Table 1.

Summary of the reviewed antifolates as antibiotic agents, including their modes of action, indications, mode of administration and toxicity issues.

Drug		Mode of Action	Indication	Administration	Toxicity	References
Mafenide		Unknown	Severe burns wounds	Topical: creams or powders for solution	Metabolic acidosis, allergies	[31,32,33,34,35,36,37,38]
Silver Sulfadiazine		DHPS inhibitor + silver biocide effect	Burns and ulcers	Topical: creams or hydrogels	Allergies, sensitivity to silver or propylene glycol. Rare: hemolysis, argyria or pseudo-eschar formation	[32,33,39,40,41,42]
Sulfadiazine		DHPS inhibitor	Urinary tract infections, otitis media, encephalitis, meningitis. Prophylaxis for rheumatic fevers. Parasitic infections: malaria and toxoplasmosis	Oral: tablets	Allergies and gastrointestinal upset. Rare: encephalopathies, renal failure, nephrolithiasis	[43,44,45,47,48,49]
Sulfacetamide		DHPS inhibitor	Skin, ocular and urinary tract infections	Ophthalmic: solution/drops Topical: ointment or lotions Vaginal: creams	Rare: mild cutaneous reactions. Category C drug in pregnancy	[50,51,52,53,54,55]
Sulfisoxazole		DHPS inhibitor	Severe, repeated, or long-lasting urinary tract infections, meningococcal meningitis, acute otitis media, ocular infections, etc.	Oral: tablets or suspensions with or without erythromycin	Rare. Allergies, gastrointestinal disturbances	[56,57,58,59,60,61,62,63,64,65,66]
Co-trimoxazole	Sulfamethoxazole	DHPS inhibitor	Bacterial bronchitis, prostatitis and urinary tract infections.	Oral: tablets of both compounds (co-trimoxazole)	Allergies, nausea, vomiting, diarrhea and hematologic alterations. Category D drug in pregnancy	[8,67,68,69,70,71,72,73,74]
	Trimethoprim	DHFR inhibitor
Dapsone		DHPS inhibitor	Leprosy. Prophylaxis for co-trimoxazole-resistant P. jirovecii infections. With pyrimethamine: malaria	Oral: tablets or suspensions Topical: gels	Hemolysis (usually mild), dapsone syndrome, gastrointestinal upset. Category C drug in pregnancy	[75,76,77,78,79,80,81,82,83]
Antimalarial Agents	Proguanil	DHFR inhibitor	Malaria treatment and prophylaxis	Oral: tablets	Hypersensitivity reactions, bone marrow suppression	[3,84,85,86]
	Pyrimethamine	DHFR inhibitor
	Sulfadoxine	DHPS inhibitor