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Carbapenem-resistant Enterobacteriaceae represent a crucial global public health issue. The challenges associated with carbapenem-resistant Enterobacteriaceae are multifaceted. This review article aims to explore and comprehend the emerging challenges and the latest developments in the management of carbapenem-resistant Enterobacteriaceae infections. A comprehensive literature search was conducted using databases such as PubMed, Cochrane Library, and Embase. Studies published from database inception until May 2024 were included. Articles were selected based on relevance, study design, and quality. Data from clinical trials, observational studies, and reviews were synthesized to provide a detailed overview of the current state of knowledge on carbapenem-resistant Enterobacteriaceae. The review identifies key epidemiological trends, including geographic variations and risk factors associated with carbapenem-resistant Enterobacteriaceae. Mechanisms of resistance are elucidated, focusing on carbapenemase production and other related factors. Current treatment options are assessed, with an emphasis on newer antibiotic combinations such as ceftazidime/avibactam, meropenem/vaborbactam, ceftolozane/tazobactam, and cefepime/enmetazobactam. The review also highlights emerging therapeutic approaches, including novel antibiotics and non-traditional approaches like phage therapy, fecal microbiota transplantation, probiotics, antimicrobial peptides, vaccines, and herbal drugs. Additionally, the review also reflects on effective infection prevention and control strategies. While research efforts to explore newer combinations and alternate approaches to treat carbapenem-resistant Enterobacteriaceae infections are crucial, the importance of stringent infection prevention and control strategies cannot be overstated. This dual focus is essential to address both the immediate and long-term challenges posed by carbapenem-resistant Enterobacteriaceae
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