Use of adjuvants to improve antibiotic efficacy and reduce the burden of antimicrobial resistance.

Abstract

Introduction: The increase of antibiotic resistance, together with the absence of novel antibiotics, makes mandatory the introduction of novel strategies to optimize the use of existing antibiotics. Among them, the use of molecules that increase their activity looks promising.

Areas covered: Different categories of adjuvants were reviewed. Anti-resistance adjuvants increase the activity of antibiotics by inhibiting antibiotic resistance determinants. Anti-virulence approaches focus on the infection process itself; reducing virulence in combination with an antibiotic can improve therapeutic efficacy. Combination of phages with antibiotics can also be useful, since they present different mechanisms of action and targets. Finally, combining antibiotics with adjuvants in the same molecule may serve to improve antibiotics' efficacy and overcome potential problems of differential pharmacokinetics/pharmacodynamics.

Expert opinion: The successful combination of inhibitors of β-lactamases with β-lactams has shown that adjuvants can improve the efficacy of current antibiotics. In this sense, novel anti-resistance adjuvants able to inhibit efflux pumps are still needed, as well as anti-virulence compounds that improve the efficacy of antibiotics by interfering with the infection process. Although adjuvants may present different pharmacodynamics/pharmacokinetics than antibiotics, conjugates containing both compounds can solve this problem. Finally, already approved drugs can be a promising source of antibiotic adjuvants.