Figure 2. Systemically administered traditional antibiotics in clinical use and clinical trials excluding antitubercular agents.
(A) Cellular targets of traditional antibiotics in clinical use and the clinical pipeline and their resistance mechanisms; (B) Modes of action (MoA) of established and novel traditional antibiotics; (C) Modes of resistance (MoR) of traditional antibiotics; (D) Timeline of the introduction of antibiotics (blue) and examples of resistance identification (red): golden age of antibiotics (blue arrows), introduction of the WHO Pathogen Priority List in 2017 (bold blue; World Health Organization, 2017), natural products (bold), synthetic derived antibiotics (italic), agents not in clinical use anymore (grey); 1. Cell wall synthesis: β‐lactams (penicillins, cephalosporins, carbapenems, monobactams), glycopeptides, phosphonates; 2. Protein synthesis: tetracyclins, aminoglycosides, macrolides, lincosamides, streptogramins, oxazolidinones, amphenicols, pleuromutilins, fusidic acid*; 3. DNA/ RNA synthesis and replication: quinolones, nitroheterocycles (nitroimidazoles, nitrofurans), ansamycins; 4. Folic acid synthesis: sulfonamides, diaminopyrimidines; 5. Cell membrane synthesis and integrity: polymyxins, lipopeptides; 6. Cell division: benzamide; 7. Fatty acid synthesis: afabicin; *approval by European Medicines Agency (EMA).