Abstract Introduction In the wake of Hurricane Maria, many US hospitals experienced massive drug shortages requiring substitution with alternative therapies. Our regional center experienced an increased incidence of Carbapenem-Polymyxin-Quat-Resistant Acinetobacter baumannii(CPQRA) infections, compared to a previous year of no infections. Here we describe a successful interdisciplinary approach to its eradication. Methods We conducted a retrospective review of CPQRA outbreaks for November and December 2018 in the burn ICU. De-identified data was collected and analyzed. In collaboration with the state’s department of health and epidemiology section, whole-genome sequencing was carried out on bacterial isolates. In addition, we instituted adenosine triphosphate (ATP) monitoring on all surfaces, a process of rapidly measuring actively growing microorganisms. Results Resistant Acinetobacter was isolated from five ICU patients, two of whom died with CPQRA bacteremia, producing a case-fatality rate of 40%. The two cases that died both suffered traumatic injuries with multiple fractures in addition to an average TBSA of 58%.Non-fatal cases suffered no other traumatic injuries and had an average TBSA of 51%.During this period, genitourinary irrigant (neomycin-Polymyxin B) and polymyxin ointment were the primary topical agents for wound care. Whole genome sequencing revealed a qacEdelta1 positive strain and identified the primary source as a patient that returned from a long-term care facility carrying the converted A. Baumannii infection. ATP testing also showed increased levels in patient rooms and surgical suite. Conclusions As a result of these findings, we achieved eradication by developing new and reinforcing traditional practices of infection control. This included UV light therapy to all ICU rooms and surgical suite, oversight of environmental services procedures, rigorous enforcement of hospital infection control procedures, auditing hand hygiene, increased efforts in antibiotic stewardshipand discontinuing Polymyxin containing topicals. By January 2019 there were no new cases of CPQRA in the ICU. This study shows that the resistance and rapid spread of CPQRA can be controlled with the cooperation of hospital staff, environmental services, infection control, pharmacy and the state’s department of health. With the coordinated efforts of all parties, we were able to successfully eradicate a virulent and fatal resistant A. baumannii strain. Applicability of Research to Practice Describe an approach to eradicating resistant organisms and provide a roadmap to characterize the source, implement control measures to terminate an outbreak, and institute preventive measures.