In an immunocompromised patient whose cerebrospinal fluid (CSF) a week ago showed elevated protein and neutrophilic pleocytosis, and whose fresh brain biopsy today detects only the blaKPC (Klebsiella pneumoniae carbapenemase) gene by polymerase chain reaction (PCR), with a rapidly rising peripheral neutrophil count, what does this indicate about the likely diagnosis and the nature of the brain lesions?

Brain Biopsy Detecting Only KPC Gene with Rising Neutrophils: Bacterial Brain Abscess

This clinical picture—KPC PCR-positive brain tissue, rapidly rising peripheral neutrophils, and brain lesions—indicates a bacterial brain abscess caused by carbapenemase-producing Klebsiella pneumoniae, not a primary CNS lymphoma or viral/fungal infection. The prior CSF findings of elevated protein and leukocytes one week ago likely represented early meningeal inflammation from the developing parenchymal infection, while the current brain biopsy molecular detection of blaKPC confirms active bacterial invasion of brain tissue 1.

Why This Is Bacterial Brain Abscess, Not Other CNS Pathology

The KPC PCR Finding Is Diagnostic of Bacterial Infection

• Detection of the blaKPC carbapenemase gene by PCR in brain biopsy tissue directly indicates the presence of carbapenemase-producing Klebsiella pneumoniae or other KPC-producing Enterobacterales in the brain parenchyma 1, 2.
• KPC-producing bacteria are highly drug-resistant Gram-negative bacilli causing infections with significant morbidity and mortality, and the blaKPC gene is most commonly carried by K. pneumoniae 1, 2.
• The detection of blaKPC by PCR represents direct molecular evidence of bacterial DNA in the brain tissue, confirming active bacterial infection rather than sterile inflammation or malignancy 3.

Rising Peripheral Neutrophils Reflect Systemic Bacterial Response

• Progressive and drastic neutrophil elevation in peripheral blood is the hallmark of acute bacterial infection, not viral encephalitis, fungal meningitis, or CNS lymphoma 1.
• In bacterial meningitis and brain abscess, peripheral leukocytosis with neutrophil predominance is expected as part of the systemic inflammatory response 1.
• The combination of rising neutrophils with KPC-positive brain tissue confirms an ongoing, severe bacterial infection requiring immediate targeted antimicrobial therapy 1.

The Prior CSF Findings Are Consistent with Bacterial CNS Infection

• One week ago, CSF showed elevated protein and leukocytes (pleocytosis), which are nonspecific findings that can occur in bacterial, tuberculous, fungal, or viral CNS infections 1, 4.
• However, when combined with today's brain biopsy showing KPC DNA and rising peripheral neutrophils, the prior CSF abnormalities retrospectively represent early bacterial meningeal inflammation or ventriculitis secondary to the developing brain abscess 1.
• CSF in bacterial brain abscess may show elevated protein (often >1 g/L) and pleocytosis, but the cell count and differential depend on whether the abscess has ruptured into the ventricular system 1, 4.

What the Brain Lesions Represent

Brain Lesions Are Bacterial Abscesses

• The brain lesions visualized on imaging (presumably MRI or CT) represent bacterial abscesses—localized collections of pus within the brain parenchyma caused by KPC-producing K. pneumoniae 1.
• Brain abscesses typically appear as ring-enhancing lesions with surrounding edema on contrast-enhanced MRI, which can be confused with CNS lymphoma, metastases, or tuberculomas 1.
• The definitive diagnosis is made by brain biopsy with molecular detection of bacterial DNA (in this case, blaKPC), which distinguishes bacterial abscess from other ring-enhancing lesions 1, 3.

Why Not CNS Lymphoma?

• Primary CNS lymphoma (PCNSL) typically presents with contrast-enhancing brain lesions, elevated CSF protein, and increased CSF leukocyte count 1.
• However, PCNSL does not cause detection of bacterial carbapenemase genes in brain tissue, nor does it produce the rapidly rising peripheral neutrophilia seen in this patient 1.
• PCNSL is diagnosed by stereotactic biopsy showing diffuse large B-cell lymphoma histopathology, not by PCR detection of bacterial resistance genes 1.

Why Not Tuberculous Meningitis?

• Tuberculous (TB) meningitis presents with lymphocytic pleocytosis, markedly elevated CSF protein (>1 g/L), low CSF glucose (CSF/plasma ratio <0.5), and a subacute course 4, 5.
• TB meningitis would be diagnosed by detection of Mycobacterium tuberculosis DNA by TB PCR, not by detection of blaKPC carbapenemase genes 4.
• The rising peripheral neutrophils and detection of KPC DNA in brain tissue are inconsistent with TB meningitis, which typically shows lymphocytic predominance and requires TB-specific molecular testing 4, 5.

Immediate Management: Targeted Antimicrobial Therapy for KPC

First-Line Treatment for KPC-Producing Brain Abscess

• For infections caused by KPC-producing carbapenem-resistant Enterobacterales (CRE), novel β-lactam agents such as ceftazidime/avibactam and meropenem/vaborbactam should be the first-line treatment options 1.
• Ceftazidime/avibactam has favorable efficacy and safety in patients with KPC-producing CRE infections, with improved clinical outcomes compared to traditional antibiotic regimens 1.
• Imipenem/relebactam and cefiderocol may also be considered as alternative agents 1.

Why Traditional Carbapenems Are Ineffective

• Carbapenem antibiotics are generally not effective against KPC-producing organisms because the KPC enzyme hydrolyzes carbapenems, rendering them inactive 1, 2.
• Resistance to the carbapenem antibiotic ertapenem is common and a better indicator of the presence of KPCs 2.
• Traditional antibiotic regimens (including colistin-based combinations) have poor efficacy and unfavorable toxicity profiles, with approximately one in three patients dying and <70% achieving clinical or microbiological response 1.

Adjunctive Measures for Brain Abscess

• Neurosurgical consultation is essential for consideration of stereotactic aspiration or excision of the abscess, especially if the lesion is large (>2.5 cm), causing mass effect, or not responding to antimicrobial therapy (general medical knowledge).
• Serial imaging (MRI) should be performed to monitor abscess size and response to therapy (general medical knowledge).
• Prolonged antimicrobial therapy (typically 6-8 weeks) is required for bacterial brain abscess, with duration guided by clinical and radiographic response (general medical knowledge).

Critical Diagnostic Pitfalls to Avoid

Do Not Delay Antimicrobial Therapy Waiting for Culture Results

• KPC-producing bacteria are often misidentified by routine microbiological susceptibility testing and incorrectly reported as sensitive to carbapenems 2.
• Time from blood culture collection to the start of active antibiotic therapy influences the outcome of critically ill patients with bloodstream infection caused by KPC-producing K. pneumoniae 1.
• Rapid testing strategies (such as PCR for blaKPC) should guide antibiotic therapy immediately, without waiting for conventional culture and susceptibility results 1, 3.

Do Not Confuse This with Sterile Post-Neurosurgical Inflammation

• The detection of bacterial DNA (blaKPC) in brain tissue confirms active infection, not sterile inflammation or contamination 3.
• The combination of KPC-positive biopsy, rising neutrophils, and brain lesions mandates immediate targeted antimicrobial therapy, not observation or corticosteroids alone 1.

Ensure Source Control and Rule Out Systemic Dissemination

• Blood cultures should be obtained to assess for concurrent bacteremia, which is common in patients with KPC-producing CRE infections and influences prognosis 1.
• Imaging of other potential sources (chest, abdomen, urinary tract) should be performed to identify the primary source of infection and rule out metastatic abscesses (general medical knowledge).