Related Experiment Video
Updated: Mar 9, 2026
Quadruple-Checkerboard: A Modification of the Three-Dimensional Checkerboard for Studying Drug Combinations
Published on: July 24, 2021
A novel combination approach of human polyclonal IVIG and antibiotics against multidrug-resistant Gram-positive
Mariam Madkour Sallam1, Khaled Abou-Aisha1, Mohamed El-Azizi1
1Department of Microbiology, Immunology, and Biotechnology, Faculty of Pharmacy and Biotechnology, German University in Cairo, New Cairo City, Cairo, Egypt.
Background:
Gram-positive bacteria, especially methicillin-resistant Staphylococcus aureus (MRSA) and enterococci, have shown a remarkable ability to develop resistance to antimicrobial agents.
Objective:
We aimed to assess possible enhancement of the antimicrobial activity of vancomycin, amoxicillin, clarithromycin, and azithromycin by human polyclonal intravenous immunoglobulin G (IVIG) against 34 multidrug-resistant (MDR) bacterial isolates, including MRSA, Enterococcus faecium, and Enterococcus faecalis.
Materials And Methods:
Double combinations of the antibiotics with the IVIG were assessed by checkerboard assay, where the interaction was evaluated with respect to the minimum inhibitory concentration (MIC) of the antibiotics. The results of the checkerboard assay were verified in vitro using time-kill assay and in vivo using an invasive sepsis murine model.
Results:
The checkerboard assay showed that IVIG enhanced the antimicrobial activity of amoxicillin and clarithromycin against isolates from the three groups of bacteria, which were resistant to the same antibiotics when tested in the absence of IVIG. The efficacy of vancomycin against 15% of the tested isolates was enhanced when it was combined with the antibodies. Antagonism was demonstrated in 47% of the E. faecalis isolates when clarithromycin was combined with the IVIG. Synergism was proved in the time-kill assay when amoxicillin was combined with the antibodies; meanwhile, antagonism was not demonstrated in all tested combinations, even in combinations that showed such response in checkerboard assay.
Conclusion:
The suggested approach is promising and could be helpful to enhance the antimicrobial activity of not only effective antibiotics but also antibiotics that have been proven to be ineffective against MDR bacteria. To our knowledge, this combinatorial approach against MDR bacteria, such as MRSA and enterococci, has not been investigated before.
Insights
Human intravenous immunoglobulin G (IVIG) can boost the effectiveness of certain antibiotics against multidrug-resistant bacteria like MRSA. This combination therapy shows promise for combating resistant infections.
Area of Science:
- Microbiology and Infectious Diseases
- Immunology
- Pharmacology
Background:
- Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA) and enterococci, exhibit significant resistance to existing antimicrobial agents.
- The rise of multidrug-resistant (MDR) bacteria poses a critical global health challenge, necessitating novel therapeutic strategies.
Purpose of the Study:
- To evaluate the potential of human polyclonal intravenous immunoglobulin G (IVIG) to enhance the antimicrobial activity of vancomycin, amoxicillin, clarithromycin, and azithromycin.
- To assess this enhancement against a panel of 34 multidrug-resistant bacterial isolates, specifically MRSA, Enterococcus faecium, and Enterococcus faecalis.
Main Methods:
- Checkerboard assay was employed to determine the minimum inhibitory concentrations (MICs) of antibiotic-IVIG combinations.
- In vitro time-kill assays and in vivo invasive sepsis murine models were utilized to validate checkerboard assay findings.
Main Results:
- IVIG significantly enhanced the antimicrobial activity of amoxicillin and clarithromycin against resistant bacterial isolates.
- Vancomycin efficacy was improved in 15% of isolates when combined with IVIG; however, antagonism was observed in 47% of E. faecalis isolates with clarithromycin-IVIG.
- Synergistic effects were confirmed via time-kill assays for amoxicillin-IVIG, with antagonism not consistently observed across all combinations.
Conclusions:
- The combinatorial approach of using IVIG with antibiotics demonstrates potential for enhancing antimicrobial activity, even against previously ineffective drugs.
- This strategy offers a promising avenue for combating multidrug-resistant bacteria, including MRSA and enterococci.
- This represents a novel investigation into combinatorial therapy against MDR bacteria.
More Related Videos
12:03Antimicrobial Synergy Testing by the Inkjet Printer-assisted Automated Checkerboard Array and the Manual Time-kill Method
Published on: April 18, 2019
11:17Multiplex Therapeutic Drug Monitoring by Isotope-dilution HPLC-MS/MS of Antibiotics in Critical Illnesses
Published on: August 30, 2018
Related Concept Videos
01:27Combined Effects of Drugs: Synergism
Such synergistic combinations...
01:28Acute Pyelonephritis II: Diagnostic Studies and Management
00:57Antibiotic Selection
01:16Treating Helicobacter pylori in Peptic Ulcers: Antimicrobial Therapy
01:30Development of Antibiotic Resistance
01:24Drugs for Treatment of Crohn's Disease in IBD Using Biologic Agents: Anti-TNF