Interaction of purulent material with antibiotics used to treat Pseudomonas infections

Area of Science:

• Microbiology
• Pharmacology
• Infectious Diseases

Background:

• Gram-negative bacillemia with abscess formation is associated with poor patient outcomes.
• Understanding antibiotic interactions with purulent material is crucial for effective treatment.

Purpose of the Study:

• To investigate the impact of purulent material on the activity of polymyxin B, colistin sulfate, gentamicin, and carbenicillin.
• To identify factors influencing antibiotic efficacy in the presence of abscesses.

Main Methods:

• Antibiotics (polymyxin B, colistin sulfate, gentamicin, carbenicillin) were incubated with purulent material (pus).
• Antibiotic concentrations and activity were measured before and after incubation.
• Binding studies were conducted using various agents like protamine sulfate and salts.

Main Results:

• Carbenicillin activity was not significantly affected by pus.
• Polymyxin B, colistin sulfate, and gentamicin concentrations were substantially reduced by pus, decreasing from 100 µg/ml to 3-6 µg/ml.
• Purulent sediment bound large amounts of gentamicin (>700 µg/ml) and polymyxin B/colistin sulfate (>1500 µg/ml).
• This binding was rapid, temperature-independent (4°C and 37°C), stable for 24-48 hours, and pH-sensitive.
• Antibiotic activity could be recovered by high salt concentrations or other agents, suggesting binding over inactivation.

Conclusions:

• Purulent material significantly reduces the efficacy of polymyxin B, colistin sulfate, and gentamicin.
• These findings highlight potential challenges in treating gram-negative bacillemia with abscesses using these antibiotics.
• Carbenicillin may be a more reliable option in such clinical scenarios due to its stability in pus.