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da Cruz VF, Machinski E, da Silva Oliveira Filho AR, Conde RA, Varone BB, Gobbi RG, Helito CP, Leal DP. Effectiveness of intra-articular vancomycin in preventing prosthetic joint infections in hip and knee arthroplasty: A systematic review and meta-analysis of RCT's. J Orthop 2025; 66:25-33. [PMID: 39872993 PMCID: PMC11763160 DOI: 10.1016/j.jor.2024.12.025] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/09/2024] [Accepted: 12/23/2024] [Indexed: 01/30/2025] Open
Abstract
Introduction This study aimed to evaluate the effectiveness and safety of intra-articular vancomycin powder in reducing prosthetic joint infections (PJIs) in primary hip and knee arthroplasty through a meta-analysis of randomized controlled trials (RCTs). Methods A research in Pubmed, Embase and Cochrane databases was performed to identify randomized clinical trials comparing intra-articular vancomycin use to conventional antibiotic prophylaxis in total hip or knee arthroplasty patients, assessing postoperative infection rates, adverse drug reactions, and venous thrombotic events. Statistical analysis was performed using R (RStudio 2024.04.2), and heterogeneity was assessed with the I2 test. Results A total of 1485 patients from five randomized clinical trials were included, with 737 receiving intra-articular vancomycin. The infection rate was 0.54 % in the intervention group and 1.73 % in the control group (RR 0.37; 95 % CI 0.02-8.95; p = 0.369; I2 = 49 %), showing no statistically significant difference between the groups. Adverse reactions to the glycopeptide were reported in six cases (0.8 %) in the intervention group compared to four cases (0.5 %) in the control group (RR 1.50; 95 % CI 1.50-150; p = 0.001; I2 = 0 %). Regarding thrombotic events, there was one case in 647 patients in the intervention group and three cases in 660 patients in the control group (RR 0.45; 95 % CI 0.03-7.02; p = 0.169; I2 = 0 %). Conclusion Although no significant difference was found, the intervention group showed a trend toward lower infection rates. Additional RCTs with larger sample sizes are required to confirm these findings. Trial registration The prospective registration of the meta-analysis was conducted on PROSPERO in July 2024 with the protocol number 565988.
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Affiliation(s)
| | - Elcio Machinski
- Universidade Estadual de Ponta Grossa (UEPG), Ponta Grossa, Brazil
| | | | - Rodrigo Arruda Conde
- Fundación Barceló - Instituto Universitario de Ciencias de la Salud, Buenos Aires, Argentina
| | - Bruno Butturi Varone
- Instituto de Ortopedia, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, Brazil
| | - Riccardo Gomes Gobbi
- Instituto de Ortopedia, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, Brazil
- HCor, Hospital do Coração, São Paulo, SP, Brazil
| | - Camilo Partezani Helito
- Instituto de Ortopedia, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, Brazil
| | - Daniel Peixoto Leal
- Instituto de Ortopedia, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, Brazil
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Zhu Z, Tung TH, Su Y, Li Y, Luo H. Intrawound vancomycin powder for prevention of surgical site infections in primary joint arthroplasty: an umbrella review of systematic reviews and meta-analyses. Int J Surg 2025; 111:3508-3524. [PMID: 40035719 DOI: 10.1097/js9.0000000000002316] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2024] [Accepted: 02/23/2025] [Indexed: 03/06/2025]
Abstract
OBJECTIVES The aim of this umbrella review is to explore the effect of intrawound vancomycin on the incidence of infection and wound complications in patients undergoing primary joint arthroplasty. METHODS Two authors conducted a systematic search of PubMed, EMBASE, Medline, and the Cochrane Central Register of Controlled Trials from inception to 15 October 2023. All systematic reviews and meta-analyses examining the effect of intrawound vancomycin on the incidence of infection and wound complications in primary joint arthroplasty were included. Two authors independently screened and extracted the data from the studies, evaluated the methodological quality of the included studies using the Assessment of Multiple Systematic Reviews scale, and assessed the publication bias and small-sample effects. RESULTS Our umbrella review includes a total of five systematic reviews, comprising 16 retrospective studies. The pooled results indicate that intrawound vancomycin significantly reduces overall infection rates [odds ratio (OR): 0.41; 95% confidence interval (CI): 0.30-0.54, P < 0.001], superficial infections (OR: 0.51; 95% CI: 0.26-0.97, P = 0.04), and periprosthetic joint infection rates (OR: 0.38; 95% CI: 0.28-0.52, P < 0.001) among patients undergoing primary joint arthroplasty. However, vancomycin did not increase the risk of aseptic wound complications (OR: 1.34; 95% CI: 0.88-2.04, P = 0.17) and prolong wound healing (OR: 1.40; 95% CI: 0.87-2.26, P = 0.17). CONCLUSIONS Based on the available research, our umbrella review demonstrates that intrawound vancomycin significantly reduces infection rates in primary joint arthroplasty, including periprosthetic joint and superficial infections, without increasing wound complications. However, given the inclusion of studies with varying quality, these findings should be interpreted with caution. Further high-quality studies are needed to better confirm its long-term safety, cost-effectiveness, and overall clinical utility.
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Affiliation(s)
- Zhong Zhu
- Department of Orthopedic, Taizhou Hospital of Zhejiang Province affiliated to Wenzhou Medical University, Linhai, Zhejiang, China
| | - Tao-Hsin Tung
- Evidence-based Medicine Center, Taizhou Hospital of Zhejiang Province affiliated to Wenzhou Medical University, Linhai, Zhejiang, China
| | - Yongwei Su
- Department of Orthopedic, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning, China
| | - Yimin Li
- Department of Orthopedic, Taizhou Hospital of Zhejiang Province affiliated to Wenzhou Medical University, Linhai, Zhejiang, China
| | - Hua Luo
- Department of Orthopedic, Taizhou Hospital of Zhejiang Province affiliated to Wenzhou Medical University, Linhai, Zhejiang, China
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Lin CY, Liu CL, Lo HL, Hao SY, Huang WH, Chang HM, Chen TC. Effectiveness of Local Antibiotics for Infection Prevention in Primary Joint Arthroplasty: A Systematic Review and Meta-Analysis. Antibiotics (Basel) 2025; 14:214. [PMID: 40149026 PMCID: PMC11939600 DOI: 10.3390/antibiotics14030214] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2024] [Revised: 01/30/2025] [Accepted: 02/17/2025] [Indexed: 03/29/2025] Open
Abstract
Background/Objectives: To evaluate the effectiveness of local antibiotic prophylaxis (e.g., powder, bone cement, intraosseous injection) in reducing periprosthetic joint infections (PJI) and deep wound infections in adults undergoing primary joint replacement surgery. Methods: A comprehensive search of PubMed, EMBASE, and the Cochrane Library was conducted from inception to 7 September 2024, including randomized controlled trials (RCTs) and cohort studies without language restrictions. Quality assessment was performed using the Cochrane Risk of Bias (RoB) 2.0 for RCTs and the Newcastle-Ottawa Scale (NOS) for cohort studies. Infection rates were extracted and analyzed using risk ratios (RR) or odds ratios (OR) in a random-effects model with Review Manager (RevMan) 5.4. Sensitivity analysis and meta-regression were also performed to validate the study results and possible risk factors. Results: Twelve RCTs and 21 cohort studies were included in the review. Vancomycin powder in the cohort studies demonstrated statistical significance (OR = 0.47, 95% confidence interval (CI): 0.36-0.61, I2 = 0%), in contrast to the results in the RCTs (RR = 0.37, 95% CI: 0.06-2.47, I2 = 49%). Sensitivity analyses confirmed the robustness and statistical significance of these findings. Both the control and treatment groups primarily cultured Gram-positive pathogens, including in the overall data and specifically for vancomycin powder. The evidence for the use of intraosseous injection (RR of RCTs not estimable, I2 not applicable; OR of cohorts = 0.12, 95% CI: 0.02-0.63, I2 = 0%) and bone cement (RR of RCTs = 0.40, 95% CI: 0.14-1.17, I2 = 56%; OR of cohorts = 1.88, 95% CI: 1.25-2.82, I2 not applicable) was inconclusive. Smoking was identified as an important risk factor for post-operative infection. Further research, including more robust trials and cohort studies, is needed to confirm these findings. Conclusions: Local administration of vancomycin powder appears effective in preventing deep wound infection after arthroplasty.
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Affiliation(s)
- Chia-Yu Lin
- Department of Pharmacy, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University, Kaohsiung 80145, Taiwan; (C.-Y.L.); (C.-L.L.); (S.-Y.H.); (W.-H.H.); (H.-M.C.)
- Department of Pharmacy, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807377, Taiwan
| | - Chiung-Li Liu
- Department of Pharmacy, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University, Kaohsiung 80145, Taiwan; (C.-Y.L.); (C.-L.L.); (S.-Y.H.); (W.-H.H.); (H.-M.C.)
| | - Hon-Lok Lo
- Department of Orthopedics, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807377, Taiwan;
| | - Shao-Yuan Hao
- Department of Pharmacy, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University, Kaohsiung 80145, Taiwan; (C.-Y.L.); (C.-L.L.); (S.-Y.H.); (W.-H.H.); (H.-M.C.)
- Department of Pharmacy, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807377, Taiwan
| | - Wei-Hsuan Huang
- Department of Pharmacy, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University, Kaohsiung 80145, Taiwan; (C.-Y.L.); (C.-L.L.); (S.-Y.H.); (W.-H.H.); (H.-M.C.)
- Department of Pharmacy, Kaohsiung Medical University Gangshan Hospital, Kaohsiung Medical University, Kaohsiung 820111, Taiwan
| | - Hsiu-Mei Chang
- Department of Pharmacy, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University, Kaohsiung 80145, Taiwan; (C.-Y.L.); (C.-L.L.); (S.-Y.H.); (W.-H.H.); (H.-M.C.)
- Department of Pharmacy, Kaohsiung Medical University Gangshan Hospital, Kaohsiung Medical University, Kaohsiung 820111, Taiwan
| | - Tun-Chieh Chen
- Division of Infectious Diseases, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807377, Taiwan
- School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807378, Taiwan
- Center for Tropical Medicine and Infectious Disease Research, Kaohsiung Medical University, Kaohsiung 807378, Taiwan
- Center for Medical Education and Humanizing Health Professional Education, Kaohsiung Medical University, Kaohsiung 807378, Taiwan
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Tsai MT, Hu YN, Roan JN, Kan CD, Wang YC, Luo CY, Chou CH. Topical Vancomycin Paste Over the Sternal Edge During Cardiac Surgery: Effects of Renal Function and Body Size on Systemic Exposure. Clin Ther 2025; 47:135-142. [PMID: 39706762 DOI: 10.1016/j.clinthera.2024.11.024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2024] [Revised: 11/25/2024] [Accepted: 11/26/2024] [Indexed: 12/23/2024]
Abstract
PURPOSE Intraoperative topical vancomycin has been widely used in several surgical fields to prevent wound infection. However, there have been limited studies on the systemic exposure of topical vancomycin. The aim of this study was to investigate systemic exposure after topical vancomycin over the sternal edge in cardiac surgical patients. The impact of impaired renal function and body size on the exposure was also examined. METHODS Topical vancomycin (2.5 g) was applied to the sternal edge in 129 adult cardiac surgical patients. Plasma concentrations were measured on postoperative days 0 through 7 and analyzed using linear mixed-effects models. FINDINGS Sixty (46.5%) patients were in chronic kidney disease stages 3 to 5, including 20 patients in end-stage renal disease (ERSD) status with regular hemodialysis preoperatively. A total of 377 plasma vancomycin levels were modeled. It was reported that there was a 7.7% increase in vancomycin level per postoperative day for patients with ESRD in contrast to a decrease of 6.1% each day for patients without ESRD. Every increase of 1 mL/min/1.73 m2 in the estimated glomerular filtration rate is associated with a 0.9% decline in vancomycin concentration. Increasing body surface area (BSA) by 0.1 m2 reduces the vancomycin level by 6.3%. Model simulations using 10,000 replicates reported that the probability of vancomycin level >10 mg/L declines to near 0 within 1 week after surgery in patients without ESRD, even in subjects with low estimated glomerular filtration rate and BSA. For the ESRD group with a BSA <2 m2, the chance of vancomycin >10 mg/L is up to 20% to 30%. IMPLICATIONS Plasma exposure after topical vancomycin for the sternal edge is influenced by renal function and body size. The low probability of significant plasma vancomycin levels supports the typical fixed-dose strategy. For patients with ESRD receiving hemodialysis, accumulation of plasma vancomycin is worth cautioning.
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Affiliation(s)
- Meng-Ta Tsai
- Institute of Clinical Pharmacy and Pharmaceutical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Division of Cardiovascular Surgery, Department of Surgery, National Cheng Kung University Hospital and College of Medicine, Tainan, Taiwan
| | - Yu-Ning Hu
- Division of Cardiovascular Surgery, Department of Surgery, National Cheng Kung University Hospital and College of Medicine, Tainan, Taiwan
| | - Jun-Neng Roan
- Division of Cardiovascular Surgery, Department of Surgery, National Cheng Kung University Hospital and College of Medicine, Tainan, Taiwan
| | - Chung-Dann Kan
- Division of Cardiovascular Surgery, Department of Surgery, National Cheng Kung University Hospital and College of Medicine, Tainan, Taiwan
| | - Yi-Chen Wang
- Division of Cardiovascular Surgery, Department of Surgery, E-Da Hospital/I-Shou University, Kaohsiung, Taiwan
| | - Chwan-Yau Luo
- Division of Cardiovascular Surgery, Department of Surgery, Kaohsiung Medical University Chung-Ho Memorial Hospital, Kaohsiung, Taiwan
| | - Chen-Hsi Chou
- Institute of Clinical Pharmacy and Pharmaceutical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan; School of Pharmacy, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
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Laudet F, Gay A, Dutronc H, Fabre T, Meynard P, Costes S. Does the use of topical vancomycin during primary hip or knee arthroplasty protect from infections? Orthop Traumatol Surg Res 2025; 111:103984. [PMID: 39236995 DOI: 10.1016/j.otsr.2024.103984] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/03/2023] [Revised: 04/27/2024] [Accepted: 06/27/2024] [Indexed: 09/07/2024]
Abstract
BACKGROUND Infection is one of the main complications of hip and knee arthroplasties. Topical application vancomycin to prevent postoperative infections is efficient in spine surgery, and is spreading in prosthetic surgery. However, its clinical relevance and safety are still under debate. Thus, we conducted the present study to (1) assess whether topical vancomycin reduces peri-prosthetic infection rate, and (2) investigate its influence on surgical wound complications. HYPOTHESIS Our hypothesis was that topical administration of diluted vancomycin during arthroplasty would reduce infection rate within the first postoperative year. MATERIAL AND METHODS In total, 1900 hip and knee arthroplasties were performed between 2014 and 2021 in a single hospital. From July 2018 and December 2021, 910 prostheses were implanted with intra-articular instillation of vancomycin and tranexamic acid. From November 2014 to June 2018, 990 prostheses were set up without vancomycin. During a follow-up of minimum 12 months, we reported periprosthetic infections occurring during the first postoperative year, as well as vancomycin-induced general or cutaneous complications. RESULTS We observed periprosthetic infections in 9/990 cases (0.91%) of the control group and 10/910 cases (1.1%) of the vancomycin group (p = 0.82). In parallel, we observed wound complications (erythema, seroma, hematoma, dehiscence and delay in wound healing) in 19/990 (1.9%) and 10/910 cases (1.1%) of the control and vancomycin group, respectively (p = 0.19). There were no general complications resulting from the application of vancomycin. DISCUSSION Topical diluted vancomycin does not reduce periprosthetic infection risk, and has no effect on the occurrence of surgery wound complications. Considering the present findings, the use of vancomycin cannot be recommended in current practice to prevent infections following hip and knee arthroplasties. Finally, its use does not induce any specific complications, whether local (cicatrisation) or general (related to ototoxicity or nephrotoxicity). LEVEL OF EVIDENCE III; case control study.
