What is the recommended treatment regimen for a pregnant patient with tuberculosis (TB), possibly coinfected with Human Immunodeficiency Virus (HIV)?

Treatment of Tuberculosis in Pregnancy

Pregnant women with tuberculosis, including those with HIV coinfection, should be treated immediately with a rifamycin-based regimen consisting of isoniazid, rifampin, and ethambutol, with pyrazinamide now recommended for HIV-infected pregnant women despite historical U.S. hesitancy. 1

Core Treatment Regimen for Pregnant Women

Standard Drug-Susceptible TB

• The initial treatment regimen should consist of isoniazid, rifampin, and ethambutol for pregnant women with tuberculosis 2
• Treatment must be started without delay, as untreated tuberculosis poses greater risk to both mother and fetus than the medications themselves 2, 3
• All pregnant women receiving isoniazid must receive pyridoxine (vitamin B6) supplementation at 25 mg/day to prevent neurotoxicity 2, 1

Special Consideration for HIV-Infected Pregnant Women

• For HIV-infected pregnant women specifically, the benefits of including pyrazinamide in the treatment regimen outweigh potential risks to the fetus 1
• This represents a departure from traditional U.S. practice, where pyrazinamide was historically avoided in pregnancy due to inadequate teratogenicity data 1
• International organizations have long recommended routine pyrazinamide use in pregnancy, and this is now endorsed for HIV-infected pregnant women 1

Medications Absolutely Contraindicated in Pregnancy

Aminoglycosides

• Streptomycin, kanamycin, amikacin, and capreomycin are absolutely contraindicated in all pregnant women due to fetal ototoxicity, causing congenital deafness in approximately 17% of exposed fetuses 1, 2

Other Agents to Avoid

• Fluoroquinolones should be avoided if possible during pregnancy due to association with arthropathies in young animals, though they may be considered in MDR-TB when benefits outweigh risks 2, 4
• Pyrazinamide should generally be avoided in the first trimester for non-HIV-infected pregnant women due to lack of teratogenicity data 1

Treatment Duration

• If pyrazinamide is not included in the regimen, the minimum duration of therapy is 9 months 2
• The standard 9-month regimen consists of isoniazid and rifampin throughout, with ethambutol in the initial phase until drug susceptibility is confirmed 2
• For HIV-infected pregnant women receiving pyrazinamide, treatment duration follows standard protocols with close monitoring 1

Critical Drug Interactions in HIV-Coinfected Patients

Rifamycin-Antiretroviral Interactions

• Rifampin should not be administered with protease inhibitors or nonnucleoside reverse transcriptase inhibitors 1
• Rifabutin is an acceptable alternative to rifampin but requires dose adjustments: reduce to 150 mg/day (from 300 mg) with indinavir, nelfinavir, or amprenavir; reduce to 150 mg every other day or three times weekly with ritonavir 1
• Rifabutin should not be used with hard-gel saquinavir or delavirdine 1
• Rifabutin can be increased to 450 mg/day when coadministered with efavirenz 1

Monitoring During Treatment

• Close monitoring of liver function is essential, as pregnancy may increase vulnerability to isoniazid hepatotoxicity 2, 3
• Baseline liver function tests should be obtained, followed by regular monitoring particularly during the first two months of treatment 2
• For HIV-coinfected patients, screening of antimycobacterial drug levels may be necessary to prevent emergence of MDR-TB, especially in patients with advanced HIV disease and potential malabsorption 5

Multidrug-Resistant TB in Pregnancy

• MDR-TB in pregnant women requires consultation with an expert in tuberculosis management 1
• Treatment must be individualized based on drug susceptibility testing of the M. tuberculosis isolate 1
• Most MDR-TB regimens include a fluoroquinolone (levofloxacin or moxifloxacin preferred over older agents) 1, 4
• Aminoglycosides remain absolutely contraindicated in pregnancy even for MDR-TB 1, 2
• For eligible MDR-TB patients (excluding pregnant women), the 6-month BPaLM regimen is preferred, but pregnancy is an exclusion criterion 4

Breastfeeding Considerations

• Breastfeeding should not be discouraged for women being treated with first-line anti-tuberculosis drugs, as small concentrations in breast milk do not produce toxic effects in the nursing infant 2, 6
• However, drugs in breast milk should not be considered effective treatment for tuberculosis in the nursing infant 2
• Breastfeeding should continue during prophylaxis and treatment 7, 6

Common Pitfalls to Avoid

• Never delay treatment while awaiting drug susceptibility results if the patient has confirmed or suspected active TB 1
• Do not reflexively avoid pyrazinamide in HIV-infected pregnant women based on outdated U.S. guidelines 1
• Do not use aminoglycosides under any circumstances in pregnancy, even for drug-resistant TB 1, 2
• Termination of pregnancy is not medically indicated for women taking first-line anti-tuberculosis drugs 2
• Ensure pyridoxine supplementation is prescribed with isoniazid to prevent neurotoxicity 1, 2

Directly Observed Therapy

• All pregnant women with TB should receive directly observed therapy (DOT) to ensure adherence, which is especially difficult in pregnancy due to fear of medications and pregnancy-related nausea 5, 3
• Fixed-dose combinations provide a realistic alternative to direct observation that minimizes opportunity for selective medication taking 8