Concepedia

Concept

drug resistance

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Beta-Lactamase Emergence

1936 - 1965

During 1936 to 1965, the dominant research trajectory emphasized mechanistic and pharmacodynamic understanding of penicillin action, including how penicillin interacts with bacterial targets and how drug concentrations relate to effect. A central thread traced the enzymatic inactivation of penicillin by penicillinases, the ensuing evolution of penicillin derivatives to resist degradation, and the patterns of resistance observed in Staphylococcus and other bacteria, with clear implications for infection control and stewardship. Efforts also explored chemical optimization of penicillin derivatives and strategies to enhance therapeutic efficacy while considering safety and immunological dimensions.

Mechanistic and pharmacodynamic exploration of penicillin action, including in vitro activity, concentration‑response relationships, enzymatic targets, and chemical nature of penicillin interactions that underpin antimicrobial efficacy and resistance mechanisms [1], [6], [10], [12], [13], [19].

Discovery and characterization of bacterial enzymes that inactivate penicillin (penicillinases), their substrates/inhibitors, and the evolution of penicillin derivatives to overcome enzymatic degradation [4], [15], [16], [18], [20].

Patterns of resistance development in Staphylococcus and other pathogens, including MIC‑level resistance and implications for infection control and antimicrobial stewardship [5], [7], [14], [18].

Chemistry and optimization of penicillin derivatives and therapeutic strategies, addressing penicillin as a chemotherapeutic agent, its chemical nature, and derivative exploration to enhance activity [3], [12], [15], [16].

Immunological dimensions of penicillin use, including penicillin antigen formation and hypersensitivity to penicillin derivatives, informing safety and immune response considerations [8], [9], [17].

Genetic-Molecular Transporter Architecture

1966 - 1992

Transporter-Mediated Resistance Spread

1993 - 1999

Genotype-Driven Resistance

2000 - 2006

Cross-Talk Driven Resistance

2007 - 2013

Adaptive Resistance Across Therapies

2014 - 2024