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Affiliation(s)
- François Laudet
- Département d'Orthopédie-Traumatologie, Hôpital Robert Boulin, 112 rue de la Marne, 33500 Libourne, France.
| | - Alice Gay
- Département d'Orthopédie-Traumatologie, CHU de Bordeaux, Site Pellegrin, Place Amélie Raba-Léon, 33076 Bordeaux, France
| | - Hervé Dutronc
- Département de Maladies Infectieuse et Tropicales, CHU de Bordeaux, Site Pellegrin, Place Amélie Raba-Léon, 33076 Bordeaux, France
| | - Thierry Fabre
- Département d'Orthopédie-Traumatologie, CHU de Bordeaux, Site Pellegrin, Place Amélie Raba-Léon, 33076 Bordeaux, France
| | - Pierre Meynard
- Département d'Orthopédie-Traumatologie, Hôpital Robert Boulin, 112 rue de la Marne, 33500 Libourne, France
| | - Stéphane Costes
- Département d'Orthopédie-Traumatologie, Hôpital Robert Boulin, 112 rue de la Marne, 33500 Libourne, France
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Spiegel C, Ünalan B, Kaserbacher A, Arora R, Coraça-Huber DC. Eicosapentaenoic Acid and Docosahexaenoic Acid as an Antimicrobial Agent in Orthopedics-An In Vitro Study About the Race for Surface. Pathogens 2025; 14:57. [PMID: 39861018 PMCID: PMC11768219 DOI: 10.3390/pathogens14010057] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2024] [Revised: 01/03/2025] [Accepted: 01/09/2025] [Indexed: 01/27/2025] Open
Abstract
BACKGROUND The burden of prosthetic joint infection in combination with antibiotic-resistant bacterial strains is a rising dilemma for patients experiencing total joint replacements. Around 0.8-2% of patients experience prosthetic joint infections, while up to 21% of patients are considered fatal cases after 5 years. Staphylococcus aureus is one of the main reasons for prosthetic joint infections. Its capability of forming biofilms and developing mechanisms against antibiotics is one of the most dangerous clinical topics being currently discussed. Previous studies have shown the promising results of omega-3 fatty acids as an antimicrobial agent against Staphylococcus aureus. Though an antimicrobial effect has been examined, the influence of polyunsaturated fatty acids on Staphylococcus aureus in the presence of human osteoblasts has not been reported yet. In this study, we aimed to investigate the influence of omega-3 fatty acids on the biofilm formation of Staphylococcus aureus ATCC 29213 in the presence of hFOB 1.19 cells. The co-culture setup helped to examine the influence of omega-3 fatty acids on the race for surface to simulate prosthetic joint infections. METHODS In this study, we tested Staphylococcus aureus ATCC 29213 co-cultured with human fetal osteoblasts hFOB 1.19 in the presence of sub-MIC and MIC concentrations of docosahexaenoic acid (1.25 mg/L, 2.5 mg/L) and eicosapentaenoic acid (0.15 mg/L, 0.3 mg/L) after 1, 6 and 24 h of incubation. After establishing the co-culture, cell culture and biofilm, we performed colony-forming unit counting and cell counting to examine cell survivability. In addition, we carried out scanning electron microscopy to study the race for surface behaviour of the cells. RESULTS We found a protective influence of omega-3 fatty acids on osteoblasts when present in co-culture with Staphylococcus aureus after 6 h of incubation. Omega-3 fatty acids increase the cell survival of osteoblasts after 6 h in a co-culture with bacteria and are able to influence the race for surface. In this study, the strain of Staphylcoccus aureus ATCC 29213 showed signs of growth inhibition within the first 6 h. CONCLUSIONS Omega-3 fatty acids can be a valuable antimicrobial agent in terms of decreasing the risk of on-site infection during surgery. Omega-3 fatty acids were shown to decrease the bacterial load within the first 6 h of incubation and increase the survivability of osteoblasts.
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Affiliation(s)
- Christopher Spiegel
- Research Laboratory for Biofilms and Implant Associated Infections (BIOFILM LAB), University Hospital for Orthopaedics and Traumatology, Medical University of Innsbruck, Müllerstraße 44, 6020 Innsbruck, Austria; (B.Ü.); (A.K.); (D.C.C.-H.)
| | - Burak Ünalan
- Research Laboratory for Biofilms and Implant Associated Infections (BIOFILM LAB), University Hospital for Orthopaedics and Traumatology, Medical University of Innsbruck, Müllerstraße 44, 6020 Innsbruck, Austria; (B.Ü.); (A.K.); (D.C.C.-H.)
| | - Andreas Kaserbacher
- Research Laboratory for Biofilms and Implant Associated Infections (BIOFILM LAB), University Hospital for Orthopaedics and Traumatology, Medical University of Innsbruck, Müllerstraße 44, 6020 Innsbruck, Austria; (B.Ü.); (A.K.); (D.C.C.-H.)
| | - Rohit Arora
- Department of Orthopaedics and Traumatology, Medical University of Innsbruck, Anichstraße 35, 6020 Innsbruck, Austria;
| | - Débora C. Coraça-Huber
- Research Laboratory for Biofilms and Implant Associated Infections (BIOFILM LAB), University Hospital for Orthopaedics and Traumatology, Medical University of Innsbruck, Müllerstraße 44, 6020 Innsbruck, Austria; (B.Ü.); (A.K.); (D.C.C.-H.)
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Li X, Lai J, Yang X, Xu H, Xiang S. Intra-articular injection of vancomycin after arthrotomy closure following gentamicin-impregnated bone cementation in primary total knee arthroplasty provides a high intra-articular concentration while avoiding systemic toxicity: a prospective study. J Orthop Surg Res 2024; 19:856. [PMID: 39702402 DOI: 10.1186/s13018-024-05357-9] [Citation(s) in RCA: 7] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/03/2024] [Accepted: 12/10/2024] [Indexed: 12/21/2024] Open
Abstract
BACKGROUND This study aimed to elucidate the safety and intra-articular elution profiles of vancomycin and gentamicin bone cement in patients undergoing primary total knee arthroplasty (TKA), with a focus on serum safety thresholds and therapeutic efficacy. METHODS Consecutive patients who underwent unilateral primary TKA were prospectively enrolled. The implants were fixed using gentamicin-impregnated bone cement, and after arthrotomy closure, 1000 mg of vancomycin suspended in 25 mL of normal saline was directly injected into the joint. Peripheral venous blood and drain fluid samples were collected 2, 8, and 24 h postoperatively. The serum and intra-articular concentrations of vancomycin and gentamicin were analyzed using liquid chromatography-tandem mass spectrometry within 24 h. RESULTS Clinical data reflecting renal and liver function were recorded preoperatively, and at 24 and 72 h postoperatively. A total of 100 patients were included. At 2, 8, and 24 h postoperatively, the serum vancomycin concentration was 7.0 ± 2.0, 5.7 ± 1.8, and 3.6 ± 1.4 µg/mL, respectively, while the intra-articular concentration was 468.5 (interquartile range [IQR] 286.0 to 774.8), 139.5 (IQR 52.0 to 295.3), and 34.4 (IQR 22.2 to 56.8) µg/mL, respectively; 33.2 (IQR 19.5 to 80.5) mg vancomycin was lost in drainage fluid at 24 h postoperatively. For gentamicin, the overall intra-articular concentration was 70.4 (IQR 35.4 to 109.2), 33.8 (IQR 17.8 to 73.9), and 21.1 (IQR 12.2 to 36.0) µg/mL at 2, 8, and 24 h postoperatively, respectively, with an undetectable serum concentration. No cases of acute renal injury, liver injury, ototoxicity, or anaphylaxis were observed. CONCLUSIONS Intra-articular injection of 1000 mg vancomycin after arthrotomy closure combined with gentamicin-impregnated bone cement provided a therapeutic intra-articular concentration while avoiding systemic toxicity over the initial 24 h after primary TKA. Therefore, intra-articular vancomycin administration may offer a safer alternative to intravenous antibiotics, reducing systemic toxicity; however, further large-scale studies are necessary. TRIAL REGISTRATION ClinicalTrials. Gov (registration number: NCT05338021).
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Affiliation(s)
- Xuwen Li
- Department of Traumatology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China
| | - Junhao Lai
- Department of Joint Surgery, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, 266000, China
| | - Xue Yang
- Operation Room, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China
| | - Hao Xu
- Department of Joint Surgery, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, 266000, China
| | - Shuai Xiang
- Department of Joint Surgery, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, 266000, China.
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R S, P S, Gh S, S B, M E, Ja B. Analysis of systemic serum vancomycin levels following intraarticular application in primary total joint arthroplasty. Arch Orthop Trauma Surg 2024; 145:60. [PMID: 39694929 DOI: 10.1007/s00402-024-05688-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/24/2024] [Accepted: 10/08/2024] [Indexed: 12/20/2024]
Abstract
INTRODUCTION Periprosthetic joint infection (PJI) is a serious complication following primary total joint arthroplasty (TJA). PJI accounts for 15-25% of revision surgeries, therefore it is associated with PJI is associated with substantial patient morbidity and mortality as well as increased healthcare expenditures due to complex treatment strategies. Recently, intraoperative local application of vancomycin powder is increasingly being used in primary total hip and knee arthroplasty (THA, TKA) as an additive strategy for PJI prevention. Whereas local vancomycin concentrations have already been investigated in prior studies, evidence on systemic vancomycin levels and potential adverse drug reactions (ADR) is limited. Purpose of this study was to investigate systemic vancomycin levels following intraarticular application in primary TJA. MATERIALS AND METHODS This pilot study is a prospective analysis of patients undergoing primary THA and TKA between April and July 2023. One gram of vancomycin powder was applied to the prosthesis prior to wound closure. Serum vancomycin levels were measured at two standardised time points, 24 and 48 h postoperatively. RESULTS In total, 103 patients were included, and the patient collective was further stratified by surgical procedure into a THA subgroup (n = 52) and a TKA subgroup (n = 51). Mean serum vancomycin levels showed a significant group difference at both time points (24 h: p < 0.001; 48 h: p = 0.044) with higher serum vancomycin concentrations in the THA cohort. Mean serum vancomycin levels in THA patients were 1.25 μg/ml (range 0.00-7.00 μg/ml) after 24 h and 0.34 μg/ml (range 0.00-4.80 μg/ml) 48 h postoperatively. In TKA, no systemic vancomycin levels were detected. Vancomycin concentrations did not reach therapeutic levels in any patient. No ADR was detected in the whole study collective. CONCLUSION Following intraarticular administration of vancomycin powder, no systemic vancomycin levels within the therapeutic range were detected, thus it may serve as a safe and cost-effective adjunct to strategies for prevention of PJI.
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Affiliation(s)
- Stauss R
- School of Medicine and Health Sciences, Division of Orthopaedics at Campus Pius-Hospital, Carl von Ossietzky Universität Oldenburg, Georgstraße 12, 26121, Oldenburg, Germany.
| | - Savov P
- School of Medicine and Health Sciences, Division of Orthopaedics at Campus Pius-Hospital, Carl von Ossietzky Universität Oldenburg, Georgstraße 12, 26121, Oldenburg, Germany
| | - Seeber Gh
- School of Medicine and Health Sciences, Division of Orthopaedics at Campus Pius-Hospital, Carl von Ossietzky Universität Oldenburg, Georgstraße 12, 26121, Oldenburg, Germany
- Department of Orthopedics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Brand S
- School of Medicine and Health Sciences, Division of Orthopaedics at Campus Pius-Hospital, Carl von Ossietzky Universität Oldenburg, Georgstraße 12, 26121, Oldenburg, Germany
| | - Ettinger M
- School of Medicine and Health Sciences, Division of Orthopaedics at Campus Pius-Hospital, Carl von Ossietzky Universität Oldenburg, Georgstraße 12, 26121, Oldenburg, Germany
| | - Beheshty Ja
- School of Medicine and Health Sciences, Division of Orthopaedics at Campus Pius-Hospital, Carl von Ossietzky Universität Oldenburg, Georgstraße 12, 26121, Oldenburg, Germany
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Egerci OF, Yapar A, Dogruoz F, Selcuk H, Kose O. Preventive strategies to reduce the rate of periprosthetic infections in total joint arthroplasty; a comprehensive review. Arch Orthop Trauma Surg 2024; 144:5131-5146. [PMID: 38635048 PMCID: PMC11602800 DOI: 10.1007/s00402-024-05301-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/12/2023] [Accepted: 03/24/2024] [Indexed: 04/19/2024]
Abstract
The increasing frequency of total hip (THA) and knee arthroplasties (TKA) is marred by the rise in periprosthetic joint infections (PJIs) and surgical site infections (SSIs), with PJIs incurring costs over $1.62 billion as of 2020 and individual case management averaging $90,000. SSIs additionally burden the U.S. healthcare economy with billions in expenses annually. PJI prevalence in primary THA and TKA ranges from 0.5% to 2.4%, spiking to 20% in revisions and representing 25% of TKA revision causes. Projections estimate up to 270,000 annual PJI cases by 2030. Often caused by gram-positive bacteria, particularly methicillin-resistant staphylococci, these infections demand preventive measures. This review dissects PJI prevention across preoperative, intraoperative, and perioperative phases, aligning with evidence-based CDC and WHO guidelines. Preoperative measures include managing diabetes, obesity, tobacco use, Staphylococcus aureus screening and nasal decolonization, nutritional optimization, and management of inflammatory arthropathies. Intraoperatively, antibiotic prophylaxis, skin preparation, operative room environmental controls, surgical technique precision, and irrigation options are scrutinized. Perioperative concerns focus on anticoagulation, blood management, and infection risk mitigation. Integrating these strategies promotes a patient-centric care model, aiming to reduce PJI incidence, improve patient outcomes, and increase care cost-effectiveness in joint arthroplasty.
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Affiliation(s)
- Omer Faruk Egerci
- Department of Orthopedics and Traumatology, Antalya Training and Research Hospital, Antalya, Turkey
| | - Aliekber Yapar
- Department of Orthopedics and Traumatology, Antalya Training and Research Hospital, Antalya, Turkey
| | - Fırat Dogruoz
- Department of Orthopedics and Traumatology, Antalya Training and Research Hospital, Antalya, Turkey
| | - Huseyin Selcuk
- Department of Orthopedics and Traumatology, Antalya Training and Research Hospital, Antalya, Turkey
| | - Ozkan Kose
- Department of Orthopedics and Traumatology, Antalya Training and Research Hospital, Antalya, Turkey.
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Bruyninckx S, Metsemakers WJ, Depypere M, Henckaerts L, van den Hout E, Onsea J, Ghijselings S, Vles GF. Local antibiotic delivery via intra-articular catheter infusion for the treatment of periprosthetic joint infection: a systematic review. Arch Orthop Trauma Surg 2024; 144:5177-5189. [PMID: 38691147 DOI: 10.1007/s00402-024-05341-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/27/2024] [Accepted: 04/14/2024] [Indexed: 05/03/2024]
Abstract
INTRODUCTION There is an increasing interest in the use of intra-articular (IA) antibiotic infusion as a stand-alone or adjuvant therapy to standard revision surgery for periprosthetic joint infection (PJI). The objective of this systematic review is to evaluate the evidence with respect to this up-and-coming treatment modality. METHODS A systematic review of studies published until April 2023 was conducted using PubMed, Embase, MEDLINE and Cochrane databases. Quality assessment was performed with the National Institute of Health quality assessment tool. Inclusion criteria were adult patients (≥ 18 years) with a mean follow-up of ≥ 11 months and a score ≥ 6 on the National Institute of Health quality assessment tool. Primary outcome was eradication of infection. RESULTS 15 articles, encompassing 631 PJIs in 626 patients, were included in the final analysis, all level IV case series. The majority was treated with single-stage revision with adjuvant IA antibiotic infusion (79.1%). The remaining PJIs were treated with stand-alone IA antibiotic infusion (12.2%), DAIR (debridement, antibiotics and implant retention) with adjuvant IA antibiotic infusion (5.7%) or two-stage revision with adjuvant IA antibiotic infusion (3.0%). Mean duration of IA antibiotic infusion was 19 days (range 3-50). An overall failure rate of approximately 11% was found. In total 117 complications occurred, 71 were non-catheter-related and 46 were catheter-related. The most common catheter-related complications were premature loss of the catheter (18/46) and elevated blood urea nitrogen (BUN) and creatinine levels (12/46). CONCLUSIONS Due to the lack of comparative studies the (added) benefit of IA antibiotic infusion in the treatment of PJI remains uncertain. Based on the current evidence, we would advise against using it as a stand-alone treatment. A prospective randomized controlled trial using a well-described infusion protocol is needed to see if the potential benefits justify the increased costs and potential complications of this treatment modality.
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Affiliation(s)
- S Bruyninckx
- Department of Orthopaedic Surgery, University Hospitals Leuven, Herestraat 49, 3000, Leuven, Belgium.
| | - W J Metsemakers
- Department of Trauma Surgery, University Hospitals Leuven, Herestraat 49, 3000, Leuven, Belgium
- Department of Development and Regeneration, KU Leuven, Herestraat 49-Box 805, 3000, Leuven, Belgium
| | - M Depypere
- Department of Laboratory Medicine, University Hospitals Leuven, Herestraat 49, 3000, Leuven, Belgium
- Department of Microbiology, Immunology and Transplantation, University Hospitals Leuven, Herestraat 49, 3000, Leuven, Belgium
| | - L Henckaerts
- Department of Microbiology, Immunology and Transplantation, University Hospitals Leuven, Herestraat 49, 3000, Leuven, Belgium
- Department of General Internal Medicine, University Hospitals Leuven, Herestraat 49, 3000, Leuven, Belgium
- Laboratory for Clinical Infectious and Inflammatory Disorders, KU Leuven, Herestraat 49, Leuven, Belgium
| | - E van den Hout
- Department of General Internal Medicine, University Hospitals Leuven, Herestraat 49, 3000, Leuven, Belgium
- Laboratory for Clinical Infectious and Inflammatory Disorders, KU Leuven, Herestraat 49, Leuven, Belgium
| | - J Onsea
- Department of Trauma Surgery, University Hospitals Leuven, Herestraat 49, 3000, Leuven, Belgium
- Department of Development and Regeneration, KU Leuven, Herestraat 49-Box 805, 3000, Leuven, Belgium
| | - S Ghijselings
- Department of Orthopaedic Surgery, University Hospitals Leuven, Herestraat 49, 3000, Leuven, Belgium
| | - G F Vles
- Department of Orthopaedic Surgery, University Hospitals Leuven, Herestraat 49, 3000, Leuven, Belgium
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11
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Doxey SA, Urdahl TH, Solaiman RH, Wegner MN, Parikh H, Cunningham BP, Horst PK. Intrawound vancomycin powder in primary total knee arthroplasty: Does it reduce early postoperative infection? Knee 2024; 51:312-319. [PMID: 39476511 DOI: 10.1016/j.knee.2024.10.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/16/2024] [Revised: 09/12/2024] [Accepted: 10/16/2024] [Indexed: 12/07/2024]
Abstract
BACKGROUND The purpose of this retrospective analysis of a prospective quality control project was to determine whether the use of intrawound vancomycin powder (IVP) decreases the rate prosthetic joint infection (PJI) within 90-days following primary total knee arthroplasty (TKA). METHODS From October 2021-September 2022, a prospective quality control project was undertaken in which 10 high-volume arthroplasty surgeons alternated between using IVP and not using IVP each month. Patients who received IVP were compared to those who did not. The primary outcome was culture positive PJI within 90-days following primary total knee arthroplasty. Secondary outcomes included overall reoperation rate, wound complications, and readmission within 90-days post-operatively. RESULTS A total of 1,317 primary TKA patients were identified for analysis. Fifty-six and seven tenths percent (n = 747) of patients were included in the IVP group and 43.3% (n = 570) patients were included in the non-IVP group. The overall PJI rate was 0.5%. There was no difference in 90-day culture positive PJI rates between the groups (0.7% vs. 0.2%, p = 0.24). The overall reoperation rate did not differ between the IVP and non-IVP group (6.4% vs. 4.6%, p = 0.15). Reoperation for suspected infection was not statistically different by IVP administration (1.2% vs. 0.5%, p = 0.25). Additionally, there were no differences in the incidence of wound complications (p = 0.80) or readmissions (p = 0.15). CONCLUSIONS The overall infection rate for this cohort was low. IVP was not associated with decreased culture positive PJI, wound complications, reoperation or readmission rates. Further analysis of IVP use in TKA should be undertaken to fully determine its efficacy and safety profile.
