EFFECT OF ANTIBIOTICS ON THE GROWTH OF GRAM-NEGATIVE BACTERIA IN CONTINUOUS FLOW CULTURE
I: STUDIES ON SINGLE CULTURE OF ESCHERICHIA COLI AND PSEUDOMONAS AERUGINOSA
1982 Volume 30 Issue 5 Pages 499-508
Details
1982 Volume 30 Issue 5 Pages 499-508
A continuous flow culture has been developed as in vitro model of bacterial growth and drug concentrations in the body. On the other hand, the antibiotic sensitivity of bacteria has been tested by static culture using liquid and solid media. This study was designed to analyze the antimicrobial activities of several antibiotics (ampicillin, nalidixic acid, cefsulodin and gentamicin) on gram-nagative bacteria such as Escherichia coli and Pseudomonas aeruginosa, cultured by the continuous flow system.
When a portion of medium containing 16 times the MIC of the test antibiotic was introduced to the culture vessel containing steady state bacterial cells (2×107/ml), a marked decrease in the bacterial cells in the culture vessel was observed. Escherichia coli was completely eradicated or reduced to 102 to 103 per ml by 64 times MIC of gentamicin or other drugs such as nalidixic acid, ampicillin and cefsulodin. The effect of the antibiotics in eliminating Pseudomonas aeruginosa was not as significant as with Escherichia coli when the same antibiotic concentration was added to the reservoir medium or introduced directly to the vessel.
We also determined the time required to attain the steady state of cell growth after drastic reduction of the cell density by introduction of antibiotics to the vessel as a one-compartment model of drug absorption and excretion.
Our results suggest that the inhibitory effects of antibiotics on the growth of steady state gramnegative bacteria are quite different from the effects determined by the conventional static culture. Since the dilution rate of the drug is not proportional to the dilution rate of the cells in the culture vessel, the results obtained from such experiments should be interpreted carefully. However, the information obtained might provide a basis for making a time schedule for drug administrations to patients. Thus, we believe that use of a continuous flow culture system to study the effect of antimicrobial agents in the dynamic state is meaningful and provides important information concerning the chemotherapy of bacterial infections.
