Long wait ends: New LTBI guidelines ready
June 1, 2000 4 minutes read
Long wait ends: New LTBI guidelines ready
Some doctors remain fretful about PZA
New guidelines for preventive therapy are available — finally — from the American Thoracic Society in New York City and the Centers for Disease Control and Prevention (CDC) in Atlanta.
One measure of how long they’ve been gestating is that by now, most people have begun calling the activity by its new and somewhat fancier-sounding name, "treatment of latent TB infection," or LTBI. "We’ve been talking about these guidelines for such a long time that it’s great to finally have them out here," says Ed Nardell, MD, chief of pulmonary medicine at Harvard Medical School’s Cambridge Hospital and TB control officer for the Massachusetts State Department of Health. "Now we can start implementing them and see how they work."
Just as expected, several changes proposed for the new directives made it into the final version. They include the following:
• Nine months of isoniazid (INH) is now considered the optimal regimen for treatment of LTBI, both for HIV-positive and HIV-negative individuals. That replaces previous recommendations of six months of INH for HIV-negative patients and 12 for HIV-positive.
• Instead of widespread tuberculin skin testing, programs should focus their energy on targeting high-risk groups whose members will benefit from preventive therapy.
• The newcomer on the list, a short-course regimen, consists of two months of rifampin (RIF) and pyrazinamide (PZA). It’s recommended for both HIV-negative and -positive groups and can be given either daily or biweekly (with direct observation).
With the short-course regimen, two caveats apply: More data are needed to dispel lingering doubts about toxicity from the PZA component, and, for HIV-infected persons taking antiretroviral therapy, there is the potential for drug interactions.
• Laboratory baseline testing and follow-up lab monitoring are no longer recommended; instead, patients should simply be monitored clinically on a monthly basis for signs of adverse reactions. Exceptions to the no-labs rule include the HIV-infected, pregnant and postpartum women, and patients with a history of liver disease.
• For infants, children, and adolescents, there are no changes; in that group, nine months of INH remains the best choice.
For the skeptical and the fretful, TB experts who’ve escorted the new recommendations through their long gestation offer reassurance.
For those worried about PZA’s potential for toxicity, it should help to hear [as did the audience at the recent American Thoracic Society meeting in Toronto] that early reports for the regimen look good, says Rick O’Brien, MD, chief of the research and evaluation branch of the Division of TB Elimination at the CDC. "Early data indicate pretty good acceptability," he says. "There’s no question people have more trouble with PZA than INH when it comes to gastric intolerance, but it’s likely that the lower dosage range we recommend is much better."
To program administrators wondering how they’ll ever get nine months of INH into patients who already loathe taking six, O’Brien offers empathy. "Programs and individual practitioners are certainly within the scope of the recommendations if they keep using six months of INH," he says. He makes sure his own patients get in at least six months, he adds; then, if the patient has shown good motivation and compliance, O’Brien offers the option of extra protection with an additional three months.
And for those miffed that four months of RIF didn’t get a higher rating, there’s an olive branch. "There are actually clinical trial data showing that RIF alone may be as effective, or even more effective, than six months of INH," O’Brien says. The lower numeric rating reflects only that there’s been no randomized clinical trial done yet; clinicians wanting to try out four months of RIF should take comfort in the regimen’s letter grade. "That’s the one that really matters," he adds.
Some physicians object to short course
Does that mean everyone’s happy? Not exactly. The new short-course regimen of RIF/PZA is "a major mistake,"says John Sbarbaro, MD, MPH, medical director of University Physicians Inc. at the school of medicine of the University of Colorado Health Sciences Center in Denver. "And [Michael] Iseman is with me on this." Iseman is chief of clinical mycobacteriology service in the infectious disease section at National Jewish Hospital in Denver. If Sbarbaro’s concerns could be summed up in three letters, they’d be P, Z, and A.
"When you use a toxic regimen, you’re asking for trouble," he says. "Why not take rifampin for three months instead? You’d probably have the same impact, and you wouldn’t be taking obnoxious drugs." Just watch, Sbarbaro adds: If a few people have adverse reactions, and the new regimen gets a bad rap on the street, it’ll be headed down the same dismal road as INH, the drug many people still associate — albeit unfairly — with hepatitis, he says.
Oh, and one more thing: "PZA works not in the cell where the bugs are, but in the extra-pulmonary areas around the caseous material in the lung," he says. "PZA doesn’t kill bugs in the cell. And that’s where preventive therapy is aimed."
Sbarbaro isn’t the only guy with a complaint. "With RIF/PZA, frankly, I worry about compliance," says Jeff Starke, MD, associate professor of Clinical Pediatrics at Baylor University College of Medicine and chief of Pediatrics at Ben Taub Hospital, both in Houston. "I worry that people won’t like the PZA, and they’ll stop taking it."
To view the new ATS/CDC guidelines on treatment of latent TB disease in adults and children on-line, go to www.thoracic.org, or www.cdc.gov/MMWR.
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