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Affiliation(s)
- Stephen A Doxey
- Department of Orthopaedic Surgery, TRIA Orthopaedic Institute, Bloomington, MN, USA; Department of Orthopaedic Surgery, Park Nicollet Methodist Hospital, St. Louis Park, MN, USA.
| | - Torben H Urdahl
- Department of Orthopaedic Surgery, University of Minnesota, Minneapolis, MN, USA.
| | - Rafat H Solaiman
- Department of Orthopaedic Surgery, University of Minnesota, Minneapolis, MN, USA.
| | - Mariah N Wegner
- Department of Orthopaedic Surgery, University of Minnesota, Minneapolis, MN, USA.
| | - Harsh Parikh
- Department of Orthopaedic Surgery, TRIA Orthopaedic Institute, Bloomington, MN, USA; Department of Orthopaedic Surgery, Park Nicollet Methodist Hospital, St. Louis Park, MN, USA.
| | - Brian P Cunningham
- Department of Orthopaedic Surgery, TRIA Orthopaedic Institute, Bloomington, MN, USA; Department of Orthopaedic Surgery, Park Nicollet Methodist Hospital, St. Louis Park, MN, USA; Department of Orthopaedic Surgery, University of Minnesota, Minneapolis, MN, USA.
| | - Patrick K Horst
- Department of Orthopaedic Surgery, TRIA Orthopaedic Institute, Bloomington, MN, USA; Department of Orthopaedic Surgery, Park Nicollet Methodist Hospital, St. Louis Park, MN, USA; Department of Orthopaedic Surgery, University of Minnesota, Minneapolis, MN, USA.
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12
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Mills H, Donnelly L, Platt S. Locally Delivered Antibiotics in Fracture-Related Infection. Cureus 2024; 16:e73210. [PMID: 39650921 PMCID: PMC11624964 DOI: 10.7759/cureus.73210] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/06/2024] [Indexed: 12/11/2024] Open
Abstract
The prevention and treatment of fracture-related infections (FRIs) pose significant challenges in orthopaedic trauma care, with current practices predominantly relying on systemic antibiotic administration. However, locally delivered antibiotics achieve substantially higher tissue concentrations and minimise systemic side effects. Whilst extensively researched in periprosthetic joint infections (PJIs), the use of local delivery methods is increasingly prevalent in FRI prevention and treatment. Various local delivery methods such as powders, aqueous injections and carriers such as cement, bone graft, bioceramics, polymers and hydrogels have been explored. Biodegradable antibiotic carriers offer a promising alternative to non-absorbable carriers (i.e., cement), which necessitate surgical removal. There is good evidence for the use of local antibiotics in preventing and treating FRI, particularly in high-risk fractures or in treating more severe, resistant infections. Despite theoretical concerns, reports of adverse events in human studies are rare. To enhance our understanding of the safety and efficacy of these methods across various fracture patterns, further prospective randomised controlled trials are warranted. This article describes the current strategies and methodologies for FRI prevention and treatment and reviews the existing evidence base.
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Affiliation(s)
- Henry Mills
- Orthopaedics, Gold Coast University Hospital, Gold Coast, AUS
| | - Liam Donnelly
- Trauma and Orthopaedics, London North West University Healthcare National Health Service Trust, London, GBR
| | - Simon Platt
- Orthopaedics, Gold Coast University Hospital, Gold Coast, AUS
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13
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Zhang Q, Sun X, Pan JB, Kong G. Feasibility of mNGS in joint replacement patients exhibiting elevated ESR and CRP levels without an underlying diagnosis. Eur J Med Res 2024; 29:515. [PMID: 39456072 PMCID: PMC11515214 DOI: 10.1186/s40001-024-02118-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2024] [Accepted: 10/16/2024] [Indexed: 10/28/2024] Open
Abstract
OBJECTIVE The aim of this study is to investigate the viability of performing initial artificial joint replacement surgery in patients presenting with unexplained elevations in erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels. METHODS A cohort of 22 patients, comprising 11 cases each for knee and hip joint replacements, who underwent initial artificial joint replacement surgery between November 2020 and January 2022, was recruited. All patients exhibited elevated levels of ESR and CRP prior to surgery, the etiology of which remained undetermined. Intraoperatively, joint effusion and periarticular tissues were preserved for subsequent bacterial culture and metagenomic next-generation sequencing (mNGS). Postoperatively, a combination of intravenous and local antibiotics was administered for anti-infective management. In cases where bacterial culture and/or mNGS yielded positive results, patients were diagnosed with periprosthetic joint infections (PJI) and underwent one-stage revision; conversely, negative findings led to the discontinuation of intravenous and local antibiotics therapy. RESULTS Among the cohort of 22 patients, bacterial cultures yielded negative results, while mNGS identified bacterial infection in 14 patients (63.63%), viral infection in 1 patient (4.55%), and yielded negative results in 7 patients (31.82%). All surgical incisions achieved per primam. Subsequent follow-up assessments conducted for more than 1 year postoperatively revealed absence of PJI among the patients, all of whom exhibited satisfactory progress in their rehabilitation exercises. Notably, the Knee Society Score (KSS) for knee joint patients significantly improved from a preoperative mean of 48.7 ± 3.3 points to 84.3 ± 2.2 points postoperatively, whereas the Harris Hip Score for hip joint patients increased significantly from preoperative mean of 50.6 ± 3.6 points to 87.1 ± 1.6 points (P < 0.01). CONCLUSION In cases where patients present with unexplained elevations in ESR and CRP levels, primary artificial joint replacement can be undertaken following a one-stage revision approach for PJI.
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Affiliation(s)
- Qi Zhang
- Department of Osteoarthritis, Yantai City Yantai Shan Hospital, No. 91 of Jiefang Road, Zhifu District, Yantai, 264001, China
| | - Xuan Sun
- Pharmacy Intravenous Admixture Services, Yantai City Yantai Shan Hospital, No. 91 of Jiefang Road, Zhifu District, Yantai, 264001, China
| | - Jing-Bo Pan
- Department of Osteoarthritis, Yantai City Yantai Shan Hospital, No. 91 of Jiefang Road, Zhifu District, Yantai, 264001, China
| | - Gang Kong
- Department of Osteoarthritis, Yantai City Yantai Shan Hospital, No. 91 of Jiefang Road, Zhifu District, Yantai, 264001, China.
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Li Y, Wuermanbieke S, Wang F, Mu W, Ji B, Guo X, Zou C, Chen Y, Zhang X, Cao L. Efficacy and safety of intra-articular-only meropenem after one-stage revision for treating Escherichia coli-induced periprosthetic joint infection in a rat model. Bone Joint Res 2024; 13:546-558. [PMID: 39362652 PMCID: PMC11449542 DOI: 10.1302/2046-3758.1310.bjr-2024-0119.r1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/05/2024] Open
Abstract
Aims The optimum type of antibiotics and their administration route for treating Gram-negative (GN) periprosthetic joint infection (PJI) remain controversial. This study aimed to determine the GN bacterial species and antibacterial resistance rates related to clinical GN-PJI, and to determine the efficacy and safety of intra-articular (IA) antibiotic injection after one-stage revision in a GN pathogen-induced PJI rat model of total knee arthroplasty. Methods A total of 36 consecutive PJI patients who had been infected with GN bacteria between February 2015 and December 2021 were retrospectively recruited in order to analyze the GN bacterial species involvement and antibacterial resistance rates. Antibiotic susceptibility assays of the GN bacterial species were performed to screen for the most sensitive antibiotic, which was then used to treat the most common GN pathogen-induced PJI rat model. The rats were randomized either to a PJI control group or to three meropenem groups (intraperitoneal (IP), IA, and IP + IA groups). After two weeks of treatment, infection control level, the side effects, and the volume of antibiotic use were evaluated. Results Escherichia coli was the most common pathogen in GN-PJI, and meropenem was the most sensitive antibiotic. Serum inflammatory markers, weightbearing activity, and Rissing score were significantly improved by meropenem, especially in the IA and IP + IA groups ( p < 0.05). Meropenem in the IA group eradicated E. coli from soft-tissue, bone, and prosthetic surfaces, with the same effect as in the IP + IA group. Radiological results revealed that IA and IP + IA meropenem were effective at relieving bone damage. Haematoxylin and eosin staining also showed that IA and IP + IA meropenem improved synovial inflammation and bone destruction. No pathological changes in the main organs or abnormal serum markers were observed in any of the meropenem-treated rats. The IA group required the lowest amount of meropenem, followed by the IP and IP + IA groups. Conclusion IA-only meropenem with a two-week treatment course was effective and safe for PJI control following one-stage revision in a rat model, with less meropenem use.
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Affiliation(s)
- Yicheng Li
- Department of Orthopaedics, First Affiliated Hospital of Xinjiang Medical University, Urumqi, China
| | - Shalitanati Wuermanbieke
- Department of Sports Medicine, Karamay Hospital of People’s Hospital of Xinjiang Uygur Autonomous Region, Karamay, China
| | - Fei Wang
- Department of Orthopaedics, First Affiliated Hospital of Xinjiang Medical University, Urumqi, China
| | - Wenbo Mu
- Department of Orthopaedics, First Affiliated Hospital of Xinjiang Medical University, Urumqi, China
| | - Baochao Ji
- Department of Orthopaedics, First Affiliated Hospital of Xinjiang Medical University, Urumqi, China
| | - Xiaobin Guo
- Department of Orthopaedics, First Affiliated Hospital of Xinjiang Medical University, Urumqi, China
| | - Chen Zou
- Department of Orthopaedics, First Affiliated Hospital of Xinjiang Medical University, Urumqi, China
| | - Yanyang Chen
- Department of Orthopaedics, Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases, Shanghai Institute of Traumatology and Orthopaedics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Xiaogang Zhang
- Department of Orthopaedics, First Affiliated Hospital of Xinjiang Medical University, Urumqi, China
| | - Li Cao
- Department of Orthopaedics, First Affiliated Hospital of Xinjiang Medical University, Urumqi, China
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15
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Doxey SA, Urdahl TH, Solaiman RH, Wegner MN, Cunningham BP, Horst PK. Intrawound Vancomycin Powder in Primary Total Hip Arthroplasty: A Prospective Quality Control Study. J Arthroplasty 2024; 39:S327-S331. [PMID: 38599528 DOI: 10.1016/j.arth.2024.03.063] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/15/2023] [Revised: 03/20/2024] [Accepted: 03/21/2024] [Indexed: 04/12/2024] Open
Abstract
BACKGROUND The purpose of this retrospective analysis of a prospective quality control project was to determine whether the use of intrawound vancomycin powder (IVP) decreases the rate of periprosthetic joint infection (PJI) within 90 days following primary total hip arthroplasty (THA). METHODS From October 2021 to September 2022, a prospective quality control project was undertaken in which 10 high-volume THA surgeons alternated between using and not using IVP each month while keeping other perioperative protocols unchanged. A retrospective analysis of the project was performed to compare the group of patients who received IVP to the group of patients who did not. The primary outcome was a culture positive infection within 90 days following primary THA. Secondary outcomes included gram-positive culture, overall reoperation rate, wound complications, readmission, and wound complications within 90 days post-operatively. A total of 1,193 primary THA patients were identified for analysis. There were 523 (43.8%) patients who received IVP and were included in the IVP group, while 670 (56.2%) did not and were included in the non-IVP group. Age, body mass index, and sex were similar between the 2 groups (P > .25). RESULTS The IVP group had a higher rate of culture positive joint infections (1.7 [0.8, 3.2] versus 0.3% [0.04, 1.1], P = .01) than the non-IVP group. All PJI's were found to have gram positive bacteria in both groups. The IVP group had a higher overall reoperation rate than the non-IVP group (6.1 [4.2, 8.5] versus 2.4% [1.4, 3.9], P < .01). The IVP group had a higher reoperation rate for any wound complication compared to non-IVP patients (2.7 [1.5, 4.5] versus 0.7% [0.2, 1.7], P < .01). The overall readmission rate (6.1 [4.2, 8.5] versus 2.8% [1.7, 4.4], P < .01), as well as readmission for suspected infection (2.1 [1.1, 3.7] versus 0.6% [0.02, 1.5], P = .03), were higher in the IVP group. CONCLUSIONS The use of IVP in primary THA was associated with a higher rate of PJI, overall reoperation, reoperation for wound complications, and readmission in a prospective quality control project. Until future prospective randomized studies determine the safety and efficacy of IVP in THA conclusively, we advocate against its utilization.
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Affiliation(s)
- Stephen A Doxey
- Department of Orthopaedic Surgery, TRIA Orthopaedic Institute, Bloomington, Minnesota; Department of Orthopaedic Surgery, Park Nicollet Methodist Hospital, St. Louis Park, Minnesota
| | - Torben H Urdahl
- Department of Orthopaedic Surgery, University of Minnesota, Minneapolis, Minnesota
| | - Rafat H Solaiman
- Department of Orthopaedic Surgery, University of Minnesota, Minneapolis, Minnesota
| | - Mariah N Wegner
- Department of Orthopaedic Surgery, University of Minnesota, Minneapolis, Minnesota
| | - Brian P Cunningham
- Department of Orthopaedic Surgery, TRIA Orthopaedic Institute, Bloomington, Minnesota; Department of Orthopaedic Surgery, Park Nicollet Methodist Hospital, St. Louis Park, Minnesota
| | - Patrick K Horst
- Department of Orthopaedic Surgery, TRIA Orthopaedic Institute, Bloomington, Minnesota; Department of Orthopaedic Surgery, Park Nicollet Methodist Hospital, St. Louis Park, Minnesota; Department of Orthopaedic Surgery, University of Minnesota, Minneapolis, Minnesota
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Coles VE, Puri L, Bhandari M, Wood TJ, Burrows LL. The effects of chlorhexidine, povidone-iodine and vancomycin on growth and biofilms of pathogens that cause prosthetic joint infections: an in-vitro model. J Hosp Infect 2024; 151:99-108. [PMID: 38992843 DOI: 10.1016/j.jhin.2024.06.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2024] [Revised: 06/11/2024] [Accepted: 06/23/2024] [Indexed: 07/13/2024]
Abstract
BACKGROUND Chlorhexidine gluconate (CHG) and povidone-iodine (PI) are commonly used to prevent prosthetic joint infection (PJI) during total joint replacement; however, their effective concentrations and impact on biofilms are not well defined. AIM To determine: (1) the in-vitro minimum inhibitory concentration of CHG and PI against model PJI-causing organisms and clinical isolates; (2) their impact on biofilm formation; (3) whether there is a synergistic benefit to combining the two solutions; and (4) whether adding the antibiotic vancomycin impacts antiseptic activity. METHODS We measured in-vitro growth and biofilm formation of Staphylococcus epidermidis, meticillin-sensitive and meticillin-resistant Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa and Candida albicans, as well as recent clinical isolates, in the presence of increasing concentrations of CHG and/or PI. Checkerboard assays were used to measure potential synergy of the solutions together and with vancomycin. FINDINGS CHG and PI inhibited growth and biofilm formation of all model organisms tested at concentrations of 0.0004% and 0.33% or lower, respectively; highly dilute concentrations paradoxically increased biofilm formation. The solutions did not synergize with one another and acted independently of vancomycin. CONCLUSION CHG and PI are effective at lower concentrations than typically used, establishing baselines to support further clinical trials aimed at optimizing wound disinfection. There is no synergistic advantage to using both in combination. Vancomycin is effective at inhibiting the growth of S. epidermidis and S. aureus; however, it stimulates P. aeruginosa biofilm production, suggesting in the rare case of P. aeruginosa PJI, it could exacerbate infection.
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Affiliation(s)
- V E Coles
- Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada; Michael G. DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, Ontario, Canada
| | - L Puri
- Hamilton Arthroplasty Group, Hamilton Health Sciences Juravinski Hospital, Hamilton, Ontario, Canada
| | - M Bhandari
- Department of Orthopaedic Surgery, McMaster University, Hamilton, Ontario, Canada
| | - T J Wood
- Hamilton Arthroplasty Group, Hamilton Health Sciences Juravinski Hospital, Hamilton, Ontario, Canada; Department of Orthopaedic Surgery, McMaster University, Hamilton, Ontario, Canada
| | - L L Burrows
- Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada; Michael G. DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, Ontario, Canada.
