Co-agents as Therapy Against Anaerobic Pathogens

A synergist for an antibiotic combination, the antibiotic combination comprising:

• a diaminopyridine in a pharmaceutically acceptable form selected from one or more of a salt, phosphate, acid, and ester, in which the diaminopyridine may be substituted for an inhibitor of bacterial dihydrofolate reductase, any of which will when used singly have:
• (a) some activity against an aerobic bacteria in an aerobic environment;
• and (b) no activity against one or more obligate anaerobic bacteria in an anaerobic environment;
• and
• a sulfonamide in a pharmaceutically acceptable form selected from one or more of a salt, phosphate, acid, and ester, in which the sulfonamide may be substituted for an inhibitor of bacterial dihydropteroate synthase, any of which will when used singly have:
• (a) some activity against an aerobic bacteria in an aerobic environment;
• and (b) no activity against one or more obligate anaerobic bacteria in an anaerobic environment;
• wherein the diaminopyridine and the inhibitor of bacterial dihydrofolate reductase will inhibit or inactive a dihydrofolate reductase enzyme of the one or more obligate anaerobic bacteria, and wherein the sulfonamide and the inhibitor of bacterial dihydropteroate synthase will inhibit or inactive a dihydropteroate synthase enzyme of the one or more obligate anaerobic bacteria, and
• the synergist comprising at least:
• a fosfomycin in a pharmaceutically acceptable form selected from one or more of a salt, phosphate, amine, acid, and ester, in which the fosfomycin may be substituted for an inhibitor of bacterial UDP-GlcNAc enolpyruvyl transferase (MurA), any of which will when used singly have:
• (a) some activity against an aerobic bacteria in an aerobic environment;
• and (b) no activity against one or more obligate anaerobic bacteria in an anaerobic environment;
• wherein the synergist with the antibiotic combination causes synergistic action so as to transform therapeutic potential of the antibiotic combination, so that the synergist with the antibiotic combination are active against the one or more obligate anaerobic bacteria in the anaerobic environment.

A kit containing pharmaceutically acceptable co-agents for utilization as pharmacotherapy against one or more pathogenic anaerobes in an anaerobic environment, the kit comprising at least:

• a first co-agent in a therapeutically effective amount for delivery of the first co-agent in 24 hours, the first co-agent being a fosfomycin in a pharmaceutically acceptable form selected from one or more of a salt, phosphate, acid, amine, and ester, wherein the first co-agent when used alone in an aerobic environment is an inhibitor of bacterial UDP-GlcNAc enolpyruvyl transferase;
• a second co-agent in a therapeutically effective amount for delivery of the second co-agent in 24 hours, the second co-agent being a diaminopyridine in a pharmaceutically acceptable form selected from one or more of a salt, phosphate, acid, and ester, wherein the second co-agent when used alone in an aerobic environment is an inhibitor of bacterial dihydrofolate reductase;
• a third co-agent in a therapeutically effective amount for delivery of the third co-agent in 24 hours, the third co-agent being a sulfonamide in a pharmaceutically acceptable form selected from one or more of a salt, phosphate, acid, and ester, wherein the second co-agent when used alone in an aerobic environment is an inhibitor bacterial dihydropteroate synthase;
• and
• optionally at least one diluent for any one or more of the first co-agent, the second co-agent, and the third co-agent, wherein the first co-agent, the second co-agent and the third co-agent are in one or more vehicles, the one or more vehicles comprising a sufficient amount for at least one delivery in the 24 hours, wherein the kit is for delivery of a therapeutically effective amount of the first co-agent and a therapeutically effective amount of the second co-agent and therapeutically effective amount of the third co-agent for at least one delivery to a subject for treating or preventing an infection from one or more obligate anaerobic bacteria.