Antimicrobial activity and pathogen mutation prevention of originator and generics of cefepime, linezolid and piperacillin/tazobactam against clinical isolates of Staphylococcus aureus
ABSTRACT: Objectives: Although generic medicinal products are required to have the same qualitative and quantitative composition of the active substance as their reference originator product, patients and health care professionals express concerns about their interchangeability and safety. Therefor...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-09-01
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| Series: | Journal of Global Antimicrobial Resistance |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2213716523001121 |
| _version_ | 1797689492490944512 |
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| author | Felix Bergmann Alina Nussbaumer-Pröll Beatrix Wulkersdorfer Sabine Eberl Werner Ruppitsch Sarah Lepuschitz Markus Zeitlinger |
| author_facet | Felix Bergmann Alina Nussbaumer-Pröll Beatrix Wulkersdorfer Sabine Eberl Werner Ruppitsch Sarah Lepuschitz Markus Zeitlinger |
| author_sort | Felix Bergmann |
| collection | DOAJ |
| description | ABSTRACT: Objectives: Although generic medicinal products are required to have the same qualitative and quantitative composition of the active substance as their reference originator product, patients and health care professionals express concerns about their interchangeability and safety. Therefore, the present study investigated the antimicrobial activity and pathogen mutation prevention of original and generic cefepime, linezolid and piperacillin/tazobactam against Staphylococcus aureus. Methods: Two generic formulations of cefepime, linezolid and piperacillin/tazobactam were tested against their respective originator products. Susceptibility testing was performed with twenty-one clinical isolates of S. aureus and ATCC-29213 using broth microdilution. Time kill curves (TKC) were performed with ATCC-29213 at drug concentrations above and below the respective minimum inhibitory concentrations (MIC). Mutation prevention concentration was determined for each drug formulation against ATCC-29213. All experiments were performed in triplicate. Mutant colonies from mutation prevention concentration (MPC) experiments were genotypically tested by sequence analysis. Results: MIC ratios between contiguous originator and generic drugs were similar for each isolate. No visual differences were observed in TKCs between originator and generic substances. The MPC did not differ between different formulations of the same substance. Although sequence analysis of mutant colonies revealed genomic differences compared with the original ATCC-29213, no differences in mutation frequencies were observed between clinical isolates and ATCC-29213 treated with originator or generic substances. Conclusions: Similar antimicrobial activity and pathogen mutation prevention was observed between contiguous substances. These results support the interchangeability of generic and originator drug formulations with the same active ingredient. |
| first_indexed | 2024-03-12T01:46:20Z |
| format | Article |
| id | doaj.art-54e81e145a4d4c9da0e2697e81b26cc6 |
| institution | Directory Open Access Journal |
| issn | 2213-7165 |
| language | English |
| last_indexed | 2024-03-12T01:46:20Z |
| publishDate | 2023-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Global Antimicrobial Resistance |
| spelling | doaj.art-54e81e145a4d4c9da0e2697e81b26cc62023-09-09T04:55:15ZengElsevierJournal of Global Antimicrobial Resistance2213-71652023-09-0134179185Antimicrobial activity and pathogen mutation prevention of originator and generics of cefepime, linezolid and piperacillin/tazobactam against clinical isolates of Staphylococcus aureusFelix Bergmann0Alina Nussbaumer-Pröll1Beatrix Wulkersdorfer2Sabine Eberl3Werner Ruppitsch4Sarah Lepuschitz5Markus Zeitlinger6Medical University of Vienna, Department of Clinical Pharmacology, Vienna, Austria; Medical University of Vienna, Clinical Division of Plastic and Reconstructive Surgery, Department of Surgery, Vienna, AustriaMedical University of Vienna, Department of Clinical Pharmacology, Vienna, AustriaMedical University of Vienna, Department of Clinical Pharmacology, Vienna, AustriaMedical University of Vienna, Department of Clinical