Incidence of Infection and Antimicrobial Consumption in Ventricular Assist Device (VAD) Recipients at the Prince Charles Hospital (TPCH): A Retrospective Analysis.

BACKGROUND: Ventricular assist devices (VADs) are frequently used as a bridge to heart transplant; however, infections are a common cause of increased morbidity and mortality. The optimal prophylactic antimicrobial regimen has not been effectively evaluated in literature. METHODS: Forty-three (43) patients received a VAD over the 5-year study period (2012-2017) at The Prince Charles Hospital (TPCH), Brisbane Australia. Of these, 41 patients were followed from implantation until transplantation or death. Antimicrobial prophylactic regimens and individual episodes of infection were recorded. The infection profiles, including types and incidence were compared to published literature using definitions from the International Society for Heart and Lung Transplantation (ISHLT) guidelines for consistency. RESULTS: Median duration of VAD insertion was 79 days (IQR: 36-167). Patients received aztreonam, fluconazole and vancomycin (median duration 8 days). Twenty-two (22) (53.6%) patients experienced a VAD-specific and/or a VAD-related infective episode. Incidence of infection in the study cohort was 0.60 infections per 100 patient days. Thirteen (13) patients (31.7%) experienced 16 VAD-specific infections which were all driveline infections. Thirteen (13) patients (31.7%) experienced 14 VAD-related infections. The predominant VAD-related infection type was bacteraemia (36%). Predominant bacterial profiles of VAD-specific as well as VAD related infections were gram positive. Only three episodes had a gram negative as a causative pathogen which occurred much later post VAD insertion. Median time till VAD-specific or VAD-related infection was 46 and 15 days respectively. Obesity was significantly associated with increased risk of infection (HR: 3.2; 95% CI: 1.3-7.4). CONCLUSIONS: Infection is a common complication of VAD implantation. In our study population gram positive bacteria were the predominant causative pathogen. Based on the micro-organism profile there may be scope for a narrowing of the antibiotic regimen. A larger, multicentre study would be able to accurately guide a change. The information gathered in our study offers a strong foundation for such a multicentre study.

Study Protocol for a Pilot, Open-Label, Prospective, and Observational Study to Evaluate the Pharmacokinetics of Drugs Administered to Patients during Extracorporeal Circulation; Potential of In Vivo Cytochrome P450 Phenotyping to Optimise Pharmacotherapy.

Pharmacokinetic alterations of medications administered during surgeries involving cardiopulmonary bypass (CPB) and extracorporeal membrane oxygenation (ECMO) have been reported. The impact of CPB on the cytochrome P450 (CYP) enzymes' activity is the key factor. The metabolic rates of caffeine, dextromethorphan, midazolam, omeprazole, and Losartan to the CYP-specific metabolites are validated measures of in vivo CYP 1A2, 2D6, 3A4, 2C19, and 2C9 activities, respectively. The study aim is to assess the activities of major CYPs in patients on extracorporeal circulation (EC). This is a pilot, prospective, open-label, observational study in patients undergoing surgery using EC and patients undergoing laparoscopic cholecystectomy as a control group. CYP activities will be measured on the day, and 1-2 days pre-surgery/3-4 days post-surgery (cardiac surgery and Laparoscopic cholecystectomy) and 1-2 days after starting ECMO, 1-2 weeks after starting ECMO, and 1-2 days after discontinuation from ECMO. Aforementioned CYP substrates will be administered to the patient and blood samples will be collected at 0, 1, 2, 4, and 6 h post-dose. Major CYP enzymes' activities will be compared in each participant on the day, and before/after surgery. The CYP activities will be compared in three study groups to investigate the impact of CYPs on EC.