Review Study Does Not Recommend Adding Antibiotics to Standard IPF Care

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by Marta Figueiredo PhD |

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Adding co-trimoxazole or doxycycline — two broad-spectrum antibiotics — to standard care does not significantly slow lung function decline or prolong survival in people with idiopathic pulmonary fibrosis (IPF), a review study has found.

This approach was instead associated with a higher risk of side effects, specifically gastrointestinal issues.

While changes in lung bacteria were previously linked to IPF progression, these findings, based on data from four clinical trials, do not support the use of antibiotics for the treatment of this patient population, the researchers noted.

The review study, “The effect of additional antimicrobial therapy on the outcomes of patients with idiopathic pulmonary fibrosis: a systematic review and meta-analysis,” was published in the journal Respiratory Research.

An increasing number of studies suggest that lung microbes and infections contribute to IPF development and progression. Particularly, increased bacterial load and/or lower bacterial diversity have been associated with IPF progression and poorer survival.

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Data from previous studies in animal and cellular models of pulmonary fibrosis also support this association, with antibiotic treatment lessening lung scarring (fibrosis) and improving survival.

“Based on these promising findings, the effect of the additional use of [antibiotics] such as doxycycline, co-trimoxazole, and macrolides on the outcomes of IPF patients have been assessed in further clinical studies,” the researchers wrote.

However, some of these trials have found a protective effect, while others have not.

Now, a team of researchers in Taiwan systematically reviewed published studies up to May 2021 reporting results from randomized controlled trials that compared the efficacy of additional antibiotic therapy against a placebo or standard care in adults with IPF.

From a total of 20 studies accessed for eligibility, four — covering 528 patients given broad-spectrum antibiotics and 527 patients receiving a placebo or usual care — were included in the analysis.

Three studies conducted in the U.K. compared the effects of co-trimoxazole with those of a placebo, while one study conducted in the U.S. tested either co-trimoxazole or doxycycline against standard care. All patients received standard care.

In total, 402 participants were given co-trimoxazole, and 126 patients received doxycycline. Treatment duration across studies ranged from three months to 3.5 years.

The meta-analysis’ main goal was to assess changes in the rates of all-cause mortality, while secondary goals included changes in lung function — as assessed with forced vital capacity and diffusing capacity of the lung for carbon monoxide — as well as the risk of adverse events, or side effects.

Results showed that all-cause mortality rates were similar between patients given additional antibiotics (15%) and those who did not receive such treatment (14%). Also, there were no significant differences between the groups in terms of changes in lung function.

However, additional use of antibiotics was significantly associated with an increased risk of adverse events, especially gastrointestinal problems, such as diarrhea and vomiting.

Patients receiving antibiotics were also more likely to have skin-related side effects, such as skin rash, than those given a placebo or standard care alone, but this difference did not reach statistical significance.

Most of these adverse events were not fatal or serious.

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These findings highlight that adding antibiotics — in this case, co-trimoxazole and doxycycline — to standard care “did not provide additional benefits for patients with IPF in terms of mortality and [lung function],” relative to placebo or usual care alone.

“In contrast, these agents were significantly associated with a higher risk of [adverse events], especially gastrointestinal toxicity,” the investigators wrote.

“Based on these findings, the additional use of antimicrobial therapy for patients with IPF is not recommended,” the team concluded.

Still, they noted that the number of included studies and patients was relatively small, as was the adherence to study medication, raising the question of whether the insignificant effect of additional antibiotics could be due to poor adherence.

“Further studies with better adherence are warranted to solve this issue,” the team wrote, adding that future research should also test other antibiotics and analyze their effects in the number or type of lung microbes seen in IPF patients.