Pharmacology, Vienna, AustriaAGES - Austrian Agency for Health and Food Safety, Institute of Medical Microbiology and Hygiene, Vienna, AustriaAGES - Austrian Agency for Health and Food Safety, Institute of Medical Microbiology and Hygiene, Vienna, AustriaMedical University of Vienna, Department of Clinical Pharmacology, Vienna, Austria; Corresponding author. Mailing Address: Department of Clinical Pharmacology, Währinger Gürtel 18–20, 1090 Vienna, Austria.ABSTRACT: Objectives: Although generic medicinal products are required to have the same qualitative and quantitative composition of the active substance as their reference originator product, patients and health care professionals express concerns about their interchangeability and safety. Therefore, the present study investigated the antimicrobial activity and pathogen mutation prevention of original and generic cefepime, linezolid and piperacillin/tazobactam against Staphylococcus aureus. Methods: Two generic formulations of cefepime, linezolid and piperacillin/tazobactam were tested against their respective originator products. Susceptibility testing was performed with twenty-one clinical isolates of S. aureus and ATCC-29213 using broth microdilution. Time kill curves (TKC) were performed with ATCC-29213 at drug concentrations above and below the respective minimum inhibitory concentrations (MIC). Mutation prevention concentration was determined for each drug formulation against ATCC-29213. All experiments were performed in triplicate. Mutant colonies from mutation prevention concentration (MPC) experiments were genotypically tested by sequence analysis. Results: MIC ratios between contiguous originator and generic drugs were similar for each isolate. No visual differences were observed in TKCs between originator and generic substances. The MPC did not differ between different formulations of the same substance. Although sequence analysis of mutant colonies revealed genomic differences compared with the original ATCC-29213, no differences in mutation frequencies were observed between clinical isolates and ATCC-29213 treated with originator or generic substances. Conclusions: Similar antimicrobial activity and pathogen mutation prevention was observed between contiguous substances. These results support the interchangeability of generic and originator drug formulations with the same active ingredient.http://www.sciencedirect.com/science/article/pii/S2213716523001121AntibioticsMICMPCBioequivalenceS. aureusGenome |
| spellingShingle | Felix Bergmann Alina Nussbaumer-Pröll Beatrix Wulkersdorfer Sabine Eberl Werner Ruppitsch Sarah Lepuschitz Markus Zeitlinger Antimicrobial activity and pathogen mutation prevention of originator and generics of cefepime, linezolid and piperacillin/tazobactam against clinical isolates of Staphylococcus aureus Journal of Global Antimicrobial Resistance Antibiotics MIC MPC Bioequivalence S. aureus Genome |
| title | Antimicrobial activity and pathogen mutation prevention of originator and generics of cefepime, linezolid and piperacillin/tazobactam against clinical isolates of Staphylococcus aureus |
| title_full | Antimicrobial activity and pathogen mutation prevention of originator and generics of cefepime, linezolid and piperacillin/tazobactam against clinical isolates of Staphylococcus aureus |
| title_fullStr | Antimicrobial activity and pathogen mutation prevention of originator and generics of cefepime, linezolid and piperacillin/tazobactam against clinical isolates of Staphylococcus aureus |
| title_full_unstemmed | Antimicrobial activity and pathogen mutation prevention of originator and generics of cefepime, linezolid and piperacillin/tazobactam against clinical isolates of Staphylococcus aureus |
| title_short | Antimicrobial activity and pathogen mutation prevention of originator and generics of cefepime, linezolid and piperacillin/tazobactam against clinical isolates of Staphylococcus aureus |
| title_sort | antimicrobial activity and pathogen mutation prevention of originator and generics of cefepime linezolid and piperacillin tazobactam against clinical isolates of staphylococcus aureus |
| topic | Antibiotics MIC MPC Bioequivalence S. aureus Genome |
| url | http://www.sciencedirect.com/science/article/pii/S2213716523001121 |
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