Genesis of Antibiotic Resistance (AR) XXXX: Combination Therapy (Colistin And Tigecycline) For External Ventricular Device (EVD)‐Related Ventriculitis Gale Traumatic Brain Injury (TBI): Critical Appraisal
Authors: Mendoza Jonathan , Contreras Laura , Pointdexter Ursula , Theiss Savanna , Clark Stephanie , Ledezama Claudia , Martinez Azalia , Villarreal Diego , Munoz‐Chacon Jesus E. , Gayton Edith , Galindo Rocio , Soto Maria , Nunez Pedro , Kannan Subburaj 
Published: June 2021

To determine the role of AR in irreversible coma subsequent to TBI, a case report has been critically appraised (J Neurosci Rural Pract. 2016 Jul–Sep; 7(3):450–2). Day 1: A 75‐year‐old patient with small right subdural hematoma with frontal contusion upon admission to Intensive Care Unit (ICU) had Glasgow Coma Scale (GCS) 7 (E1V1M5) with bilateral equal and reacting pupils treated with Colistin and tigecycline for management of external ventricular device (EVD)‐related ventriculitis. EVD was placed for monitoring of intracranial pressure (ICP). The patient was in treatment with ceftriaxone 1 g/12 hourly for aspiration pneumonia. Day 3: GCS drooped to 4 (E1M3Vt). Day 4: Patient developed a fever (up to 103°F) suspected to be of EVD associated ventriculitis. Antibiotics were empirically upgraded to vancomycin and ceftazidime. Cerebrospinal fluid (CSF) culture and sensitivity revealed A. baumannii sensitive only to colistin and tigecycline and resistant to all other antibiotics including carbapenems. Day 4: Intravenous colistin was started at the dose of 2 million International Units (IU) 8 hourly and 200,000 IU through intraventricular route daily. Tigecycline was administered intravenously at a loading dose of 100 mg followed by 50 mg twice daily. CSF culture after 3 days of starting colistin (7th day of treatment) and tigecycline was negative. On day 8th however, there was a progressive decline in GCS to 2 (E1M1Vt). Due to declining renal function, iv dose of colistin was decreased to 2 million IU 24 hourly on the 12th day of starting colistin. Intravenous colistin and tigecycline were continued for 14 days (Total period of treatment 21 days) subsequent to withdrawal of life support as poor neurological outcome anticipated. From the 12th day of treatment a. culture and sensitivity lab test on the patient's CSF, b. antibiogram, and c. information on the implementation of antibiotics timeout (ATO) was not presented in the case report. It is acknowledged that up until 8th‐day appropriate measures reflecting ATO was in practice. However, from 12th day onwards aforesaid factors reflecting the evolution of AR has not been attempted. Taken together, it is suggested that the factors that govern the AR, was inadequately monitored from day 12th to the time of withdrawal of life support. Contrary to the claim of, “successful microbiological cure”, it is suggested that progression of AR overwhelmed the lymphatic system with sepsis inducing neurotoxicity, nephrotoxicity and possibly antibiotics induced toxic shock syndrome, In the absence of acute physiology and chronic health evaluation II score, sequential organ failure assessment, systemic inflammatory response syndrome score, injury severity score, exclusively based GCS to 2 (E1M1Vt) the life support has been withdrawn. The profile of antibiotic resistance pathogenic microbes (ARP) and its role in septicemia leading up to multi organ system failure has not been addressed adequately. Considering the age as pivotal factor, administering the tigecycline as a component of multidrug and multi‐route therapy is a serious risk factor with potential site for colonization for ARP. Lack of adequately qualified Intensive Care Unit personnel, improper intraventricular catheter handling, and CSF sampling only when clinically necessary, and periodic replacement of drainage catheter with maximum care could have eliminated the plausible cause for the septicemia in addition to the parameters defining sepsis and septic shock(sepsis‐3).Support or Funding InformationSupported by the Professional Development Funds by SWTJC to Subburaj Kannan.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.