FABULOUS—Treatment failures in the primary absence of phenotypic resistance

Short description

In many infections, even proper antibiotic treatment does not lead to the expected therapeutic success. In the case of treatment with antibiotics, the doctor usually first decides which antibiotic to prescribe based on the type of infection. If resistance to the antibiotic already prescribed is detected, the therapy will be specifically adapted to the respective resistance pattern present. Even with such calculated antibiotic treatment tailored to the bacterial pathogen, therapy failure can occur in about five to 25 percent of cases, meaning that the bacteria are not eliminated or no clinical improvement is observed. There can be various reasons for such therapy failure, such as individual factors of the affected patient or adaptations on the part of the infecting bacteria. This is where the FABULOUS project comes in: Within the framework of the project, bacterial pathogens isolated from clinical infections are examined. The focus is on possible antibiotic resistance and antibiotic tolerance abilities, which have so far not been or only very limitedly detectable in clinical-diagnostic practice. FABULOUS particularly focuses on pathogen samples from the DZIF project TIARA.

Daily laboratory routine in the FABULOUS project: researchers determine heteroresistance in bacterial strains. Heteroresistance is a possible cause of antibiotic failure. This phenomenon occurs when at least a small number of bacteria in a population show antimicrobial resistances.

© Bea Schneider

In the FABULOUS project (Treatment failures in the primary absence of phenotypic resistance: a deep assessment for underlying causes to improve diagnostic and therapeutic approaches), pathogens from clinical infections are examined very closely. FABULOUS is anchored in the project "Targeting microbiota- and treatment-derived determinants of infection" and analyses possible causes of antibiotic therapy failure as a proof-of-concept project.

In clinical practice, an antibiotic is usually administered for a bacterial infection that has been confirmed sensitive to the bacterial pathogen in diagnostic testing. If the pathogen is still detectable after more than 48 hours, treatment failure is assumed. This can have different reasons on the patient's side as well as on the pathogen's side. FABULOUS focuses on the bacterial side, including the correct dosage of antibiotics administered. The latter point is being investigated in particular in patients who have undergone abdominal surgery, for whom plasma samples are available for as part of the DZIF project TIARA, from which the antibiotic concentration during the infection can be determined.

Apart from the resistance of bacteria to antibiotics usually detected in microbiological diagnostic laboratories, there are many other ways in which bacteria counteract eradication by antibiotics, for example through antibiotic tolerance. When bacteria slow down their division and enter a dormant phase, they can escape those active substances of antibiotics that aim to reduce the multiplication of bacteria.

Using different methods of microbiology and genome-based analytics, the FABULOUS project will investigate such mechanisms. One goal is to draw attention to such mechanisms and, if possible, to formulate recommendations on how such effects can be detected in routine diagnostics in the future.

In the long term, FABULOUS should contribute to improved routine diagnostics with improved effectiveness of the antibiotics used.