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Jarusriwanna A, Mu W, Parvizi J. Local Antibiotic Infusion in Periprosthetic Joint Infection Following Total Hip Arthroplasty. J Clin Med 2024; 13:4848. [PMID: 39200989 PMCID: PMC11355570 DOI: 10.3390/jcm13164848] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2024] [Revised: 08/08/2024] [Accepted: 08/14/2024] [Indexed: 09/02/2024] Open
Abstract
Local antibiotic infusion has emerged as a promising adjunctive therapy, delivering high concentrations of antibiotics directly to the infection site. This approach aims to enhance eradication of pathogens while minimizing systemic side effects associated with prolonged antibiotic use. This narrative review encompassed 10 articles focused on all three procedures of surgical intervention for periprosthetic joint injection (PJI) following total hip arthroplasty (THA): debridement, antibiotics, and implant retention (DAIR), single-stage revision arthroplasty, and two-stage revision arthroplasty. Recent studies report success rates ranging from 90 to 100% in patients undergoing DAIR, 82 to 100% in single-stage revision arthroplasty, and 80% in two-stage revision arthroplasty. The adjunctive use of local antibiotic infusion alongside surgical treatment for PJI following THA provides high success rates and is associated with low systemic complications, such as renal toxicity. Further research, particularly high-quality randomized controlled trials (RCTs), is warranted to validate and refine treatment protocols, ensuring consistent efficacy and safety.
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Affiliation(s)
- Atthakorn Jarusriwanna
- Rothman Orthopaedic Institute, Thomas Jefferson University, Philadelphia, PA 19107, USA; (A.J.); (W.M.)
- Department of Orthopaedics, Faculty of Medicine, Naresuan University, Phitsanulok 65000, Thailand
| | - Wenbo Mu
- Rothman Orthopaedic Institute, Thomas Jefferson University, Philadelphia, PA 19107, USA; (A.J.); (W.M.)
- Department of Orthopaedics, First Affiliated Hospital of Xinjiang Medical University, Ürümqi 830011, China
| | - Javad Parvizi
- Department of Surgical Sciences, Orthopedics and Traumatology, School of Medicine, Acibadem University, Istanbul 34752, Türkiye
- Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA 19107, USA
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Mulpur P, Jayakumar T, Yakkanti RR, Apte A, Hippalgaonkar K, Annapareddy A, Masilamani ABS, Reddy AVG. Efficacy of Intrawound Vancomycin in Prevention of Periprosthetic Joint Infection After Primary Total Knee Arthroplasty: A Prospective Double-Blinded Randomized Control Trial. J Arthroplasty 2024; 39:1569-1576. [PMID: 38749600 DOI: 10.1016/j.arth.2024.01.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/25/2023] [Revised: 12/21/2023] [Accepted: 01/02/2024] [Indexed: 07/17/2024] Open
Abstract
BACKGROUND Periprosthetic joint infection (PJI) after total knee arthroplasty (TKA) is a devastating complication. Intrawound vancomycin powder has been shown to reduce infection rates in spine surgery, but its role in arthroplasty remains controversial. This prospective randomized control trial aimed to evaluate the efficacy of intrawound vancomycin in preventing PJI after primary TKA. METHODS A total of 1,022 patients were randomized to the study group (n = 507, who received 2 grams intrawound vancomycin powder before arthrotomy closure) or to the control group (n = 515, no local vancomycin) with a minimum follow-up of 12-months. The primary outcome was the incidence of PJI or surgical site infection (SSI). Secondary outcomes included associated minor complications such as stitch abscess, persistent wound drainage, and delayed stitch removal. Other parameters evaluated include reoperation rates and incidences of nephrotoxicity. RESULTS The overall infection rate in 1,022 patients was 0.66%. There was no significant difference in PJI rate in the study group (N = 1; 0.2%) versus the control group (N = 3; 0.58%), P = .264. Reoperation rates in the study group (N = 4; 0.78%) and control (N = 5; 0.97%), and SSI rates in the study (N = 1; 0.2%) and control groups (N = 2; 0.38%) were comparable. The Vancomycin cohort, however, demonstrated a significantly higher number of minor wound complications (n = 67; 13.2%) compared to the control group (n = 39; 7.56%, P < .05). Subgroup analysis showed diabetics in the study group to also have a higher incidence of minor wound complications (24 [14.1%] versus 10 [6.2%]; P < 05]. Multivariate analyses found that vancomycin use (odds ratio = 1.64) and smoking (odds ratio = 1.85) were associated with an increased risk of developing minor wound complications. No cases of nephrotoxicity were reported. CONCLUSIONS Intrawound vancomycin powder does not appear to reduce PJI/SSI rate in primary total knee arthroplasties, including high-risk groups. Although safe from a renal perspective, intrawound vancomycin was associated with an increase in postoperative aseptic wound complications. Intrawound vancomycin may not be effective in reducing the rate of PJI in primary TKA.
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Affiliation(s)
- Praharsha Mulpur
- Sunshine Bone and Joint Insitute, KIMS-Sunshine Hospitals, Hyderabad, India
| | - Tarun Jayakumar
- Sunshine Bone and Joint Insitute, KIMS-Sunshine Hospitals, Hyderabad, India
| | - Ramakanth R Yakkanti
- Division of Arthroplasty, Rothman Orthopedics at Advent Health, Orlando, Florida
| | - Aditya Apte
- Sunshine Bone and Joint Insitute, KIMS-Sunshine Hospitals, Hyderabad, India
| | | | - Adarsh Annapareddy
- Sunshine Bone and Joint Insitute, KIMS-Sunshine Hospitals, Hyderabad, India
| | | | - A V Gurava Reddy
- Sunshine Bone and Joint Insitute, KIMS-Sunshine Hospitals, Hyderabad, India
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Hall S, Grayson J, Grant G, Vertullo C, Anoopkumar-Dukie S. In Vitro Evaluation of Vancomycin-Induced Toxicity in Human Primary Knee Chondrocytes. Int J Toxicol 2024; 43:177-183. [PMID: 37989131 PMCID: PMC10916344 DOI: 10.1177/10915818231216413] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2023]
Abstract
Septic arthritis as a complication of orthopaedic joint surgery can have catastrophic outcomes for patients. To minimise infection risk associated with elective orthopaedics, topical vancomycin during surgery has become increasingly common. Evidence suggests that high concentrations of vancomycin, following direct application of the drug to the joint, are toxic towards various local cell types in the joint, including chondrocytes. However, the mechanism of this vancomycin tissue toxicity is yet to be determined. The aim of this study was to evaluate the toxicity of vancomycin on chondrocytes and the mechanisms of cell death involved. Human primary knee chondrocytes were exposed to vancomycin (1.25-10 mg/mL) for 24 h and their viability assessed using the resazurin reduction assay in vitro. Specific cell death mechanisms and their contributors, including reactive oxygen species (ROS) production and apoptosis, were measured. This study showed that high concentrations of vancomycin (5 and 10 mg/mL) were toxic towards human primary knee chondrocyte cells, while lower concentrations (1.25 and 2.5 mg/mL) were not. Cell death studies found that this occurred through an apoptotic pathway. This study provides additional support that vancomycin in high doses is toxic towards chondrocytes and preliminary evidence that this toxicity occurs via apoptotic cell death mechanisms.
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Affiliation(s)
- Susan Hall
- School of Pharmacy and Medical Sciences, Griffith University, Gold Coast, Australia
| | - Jane Grayson
- School of Health Sciences, The University of Sydney, Glebe, Australia
| | - Gary Grant
- School of Pharmacy and Medical Sciences, Griffith University, Gold Coast, Australia
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20
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Wang B, Li S, Zhang J, Wu D, Huang X, Liu D, Du J. Intrawound vancomycin powder in orthopaedic surgery as surgical site wound infection prophylaxis: A meta-analysis. Int Wound J 2023; 20:3673-3681. [PMID: 37309291 PMCID: PMC10588340 DOI: 10.1111/iwj.14258] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2023] [Revised: 05/09/2023] [Accepted: 05/20/2023] [Indexed: 06/14/2023] Open
Abstract
A meta-analysis research was executed to appraise the consequence of intrawound vancomycin powder (IWVP) in orthopaedic surgery (OPS) as surgical site wound infection (SSWI) prophylaxis. Inclusive literature research till March 2023 was carried out and 2756 interconnected researches were revised. Of the 18 picked researches enclosed 13 214 persons with OPS were in the used researches' starting point, 5798 of them were utilising IWVP, and 7416 were control. Odds ratio (OR) in addition to 95% confidence intervals (CIs) were used to appraise the consequence of the IWVP in OPS as SSWI prophylaxis by the dichotomous approaches and a fixed or random model. IWVP had significantly lower SSWIs (OR, 0.61; 95% CI, 0.50-0.74, P < .001), deep SSWIs (OR, 0.57; 95% CI, 0.36-0.91, P = .02), and superficial SSWIs (OR, 0.67; 95% CI, 0.46-0.98, P = .04) compared with control in persons with OPS. IWVP had significantly lower SSWIs, deep SSWIs, and superficial SSWIs compared with control in persons with OPS. However, when interacting with its values, caution must be taken and more research is needed to confirm this finding.
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Affiliation(s)
- Bin Wang
- Orthopedics DepartmentAir Force Medical CenterBeijingChina
| | - Songlin Li
- Orthopedics DepartmentAir Force Medical CenterBeijingChina
| | - Jinkang Zhang
- Orthopedics DepartmentAir Force Medical CenterBeijingChina
| | - Di Wu
- Orthopedics DepartmentAir Force Medical CenterBeijingChina
| | - Xiaogang Huang
- Orthopedics DepartmentAir Force Medical CenterBeijingChina
| | - Dongzhou Liu
- Orthopedics DepartmentAir Force Medical CenterBeijingChina
| | - Junjie Du
- Orthopedics DepartmentAir Force Medical CenterBeijingChina
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21
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Hu M, Zhang Y, Yang X, Wang Y, Xu H, Xiang S. Intraarticular vancomycin decreased the risk of acute postoperative periprosthetic joint infection without increasing complication in primary total joint arthroplasty-a prospective study. Int J Infect Dis 2023; 136:64-69. [PMID: 37714404 DOI: 10.1016/j.ijid.2023.09.004] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2023] [Revised: 09/03/2023] [Accepted: 09/09/2023] [Indexed: 09/17/2023] Open
Abstract
OBJECTIVES To investigate the preventive effect of intraarticularly administered vancomycin on acute postoperative periprosthetic joint infection (PJI) in total joint arthroplasty (TJA). METHODS Consecutive patients who underwent unilateral primary TJA were prospectively enrolled. The patients were divided into vancomycin group and control group according to whether 1 g of vancomycin powder suspended in 30 ml normal saline was intraarticularly administered after arthrotomy closure. Acute postoperative PJI and aseptic wound complication were evaluated within 3 months postoperatively. Vancomycin-associated toxicity including acute renal failure, ototoxicity and anaphylaxis was also evaluated. RESULTS In terms of demographic parameters and comorbidities, no significant difference was found between the two groups. Intra-articular vancomycin significantly lowered the risk of acute postoperative PJI after primary TJA (P = 0.015) and primary total knee arthroplasty (P = 0.031). However, for patients who underwent total hip arthroplasty, the PJI rate was comparable between the two groups. Overall, the risk of aseptic wound complication between the two groups was also similar. Vancomycin-associated acute renal injury, ototoxicity, or anaphylaxis was not observed. CONCLUSIONS Intra-articular injection of 1 g of vancomycin suspension after arthrotomy closure during TJA lowered the risk of acute postoperative PJI without increasing the risk of aseptic wound complication and vancomycin-associated systemic toxicity.
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Affiliation(s)
- Mingwei Hu
- Department of Joint Surgery, the Affiliated Hospital of Qingdao University, Qingdao, Shandong, China
| | - Yifan Zhang
- Department of Joint Surgery, the Affiliated Hospital of Qingdao University, Qingdao, Shandong, China
| | - Xue Yang
- Department of Operation Room, the Affiliated Hospital of Qingdao University, Qingdao, Shandong, China
| | - Yingzhen Wang
- Department of Joint Surgery, the Affiliated Hospital of Qingdao University, Qingdao, Shandong, China
| | - Hao Xu
- Department of Joint Surgery, the Affiliated Hospital of Qingdao University, Qingdao, Shandong, China
| | - Shuai Xiang
- Department of Joint Surgery, the Affiliated Hospital of Qingdao University, Qingdao, Shandong, China.
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22
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Mancino F, Yates PJ, Clark B, Jones CW. Use of topical vancomycin powder in total joint arthroplasty: Why the current literature is inconsistent? World J Orthop 2023; 14:589-597. [PMID: 37662663 PMCID: PMC10473911 DOI: 10.5312/wjo.v14.i8.589] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/28/2022] [Revised: 03/28/2023] [Accepted: 04/20/2023] [Indexed: 08/17/2023] Open
Abstract
Periprosthetic joint infection (PJI) is a rare but terrible complication in hip and knee arthroplasty, and the use of topical vancomycin powder (VP) has been investigated as a tool to potentially reduce its incidence. However, there remains no consensus on its efficacy. Therefore, the aim of this review is to provide an overview on the application of topical vancomycin in orthopaedic surgery focusing on the recent evidence and results in total joint arthroplasty. Several systematic reviews and meta-analyses on topical VP in hip and knee arthroplasty have been recently published reporting sometimes conflicting results. Apart from all being limited by the quality of the included studies (mostly level III and IV), confounding variables are often included potentially leading to biased conclusions. If taken into consideration the exclusive use of VP in isolation, the available data, although very limited, suggest that it does not reduce the infection rate in routine primary hip and knee arthroplasty. Therefore, we still cannot advise for a routinary application. A properly powered randomized-controlled trial would be necessary to clarify the role of VP in hip and knee arthroplasty. Based on the analysis of the current evidence, the use of topical VP appears to be safe when used locally in terms of systemic adverse reactions, hence, if proven to be effective, it could bring great benefits due to its low cost and accessibility.
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Affiliation(s)
- Fabio Mancino
- Department of Orthopaedics, Fiona Stanley Hospital, Perth 6150, Australia
| | - Piers J Yates
- Department of Orthopaedics, Fiona Stanley Hospital, Perth 6150, Australia
- Department of Orthopaedics, The Orthopaedic Research Foundation of Western Australia, Perth 6010, Australia
- Department of Orthopaedics, University of Western Australia, Perth 6009, Australia
| | - Benjamin Clark
- Department of Infectious Diseases, Fiona Stanley Hospital, Perth 6150, Australia
| | - Christopher W Jones
- Department of Orthopaedics, Fiona Stanley Hospital, Perth 6150, Australia
- Department of Orthopaedics, The Orthopaedic Research Foundation of Western Australia, Perth 6010, Australia
- Department of Orthopaedics, Curtin University, Perth 6102, Australia
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23
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Affiliation(s)
- Fabio Mancino
- Department of Trauma and Orthopaedic Surgery, University College Hospital, London, UK
- Princess Grace Hospital, London, UK
| | - Vanya Gant
- Department of Microbiology, University College Hospital, London, UK
| | - Dominic R M Meek
- Department of Trauma and Orthopaedic Surgery, Queen Elizabeth University Hospital, Glasgow, UK
| | - Fares S Haddad
- Princess Grace Hospital, London, UK
- University College London Hospitals NHS Foundation Trust, London, UK
- The Bone & Joint Journal , London, UK
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24
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Steadman W, Chapman PR, Schuetz M, Schmutz B, Trampuz A, Tetsworth K. Local Antibiotic Delivery Options in Prosthetic Joint Infection. Antibiotics (Basel) 2023; 12:752. [PMID: 37107114 PMCID: PMC10134995 DOI: 10.3390/antibiotics12040752] [Citation(s) in RCA: 35] [Impact Index Per Article: 17.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2023] [Revised: 04/03/2023] [Accepted: 04/07/2023] [Indexed: 04/29/2023] Open
Abstract
Prosthetic Joint Infection (PJI) causes significant morbidity and mortality for patients globally. Delivery of antibiotics to the site of infection has potential to improve the treatment outcomes and enhance biofilm eradication. These antibiotics can be delivered using an intra-articular catheter or combined with a carrier substance to enhance pharmacokinetic properties. Carrier options include non-resorbable polymethylmethacrylate (PMMA) bone cement and resorbable calcium sulphate, hydroxyapatite, bioactive glass, and hydrogels. PMMA allows for creation of structural spacers used in multi-stage revision procedures, however it requires subsequent removal and antibiotic compatibility and the levels delivered are variable. Calcium sulphate is the most researched resorbable carrier in PJI, but is associated with wound leakage and hypercalcaemia, and clinical evidence for its effectiveness remains at the early stage. Hydrogels provide a versatile combability with antibiotics and adjustable elution profiles, but clinical usage is currently limited. Novel anti-biofilm therapies include bacteriophages which have been used successfully in small case series.
