Para-aminosalicylic acid: the return of an old friend

Para-aminosalicylic acid (PAS) is one of the last remaining drugs available to treat extensively drug-resistant (XDR) tuberculosis. Good outcomes (81% 5 year survival) were documented when PAS was first used with streptomycin, yet results of PAS with remaining potentially effective drugs for the treatment of XDR tuberculosis are poor (mortality 30-90%). In this Review, we assess published work regarding recommendations for PAS dosing in relation to efficacy and tolerance. PAS 20 g daily acoompanied only by streptomycin is better in prevention of streptomycin resistance than PAS 10 g or 5 g daily. When accompanied by isonazid, a more potent drug than streptomycin, treatment success with PAS 20 g daily is similar to that of PAS 10 g daily. In contemporary, relatively weak XDR tuberculosis regimens, the recommended doseage of PAS 8-12 g in two to three doses daily is probably insufficient. Furthermore, once daily PAS could be considered, because substantial research suggests no worse intolerance than with multiple daily PAS doses. In most countries, PAS is now available in a granular, slow-release formulation that seems well tolerated, but efficacy has never been formally assessed. Once daily dosing with granular PAS might achieve high peak concentrations and a long interval above minimum inhibitory concentration, with the advantage of improved supervision of drug intake.