Advances in the management of pneumonia caused by drug-resistant bacteria: from antimicrobial optimisation to integrated treatment adaptation

Management of drug-resistant bacterial pneumonia has become increasingly precise, but early precision does not remove the need to reinterpret the patient's course during illness. Active and appropriate empirical therapy, informed by local epidemiology, remains essential, yet treatment often begins before the definitive microbiological profile is available or adequate drug exposure can be confirmed. While rapid diagnostics and pharmacological optimisation can narrow this initial uncertainty, the harder problem arises when antimicrobial treatment appears plausible but the patient shows delayed improvement, clinical deterioration, or incomplete recovery. These trajectories should not be treated as a single form of antibiotic failure. Instead, they require reassessment of whether the dominant limitation is persistent infection, inadequate drug exposure, dysregulated host response, a non-infectious mimic, or repair-limited recovery. In this Review, we propose a trajectory-guided conceptual framework that links management to the process most likely to limit recovery and distinguishes clinically implementable interventions from emerging translational concepts.