Antibiotic prophylaxis (AP) for an inpatient surgical care unit (SCU) and also intensive care unit (ICU) remains a controversial treatment option. Though in a many instances AP is considered as an invaluable measure to minimize the mortality rate, in other instances AP has been shown to exacerbate the Antibiotic Resistance Pathogen (ARP) induced mortality rate in both SCU and ICU. A rationale is presented to purge the practice of AP in STBI/TBI admitted in ICU to Rout AR Induced Mortality. In a case report where the role of “Colonization Pressure” (CP) (i.e., the proportion of other patients colonized with ARP) analysis indicate, that in an ICU the average expected median time until the acquisition of Vancomycin‐Resistant Enterococci (VRE) ‐ is approximately 19 days when both antibiotic pressure and CP are 25% but 6 days when CP is 75% and antibiotic pressure is 25%. In an another case report, 250 trauma patients in a Surgical Intensive Care Unit (SICU) requiring an one or more surgical modality requiring a stay of 3 days or more received AP by 1 antibiotic (Cefoxitin sodium or ampicillin sodium/sulbactam sodium) for 24 hours (SHORT group or 1 or more antibiotics ( a combination of piperacillin sodium sterile and tazobactam sodium, or the combination of ampicillin, gentamicin sulfate, and metronidazole) prophylaxis administered longer than 24 hours with multiple antibiotics fail to improve morbidity. In a case report focused on patients admitted to the trauma intensive care unit (TICU) from January, 2001 through December, 2004 with blunt, non‐operative traumatic brain injury who is managed solely with an intracranial pressure (ICP) monitor, among those receiving no antibiotics prior to or during ICP monitoring ; and those already receiving antibiotics at the time of ICP monitor insertion were, n = 84. This study concluded that AP does not reduce the CNS infection rate and is associated with more MDR pathogens in any subsequent infectious complications. In a study aimed to determine the role of nosocomial transmission in both deployed hospitals and receiving military medical centers (MEDCENs) eighteen thousand five hundred sixty of 21,272 patients (2005 to 2009) were screened for Multidrug‐resistant organism (MDRO) colonization. Although colonization with Acinetobacter (ACB) declined during the following 5 years, an increase ARP including extended spectrum β‐lactamase (ESBL) ‐producing Enterobacteriaceae were shown to be increasing. However, the risk of ARP selection caused by the antibiotic administration for 48 hours or more, outweighed potential benefits. A study aimed to determine the impact of prolonged use of CNS device for dispensing AP as a factor in inducing the ARP and Clostridium difficile where, patient receiving AP, n = 116, and control group patients had mean APACHE II scores of 17.7 ± 9.2 and 15.1 ± 10.6 with 53.4 and 24.6 % receiving craniotomies. A higher incidence of ARP in patients receiving prolonged AP with a CNS device, but incidence of C. difficile were not significant compared to controls. Taken together, in the absence of Glasgow Coma Scale (GCS) rating upon admission of STBI/TBI patients in ICU, performing culture and sensitivity assay in CSF, implementing prudent antibiotic stewardship and implementing Antibiotic Time Out (ATO) followed by induction of “Trans” state possibly to make suggestions enabling a psychological propensity to sojourn the infectious state would limit the AR induced mortality.Support or Funding InformationSupported by Professional Development funds of SWTJC to Subburaj KannanThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.