneumoniae meningitis in Canada: A case report

Abstract

Introduction

Hypervirulent Klebsiella pneumoniae has emerged as a cause of fulminant metastatic infections, particularly prevalent amongst patients in Asia, but increasing in many areas worldwide. This report describes a fatal case of community-acquired Klebsiella pneumoniae in Canada causing meningitis complicated by several neurological complications.

Case presentation

A 58-year-old male with a long-standing history of poorly controlled type two diabetes mellitus presented with a two-day history of confusion, fatigue, and fall. He was febrile and tachycardic, and had laboratory findings consistent with diabetic ketoacidosis. Despite initial broad-spectrum antimicrobials, he deteriorated neurologically, prompting intubation. Lumbar puncture yielded frankly purulent cerebral spinal fluid (CSF), and both blood and CSF cultures grew Klebsiella pneumoniae sensitive to Ceftriaxone. Brain imaging revealed leptomeningeal inflammation, ventriculitis, and non-occlusive thrombi of the right internal jugular vein and superior sagittal sinus. A liver abscess was also discovered, a finding commonly reported with hypervirulent Klebsiella pneumoniae infections. Anticoagulation was initiated while balancing the risk of intracranial hemorrhage. Despite aggressive critical care measures, repeat imaging demonstrated diffuse cerebral edema with evolving global anoxic injury. A nuclear medicine cerebral perfusion scan showed absent cerebral blood flow, and goals of care were transitioned to comfort measures. The patient passed away shortly thereafter.

Conclusion

This case highlights the rapid progression and complexity of hypervirulent Klebsiella pneumoniae. Metastatic sites of infection and antimicrobial resistance should be considered and may alter management, including antibiotic choice and percutaneous drainage of silent sites of infection.

Introduction

Hypervirulent Klebsiella pneumoniae (HvKp) is an increasingly recognized virulent phenotype capable of causing disseminated, fulminant infections [1], [2], [3]. Unlike classical Klebsiella pneumoniae (CKp) which typically cause nosocomial infections in immunocompromised hosts, HvKp is predominantly community-acquired in immunocompetent hosts. HvKp has been recognized in Eastern Europe and Asia [4], but has more recently been identified in the rest of Europe and North America [4], [5], [6]. Unlike CKp, HvKp infected hosts often demonstrate multiple sites of infection, including meningitis, liver abscess, endophthalmitis, necrotizing fasciitis, pneumonia, and more [3], [7]. The mortality rate can reach 55% depending on the site of infection, and is particularly high amongst patients with CNS infections [8], [9], [10].

Case presentation

A 58-year-old male with a history of poorly controlled type two diabetes mellitus (hemoglobin A1C 11.1%), hypertension and dyslipidemia, presented to our emergency department with two days of fatigue, anorexia, and an unwitnessed fall. In the hours before presentation he was confused and combative. There was no recent travel or infectious exposures. Home medications were Empagliflozin, Sitagliptin, Rosuvastatin, Gliclazide and Metformin. In the emergency department, he was found to be febrile (38.7°C), tachycardic (122 beats/minute), and mildly tachypneic (24 breaths/minute); other vital signs were normal. Physical examination was otherwise unremarkable, apart from disorientation and agitation. There was no neck stiffness or focal neurological deficits. Laboratory results are summarized in Supplementary Table 1, abnormalities included leukocytosis and anion-gap metabolic acidosis with elevated ketones and near-normal serum glucose, consistent with euglycemic diabetic ketoacidosis. Chest radiography was normal, and electrocardiogram revealed sinus tachycardia. A non-contrast head CT scan was performed in the Emergency Department and reported as normal by the radiologist.

Blood cultures, urine culture and nasopharyngeal swab for viruses were obtained. Broad-spectrum antibiotics were initiated within 3 h of hospital presentation with Ceftriaxone, Vancomycin and Ampicillin for empiric coverage of bacterial meningitis, along with Acyclovir for potential viral encephalitis. He received intravenous insulin and fluids to treat euglycemic diabetic ketoacidosis and was admitted to the intensive care unit. Approximately 12 h from hospital presentation, he deteriorated neurologically with a sudden decrease in Glasgow Comma Scale (GCS) from 14 to 6 and development of a right dilated pupil. He was emergently intubated and was hemodynamically unstable requiring multiple vasopressor infusions to maintain blood pressure targets.

