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Meropenem: a microbiological overview
1Infection Research Department, Zeneca Pharmaceuticals, Macclesfield, Cheshire, UK.
Abstract:
Meropenem is a parenteral carbapenem antibiotic which has excellent bactericidal activity in vitro against almost all clinically significant aerobes and anaerobes. Its high activity is explained by ease of entry into bacteria combined with good affinity for essential penicillin binding proteins, including those associated with cell lysis. Breadth of spectrum is due, in part, to stability to all serine-based beta-lactamases, including those which hydrolyse third-generation cephalosporins. Meropenem has an antibacterial spectrum which is broadly similar to that of imipenem but, whilst slightly less active against staphylococci and enterococci, it is more active against Pseudomonas aeruginosa, all Enterobacteriaceae and Haemophilus influenzae. Amongst common human pathogens, only methicillin-resistant staphylococci and Enterococcus faecium are uniformly resistant to meropenem. The meropenem MICs for penicillin-resistant Streptococcus pneumoniae are higher than for penicillin-susceptible strains but the organisms remain susceptible. Clinical susceptibility in vitro to meropenem is defined by MICs of < or = 4 mg/L, intermediate susceptibility by MICs of 8 mg/L and MICs of > or = 16 mg/L define resistance; equivalent figures for zones of growth inhibition are > or = 14 (susceptible), 12-13 (intermediate) and < or = 11 (resistant) mm. Studies in guinea pig models of systemic infection and infections localised to the lungs, urinary tract and the central nervous system, some of which used immunocompromised animals, confirm the potential of meropenem demonstrated in vitro. These factors, combined with the human plasma, tissue or urinary concentrations of meropenem which exceed modal MICs for the pathogens isolated in clinical trials for most or all of the recommended 8 h dosing interval, predict that meropenem should be efficacious in the treatment of infections at many body sites.
Insights
Meropenem exhibits broad-spectrum bactericidal activity against most bacteria, including Pseudomonas aeruginosa and Enterobacteriaceae. Its efficacy is supported by in vitro data and animal studies, predicting successful treatment for various infections.
Area of Science:
- Pharmacology and Microbiology
- Antibiotic Resistance
- Infectious Diseases
Background:
- Meropenem is a carbapenem antibiotic with broad-spectrum bactericidal activity.
- Its effectiveness stems from bacterial cell entry and affinity for penicillin-binding proteins.
- Meropenem is stable against serine-based beta-lactamases, enhancing its spectrum of activity.
Purpose of the Study:
- To evaluate the in vitro and in vivo activity of meropenem.
- To compare meropenem's spectrum with imipenem.
- To assess meropenem's potential for treating various infections.
Main Methods:
- In vitro susceptibility testing against clinical pathogens.
- Comparison of meropenem and imipenem activity.
- Evaluation in guinea pig models of systemic and localized infections.
Main Results:
- Meropenem shows excellent activity against most aerobes and anaerobes.
- It is more active than imipenem against Pseudomonas aeruginosa, Enterobacteriaceae, and Haemophilus influenzae.
- Clinical susceptibility is defined by MICs ≤ 4 mg/L and growth inhibition zones ≥ 14 mm.
Conclusions:
- Meropenem demonstrates broad-spectrum activity and stability against beta-lactamases.
- In vitro and animal studies predict meropenem's efficacy in treating diverse infections.
- Achieved therapeutic concentrations support meropenem's use across multiple body sites.