Plain Language Summary Carbapenems are a subclass of antibiotic used to treat infections caused by Gram-negative bacteria, particularly in resistant and multidrug-resistant (MDR) infections where penicillin and cephalosporins are no longer effective. However, carbapenem-resistant Enterobacterales (CRE) have emerged due to acquisition of carbapenemase enzymes, most prevalent types are KPC, VIM, IMP, NDM, and OXA-48; infections caused by these bacteria have disseminated globally in both the healthcare and community setting. Resulting in a significant public health issue and clinical burden, these CRE infections are associated with increased morbidity and mortality, in part because carbapenems are the last therapeutic line of defense against resistant and MDR bacterial infections. The author wanted to investigate current US and global epidemiology of carbapenem-resistant infections, identify factors driving changes, as well as diagnostic technologies, and reporting or surveillance methods in place to track trends and inform therapeutic protocols and development. Overall, carbapenemase enzymes originally only reported in one country or region in 2006-2007, by 2013 and onwards have spread not only to surrounding countries but to other continents, which has impacted antibiotic resistance patterns and susceptibility. Increasing human travel and environmental factors, such as livestock care, food distribution, sewage, and recreational water, have contributed to global dissemination of CRE. Active surveillance programs are key to tracking resistance in real time, in order to update susceptibility breakpoints and epidemiology, which can inform antibiotic treatment choices, management guidelines, and the development of new therapeutics. Together, these factors will help to identify, control, and treat the spread of carbapenem resistance. The global emergence of carbapenemase-producing bacteria capable of hydrolyzing the once effective carbapenem antibiotics is considered a contemporary public health concern. Carbapenemase enzymes, once constrained to isolates of Klebsiella pneumoniae, are now routinely reported in different bacteria within the Enterobacterales order of bacteria, creating the acronym CRE which now defines Carbapenem-Resistant Enterobacterales. CRE harboring different types of enzymes, including the most prevalent types KPC, VIM, IMP, NDM, and OXA-48, are now routinely reported and more importantly, are now frequently present in many infections world-wide. Defining and updating the contemporary epidemiology of both the US and global burden of carbapenem-resistant infections is now more important than ever. This review describes the global distribution and continued evolution of carbapenemases which continue to spread at alarming rates. Informed understanding of the current epidemiology of CRE, coupled with advances in antibiotic options, and the use rapid diagnostics offers the potential for rapid identification and management of carbapenem-resistant infections.
