Rethinking Tuberculosis Therapy for the Very Old: Fluoroquinolone Regimens Emerge as a Safer Bet

Tuberculosis in the very old is one of the quiet blind spots of modern infectious disease medicine. While global control programs have focused heavily on reducing transmission in younger, more mobile populations, the fastest-growing group of patients in many tuberculosis-endemic countries is now over the age of seventy. These patients bring with them a biological landscape that is fundamentally different from that of younger adults: immune systems reshaped by immunosenescence, kidneys and livers that metabolize drugs more slowly, and a heavy burden of chronic comorbidities that complicate every therapeutic decision. A new retrospective study from Beijing Chest Hospital, Capital Medical University, published in BMC Geriatrics, argues that the standard drug cocktail used for decades to treat pulmonary tuberculosis may be poorly suited to this population, and that fluoroquinolone-containing regimens deserve a much closer look.

The study, led by Zhengshu Ye and Yun Zhang with corresponding author Xinting Yang, enrolled 184 newly diagnosed pulmonary tuberculosis patients aged seventy years and older in 2023. All patients were treated at a single center, and each received one of four initial anti-tuberculosis regimens. Two of these were conventional: the standard quadruple therapy known as HR(L2)ZE, combining isoniazid, rifampicin or rifapentine, pyrazinamide, and ethambutol, and a triple therapy, HR(L2)E, which omits pyrazinamide. The other two replaced pyrazinamide with a fluoroquinolone, producing a fluoroquinolone-containing quadruple regimen and a fluoroquinolone-containing triple regimen. The researchers then compared treatment success rates and adverse event rates across the four groups, using multivariate logistic regression and propensity score matching to adjust for the inevitable baseline differences between patients who received different drugs.

The central concern motivating the study is pyrazinamide, a drug that has been a pillar of first-line tuberculosis therapy since the 1980s. Pyrazinamide is prized for its sterilizing activity against semi-dormant bacilli hiding in acidic intracellular environments, which allows treatment courses to be shortened from nine months to six. But that potency comes at a price. The drug is hepatotoxic, can precipitate severe liver injury, and interferes with uric acid excretion, raising the risk of gouty attacks. In patients over seventy, whose hepatic reserve is diminished and whose joints may already be compromised by degenerative disease, these toxicities are not merely inconvenient; they can force treatment interruption, drive drug resistance through incomplete therapy, and ultimately cost lives.

The results of the comparison were striking. Treatment success rates and overall adverse event rates differed significantly across the four groups, with a P value below 0.001. Compared with the standard HR(L2)ZE quadruple regimen, both fluoroquinolone-containing triple and quadruple regimens achieved significantly higher treatment success rates and lower risks of treatment failure and adverse events. In other words, swapping out pyrazinamide for a fluoroquinolone did not compromise efficacy; if anything, it appeared to strengthen it in this elderly cohort, while simultaneously making the treatment easier to tolerate.

To test whether these differences were genuine rather than artifacts of how patients were selected for each regimen, the researchers performed multivariate logistic regression, adjusting for age, gender, sputum smear status, and serum albumin level, a marker of nutritional status that is strongly associated with tuberculosis outcomes. Even after these adjustments, the fluoroquinolone-containing triple and quadruple regimens remained independently associated with improved clinical safety and efficacy. This is an important analytical step, because serum albumin and smear status are exactly the kinds of variables that could confound a simple comparison: sicker, more bacterially burdened patients might be steered toward more aggressive regimens, making those regimens look worse than they are.

The most dramatic finding came from the propensity score matching analysis, a statistical technique that pairs patients from different treatment groups who have similar baseline characteristics, thereby minimizing selection bias. When the standard HR(L2)ZE group was matched against the fluoroquinolone-containing quadruple group, the conventional regimen was associated with a dramatically higher risk of adverse events, with an odds ratio of 16.87 and a 95 percent confidence interval of 4.85 to 70.33, and a P value below 0.001. An odds ratio of that magnitude, even with the wide confidence interval that comes from a modest sample size, suggests that elderly patients on the standard regimen face a risk of harmful side effects that is more than an order of magnitude greater than their peers on the fluoroquinolone-based alternative.

