Genesis of Antibiotic Resistance (AR) LII: Laminar to Turbulent flow transition triggered by “Physiological Shunt” Induce Hypoxia (Anoxia?) Augmenting AR Clinical Persister (S) (ARCP)
Authors: Torres Jorge , Soto Elsa , Cerrillo Veronica , Barrientos April , Botello Cynthia , Mendoza Jonathan , Kannan Subburaj 
Published: April 2020

The mechanism(s) of biosimilar induced adverse clinical events in inflammatory disorders and its impact on the evolution of ARCP inherent on the incidence of morbidity and the mortality rate remains to be substantiated. A biosimilar to Neulasta (Pegfilgrastim) administered for myelosuppressive chemotherapy has been reported to have a clinically significant incidence of febrile neutropenia. Similar modalities with other biosimilars have also been presented (Int J Hematol.2010 Dec;92(5):765–8; Case Rep Nephrol Urol. 2012 Jul–Dec; 2(2): 165–171); The contraindication for the original formulation is reported to be acute respiratory distress syndrome (ARDS), Glomerulonephritis (GN), Leukocytosis, and Capillary Leak Syndrome (CLS). As per the differential diagnosis for the febrile neutropenia could be of acute respiratory distress syndrome (ARDS) with or without pulmonary edema. Under such clinical presentation tissue hypoxia (Stagnant anoxia (Hypoxicischemic injury), Anoxic anoxia?) with or without “Sweet Syndrome” with an unknown etiology waning the ventilation‐perfusion coupling in patients undergoing chemo/radiation therapy for clinical oncology modalities (J. Clin. Med. 2019, 8(2), 143). CLS has been ascribed with reversible plasma extravasation and loss of net filtration pressure gradient (NFP) in the microcirculation which is analogous to sepsis, septic shock, septicemia impelled hypotension possibly (hypovolemic shock?) with the end result of multiple organ failure (Kidney International, 2017: 92:1, 37). It is hypothesized that such clinical presentation of ensuing hypoxia (plausibly systemic anoxia?) causing VA/Q (VA = alveolar ventilation; Q= blood flow) is below normal which is about 2% of cardiac output (CO) referred to as “shunted blood” (deoxygenated). The total amount of “shunted blood” in the capillary bed – microcirculation per minute is “Physiological shunt” with dysregulated net filtration pressure (NFP) potentially a state of critical closing pressure (CCP) ebb the capillary exchange. Under such physiological sate declining perfusion pressure / perfusion index (PI) and tissue pO2 causing progressive hypoxia and/or anoxia. It is suggested that hypoxia serve as a trigger for generating an adverse pressure gradient impacting the expression pattern of
antibiotic
resistance
gene(s)
repertoire (ARCP). Altered ARGR expression profile is known to cause selection pressure on ARCP. In particular, ensuing anaerobic milieu in vivo, engender selection pressure on anaerobic AR pathogens including Gram negative rods, Gram‐positive cocci, Gram‐positive spore‐ and non‐spore‐forming bacilli and Gram‐negative cocci resulting in an aberrant expression pattern of ARGR. Taken together, such the clinical presentation would likely to lead to patients treated with biosimilar(s) become unresponsive to antibiotic therapy leading to an emergence of ARCP impairing the ability for clinical stratification and a defined point of clinical intervention preempting an instant CCP subsequent emergence Antibiotic Resistance Pandemic (ARP).

Support or Funding Information

Supported by professional development funds by SWTJC to Subburaj Kannan