Running Short on TB Drugs: A Survey of California’s Tuberculosis Programs, 2023

Shortages of tuberculosis (TB) drugs keep recurring in the United States. Manufacturers leave the U.S. market, supply chains are inefficient, and active ingredients for import run short. In 2012, isoniazid was unavailable for several months — the last severe shortage — and in recent years supplies have faltered again. Scott A. Nabity of the California Department of Public Health and colleagues, with the California TB Controllers Association and CDC, surveyed California's TB programs to measure the damage.

Why these drugs matter

Isoniazid (INH) and rifampin (RIF) are the backbone of treatment for drug-susceptible TB. Rifapentine (RPT), a long-acting relative of rifampin, is part of newer, shorter first-line regimens for both latent TB infection and TB disease:

• 3HP: three months of weekly isoniazid and rifapentine, for latent TB infection;
• 4HPMZ: four months of isoniazid, rifapentine, moxifloxacin and pyrazinamide, for drug-sensitive TB disease.

California reports about a fifth of all U.S. TB cases, and buying TB drugs there is split among 61 local TB programs — much as it is split among U.S. states and territories. Those programs vary enormously, from zero to 508 cases a year on average during 2016–2021.

The survey

From January 29 to March 17, 2023, every program's TB controller and manager was asked about delays (short interruptions of a few weeks or less) and unavailability (longer interruptions that could force changes in practice) of oral first- and second-line TB drugs over the previous 12 months, and to rate the importance of a stable supply against their other priorities.

• 54 programs (89%) responded, including every program averaging 15 or more cases a year.
• On a scale of 1 to 10, programs rated a stable drug supply at 8.6 on average, and high-caseload programs at 9.4.
• Of the 50 programs that had at least one TB case in 2016–2021, 32 (64%) had experienced a delay or shortage of at least one oral first-line TB drug.

The survey covered first-line drugs (rifampin, rifapentine, isoniazid, rifabutin, pyrazinamide and ethambutol) and second-line drugs (cycloserine, ethionamide, levofloxacin, linezolid, moxifloxacin, para-aminosalicylate and pretomanid); bedaquiline and clofazimine were excluded because they are obtained differently.

The consequences

Drug interruptions were frequent in 2022, and they:

• delayed the start of treatment;
• forced permanent changes to regimens;
• held back the use of shorter courses for latent infection and for TB disease;
• led to preventable harm to patients, programs reported.

The response

To keep meeting treatment standards and keep moving toward eliminating TB, California set up a centralized buffer supply of several TB drugs. A steadier national supply could prevent some of the clinical and program harms that interruptions cause.

The survey looked back in time and relied on memory, and programs may have interpreted "delay" and "unavailability" differently.

Sources

Based on Nabity SA, Agraz-Lara R, Bravo A, et al., "Notes from the Field: Supply Interruptions of First- and Second-Line Oral Drugs to Treat Tuberculosis During the Previous 12 Months — California, January–March, 2023," MMWR, Centers for Disease Control and Prevention; in the public domain.