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Affiliation(s)
- William Steadman
- Jamieson Trauma Institute, Royal Brisbane and Women’s Hospital, Herston, Brisbane 4029, Australia
- Department of Orthopaedics, Royal Brisbane and Women’s Hospital, Herston, Brisbane 4029, Australia
- Faculty of Health, Queensland University of Technology, Brisbane 4059, Australia
| | - Paul R. Chapman
- Jamieson Trauma Institute, Royal Brisbane and Women’s Hospital, Herston, Brisbane 4029, Australia
- Herston Infectious Disease Institute, Royal Brisbane and Women’s Hospital, Herston, Brisbane 4029, Australia
- Department of Infectious Diseases, Royal Brisbane and Women’s Hospital, Herston, Brisbane 4029, Australia
| | - Michael Schuetz
- Jamieson Trauma Institute, Royal Brisbane and Women’s Hospital, Herston, Brisbane 4029, Australia
- Department of Orthopaedics, Royal Brisbane and Women’s Hospital, Herston, Brisbane 4029, Australia
- Faculty of Health, Queensland University of Technology, Brisbane 4059, Australia
| | - Beat Schmutz
- Jamieson Trauma Institute, Royal Brisbane and Women’s Hospital, Herston, Brisbane 4029, Australia
- School of Mechanical, Medical and Process Engineering, Faculty of Engineering, Queensland University of Technology, Brisbane 4000, Australia
- Centre for Biomedical Technologies, Queensland University of Technology, Brisbane 4059, Australia
- Australian Research Council Training Centre for Multiscale 3D Imaging, Modelling, and Manufacturing, Queensland University of Technology, Brisbane 4059, Australia
| | - Andrej Trampuz
- Center for Musculoskeletal Surgery, Septic Unit Charité-Universitätsmedizin, 10117 Berlin, Germany
| | - Kevin Tetsworth
- Department of Orthopaedics, Royal Brisbane and Women’s Hospital, Herston, Brisbane 4029, Australia
- School of Medicine, University of Queensland, Brisbane 4029, Australia
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25
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Mu W, Ji B, Cao L. Single-stage revision for chronic periprosthetic joint infection after knee and hip arthroplasties: indications and treatments. ARTHROPLASTY 2023; 5:11. [PMID: 36864484 PMCID: PMC9979399 DOI: 10.1186/s42836-023-00168-5] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2022] [Accepted: 01/16/2023] [Indexed: 03/04/2023] Open
Abstract
Single-stage revision for chronic periprosthetic joint infection has been introduced 40 years ago. This option is gaining more and more attention as well as popularity. It is a reliable treatment for the chronic periprosthetic joint infection after knee and hip arthroplasties when implemented by an experienced multi-disciplinary team. However, its indications and corresponding treatments remain controversial. This review focused on the indications and specific treatments related to the option, with an attempt to help surgeons to use this method with more favorable outcomes.
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Affiliation(s)
- Wenbo Mu
- grid.412631.3Department of Orthopedics, the First Affiliated Hospital of Xinjiang Medical University, Urumqi, 830011 Xinjiang China ,grid.13394.3c0000 0004 1799 3993Department of Pharmacognosy, School of Pharmacy, Xinjiang Medical University, Urumqi, 830011 Xinjiang China
| | - Baochao Ji
- grid.412631.3Department of Orthopedics, the First Affiliated Hospital of Xinjiang Medical University, Urumqi, 830011 Xinjiang China
| | - Li Cao
- Department of Orthopedics, the First Affiliated Hospital of Xinjiang Medical University, Urumqi, 830011, Xinjiang, China.
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26
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Abuzaiter W, Bolton CA, Drakos A, Drakos P, Hallan A, Warchuk D, Woolfrey KGH, Woolfrey MR. Is Topical Vancomycin an Option? A Randomized Controlled Trial to Determine the Safety of the Topical Use of Vancomycin Powder in Preventing Postoperative Infections in Total Knee Arthroplasty, as Compared With Standard Postoperative Antibiotics. J Arthroplasty 2023:S0883-5403(23)00060-8. [PMID: 36736635 DOI: 10.1016/j.arth.2023.01.040] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/12/2022] [Revised: 01/22/2023] [Accepted: 01/23/2023] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND The demand for total knee arthroplasties (TKAs) is expected to rise in the coming decades, increasing the burden of periprosthetic joint infections (PJIs). The use of intrawound vancomycin powder (VP) has proven to be effective in reducing the incidence of PJIs after spinal surgery. That said, its effectiveness in TKA remains unclear. This trial aims to examine the efficacy of intrawound vancomycin powder first versus standard postoperative antibiotics in preventing PJIs after TKA. METHODS This study was a double-blinded, noninferiority, randomized controlled trial. All participants received standard preoperative intravenous (IV) antibiotics (Cefazolin/Vancomycin) within 60 minutes of skin incision. Patients in the treatment group received 1 gram of VP applied intraoperatively by the orthopedic surgeon (500 mg directly on the prosthesis, 500 mg above the closed joint capsule). These patients did not receive postoperative antibiotics. Patients in the control group received standard postoperative IV antibiotics. The primary outcome was the incidence of acute surgical site infection within 42 days of procedure. RESULTS There were 80 patients randomized to the treatment group and 85 patients randomized to the control. Groups were matched with respect to baseline characteristics, including average age (66 versus 64), BMI (35.7 versus 33.4), and diabetics (16 versus 13). The trial was halted at 1 year as a significantly greater proportion (P = .03) of patients in the treatment group (n = 3, 3.75%) were diagnosed with PJIs compared to the control (n = 0). CONCLUSION Our trial demonstrated the intrawound application of VP to be inferior to standard postoperative IV antibiotics in reducing the incidence of PJIs after TKA.
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Affiliation(s)
- Wesam Abuzaiter
- Brant Community Healthcare System, Pharmacy, Brantford, Canada; University of Waterloo, Pharmacy, Waterloo, Canada
| | - Caralee A Bolton
- Brant Community Healthcare System, Orthopaedics, Brantford, Canada
| | | | - Paul Drakos
- Department of Kinesiology, McMaster University, Hamilton, Canada
| | - Alam Hallan
- Brant Community Healthcare System, Pharmacy, Brantford, Canada; Hamilton Health Sciences, Pharmacy, Hamilton, Canada
| | - David Warchuk
- Brant Community Healthcare System, Orthopaedics, Brantford, Canada
| | - Karen G H Woolfrey
- Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ontario, Canada; Brant Community Healthcare System, Brantford, Canada
| | - Michael R Woolfrey
- Brant Community Healthcare System, Orthopaedics, Brantford, Canada; Division of Orthopaedic Surgery, McMaster University, Hamilton, Canada
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27
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Bourget-Murray J, Azad M, Gofton W, Abdelbary H, Garceau S, Grammatopoulos G. Is the routine use of local antibiotics in the management of periprosthetic joint infections justified? Hip Int 2023; 33:4-16. [PMID: 36447342 DOI: 10.1177/11207000221139467] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/05/2022]
Abstract
Periprosthetic joint infection (PJI) following total hip and total knee arthroplasty continues to be a leading cause of re-operation and revision arthroplasty. Not only is the treatment of PJI notoriously challenging, but success rates are variable. Regardless of the surgical strategy used, successful management of PJI requires a comprehensive surgical debridement focused at eradicating the underlying biofilm followed by appropriate antimicrobial therapy. Although systemic antimicrobial delivery continues to be a cornerstone in the treatment of PJI, many surgeons have started using local antibiotics to deliver higher concentrations of antibiotics directly into the vulnerable joint and adjacent soft tissues, which often have compromised vascularity. Available evidence on the use of topical powder, bone cement, and calcium sulphate carriers for local delivery of antibiotics during the initial treatment of PJI is limited to studies that are extremely heterogeneous. There is currently no level-1 evidence to support routinely using these products. Further, appropriately powered, prospective studies are needed to quantify the safety and efficacy of antibiotic-located calcium-sulphate carriers to justify their added costs. These products should not encourage surgeons to deviate from best practice guidelines, such as those recommended during the International Consensus Meeting on Musculoskeletal Infections.
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Affiliation(s)
| | - Marisa Azad
- Division of Infectious Diseases, Department of Medicine, Mayo Clinic, Rochester, MN, USA
| | - Wade Gofton
- Division of Orthopaedic Surgery, The Ottawa Hospital, Ottawa, Ontario, Canada
| | - Hesham Abdelbary
- Division of Orthopaedic Surgery, The Ottawa Hospital, Ottawa, Ontario, Canada
| | - Simon Garceau
- Division of Orthopaedic Surgery, The Ottawa Hospital, Ottawa, Ontario, Canada
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28
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Systematic Review and Meta-Analysis of Intrawound Vancomycin in Total Hip and Total Knee Arthroplasty: A Continued Call for a Prospective Randomized Trial. J Arthroplasty 2022; 37:1405-1415.e1. [PMID: 35314283 DOI: 10.1016/j.arth.2022.03.047] [Citation(s) in RCA: 26] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/18/2022] [Accepted: 03/12/2022] [Indexed: 02/02/2023] Open
Abstract
BACKGROUND Periprosthetic joint injection (PJI) is a rare, but life-altering complication of total joint arthroplasty (TJA). Though intrawound vancomycin powder (IVP) has been studied in other orthopedic subspecialties, its efficacy and safety in TJA has not been established. METHODS PubMed and MEDLINE databases were used to identify studies utilizing IVP in primary and revision total hip (THA) and knee arthroplasty (TKA). Postoperative PJI data were pooled using random effect models with results reported as odds ratios (ORs) and 95% confidence intervals (CIs). Studies were weighted by the inverse variance of their effect estimates. RESULTS Overall, 16 of the 1871 studies identified were pooled for final analysis, yielding 33,731 patients totally. Of these, 17 164 received IVP. In aggregate, patients who received IVP had a decreased rate of PJI (OR 0.46, P < .05). Separately, TKA and THA patients who received IVP had lower rates of PJI (OR 0.41, P < .05 and OR 0.45, P < .05, respectively). Aggregate analysis of primary TKA and THA patients also revealed a decreased PJI rate (OR 0.44, P < .05). Pooled revision TKA and THA patients had a similar decrease in PJI rates (OR 0.30, P < .05). Although no publication bias was appreciated, these findings are limited by the low-quality evidence available. CONCLUSION While IVP may reduce the risk of PJI in primary and revision TJA, its widespread use cannot be recommended until higher-quality data, such as that obtained from randomized control trials, are available. This study underscores the continued need for more rigorous studies before general adoption of this practice by arthroplasty surgeons.
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29
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Marston S, Mirick Mueller G, Sabin A, Hansen GT, Lindgren B, Aparicio C, Armstrong AR, Larsen OH, Schmidt A, Kyle R, Gustilo R, Tsukayama D, Bechtold J, Bue M. Systemic versus free antibiotic delivery in preventing acute exogenous implant related infection in a rat model. J Orthop Res 2022; 40:429-438. [PMID: 33913540 DOI: 10.1002/jor.25052] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/01/2020] [Revised: 12/15/2020] [Accepted: 04/12/2021] [Indexed: 02/04/2023]
Abstract
We studied systemic ceftriaxone, and free/local tobramycin and doxycycline in a controlled rat model representing a generic acute exogenous joint infection. We hypothesized that evidence of infection (quantitative colony forming units [CFU], qualitative scanning electron microscopy [SEM], histopathology) (1a) would be reduced with local versus systemic antibiotic, (1b) any antibiotic would be superior to control, (2) there would be a difference among antibiotics, and (3) antibiotic would not be detectable in serum at 4-week euthanasia. Study groups included infected and noninfected (1) control (no treatment), (2) systemic ceftriaxone (daily), (3) local tobramycin, and (4) local doxycycline (10 rats/group; power = 0.8). With IACUC approval, a reliable acute exogenous joint infection was created by slowly injecting 50-μl, 104 CFU Staphylococcus aureus, into the distal femoral medullary canal. The antibiotic formulation was introduced locally to the femoral canal and joint space. After 4 weeks, serum, pin, bone, and synovium were obtained. CFU/ml of bone and synovium were quantified using macrotiter method. SEM imaged biofilm on the surface of the pin, histopathology identified tissue response, liquid chromatography/mass spectrometry quantified plasma antibiotic. (1) Groups receiving any antibiotic reported lower CFU/ml in synovium compared with no treatment. (2) In the synovium, free/local tobramycin reduced CFU/ml to a greater extent than free/local doxycycline (p < 0.05). (3) Antibiotic in plasma after the local application was nondetectable in all groups after 4 weeks. SEM revealed no difference in biofilm on pin among all groups.
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Affiliation(s)
- Scott Marston
- University of Minnesota, Minneapolis, Minnesota, USA
| | | | - Arick Sabin
- Hennepin Healthcare Research Institute, Minneapolis, Minnesota, USA
| | - Glen T Hansen
- University of Minnesota, Minneapolis, Minnesota, USA.,Hennepin Healthcare Research Institute, Minneapolis, Minnesota, USA
| | | | | | | | - Ole H Larsen
- Department of Clinical Biochemistry, Aarhus University Hospital, Aarhus, Denmark
| | - Andrew Schmidt
- University of Minnesota, Minneapolis, Minnesota, USA.,Hennepin Healthcare Research Institute, Minneapolis, Minnesota, USA
| | - Richard Kyle
- University of Minnesota, Minneapolis, Minnesota, USA.,Hennepin Healthcare Research Institute, Minneapolis, Minnesota, USA
| | - Ramon Gustilo
- University of Minnesota, Minneapolis, Minnesota, USA.,Hennepin Healthcare Research Institute, Minneapolis, Minnesota, USA
| | - Dean Tsukayama
- University of Minnesota, Minneapolis, Minnesota, USA.,Hennepin Healthcare Research Institute, Minneapolis, Minnesota, USA
| | - Joan Bechtold
- University of Minnesota, Minneapolis, Minnesota, USA.,Hennepin Healthcare Research Institute, Minneapolis, Minnesota, USA
| | - Mats Bue
- Department of Orthopaedic Surgery, Aarhus University Hospital, Aarhus, Denmark.,Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
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Duan MY, Zhang HZ. Vancomycin lavage for the incidence of acute surgical site infection following primary total hip arthroplasty and total knee arthroplasty. World J Clin Cases 2022; 10:71-78. [PMID: 35071507 PMCID: PMC8727268 DOI: 10.12998/wjcc.v10.i1.71] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/10/2021] [Revised: 10/21/2021] [Accepted: 11/29/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Surgical site infection is a rare but serious complication associated with total joint arthroplasty (TJA). There are limited data on the effectiveness of intrawound irrigation with vancomycin solution (1000 mg/L; 2 L) before wound closure for preventing acute surgical site infection following primary total hip arthroplasty (THA) and total knee arthroplasty (TKA).
AIM To investigate the effectiveness of prophylactic intraoperative application of vancomycin (1000 mg/L; 2 L) solution vs. plain irrigation in reducing the incidence of acute surgical site infection following primary THA and TKA.
METHODS A retrospective review of 2725 consecutive patients undergoing THA or TKA from January 2012–December 2019 was performed. These patients received either intrawound irrigation with normal saline before wound closure between January 2012 and December 2015 (group 1, 1018 patients; 453 undergoing THA and 565 undergoing TKA) or intrawound irrigation with vancomycin solution (1000 mg/L) before wound closure between January 2016 and December 2019 (group 2, 1175 patients; 512 undergoing THA and 663 undergoing TKA). The outcomes were the incidences of postoperative surgical site infection and wound healing complications within 3 mo of primary TJA.
RESULTS There were no significant demographic differences between the 2 groups. There was a significantly higher incidence of acute infection at the surgical site in patients who received intrawound irrigation with normal saline before wound closure than in those who received intrawound irrigation with vancomycin solution (1000 mg/L; 2 L) before wound closure (overall incidence of infection: group 1, 2.46% vs group 2, 0.09%, P < 0.001). There was no significant difference in the incidence of wound healing complications between the two groups.
CONCLUSION Prophylactic irrigation with vancomycin solution (1000 mg/L; 2 L) significantly decreases the incidence of acute surgical site infection after primary TJA. This strategy is a safe, efficacious, and inexpensive method for reducing the incidence of acute surgical site infection after TJA.
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Affiliation(s)
- Ming-Yi Duan
- Department of Orthopedics, Joint Surgery and Sports Medicine, First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning Province, China
| | - Hang-Zhou Zhang
- Department of Orthopedics, Joint Surgery and Sports Medicine, First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning Province, China
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Vancomycin is effective in preventing Cutibacterium acnes growth in a mimetic shoulder arthroplasty. J Shoulder Elbow Surg 2022; 31:159-164. [PMID: 34352403 DOI: 10.1016/j.jse.2021.06.015] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/15/2021] [Revised: 06/19/2021] [Accepted: 06/28/2021] [Indexed: 02/01/2023]
Abstract
BACKGROUND Intra-incisional deposition of vancomycin powder is a strategy to limit Cutibacterium acnes infection after shoulder surgery. Unfortunately, limited research exists examining the effectiveness of vancomycin in a clinically relevant joint infection model. This basic science study investigated the efficacy of vancomycin administration as prophylaxis for C acnes growth in vitro using a mimetic shoulder arthroplasty. METHODS A new bioartificial shoulder joint mimetic implant (S-JIM) was used to investigate the effect of vancomycin powder on C acnes growth within the first 48 hours after surgery. The impact of vancomycin was assessed on a skin-derived (ATCC 11827) C acnes strain and a periprosthetic joint infection-derived strain. C acnes strains were applied to titanium alloy foil and embedded beneath multiple layers of collagen-impregnated cellulose scaffold strips containing human shoulder joint capsular fibroblasts, facilitating the development of an oxygen gradient with an anaerobic environment around the foil and inner layers. Ten milligrams of vancomycin powder was applied between the C acnes layer and the human cell-containing scaffold strips to model direct antibiotic application, and intravenous vancomycin prophylaxis was modeled by adding vancomycin in media at 5 or 20 μg/mL. After 48 hours, the C acnes inoculum layer was subcultured from each S-JIM onto agar plates to assess the formation of viable C acnes colonies. Primary human shoulder capsule cells were assessed microscopically to detect any detrimental effects of vancomycin on cellular integrity. RESULTS Agar plates inoculated with extracts from untreated S-JIMs consistently resulted in the growth of large numbers of C acnes colonies, whereas treatments with vancomycin powder or vancomycin in media at 20-μg/mL dilution effectively prevented the recovery of any C acnes colonies. The lowest vancomycin dilution tested (5 μg/mL) was insufficient to prevent the recovery of C acnes colonies. Vancomycin powder had no discernible short-term impact on shoulder capsule cell morphology, and the presence of these cells had no discernible impact on vancomycin degradation over time. CONCLUSIONS Vancomycin administration effectively prevented C acnes growth in a bioartificial S-JIM. These results support the hypothesis that intra-incisional vancomycin application may limit C acnes prosthetic joint infections.
