Emerging superbugs: The threat of Carbapenem Resistant Enterobacteriaceae

Abstract

Carbapenem-resistant Enterobacteriaceae (CRE) are gram-negative bacteria that are resistant to carbapenems, a group of antibiotics considered as the last-resource for the treatment of infections caused by multidrug-resistant bacteria. CRE constitutes a major threat to health care systems because infections caused by these pathogens are difficult to treat and are commonly associated with high mortality due to the limited availability of effective antibiotics. While infection prevention and timely detection are of vital importance to control CRE infections, developing new and effective anti-CRE therapies is also crucial. Accumulating evidence indicates that gut microbiota alteration (dysbiosis) is associated with an increased intestinal colonization with CRE and consequently with higher risk of developing CRE infections. Importantly, therapeutic interventions aimed to modify the gut microbiota composition via fecal microbiota transplantation (FMT) have been explored in various clinical settings with some of them showing promising results, although larger clinical trials are needed to confirm the efficacy of this strategy. Here, we highlight the challenges associated with the emergence of CRE infections.

Development of a Novel Antibacterial Peptide, PAM-5, via Combination of Phage Display Selection and Computer-Assisted Modification

“…Clearly demonstrated from the SEM images, extensive surface disruption and shape deformity characterized by surface roughening and corrugation, blebbing formation and micelles were seen for PAM-5-treated P. aeruginosa and E. coli but not on untreated bacteria. These changes resembled the surface disruptions that were caused by several membrane-active ABPs from other studies [ 47 , 50 , 63 , 64 , 65 ] which possess the similar extent of cationicity and amphipathicity as PAM-5. As proposed by these studies, the two peptide features may allow these peptides to engage with multiple anionic sites of bacterial membranes in a non-ligand-selective manner.…”

“…Apart from this, PAM-5 was also found active against a panel of Gram-negative bacteria, including some multidrug-resistant clinical isolates at the MBCs that ranged from 4 µg/mL to 32 µg/mL. Interestingly, the bactericidal effect of PAM-5 was not compromised by a clinical isolate of carbapenem-resistant K. pneumoniae , which is commonly regarded as a superbug [ 47 ]. Clearly demonstrated by these findings, the non-bacterial-specific action by PAM-5 may render this peptide with the ability to inhibit or kill a broad spectrum of pathogenic bacteria, where a single antibacterial agent is able to kill bacteria from different families such as Pseudomonadaceae ( P. aeruginosa ), Enterobacteriaceae ( E. coli, K. pneumoniae, Salmonella Typhi, Shigella flexneri ) and Moraxellaceae ( A. baumannii, A. junii ).…”

APTC-C-SA01: A Novel Bacteriophage Cocktail Targeting Staphylococcus aureus and MRSA Biofilms

“…Such infections mainly affect patients who have been hospitalized long-term, often in intensive care units, patients who have been administered antimicrobial drugs long-term, or those who have undergone invasive treatment or with low immunity such as in the context of cancer. Those patients are often vulnerable to hospital-acquired superbug infections in the form of either respiratory infections or direct contact infections [ 4 , 5 , 6 , 7 , 8 ].…”

Insights into Carbapenem Resistance in Vibrio Species: Current Status and Future Perspectives

“…For instance, all V. vulnificus strains carrying the New Delhi metallo-ß-lactamase ( bla NDM-1 ) (gene that encodes carbapenemase which make the bacteria resistant to carbapenems) sampled from the recreational beaches in Nigeria were found to be resistant to at least 17 antibiotics, with the highest record of 24 types [ 60 ]. Moreover, infections induced by carbapenem-resistant Enterobacteriaceae are challenging to treat and associated with increased mortality rates due to the minimal treatment options available [ 61 ].…”