Current and future treatment options for infections caused by multidrug-resistant Gram-negative pathogens

The spread of multidrug-resistant, extensively drug-resistant and pan-drug-resistant pathogens is causing an unprecedented public health crisis. The limited current therapeutic options led to the revival of two 'old' antibiotics - colistin and fosfomycin - for which a better understanding of their pharmacokinetics in the critically ill patient and in specific body compartments is required. Tigecycline's use in clinical practice for nonapproved indication based on its in vitro activity against problematic pathogens requires caution and probably higher doses. Furthermore, all three antibiotics should be used as part of combination regimens in order to prevent resistance and optimize outcomes. The development of new antibacterials in the near future, namely combinations of avibactam, ceftolozane/tazobactam and plazomicin, seems promising; however, they will only partially address current mechanisms of resistance.