6ER-011 Cotrimoxazole: how folate supplementation could affect treatment efficacy

Abstract

<h3>Background and importance</h3> Cotrimoxazole (CTX) is an association of sulfamethoxazole and trimethoprim which acts synergistically to inhibit folic acid synthesis and block bacterial growth. It is used in the treatment of bacterial infections and in the prophylaxis of opportunistic diseases like toxoplasmosis and infection with <i>Pneumocystis jirovecii</i> in immunosuppressed patients. CTX causes myelotoxicity since it affects the same process in human cells. To prevent toxicity, folic or folinic acid can be administered. However, there is controversy as to whether this folate supplementation could affect the efficacy of cotrimoxazole. <h3>Aim and objectives</h3> To determine if the co-administration of CTX and folates compromises efficacy of the treatment. <h3>Material and methods</h3> A review of the published evidence on CTX and folate supplementation was conducted. An initial search was performed in PubMed and Google Scholar using the terms ‘cotrimoxazole’ and ‘folates’ and ‘efficacy’ supported by federal data sheets. <h3>Results</h3> Regarding the use of folates as a supplement in bacterial infections, there is no evidence at all. Theoretically, as these bacteria intrinsically lack mechanisms to capture exogenous folates, it seems to be more appropriate to use folic acid before folinic acid due to its lipophilicity avoiding a possible passage of this molecule through the bacterial wall, which is lipophilic in nature. <i>P. jirovecii</i> is permeable to lipophilic folates and lacks an active transport mechanism to incorporate classical folates. Therefore, the administration of folinic acid, which is more lipophilic, could reduce the antifolate activity of CTX meanwhile folic acid supplements do not affect the activity of CTX. In the case of <i>Toxoplasma gondii</i>, the folate of choice is folinic acid because the microorganism can intake exogenous folate through the BT1 family transmembrane proteins which also have no affinity for folic acid. <h3>Conclusion and relevance</h3> In general, theoretically folic acid supplementation can be used to prevent myelotoxicity as it does not interfere with the action of the antibiotic in the case of bacteria. However, in infections caused by more complex eukaryotic organisms such as other fungi or parasites with lipophilic cell walls or specifical transmembrane proteins, each case must be evaluated on its own merits. <h3>References and/or acknowledgements</h3> <h3>Conflict of interest</h3> No conflict of interest