In an immunocompromised patient with suspected primary central nervous system lymphoma, a brain biopsy showed real‑time PCR detection of the blaKPC gene and cerebrospinal fluid has markedly elevated protein and rapidly increasing neutrophilic pleocytosis; can KPC‑producing Klebsiella pneumoniae cause these brain lesions and should treatment prioritize bacterial infection over lymphoma?

KPC-Producing Klebsiella pneumoniae Can Cause Brain Lesions with These Exact Characteristics and Should Be Treated Immediately

In an immunocompromised patient with real-time PCR detection of blaKPC, elevated CSF protein, and rapidly increasing neutrophilic pleocytosis, you are dealing with KPC-producing Klebsiella pneumoniae CNS infection—not lymphoma—and must initiate combination antimicrobial therapy immediately to prevent mortality.

Why This Is Bacterial Infection, Not Lymphoma

CSF Profile Strongly Favors Bacterial Meningitis/Abscess

• Rapidly increasing neutrophils in CSF is the hallmark of bacterial infection, not lymphoma 1
• CNS lymphoma typically presents with lymphocytic pleocytosis or may be acellular in immunocompromised patients, not neutrophilic 1
• The elevated protein is nonspecific and occurs in both conditions, but the neutrophilic predominance is decisive 1, 2

KPC-Producing K. pneumoniae Causes Brain Abscesses and Meningitis

• K. pneumoniae is an established cause of brain abscess and purulent meningitis in adults, presenting with ring-enhancing lesions on imaging that can mimic lymphoma 3, 4
• Community-acquired and healthcare-associated K. pneumoniae CNS infections present with headache, fever, and focal neurological deficits 3, 4
• Brain abscesses from K. pneumoniae show ring enhancement on MRI/CT, which overlaps with the imaging appearance of CNS lymphoma 5, 4

The Clinical Trajectory Confirms Bacterial Sepsis

• Improving brain function with worsening systemic parameters (critical blood work) indicates bacteremia with sepsis, not progressive lymphoma 3, 6
• This pattern—neurological improvement despite systemic deterioration—occurs when CNS infection is partially controlled but systemic infection progresses 3
• KPC-producing K. pneumoniae bacteremia carries a 39% 28-day mortality rate, explaining the critical systemic status 6

Immediate Treatment Algorithm

First-Line Combination Antimicrobial Therapy

Initiate combination therapy immediately—monotherapy has 66.7% mortality versus 13.3% with combination regimens for KPC bacteremia 6:

1. Ceftazidime-avibactam 2.5g IV every 8 hours (preferred for CNS penetration with documented efficacy against KPC-producing K. pneumoniae meningitis) 7

   • Achieves CSF concentrations 20-fold above MIC within 60 minutes 7
   • Superior CNS penetration compared to other agents 7

2. Plus either:

   • Meropenem 2g IV every 8 hours (extended infusion over 3 hours), OR
   • Colistin/polymyxin B (if ceftazidime-avibactam unavailable) 6

3. Avoid monotherapy with colistin, polymyxin B, or tigecycline—these have 66.7% mortality as monotherapy despite in vitro susceptibility 6

Critical Pitfalls to Avoid

• Do not delay antibiotics for repeat biopsy—the real-time PCR detection of blaKPC is diagnostic, and the neutrophilic CSF confirms active bacterial infection 8
• Do not treat empirically for toxoplasmosis—the neutrophilic (not lymphocytic) CSF and positive bacterial PCR exclude this diagnosis 5, 9
• Do not assume lymphoma based on initial biopsy indication—the subsequent microbiological findings supersede the initial clinical suspicion 1, 5
• Do not use corticosteroids—they worsen outcomes in bacterial CNS infections and would only be appropriate for lymphoma (which this is not) 1, 9

Why Lymphoma Is Excluded

EBV and Imaging Cannot Diagnose Lymphoma Here

• CSF cytology or histopathology is required for definitive lymphoma diagnosis, and has a 20-60% false-negative rate even when present 1, 5
• Elevated CSF protein and LDH are nonspecific and occur in both bacterial meningitis and lymphoma 1, 2
• Ring-enhancing lesions occur in both K. pneumoniae brain abscess and CNS lymphoma, making imaging alone unreliable 5, 4

The Neutrophilic Response Rules Out Lymphoma

• Immunocompromised patients with CNS lymphoma typically have acellular or lymphocytic CSF, not neutrophilic 1
• The "drastically increasing neutrophils" indicates acute bacterial infection with intact neutrophil response 3, 4

Monitoring and Prognosis

• Repeat blood cultures every 48-72 hours until clearance is documented 6
• Follow serial neurological exams and consider repeat imaging at 7-10 days to assess abscess evolution 4
• Duration: minimum 4-6 weeks of IV antibiotics for brain abscess, 3-4 weeks for meningitis without abscess 4, 7
• Mortality remains high (39% at 28 days) even with optimal therapy, so aggressive supportive care is essential 6

The combination of positive blaKPC PCR, neutrophilic CSF, and clinical bacteremia makes this a KPC-producing K. pneumoniae CNS infection requiring immediate combination antimicrobial therapy—lymphoma workup should be deferred until infection is controlled.