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Antibacterial activity of imipenem: the first thienamycin antibiotic
Abstract:
Imipenem (N-formimidoyl thienamycin) is the first representative of a new class of beta-lactam antibiotics--the carbapenems. Imipenem has an unusually broad spectrum, high potency, and no cross-resistance with other beta-lactam antibiotics. Susceptible gram-negative species include Pseudomonas aeruginosa, Serratia, and Enterobacter. Activity is high against Staphylococcus aureus, most group D streptococci, and Staphylococcus epidermidis but is variable against methicillin-resistant S. aureus. Imipenem is more active against Bacteroides than are other beta-lactam agents, chloramphenicol, metronidazole, and clindamycin. The minimal inhibitory concentrations (MICs) for 98% of 30,655 isolates--excluding those of the three resistant species (Pseudomonas maltophilia, Pseudomonas cepacia, and Streptococcus faecium)--were less than 8 micrograms/ml, the susceptibility breakpoint adopted for clinical trials. Imipenem is bactericidal (minimal bactericidal concentrations (MBCs] less than twice the MICs). For P. aeruginosa, MBCs of imipenem are less influenced by high inoculum density rather than are MBCs of antipseudomonal penicillins and cephalosporins. Stability of imipenem to diverse classes of plasmid-mediated and chromosomal beta-lactamases accounts for its lack of cross-resistance with other beta-lactam antibiotics. Imipenem is also active against P. aeruginosa with non-lactamase-mediated resistance to classical beta-lactam agents. Efficacy of imipenem was shown in animal models, including septicemia in normal and neutropenic rodents and P. aeruginosa pneumonia. Imipenem also has a unique postantibiotic effect against P. aeruginosa in vivo.
Insights
Imipenem, a novel carbapenem antibiotic, demonstrates broad-spectrum activity and high potency against numerous bacteria, including resistant strains. Its stability against beta-lactamases ensures efficacy where other antibiotics fail.
Area of Science:
- Microbiology
- Pharmacology
- Infectious Diseases
Background:
- Imipenem represents a new class of beta-lactam antibiotics, the carbapenems.
- It exhibits a broad spectrum of activity and high potency.
- Notably, it shows no cross-resistance with existing beta-lactam antibiotics.
Purpose of the Study:
- To evaluate the antimicrobial spectrum and potency of imipenem.
- To assess its activity against various bacterial species, including resistant strains.
- To investigate its bactericidal properties and stability against beta-lactamases.
Main Methods:
- Antimicrobial susceptibility testing was performed on a large number of bacterial isolates.
- Minimal inhibitory concentrations (MICs) and minimal bactericidal concentrations (MBCs) were determined.
- Activity against specific resistant pathogens and in animal models was assessed.
Main Results:
- Imipenem demonstrated high potency against Gram-negative species like Pseudomonas aeruginosa, Serratia, and Enterobacter.
- It was highly active against Staphylococcus aureus and Staphylococcus epidermidis, with variable activity against methicillin-resistant S. aureus.
- Imipenem showed superior activity against Bacteroides compared to other agents and was effective against P. aeruginosa with non-lactamase-mediated resistance.
Conclusions:
- Imipenem possesses a broad spectrum of activity, high potency, and unique resistance profiles.
- Its stability to beta-lactamases contributes to its effectiveness against a wide range of bacteria.
- Imipenem shows promise as a potent therapeutic agent, particularly for infections caused by resistant organisms.