Table 4 First-line and second-line drugs used for the treatment of drug-resistant TB (WHO classification)

From: Tuberculosis

Class Mechanism of action Drugs Key adverse events Important practice points
Group A: fluoroquinolones
Fluoroquinolones Inhibition of DNA gyrase • Levofloxacin
• Moxifloxacin
• Gatifloxacin*
QTc prolongation (levofloxacin less so than moxifloxacin) • Monitor QTc when fluoroquinolones are combined with other QTc-prolonging agents, for example, bedaquiline or clofazimine
• Levofloxacin is the fluoroquinolone of choice in bedaquiline-containing regimens
Group B: second-line injectable anti-TB drugs
Aminoglycosides Inhibition of protein synthesis • Kanamycin
• Amikacin
• Capreomycin
• (Streptomycin)
• Nephrotoxicity (all)
• Ototoxicity (all)
• Electrolyte derangement (all)
• Avoid combination of aminoglycosides with other potentially nephrotoxic agents, for example, tenofovir or amphotericin B
• Use with caution in patients with diabetes mellitus or renal disease
Group C: core second-line agents
Thioamides Inhibition of cell wall synthesis • Ethionamide
• Prothionamide
• Nausea and vomiting (all)
• Hypothyroidism (all)
• If nausea and vomiting persist, consider drug-induced hepatitis or pancreatitis
• Monitor thyroid-stimulating hormone levels in patients receiving ethionamide
Oxazolidinones Inhibition of protein synthesis • Cycloserine
• Terizidone
• Linezolid
• Clofazimine
• CNS effects, including psychosis, confusion and depression (terizidone and cycloserine)
• Peripheral neuropathy (linezolid)
• Myelosuppression (linezolid)
• Ocular toxicity (linezolid)
• QTc prolongation (clofazimine)
• Skin and conjunctival pigmentation (clofazimine)
• Avoid concomitant use of linezolid with zidovudine, stavudine or didanosine; if myelosuppression occurs, stop linezolid use and transfuse as appropriate
• Monitor QTc when using clofazimine, especially when combined with QTc-prolonging agents
Group D: add-on agents
D1, various classes: isonicotinic acid hydrazide (high-dose isoniazid); nicotinamide analogue (pyrazinamide); aminoalcohols (ethambutol) Inhibition of mycolic acid synthesis High-dose isoniazid • Hepatotoxicity
• Peripheral neuropathy
• CNS toxicity
Use with pyridoxine to prevent peripheral neuropathy
Disruption of plasma membranes Pyrazinamide • Hepatotoxicity
• Gout
Inhibition of cell wall synthesis Ethambutol Ocular toxicity
D2, various classes: diarylquinoline (bedaquiline); nitro-dihydro-imidazooxazole (delamanid) Inhibition of mitochondrial ATP synthase Bedaquiline • QTc prolongation
• Arthralgia
• Hepatitis
• Headache
• Close monitoring of QTc is recommended
• Efavirenz should be changed to nevirapine or a protease inhibitor because of reduced bedaquiline exposure. Alternatively, an integrase inhibitor can be used
Inhibition of mycolic acid synthesis Delamanid • Nausea
• Vomiting
• Dizziness
• QTc prolongation
• Close monitoring of QTc is recommended
• No significant anticipated drug–drug interactions with antiretroviral drugs
D3, various classes: amino-phenol (para-aminosalicylic acid); carbapenems; thiosemicarbazone (thiocetazone) Inhibition of DNA precursor synthesis Para-aminosalicylic acid Gastrointestinal toxicity Monitor thyroid-stimulating hormone levels in patients receiving para-aminosalicylic acid
Inhibition of peptidoglycan synthesis Imipenem plus cilastatin or meropenem plus clavulanate (available orally with amoxicillin) Seizures Monitor for CNS adverse events
Inhibition of mycolic acid synthesis Thiocetazone§ Severe skin reactions (for example, Stevens–Johnson syndrome and toxic epidermal necrolysis), especially in patients with HIV infection Close monitoring for severe skin reactions; avoid use if the patient is HIV-positive
  1. CNS, central nervous system; QTc, corrected QT interval; TB, tuberculosis.
  2. *This drug is being assessed for inclusion in the 2017 Essential Medicines List.
  3. Streptomycin can be used when the isolate is susceptible and none of the other injectable drugs are available.
  4. §Only use in HIV-negative individuals.