Purpose: The World Health Organization (WHO) in 2017 classified some carbapenem-resistant Gram-negative bacteria into a critical criterial group for research and development. This study reviews the need to prioritize the water matrices as hotspot in the development and transfer of antibiotic resistance determinants, where future total resistant superbug may emerge. Methods: Published articles on Google Scholars, PubMed/Medline Search and other search tools were selected, with special interest in articles published in indexed journals. Search criteria were based on antibiotic resistance, antibiotic resistance determinants and emerging trend in the reported trend of antibiotic resistance among bacteria from water matrices. Results: Research reports around the globe have identified carbapenem-resistant Gram-negative bacteria (CRGNB) in water matrices. These CRGNB have also been found to be resistant to other antibiotics in the last line of defence. Molecular typing of some carbapenem-resistant Enterobacteriaceae (CRE) in the environment through pulsed-field electrophoresis showed them to be the same as those in the hospital settings. CRGNB from various water matrices have been reported to harbour carbapenem resistance genes with phenotypic expression of carbapenemases' production. Water habitat provides a conducive environment for the development and spread of carbapenem resistance. Factors like residual antibiotics (RAbs), metals, biocide and water-borne mutagens aid the emergence of the resistance in water matrices. Irrespective of where it was contacted, carbapenem-resistant bacteria have poor prognosis. This is exemplified by resistance to 26 different antibiotics recently in the USA. The human health risk associated with the use of water harbouring these pathogens for irrigating fruits and vegetables may be alarming. Conclusion: The reports of the rising trend of antibiotic resistance also necessitate prioritizing water matrices when addressing the problems from the reservoir. Surveillance and strict isolation, education and enlightenment, strict compliance with multiple barrier approach of the WHO and more search for more potent antibiotics remain some of the antidotes against the development and spread of resistance through the water matrices as discussed in this article.

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