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Lawrie CM, Kazarian GS, Barrack T, Nunley RM, Barrack RL. Intra-articular administration of vancomycin and tobramycin during primary cementless total knee arthroplasty : determination of intra-articular and serum elution profiles. Bone Joint J 2021; 103-B:1702-1708. [PMID: 34719272 DOI: 10.1302/0301-620x.103b11.bjj-2020-2453.r1] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
AIMS Intra-articular administration of antibiotics during primary total knee arthroplasty (TKA) may represent a safe, cost-effective strategy to reduce the risk of acute periprosthetic joint infection (PJI). Vancomycin with an aminoglycoside provides antimicrobial cover for most organisms isolated from acute PJI after TKA. However, the intra-articular doses required to achieve sustained therapeutic intra-articular levels while remaining below toxic serum levels is unknown. The purpose of this study is to determine the intra-articular and serum levels of vancomycin and tobramycin over the first 24 hours postoperatively after intra-articular administration in primary cementless TKA. METHODS A prospective cohort study was performed. Patients were excluded if they had poor renal function, known allergic reaction to vancomycin or tobramycin, received intravenous vancomycin, or were scheduled for same-day discharge. All patients received 600 mg tobramycin and 1 g of vancomycin powder suspended in 25 cc of normal saline and injected into the joint after closure of the arthrotomy. Serum from peripheral venous blood and drain fluid samples were collected at one, four, and 24 hours postoperatively. All concentrations are reported in µg per ml. RESULTS A total of 22 patients were included in final analysis. At one, four, and 24 hours postoperatively, mean (95% confidence interval (CI)) serum concentrations were 2.4 (0.7 to 4.1), 5.0 (3.1 to 6.9), and 4.8 (2.8 to 6.9) for vancomycin and 4.9 (3.4 to 6.3), 7.0 (5.8 to 8.2), and 1.3 (0.8 to 1.8) for tobramycin; intra-articular concentrations were 1,900.6 (1,492.5 to 2,308.8), 717.9 (485.5 to 950.3), and 162.2 (20.5 to 304.0) for vancomycin and 2,105.3 (1,389.9 to 2,820.6), 403.2 (266.6 to 539.7), and 98.8 (0 to 206.5) for tobramycin. CONCLUSION Intra-articular administration of 1 g of vancomycin and 600 mg of tobramycin as a solution after closure of the arthrotomy in primary cementless TKA achieves therapeutic intra-articular concentrations over the first 24 hours postoperatively and does not reach sustained toxic levels in peripheral blood. Cite this article: Bone Joint J 2021;103-B(11):1702-1708.
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Affiliation(s)
- Charles Murray Lawrie
- Miami Orthopedics and Sports Medicine Institute, Baptist Health South Florida, Miami, Florida, USA
| | - Gregory S Kazarian
- Department of Orthopedic Surgery, Hospital for Special Surgery, Weill-Cornell Medical School, New York, New York, USA
| | - Toby Barrack
- Department of Orthopedic Surgery, Washington University in Saint Louis School of Medicine, Saint Louis, Missouri, USA
| | - Ryan M Nunley
- Department of Orthopedic Surgery, Washington University in Saint Louis School of Medicine, Saint Louis, Missouri, USA
| | - Robert L Barrack
- Department of Orthopedic Surgery, Washington University in Saint Louis School of Medicine, Saint Louis, Missouri, USA
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Xi W, Hegde V, Zoller SD, Park HY, Hart CM, Kondo T, Hamad CD, Hu Y, Loftin AH, Johansen DO, Burke Z, Clarkson S, Ishmael C, Hori K, Mamouei Z, Okawa H, Nishimura I, Bernthal NM, Segura T. Point-of-care antimicrobial coating protects orthopaedic implants from bacterial challenge. Nat Commun 2021; 12:5473. [PMID: 34531396 PMCID: PMC8445967 DOI: 10.1038/s41467-021-25383-z] [Citation(s) in RCA: 41] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2021] [Accepted: 07/29/2021] [Indexed: 11/24/2022] Open
Abstract
Implant related infections are the most common cause of joint arthroplasty failure, requiring revision surgeries and a new implant, resulting in a cost of $8.6 billion annually. To address this problem, we created a class of coating technology that is applied in the operating room, in a procedure that takes less than 10 min, and can incorporate any desired antibiotic. Our coating technology uses an in situ coupling reaction of branched poly(ethylene glycol) and poly(allyl mercaptan) (PEG-PAM) polymers to generate an amphiphilic polymeric coating. We show in vivo efficacy in preventing implant infection in both post-arthroplasty infection and post-spinal surgery infection mouse models. Our technology displays efficacy with or without systemic antibiotics, the standard of care. Our coating technology is applied in a clinically relevant time frame, does not require modification of implant manufacturing process, and does not change the implant shelf life.
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Affiliation(s)
- Weixian Xi
- Department of Chemical and Biomolecular Engineering, University of California Los Angeles, Los Angeles, CA, United States
- Department of Orthopaedic Surgery, Orthopaedic Hospital Research Center, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, CA, United States
| | - Vishal Hegde
- Department of Orthopaedic Surgery, Orthopaedic Hospital Research Center, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, CA, United States
| | - Stephen D Zoller
- Department of Orthopaedic Surgery, Orthopaedic Hospital Research Center, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, CA, United States
| | - Howard Y Park
- Department of Orthopaedic Surgery, Orthopaedic Hospital Research Center, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, CA, United States
| | - Christopher M Hart
- Department of Orthopaedic Surgery, Orthopaedic Hospital Research Center, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, CA, United States
| | - Takeru Kondo
- Weintraub Center for Reconstructive Biotechnology, Division of Advanced Prosthodontics, University of California Los Angeles School of Dentistry, Los Angeles, CA, United States
| | - Christopher D Hamad
- Department of Orthopaedic Surgery, Orthopaedic Hospital Research Center, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, CA, United States
| | - Yan Hu
- Department of Orthopaedic Surgery, Orthopaedic Hospital Research Center, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, CA, United States
| | - Amanda H Loftin
- Department of Orthopaedic Surgery, Orthopaedic Hospital Research Center, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, CA, United States
| | - Daniel O Johansen
- Department of Orthopaedic Surgery, Orthopaedic Hospital Research Center, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, CA, United States
| | - Zachary Burke
- Department of Orthopaedic Surgery, Orthopaedic Hospital Research Center, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, CA, United States
| | - Samuel Clarkson
- Department of Orthopaedic Surgery, Orthopaedic Hospital Research Center, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, CA, United States
| | - Chad Ishmael
- Department of Orthopaedic Surgery, Orthopaedic Hospital Research Center, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, CA, United States
| | - Kellyn Hori
- Department of Orthopaedic Surgery, Orthopaedic Hospital Research Center, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, CA, United States
| | - Zeinab Mamouei
- Department of Orthopaedic Surgery, Orthopaedic Hospital Research Center, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, CA, United States
| | - Hiroko Okawa
- Weintraub Center for Reconstructive Biotechnology, Division of Advanced Prosthodontics, University of California Los Angeles School of Dentistry, Los Angeles, CA, United States
| | - Ichiro Nishimura
- Weintraub Center for Reconstructive Biotechnology, Division of Advanced Prosthodontics, University of California Los Angeles School of Dentistry, Los Angeles, CA, United States
| | - Nicholas M Bernthal
- Department of Orthopaedic Surgery, Orthopaedic Hospital Research Center, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, CA, United States.
| | - Tatiana Segura
- Department of Chemical and Biomolecular Engineering, University of California Los Angeles, Los Angeles, CA, United States.
- Department of Biomedical Engineering, Neurology, Dermatology, Duke University, Durham, NC, United States.
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Wong MT, Sridharan SS, Davison EM, Ng R, Desy NM. Can Topical Vancomycin Prevent Periprosthetic Joint Infection in Hip and Knee Arthroplasty? A Systematic Review. Clin Orthop Relat Res 2021; 479:1655-1664. [PMID: 33929342 PMCID: PMC8277283 DOI: 10.1097/corr.0000000000001777] [Citation(s) in RCA: 30] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/08/2021] [Accepted: 03/24/2021] [Indexed: 02/06/2023]
Abstract
BACKGROUND Periprosthetic joint infection (PJI) after hip and knee arthroplasty is a leading cause of revision surgery, inferior function, complications, and death. The administration of topical, intrawound vancomycin (vancomycin powder) has appeared promising in some studies, but others have found it ineffective in reducing infection risk; for that reason, a high-quality systematic review of the best-available evidence is needed. QUESTIONS/PURPOSES In this systematic review, we asked: (1) Does topical vancomycin (vancomycin powder) reduce PJI risk in hip and knee arthroplasty? (2) Does topical vancomycin lead to an increased risk of complications after hip and knee arthroplasty? METHODS A search of Embase, MEDLINE, and PubMed databases as of June 2020 was performed according to Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Studies comparing topical vancomycin in addition to standard infection prevention regimens (such as routine perioperative intravenous antibiotics) with standard regimens only in primary hip and knee arthroplasty were identified. Patients 18 years or older with a minimum follow-up of 3 months were included. No restrictions on maximal loss to follow-up or PJI definition were imposed. Studies were excluded if they included patients with a history of septic arthritis, used an antibiotic other than vancomycin or a different route of administration for the intervention, performed additional interventions that differed between groups, or omitted a control group. A total of 2408 studies were screened, resulting in nine eligible studies reviewing 3371 patients who received topical vancomycin (vancomycin powder) during a primary THA or TKA and 2884 patients who did not receive it. Groups were comparable with respect to duration of follow-up and loss to follow-up when reported. Study quality was assessed using the Newcastle-Ottawa scale, showing moderate-to-high quality for the included studies. The risks of PJI and overall complications in the topical vancomycin group were compared with those in the control group. RESULTS One of nine studies found a lower risk of PJI after primary THA or TKA, while eight did not, with odds ratios that broadly bracketed the line of no difference (range of odds ratios across the nine studies 0.09 to 1.97). In the six studies where overall complications could be compared between topical vancomycin and control groups in primary THA or TKA, there was no difference in overall complication risks with vancomycin (range of ORs across the six studies 0.48 to 0.94); however, we caution that these studies were underpowered to detect differences in the types of uncommon complications associated with vancomycin use (such as allergy, ototoxicity, and nephrotoxicity). CONCLUSION In the absence of clear evidence of efficacy, and without a sufficiently large evidence base reporting on safety-related endpoints, topical vancomycin (vancomycin powder) should not be used in routine primary THA and TKA. Adequately powered, multicenter, prospective trials demonstrating clear reductions in infection risk and large registry-driven audits of safety-related endpoints are required before the widespread use of topical vancomycin can be recommended. LEVEL OF EVIDENCE Level III, therapeutic study.
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Affiliation(s)
| | | | | | - Richard Ng
- University of Calgary, Calgary, AB, Canada
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Buchalter DB, Teo GM, Kirby DJ, Schwarzkopf R, Aggarwal VK, Long WJ. Does the Organism Profile of Periprosthetic Joint Infections Change With a Topical Vancomycin Powder and Dilute Povidone-Iodine Lavage Protocol? J Arthroplasty 2021; 36:S314-S319. [PMID: 33526397 DOI: 10.1016/j.arth.2020.12.036] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/19/2020] [Revised: 12/14/2020] [Accepted: 12/22/2020] [Indexed: 02/02/2023] Open
Abstract
BACKGROUND While vancomycin powder and dilute povidone-iodine (VIP) is associated with fewer total joint arthroplasty (TJA) periprosthetic joint infections (PJI), its effect on PJI organism profiles is unclear. This study evaluates primary TJA PJI organism profiles before and after the implementation of a VIP protocol. METHODS In total, 18,299 primary TJAs performed at a university-affiliated, not-for-profit orthopedic hospital from before (1/2012-12/2013) and after (1/2016-12/2019) a VIP protocol was initiated were reviewed to identify deep PJIs that occurred within 90 days of the index arthroplasty as defined by the Musculoskeletal Infection Society guidelines. Demographics, overall organism incidence (n/TJAs), and relative organism incidence (n/PJIs) from the two cohorts were compared. RESULTS In total, 103 TJA PJIs were identified (pre-VIP: 32/3982; VIP: 71/14,317). Following the introduction of VIP, the overall and relative incidence of coagulase-negative staphylococcal TJA PJIs significantly decreased (overall: 0.20% to 0.04%, P = .004; relative: 25.00% to 8.45%, P = .031). In response, the relative incidence of MSSA TJA PJIs significantly increased (18.75% to 40.85%, P = .042). Broken down by arthroplasty type, VIP was associated with a significantly lower overall incidence of coagulase-negative staphylococcal total knee arthroplasty (TKA) PJIs (0.27% to 0.06%, P = .015), a significantly lower overall incidence of MRSA TKA PJIs (0.18% to 0.03%, P = .031), and a nonsignificant decrease in the overall incidence of gram-negative TKA PJIs (0.18% to 0.04%, P = .059). No organism profile changes were found in total hip arthroplasty PJIs. CONCLUSION VIP is not associated with more difficult to treat primary TJA PJIs. While promising, these findings require a prospective randomized controlled trial for confirmation. LEVEL OF EVIDENCE Level III, Retrospective cohort study.
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Affiliation(s)
| | - Greg M Teo
- Department of Orthopedic Surgery, NYU Langone Health, New York, NY
| | - David J Kirby
- Department of Orthopedic Surgery, NYU Langone Health, New York, NY
| | - Ran Schwarzkopf
- Department of Orthopedic Surgery, NYU Langone Health, New York, NY
| | - Vinay K Aggarwal
- Department of Orthopedic Surgery, NYU Langone Health, New York, NY
| | - William J Long
- Department of Orthopedic Surgery, NYU Langone Health, New York, NY
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Mu W, Xu B, Guo W, Ji B, Wahafu T, Cao L. Outcome of Irrigation and Debridement With Topical Antibiotics Delivery for the Management of Periprosthetic Joint Infection Occurring Within 3 Months Since the Primary Total Joint Arthroplasty. J Arthroplasty 2021; 36:1765-1771. [PMID: 33358609 DOI: 10.1016/j.arth.2020.11.033] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/17/2020] [Revised: 11/21/2020] [Accepted: 11/23/2020] [Indexed: 02/02/2023] Open
Abstract
BACKGROUND Irrigation and debridement with modular component exchange is appealing for surgeons to treat early-stage periprosthetic joint infection (PJI). However, the indication, perioperative protocol, and success rate remain controversial. This study is the first one to present results of debridement, antibiotics, and implant retention (DAIR) with integrated MIT (modular component exchange, povidone-iodine and topical antibiotics delivery) protocol for treating PJI occurring within 3 months since the primary total joint arthroplasty. METHODS We retrospectively analyzed patients who received DAIR with MIT protocol in our department between January 2011 and May 2018. Topical antibiotics were delivered in all cases. Topical antibiotics infusion was applied for those infected with multidrug-resistant bacteria, fungus, polymicrobial infection, and culture negative one. Failure was defined as additional surgical intervention for infection after DAIR; persistent sinus tract, drainage or excessive joint pain; need for suppressive antibiotics therapy due to the infection; infection relapse with the same pathogen; reinfection with different microorganism; and infection-related death. RESULTS A total of 73 patients with a mean age of 63.30 ± 10.97 years were included in this study, including 43 men and 30 women. There are 41 knees and 32 hips. Thirty patients had sinus tract. With a mean follow-up of 63.79 ± 18.57 months, there were 9 failures in total with an overall success rate of 87.67%. The success rate was 88.57% and 86.84% for those receiving topical antibiotics infusion postoperatively and those without. CONCLUSIONS DAIR with a standard MIT protocol is a viable and safe option for PJI occurring within 3 months since the primary total joint arthroplasty. LEVEL OF EVIDENCE Level 4, therapeutic study.
