INTRODUCTION: It is hypothesized that systemically administered antibiotics penetrate wound sites more effectively during negative pressure wound therapy (NPWT). However, there is a lack of clinical data from patients who receive NPWT for deep sternal wound infection (DSWI) after open-heart surgery. Here, we evaluated vancomycin penetration into exudate in this patient group. PATIENTS AND METHODS: For this prospective observational study, we enrolled 10 consecutive patients treated with NPWT for post-sternotomy DSWI. On the first sampling day, serum and exudate samples were synchronously collected at 0 (pre-dose), 0.5, 1, 2, 3 and 6 h after vancomycin administration. On the following three consecutive days, additional samples were collected, only before vancomycin administration. RESULTS: The ratio of average vancomycin concentration in wound exudate to in serum was higher for free (unbound) (1.51 ± 0.53) than for total (bound + unbound) (0.91 ± 0.29) concentration (p = 0.049). The percentage of free vancomycin was higher in wound exudate than serum (0.79 ± 0.19 vs. 0.46 ± 0.16; p = 0.04). Good vancomycin wound penetration was maintained on the following three days (vancomycin trough exudate-to-serum concentration ratio > 1). The total hospital stay was significantly longer in patients with DSWI (46 ± 11.6 days) versus without DSWI (14 ± 11.7 days) (p < 0.001). There was no in-hospital or 90-day mortality. Two patients experienced late DSWI recurrence. All-cause mortality was 4.8% during a median follow-up of 2.5 years. CONCLUSION: Vancomycin effectively penetrates wound exudate in patients receiving NPWT for DSWI after open-heart surgery.The protocol for this study was registered at ClinicalTrials.gov on July 16, 2024 (NCT06506032).

Vancomycin effectively penetrates into wound exudate in patients receiving NPWT to treat post-sternotomy DSWI after open-heart surgery.NPWT promotes the penetration of vancomycin into the infection site.

Department of Cardiac Surgery University Hospital Ostrava Ostrava Czech Republic

Department of Clinic Subjects Faculty of Medicine University of Ostrava Ostrava Czech Republic

Department of Clinical Pharmacology Faculty of Medicine University of Ostrava Ostrava Czech Republic

Department of Clinical Pharmacology Institute of Laboratory Medicine University Hospital Ostrava Ostrava Czech Republic

Department of Environmental Engineering Faculty of Mining and Geology VŠB Technical University of Ostrava Ostrava Czech Republic

Department of Pharmacology Faculty of Medicine Masaryk University Brno Czech Republic

Hospital Pharmacy Masaryk Memorial Cancer Institute Brno Czech Republic

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Perezgrovas-Olaria R, Audisio K, Cancelli G, et al. . Deep sternal wound infection and mortality in cardiac surgery: a meta-analysis. Ann Thorac Surg. 2023;115(1):272–280. doi: 10.1016/j.athoracsur.2022.04.054. PubMed DOI

Floros P, Sawhney R, Vrtik M, et al. . Risk factors and management approach for deep sternal wound infection after cardiac surgery at a tertiary medical centre. Heart Lung Circ. 2011;20(11):712–717. doi: 10.1016/j.hlc.2011.08.001. PubMed DOI

Baillot R, Cloutier D, Montalin L, et al. . Impact of deep sternal wound infection management with vacuum-assisted closure therapy followed by sternal osteosynthesis: a 15-year review of 23 499 sternotomies. Eur J Cardiothorac Surg. 2010;37(4):880–887. doi: 10.1016/j.ejcts.2009.09.023. PubMed DOI

Sears ED, Wu L, Waljee JF, et al. . The impact of deep sternal wound infection on mortality and resource utilization: a population-based study. World J Surg. 2016;40(11):2673–2680. doi: 10.1007/s00268-016-3598-7. PubMed DOI

Filsoufi F, Castillo JG, Rahmanian PB, et al. . Epidemiology of deep sternal wound infection in cardiac surgery. J Cardiothorac Vasc Anesth. 2009;23(4):488–494. doi: 10.1053/j.jvca.2009.02.007. PubMed DOI

Omran AS, Karimi A, Ahmadi SH, et al. . Superficial and deep sternal wound infection after more than 9000 coronary artery bypass graft (CABG): incidence, risk factors and mortality. BMC Infect Dis. 2007;7(1):112. doi: 10.1186/1471-2334-7-112. PubMed DOI PMC

Juhl AA, Hody S, Videbaek TS, et al. . Deep sternal wound infection after open-heart surgery: a 13-year single institution analysis. Ann Thorac Cardiovasc Surg. 2017;23(2):76–82. doi: 10.5761/atcs.oa.16-00196. PubMed DOI PMC

Kubota H, Miyata H, Motomura N, et al. . Deep sternal wound infection after cardiac surgery. J Cardiothorac Surg. 2013;8(1):132. doi: 10.1186/1749-8090-8-132. PubMed DOI PMC

Lu JCY, Grayson AD, Jha P, et al. . Risk factors for sternal wound infection and mid-term survival following coronary artery bypass surgery. Eur J Cardiothorac Surg. 2003;23(6):943–949. doi: 10.1016/S1010-7940(03)00137-4. PubMed DOI

Gårdlund B, Bitkover CY, Vaage J.. Postoperative mediastinitis in cardiac surgery - microbiology and pathogenesis. Eur J Cardiothorac Surg. 2002;21(5):825–830. doi: 10.1016/s1010-7940(02)00084-2. PubMed DOI

