Limitations of beta-lactam therapy for infections caused by susceptible Gram-positive bacteria.

Penicillin and related beta-lactam agents have been the most widely used and most important antimicrobials in medical history, and remain the recommended therapy for many infectious diseases 85 years after the discovery of penicillin by Alexander Fleming. Yet the efficacy of these agents has been undermined by two factors - the emergence of clinically significant resistance to the antimicrobial activity of these agents, and clinical situations in which these drugs may be suboptimal (even though the bacterial pathogens are not "resistant" to the drugs). Observations in experimental infection models in animals (group A streptococcal myositis, pneumococcal meningitis and pneumonia, group B streptococcal sepsis) and in some cases clinical studies suggest that monotherapy with beta-lactam antibiotics may be inferior to treatment with other types of antibiotics, alone or in combination with beta-lactams - even in situations where the bacterial pathogens remain fully "susceptible" to beta-lactams in vitro.