Aims. This study aimed to assess the risk of acute kidney injury (AKI) associated with combined intravenous (IV) and topical antibiotic therapy in patients undergoing treatment for periprosthetic joint infections (PJIs) following total knee arthroplasty (TKA), utilizing the Kidney Disease: Improving Global Outcomes (KDIGO) criteria for classification. Methods. We conducted a retrospective analysis of 162 knees (162 patients) that received treatment for PJI post-TKA with combined IV and topical antibiotic infusions at a single academic hospital from 1 January 2010 to 31 December 2022. The incidence of AKI was evaluated using the KDIGO criteria, focussing on the identification of significant predictors and the temporal pattern of AKI development. Results. AKI was identified in 9.26% (15/162) of the cohort, predominantly presenting as stage 1 AKI, which was transient in nature and resolved prior to discharge. The analysis highlighted moderate anaemia and lower baseline serum creatinine levels as significant predictors for the development of AKI. Notably, the study found no instances of severe complications such as wound dehiscence, skin erosion, or the need for haemodialysis following treatment. Conclusion. The findings suggest that the combined use of IV and topical antibiotic therapy in the management of PJIs post-TKA is associated with a low incidence of primarily transient stage 1 AKI. This indicates a potentially favourable renal safety profile, advocating for further research to confirm these outcomes and potentially influence treatment protocols in PJI management. Cite this article: Bone Joint Res 2024;13(10):525–534

Aims. There is increasing evidence to support the use of topical antibiotics to prevent surgical site infections. Although previous research suggests a minimal nephrotoxic risk with a single dose of vancomycin powder, fracture patients often require multiple procedures and receive additional doses of topical antibiotics. We aimed to determine if cumulative doses of intrawound vancomycin or tobramycin powder for infection prophylaxis increased the risk of drug-induced acute kidney injury (AKI) among fracture patients. Methods. This cohort study was a secondary analysis of single-centre Program of Randomized Trials to Evaluate Pre-operative Antiseptic Skin Solutions in Orthopaedic Trauma (PREP-IT) trial data. We included patients with a surgically treated appendicular fracture. The primary outcome was drug-induced AKI. The odds of AKI per gram of vancomycin or tobramycin powder were calculated using Bayesian regression models, which adjusted for measured confounders and accounted for the interactive effects of vancomycin and tobramycin. Results. Of the 782 included patients (mean age 48 years (SD 20); 59% male), 83% (n = 648) received at least one vancomycin dose (cumulative range 1 to 12 g). Overall, 45% of the sample received at least one tobramycin dose (cumulative range 1.2 to 9.6 g). Drug-induced AKI occurred in ten patients (1.2%). No association was found between the cumulative dose of vancomycin and drug-induced AKI (odds ratio (OR) 1.08 (95% credible interval (CrI) 0.52 to 2.14)). Additional doses of tobramycin were associated with a three-fold increase in the adjusted odds of drug-induced AKI (OR 3.66 (95% CrI 1.71 to 8.49)). Specifically, the risk of drug-induced AKI rose substantially after 4.8 g of tobramycin powder (7.5% (95% CrI 1.0 to 35.3)). Conclusion. Cumulative doses of vancomycin were not associated with an increased risk of drug-induced AKI among fracture patients. While the risk of drug-induced AKI remains less than 4% with three or fewer 1.2 g tobramycin doses, the estimated risk increases substantially to 8% after four cumulative doses. Level of evidence: Therapeutic Level III. Cite this article: Bone Jt Open 2022;3(4):284–290

