What is the recommended treatment for a patient with central nervous system (CNS) melioidosis, particularly one with underlying medical conditions such as diabetes or chronic kidney disease?

Treatment of CNS Melioidosis

For CNS melioidosis in patients with underlying conditions like diabetes or chronic kidney disease, initiate high-dose intravenous meropenem (preferred over ceftazidime for severe CNS infections) for at least 10-14 days, followed by oral trimethoprim-sulfamethoxazole for 12-20 weeks, with mandatory dose adjustments for renal impairment. 1

Acute Phase Treatment (Intensive Phase)

First-Line Antibiotic Selection

• Meropenem is the preferred carbapenem for CNS melioidosis and should be strongly considered as first-line therapy, particularly in critically ill patients with CNS involvement 1
• All B. pseudomallei isolates demonstrate sensitivity to meropenem and imipenem 1
• Ceftazidime remains an acceptable alternative, though meropenem is preferred for severe disease 2, 3
• Never use ertapenem, azithromycin, or moxifloxacin as these agents show resistance and should never be used for melioidosis 1

Dosing and Duration

• Administer intravenous therapy for at least 10-14 days (some sources recommend up to 6 weeks for CNS involvement) 1, 4, 3
• Critical dosage adjustment required: In patients with creatinine clearance ≤50 mL/min, dose reduction is mandatory to prevent seizures 5
• The FDA label specifically warns that seizures occur most commonly in patients with CNS disorders and compromised renal function 5

Special Considerations for Renal Impairment

• Monitor creatinine clearance regularly as renal function can deteriorate rapidly in elderly patients with diabetes and chronic kidney disease 1
• Close adherence to recommended dosage regimens is essential, especially in patients with factors predisposing to convulsive activity 5
• If focal tremors, myoclonus, or seizures occur, evaluate neurologically and consider decreasing or discontinuing meropenem 5

Critical Drug Interaction Warning

• Do not use meropenem concomitantly with valproic acid or divalproex sodium as carbapenems reduce valproic acid concentrations below therapeutic range, increasing breakthrough seizure risk 5
• If the patient requires anticonvulsant therapy for seizure control, consider supplemental anticonvulsant therapy that does not interact with carbapenems 5

Eradication Phase (Maintenance Therapy)

Standard Regimen

• Follow intensive phase with oral trimethoprim-sulfamethoxazole (TMP-SMX) for 12-20 weeks to prevent relapse 1, 2, 3
• Standard dosing: trimethoprim 8 mg/kg/day plus sulfamethoxazole 40 mg/kg/day, divided into two doses 1
• This prolonged eradication phase is essential as even with 20 weeks of treatment, 10% of patients relapse 6

Alternative Regimens

• For patients unable to tolerate TMP-SMX, consider amoxicillin-clavulanate as second-line eradication therapy 2, 3
• Some protocols include doxycycline in combination with TMP-SMX, though this is more common in non-CNS melioidosis 4, 3, 7

Surgical Management

• Drainage of abscesses is essential whenever possible in addition to antibiotic therapy 2, 3
• For brain abscesses, surgical intervention (stereotactic aspiration or open drainage) followed by appropriate antibiotic therapy improves outcomes 4
• All surgically treated patients in one series had good outcomes when surgery was combined with prolonged antibiotic therapy 4

Monitoring and Neurological Assessment

• Assess neurological status daily for improvement or deterioration 1
• Monitor for signs of treatment failure including persistent fever (median time to fever resolution is 9 days even with appropriate therapy) 6
• Continue anticonvulsant therapy in patients with known seizure disorders throughout meropenem treatment 5

Critical Medications to Avoid

Nephrotoxic Agents

• Avoid NSAIDs and COX-2 inhibitors as they are nephrotoxic and will worsen renal function in patients with chronic kidney disease 1
• Avoid spironolactone due to hyperkalemia risk in renal impairment 1

Anticoagulation Considerations

• If the patient has concurrent atrial fibrillation requiring anticoagulation, defer initiation until CNS imaging confirms no active intracranial bleeding and clinical stability is achieved 1
• NOACs demonstrate lower intracranial bleeding risk compared to warfarin in elderly patients if anticoagulation becomes necessary 1

Common Pitfalls to Avoid

• Do not use inadequate treatment duration: The two-phase approach (intensive followed by eradication) is mandatory; premature discontinuation leads to relapse 2, 3, 6
• Do not miss dose adjustments in renal impairment: Failure to adjust meropenem dosing increases seizure risk significantly 5
• Do not assume treatment failure early: Response to therapy is slow with median time to fever resolution of 9 days 6
• Do not overlook abscess drainage: Medical therapy alone is insufficient when drainable collections are present 4, 2

Prognosis and Expected Outcomes

• Mortality in treated melioidosis remains 40% in some endemic areas, emphasizing the importance of early diagnosis and appropriate therapy 6
• With appropriate surgical drainage and prolonged two-phase antibiotic therapy, good outcomes are achievable in CNS melioidosis 4
• The presence of diabetes increases relative risk of infection by up to 100-fold and may complicate management 7