Sharma M, Berriel-Cass D, Baran J.. Sternal surgical-site infection following coronary artery bypass graft: prevalence, microbiology, and complications during a 42-month period. Infect Control Hosp Epidemiol. 2004;25(6):468–471. doi: 10.1086/502423. PubMed DOI

Polykandriotis E, Horch RE, Jost M, et al. . Can systemically administered antibiotics be detected in wound tissues and surfaces under negative pressure wound therapy? Int Wound J. 2019;16(2):503–510. doi: 10.1111/iwj.13063. PubMed DOI PMC

Müller M, Dela Peña A, Derendorf H.. Issues in pharmacokinetics and pharmacodynamics of anti-infective agents: distribution in tissue. Antimicrob Agents Chemother. 2004;48(5):1441–1453. doi: 10.1128/AAC.48.5.1441-1453.2004. PubMed DOI PMC

Ida Y, Matsumura H, Onishi M, et al. . Measurement of vancomycin hydrochloride concentration in the exudate from wounds receiving negative pressure wound therapy: a pilot study. Int Wound J. 2016;13(2):204–208. doi: 10.1111/iwj.12260. PubMed DOI PMC

Rowan MP, Niece KL, Rizzo JA, et al. . Wound penetration of cefazolin, ciprofloxacin, piperacillin, tazobactam, and vancomycin during negative pressure wound therapy. Adv Wound Care (New Rochelle). 2017;6(2):55–62. doi: 10.1089/wound.2016.0698. PubMed DOI PMC

Horan TC, Andrus M, Dudeck MA.. CDC/NHSN surveillance definition of health care-associated infection and criteria for specific types of infections in the acute care setting. Am J Infect Control. 2008;36(5):309–332. doi: 10.1016/J.AJIC.2008.03.002. PubMed DOI

Rybak M, Lomaestro B, Rotschafer JC, et al. . Therapeutic monitoring of vancomycin in adult patients: a consensus review of the American Society of Health-System Pharmacists, the Infectious Diseases Society of America, and the Society of Infectious Diseases Pharmacists. Am J Health Syst Pharm. 2009;66(1):82–98. doi: 10.2146/AJHP080434. PubMed DOI

Brozmanová H, Kacířová I, Uřinovská R, et al. . New liquid chromatography-tandem mass spectrometry method for routine TDM of vancomycin in patients with both normal and impaired renal functions and comparison with results of polarization fluoroimmunoassay in light of varying creatinine concentrations. Clin Chim Acta. 2017;469:136–143. doi: 10.1016/J.CCA.2017.04.003. PubMed DOI

Brozmanová H, Šištík P, Ďuricová J, et al. . Liquid chromatography-tandem mass spectrometry methods for quantification of total and free antibiotic concentrations in serum and exudate from patients with post-sternotomy deep sternal wound infection receiving negative pressure wound therapy. Clin Chim Acta. 2024;554:117704. doi: 10.1016/J.CCA.2023.117704. PubMed DOI

R Core Team . R: A Language and Environment for Statistical Computing. Vienna, Austria: R Foundation for Statistical Computing; 2024. https://www.R-project.org.

Tegnell A, Arén C, Ohman L.. Coagulase-negative staphylococci and sternal infections after cardiac operation. Ann Thorac Surg. 2000;69(4):1104–1109. doi: 10.1016/S0003-4975(99)01563-5. PubMed DOI

Horan TC, Gaynes RP, Martone WJ, et al. . CDC definitions of nosocomial surgical site infections, 1992: A modification of CDC definitions of surgical wound infections. Am J Infect Control. 1992;20(5):271–274. doi: 10.1016/S0196-6553(05)80201-9. PubMed DOI

Graf K, Ott E, Vonberg RP, et al. . Economic aspects of deep sternal wound infections. Eur J Cardiothorac Surg. 2010;37(4):893–896. doi: 10.1016/j.ejcts.2009.10.005. PubMed DOI

Sjögren J, Gustafsson R, Nilsson J, et al. . Clinical outcome after poststernotomy mediastinitis: vacuum-assisted closure versus conventional treatment. Ann Thorac Surg. 2005;79(6):2049–2055. doi: 10.1016/J.ATHORACSUR.2004.12.048. PubMed DOI

Morykwas MJ, Argenta LC, Shelton-Brown EI, et al. . Vacuum-assisted closure: a new method for wound control and treatment: animal studies and basic foundation. Ann Plast Surg. 1997;38(6):553–562. doi: 10.1097/00000637-199706000-00001. PubMed DOI

Skhirtladze K, Hutschala D, Fleck T, et al. . Impaired target site penetration of vancomycin in diabetic patients following cardiac surgery. Antimicrob Agents Chemother. 2006;50(4):1372–1375. doi: 10.1128/AAC.50.4.1372-1375.2006. PubMed DOI PMC

Sun H, Maderazo EG, Krusell AR.. Serum protein-binding characteristics of vancomycin. Antimicrob Agents Chemother. 1993;37(5):1132–1136. doi: 10.1128/AAC.37.5.1132. PubMed DOI PMC

Cutting KF. Wound exudate: composition and functions. Br J Community Nurs. 2003;8(9 Suppl):suppl 4–suppl 9. doi: 10.12968/bjcn.2003.8.Sup3.11577. PubMed DOI

Reuter SE, Stocker SL, Alffenaar JWC, et al. . Optimal practice for vancomycin therapeutic drug monitoring: position statement from the anti-infectives committee of the international association of therapeutic drug monitoring and clinical toxicology. Ther Drug Monit. 2022;44(1):121–132. doi: 10.1097/FTD.0000000000000944. PubMed DOI

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