What is the recommended treatment regimen for a pregnant woman with active tuberculosis, including which first‑line drugs are safe, which are contraindicated, and any necessary adjuncts?

Safety of TB Drugs in Pregnancy

Pregnant women with active tuberculosis should receive immediate treatment with isoniazid, rifampin, and ethambutol plus pyridoxine 25 mg daily, because untreated TB poses far greater risks to mother and fetus than these medications, which have no documented teratogenic effects in humans. 1

Safe First-Line Medications

• Isoniazid, rifampin, and ethambutol are the three core drugs that should be initiated without delay in pregnant women with active TB. 1
• These medications cross the placenta but have no documented teratogenic effects in humans despite decades of use. 1, 2
• Pyridoxine (vitamin B6) 25 mg daily is mandatory for all pregnant women receiving isoniazid to prevent peripheral neurotoxicity. 1, 3

Absolutely Contraindicated Medications

• Streptomycin and all aminoglycosides (kanamycin, amikacin, capreomycin) must never be used during pregnancy. 1
• Streptomycin causes congenital deafness in approximately 17% of exposed fetuses, ranging from mild hearing loss to bilateral deafness. 1, 2
• Ethionamide and prothionamide should be avoided due to potential teratogenic effects. 1

Pyrazinamide: The U.S. Exception

• In the United States, pyrazinamide is not routinely recommended during pregnancy due to insufficient teratogenicity data, despite WHO endorsement. 1
• Some U.S. jurisdictions have used pyrazinamide in pregnancy without reported adverse events, but this remains controversial. 1
• When pyrazinamide is omitted, extend total treatment duration to 9 months instead of the standard 6 months. 1

Fluoroquinolones: Use Only When Essential

• Fluoroquinolones should be avoided when possible due to arthropathy risk observed in young animals. 1
• They may be considered only for essential treatment of drug-resistant tuberculosis when safer alternatives are not available. 1

Treatment Regimen Without Pyrazinamide

• Initial phase: 2 months of isoniazid + rifampin + ethambutol given daily. 1
• Continuation phase: 7 months of isoniazid + rifampin for a total of 9 months. 1
• This extended duration compensates for the absence of pyrazinamide's sterilizing activity. 1

Critical Monitoring Requirements

• Obtain baseline liver function tests, then monitor at weeks 2,4, and 8 during the first two months of therapy. 1, 3
• Pregnancy may increase susceptibility to isoniazid-related hepatotoxicity, making close monitoring essential. 1
• If transaminases exceed 3-5 times the upper limit of normal, temporarily discontinue isoniazid and consider restarting after normalization. 3

Breastfeeding Guidance

• Breastfeeding is encouraged for women receiving isoniazid, rifampin, and ethambutol. 1, 4
• Drug concentrations in breast milk are too low to cause infant toxicity but also insufficient to provide therapeutic treatment for the infant. 1, 4
• Continue pyridoxine 25 mg daily for the mother during breastfeeding. 4
• The infant requires independent evaluation and prophylaxis regardless of breastfeeding status. 4

Important Drug Interactions

• Rifampin reduces the efficacy of combined oral contraceptives; discuss alternative contraception methods. 1
• In patients receiving corticosteroids, double the maintenance steroid dose because rifampin induces hepatic enzymes that accelerate steroid metabolism. 1
• Isoniazid should not be administered with food, as bioavailability is significantly reduced. 3

Common Pitfalls to Avoid

• Never substitute streptomycin for ethambutol even when a four-drug regimen is indicated; ethambutol remains the preferred companion drug. 1
• Do not delay treatment while waiting for drug susceptibility results if active TB is suspected; the risks of untreated disease far outweigh medication risks. 1
• Termination of pregnancy is not medically indicated for women taking first-line antituberculosis drugs. 1, 2
• Do not reflexively avoid all TB medications due to pregnancy; the greater danger is untreated maternal tuberculosis. 1, 5

Special Clinical Scenarios

• For HIV-infected pregnant women, the same TB regimen applies, but avoid rifampin-based regimens if protease inhibitors are needed; consider rifabutin or non-rifamycin regimens. 6
• For drug-resistant TB, consultation with a TB expert is essential, as treatment must be individualized based on susceptibility patterns while avoiding contraindicated agents. 1
• Neonates of isoniazid-treated mothers should be carefully observed for any evidence of adverse effects, though serious complications are rare. 3