Antibacterial therapy in central nervous system infections - breakpoints versus minimal inhibitory concentrations...

Breakpoints to define the susceptibility of pathogens to antibiotics are becoming increasingly popular as guidance for antimicrobial therapy. Some breakpoints consider divergent concentrations of antibiotics in different compartments, others list one breakpoint for infections at all sites. Compared to the determination of exact minimal inhibitory concentrations (MICs) and relation of these MICs to concentrations achievable in ventricular CSF, the exclusive use of breakpoints for central nervous system (CNS) infections is a setback. The lack of the determination of exact MICs may be a risk, particularly when no clinical breakpoints for CNS infections have been defined. Moreover, the current practice of MIC determination of β-lactam/β-lactamase inhibitor combinations with fixed β-lactamase inhibitor concentrations ignores that often these β-lactamase inhibitor concentrations are not attained in CSF with established antibiotic regimens. In CNS infections, we strongly recommend the exact determination of MICs and their interpretation in relation to the true antibiotic concentrations in the infected compartment.