Protecting Good Bacteria with Adjusted Antibiotic Doses During Treatment

Researchers at the University of St Andrews, in collaboration with international teams, have discovered that adjusting antibiotic doses in tuberculosis treatment can protect beneficial bacteria in the body. The study, published in The Lancet Microbe, found that certain antibiotic combinations, especially those with lower rifampicin dosages, allowed for faster recovery of the body's essential microbiota.

The human body coexists with billions of microorganisms, collectively known as the microbiota. While a majority of these are beneficial and play crucial roles in immunity and digestion, a tiny fraction can cause diseases, necessitating the use of antibiotics. However, a side effect of antibiotic use, especially in tuberculosis (TB) treatment, is the unintentional destruction of beneficial bacteria.

The Dual Challenge of AntibioticsTreatment: Eradicating 'Bad' Bacteria While Safeguarding the 'Good

The study focused on the impact of various antibiotic combinations on the respiratory microbiome of TB patients. The researchers found that the most significant "killing effect" of the antibiotics on the microbiota was evident during the first two weeks of treatment. But most bacteria began to recover after this period, reaching pre-treatment levels within two months.

Tuberculosis is often treated with combinations of four antibiotics. Seven of these combinations were studied. While all combinations had a depressing effect on the microbial community, only two combinations – one containing 35 milligrams per kilogram of rifampicin, and the other containing 20 milligrams per kilogram of rifampicin, supplemented by 400mg of moxifloxacin – achieved significant killing of the microbiota.

Importantly, microbiota recovered faster in the latter combination which contained a lower dose of rifampicin. This implies that a carefully balanced antibiotic course can achieve the purpose of killing the disease-causing bacteria while preserving the useful ones that the body needs to recover to full health.

Commenting on these findings, the lead researcher, Dr. Wilber Sabiiti, from the University of St Andrews' School of Medicine, said: “For a long time, assessment of drug safety has only focused on the effect caused against human body organs such as the liver and the brain. This has neglected the effect caused against the useful microorganisms that live with humans and make them thrive. Many studies prior to ours have shown how the presence of these microorganisms helps educate human immunity to resist infections and prevent allergies and diseases like asthma. It is therefore crucial that the view of drug safety is expanded to include the safety of useful microorganisms in the human body.”

The study employed RNA, a genetic molecule linked with live cells, enabling the team to exclusively measure microorganisms that were alive before and after antibiotic exposure. This approach is in contrast to many previous studies that relied on DNA, which remains stable long after cell death, making it a less accurate indicator of live bacteria post-antibiotic exposure.

The research also touched on the concerning rise of antibiotic-resistant bacteria. Prolonged exposure to antibiotics can lead bacteria to develop resistance, turning areas rich in microorganisms, like the lungs and gut, into potential breeding grounds for superbugs. Further studies are required to understand this phenomenon better and devise strategies to prevent the emergence of antibiotic resistance.

The collaborative study involved participants and researchers from Tanzania and universities in the Netherlands, Germany, and the UK, representing the Pan African Consortium for Evaluation of anti-TB Antibiotics (PanACEA).