How should I manage a patient with a confirmed KPC‑producing Klebsiella pneumoniae brain abscess who has CSF neutrophilic pleocytosis and marked peripheral neutrophilia?

Management of KPC-Producing Klebsiella pneumoniae Brain Abscess with CSF Neutrophilic Pleocytosis and Marked Peripheral Neutrophilia

Proceed immediately with neurosurgical aspiration or excision combined with aggressive combination antimicrobial therapy, as this represents a life-threatening infection requiring both source control and multi-drug treatment to achieve survival. 1, 2

Immediate Surgical Intervention

Neurosurgical aspiration should be performed as soon as possible—ideally within 24 hours of diagnosis—as this reduces mortality from 24% to 9% and provides critical diagnostic material for culture-directed therapy. 1, 2

• Aspiration is preferred over excision in most cases, providing both therapeutic benefit (reducing intracranial pressure and bacterial load) and diagnostic confirmation through pus sampling 1, 3
• Send aspirated material for aerobic and anaerobic cultures, histopathological analysis, and store additional samples for molecular diagnostics if initial cultures remain negative 1, 2
• Excision may be considered for superficial abscesses in non-eloquent areas or posterior fossa locations, particularly given KPC organisms are difficult-to-treat pathogens 1, 2

Antimicrobial Therapy Strategy

Initiate combination antimicrobial therapy immediately, as monotherapy with colistin-polymyxin B or tigecycline carries 66.7% mortality compared to 13.3% with combination regimens in KPC bacteremia. 4

Recommended Combination Regimen:

• High-dose meropenem (2g IV every 8 hours as prolonged infusion) PLUS polymyxin B or colistin PLUS tigecycline as the empirical backbone 1, 4
• Consider adding intrathecal or intraventricular amikacin (5-30mg daily) given the CNS location and documented success in the only reported case of KPC brain abscess 5
• Add oral sulfamethoxazole-trimethoxazole if susceptibility testing permits, as this was used successfully in the single reported KPC brain abscess case 5

Critical Dosing Considerations:

• Perform therapeutic drug monitoring (TDM) for meropenem, polymyxins, and aminoglycosides to optimize CNS penetration and minimize nephrotoxicity 1
• High-dose meropenem with prolonged infusion achieves better CNS penetration despite carbapenem resistance 1
• Duration: 6-8 weeks of intravenous therapy for aspirated brain abscesses 1, 3, 2

Understanding the CSF Findings

The neutrophilic pleocytosis you're observing is consistent with both bacterial brain abscess and can mimic CNS infection patterns—do not let this mislead you into thinking this is viral or autoimmune. 1

• CSF neutrophilic pleocytosis occurs in bacterial meningitis and brain abscess, particularly with KPC organisms 1
• Persistent neutrophilic pleocytosis has been observed with certain bacterial CNS infections and does not rule out brain abscess 1
• The marked peripheral neutrophilia reflects systemic inflammatory response to severe bacterial infection 1
• CSF findings in brain abscess can show neutrophil predominance with elevated protein and low glucose, mimicking bacterial meningitis 1

Critical Monitoring Protocol

Perform repeat brain MRI every 2 weeks until clinical cure is evident, and prepare for repeat aspiration if no volume reduction occurs by 4 weeks. 1, 2

• Immediate imaging is required for any clinical deterioration 1, 2
• Lack of abscess regression by 4 weeks post-aspiration is unusual and mandates repeat intervention 1, 2
• Approximately 21% of aspiration cases require repeat procedures 2
• Monitor for rupture risk (occurs in 10-35% of cases with 27-50% mortality), especially given proximity to ventricles 2, 6

Adjunctive Management

• Administer dexamethasone only for severe symptoms from perifocal edema or impending herniation—not routinely, as it may impair antimicrobial penetration 3, 2
• Do not use prophylactic antiepileptics unless seizures occur 3
• Consider external ventricular drainage if obstructive hydrocephalus develops 2, 6

Common Pitfalls to Avoid

Do not rely on routine susceptibility testing alone—KPC organisms are often misidentified as carbapenem-sensitive, particularly if ertapenem resistance is not specifically tested. 7

• Carbapenem antibiotics as monotherapy are generally ineffective against KPC organisms despite reported susceptibility 7
• Do not use monotherapy with polymyxins or tigecycline—mortality reaches 66.7% versus 13.3% with combination therapy 4
• Do not delay surgery waiting for antimicrobials to work—source control is essential for survival 1, 2
• Do not prolong antimicrobial therapy beyond 6-8 weeks based solely on residual contrast enhancement, which may persist 3-6 months after clinical cure 1, 2

Prognosis and Long-Term Considerations

• KPC-producing organisms carry significant morbidity and mortality even with optimal treatment 7, 4
• Long-term sequelae occur in approximately 45% of patients at 6 months, including focal neurological deficits and neurocognitive impairment 3, 2
• Plan for specialized neurorehabilitation referral 3, 2
• The single reported case of KPC brain abscess achieved cure with combination IV/intrathecal therapy plus surgical drainage, providing a roadmap for your approach 5