Our project relies on a close collaboration between infectious disease specialists, microbiologists and cardiologists, as well as intensive care specialists and surgeons (see organigram). In the following, we outline our research plan for the first three years and provide a perspective for the continuing project period.
Actually, we propose to prospectively characterize patients with defined bacterial infections in order to create a platform/database including clinical characteristics and biological material, which will be investigated both immediately as well as collected in a biobank for in-depth pathophysiological studies later on.
In the first project period (year 1-2) our emphasis will be mostly dedicated towards Aims Ia-d, f, g, i and IIc-e. In the 3rd year and in the second project period (years 4-6) our emphasis will shift more towards comparisons of microbiota either longitudinally in the same patient or cross sectional in groups of individuals with the same disease entity or towards NGS analyses for bacterial profiling (Aims Ie-h and IIa-e). The close collaboration with biostatisticians will be key to both project-phases allowing to integrate the "big" data into knowledge and scientific value.
Aim I: Characterization of difficult-to-treat bacterial Infections Research infrastructure
Ia. Establishment of the 'Chronic and Persistent Bacterial Infection Database' (CPBID) linking aims Ia-Ii and a biobank of samples directly derived from patients
Ib. Characterize patient epidemiology, treatment, bacterial species and antimicrobial susceptibility of patients within CPBID and establish prediction models for relevant clinical outcomes
Patient environment and risk factors
Ic. Determine comorbidities, comedications, life style and other environmental factors as well as assess the respective influence on susceptibility to infection
Id. Determine patient reported outcomes, experiences, needs and perspectives
Ie. Determine skin bacterial microbiota profiles associated with invasive bacterial infections
Bacterial growth dynamics and persisters
If. Characterize growth dynamics and antibiotic tolerance of bacteria directly derived from patients
Ig. Characterize patient and bacterial factors associated with higher persister rates
Ih. Determine the genetic evolution of a specific pathogen in an individual host over time using whole genome sequencing (WGS) and RNA sequencing
Ii. Characterize burn wound colonization and transition to infection and sepsis
Aim II: Personalized treatment of difficult-to-treat bacterial Infections Treatment monitoring
IIa. Assess predictors for treatment failure/break-through infection or infection relapse
IIb. Determine the inflammatory marker kinetics and treatment response
IIc. Determine the use of diagnostic imaging for diagnosis and follow-up in bacterial infections
Improvement of diagnostics and influence on therapy
IId. Determine the impact of increased diagnostics on survival and cure rate of patients
IIe. Assess influence of culture-free molecular techniques diagnostics to improve diagnostics and therapy