High Dose Tigecycline-Induced Mitochondrial Dysfunction-Associated Acute Metabolic Acidosis: A Retrospective Study

Abstract

Background: Tigecycline (TGC) is a last resort antibiotic having broad spectrum antibacterial activity against gram-negative bacteria. Beyond its standard dosing regimen, a double dosing regimen has been practicing for last couple of years to achieve adequate drug concentration in the targeted body tissues. TGC interferes with the mitochondrial protein translation process and may lead to non-anion gap acute metabolic acidosis (NAGAMA) with low blood-pH level. The main objective of this retrospective study was to evaluate the frequency of high dose TGC-induced NAGAMA events in the South Asian critically ill patients. Methods: The retrospective data of 24 critically ill patients of an intensive care unit (ICU) were considered for this study. Patients of this study received high dose of TGC. Including all necessary laboratory data, patients’ anion gap, blood-pH level data in pre and post-TGC therapy were also recorded from the ICU’s clinical-record archive. All the data were analyzed to find out the significance of NAGAMA event with high dose TGC therapy. Results: Among the patients administered with high dose TGC, 45.83% (11; n=24) of patients were experienced with NAGAMA event and in every 2.18 patients, 1 patient developed this event. Among those 11 patients, 63.64% of patients were recovered within 24 hours after stopping the TGC therapy and the rest of the patients (36.36%) were recovered within 48 hours, where 4 patients required therapeutic intervention to overcome the NAGAMA event. Conclusion: High dose TGC-induced NAGAMA event is an unusual event, globally. Mitochondrial toxicity is a TGC-associated adverse event and the related NAGAMA is a detrimental clinical consequence. However, the complete mechanism of this event is even not fully clear but, caution should be taken in the use of high dose TGC mostly in the critically ill patients.