Epidemiology of carbapenem-resistant Gram-negative infections globally

The spread of carbapenem-resistant Gram-negative bacteria (GNB) with changes in institutional epidemiology continues to evolve worldwide. The purpose of this review is to evaluate new data with regard to the epidemiology, mechanisms of resistance and the impact of carbapenem resistance on mortality.

The rapid expansion of acquired carbapenem resistance is increasingly propagated by mobile genetic elements such as epidemic plasmids that transfer carbapenemase genes within and between GNB. The risk of acquisition of carbapenem-resistant Acinetobacter baumannii increases four-fold with carbapenem exposure and new meta-analyses have confirmed excess mortality associated with carbapenem-resistant Pseudomonas aeruginosa. Carbapenemase-producing Klebsiella pneumoniae, the most commonly encountered carbapenemase-producing Enterobacterales (CPE) and a major cause of high-mortality hospital-related infections, represents the most rapidly growing global threat. Carbapenem use in patients colonized with such genotypes, leads to an increase in CPE abundance in the gastrointestinal tract, which in turn increases the risk of blood-stream infections four-fold.

High-resistance rates in carbapenem-resistant GNB in many countries will inevitably complicate treatment of serious infections in vulnerable patient groups and should accelerate global attempts to overcome the impediments we face with regard to effective antimicrobial stewardship and infection prevention and control programs.