Urgent neuroimaging was obtained. CT angiography and CT perfusion demonstrated global prolongation of time-to-maximum (Tmax) values without large vessel occlusion. Lumbar puncture yielded purulent cerebral spinal fluid, with white blood cells of 78,250 cells/uL (85% neutrophils) and Gram stain revealing Gram-negative rods. Opening pressure measured in the lateral decubitus position was > 50 cm H₂O. MRI brain revealed diffuse leptomeningeal enhancement, ventriculitis, and non-occlusive thrombosis of the right internal jugular vein, superior sagittal sinus, and right transverse and sigmoid sinuses, consistent with septic cerebral venous sinus thrombosis (Fig. 1). Neurosurgery consultation for consideration of surgical decompression was obtained but no intervention was offered due to poor candidacy for intervention. Anticoagulation was initiated with intravenous heparin.

Fig. 1.

I. Brain Magnetic Resonance Imaging during admission. (A) Axial T2-Weighted Fluid-Attenuated Inversion Recovery (T2 FLAIR) image demonstrates diffuse hyperintense signal in the sulci and layering hyperintense fluid in the ventricles (arrows) and in keeping with leptomeningitis and ventriculitis, respectively. (B) Axial Diffusion Weighted Imaging (DWI) image shows diffuse cortical hyperintensity suggestive of hypoxic injury. Axial (C) and coronal (D) post-gadolinium T1-weighted images show non-occlusive thrombosis of the right internal jugular vein, right transverse sinus, and superior sagittal sinus (yellow arrowheads). (E) Maximum Intensity Projection (MIP) of Susceptibility-Weighted Imaging (SWI) shows a diffuse engorgement of cortical veins, suggestive of venous congestion. II. Computed Tomography (CT) and CT Perfusion Imaging. Initial non-contrast CT head (A) at admission shows normal ventricles and sulci. However, there was markedly elevated values throughout the brain parenchyma on CT perfusion time-to-maximum (Tmax) color map (B), in keeping with delayed perfusion. (C) Non-contrast CT head performed three days later demonstrates diffuse brain edema with completely effaced ventricle and sulci. (D) Contrast-enhanced CT chest image shows right lower lobe consolidation with areas of hypoenhancement (arrow), consistent with necrotizing pneumonia. (E) Contrast-enhanced CT abdomen demonstrates an ill-defined hypodense lesion in the right liver (arrow), in keeping with of a small abscess.

Due to the rapid clinical deterioration, antibiotics were broadened to meropenem in the event of cephalosporin-resistant Gram-negative organisms. On hospital day 2, blood and CSF cultures resulted with growth of Klebsiella pneumoniae susceptible to beta-lactamase/beta-lactamase inhibitor combinations, cephalosporins, ciprofloxacin, trimethoprim-sulfamethoxazole and aminoglycosides. CSF studies for Acid Fast Bacilli, fungi, cryptococcal antigen and viruses were negative. Nasopharyngeal swab for COVID-19 and Influenza was negative. Antimicrobials were rationalized to Ceftriaxone. Infectious Disease specialists were consulted; genetic testing for determinants of hypervirulence was not performed due to the patient’s poor prognosis. On hospital day 3, CT imaging of the chest revealed evidence of necrotizing pneumonia of the right lower lobe without abscess formation. CT imaging of the abdomen revealed a 2.0 × 2.4 × 1.4 cm segment-8 liver lesion suspicious for liver abscess. Drainage of the liver abscess was deferred due to its small size outweighing the risk of the procedure.

Metabolic derangements from diabetic ketoacidosis were corrected by hospital day 1. He remained hemodynamically unstable requiring vasopressor support. Neurological examination demonstrated minimally reactive dilated pupils, with absence of other brainstem reflexes and GCS 3 T since hospital day 2. Repeat non-contrast CT and CT perfusion on hospital day 4 and 6 revealed evolving diffuse hypoxic brain injury. A summary of CT imaging results is presented in Fig. 1. On hospital day 6, a nuclear medicine cerebral perfusion scan confirmed absent cerebral blood flow. After a meeting with substitute decision makers, care was transitioned to a palliative approach and life-sustaining therapies were withdrawn.

Discussion

HvKp is an increasingly prevalent variant of Klebsiella pneumoniae with higher mortality for which clinicians need to exercise an increased sense of awareness [3], [11]. To our knowledge, this is the first reported case of community-acquired meningitis with HvKp in Canada which proved rapidly progressive and fatal within a short period of symptom onset. Although hypervirulence was not microbiologically confirmed, this case illustrates that in non-endemic settings, community-acquired Klebsiella pneumoniae CNS infection with metastatic or atypical foci should prompt early consideration of HvKp, comprehensive evaluation for disseminated infection, and source control where feasible.

