An estimated 13 million Americans are infected with Mycobacterium tuberculosis, most of them asymptomatic with latent tuberculosis infection.
This is a medical illustration of drug-resistant Mycobacterium tuberculosis from the CDC's Antibiotic Resistance Threats in the United States, 2019.
So it's fitting that the CDC this month published what it identified as the first comprehensive guidelines for the treatment of LTBI(www.cdc.gov) since 2000, when the American Thoracic Society issued its guidelines. The new guidelines, which the CDC developed with the National Tuberculosis Controllers Association and published Feb. 14 in the agency's Morbidity and Mortality Weekly Report, updates clinicians and others with information about several new regimens that have been evaluated in clinical trials since then.
The guidelines, which are based on a systematic literature review, make new recommendations for the most effective and least toxic regimens for treatment of LTBI among people in the United States. Among these is a recommendation that clinicians work with patients to determine the best treatment regimen, prescribe shorter regimens and provide support and resources to help patients complete treatment successfully.
The agency encouraged physicians to review the new guidelines and, if necessary, to contact state and local TB control offices(www.cdc.gov) for additional information on diagnosing and treating LTBI.
The CDC added that it also offers other resources and tools(www.cdc.gov) to help health care professionals and patients address LTBI.
- Updated guidelines for the treatment of latent tuberculosis infection -- identified as the first comprehensive LTBI guidelines since 2000 -- were published Feb. 14 in the CDC's Morbidity and Mortality Weekly Report.
- The guidelines recommend three preferred and two alternative treatment regimens.
- A member of the AAFP's Commission on Health of the Public and Science told AAFP News that FPs in particular should screen individuals at high risk and provide treatment.
The guidelines recommend three preferred and two alternative treatment regimens.
The three preferred regimens, chosen for effectiveness, safety and high treatment completion rates, are rifamycin-based. They are
- three months of once-weekly isoniazid plus rifapentine for adults and children older than age 2, regardless of HIV status;
- four months of daily rifampin; or
- three months of daily isoniazid plus rifampin.
Rifamycin-based regimens have a long list of drug interactions, including warfarin, oral contraceptives, azoles and HIV antiretroviral therapy.
The alternative recommended regimens are six or nine months of daily isoniazid, with six months being preferred for HIV-negative adults and children. These regimens also are recommended for individuals who are unable to take a rifamycin-based regimen due to drug intolerability or drug-drug interactions.
Sarah Coles, M.D., of Phoenix, a member of the AAFP's Commission on Health of the Public and Science, told AAFP News that the guideline reported the shorter-duration regimens had higher completion rates and less toxicity, with similar efficacy to longer monotherapy regimens with isoniazid.
"Make sure to carefully check your patient's medication list to evaluate for possible drug-drug interactions before prescribing rifamycin-based regimens," she added.
Screening for LTBI
The United States Preventive Services Task Force recommends screening for LTBI(www.uspreventiveservicestaskforce.org) in populations that are at increased risk, a recommendation that the AAFP supports.
These populations include patients who were born in or are former residents of countries with increased TB prevalence and people who live in or have lived in high-risk congregate settings, such as homeless shelters or correctional facilities, Coles said.
"The best way to catch these individuals is to be familiar with risk factors, identify risk factors during office visits and to screen these patients with either tuberculin skin tests or interferon-gamma release assays, like the T-Spot or QuantiFERON-TB Gold," she said.
Latent TB is defined as infection with M. tuberculosis in the absence of clinical illness. Individuals with LTBI are asymptomatic but have an immune response to M. tuberculosis antigens. Family physicians should remember that just because a patient is asymptomatic, that doesn't mean their latent infection won't transition to active TB.
To diagnose LTBI, active TB must be excluded, Coles said.
"This would require a history and physical looking for signs and symptoms of active TB, and a chest X-ray," she said. "If the X-ray shows pulmonary infiltrates, hilar lymphadenopathy, cavitary lesions or if the patient has symptoms consistent with active TB, sputum should be obtained for acid-fast bacilli smear and culture. Symptoms of active TB include cough, fever, hemoptysis, night sweats and weight loss."
Coles said she has treated LTBI in her practice, and on several occasions has identified LTBI through screening and managed treatment.
"My most recent case involved a woman who immigrated from a county with high prevalence of TB," she said. "Due to multiple drug-drug interactions, she was unable to get a rifamycin-based regimen. She completed the six-month isoniazid regimen and tolerated the treatment very well."
Coles said the new guidelines sought to answer the question "Which regimens for treatment of LTBI have the greatest effectiveness and least toxicity?"
As for limitations of the guideline, she said hepatotoxicity was the only comparative measure of toxicity evaluated and she noted that the guidelines didn't provide recommendations or evaluate evidence regarding whom to test and treat, or management of side effects.
In addition, Coles pointed out that intermittent regimens are recommended to be administered via directly observed therapy "This may increase cost or create a barrier for patients who have difficulty getting to appointments."
Additionally, when choosing a regimen, she said family physicians should consider cost, feasibility, comorbidities, drug interactions and patient preferences.
Finally, Coles said the treatment of LTBI is well within the scope of family medicine.
"Family physicians should be screening individuals at high risk and then providing treatment as appropriate," she said. "Patients feel safest and most supported in their primary care home, and we can help monitor for adherence to medication regimen, evaluate for side effects and identify the right patients for treatment."
Related AAFP News Coverage
CDC Updates TB Recommendations for Health Care Workers