What is the recommended management of active tuberculosis in a pregnant woman?

Management of Active Tuberculosis in Pregnancy

Pregnant women with active tuberculosis should be treated immediately with isoniazid, rifampin, and ethambutol, plus pyridoxine 25 mg daily, because untreated tuberculosis poses far greater risks to both mother and fetus than the medications themselves. 1

Initial Treatment Regimen

Core Three-Drug Regimen

• Start isoniazid (INH), rifampin (RIF), and ethambutol (EMB) without delay when tuberculosis is suspected or confirmed, as untreated disease increases risks of low birth weight, congenital tuberculosis, and maternal mortality 1, 2
• Add pyridoxine (vitamin B6) 25 mg daily to all pregnant women receiving isoniazid to prevent peripheral neurotoxicity 1, 2
• These three drugs cross the placenta but have no documented teratogenic effects in humans 1, 3

Pyrazinamide Controversy

• Pyrazinamide is NOT routinely recommended in the United States during pregnancy due to insufficient teratogenicity data, despite WHO and IUATLD endorsement 1
• Some U.S. public health jurisdictions have used pyrazinamide in pregnancy without reported adverse events 1
• If pyrazinamide is excluded, extend treatment duration to 9 months minimum (versus 6 months with pyrazinamide) 1, 2, 4

Absolutely Contraindicated Medications

Aminoglycosides

• Never use streptomycin, kanamycin, amikacin, or capreomycin during pregnancy 1, 2
• Streptomycin causes congenital deafness in approximately 17% of exposed fetuses, with eighth nerve damage ranging from mild hearing loss to bilateral deafness 1, 2
• Even when drug resistance is suspected, select alternative second-line agents rather than aminoglycosides 2

Other Agents to Avoid

• Fluoroquinolones should be avoided if possible due to arthropathy risk in young animals, though they may be considered when essential for drug-resistant tuberculosis 1, 2
• Ethionamide has reported nonspecific teratogenic effects and should be avoided 1, 2

Treatment Duration Algorithm

Drug-Susceptible Tuberculosis

• With pyrazinamide: 2 months of INH + RIF + EMB + PZA, followed by 4 months of INH + RIF (total 6 months) 4
• Without pyrazinamide: 2 months of INH + RIF + EMB, followed by 7 months of INH + RIF (total 9 months) 1, 2, 4

Drug-Resistant Tuberculosis

• Consult a tuberculosis expert immediately for individualized regimen based on susceptibility testing 4, 5
• Counsel the patient about known and unknown fetal risks of second-line agents 1

Monitoring During Treatment

Hepatotoxicity Surveillance

• Obtain baseline liver function tests (AST, ALT, bilirubin) before starting therapy 2, 6
• Repeat liver enzymes at weeks 2,4, and 8 during the first two months, as pregnancy may increase susceptibility to isoniazid-induced hepatotoxicity 2, 6, 3
• Educate patients to report fever, malaise, vomiting, jaundice, or abdominal pain immediately and stop medications if these occur 6

If Drug-Induced Liver Injury Occurs

• Discontinue all hepatotoxic drugs immediately (INH, RIF, PZA) and start a non-hepatotoxic bridge regimen 6
• Use streptomycin plus ethambutol with extreme caution as a bridge (streptomycin carries ototoxicity risk but may be necessary temporarily) 6
• Reintroduce drugs sequentially after liver function normalizes: start INH first, then add RIF after 2-3 days, then PZA if needed 6

Breastfeeding Guidance

Safety of First-Line Agents

• Breastfeeding should be encouraged for women taking INH, RIF, and EMB, as drug concentrations in breast milk are too low to cause infant toxicity 1, 2
• Provide pyridoxine 25 mg daily to both mother and nursing infant when isoniazid is used 1, 2, 6
• Drugs in breast milk do NOT constitute effective treatment for tuberculosis in the infant; full therapeutic doses must be given directly if the infant requires treatment 1, 6

Fluoroquinolone Considerations

• Fluoroquinolones during breastfeeding are acceptable when needed for drug-resistant tuberculosis, as maternal treatment benefit outweighs theoretical risks 7, 6

Critical Pitfalls to Avoid

Common Errors

• Do not delay treatment waiting for the first trimester to end in any pregnant woman with active tuberculosis 2, 3
• Do not substitute streptomycin for ethambutol even when four-drug therapy is indicated 1
• Do not use 6-month regimens without pyrazinamide; this leads to treatment failure and relapse 2, 7
• Do not continue hepatotoxic drugs while "monitoring closely" after liver injury develops; this can cause fulminant hepatic failure 6

Pregnancy-Specific Considerations

• Termination of pregnancy is NOT medically indicated for women taking first-line antituberculosis drugs 1, 2, 8
• Rifampin reduces oral contraceptive efficacy; discuss alternative contraception methods 2
• Double corticosteroid doses if needed because rifampin induces hepatic enzymes that accelerate steroid metabolism 2

Special Clinical Scenarios

Extrapulmonary Tuberculosis

• Use the same 6-9 month regimen as for pulmonary disease in most cases 4
• Extend to 12 months for miliary TB, bone/joint TB, and tuberculous meningitis in infants and children 4
• Consider adjunctive corticosteroids for tuberculous pericarditis and meningitis to reduce complications 4

HIV Co-infection

• Screen antimycobacterial drug levels in pregnant women with advanced HIV disease to prevent malabsorption and emergence of multidrug-resistant tuberculosis 4
• Treatment response may be less satisfactory in immunocompromised hosts; therapeutic decisions require close monitoring 4