Template:ID-Tuberculous meningitis

• Tuberculous meningitis

• First-line therapy (dosing information: [1][2][3])

• Isoniazid
• Rifampin
• Rifabutin
• Pyrazinamide
• Ethambutol

• Second-line therapy (dosing information: [4][5][6])

• Cycloserine
• Ethionamide
• Streptomycin
• Amikacin
• Kanamycin
• Capreomycin
• p-Aminosalicylic acid
• Levofloxacin
• Moxifloxacin
• Gatifloxacin

• Tuberculous meningitis caused by susceptible Mycobacterium tuberculosis

• Intensive phase (adult)

• Preferred regimen: Isoniazid 5 mg/kg (max: 300 mg) for 2 months AND Rifampin 10 mg/kg (max: 600 mg) for 2 months AND Pyrazinamide 15–30 mg/kg (max: 2 g) for 2 months AND Ethambutol 15–20 mg/kg (max: 1 g) for 2 months

• Continuation phase (adult)

• Preferred regimen: Isoniazid 5 mg/kg (max: 300 mg) for 7–10 months AND Rifampin 10 mg/kg (max: 600 mg) for 7–10 months

• Intensive phase (pediatric)

• Preferred regimen: Isoniazid 10–15 mg/kg (max: 300 mg) for 2 months AND Rifampin 10–20 mg/kg (max: 600 mg) for 2 months AND Pyrazinamide 15–30 mg/kg (max: 2 g) for 2 months AND Ethambutol 15–20 mg/kg (max: 1 g) for 2 months

• Continuation phase (pediatric)

• Preferred regimen: Isoniazid 10–15 mg/kg (max: 300 mg) for 7–10 months AND Rifampin 10–20 mg/kg (max: 600 mg) for 7–10 months

Note (1): World Health Organization guidelines recommend that Ethambutol should be replaced by Streptomycin in tuberculous meningitis. Streptomycin is contraindicated in pregnancy.

Note (2): A 9– to 12–month course of treatment is recommended for tuberculous meningitis.

Note (3): Adjuvant Dexamethasone 0.3–0.4 mg/kg/day (max: 24 mg) is recommended unless drug resistance is suspected.

Note (4): Liaise with microbiology laboratory about genotype testing for drug resistance if there is high risk for MDR-TB.

• Tuberculous meningitis caused by Mycobacterium tuberculosis resistant to isoniazid or rifampin

• Isoniazid monoresistance

• Substitute fluoroquinolone for isoniazid in intensive phase regimen.
• Continue treatment with rifampin, pyrazinamide, and fluoroquinolone for 12 months.

• Rifampin monoresistance

• Substitute Fluoroquinolones for Rifampin in intensive phase regimen.
• Continue treatment with isoniazid, pyrazinamide, and fluoroquinolone for 18 months.

• MDR-TB (resistant to Isoniazid and Rifampin)

• MDR tuberculosis therapy should be considered if there is a history of prior tuberculosis treatment, contact with a patient with MDR tuberculosis, or a poor clinical response to first-line TB therapy within 2 weeks despite a firm diagnosis and an adequate adherence to treatment.
• Second-line agents such as Aminoglycosides penetrate the BBB only in the presence of inflamed meninges, and Fluoroquinolones, while able to penetrate into the CNS, have lower CSF levels than in the serum or brain parenchyma.
• Consult infectious disease specialist.

• XDR-TB (resistant to Isoniazid, Rifampin, Fluoroquinolones, and either Capreomycin, Kanamycin, or Amikacin)

• Consider Ethionamide or Cycloserine to build the treatment regimen.
• Consult infectious disease specialist.

Septic thrombosis of cavernous or dural venous sinus ⇧ Return to Top ⇧

• Septic thrombosis of cavernous or dural venous sinus

• Empiric antimicrobial therapy

• Preferred regimen: (Nafcillin 2 g IV q4h or Oxacillin 2 g IV q4h) AND (Ceftriaxone 2 g IV q12h or Cefotaxime 8–12 g/day IV q4–6h) AND Metronidazole 7.5 mg/kg IV q6h

Note (1): Vancomycin 30–45 mg/kg IV q8–12h could be substituted for nafcillin or oxacillin if the risk of MRSA is high.

Note (2): The optimal duration of therapy remains unclear. A 3– to 4–week course of treatment is usually recommended.

• Specific anatomic considerations

• Cavernous sinus

• Preferred regimen: Vancomycin 30–45 mg/kg IV q8–12h AND (Ceftriaxone 2 g IV q12h or Cefotaxime 8–12 g/day IV q4–6h) AND Metronidazole 7.5 mg/kg IV q6h

Note: Daptomycin 8–12 mg/kg IV q24h OR Linezolid 600 mg IV q12h could be considered for patients unable to tolerate vancomycin.

