A Comprehensive Monograph on Imipenem: Pharmacology, Clinical Efficacy, and Evolving Challenges

I. Introduction and Drug Profile

1.1. Historical Context and Development: From Thienamycin to a Clinical Cornerstone

Imipenem (DrugBank ID: DB01598) is a semi-synthetic β-lactam antibiotic that marked the genesis of the carbapenem class, a group of agents that have become indispensable in the management of severe bacterial infections.[1] Its development originated from the natural product thienamycin, which is produced by the soil bacterium

Streptomyces cattleya.[2] While thienamycin demonstrated exceptionally potent and broad-spectrum antibacterial activity, its inherent chemical instability in aqueous solutions rendered it clinically unviable.[2]

In a significant feat of medicinal chemistry, scientists at Merck in the mid-1970s embarked on a lengthy trial-and-error process to modify the thienamycin structure, seeking a derivative that retained the parent compound's potent activity while possessing the necessary stability for therapeutic use.[2] This research culminated in the synthesis of imipenem, which was patented in 1975 and received its first approval from the U.S. Food and Drug Administration (FDA) in 1985.[2] The introduction of imipenem established the carbapenem class, which is characterized by high resistance to the β-lactamase enzymes produced by many multi-drug resistant (MDR) Gram-negative bacteria. This property has made carbapenems, and imipenem in particular, critical last-resort agents for infections not readily treated with other antibiotics.[2]