Pharmacokinetic-Pharmacodynamic and Clinical Considerations for Extended- and Continuous-Infusion Antibiotics

Antibiotics are the most widely used treatment for infections yet there has been minimal antibiotic discovery in recent years despite rising drug resistance and treatment failures. A better understanding of antibiotic pharmacokinetics (PK) and pharmacodynamics (PD), along with the development of novel dosing strategies, such as extended (EI) and continuous infusions (CI), has helped to overcome these barriers. Studies have consistently demonstrated that EI/CI administration of beta-lactams and vancomycin in particular, improves PK-PD target attainment compared to intermittent infusions. However, the effects of EI/CI on clinical outcomes, including efficacy and safety, remain controversial. Emerging data focus on patient populations with altered PK that may benefit from EI/CI beta-lactams or vancomycin (e.g., critically ill, cystic fibrosis, or outpatient parenteral antibiotic therapy). Logistical barriers limit EI/CI use in practice, including intravenous access, drug stability and drug incompatibility. This review highlights beta-lactam and vancomycin PK-PD, EI/CI dosing strategies and relevant evidence for practice.