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Therapeutic activity of meropenem in experimental infections
J R Edwards1, S Williams, K Nairn
1Antibiotic Development Group, Bioscience I, ICI Pharmaceuticals, Macclesfield, Cheshire, UK.
Abstract:
Meropenem and comparative antibiotics were evaluated in five models of infection. All antibiotics were administered parenterally; imipenem was used in combination with cilastatin but meropenem and other agents were given alone. Generalized infections in mice caused by Staphylococcus aureus, Streptococcus pneumoniae, Escherichia coli, Serratia marcescens, Proteus mirabilis or Pseudomonas aeruginosa all responded to low doses of meropenem or imipenem. Immunocompromised mice infected with Ps. aeruginosa responded to slightly higher doses of meropenem or gentamicin but required four to seven times the dose of other agents. Those given a greater challenge of Ps. aeruginosa were treated most successfully by meropenem. Treatment with meropenem, imipenem or ceftazidime caused significant reductions of E. coli in the urinary bladder and kidneys of mice challenged per urethram. Infection with Ps. (Xanthomonas) maltophilia localized to the subcutaneous neck tissue of guinea pigs was also treated successfully. Lung infections caused by Ps. aeruginosa in guinea pigs were treated effectively by meropenem, imipenem, and ceftazidime at the dose of 10 mg/kg but only meropenem eradicated bacteria from all the tissues examined. These results demonstrate that meropenem has excellent antibacterial activity in vivo in both normal and immunocompromised animals and in some models of infection is superior to imipenem.
Insights
Meropenem demonstrates potent in vivo antibacterial activity against various pathogens in multiple infection models. In several cases, meropenem proved superior to imipenem, especially in immunocompromised models.
Area of Science:
- Infectious Diseases
- Pharmacology
- Microbiology
Background:
- Carbapenem antibiotics are crucial for treating severe bacterial infections.
- Meropenem is a broad-spectrum carbapenem with established efficacy.
- Comparative efficacy studies are essential for guiding clinical antibiotic selection.
Purpose of the Study:
- To evaluate the in vivo efficacy of meropenem against a range of bacterial pathogens.
- To compare meropenem's performance with other antibiotics, including imipenem, in diverse infection models.
- To assess meropenem's effectiveness in both normal and immunocompromised animal models.
Main Methods:
- Utilized five distinct animal models of infection (mice and guinea pigs).
- Administered antibiotics parenterally, including meropenem, imipenem-cilastatin, ceftazidime, and gentamicin.
- Inoculated animals with various Gram-positive and Gram-negative bacteria, including Staphylococcus aureus, Streptococcus pneumoniae, Escherichia coli, Serratia marcescens, Proteus mirabilis, Pseudomonas aeruginosa, and Xanthomonas maltophilia.
Main Results:
- Meropenem and imipenem showed efficacy in generalized infections across multiple bacterial species at low doses.
- Meropenem was highly effective in immunocompromised mice infected with Pseudomonas aeruginosa, often requiring lower doses than other agents.
- Meropenem demonstrated superior eradication of Pseudomonas aeruginosa in guinea pig lung infections compared to imipenem and ceftazidime.
Conclusions:
- Meropenem exhibits excellent in vivo antibacterial activity in normal and immunocompromised animal models.
- Meropenem's efficacy in certain infection models surpasses that of imipenem.
- These findings support meropenem's role as a potent therapeutic option for serious bacterial infections.