Paying More Attention to Antibiotic Dosage Could Improve Clinical Outcomes for Cystic Fibrosis Patients

Children and young adults with cystic fibrosis (CF) whose lung infections have been treated with suboptimal doses of antibiotics undergo less changes in pulmonary microbial diversity during intravenous treatment, and their levels of microbial diversity are higher 30 days later. Shows of researchers for children. In contrast, patients treated at therapeutic doses showed greater decreases in microbial lung diversity and significantly lower levels of diversity at the end of antibiotic therapy and 30 days later.

"With the subtherapeutic treatment group, this could represent a" basement effect "where it is more difficult to reduce diversity when it is already low, and patients in the subtherapeutic group had a more severe disease. advanced than those in the therapeutic group, which could influence the results, "says Andrea Hahn, MD, MS, infectious disease specialist at the National Children's Health System and lead author of the study.

The results, published online on February 22, 2019, in Scientific reports, clearly establish the importance of the interaction between basic microbial diversity and lung function and have the potential to improve clinical practice, writes the research team.

In the United States, more than 30,000 people have cystic fibrosis, a genetic disorder that causes recurrent lung infections that progressively deplete lung function over time. People with this condition must frequently be hospitalized for these infections, called acute pulmonary exacerbations (APEs), usually treated with the help of antibiotics. These often include beta-lactams, a clbad of antibiotics including penicillin and a multitude of other structurally related compounds.

The worsening of lung function in CF patients has been badociated with a decrease in microbial diversity in the lungs, a factor that could be caused by the repeated administration of antibiotics to treat EPA. Although it is well known that patients often do not reach the therapeutic doses of antibiotics that effectively eradicate their infections, it is unclear how microbial diversity is altered in patients receiving subtherapeutic doses. compared to patients receiving therapeutic doses.

To investigate this issue, Dr. Hahn and his colleagues recruited 20 patients aged 1 to 21 years treated for EPAs with beta-lactam antibiotics at Children's National. For each patient, the researchers collected four samples of respiratory fluid:

• When the participants in the study were well
• While they had an EPA
• Just after the end of their antibiotic treatment and
• Again at least 30 days later.

They subjected each sample to genetic testing to determine the types of bacteria present and their relative abundance. The research team also collected blood samples from each patient during antibiotic treatment, as well as data on lung function.

These 20 patients followed 31 antibiotic treatments during the study period, which lasted from March 2015 to August 2016. Dr. Hahn and colleagues found that only about 45% of these treatments were considered therapeutic. , the concentrations in the blood of these drugs increasing enough to effectively treat their infections.

Dr. Hahn and his colleagues suspect that patients who do not often reach therapeutic concentrations of antibiotics in the blood can be genetically predisposed to rapidly metabolize beta-lactam antibiotics. Repeated sub-therapeutic antibiotic treatments could significantly reduce microbial diversity without effectively eliminating infections, resulting in more lung damage that negatively affects lung function over time.

Dr. Hahn adds that it would eventually be possible to avoid this effect by closely monitoring the blood levels of antibiotics from patients with CF in real time, in order to ensure that each EPA is treated with a dosage at a therapeutic level.

"What this study shows is that the levels of antibiotics we give are probably playing a role in patients' ability to recover basic diversity," she says. "If we pay more attention to drug levels when using these types of antibiotics to ensure that the dosage is sufficient, we could potentially improve the clinical outcomes of patients with the time."