Related Experiment Videos
[In vitro synergistic effects of tazobactam/piperacillin with various antibiotics]
K Nishida1, K Niidome, M Hashimoto
1Department of Microbiology, Kyoto Pharmaceutical University.
Abstract:
We investigated in vitro synergistic effects of tazobactam/piperacillin (TAZ/PIPC), a combination drug of tazobactam (TAZ) and piperacillin (PIPC) in the ratio of 1:4, with several other antibiotics against Pseudomonas aeruginosa, Serratia marcescens and methicillin-resistant Staphylococcus aureus (MRSA). Synergistic effects of TAZ/PIPC with each of tobramycin (TOB), netilmicin (NTL), fosfomycin (FOM), ciprofloxacin, minocycline or cefoperazone were observed against all bacteria tested in the checkerboard dilution method. No antagonistic effect was observed in combination of TAZ/PIPC with other antibiotics. Against P. aeruginosa, a combination of TAZ/PIPC with NTL was the most effective, with an average fractional inhibitory concentration (FIC) index of 0.459. And a combination of TAZ/PIPC with FOM was the most the effective against S. marcescens and MRSA. TAZ/PIPC combined with TOB or FOM showed bactericidal effect against P. aeruginosa No. 11, S. marcescens No. 39 and S. aureus O-62 at concentrations of the drugs that showed only bacteriostatic activity individually. Phase-contrast micrographic observations of P. aeruginosa No. 11 and S. marcescens No. 39 demonstrated that the bacterial cells treated with TAZ/PIPC were in filamentous forms and those treated with TOB or FOM were nearly normal. The combination of TAZ/PIPC with TOB or FOM induced filamentous cells with spheroplast-like structures and lysis. Those results suggest that the combination of TAZ/PIPC with aminoglycosides or FOM were useful in the treatment of infections by P. aeruginosa, S. marcescens and MRSA, especially those caused by beta-lactamase-producing strains.
Insights
The combination of tazobactam/piperacillin with aminoglycosides or fosfomycin shows synergistic effects against Pseudomonas aeruginosa, Serratia marcescens, and MRSA. These combinations demonstrate enhanced bactericidal activity, offering potential for treating resistant bacterial infections.
Area of Science:
- Microbiology
- Pharmacology
- Infectious Diseases
Background:
- Antibiotic resistance is a growing global health threat.
- Beta-lactamase-producing bacteria, including MRSA, pose significant treatment challenges.
- Combination antibiotic therapy is explored to overcome resistance mechanisms.
Purpose of the Study:
- To investigate the in vitro synergistic effects of tazobactam/piperacillin (TAZ/PIPC) in combination with other antibiotics.
- To evaluate the efficacy of these combinations against key resistant pathogens: Pseudomonas aeruginosa, Serratia marcescens, and methicillin-resistant Staphylococcus aureus (MRSA).
- To determine the morphological changes induced by effective drug combinations.
Main Methods:
- Checkerboard dilution method was employed to assess synergistic effects.
- Fractional Inhibitory Concentration (FIC) index was calculated to quantify synergy.
- Phase-contrast microscopy was used to observe bacterial cell morphology.
Main Results:
- Synergistic effects were observed for TAZ/PIPC combined with tobramycin, netilmicin, fosfomycin, ciprofloxacin, minocycline, or cefoperazone against all tested bacteria.
- The most effective combinations were TAZ/PIPC with netilmicin against P. aeruginosa (FIC index 0.459) and TAZ/PIPC with fosfomycin against S. marcescens and MRSA.
- Bactericidal effects were noted for TAZ/PIPC with tobramycin or fosfomycin against specific strains, inducing filamentous cells, spheroplasts, and lysis.
Conclusions:
- Combination of TAZ/PIPC with aminoglycosides (tobramycin, netilmicin) or fosfomycin exhibits significant in vitro synergy against P. aeruginosa, S. marcescens, and MRSA.
- These combinations demonstrate enhanced bactericidal activity compared to individual agents.
- The findings suggest potential utility in treating infections caused by beta-lactamase-producing strains of these pathogens.