Related Experiment Video

Updated: May 6, 2026

Novel Diagnostics in Revision Arthroplasty: Implant Sonication and Multiplex Polymerase Chain Reaction

Novel Diagnostics in Revision Arthroplasty: Implant Sonication and Multiplex Polymerase Chain Reaction

Published on: December 3, 2017

When the meningitis-encephalitis panel is negative: off-label joint infection PCR detects CTX-M ESBL-producing

Márk Kozák¹, Levente Majoros², Ferenc Bodnár²

¹Department of Infectology, Faculty of Medicine, University of Debrecen, 2-26 Bartok Bela Street, Debrecen, 4031, Hungary. kozak.mark@med.unideb.hu.

BMC Infectious Diseases

|May 4, 2026

Abstract:

Spontaneous Gram-negative bacillary meningitis in adults is rare and carries high mortality, particularly in elderly patients with significant comorbidities. Although multiplex meningitis-encephalitis (ME) panels have improved diagnostic turnaround time, their limited pathogen spectrum may reduce sensitivity for certain clinically relevant Gram-negative organisms. We report a 78-year-old man presenting with acute meningoencephalitis, septic deterioration, and cerebrospinal fluid (CSF) findings strongly suggestive of bacterial infection. Despite marked neutrophilic pleocytosis and elevated protein levels, the multiplex ME panel was negative. Blood cultures subsequently yielded Proteus mirabilis. Given the discordance between inflammatory CSF findings and routine molecular testing, following interdisciplinary consultation, an off-label BioFire^® Joint Infection multiplex PCR panel was performed directly on CSF. The assay identified Proteus mirabilis harboring a cefotaximase-Munich (CTX-M)-type extended-spectrum β-lactamase (ESBL) resistance determinant. Based on this result, antimicrobial therapy was escalated from ceftriaxone-based empiric treatment to meropenem prior to availability of phenotypic susceptibility data. Despite early pathogen identification and targeted antimicrobial therapy, the patient died due to multiorgan dysfunction secondary to severe sepsis. This case suggests a potential diagnostic limitation of standard ME panels in selected high-risk scenarios and indicates that selective off-label use of broader multiplex PCR platforms may provide additional clinically relevant information in carefully selected patients. In the setting of high clinical suspicion and negative routine multiplex testing, rapid resistance-gene detection may provide actionable information within a decisive therapeutic window and support timely antimicrobial optimization in severe Gram-negative central nervous system infections. Further studies are required to evaluate the diagnostic performance and clinical impact of such approaches. Written informed consent for publication was obtained from the patient's next of kin, and the study was conducted in accordance with institutional and ethical standards.Clinical trial number Not applicable.

Insights

Standard multiplex meningitis panels may miss rare Gram-negative bacteria, like Proteus mirabilis, in elderly patients. Off-label PCR use on cerebrospinal fluid identified resistance genes, aiding treatment, though the patient unfortunately died.

Area of Science:

Infectious Diseases
Neurology
Clinical Microbiology

Background:

Spontaneous Gram-negative bacillary meningitis is rare but deadly, especially in elderly patients with comorbidities.
Standard multiplex meningitis-encephalitis (ME) panels may have limited sensitivity for certain Gram-negative pathogens.
Early diagnosis and targeted treatment are crucial for improving outcomes in bacterial meningitis.

Purpose of the Study:

To report a case of Gram-negative meningitis missed by standard ME panels.
To highlight the potential utility of off-label multiplex PCR in diagnosing difficult cases.
To emphasize the importance of rapid resistance gene detection for antimicrobial optimization.

Main Methods:

A case report of a 78-year-old male with acute meningoencephalitis.
Initial diagnosis using cerebrospinal fluid (CSF) analysis and standard multiplex ME panel.
Subsequent off-label use of a multiplex PCR panel for joint infections directly on CSF.
Blood cultures for pathogen identification and resistance gene detection.

Main Results:

CSF analysis showed inflammation, but the standard ME panel was negative.
Blood cultures identified Proteus mirabilis.
Off-label CSF PCR detected Proteus mirabilis with an extended-spectrum β-lactamase (ESBL) resistance gene (CTX-M).
Antimicrobial therapy was escalated to meropenem based on PCR results before susceptibility data.

Conclusions:

Standard ME panels may fail to detect certain Gram-negative pathogens in meningitis.
Off-label use of broader multiplex PCR panels can provide critical diagnostic information in select cases.
Rapid resistance gene detection in CSF can guide timely antimicrobial escalation in severe Gram-negative CNS infections, despite a fatal outcome in this case.

