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Aztreonam vs. gentamicin in experimental peritonitis and intra-abdominal abscess formation
R G Sawyer1, R B Adams, T L Pruett
1Department of Surgery, University of Virginia Surgical Infectious Disease Laboratory, Charlottesville.
Abstract:
The activity of gentamicin is known to be decreased in acidic environments, and both the peritoneum during peritonitis and the interior of abscesses have been shown to be acidic and hypoxic. The activity of beta-lactam antibiotics is felt to be relatively less diminished under the same circumstances. We determined that the minimum inhibitory concentration of gentamicin against one pathogenic strain of Escherichia coli increased eight-fold, to 8 mugm/mL, when testing conditions were changed from normoxic and neutral to hypoxic and acidic, whereas the MIC of aztreonam doubled under the same conditions, to 0.25 mugm/mL. In further experiments in a murine model of mixed Escherichia coli/Bacteroides fragilis intra-abdominal abscesses, we demonstrated that a combination of aztreonam and clindamycin was superior to a combination of gentamicin and clindamycin in terms of completely preventing abscess formation (33% vs. 0%) and eliminating Escherichia coli from abscesses that did form (100% vs. 61%).
Insights
Gentamicin
Area of Science:
- Microbiology
- Pharmacology
- Infectious Diseases
Background:
- Acidic and hypoxic environments, common in infections like peritonitis and abscesses, reduce gentamicin activity.
- Beta-lactam antibiotics show less susceptibility to these environmental conditions.
- Understanding antibiotic efficacy in challenging infection sites is crucial for treatment selection.
Purpose of the Study:
- To compare the activity of gentamicin and aztreonam under simulated acidic and hypoxic infection conditions.
- To evaluate the in vivo efficacy of antibiotic combinations in a murine model of intra-abdominal abscesses.
Main Methods:
- Determined minimum inhibitory concentrations (MICs) of gentamicin and aztreonam against Escherichia coli under normoxic/neutral and hypoxic/acidic conditions.
- Utilized a murine model of mixed Escherichia coli/Bacteroides fragilis intra-abdominal abscesses.
- Administered combinations of aztreonam/clindamycin and gentamicin/clindamycin to assess abscess prevention and bacterial eradication.
Main Results:
- Gentamicin's MIC increased eight-fold to 8 µg/mL in hypoxic, acidic conditions, while aztreonam's MIC doubled to 0.25 µg/mL.
- The aztreonam/clindamycin combination completely prevented abscess formation in 33% of mice, compared to 0% for gentamicin/clindamycin.
- Escherichia coli eradication was significantly higher with aztreonam/clindamycin (100%) versus gentamicin/clindamycin (61%).
Conclusions:
- Aztreonam maintains better activity than gentamicin in simulated abscess environments.
- The combination of aztreonam and clindamycin demonstrates superior efficacy in preventing and treating intra-abdominal abscesses compared to gentamicin and clindamycin.
- These findings suggest aztreonam-based regimens may be more effective for infections with acidic and hypoxic characteristics.