Systematic Review of Carbapenem Resistant Gram-negative Infective Endocarditis, Treatment Options and Outcomes

Background: Gram negative infective endocarditis is rare and usually associated with intravenous drug use or significant healthcare exposure and prosthetic cardiac valves or devices. Carbapenem resistance is a growing concern worldwide with limited drug options for these infections especially serious high inoculum infections such as endocarditis. Methods: A systematic review examining treatment options and outcomes was conducted with identification of 12 cases in the literature. Results: Pseudomonas aeruginosa was the most common organism with left sided valvular involvement being most common. 18 different antibiotic regimens were used with surgery occurring in 5 cases (42%). In hospital mortality was 33% which increased at 6 months post episode. Increased age (p= 0.056) and CCI (p=0.006) appeared to be associated with death. Microbiological cure was more common in patients who received combination therapy with 2 active agents (75% successful) and combination therapy including an active beta-lactam agent (100% successful) but these did not meet statistical significance. Conclusions: Recommendations for management of this rare condition based on this systematic review and other available evidence are summarised in this review. Management should generally involve multidisciplinary teams, combination therapy with at least 2 active agents including a beta-lactam agent where possible with consideration of surgery in all cases. Evidence is however limited with need for ongoing publication of cases and further research to guide therapy in the future.