Aims. High-energy injuries can result in multiple complications, the most prevalent being infection. Vancomycin powder has been used with increasing frequency in orthopaedic trauma given its success in reducing infection following spine surgery. Additionally, large, traumatic injuries require wound coverage and management by dressings such as negative pressure wound therapy (NPWT). NPWT has been shown to decrease the ability of antibiotic cement beads to reduce infection, but its effect on antibiotic powder is not known. The goal of this study was to determine if NPWT reduces the efficacy of topically applied antibiotic powder. Methods. Complex musculoskeletal wounds were created in goats and inoculated with a strain of Staphylococcus aureus modified to emit light. Six hours after contaminating the wounds, imaging, irrigation, and debridement and treatment application were performed. Animals received either vancomycin powder with a wound pouch dressing or vancomycin powder with NPWT. Results. There were no differences in eradication of bacteria when vancomycin powder was used in combination with NPWT (4.5% of baseline) compared to vancomycin powder with a wound pouch dressing (1.7% of baseline) (p = 0.986), even though approximately 50% of the vancomycin was recovered in the NPWT exudate canister. Conclusion. The antimicrobial efficacy of the vancomycin powder was not diminished by the application of NPWT. These topical and locally applied therapies are potentially effective tools that can provide quick, simple treatments to prevent infection while providing coverage. By reducing the occurrence of infection, the recovery is shortened, leading to an overall improvement in quality of life. Cite this article: Bone Joint Res 2021;10(2):149–155

It has been shown in experimental animals that the living cells in a bone autograft can make an important contribution to osteogenesis. However, some common clinical techniques, such as the topical use of antibiotic powders on grafts or on the graft bed, are likely to damage or kill the cells. In this experimental study in rats, bone isografts dusted with chloramphenicol or methicillin powder or with Polybactrin spray before subcutaneous implantation produced little or no new bone over a period of two weeks whereas untreated, control grafts showed abundant osteogenesis, as did grafts pretreated with solutions of antibiotics. The effect of short-term storage of the grafts for 3 to 24 hours in air, saline or culture medium before implantation was also examined. Grafts stored in culture medium generally did as well as, or better than, fresh control grafts whereas immersion in saline inhibited osteogenesis. The importance of these results for clinical bone grafting is discussed.

Aims. Biofilm-related infection is a major complication that occurs in orthopaedic surgery. Various treatments are available but efficacy to eradicate infections varies significantly. A systematic review was performed to evaluate therapeutic interventions combating biofilm-related infections on in vivo animal models. Methods. Literature research was performed on PubMed and Embase databases. Keywords used for search criteria were “bone AND biofilm”. Information on the species of the animal model, bacterial strain, evaluation of biofilm and bone infection, complications, key findings on observations, prevention, and treatment of biofilm were extracted. Results. A total of 43 studies were included. Animal models used included fracture-related infections (ten studies), periprosthetic joint infections (five studies), spinal infections (three studies), other implant-associated infections, and osteomyelitis. The most common bacteria were Staphylococcus species. Biofilm was most often observed with scanning electron microscopy. The natural history of biofilm revealed that the process of bacteria attachment, proliferation, maturation, and dispersal would take 14 days. For systemic mono-antibiotic therapy, only two of six studies using vancomycin reported significant biofilm reduction, and none reported eradication. Ten studies showed that combined systemic and topical antibiotics are needed to achieve higher biofilm reduction or eradication, and the effect is decreased with delayed treatment. Overall, 13 studies showed promising therapeutic potential with surface coating and antibiotic loading techniques. Conclusion. Combined topical and systemic application of antimicrobial agents effectively reduces biofilm at early stages. Future studies with sustained release of antimicrobial and biofilm-dispersing agents tailored to specific pathogens are warranted to achieve biofilm eradication. Cite this article: Bone Joint Res 2022;11(10):700–714

