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[The combined effects of aspoxicillin with aminoglycoside antibiotics on Pseudomonas aeruginosa]
T Matsushita1, O Kasuga, T Yamaguchi
1Biological Research Laboratory, Tanabe Seiyaku Co., Ltd.
Abstract:
Combined actions of aspoxicillin (ASPC) with several aminoglycosides (AGs) against various Pseudomonas aeruginosa strains were examined using the checker board method and experimental infection of mice, and the actions were compared with those of piperacillin (PIPC) and mezlocillin (MZPC). 1. The combination of ASPC with gentamicin, amikacin (AMK) or tobramycin showed synergistic activities against 81.9-95.5% of the test strains. These frequencies were higher than those of reference penicillins (PCs). Mean values of FIC index for combinations between ASPC and AGs were smaller than 0.5, thus, the combinations showed the strongest synergism among the PCs tested. 2. ASPC combined with AGs showed synergistic actions on experimental mouse infections caused by strains of P. aeruginosa. The potency of ASPC was the same as that of PIPC, but MZPC had a weaker activity than ASPC or PIPC. 3. Schedule of administration of ASPC and AMK was examined using experimental infection in mice caused by P. aeruginosa. When AMK was administered first, a synergism was clearly observed when ASPC was administered within 1 hour of the AMK administration. When ASPC was administered first, a synergism was observed when AMK was administered within 4 hours of the ASPC administration. 4. Influences of AMK and ASPC or reference PCs on growth of P. aeruginosa 22 were examined at lower concentrations than MIC. AMK showed a bacteriostatic action on the test strain at 1/4 MIC. But no influence was observed at lower concentrations than 1/4 MIC of AMK. ASPC and reference PCs showed slight effects on growth of the test strain at concentrations of 1/32 MIC of PIPC, 1/128 MIC of MZPC and 1/256 MIC of ASPC. The PCs showed bactericidal action against the test strain at these concentrations when combined with 1/4 MIC of AMK.
Insights
The combination of aspoxicillin (ASPC) with aminoglycosides (AGs) demonstrates strong synergistic activity against Pseudomonas aeruginosa strains, outperforming other penicillins in both in vitro and in vivo models.
Area of Science:
- Microbiology
- Pharmacology
- Infectious Diseases
Background:
- Pseudomonas aeruginosa is a significant opportunistic pathogen.
- The development of effective antimicrobial strategies against P. aeruginosa is crucial.
Purpose of the Study:
- To evaluate the synergistic activity of aspoxicillin (ASPC) in combination with aminoglycosides (AGs) against Pseudomonas aeruginosa.
- To compare the efficacy of ASPC-AG combinations with reference penicillins (piperacillin and mezlocillin).
Main Methods:
- Checkerboard method for in vitro synergy testing.
- Murine models of experimental infection to assess in vivo efficacy.
- Evaluation of drug administration timing and sub-inhibitory concentration effects.
Main Results:
- ASPC combined with gentamicin, amikacin (AMK), or tobramycin exhibited synergistic activity against 81.9-95.5% of P. aeruginosa strains.
- These combinations showed stronger synergism (FIC index < 0.5) than reference penicillins.
- Synergistic effects were confirmed in experimental mouse infections, with ASPC demonstrating potency comparable to piperacillin.
- Optimal synergistic activity was observed when AMK was administered within 1 hour of ASPC, or within 4 hours when ASPC was administered first.
Conclusions:
- ASPC in combination with AGs represents a highly synergistic therapeutic option against P. aeruginosa.
- The timing of administration for ASPC and AMK significantly influences their combined efficacy.
- ASPC-AG combinations show promise for treating P. aeruginosa infections, potentially offering advantages over existing penicillin therapies.