• Lateral sinus

• Preferred regimen: Cefepime 2 g IV q8h AND Metronidazole 500 mg IV q8h AND Vancomycin 15-20 IV mg/kg
• Alternative regimen: Meropenem 1-2 g IV q8h AND Linezolid 600 mg IV q12h

• Superior sagittal sinus

• Preferred regimen: Ceftriaxone 2 g IV q12h AND Vancomycin 15–20 mg/kg AND Dexamethasone
• Alternative regimen: Meropenem 1–2 g IV q8h AND Vancomycin 15–20 mg/kg AND Dexamethasone

• Pathogen-directed antimicrobial therapy

• Staphylococcus aureus, methicillin-resistant (MRSA)

• Preferred regimen: Vancomycin 15–20 mg/kg/dose IV q8–12h for 4–6 weeks
• Alternative regimen: Linezolid 600 mg PO/IV q12h for 4–6 weeks OR TMP-SMX 5 mg/kg/dose PO/IV q8–12h for 4–6 weeks
• Pediatric dose: Vancomycin 15 mg/kg/dose IV q6h OR Linezolid 10 mg/kg/dose PO/IV q8h

Note (1): Surgical evaluation for incision and drainage of contiguous sites of infection or abscess is recommended whenever possible.

Note (2): Consider the addition of Rifampin 600 mg qd or 300–450 mg bid to vancomycin.

Subdural empyema ⇧ Return to Top ⇧

• Subdural empyema

• Causative pathogens

• More common

• Streptococcus milleri
• Other streptococci and enterococci
• Aerobic Gram-negative bacilli (Haemophilus influenzae, Proteus, Escherichia coli, Pseudomonas, Klebsiella, Acinetobacter, Salmonella, Morganella, Eikenella)
• No growth

• Less common

• Streptococcus pneumoniae
• Staphylococcus aureus, coagulase-negative staphylococci
• Anaerobic Gram-positive cocci (Veillonella, Peptostreptococcus, others)
• Anaerobic Gram-negative bacilli (Bacteroides, Fusobacterium, Prevotella)

• Empiric antimicrobial therapy

Note (1): The choice of antimicrobial agent should be based on Gram stain results and directed against the likely causative microorganisms in the specific clinical setting.

Note (2): Metronidazole is recommended if anaerobes are suspected. Metronidazole is not necessary for antianaerobic activity if Meropenem is used.

Note (3): For coverage of aerobic Gram-negative bacilli, empiric therapy with Cefepime, Ceftazidime, or Meropenem is appropriate.

Note (4): Depending on the clinical response, parenteral antimicrobial therapy should be administered for 3 to 4 weeks after drainage. Parenteral or oral therapy is frequently continued for up to a total of 6 weeks of therapy.

Note (5): A longer course of treatment (minimum of 6–8 weeks) may be required if the patient has accompanying osteomyelitis.

Note (6): Consider adjunctive medications including prophylactic anticonvulsants, corticosteroids, and mannitol if clinically indicated.

• Intracranial subdural empyema with unclear source of infection

• Preferred regimen: (Nafcillin 2 g IV q4h or Oxacillin 2 g IV q4h) AND (Ceftriaxone 2 g IV q12h or Cefotaxime 8–12 g/day IV q4–6h) AND Metronidazole 7.5 mg/kg IV q6h

Note: Vancomycin should be used in place of nafcillin or oxacillin if MRSA is suspected or if penicillin allergy is present.

• Intracranial subdural empyema associated with sinusitis or otitis media

• Preferred regimen: (Nafcillin 2 g IV q4h or Oxacillin 2 g IV q4h) AND (Ceftriaxone 2 g IV q12h or Cefotaxime 8–12 g/day IV q4–6h) AND Metronidazole 7.5 mg/kg IV q6h

Note: Vancomycin should be used in place of nafcillin or oxacillin if MRSA is suspected or if penicillin allergy is present.

• Intracranial subdural empyema after cranial trauma

• Preferred regimen: Nafcillin 2 g IV q4h or Oxacillin 2 g IV q4h

Note: Vancomycin should be used in place of nafcillin or oxacillin if MRSA is suspected or if penicillin allergy is present.

• Intracranial subdural empyema after neurosurgical procedures

• Preferred regimen: Vancomycin 30–45 mg/kg/day IV q8–12h AND Ceftazidime 2 g IV q8h

• Intracranial subdural empyema in neonates (usually associated with meningitis)

• Infants < 1 month

• Preferred regimen: Ampicillin 200 mg/kg/day IV q4h AND Cefotaxime 200 mg/kg/day IV q6h

• Infants 1–3 months

• Preferred regimen: Ampicillin 200 mg/kg/day IV q4h AND (Cefotaxime 200 mg/kg/day IV q6h OR Ceftriaxone 100 mg/kg/day IV q12h)

• Infants > 3 months

• Preferred regimen: Vancomycin 60 mg/kg/day IV q6h AND (Cefotaxime 200 mg/kg/day IV q6h OR Ceftriaxone 100 mg/kg/day IV q12h OR Cefepime 150 mg/kg/day IV q8h)

• Spinal subdural empyema

• Preferred regimen: Nafcillin 2 g IV q4h or Oxacillin 2 g IV q4h

Note: Vancomycin should be used in place of nafcillin or oxacillin if MRSA is suspected or if penicillin allergy is present.

• Pathogen-directed antimicrobial therapy

• Staphylococcus aureus, methicillin-resistant (MRSA)

• Preferred regimen: Vancomycin 30–45 mg/kg/day IV q8–12h for 4–6 weeks
• Alternative regimen: Linezolid 600 mg PO/IV q12h for 4–6 weeks OR TMP-SMX 5 mg/kg/dose PO/IV q8–12h for 4–6 weeks
• Pediatric dose: Vancomycin 15 mg/kg/dose IV q6h OR Linezolid 10 mg/kg/dose PO/IV q8h

Note: Consider the addition of Rifampin 600 mg qd or 300–450 mg bid to vancomycin.