Introduction. The use of irrigation solution during surgical procedures is a common and effective practice in reduction of bioburden and the risk of subsequent infection. The optimal irrigation solution to accomplish this feat remains unknown. Many surgeons commonly add topical antibiotics to irrigation solutions assuming this has topical effect and eliminates bacteria. The latter reasoning has never been proven. In fact a few prior studies suggest addition of antibiotics to irrigation solution confers no added benefit. Furthermore, this practice adds to cost, has the potential for anaphylactic reactions, and may also contribute to the emergence of antimicrobial resistance. We therefore sought to compare the antimicrobial efficacy and cytotoxicity of irrigation solution containing polymyxin-bacitracin versus other commonly used irrigation solutions. Methods. Using two in vitro breakpoint assays of Staphylococcus aureus (ATCC#25923) and Escherichia coli (ATCC#25922), we examined the efficacy of a panel of irrigation solutions containing topical antibiotics (500,000U/L Polymyxin-Bacitracin 50,000U/L; Vancomycin 1g/L; Gentamicin 80mg/L), as well as commonly used irrigation solutions (Normal saline 0.9%; Povidone-iodine 0.3%; Chlorhexidine 0.05%; Castile soap 0.45%; and Sodium hypochlorite 0.125%) following 1 minute and 3 minutes of exposure. Surviving bacteria were counted in triplicate experiments. Failure to eradicate all bacteria was considered to be “not effective” for that respective solution and exposure time. Cytotoxicity analysis in human fibroblast, osteoblast, and chrondrocyte cells exposed to each of the respective irrigation solutions was performed by visualization of cell structure, lactate dehydrogenase (LDH) activity and evaluation of vital cells. Toxicity was quantified by determination of LDH release (ELISA % absorbance; with higher percentage considered a surrogate for cytotoxicity). Descriptive statistics were used to present means and standard deviation of triplicate experimental runs. Results. Polymyxin-Bacitracin, Saline and Castile soap irrigation at both exposure times were not effective at eradicating S aureus or E coli (Figure 1). In contrast, Povidone-iodine, Chlorhexidine, and Sodium hypochlorite irrigation were effective at eradicating both S aureus and E coli. Vancomycin irrigation was effective at S aureus eradication but not against E coli, whereas Gentamicin irrigation showed partial efficacy against E coli eradication but none against S aureus. The greatest cytotoxicity was seen with Chlorhexidine (49.4% ± 1.9). This was followed by Castile soap (33.2% ±3.9), Vancomycin (9.01% ±5.1), Polymyxin-Bacitracin (8.45% ±1.5), and Gentamicin irrigation (4.72% ±2.3) (Figure 2 and Figure 3 microscopy images). Povidone-iodine and Sodium hypochlorite showed least cytotoxicity (0.05% ±0.08 and 0.11%±0.19, respectively). Similar trends were seen at both exposure times and across fibroblasts, osteoblasts and chondrocytes. Discussion. This in vitro study suggests that addition of polymyxin-bacitracin to saline irrigation solution is a futile exercise. Taken within the context of its associated expense, risk of hypersensitivity and impact upon antimicrobial resistance, our findings bring its widespread clinical usage into question. Povidone-iodine may be a more effective option, with a more favorable cytotoxicity profile than the other commonly used irrigation solutions. Clinical outcomes should be studied to determine the most effective agent, concentration, and exposure time for intraoperative irrigation

The February 2014 Spine Roundup. 360 . looks at: single posterior approach for severe kyphosis; risk factors for recurrent disc herniation; dysphagia and cervical disc replacement or fusion; hang on to your topical antibiotics; cost-effective lumbar disc replacement; anxiolytics no role to play in acute lumbar back pain; and surgery best for lumbar disc herniation

