Contemporary unconventional clinical use of co-trimoxazole

In the late 1960s, the combination of trimethoprim and sulphamethoxazole (co-trimoxazole) was introduced into clinical practice and used to treat many infectious diseases, such as urinary tract infections, respiratory infections, sexually transmitted diseases, Gram-negative sepsis, enteric infections and typhoid fever. Subsequently, co-trimoxazole was reported to be effective against numerous bacterial, fungal and protozoal pathogens, including Nocardia, Listeria monocytogenes, Brucella, Stenotrophomonas maltophilia, Burkholderia, Coxiella burnetii, Tropheryma whipplei, atypical mycobacteria, and Pneumocystis jirovecii. Among protozoal infections, in addition to toxoplasmosis, co-trimoxazole has been used to treat susceptible Plasmodium falciparum, Cyclospora and Isospora infections. Several retrospective and prospective studies have demonstrated good clinical outcome with co-trimoxazole in treating invasive methicillin-resistant Staphylococcus aureus infections. We summarize herein the accumulated evidence in the literature on the new, ‘unconventional’ clinical use of co-trimoxazole during the last three decades. In the era of widespread antibiotic resistance and shortage of new antibiotic options, large-scale, well-designed studies are needed to explore the tremendous potential concealed in this well-established drug.