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In vitro activity of TNP-2092 against periprosthetic joint infection-associated staphylococci
Cody R Fisher1, Suzannah M Schmidt-Malan1, Zhenkun Ma2
1Division of Clinical Microbiology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN.
Abstract:
Staphylococci are the most common causes of periprosthetic joint infection (PJI). TNP-2092 is an investigational hybrid drug composed of rifamycin and quinolizinone pharmacophores conjugated via a covalent linker. We determined minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), and minimum biofilm bactericidal concentration (MBBC) values of TNP-2092 against 80 PJI-associated Staphylococcus aureus and Staphylococcus epidermidis isolates compared to ciprofloxacin and rifampin alone and in combination, alongside daptomycin and vancomycin. TNP-2092 exhibited the following activity against S. aureus: MIC50/MIC90, ≤0.0075/0.015 μg/mL; MBC50/MBC90, 0.5/4 μg/mL; and MBBC50/MBBC90, 0.5/2 μg/mL, and the following activity against S. epidermidis: MIC50/MIC90, ≤0.0075/0.015 μg/mL; MBC50/MBC90, 0.015/0.125 μg/mL; and MBBC50/MBBC90, 0.06/0.25 μg/mL. TNP-2092 MIC, MBC, and MBBC values were >8 μg/mL for 1 isolate, while MIC values were ≤0.25 μg/mL and MBC and MBBC values were ≤4 μg/mL for all other isolates. Results of this study show that TNP-2092 has promising in vitro activity against PJI-associated staphylococci.
Insights
TNP-2092, a novel hybrid drug, shows potent in vitro activity against Staphylococci, the primary cause of periprosthetic joint infection (PJI). This investigational compound demonstrates significant efficacy in inhibiting and killing both planktonic and biofilm-forming bacteria.
Area of Science:
- Microbiology
- Infectious Diseases
- Pharmacology
Background:
- Staphylococci are the predominant pathogens responsible for periprosthetic joint infections (PJIs).
- Effective antimicrobial agents are crucial for managing PJIs, particularly against resistant strains.
Purpose of the Study:
- To evaluate the in vitro antimicrobial activity of TNP-2092 against PJI-associated Staphylococcus isolates.
- To compare the efficacy of TNP-2092 with existing antibiotics like ciprofloxacin, rifampin, daptomycin, and vancomycin.
Main Methods:
- Minimum Inhibitory Concentration (MIC), Minimum Bactericidal Concentration (MBC), and Minimum Biofilm Bactericidal Concentration (MBBC) assays were performed.
- Testing was conducted on 80 clinical isolates of Staphylococcus aureus and Staphylococcus epidermidis recovered from PJI cases.
- TNP-2092's activity was assessed against planktonic cells and bacterial biofilms.
Main Results:
- TNP-2092 demonstrated very low MIC, MBC, and MBBC values against both Staphylococcus aureus and Staphylococcus epidermidis.
- For S. aureus, MIC50/MIC90 were ≤0.0075/0.015 μg/mL, MBC50/MBC90 were 0.5/4 μg/mL, and MBBC50/MBBC90 were 0.5/2 μg/mL.
- For S. epidermidis, MIC50/MIC90 were ≤0.0075/0.015 μg/mL, MBC50/MBC90 were 0.015/0.125 μg/mL, and MBBC50/MBBC90 were 0.06/0.25 μg/mL.
Conclusions:
- TNP-2092 exhibits potent in vitro bactericidal and biofilm-inhibiting activity against PJI-associated staphylococci.
- The investigational hybrid drug shows promising potential as a therapeutic agent for staphylococcal PJIs.
- Further clinical investigation is warranted to establish TNP-2092's efficacy and safety in treating PJIs.