Aim. The efficacy of various irrigation solutions in removing microbial contamination of a surgical wound and reducing the rate of subsequent surgical site infection (SSI), has been demonstrated extensively. However, it is not known if irrigation solutions have any activity against established biofilm. This issue is pertinent as successful management of patients with periprosthetic joint infection (PJI) includes the ability to remove biofilm established on the surface of implants and necrotic tissues. The purpose of this study was to evaluate the efficacy of various irrigation solutions in eradicating established biofilm, as opposed to planktonic bacteria, in a validated in vitro model. Method. Established biofilms of Staphylococcus aureus and Escherichia coli were exposed to different irrigation solutions that included Polymyxin 500,000U/L plus bacitracin 50,000U/L, Vancomycin 1g/L, Gentamicin 80mg/L, Normal saline 0.9%, off-the-shelf Betadine 0.3%, Chlorhexidine 0.05%, Benzalkonium 1.3g/L, Sodium hypochlorite 0.125%, and Povidone-iodine 0.5%. Each experiment was conducted in a 96-well microtiter plate with a peg lid and standardized per the MBEC assay manufacturer's protocol. Following 2 minutes of solution exposure to the irrigation solution, residual biofilms were recovered by sonication. Outcome measures for antibiofilm efficacy were residual colony forming units (CFU) and optical density (690nm). Experiments were conducted in 24 replicates and the observations recorded by two blinded observers. Statistical analysis involved t-tests with Bonferonni adjustment. Results. Povidone-iodine 0.5%, Betadine 0.3%, Benzalkonium 1.3g/L, and Sodium hypochlorite 0.125% were significantly more efficacious against S.aureus biofilm versus all other solutions (p<0.001). Against E.coli biofilm, Povidone-iodine-0.5%, Benzalkonium-1.3g/L and Sodium hypochlorite-0.125% were also most effective compared to other irrigation solutions (p<0.001). Polymyxin-bacitracin, Gentamicin, Vancomycin, and Saline solutions had minimal activity against both E.coli and S.aureus biofilms (p<0.001). Similar trends were observed using both experimental endpoints (CFU and Turbidity) and both investigators (interrater reliability; r=0.99). Conclusion. This in vitro study observed that topical antibiotic solutions do not have any activity against established biofilms. Irrigations solutions containing adequate amount of povidone-iodine, betadine, sodium hypochlorite, and benzalkonium appear to have activity against established biofilm by gram positive and gram negative organisms. The use of these irrigation solutions may need to be considered in patients with established PJI

The two-staged exchange for periprosthetic joint infection (PJI) has become the “gold standard” worldwide. Based on the first implementation of mixing antibiotics into bone cement by Prof. Buchholz in the 1970s, the ENDO-Klinik followed a distinct one staged exchange for PJI in over 85 % of all our infected cases until today. Looking carefully at current literature and guidelines for the PJI treatment, there is no clear evidence, that a two-staged procedure has a clearly higher success rate than a one-staged approach. Although postulated in relevant articles, most recommendations, e.g. duration of antibiotics, static vs. mobile spacer, interval of spacer retention, cemented vs. uncemented implant fixation, are based on Level IV to III evidence studies or expert opinions, rather than on prospective randomised or comparative data. Potentially a cemented one-stage exchange offers certain advantages, as mainly based on need for only one operative procedure, reduced antibiotics & hospitalization time and reduced relative overall costs. In order to fulfill a one-staged approach with the above described potential success, there are obligatory pre-, peri- and postoperative details, which need to be meticulously respected. The absolute mandatory infrastructural requirement is based on the clear evidence of the bacteria in combination with a distinct patient specific plan, by an experienced microbiologist, for following topical antibiotics in the bone cement with combined systemic antibiotics. Mandatory preoperative diagnostic testing is based on the joint aspiration with an exact identification of the bacteria. The presence of a positive bacterial culture and respective antibiogramm is essential, to specify the antibiotics loaded into the bone cement, which allows a high topical antibiotic elution directly at the surgical site. A specific treatment plan is generated by a microbiologist. Contraindications for a one-staged exchange include: failure of >2 previous one-staged procedures, infection spreading to the nerve-vessel bundle, unclear preoperative bacteria specification, unavailability of appropriate antibiotics, high antibiotic resistance. The surgical success relies not only on the complete removal of all preexisting hardware material (including cement and restrictors), furthermore an aggressive and complete debridement of any infected soft tissues and bone material is needed. Mixing antibiotics into the cement needs to fulfill the following criteria: Appropriate antibiogramm, adequate elution characteristics, bactericidal (exception clindamycin), powder form (never use liquid AB), maximum addition of 10 %/PMMA powder. Current principles of modern cementing techniques should be applied. Postoperative systemic antibiotic administration is usually followed for only 10–14 days (exception: streptococci). We recommend an early and aggressive mobilization within the first 8 days postoperatively, due to the cemented fixation an immediate mobilization under full weight bearing becomes possible in most cases. Persistence or recurrence of infection remains the most relevant complication in the one-staged technique. As failure rates with a two-staged exchange have been described between 9% and 20% in non-resistant bacteria, the ENDO-Klinik data shows comparative results after 8–10 years of follow up. In summary a cemented one-stage exchange offers various advantages. Mainly the need for only one operation, shorter hospitalization, reduced systemic antibiotics, lower overall cost and relative high patient satisfaction. However, a well-defined preoperative planning regime including an experienced microbiologist is absolutely mandatory

