Brigham Women's Health Center

History

2022: Comparison of efficacy of different antibiotics

Researchers at the Brigham Center for Women's Health USA in compared the effectiveness of various that antibiotics can be used with bone cement and identified the most effective that has shown promise when used against staphylococcus. In the future, this approach could potentially be used to treat bone infections and reduce the development of bacterial resistance. The University MISIS announced this on October 19, 2022.

It is not uncommon for knee or hip replacement surgery to use bone cement with antibiotics to avoid complication with bacterial infections. The material fixes the artificial joint in place, and the medicine, in turn, protects the junction from harmful bacteria. But with the rise of drug-resistant bacteria, this method requires new bacteria-resistant antibiotics.

The use of bone cement as a method of targeted drug delivery has its advantages over systemic antibiotic treatment, which requires large doses and at the same time contributes to the development of antibiotic resistance.

A team of scientists from the Brigham Center for Women's Health selected molecules for antibiotic development and screened for the presence of sensitive and drug-resistant bacteria in preclinical studies. Next, they compared in experiments on living cells and in rats the frequently used polymethylmethacrylate bone cement (PMMA) and similar cement, but already loaded with various antibiotics.

It turned out that the greatest effectiveness was shown by the double-acting antibiotic VCD-077 synthesized by scientists. The drug demonstrated the necessary kinetics of drug release without affecting the stability of bone cement. Moreover, the antibiotic has shown high efficacy against a wide range of drug-resistant bacteria, including staphylococcus, and has slowed the development of resistance in the future.

Commercial cements with antibiotics already exist on the market for October 2022, but they are all mainly with a broad-spectrum antibiotic - gentamicin. The authors of the article simulated and synthesized another antibiotic based on fluoroquinolones, capable of specifically binding to bacterial enzymes, including their mutated forms, which allowed to actively suppress DNA synthesis and cause the death of antibiotic-resistant colonies of bacteria. The researchers just compared the properties of their antibiotic with gentamicin, and their antibiotic turned out to be more effective. The new antibiotic made it possible to promptly suppress the development of infection and cause rapid bone regeneration in mouse models of staphylococcal bone infection. That is, the authors proposed an effective way to combat local infection in knee and hip endoprosthesis, which could be an alternative to systemic administration of antibiotics and related adverse reactions in patients with orthopedic infection. In general, this technology is good, but it may have one potential drawback. There is evidence that fluoroquinolones in subinhibitory concentrations themselves can cause mutations in bacteria and, subsequently, their resistance to antibiotics. Therefore, it is necessary to take into account such risks when using antibiotics and assessing the kinetics of their riliz, - said Karshieva Saida, candidate of biological sciences, leading expert of the scientific and educational center of biomedical engineering NUST MISIS.

The authors of the article note that further research is needed before clinical use in the future.