Dose optimization in surgical prophylaxis: sub-inhibitory dosing of vancomycin increases rates of biofilm formation and the rates of surgical site infection
Abstract Antibiotic stewardship is viewed as having great public health benefit with limited direct benefit to the patient at the time of administration. The objective of our study was to determine if inappropriate administration of antibiotics could create conditions that would increase the rates o...
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| Format: | Article |
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Nature Portfolio
2023-03-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-023-30951-y |
| _version_ | 1797864888397201408 |
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| author | Kimberly M. Brothers Dana M. Parker Masashi Taguchi Dongzhu Ma Jonathan B. Mandell Lance L. Thurlow Venkata C. Byrapogu Kenneth L. Urish |
| author_facet | Kimberly M. Brothers Dana M. Parker Masashi Taguchi Dongzhu Ma Jonathan B. Mandell Lance L. Thurlow Venkata C. Byrapogu Kenneth L. Urish |
| author_sort | Kimberly M. Brothers |
| collection | DOAJ |
| description | Abstract Antibiotic stewardship is viewed as having great public health benefit with limited direct benefit to the patient at the time of administration. The objective of our study was to determine if inappropriate administration of antibiotics could create conditions that would increase the rates of surgical infection. We hypothesized that sub-MIC levels of vancomycin would increase Staphylococcus aureus growth, biofilm formation, and rates of infection. S. aureus MRSA and MSSA strains were used for all experiments. Bacteria were grown planktonically and monitored using spectrophotometry. Quantitative agar culture was used to measure planktonic and biofilm bacterial burden. A mouse abscess model was used to confirm phenotypes in vivo. In the planktonic growth assay, increases in bacterial burden at ¼ MIC vancomycin were observed in USA300 JE2 by 72 h. Similar findings were observed with ½ MIC in Newman and SH1000. For biofilm formation, USA300 JE2 at ¼ and ½ MIC vancomycin increased biofilm formation by approximately 1.3- and 2.3-fold respectively at 72 h as compared to untreated controls. Similar findings were observed with Newman and SH1000 with a 2.4-fold increase in biofilm formation at ½ MIC vancomycin. In a mouse abscess model, there was a 1.2-fold increase with sub-MIC vancomycin at 3 days post infection. Our study showed that Sub-optimal vancomycin dosing promoted S. aureus planktonic growth and biofilm formation, phenotypic measures of bacterial virulence. This phenotype induced by sub-MIC levels of vancomycin was also observed to increase rates of infection and pathogenesis in our mouse model. Risks of exposure to sub-MIC concentrations with vancomycin in surgical procedures are greater as there is decreased bioavailability in tissue in comparison to other antibiotics. This highlights the importance of proper antibiotic selection, stewardship, and dosing for both surgical prophylaxis and treatment of infection. |
| first_indexed | 2024-04-09T23:00:24Z |
| format | Article |
| id | doaj.art-296df98e54804bc5a6a6e56ead6da5b4 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-09T23:00:24Z |
| publishDate | 2023-03-01 |
| publisher | Nature Portfolio |
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| series | Scientific Reports |
| spelling | doaj.art-296df98e54804bc5a6a6e56ead6da5b42023-03-22T11:01:06ZengNature PortfolioScientific Reports2045-23222023-03-011311910.1038/s41598-023-30951-yDose optimization in surgical prophylaxis: sub-inhibitory dosing of vancomycin increases rates of biofilm formation and the rates of surgical site infectionKimberly M. Brothers0Dana M. Parker1Masashi Taguchi2Dongzhu Ma3Jonathan B. Mandell4Lance L. Thurlow5Venkata C. Byrapogu6Kenneth L. Urish7Arthritis and Arthroplasty Design Group, Department of Orthopaedic Surgery, University of PittsburghArthritis and Arthroplasty Design Group, Department of Orthopaedic Surgery, University of PittsburghArthritis and Arthroplasty Design Group, Department of Orthopaedic Surgery, University of PittsburghArthritis and Arthroplasty Design Group, Department of Orthopaedic Surgery, University of PittsburghArthritis and Arthroplasty Design Group, Department of Orthopaedic Surgery, University of PittsburghDepartment of Microbiology and Immunology, University of North CarolinaArthritis and Arthroplasty Design Group, Department of Orthopaedic Surgery, University of PittsburghArthritis and Arthroplasty Design Group, Department of Orthopaedic Surgery, University of PittsburghAbstract Antibiotic stewardship is viewed as having great public health benefit with limited direct benefit to the patient at the time of administration. The objective of our study was to determine if inappropriate administration of antibiotics could create conditions that would increase the rates of surgical infection. We hypothesized that sub-MIC levels of vancomycin would increase Staphylococcus aureus growth, biofilm formation, and rates of infection. S. aureus MRSA and MSSA strains were used for all experiments. Bacteria were grown planktonically and monitored using spectrophotometry. Quantitative agar culture was used to measure planktonic and biofilm bacterial burden. A mouse abscess model was used to confirm phenotypes in vivo. In the planktonic growth assay, increases in bacterial burden at ¼ MIC vancomycin were observed in USA300 JE2 by 72 h. Similar findings were observed with ½ MIC in Newman and SH1000. For biofilm formation, USA300 JE2 at ¼ and ½ MIC vancomycin increased biofilm formation by approximately 1.3- and 2.3-fold respectively at 72 h as compared to untreated controls. Similar findings were observed with Newman and SH1000 with a 2.4-fold increase in biofilm formation at ½ MIC vancomycin. In a mouse abscess model, there was a 1.2-fold increase with sub-MIC vancomycin at 3 days post infection. Our study showed that Sub-optimal vancomycin dosing promoted S. aureus planktonic growth and biofilm formation, phenotypic measures of bacterial virulence. This phenotype induced by sub-MIC levels of vancomycin was also observed to increase rates of infection and pathogenesis in our mouse model. Risks of exposure to sub-MIC concentrations with vancomycin in surgical procedures are greater as there is decreased bioavailability in tissue in comparison to other antibiotics. This highlights the importance of proper antibiotic selection, stewardship, and dosing for both surgical prophylaxis and treatment of infection.https://doi.org/10.1038/s41598-023-30951-y |
| spellingShingle | Kimberly M. Brothers Dana M. Parker Masashi Taguchi Dongzhu Ma Jonathan B. Mandell Lance L. Thurlow Venkata C. Byrapogu Kenneth L. Urish Dose optimization in surgical prophylaxis: sub-inhibitory dosing of vancomycin increases rates of biofilm formation and the rates of surgical site infection Scientific Reports |
| title | Dose optimization in surgical prophylaxis: sub-inhibitory dosing of vancomycin increases rates of biofilm formation and the rates of surgical site infection |
| title_full | Dose optimization in surgical prophylaxis: sub-inhibitory dosing of vancomycin increases rates of biofilm formation and the rates of surgical site infection |
| title_fullStr | Dose optimization in surgical prophylaxis: sub-inhibitory dosing of vancomycin increases rates of biofilm formation and the rates of surgical site infection |
| title_full_unstemmed | Dose optimization in surgical prophylaxis: sub-inhibitory dosing of vancomycin increases rates of biofilm formation and the rates of surgical site infection |
| title_short | Dose optimization in surgical prophylaxis: sub-inhibitory dosing of vancomycin increases rates of biofilm formation and the rates of surgical site infection |
| title_sort | dose optimization in surgical prophylaxis sub inhibitory dosing of vancomycin increases rates of biofilm formation and the rates of surgical site infection |
| url | https://doi.org/10.1038/s41598-023-30951-y |
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