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Affiliation(s)
- Wenbo Mu
- Department of Orthopaedics, First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, China
| | - Boyong Xu
- Department of Orthopaedics, First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, China
| | - Wentao Guo
- Department of Orthopaedics, First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, China
| | - Baochao Ji
- Department of Orthopaedics, First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, China
| | - Tuerhongjiang Wahafu
- Department of Orthopaedics, First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, China
| | - Li Cao
- Department of Orthopaedics, First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, China
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Ushirozako H, Hasegawa T, Yamato Y, Yoshida G, Yasuda T, Banno T, Arima H, Oe S, Mihara Y, Yamada T, Ide K, Watanabe Y, Nakai K, Imada T, Matsuyama Y. Impact of intrawound vancomycin powder on prevention of surgical site infection after posterior spinal surgery. J Neurosurg Spine 2021; 34:656-664. [PMID: 34874533 DOI: 10.3171/2020.8.spine20992] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2020] [Accepted: 08/17/2020] [Indexed: 11/06/2022]
Abstract
OBJECTIVE Surgical site infection (SSI) after posterior spinal surgery is one of the severe complications that may occur despite administration of prophylactic antibiotics and the use of intraoperative aseptic precautions. The use of intrawound vancomycin powder for SSI prevention is still controversial, with a lack of high-quality and large-scale studies. The purpose of this retrospective study using a propensity score-matched analysis was to clarify whether intrawound vancomycin powder prevents SSI occurrence after spinal surgery. METHODS The authors analyzed 1261 adult patients who underwent posterior spinal surgery between 2010 and 2018 (mean age 62.3 years; 506 men, 755 women; follow-up period at least 1 year). Baseline and surgical data were assessed. After a preliminary analysis, a propensity score model was established with adjustments for age, sex, type of disease, and previously reported risk factors for SSI. The SSI rates were compared between patients with intrawound vancomycin powder treatment (vancomycin group) and those without (control group). RESULTS In a preliminary analysis of 1261 unmatched patients (623 patients in the vancomycin group and 638 patients in the control group), there were significant differences between the groups in age (p = 0.041), body mass index (p = 0.013), American Society of Anesthesiologists classification (p < 0.001), malnutrition (p = 0.001), revision status (p < 0.001), use of steroids (p = 0.019), use of anticoagulation (p = 0.033), length of surgery (p = 0.003), estimated blood loss (p < 0.001), and use of instrumentation (p < 0.001). There was no significant difference in SSI rates between the vancomycin and control groups (21 SSIs [3.4%] vs 33 SSIs [5.2%]; OR 0.640, 95% CI 0.368-1.111; p = 0.114). Using a one-to-one propensity score-matched analysis, 444 pairs of patients from the vancomycin and control groups were selected. There was no significant difference in the baseline and surgical data, except for height (p = 0.046), between both groups. The C-statistic for the propensity score model was 0.702. In the score-matched analysis, 12 (2.7%) and 24 (5.4%) patients in the vancomycin and control groups, respectively, developed SSIs (OR 0.486, 95% CI 0.243-0.972; p = 0.041). There were no systemic complications related to the use of vancomycin. CONCLUSIONS The current study showed that intrawound vancomycin powder was useful in reducing the risk of SSI after posterior spinal surgery by half, without adverse events. Intrawound vancomycin powder use is a safe and effective procedure for SSI prevention.
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Affiliation(s)
| | | | - Yu Yamato
- 2Department of Orthopedic Surgery and Division of Geriatric Musculoskeletal Health, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka
| | | | - Tatsuya Yasuda
- 3Department of Orthopaedic Surgery, Iwata City Hospital, Iwata, Shizuoka; and
| | | | | | - Shin Oe
- 2Department of Orthopedic Surgery and Division of Geriatric Musculoskeletal Health, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka
| | | | | | | | | | | | - Takaaki Imada
- 4Department of Orthopaedic Surgery, Omaezaki Municipal Hospital, Omaezaki, Shizuoka, Japan
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Kurmis AP. Eradicating Fungal Periprosthetic TKA "Super-infection": Review of the Contemporary Literature and Consideration of Antibiotic-Impregnated Dissolving Calcium Sulfate Beads as a Novel PJI Treatment Adjunct. Arthroplast Today 2021; 8:163-170. [PMID: 33855143 PMCID: PMC8024748 DOI: 10.1016/j.artd.2021.02.009] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/13/2020] [Revised: 02/07/2021] [Accepted: 02/10/2021] [Indexed: 12/17/2022] Open
Abstract
Fungal periprosthetic joint infections are an uncommon but potentially devastating complication of arthroplasty surgery. The concurrent presence of a coexistent bacterial pathogen—a so called “super-infection”—adds further complexity. With delays to definitive diagnosis and a large number of procedures before cure, the associated physical and psychological morbidity is considerable. Beyond this, the economic and resource burden can be substantial. This case report presents the successful rapid treatment of an atypical bacterial and fungal periprosthetic super-infection with two-stage revision surgery augmented with a commercially available dissolving calcium sulfate bead system permitting targeted local antifungal elution. While not the panacea for treatment, these beads provide another potentially useful tool in the atypical pathogen eradication armamentarium. Much research is still indicated to define the optimal care pathway for fungal periprosthetic super-infections.
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Affiliation(s)
- Andrew P. Kurmis
- Discipline of Medical Specialties, University of Adelaide, Adelaide, South Australia, Australia
- Department of Orthopaedic Surgery, Lyell McEwin Hospital, Elizabeth Vale, South Australia, Australia
- Corresponding author. Haydown Road, Elizabeth Vale, South Australia, 5112. Australia. Tel.: +61 8 8182 9000.
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Elution Kinetics from Antibiotic-Loaded Calcium Sulfate Beads, Antibiotic-Loaded Polymethacrylate Spacers, and a Powdered Antibiotic Bolus for Surgical Site Infections in a Novel In Vitro Draining Knee Model. Antibiotics (Basel) 2021; 10:antibiotics10030270. [PMID: 33800299 PMCID: PMC8000420 DOI: 10.3390/antibiotics10030270] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2021] [Revised: 03/02/2021] [Accepted: 03/03/2021] [Indexed: 11/17/2022] Open
Abstract
Antibiotic-tolerant bacterial biofilms are notorious in causing PJI. Antibiotic loaded calcium sulfate bead (CSB) bone void fillers and PMMA cement and powdered vancomycin (VP) have been used to achieve high local antibiotic concentrations; however, the effect of drainage on concentration is poorly understood. We designed an in vitro flow reactor which provides post-surgical drainage rates after knee revision surgery to determine antibiotic concentration profiles. Tobramycin and vancomycin concentrations were determined using LCMS, zones of inhibition confirmed potency and the area under the concentration-time curve (AUC) at various time points was used to compare applications. Concentrations of antibiotcs from the PMMA and CSB initially increased then decreased before increasing after 2 to 3 h, correlating with decreased drainage, demonstrating that concentration was controlled by both release and flow rates. VP achieved the greatest AUC after 2 h, but rapidly dropped below inhibitory levels. CSB combined with PMMA achieved the greatest AUC after 2 h. The combination of PMMA and CSB may present an effective combination for killing biofilm bacteria; however, cytotoxicity and appropriate antibiotic stewardship should be considered. The model may be useful in comparing antibiotic concentration profiles when varying fluid exchange is important. However, further studies are required to assess its utility for predicting clinical efficacy.
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Röhner E, Zippelius T, Böhle S, Rohe S, Matziolis G, Jacob B. Vancomycin is toxic to human chondrocytes in vitro. Arch Orthop Trauma Surg 2021; 141:375-381. [PMID: 32236713 DOI: 10.1007/s00402-020-03431-5] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/05/2019] [Indexed: 11/26/2022]
Abstract
INTRODUCTION Vancomycin powder (VP) is a well-established topical antibiotic used in spinal surgery to prevent surgical site infections. More recently its extension to hip and knee arthroplasty was introduced. The aim of this study was to examine toxic effects of VP on the viability of human chondrocytes. Our hypothesis was that VP damages human chondrocytes in vitro with increasing concentration and length of exposure. MATERIAL AND METHODS Primary human chondrocytes were isolated and cultured from donated human knee joints. VP was added to these cultures with increasing concentrations (0-50 mg/ml) and length of exposure (0-336 h). Toxicity and viability were analyzed using LDH und XTT Elisa assays. Cell structure and determination of vital versus dead cells were visualized using light microscopy and fluorescence microscopy. RESULTS Light microscopy and fluorescence microscopy visualized defect cell structures and cell death proportional to increasing dose and length of exposure to VP. The analysis of LDH activity data showed toxic effects on chondrocytes as early as 2,5 min after exposure to VP. XTT activity data revealed a significant toxic threshold of a VP concentration above 12.5 mg/ml. CONCLUSIONS These results show that exposure to high VP concentrations yields to a damage of human chondrocytes in vitro. Chondrotoxicity is an immediate effect that is proportional to VP concentration. Therefore, the intraarticular use of high concentrations of vancomycin powder in the presence of native cartilage tissue must be considered critically.
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Affiliation(s)
- Eric Röhner
- Department of Orthopedics, Jena University Hospital, Campus Eisenberg, Klosterlausnitzer Straße 81, 07607, Eisenberg, Germany.
| | - Timo Zippelius
- Department of Orthopedics, Jena University Hospital, Campus Eisenberg, Klosterlausnitzer Straße 81, 07607, Eisenberg, Germany
| | - Sabrina Böhle
- Department of Orthopedics, Jena University Hospital, Campus Eisenberg, Klosterlausnitzer Straße 81, 07607, Eisenberg, Germany
| | - Sebastion Rohe
- Department of Orthopedics, Jena University Hospital, Campus Eisenberg, Klosterlausnitzer Straße 81, 07607, Eisenberg, Germany
| | - Georg Matziolis
- Department of Orthopedics, Jena University Hospital, Campus Eisenberg, Klosterlausnitzer Straße 81, 07607, Eisenberg, Germany
| | - Benjamin Jacob
- Department of Orthopedics, Jena University Hospital, Campus Eisenberg, Klosterlausnitzer Straße 81, 07607, Eisenberg, Germany
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Systemic Absorption and Nephrotoxicity Associated With Topical Vancomycin Powder for Fracture Surgery. J Orthop Trauma 2021; 35:29-34. [PMID: 32569068 DOI: 10.1097/bot.0000000000001866] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 06/10/2020] [Indexed: 02/02/2023]
Abstract
OBJECTIVES To determine whether using topical vancomycin powder in fracture surgery may result in low levels of vancomycin in the serum and not result in nephrotoxicity. DESIGN Prospective observational at a single site as a substudy of the VANCO trial. SETTING Single, large urban level I trauma center. PATIENTS/PARTICIPANTS Fifty-eight patients with tibial plateau and pilon fractures randomized to the treatment arm at the principal investigator's site. INTERVENTION Topical vancomycin powder (1000 mg) applied directly in the wound over all metal implants at the time of wound closure. MAIN OUTCOME MEASUREMENTS Serum vancomycin levels at 1 hour and 6-8 hours after surgery. Secondary outcomes included serum creatinine before surgery, a day after surgery, and at 2 weeks postoperatively and complete blood count at 2 weeks postoperatively. RESULTS Except in 2 patients who also received intravenous vancomycin, none of the study patients had detectable (>5 µg/mL) serum vancomycin levels at 1 hour and 6-8 hours after surgery. One patient with a history of elevation of serum creatinine had a minor increase of serum creatinine but had undetectable vancomycin levels. None of the other patients had a clinically significant increase in creatinine levels. CONCLUSIONS Despite its relatively widespread usage, little data exist regarding the systemic levels and nephrotoxicity associated with the topical use of vancomycin powder in orthopaedic fracture surgery. These prospective data indicate that there seems to be little clinical concern regarding toxicity associated with systemic absorption of vancomycin powder in this specific clinical application. LEVEL OF EVIDENCE Therapeutic Level IV. See instructions for authors for a complete description of levels of evidence.
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Budge MD, Koch JA, Mandell JB, Cappellini AJ, Orr S, Patel S, Ma D, Nourie O, Brothers KM, Urish KL. The In Vitro Efficacy of Doxycycline over Vancomycin and Penicillin in the Elimination of Cutibacterium Acnes Biofilm. ANTIMICROBIAL COMBINATION DEVICES 2020; STP1630:53-64. [PMID: 35529525 PMCID: PMC9070841 DOI: 10.1520/stp163020200019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/14/2023]
Abstract
Cutibacterium acnes (formerly Propionibacterium acnes) is a significant pathogen in periprosthetic joint infections (PJIs) in total shoulder arthroplasty. Poor outcomes seen in PJIs are due to the established C. acnes bacterial biofilms. The prolonged nature of C. acnes infections makes them difficult to treat with antibiotics. The goal of this study was to determine the relative efficacy of vancomycin compared with penicillin and doxycycline against planktonic and mature biofilms. Clinical isolates from PJI patients as well as a laboratory strain of C. acnes were tested. Planktonic minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs) were obtained using modified clinical laboratory standard index assays. Biofilm MICs and MBCs were also obtained. The MIC was determined for both using the PrestoBlue viability stain. The MBC was determined using differential reinforced clostridial medium agar plates for colony-forming unit analysis. Using the PrestoBlue viability reagent, the planktonic MIC values for vancomycin were significantly higher than doxycycline. Across 10 strains of C. acnes, all three antibiotics had decreased efficacy when comparing planktonic and biofilm cultures. Although effective antibiotic doses ranged from 1 to 1,000 μg/mL, only doxycycline achieved inhibitory and bactericidal concentrations in all tested strains. Penicillin failed to achieve the minimum biofilm inhibitory concentration (MBIC) in 60% of tested strains, whereas vancomycin failed in 80% of tested strains. Penicillin, doxycycline, and vancomycin have similar abilities in inhibiting C. acnes growth planktonically. The MBIC for doxycycline was within the clinical dosing range, suggesting C. acnes biofilm offers minimal tolerance to these antibiotics. The MBIC for penicillin was within clinical dosing ranges in only 60% of trials, suggesting the relative tolerance of C. acnes to penicillin. The minimum biofilm bactericidal concentration (MBBC) of doxycycline showed efficacy in 90% of trials, whereas penicillin and vancomycin achieved MBBC in 15% of samples.
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Affiliation(s)
- Matthew D Budge
- NW Perrnanente, 5125 Skyline Rd. S., Salem, OR 97306-9427, USA
| | - John A Koch
- NW Perrnanente, 5125 Skyline Rd. S., Salem, OR 97306-9427, USA
- Arthritis and Arthroplasty Design Group, Dept. of Orthopaedic Surgery, 100 Technology Dr., Pittsburgh, PA 15219, USA
| | - Jonathan B Mandell
- Arthritis and Arthroplasty Design Group, Dept. of Orthopaedic Surgery, 100 Technology Dr., Pittsburgh, PA 15219, USA
| | - Alex J Cappellini
- Arthritis and Arthroplasty Design Group, Dept. of Orthopaedic Surgery, 100 Technology Dr., Pittsburgh, PA 15219, USA
| | - Sara Orr
- Arthritis and Arthroplasty Design Group, Dept. of Orthopaedic Surgery, 100 Technology Dr., Pittsburgh, PA 15219, USA
| | - Samik Patel
- Arthritis and Arthroplasty Design Group, Dept. of Orthopaedic Surgery, 100 Technology Dr., Pittsburgh, PA 15219, USA
| | - Dongzhu Ma
- Arthritis and Arthroplasty Design Group, Dept. of Orthopaedic Surgery, 100 Technology Dr., Pittsburgh, PA 15219, USA
| | - Olivia Nourie
- NW Perrnanente, 5125 Skyline Rd. S., Salem, OR 97306-9427, USA
| | - Kimberly M Brothers
- Arthritis and Arthroplasty Design Group, Dept. of Orthopaedic Surgery, 100 Technology Dr., Pittsburgh, PA 15219, USA
| | - Kenneth L Urish
- Arthritis and Arthroplasty Design Group, The Bone and Joint Center, MageeWomens Hospital of the University of Pittsburgh Medical Center, 300 Halket St., Pittsburgh, PA 15213, USA; and Dept. of Orthopaedic Surgery, Dept. of Bioengineering, and Clinical and Translational Science Institute, University of Pittsburgh, 100 Technology Dr., Pittsburgh, PA 15219, USA
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Xu H, Yang J, Xie J, Huang Z, Huang Q, Cao G, Pei F. Efficacy and safety of intrawound vancomycin in primary hip and knee arthroplasty. Bone Joint Res 2020; 9:778-788. [PMID: 33135425 PMCID: PMC7649508 DOI: 10.1302/2046-3758.911.bjr-2020-0190.r2] [Citation(s) in RCA: 28] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/05/2023] Open
Abstract
Aims The efficacy and safety of intrawound vancomycin for preventing surgical site infection in primary hip and knee arthroplasty is uncertain. Methods A systematic review of the literature was conducted, indexed from inception to March 2020 in PubMed, Web of Science, Cochrane Library, Embase, and Google Scholar databases. All studies evaluating the efficacy and/or safety of intrawound vancomycin in patients who underwent primary hip and knee arthroplasty were included. Incidence of periprosthetic joint infection (PJI), superficial infection, aseptic wound complications, acute kidney injury, anaphylactic reaction, and ototoxicity were meta-analyzed. Results were reported as odds ratios (ORs) and 95% confidence intervals (CIs). The quality of included studies was assessed using the risk of bias in non-randomized studies of interventions (ROBINS-I) assessment tool. Results Nine studies involving 4,607 patients were included. Intrawound vancomycin was associated with lower incidence of PJI (30 patients (1.20%) vs 58 control patients (2.75%); OR 0.44, 95% CI 0.28 to 0.69) and simultaneous acute kidney injury (four patients (0.28%) vs four control patients (0.35%), OR 0.71, 95% CI 0.19 to 2.55). However, it did not reduce risk of superficial infection (four patients (0.67%) vs six control patients (1.60%), OR 0.60, 95% CI 0.17 to 2.12) and was associated with higher incidence of aseptic wound complications (23 patients (2.15%) vs eight in control patients (0.96%), OR 2.39, 95% CI 1.09 to 5.23). Four studies reported no anaphylactic reactions and three studies reported no ototoxicity in any patient group. Conclusion The current literature suggests that intrawound vancomycin used in primary hip and knee arthroplasty may reduce incidence of PJI, but it may also increase risk of aseptic wound complications. Cite this article: Bone Joint Res 2020;9(11):778–788.
