β-Lactam Resistance Mechanisms: Gram-Positive Bacteria and Mycobacterium tuberculosis

The value of the beta-lactam antibiotics for the control of bacterial infection has eroded with time. Three Gram-positive human pathogens that were once routinely susceptible to beta-lactam chemotherapy-Streptococcus pneumoniae, Enterococcus faecium, and Staphylococcus aureus-now are not. Although a fourth bacterium, the acid-fast (but not Gram-positive-staining) Mycobacterium tuberculosis, has intrinsic resistance to earlier beta-lactams, the emergence of strains of this bacterium resistant to virtually all other antibiotics has compelled the evaluation of newer beta-lactam combinations as possible contributors to the multidrug chemotherapy required to control tubercular infection. The emerging molecular-level understanding of these resistance mechanisms used by these four bacteria provides the conceptual framework for bringing forward new beta-lactams, and new beta-lactam strategies, for the future control of their infections.