Antibiotic stewardship programmes in intensive care units: Why, how, and where are they leading us.

Antibiotic usage and increasing antimicrobial resistance (AMR) mount significant challenges to patient safety and management of the critically ill on intensive care units (ICU). Antibiotic stewardship programmes (ASPs) aim to optimise appropriate antibiotic treatment whilst minimising antibiotic resistance. Different models of ASP in intensive care setting, include "standard" control of antibiotic prescribing such as "de-escalation strategies"through to interventional approaches utilising biomarker-guided antibiotic prescribing. A systematic review of outcomes related studies for ASPs in an ICU setting was conducted. Forty three studies were identified from MEDLINE between 1996 and 2014. Of 34 non-protocolised studies, [1 randomised control trial (RCT), 22 observational and 11 case series], 29 (85%) were positive with respect to one or more outcome: These were the key outcome of reduced antibiotic use, or ICU length of stay, antibiotic resistance, or prescribing cost burden. Limitations of non-standard antibiotic initiation triggers, patient and antibiotic selection bias or baseline demographic variance were identified. All 9 protocolised studies were RCTs, of which 8 were procalcitonin (PCT) guided antibiotic stop/start interventions. Five studies addressed antibiotic escalation, 3 de-escalation and 1 addressed both. Six studies reported positive outcomes for reduced antibiotic use, ICU length of stay or antibiotic resistance. PCT based ASPs are effective as antibiotic-stop (de-escalation) triggers, but not as an escalation trigger alone. PCT has also been effective in reducing antibiotic usage without worsening morbidity or mortality in ventilator associated pulmonary infection. No study has demonstrated survival benefit of ASP. Ongoing challenges to infectious disease management, reported by the World Health Organisation global report 2014, are high AMR to newer antibiotics, and regional knowledge gaps in AMR surveillance. Improved AMR surveillance data, identifying core aspects of successful ASPs that are transferable, and further well-conducted trials will be necessary if ASPs are to be an effective platform for delivering desired patient outcomes and safety through best antibiotic policy.