A retrospective review of colistin utilization and patient outcomes across four private sector hospitals in South Africa to identify opportunities to optimise colistin stewardship in hospitalised patients with multi-drug resistant Gram-negative infections

A dissertation submitted to the Faculty of Health Sciences, University of the Witwatersrand, in fulfilment of the requirements for the degree of Master of Pharmacy Johannesburg, 2018.The increased prevalence of multi-drug resistant (MDR) Gram-negative infections in critically ill patients has resulted in the re-introduction of colistin as rescue therapy. Various guidelines for colistin administration have led to confusion in establishing the appropriate dose which has potential for adverse consequences including treatment failure or toxicity. Colistin, also known as Polymixin E, is a concentration-dependent bactericidal antibiotic considered to be highly nephrotoxic and neurotoxic. Colistin is used either intravenously to treat life threatening systemic infections or by nebulisation for the treatment of respiratory tract infections. Although colistin resistance has been documented in South Africa, there is no local evidence as to why and how colistin is used in hospitals and similarly compliance with current dosing guidelines is unknown. This study aimed to evaluate the utilization of colistin in order to identify stewardship opportunities regarding its’ appropriate use in the future. A retrospective electronic record review of adult patients treated with intravenous (IV) and aerosolised colistin therapy in four Gauteng private hospitals was conducted between 1 September 2015 - 30 June 2016. The following data were collected on a standardized template; patient demographics including: age, gender, weight and hospital location; laboratory indicators including: renal function markers of creatinine and estimated Glomerular Filtration Rate (eGFR), as well as, culture specimens taken and their corresponding results. With regards to the colistin therapy: the indication for use, admitting diagnosis, the prescribed dose, frequency and route of administration, duration of treatment and if prescribed in combination with another Gram-negative antibiotic was considered. The following stewardship principles were monitored in addition to appropriate dose and duration; if a culture was taken prior to the initiation of treatment, if therapy was de-escalated and if a loading dose was prescribed. Outcome measures included overall in-hospital mortality, intensive care unit length of stay and overall hospital length of stay. Furthermore, compliance to two local colistin dosing guidelines was measured and a colistin stewardship bundle was developed, including nine process measures, to enhance the appropriate use of IV colistin. A total of 237 patients were included in the study of which 212 received colistin IV and, 25 via nebulisation. The results of patients who received IV colistin therapy demonstrated an 81.2% overall compliance to the proposed colistin stewardship bundle developed from this study. Non-compliance was mainly due to incorrect maintenance doses prescribed (50%), ‘hang time’ (66%) and poor de-escalation practices (69%). Significantly shorter durations of treatment were found in patients who received higher loading doses (p=0.040) and in those that received maintenance doses of 4.5 Million Units (MU) twice daily vs 3 MU three times daily (p=0.0027). In addition, more of the patients that demised received the 3 MU three times daily maintenance doses, compared to those who survived (p=0.0037). Aerosolised colistin was only prescribed in one of the four hospitals studied. Of those patients who received aerosolised colistin, 13 were for cystic fibrosis and 12 for other nosocomial lower respiratory tract infections (LRTI’s). Compliance to appropriate dose for the cystic fibrosis patients was good at 92.3%, however, for other LRTI’s was poor at only 41.7%. This study demonstrated that there is noteworthy prevalence of MDR Gram-negative infections in South African hospitals which requires the use of colistin. In addition, the study identified many stewardship related opportunities to improve appropriate colistin utilization in particular relating to dose for both routes of administration. The implementation of a colistin stewardship bundle is necessary, as a matter of urgency, to preserve the efficacy of this last resort antibiotic.LG201