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Clostridium difficile

• 1. Initial episode

• 1.1 Mild to moderate

• Preferred regimen: Metronidazole 500 mg orally q8h
• Alternative regimen(If no improvement in 5-7 days): Vancomycin 125 mg orally q6h

• 1.2 Severe

• Preferred regimen: Vancomycin 125 mg orally q6h

• 1.3 Severe complicated

• Preferred regimen: Vancomycin 500 mg orally q6h AND Metronidazole 500 mg IV q8h
• NOTE: If ileus present, add Vancomycin 500 mg in 100 mL normal saline per rectum q6h as retention enema

• 2.Recurrence

• 2.1 First recurrence

• preferred regimen: Same as first episode but stratified by severity

• 2.2 Second recurrence

• preferred regimen: Vancomycin 125 mg 4 times daily for 14 days or 125 mg 2 times daily for 7 days or 125 mg once daily for 7 days or 125 mg once every 2 days for 8 days (4 doses) or 125 mg once every 3 days for 15 days (5 doses)

Clostridium tetani

• 1. General measures

• Preferred regimen: Patients should be placed in a quiet shaded area and protected from tactile and auditory stimulation as much as possible; All wounds should be cleaned and debrided as indicated

• 2. Immunotherapy

• Preferred regimen: Human TIG 500 units by intramuscular injection or intravenously as soon as possible AND Age-appropriate TT-containing vaccine, 0.5 cc by intramuscular injection at a separate site

• NOTE: patients without a history of primary TT vaccination should receive a second dose 1–2 months after the first dose and a third dose 6–12 months later

• 3. Antibiotic treatment

• Preferred regimen: Metronidazole 500 mg intravenously or orally every six hours OR Penicillin G 100,000–200,000 IU/kg/day intravenously, given in 2–4 divided doses

• Alternative regimen: Tetracyclines OR Macrolides OR Clindamycin OR Cephalosporins OR Chloramphenicol

• 4. Muscle spasm control

• Preferred regimen: Diazepam 5 mg intravenous OR Lorazepam 2 mg titrating to achieve spasm control without excessive sedation and hypoventilation

• Alternative regimen (1): Magnesium sulphate 5 gm (or 75mg/kg) intravenous loading dose, then 2–3 grams per hour until spasm control is achieved ± Benzodiazepines

• NOTE: Monitor patellar reflex as areflexia (absence of patellar reflex) occurs at the upper end of the therapeutic range (4mmol/L). If areflexia develops, dose should be decreased

• Alternative regimen (2): Baclofen OR Dantrolene 1–2 mg/kg intravenous/orally every 4 hours

• Alternative regimen (3): Barbiturates 100–150 mg every 1–4 hours by any route

• Alternative regimen (4): Chlorpromazine 50–150 mg by intramuscular injection every 4–8 hours

• Pediatric regimen: Lorazepam 0.1–0.2 mg/kg every 2–6 hours, titrating upward as needed; Barbiturates 6–10 mg/kg in children by any route; Chlorpromazine 4–12 mg every by intramuscular injection every 4–8 hours

• NOTE: As for Benzodiazepines, large amounts may be required (up to 600 mg/day); Oral preparations could be used but must be accompanied by careful monitoring to avoid respiratory depression or arrest

• 5. Autonomic dysfunction control

• Preferred regimen: Magnesium sulphate OR Morphine OR Esmolol

Mycobacterium abscessus

• 1.Limited, localized extrapulmonary disease

• Preferred regimen: Clarithromycin 500 mg PO twice daily ± Amikacin 10-15 mg/kg/day IV or 25 mg/kg three times weekly for 4 months

• Alternative regimen (1): Amikacin AND Cefoxitin 12 g/day typically for two weeks until clinical improvement in severe cases

• Alternative regimen (2): Amikacin AND Imipenem 500 mg IV q6-8h for two weeks until clinical improvement in severe cases
• NOTE: Osteomyelitis should be treated for as least 6 months; Infected foreign bodies should be removed

• 2.Pulmonary or serious extrapulmonary disease

• Preferred regimen: Clarithromycin 500 mg PO twice daily AND Amikacin 15 mg/kg/day IV AND Cefoxitin 2g q4h IV OR Imipenem 1g q6h IV for at least 2-4 months, if limited by adverse effects, then switch toClarithromycin 500 mg PO BID or 1000 mg XR OD OR Azithromycin 250 mg PO OD
• Alternative regimen(1): Tigecycline 100 mg IV load then 50 mg IV q12h could be substituted as one of the injectables
• Alternative regimen(2): Linezolid 600 mg PO q12h or 600 mg PO OD AND Clarithromycin could replace parental tx if not tolerated or feasible

Tuberculous

• Tuberculous meningitis (TB 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 (contraindicated in pregnancy) in tuberculous meningitis.

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.