Second-line antitubercular agents are prescribed when first-line medications fail due to drug-resistant mycobacterial strains. These drugs require strict combination therapy because of high toxicity and the risk of resistance.
Effect on mycobacteriaBactericidal or bacteriostatic depending on the drug class.
Drug combinationAlways used as part of multi-drug combination regimens.
ToxicitySignificant adverse effects involving the CNS, kidneys, and hearing.
EliminationMost compounds and their metabolites are excreted by the kidneys.
General Principles of Second-Line Therapy
Second-line agents have limited clinical use due to their high toxicity profile. They are prescribed strictly in combination with other antitubercular drugs, such as isoniazid or streptomycin.
This strategy serves two main purposes:
Enhancing the overall therapeutic efficacy of treatment.
Reducing the risk of developing mycobacterial resistance.
Second-Line Antibiotics
This group includes natural and synthetic antibiotics with various mechanisms of action against the pathogen:
Cycloserine — a broad-spectrum synthetic antibiotic. It exerts a bactericidal effect by disrupting cell wall synthesis. It readily crosses tissue barriers but causes neurotoxicity (headaches, psychosis), which is managed with vitamin B6.
Viomycin — an antibiotic of animal origin acting bacteriostatically against M. tuberculosis. Administered intramuscularly, it has marked ototoxic effects and must not be combined with aminoglycosides.
Capreomycin — a natural peptide antibiotic containing a PAS component. It is indicated for infections caused by resistant strains, though it can cause nephrotoxicity and hearing loss.
Ethionamide — a structural analogue of isoniazid. It inhibits mycolic acid synthesis and penetrates encapsulated caseous lesions. Common adverse reactions include dyspepsia and hepatotoxicity.
Pyrazinamide — acts as a prodrug, converted by the enzyme pyrazinase into pyrazinoic acid. A characteristic side effect is hyperuricemia, leading to joint pain.
PAS (para-aminosalicylic acid) — used in salt form, it acts tuberculostatically via competitive antagonism with PABA. It is effective only during the active replication phase of mycobacteria and strongly irritates the gastrointestinal mucosa.
Fluoroquinolones (ciprofloxacin, levofloxacin, moxifloxacin) and thioacetazone also complement the armamentarium of combination tuberculosis therapy.
Mnemonic
Second-line antibiotics hit hard and precise: Cycloserine needs vitamin B6 for the nerves, Viomycin and Capreomycin spare hearing and kidneys, while Pyrazinamide monitors uric acid in the joints.
Frequently asked questions
Which antibiotics belong to second-line antitubercular drugs?
Second-line antitubercular antibiotics include agents from various chemical groups, such as aminoglycosides and peptide antibiotics.
Viomycin (florimycin sulfate) — an antibiotic of animal origin.
Capreomycin (capreomycin) — a natural peptide antibiotic.
Cycloserine — a broad-spectrum antibiotic.
Kanamycin — an aminoglycoside.
Amikacin — an aminoglycoside.
Which synthetic agents belong to second-line antitubercular drugs?
Second-line synthetic antitubercular agents include several pharmacological classes:
What adverse effects are characteristic of pyrazinamide?
Pyrazinamide is associated with adverse gastrointestinal, hepatic, and metabolic effects:
Dyspepsia.
Hyperuricemia — uric acid retention clinically manifested as arthralgia (joint pain) and myalgia.
Hepatotoxicity.
Which fluoroquinolones are used in combination therapy for tuberculosis?
Synthetic antibacterial agents from the fluoroquinolone group used as second-line reserve drugs in combination tuberculosis therapy include:
Levofloxacin — a second-generation fluoroquinolone.
Moxifloxacin — a second-generation fluoroquinolone.
Ciprofloxacin.
Gatifloxacin.
Why are second-line antitubercular drugs always prescribed in combination?
Combination therapy is necessary to enhance treatment efficacy and prevent the rapid development of drug resistance in mycobacteria.
How can neurotoxicity be reduced during cycloserine treatment?
To mitigate central nervous system side effects, patients are prescribed pyridoxine (vitamin B6).
What are the features of pyrazinamide's mechanism of action?
Pyrazinamide is a prodrug: inside the bacterium, pyrazinase converts it into active pyrazinoic acid, which disrupts the pathogen's cell wall.
Why is PAS ineffective against mycobacteria outside the division phase?
PAS acts as a competitive antagonist of PABA and disrupts folate synthesis, so its activity is strictly limited to the active replication phase of the microorganisms.
Go deeper
Pharmacokinetics and hepatic metabolism of ethionamide
Mechanism of hyperuricemia and arthralgia induced by pyrazinamide
Comparative profile of fluoroquinolones in phthisiology
Competitive antagonism of PAS with PABA in folate synthesis
Cross-resistance patterns among isoniazid analogues