How to manage multidrug-resistant tuberculosis (MDR TB) in a pregnant woman?

Management of Multidrug-Resistant Tuberculosis in Pregnancy

Pregnant women with MDR-TB should be treated immediately without delay using an individualized regimen based on drug susceptibility testing, including second-line agents, while absolutely avoiding aminoglycosides due to fetal ototoxicity. 1, 2

Immediate Treatment Principles

Do not delay treatment while awaiting drug susceptibility results or considering pregnancy termination. The benefits of treating MDR-TB during pregnancy outweigh the risks to both mother and fetus, with treatment success rates of approximately 72.5% reported in recent systematic reviews. 1, 3, 4

• Untreated MDR-TB poses greater risk to mother and fetus than the medications themselves 2, 5
• Pregnancy termination is not medically indicated for women requiring MDR-TB treatment 2
• Consultation with an MDR-TB expert is essential for all cases 1, 2

Core Treatment Regimen Construction

Build the regimen using at least 4-5 effective drugs based on drug susceptibility testing of the source case or patient's isolate:

Preferred Second-Line Agents in Pregnancy:

• Fluoroquinolones (levofloxacin or moxifloxacin) - Should be included as a backbone agent despite pregnancy category C classification, as benefits outweigh theoretical arthropathy risks 1
• Bedaquiline - FDA pregnancy category B, making it one of the safer second-line options 1
• Linezolid - Associated with significantly higher treatment success when included (treatment success increases when >20% of patients in cohorts receive linezolid) 3
• Ethambutol - Safe first-line agent that should be continued if susceptibility demonstrated 2, 6
• Pyrazinamide - Now recommended for HIV-infected pregnant women; benefits outweigh risks despite limited teratogenicity data 1, 2

Absolutely Contraindicated Medications:

• All aminoglycosides (streptomycin, kanamycin, amikacin) and capreomycin - Cause congenital deafness in approximately 17% of exposed fetuses 1, 2, 6
• This contraindication holds even for MDR-TB treatment 1, 2

Essential Supportive Care

• Pyridoxine (vitamin B6) 25 mg daily - Mandatory for all pregnant women receiving isoniazid to prevent neurotoxicity 2, 6, 5
• Directly observed therapy (DOT) - Required for all MDR-TB patients to prevent treatment failure and further resistance 1

Treatment Duration and Monitoring

• Duration: 24 months after culture conversion for MDR-TB in HIV-positive patients 1
• Monthly clinical evaluations including hepatotoxicity assessment (jaundice, dark urine, abdominal pain, nausea) 7
• Baseline and serial liver function tests - Pregnancy may increase vulnerability to isoniazid hepatotoxicity 2, 6
• Post-treatment follow-up every 4 months for 24 months to monitor for relapse 1

Expected Outcomes and Adverse Events

Treatment success rates of 72.5% are achievable with appropriate regimens, though adverse events are common:

• More than half of pregnant patients (54.7%) experience at least one adverse event during treatment 3
• Most common adverse events: liver function impairment (30.4%), kidney function impairment (14.9%), hypokalemia (11.9%), hearing loss (11.8%), gastrointestinal disorders (11.8%) 3
• Favorable pregnancy outcomes occur in 73.2% of cases 3
• Most common adverse pregnancy outcomes: preterm birth (9.5%), pregnancy loss (6.0%), low birth weight (3.9%), stillbirth (1.9%) 3

Critical Pitfalls to Avoid

• Never delay treatment waiting for the second trimester or drug susceptibility results if active MDR-TB is suspected 2, 6
• Never use aminoglycosides regardless of resistance pattern - find alternative agents 1, 2, 6
• Never assume pregnancy contraindicates aggressive treatment - maternal death rates are higher with inadequate treatment 1, 4
• Never rely on breast milk drug concentrations to treat the infant if TB develops - separate full-dose therapy required 6, 7

Special Considerations for HIV Coinfection

• Rifampin should not be used with protease inhibitors or NNRTIs 2
• Rifabutin is an acceptable alternative: reduce to 150 mg/day with indinavir, nelfinavir, or amprenavir; reduce to 150 mg every other day or three times weekly with ritonavir 2
• Malabsorption syndrome may be present in HIV/TB coinfection - consider therapeutic drug monitoring if treatment response is inadequate 8

Breastfeeding Guidance

• Breastfeeding should not be discouraged - anti-TB drugs in breast milk reach only 20% or less of therapeutic levels and do not cause infant toxicity 6, 7
• Continue pyridoxine supplementation (25 mg daily) while breastfeeding 7