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Affiliation(s)
- Hong Xu
- Department of Orthopaedic Surgery and National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, China
| | - Jingli Yang
- College of Earth and Environmental Sciences, and School of Public Health, Lanzhou University, Lanzhou, China
| | - Jinwei Xie
- Department of Orthopaedic Surgery and National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, China
| | - Zeyu Huang
- Department of Orthopaedic Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Qiang Huang
- Department of Orthopaedic Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Guorui Cao
- Department of Orthopaedic Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Fuxing Pei
- Department of Orthopaedic Surgery, West China Hospital, Sichuan University, Chengdu, China
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Xiao M, Leonardi EA, Sharpe O, Sherman SL, Safran MR, Robinson WH, Abrams GD. Soaking of Autologous Tendon Grafts in Vancomycin Before Implantation Does Not Lead to Tenocyte Cytotoxicity. Am J Sports Med 2020; 48:3081-3086. [PMID: 32898431 DOI: 10.1177/0363546520951815] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
BACKGROUND Surgical site infections (SSIs) after anterior cruciate ligament (ACL) reconstruction procedures are an unfortunate complication. Soaking grafts in vancomycin before implantation has been reported to reduce the incidence of postoperative SSI after ACL reconstruction. There is potential for vancomycin to compromise graft integrity because of tenocyte toxicity. PURPOSE To examine the in vitro toxicity of varying doses of vancomycin on human tenocytes. STUDY DESIGN Controlled laboratory study. METHODS Human patellar tenocytes were isolated and expanded in vitro. Tenocytes in culture were exposed to vancomycin at 5 different concentrations (400, 1600, 3200, 6400, and 12,800 μg/mL) and 3 time intervals (2, 6, and 24 hours). The control for all series was tenocyte exposure to only culture medium for each time interval. After treatment, a 10% Cell Counting Kit-8 solution in cellular growth medium was applied to the cells to examine cytotoxicity. A live/dead assay was used to assess tenocyte viability through fluorescence microscopy and flow cytometry. Results were analyzed statistically using multivariable logistic regression models with Tukey honest significant difference post hoc tests. RESULTS Vancomycin did not cause significant changes in tenocyte viability after 2 and 6 hours of incubation at any concentration between 0 and 12,800 µg/mL. Incubation with vancomycin for 24 hours led to a significant decrease in cell viability at higher concentrations. CONCLUSION Tenocytes derived from human patellar tendons exposed to relatively high concentrations of vancomycin for short periods of time do not demonstrate significant cell death and toxicity. CLINICAL RELEVANCE Exposing tendons to vancomycin for a short period of time, such as before ACL reconstruction, is not likely to cause tenocyte toxicity because of vancomycin administration.
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Affiliation(s)
- Michelle Xiao
- Department of Orthopaedic Surgery, Stanford University School of Medicine, Palo Alto, California, USA
| | - Erika A Leonardi
- Department of Orthopaedic Surgery, Stanford University School of Medicine, Palo Alto, California, USA
| | - Orr Sharpe
- Veterans Administration Palo Alto Health Care System, Palo Alto, California, USA
| | - Seth L Sherman
- Department of Orthopaedic Surgery, Stanford University School of Medicine, Palo Alto, California, USA
| | - Marc R Safran
- Department of Orthopaedic Surgery, Stanford University School of Medicine, Palo Alto, California, USA
| | - William H Robinson
- Veterans Administration Palo Alto Health Care System, Palo Alto, California, USA.,Department of Medicine, Division of Rheumatology, Stanford University School of Medicine, Palo Alto, California, USA
| | - Geoffrey D Abrams
- Department of Orthopaedic Surgery, Stanford University School of Medicine, Palo Alto, California, USA
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Erken HY, Nusran G, Karagüven D, Yilmaz O, Kuru T. No Decrease in Infection Rate with the Use of Local Vancomycin Powder After Partial Hip Replacement in Elderly Patients with Comorbidities. Cureus 2020; 12:e10296. [PMID: 33047086 PMCID: PMC7540078 DOI: 10.7759/cureus.10296] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023] Open
Abstract
Introduction The goal of this study was to evaluate the effects of local intra-wound vancomycin powder (VP) administration to decrease surgical site infections (SSIs), particularly in elderly patients with comorbidities, after having undergone partial hip replacement in the treatment of intertrochanteric (ITF) or femoral neck fractures (FNF). Methods We retrospectively reviewed patients who underwent partial hip replacement in the treatment of ITF or FNF in one year. We divided the patients into two groups. The non vancomycin-treated group received standard systemic prophylaxis only (1 gr cefazolin IV), while the vancomycin-treated group received 1 gr of VP in the surgical wound just before surgical closure in addition to the systemic prophylaxis. We included patients of 64 years or older who also had one or more comorbidities. We compared the post-operative SSI rates between the non vancomycin-treated group and the vancomycin-treated group. Results A total of 93 patients were included in the study. We detected post-operative wound infection in six patients (6.4%). The rate of SSI was found to be 5.7% in the vancomycin-treated group and 6.9% in the non vancomycin-treated group respectively, which showed no statistically significant difference (p:0.498). The incidence of SSI was statistically higher in the patients who had a follow-up in the post-operative intensive care unit than the patients who had not any follow-up in the intensive care unit. Conclusion Local application of VP in the surgical wound was found to be ineffective in reducing the incidence of SSI after partial hip replacement in elderly patients with comorbidities.
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Affiliation(s)
- H Yener Erken
- Orthopaedics and Traumatology, Canakkale Onsekiz Mart University, Canakkale, TUR
| | - Gurdal Nusran
- Orthopaedics and Traumatology, Canakkale Onsekiz Mart University, Canakkale, TUR
| | | | - Onur Yilmaz
- Orthopaedics and Traumatology, Canakkale Onsekiz Mart University, Canakkale, TUR
| | - Tolgahan Kuru
- Orthopaedics and Traumatology, Canakkale Onsekiz Mart University, Canakkale, TUR
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Intraarticular vancomycin powder is effective in preventing infections following total hip and knee arthroplasty. Sci Rep 2020; 10:13053. [PMID: 32747743 PMCID: PMC7400548 DOI: 10.1038/s41598-020-69958-0] [Citation(s) in RCA: 32] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2019] [Accepted: 07/09/2020] [Indexed: 11/08/2022] Open
Abstract
Locally applied vancomycin is increasingly being used in primary hip and knee arthroplasty to reduce the risk of infection. Despite encouraging initial results, considerable debate remains on the basis of the data currently available. In particular, it has been unclear up to now whether local vancomycin is suitable to further reduce the risk of infection even if the rate of infection is already low (< 1%). In this monocentric retrospective cohort study, all primary total hip and knee arthroplasties performed between 2013 and 2018 were included. After a change in procedure at the hospital, 1 g vancomycin powder was applied intraarticularly before wound closure. The remaining perioperative procedure was constant over the investigation period. The follow-up was one year. The presence of an infection according to the currently valid MSIS criteria was defined as the endpoint. In patients with TKA two infections (0.3%) were observed under vancomycin prophylaxis in contrast to 44 infections (1.3%) in the control group (p = 0.033). In patients with THA two infections (0.5%) were observed under vancomycin prophylaxis and 48 infections (1.1%) in the control group without local vancomycin but this difference was statistically not significant. No wound complications requiring revision were observed as a result of the vancomycin. On the basis of the results of this study, intraarticular application of vancomycin powder in total hip and knee arthroplasty may be considered. Prospective randomized studies have to confirm this promising results prior a common recommendation.Level of Evidence III Retrospective cohort study.
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Ricciardi BF, Muthukrishnan G, Masters EA, Kaplan N, Daiss JL, Schwarz EM. New developments and future challenges in prevention, diagnosis, and treatment of prosthetic joint infection. J Orthop Res 2020; 38:1423-1435. [PMID: 31965585 PMCID: PMC7304545 DOI: 10.1002/jor.24595] [Citation(s) in RCA: 28] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/01/2019] [Accepted: 01/03/2020] [Indexed: 02/04/2023]
Abstract
Prosthetic joint infection (PJI) is a devastating complication that results in substantial costs to society and patient morbidity. Advancements in our knowledge of this condition have focused on prevention, diagnosis, and treatment, in order to reduce rates of PJI and improve patient outcomes. Preventive measures such as optimization of patient comorbidities, and perioperative antibiotic usage are intensive areas of current clinical research to reduce the rate of PJI. Improved diagnostic tests such as synovial fluid (SF) α-defensin enzyme-linked immunosorbent assay, and nucleic acid-based tests for serum, SF, and tissue cultures, have improved diagnostic accuracy and organism identification. Increasing the diversity of available antibiotic therapy, immunotherapy, and alternative implant coatings remain promising treatments to improve infection eradication in the setting of PJI.
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Affiliation(s)
- Benjamin F Ricciardi
- Center for Musculoskeletal Research, Department of Orthopaedics, University of Rochester School of Medicine
| | - Gowrishankar Muthukrishnan
- Center for Musculoskeletal Research, Department of Orthopaedics, University of Rochester School of Medicine
| | - Elysia A Masters
- Center for Musculoskeletal Research, Department of Orthopaedics, University of Rochester School of Medicine
| | - Nathan Kaplan
- Center for Musculoskeletal Research, Department of Orthopaedics, University of Rochester School of Medicine
| | - John L Daiss
- Center for Musculoskeletal Research, Department of Orthopaedics, University of Rochester School of Medicine
| | - Edward M Schwarz
- Center for Musculoskeletal Research, Department of Orthopaedics, University of Rochester School of Medicine
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Lawrie CM, Jo S, Barrack T, Roper S, Wright RW, Nunley RM, Barrack RL. Local delivery of tobramycin and vancomycin in primary total knee arthroplasty achieves minimum inhibitory concentrations for common bacteria causing acute prosthetic joint infection. Bone Joint J 2020; 102-B:163-169. [PMID: 32475280 DOI: 10.1302/0301-620x.102b6.bjj-2019-1639.r1] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
AIMS The aim of this study was to determine if the local delivery of vancomycin and tobramycin in primary total knee arthroplasty (TKA) can achieve intra-articular concentrations exceeding the minimum inhibitory concentration thresholds for bacteria causing acute prosthetic joint infection (PJI). METHODS Using a retrospective single-institution database of all primary TKAs performed between January 1 2014 and May 7 2019, we identified patients with acute PJI that were managed surgically within 90 days of the initial procedure. The organisms from positive cultures obtained at the time of revision were tested for susceptibility to gentamicin, tobramycin, and vancomycin. A prospective study was then performed to determine the intra-articular antibiotic concentration on postoperative day one after primary TKA using one of five local antibiotic delivery strategies with tobramycin and/or vancomycin mixed into the polymethylmethacrylate (PMMA) or vancomycin powder. RESULTS A total of 19 patients with acute PJI after TKA were identified and 29 unique bacterial isolates were recovered. The mean time to revision was 37 days (6 to 84). Nine isolates (31%) were resistant to gentamicin, ten (34%) were resistant to tobramycin, and seven (24%) were resistant to vancomycin. Excluding one Fusobacterium nucleatum, which was resistant to all three antibiotics, all isolates resistant to tobramycin or gentamicin were susceptible to vancomycin and vice versa. Overall, 2.4 g of tobramycin hand-mixed into 80 g of PMMA and 1 g of intra-articular vancomycin powder consistently achieved concentrations above the minimum inhibitory concentrations of susceptible organisms. CONCLUSION One-third of bacteria causing acute PJI after primary TKA were resistant to the aminoglycosides commonly mixed into PMMA, and one-quarter were resistant to vancomycin. With one exception, all bacteria resistant to tobramycin were susceptible to vancomycin and vice versa. Based on these results, the optimal cover for organisms causing most cases of acute PJI after TKA can be achieved with a combination of tobramycin mixed in antibiotic cement, and vancomycin powder. Cite this article: Bone Joint J 2020;102-B(6 Supple A):163-169.
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Affiliation(s)
- Charles M Lawrie
- Department of Orthopedic Surgery, Washington University School of Medicine, St. Louis, Missouri, USA
| | - Sally Jo
- Department of Orthopedic Surgery, Washington University School of Medicine, St. Louis, Missouri, USA
| | - Toby Barrack
- Department of Orthopedic Surgery, Washington University School of Medicine, St. Louis, Missouri, USA
| | - Stephen Roper
- Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, USA
| | - Rick W Wright
- Department of Orthopaedics and Rehabilitation, Vanderbilt University Medical Center, Nashville, Tennessee, USA
| | - Ryan M Nunley
- Department of Orthopedic Surgery, Washington University School of Medicine, St. Louis, Missouri, USA
| | - Robert L Barrack
- Department of Orthopedic Surgery, Washington University School of Medicine, St. Louis, Missouri, USA
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Harper KD, Lambert BS, O'Dowd J, Sullivan T, Incavo SJ. Clinical outcome evaluation of intraosseous vancomycin in total knee arthroplasty. Arthroplast Today 2020; 6:220-223. [PMID: 32577466 PMCID: PMC7303475 DOI: 10.1016/j.artd.2020.02.001] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/18/2019] [Revised: 01/24/2020] [Accepted: 02/01/2020] [Indexed: 02/01/2023] Open
Abstract
Background Vancomycin is a commonly used prophylactic antibiotic for total joint replacement surgery to protect against methicillin-resistant Staphylococcus aureus. Studies have suggested intraosseous (IO) infusions provide superior local tissue antibiotic concentration compared with intravenous (IV) access in total knee arthroplasty (TKA). We reviewed patients receiving IO vancomycin before TKA, comparing complication rates to a matched group receiving IV prophylactic vancomycin. Methods Retrospective review of TKA patients administered IO vancomycin (500 mg vancomycin in 200 mL normal saline), September 1, 2018 to March 1, 2019, was compared with TKAs performed with prophylactic IV vancomycin, January 1, 2018 to August 31, 2018. Before incision, an IO needle was inserted into the tibial tubercle region, delivering 100 mL of the mixed vancomycin solution. The needle was then removed and inserted into the distal femur, delivering 100 mL of the solution. Evaluation included preoperative and postoperative creatinine values, tourniquet time, and knee-related 30-day and 90-day complications. Data for primary and revision TKA surgery cases were analyzed independently. Results There were 100 primary and 29 revision TKA cases in the control (IV) arm and 100 primary and 19 revision TKA cases in the intervention (IO) arm, comprising a study group of 248 cases. There were fifteen 30-day complications and eighteen 90-day complications overall. No significant differences in the complication rate or creatinine values were identified between IO and IV groups. Conclusions IO vancomycin has an adequate safety profile in primary and revision TKA, eliminating the logistical challenge of timely prophylactic antibiotic administration.
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Affiliation(s)
- Katharine D Harper
- Department of Orthopedics & Sports Medicine, Houston Methodist Hospital, Houston, TX, USA
| | - Bradley S Lambert
- Department of Orthopedics & Sports Medicine, Houston Methodist Hospital, Houston, TX, USA.,Biomechanics Environmental Laboratory, Department of Mechanical Engineering, Texas A&M, Houston, TX, USA
| | - James O'Dowd
- Department of Orthopedics & Sports Medicine, Houston Methodist Hospital, Houston, TX, USA
| | - Thomas Sullivan
- Department of Orthopedics & Sports Medicine, Houston Methodist Hospital, Houston, TX, USA
| | - Stephen J Incavo
- Department of Orthopedics & Sports Medicine, Houston Methodist Hospital, Houston, TX, USA
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Temperature-responsive PNDJ hydrogels provide high and sustained antimicrobial concentrations in surgical sites. Drug Deliv Transl Res 2020; 9:802-815. [PMID: 30891707 DOI: 10.1007/s13346-019-00630-5] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Local antimicrobial delivery is a promising strategy for improving treatment of deep surgical site infections (SSIs) by eradicating bacteria that remain in the wound or around its margins after surgical debridement. Eradication of biofilm bacteria can require sustained exposure to high antimicrobial concentrations (we estimate 100-1000 μg/mL sustained for 24 h) which are far in excess of what can be provided by systemic administration. We have previously reported the development of temperature-responsive hydrogels based on poly(N-isopropylacrylamide-co-dimethylbutyrolactone acrylate-co-Jeffamine M-1000 acrylamide) (PNDJ) that provide sustained antimicrobial release in vitro and are effective in treating a rabbit model of osteomyelitis when instilled after surgical debridement. In this work, we sought to measure in vivo antimicrobial release from PNDJ hydrogels and the antimicrobial concentrations provided in adjacent tissues. PNDJ hydrogels containing tobramycin and vancomycin were administered in four dosing sites in rabbits (intramedullary in the femoral canal, soft tissue defect in the quadriceps, intramuscular injection in the hamstrings, and intra-articular injection in the knee). Gel and tissue were collected up to 72 h after dosing and drug levels were analyzed. In vivo antimicrobial release (43-95% after 72 h) was markedly faster than in vitro release. Drug levels varied significantly depending on the dosing site but not between polymer formulations tested. Notably, total antimicrobial concentrations in adjacent tissue in all dosing sites were sustained at estimated biofilm-eradicating levels for at least 24 h (461-3161 μg/mL at 24 h). These results suggest that antimicrobial-loaded PNDJ hydrogels are promising for improving the treatment of biofilm-based SSIs.
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