Microbiologic testing includes testing for hypermucoviscous phenotype through the “string test” whereby a loop is used to stretch a bacterial colony on an agar plate [12]. The test is considered positive when a viscous string of greater than five millimetres is formed [12], this test is not performed in our laboratory. Historically, magA and rmpA have been used as markers to confirm the presence of this hypervirulent subtype [12], [13]; however, magA has been proven less reliable in most recent testing [14]. A new working classification using five biomarkers has been proposed for the accurate identification of HvKP, including iucA, iroB, peg-344, rmpA, and rmpA2[14]. The presence of all five of these genes is associated with increased mortality [15].

Marker testing is not readily available in all centers and results may not be available in time to impact treatment decisions. We believe that HvKp diagnosis could still be clinically-suspected or diagnosed based on specific features. These include: 1) community-acquisition, 2) presence of liver abscess in the absence of biliary disease, 3) at least two sites of infection, and 4) less common sites of infection for CKp including endophthalmitis, meningitis, necrotizing fasciitis, splenic or epidural abscess, or community-acquired pneumonia [1], [2], [4], [7]. Diabetes mellitus is also an important risk factor associated with HvKp infection [8], [16]. All features were included in our case; however even the presence of one clinical feature or risk factor should raise suspicion and prompt testing for HvKp.

Following suspicion for HvKp infection, clinicians should exercise caution with early involvement of infectious disease specialists to prompt review of investigations and management. As HvKp may involve multiple sites of infection, full clinical exam in addition to cross-sectional imaging of the head, neck, chest, abdomen and pelvis should be obtained to document clinically silent sites of infection. Drainage of abscesses associated with HvKp has been shown to be associated with improved mortality and metastatic spread of infection [17].

HvKp was typically reported as a pan-sensitive micro-organism [18], as was the case for our patient. However, an increasing pattern of antimicrobial resistance has been observed in HvKp, with increasing prevalence during the COVID-19 pandemic [19]. In July 2024, the World Health Organization issued a statement warning of increasing carbapenem resistance in HvKp, a public health threat which may significantly limit treatment options in suspected cases [11]. Clinicians should consult their local microbiology laboratory for suggestions on antibiotic choice depending on site of infection.

Conclusion

We present a fatal case of HvKp in Canada presenting as community-acquired meningitis. In non-endemic settings, limited access to hypervirulence testing may delay recognition, underscoring the need for a high index of suspicion in community-acquired Klebsiella pneumoniae with metastatic or atypical foci.

CRediT authorship contribution statement

Antoine Tilmont: Writing – review & editing, Formal analysis, Data curation. Jasper Ho: Writing – review & editing, Formal analysis, Data curation. Rayyan Kinsara: Writing – review & editing, Visualization, Formal analysis. Emily Tam: Writing – review & editing, Resources. Alberto Goffi: Writing – review & editing, Resources, Project administration, Methodology, Investigation, Formal analysis, Data curation, Conceptualization. Charlie Tan: Writing – review & editing, Resources. Yingming Amy Chen: Writing – review & editing, Resources. Jamie Ghossein: Writing – review & editing, Writing – original draft, Methodology, Investigation, Formal analysis, Data curation, Conceptualization.

Author contributions

Jamie Ghossein reviewed the clinical information, performed the literature review, prepared the figures/tables, and drafted the manuscript. Antoine Tilmont reviewed the clinical presentation, assisted with data collection and critically revised the manuscript. Jasper Ho assisted with the literature review, data collation, and critical manuscript review. Rayyan Kinsara reviewed and annotated all diagnostic imaging and provided imaging interpretation, and contributed to critical manuscript revision. Charlie Tan, Yingming Amy Chen, and Emily Tam were involved in the patient’s clinical care and contributed to critical review of the manuscript. Alberto Goffi reviewed the clinical information, contributed to manuscript drafting and revisions, and provided supervision. All authors approved the final version of the manuscript.

Patient consent

Written informed consent was obtained from the patient’s legal substitute decision maker for publication of this case report and accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal on request.

Declaration of Competing Interest

The authors declare that they have no competing interests.

Appendix A. Supplementary material

Supplementary material