Abstract: Co-agent combinations and/or formulations herein unexpectedly display significantly better antimicrobial activity (e.g., more efficacy and/or more potency) against anaerobic pathogens not previously considered targets. With three or more co-agents, selected from a group of a fosfomycin, a diaminopyridine, a sulfonamide, a beta lactam antibacterial, a bacterial beta-lactamase inhibitor, a bacterial fosfomycin-modifying enzyme, and a bacterial peptidoglycan synthesis inhibitor, the therapeutic potential of the three or more co-agents is expanded by targeting a broader spectrum of pathogens. Co-agents, by unexpected synergistic action in an anaerobic environment, are now active and efficacious against difficult to treat pathogenic anaerobes (including anaerobes that cannot utilize oxygen and/or reside in an anaerobic environment, some being inhibited by oxygen), as well as pathogens considered resistant or intolerant to at least one of the co-agents when used singly in an anaerobic environment.