With a Little Help from Good Friends – Boosters for the Prevention of Undesired Enzymatic Degradation of Anti-infective Drugs

Abstract

The development of anti-infective drugs has been one of the most impressive progresses in drug therapy in the past century. However, some of the promising antibacterial and antiviral drugs lost activity after being used in therapy for some time. Typically, this is due to the development of resistance phenomena, among which the expression of drug-degrading enzymes is one major aspect. In other cases, enzymatic degradation of anti-infective drugs by mammalian enzymes in the liver (or kidney) can limit the efficacy of the drugs. In all of these cases, selection of a drug from a different class is a therapeutic opportunity. Alternatively, the original drug can be used further in combination with other compounds named boosters, pharmacokinetic enhancers or antibiotic adjuvants. These compounds are used in combination with the primary anti-infective agent, but not for their direct effects on the infection itself, but since they enhance or restore the activity of the drug. This mini-review gives an overview on the therapeutically most important classes of boosters/antibiotic enhancers, like β-lactamase inhibitors, inhibitors of CYP enzymes in HIV therapy and hepatitis C. Inhibitors of efflux pumps in pathogenic bacteria and fungi will be addressed shortly.