Yuka Manabe, M.D.
Mono-resistance: bacilli resistant to only one anti-TB drug. INH is most common
Poly-resistance: bacilli resistant in vitro to more than one anti-TB drug, with the exception of both INH & RIF.
MDR-TB (multi-drug resistant TB): bacilli resistant in vitro to both INH & RIF
- MDR-TB occurs when patients poorly adherent to therapy or when monotherapy prescribed. Can also be transmitted.
- Greatest risk for MDR-TB: 1) chronic TB with failure of primary or retreatment (sputum + at end of retreatment) 2) close contacts of MDR-TB pts, especially children <5 yrs and HIV+ pts in whom primary active disease occurs at higher rates, 3) use of poor quality drugs, 4) pts with malabsorption
XDR-TB (extremely drug resistant TB): MDR-TB bacilli also resistant in vitro to fluoroquinolones + at least 1 injectable agent (capreomycin, kanamycin, amikacin).
- Collect at least 2 sputum specimens for microscopy and culture in reputable reference lab
Streptomycin - 15 mg/kg per day (1 g/day) parenterally daily, then 3 x/wk after 2-4 months, 10 mg/kg/day in pts >59 yrs age, avoid in pregnant (fetal ototoxicity), dose adjust or avoid in renal insufficiency
Kanamycin/amikacin - 15 mg/kg, 750 mg-1 gm given daily by deep IM injection; 2-4 months, can reduce to 3x/week after; 10 mg/kg/day in pts>59 yrs age, avoid in pregnant (fetal ototoxicity), dose adjust or avoid in renal insufficiency
Ethionamide - 250 mg tablet, 15-20 mg/kg or 1 gm, usually 500 mg-1 gm daily or in divided dose, not in pregnancy
- Fluoroquinolones - moxifloxacin 400 mg daily;levofloxacin 600-800 mg daily; ofloxacin 800 mg daily, can decrease to 400 mg in continuation phase; ciprofloxacin 500-1000 mg PO daily or divided BID
- Cycloserine - 250 mg capsule, 10-15 mg/kg (max dose 1000 mg); usually 500-750 mg given in 2 doses, administer with pyridoxine 150 mg, avoid with renal failure. When possible, cycloserine should be avoided, since assiduous drug monitoring is often required in resource-rich settings.
- Capreomycin - 15 mg/day (1 g/day) daily by deep IM injection; 2-4 months, can reduce to 3x/week after; 10 mg/kg/day in pts >59 yrs age, avoid in pregnant (fetal ototoxicity), dose adjust or avoid in renal insufficiency
- p-aminosalicylic acid (PAS) - 8-12 g/day in 2 or 3 doses (4 gms BID or TID), avoid in renal insufficiency, 80% renally excreted
- Use at least 2 new drugs to which organism is susceptible to treat MDR-TB
- Second-line drugs include fluoroquinolones (moxifloxacin, ofloxacin or ciprofloxacin), aminoglycoside injectables (kanamycin or amikacin, although resistance to these drugs may occur after streptomycin use), cycloserine (should titrate based on levels), thioamides (ethionamide or prothionamide), terizidone/cyloserine (CNS side effects common)
- If susceptible to FQ, would use as best tolerated 2nd line and currently under investigation for first line in combination with at least one other active drug by susceptibility testing.
- FQ resistant quickly develops when FQ used empirically for bacterial pneumonia
- XDR-TB can occur with use of empiric algorithms for retreatment in absence of susceptibility testing. Susceptibility testing, DOT, and safeguards against further nosocomial transmission are all important in preventing/controlling XDR-TB.
- Avoid admission to general ward
- Advise pt to sleep in separate room of house
- Ban sale of second-line drugs over the counter
- Directly observed therapy (DOT) under supervision of in-country experts
- Isolation in an well-ventilated room when possible.
Streptomycin: Ototoxicity, circumoral parasthesias, nephrotoxicity
Kanamycin: injection site local reactions, ototoxicity, vertigo, reversible nephrotoxicity (dose reduce in pts with renal impairment)
Ethionamide: nausea, GI sxs, metallic taste, vomiting, psychotic reactions, hypoglycemia, hepatitis
- Fluoroquinolones: GI, CNS, hypoglycemia, Achilles tendon rupture (moxifloxacin)
- Cycloserine: dizziness, convulsions, CNS, suicide/mood alteration; administer with pyridoxine 150mg, avoid with renal failure
- Capreomycin: Ototoxicity, nephrotoxicity, nausea, rash
- p-aminosalicylic acid: GI, hypothyroidism, hepatotoxicity, coagulopathy