The technical logic behind this difference is worth unpacking. Fluoroquinolones such as levofloxacin and moxifloxacin are broad-spectrum synthetic antibiotics that inhibit bacterial DNA gyrase and topoisomerase IV, enzymes essential for DNA replication. In tuberculosis therapy they are normally reserved for multidrug-resistant disease, but they have long been considered as potential substitutes in drug-sensitive disease when first-line drugs cannot be tolerated. Their pharmacokinetic profile in older adults is comparatively manageable, and their toxicity profile, dominated by tendon effects and QT prolongation, is at least predictable and monitorable. Pyrazinamide, by contrast, imposes a metabolic burden that is difficult to anticipate in a seventy-five-year-old with borderline liver function and pre-existing hyperuricemia.

The authors are careful, appropriately, to frame their findings as associations rather than proof of causation. This was a retrospective, single-center observational study, and patients were not randomized to their regimens. Clinicians choosing a fluoroquinolone-based regimen may have done so for reasons that also correlate with better outcomes, such as earlier presentation or fewer comorbidities, although the propensity score matching was designed to blunt exactly this kind of bias. The wide confidence interval around the odds ratio reflects the limited number of matched patients, and the authors explicitly call for confirmation in prospective, multicenter studies before any change to standard practice is made.

Even with those caveats, the clinical implications are substantial. Current international guidelines largely assume that the six-month HRZE regimen is appropriate for all adults with drug-sensitive tuberculosis, with dose adjustments rather than regimen changes for the elderly. If the pattern observed here holds up in prospective trials, that assumption would need revision for patients over seventy. The authors suggest that individualized therapeutic strategies, with prudent use of pyrazinamide and rational selection of fluoroquinolone-containing regimens, may be considered for older patients. Such individualization would represent a shift from a one-size-fits-all model toward one that weighs the sterilizing power of pyrazinamide against its toxicity in a body that can no longer absorb that toxicity gracefully.

The study also highlights a broader demographic reality. As populations age in China, India, and other high-burden countries, the number of elderly tuberculosis patients will grow relentlessly, and treatment regimens designed around the pharmacology of younger bodies will increasingly fail the people who need them most. Immunosenescence blunts the inflammatory responses that normally contain the bacillus, comorbidities such as diabetes and chronic obstructive pulmonary disease multiply the risks, and polypharmacy raises the specter of drug-drug interactions that younger patients rarely face. Research like this retrospective analysis, funded by China’s national major infectious disease projects and Beijing municipal health programs, begins to fill an evidence gap that has persisted for decades. For now, the message for clinicians is cautious but clear: in the very old, the price of pyrazinamide may be higher than the benefit, and the fluoroquinolones, long relegated to the resistant-disease toolbox, may have a larger role to play in the tuberculosis ward of the aging world.

Subject of Research: Efficacy and safety of fluoroquinolone-containing tuberculosis regimens in patients aged 70 and older

Article Title: Efficacy and safety of fluoroquinolone-containing regimens in pulmonary tuberculosis patients aged 70 years and above: a retrospective study

Article References: Ye, Z., Zhang, Y., Wang, G., Zhang, J., Wang, Y., Lv, X., & Yang, X. (2026). Efficacy and safety of fluoroquinolone-containing regimens in pulmonary tuberculosis patients aged 70 years and above: a retrospective study. BMC Geriatrics. https://doi.org/10.1186/s12877-026-08451-1

Image Credits: AI Generated

DOI: 10.1186/s12877-026-08451-1

Keywords: tuberculosis, fluoroquinolone, pyrazinamide, older adults, geriatrics, drug safety, treatment outcomes, retrospective study, pulmonary tuberculosis, individualized therapy, adverse events, BMC Geriatrics