Related Experiment Video
Updated: Aug 5, 2026

Deferred Growth Inhibition Assay to Quantify the Effect of Bacteria-derived Antimicrobials on Competition
Published on: September 3, 2016
Effects of subminimal inhibitory concentrations of antibiotics in experimental infections
Abstract:
The antibacterial effects of subminimal inhibitory concentrations (sub-MICs) of antibiotics were studied in two animal models. In mice, the oral cephalosporin CGP 9000 was effective in 11 of 20 different gram-negative infections and cephalexin was effective in one of these infections, both at 50% effective doses (ED(50)) that produced peak concentrations of drug in plasms equal to one-half to one-sixteenth the minimal inhibitory concentration (MIC) for the infecting organism. In gram-positive infections, both antibiotics were effective only at concentrations above the MIC. In rabbits, sub-MICs of cephaloridine, ampicillin, and gantamicin were maintained for 6-10 hr by intravenous infusion. At steady-state concentrations equal to one half to one-eighth the MIC, the beta-lactam antibiotics caused elongation and filamentation, and gentamicin caused enlargement, of Proteus mirabilis, Escherichia coli, and Salmonella typhimurium in peritoneal exudate; the number of viable cells of each of these bacteria was temporarily reduced. In infections with E. coli and P. mirabilis, sub-MIC's of beta-lactam antibiotics and of gentamicin prolonged the survival rates for infected animals beyond those for control animals. Rabbits infected with S. typhimurium and treated with ampicillin at a concentration of one-third the MIC Tended to die sooner than did control animals.
Insights
Sub-minimal inhibitory concentrations (sub-MICs) of antibiotics showed varied antibacterial effects. While some antibiotics at sub-MICs aided survival in certain gram-negative infections, others were ineffective or even detrimental.
Area of Science:
- Microbiology
- Pharmacology
- Infectious Diseases
Background:
- Antibiotic efficacy is typically assessed at or above minimal inhibitory concentrations (MICs).
- The impact of sub-MIC antibiotic exposure on bacterial pathogens and host outcomes is less understood.
- Sub-MIC antibiotic effects can include alterations in bacterial morphology and virulence.
Purpose of the Study:
- To investigate the antibacterial effects of sub-MIC antibiotic concentrations in animal models.
- To evaluate the impact of sub-MIC antibiotic treatment on bacterial growth and host survival.
- To compare the efficacy of different antibiotics at sub-MIC levels against various bacterial infections.
Main Methods:
- Two animal models were utilized: mice and rabbits.
- Antibiotics tested included cephalosporins (CGP 9000, cephalexin, cephaloridine), ampicillin, and gentamicin.
- Sub-MICs were administered orally or intravenously, with drug concentrations measured relative to the MIC.
Main Results:
- In mice, oral cephalosporins at sub-MICs were effective against some gram-negative infections but not gram-positive ones.
- In rabbits, sub-MIC beta-lactam antibiotics induced bacterial filamentation, and gentamicin caused enlargement of Proteus mirabilis, Escherichia coli, and Salmonella typhimurium.
- Sub-MIC treatment prolonged survival in E. coli and P. mirabilis infections but shortened survival in S. typhimurium infections.
Conclusions:
- Sub-MIC antibiotic concentrations can exhibit complex and sometimes paradoxical effects on bacterial infections.
- The outcome of sub-MIC antibiotic treatment is dependent on the specific antibiotic, bacterial species, and infection model.
- Further research is needed to fully elucidate the clinical implications of sub-MIC antibiotic exposure.
Related Concept Videos
Pharmacodynamic Models: Overview
Antimicrobial Effectiveness
Microbiota Modulation by Antibiotics
Inhibitors of Bacterial Protein Synthesis
Inhibitors of Bacterial DNA Synthesis
Clinical Significance of Antibiotic Resistance

