The safety profile of trimethoprim-sulfamethoxazole regarding concomitant other drugs: a comparative analysis of adverse effects in a tertiary level adult intensive care unit

Abstract Background Trimethoprim-sulfamethoxazole (TMP-SMX) has been used clinically against many gram-positive and gram-negative bacteria, Pneumocystis, and certain protozoa. Beside its beneficial effects, it has many adverse reactions such as hyperkalemia, aplastic anemia, fulminant hepatic necrosis, hematological and neurological toxicity. Evaluation of TMP-SMX-related adverse reactions in intensive care unit (ICU) patients who generally with polipharmacy is lacking. We aimed to identify TMP-SMX-related adverse effects associated with mortality, and to determine independent predictors of this outcome, and factors associated with adverse reactions in critically ill patients who generally with polypharmacy undergoing TMP-SMX therapy. Methods This retrospective observational cohort study was conducted in a 16-bed adult medical ICU in Türkiye. To assess the impact of various factors on TMP-SMX-related adverse reactions, patients were categorized into two independent groups based on the presence or absence of adverse effects. Additionally, to analyze changes in laboratory parameters associated with TMP-SMX therapy, paired comparisons were made between pre-therapy and post-therapy values within the same patients. Statistical analyses were conducted using IBM SPSS Statistics for Windows, Version 23.0. Results Serum creatinin (sCr) elevation, AST elevation, hyperbilirubinemia, thrombocytopenia, and metabolic acidosis were significantly associated with mortality, also sCr elevation was found to be an independent risk factor for mortality. Any of drugs or diseases were increased the risk of hyperkalemia concomitant TMP-SMX. ALT elevation were significantly associated with concomitantly teicoplanin. Endocrinologic disease or respiratory causes of ICU admission were found independent risk factors for AST elevation or acidosis respectively. Thrombocytopenia was associated with concomitantly colistin-echinocandin combination. Cardiovascular diseases concomitant TMP-SMX were found to be an independent risk factor for serum creatinin (sCr) elevation. There was no relationship between sCr elevation and TMP-SMX concomitantly colistimethate. Conclusions Physicians should pay attention when prescribing TMP-SMX to patients with cardiovascular diseases. Teicoplanin, colistin-echinocandin, piperacillin tazobactam and acyclovir should be administered carefully concomitantly TMP-SMX regarding liver enzyme elevation, thrombocytopenia and hyponatremia respectively. Clinical trial Not applicable.