Read full analysis

Keywords:

Proteus mirabilis Bacterial meningitis Extended-spectrum beta-lactamase Multiplex PCR Off-label use

More Related Videos

Antigen-Capture Enzyme-Linked Immunosorbent Assay for Specific Detection of Mycoplasma pneumoniae

Antigen-Capture Enzyme-Linked Immunosorbent Assay for Specific Detection of Mycoplasma pneumoniae

Published on: February 24, 2023

Real-Time Quantification of Reactive Oxygen Species in Neutrophils Infected with Meningitic Escherichia Coli

Real-Time Quantification of Reactive Oxygen Species in Neutrophils Infected with Meningitic Escherichia Coli

Published on: April 20, 2021

Related Concept Videos

Bacterial Meningitis I: Introduction

Bacterial Meningitis I: Introduction

Bacterial meningitis is a severe, life-threatening inflammation of the meninges, particularly the pia mater and arachnoid mater, affecting the subarachnoid space, ventricles, and cerebrospinal fluid (CSF). If untreated, it can lead to significant neurological complications or death.Causative AgentsCommon pathogens vary with age and immune status. In adults, major organisms include Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae. Streptococcus agalactiae (group B...

Viral Meningitis

Viral Meningitis

Viral meningitis is the most common form of meningitis and is often referred to as aseptic meningitis to indicate the absence of bacterial involvement. It is generally milder than bacterial meningitis, with symptoms including fever, headache, stiff neck, drowsiness, nausea, photophobia, and vomiting. Rarely, more severe manifestations or death may occur. Common causative agents include enteroviruses, particularly coxsackie A and B viruses and echoviruses, all members of the Enterovirus genus...

Atypical Pneumonia

Atypical Pneumonia

Atypical pneumonia, often caused by Mycoplasma pneumoniae, is a form of pulmonary infection that differs from the classical presentation of bacterial pneumonia in both its cause and clinical symptoms. Mycoplasma pneumoniae is a pleomorphic bacterium notable for its lack of a rigid cell wall. This structural characteristic imparts resistance to beta-lactam antibiotics and significantly influences the bacterium’s behavior within the human host.Other pathogens responsible for the disease...

Bacterial Meningitis II: Pathophysiology

Bacterial Meningitis II: Pathophysiology

Bacterial meningitis typically begins when pathogens such as Neisseria meningitidis and Streptococcus pneumoniae colonize the nasopharynx and invade the bloodstream. This process is facilitated by bacterial virulence factors, such as polysaccharide capsules, which resist phagocytosis and complement-mediated killing. Less commonly, bacteria reach the central nervous system via contiguous spread from infections like otitis media or sinusitis, through congenital or acquired dural defects, or...

Encephalitis l: Introduction

Encephalitis l: Introduction

Encephalitis is inflammation of the brain parenchyma, most often due to infections or autoimmune processes. It presents with neuropsychiatric features such as fever, altered mental status, behavioral changes, cognitive dysfunction, seizures, focal deficits, and sometimes autonomic instability. In some cases, the meninges are also involved, resulting in meningoencephalitis.Infectious CausesInfectious encephalitis is most commonly viral but can also result from bacterial, fungal, or parasitic...

Pneumonia III: Complications and Assessment

Pneumonia III: Complications and Assessment

Pneumonia poses the potential for numerous complications that warrant consideration. These complications include the following:

Articles linked to this work by shared authors, journal, and citation graph.

Establishment of a novel human nervous system tissue bank: University of Debrecen tissue bank-introduction and retrospective data analysis.

Cell and tissue banking·2026

Across Kingdoms: The Bacteriome, Mycobiome, and Virome in Autoimmune Diseases: Mechanistic Insights, Therapeutic Perspectives, and the Emerging Role of COVID-19.

Nutrients·2026

Toscana virus infection acquired in Campania, Italy, in a Hungarian traveller: case report with mini-review.

Tropical diseases, travel medicine and vaccines·2026

Retrospective neutralization analysis of SARS-CoV-2 variants in early pandemic sera.

Frontiers in immunology·2026

Migraine and the Gut-Brain Axis-The Role of Microbiome-Targeted Biotics.

Nutrients·2026

Severe vitamin K deficiency-associated coagulopathy triggered by Clostridioides difficile infection and antibiotic-associated dysbiosis: A case report and literature review.

Infection·2026

See all related articles