Antibiotic therapy for severe bacterial infections

Background: Early antibiotic therapy for patients with severe infections is essential to improve outcomes. Conversely, use of overly broad antibiotic therapy for susceptible pathogens or unnecessary antibiotics in patients without bacterial infections is associated with adverse life-threatening events and superinfections. Antibiotics-induced changes in the human microbiota alter both immune and metabolic systems. Uncontrolled antibiotic use encourages emergence of antibiotic-resistant organisms. Around 50% of ICU patients receiving antibiotic therapy do not have confirmed infections, whilst de-escalation and shortened treatment duration are infrequently performed. Mortality from serious infections remains high, highlighting the need for treatment optimisation. Methods: Narrative review. Objectives: To summarise the available evidence, emerging options, and unresolved controversies in optimising antibiotic therapy in severe infections. Results: Local epidemiology, underlying illnesses, accessibility to health care systems, and diagnostic and therapeutic resources are important factors to consider. Rapid diagnostic tests combined with individualised decision-making improve the selection of antibiotic therapy. Rapid de-escalation to narrow-spectrum monotherapy and shortening of the duration of therapy should be the rule. Uncertainty still persists regarding the personalisation of therapy for difficult-to-treat resistant bacteria. Pharmacokinetic (PK) optimisation and prolonged or continuous beta-lactam use is safe and may improve outcomes. Therapeutic drug monitoring (TDM) should be used, especially when altered volume of distribution and/or drug clearance is suspected or where toxicity is likely. The impact of TDM combined with prompt dose adjustment is encouraged. Emerging technologies including rapid broad diagnostic tests and electronic antibiotic optimisation tools will further support collaboration between pharmacists, microbiologists, infectious diseases specialists, and intensivists for optimising antibiotic therapy and stewarding these precious resources.