The two-staged exchange for periprosthetic joint infection (PJI) has become the “gold standard” worldwide. Based on the first implementation of mixing antibiotics into bone cement by Prof. Buchholz in the 70's, the ENDO-Klinik followed a distinct one-staged exchange for PJI in over 85% of all our infected cases until today. Looking carefully at current literature and guidelines for the PJI treatment, there is no clear evidence, that a two-staged procedure has a clearly higher success rate than a one-staged approach. Although postulated in relevant articles, most recommendations, e.g. duration of antibiotics, static vs. mobile spacer, interval of spacer retention, cemented vs. uncemented implant fixation, are based on level IV to III evidence studies or expert opinions, rather than on prospective randomised or comparative data. Potentially a cemented one-stage exchange offers certain advantages, as mainly based on need for only one operative procedure, reduced antibiotics & hospitalization time and reduced relative overall costs. In order to fulfill a one-staged approach with the above described potential success, there are obligatory pre-, peri- and post-operative details, which need to be meticulously respected. The absolute mandatory infrastructural requirement is based on the clear evidence of the bacteria in combination with a distinct patient specific plan, by an experienced microbiologist, for the topical antibiotics in the bone cement with combined systemic antibiotics. Mandatory pre-operative diagnostic testing is based on the joint aspiration with an exact identification of the bacteria. The presence of a positive bacterial culture and respective antibiogramm is essential, to specify the antibiotics loaded to the bone cement, which allows a high topical antibiotic elution directly at the surgical site. A specific treatment plan is generated by a microbiologist. Contraindications for a one-staged exchange include: failure of > 2 previous one-staged procedures, infection spreading to the nerve-vessel bundle, unclear pre-operative bacteria specification, unavailability of appropriate antibiotics, high antibiotic resistance. The surgical success relies not only on the complete removal of all preexisting hardware material (including cement and restrictors), furthermore an aggressive and complete debridement of any infected soft tissues and bone material is needed. Mixing antibiotics to the cement needs to fulfill the following criteria: Appropriate antibiogramm, adequate elusion characteristics, bactericidal (exception clindamycin), powder form (never use liquid AB), maximum addition of 10%/PMMA powder. Current principles of modern cementing techniques should be applied. Post-operative systemic antibiotic administration is usually followed for only 10–14 days (exception: streptococci). We recommend an early and aggressive mobilization within the first 8 days post-operatively due to the cemented fixation an immediate mobilization under full weight bearing becomes possible in most cases. Persistence or recurrence of infection remains the most relevant complication in the one-staged technique. As failures rates with a two-staged exchange have been described between 9% and 20% in non-resistant bacteria, the ENDO-Klinik data shows comparative results after 8–10 years of follow up, which were confirmed independently also by some other international reports and study groups. In summary a cemented one-stage exchange offers various advantages. Mainly the need for only one operation, shorter hospitalization, reduced systemic antibiotics, lower overall cost and relatively high patient satisfaction. However a well-defined pre-operative planning regime including an experienced microbiologist is absolutely mandatory

Topically applied vancomycin powder has been used to decrease surgical site infection rates in spinal surgeries, however, randomized controlled trials in total joint arthroplasty are lacking. Application of vancomycin powder topically in the surgical site has theoretical benefit including high local concentration. In this study, we aimed to determine whether intra-operative topical antibiotics are safe and effective as IV antibiotics in preventing post-surgical site infections. The trial was a randomized controlled, double blind, non-inferiority study. All patients received pre-operative IV antibiotics (cefazolin or vancomycin) within 60 minutes of skin incision. The controlled group received two doses of post-operative IV antibiotics (two grams cefazolin or one gram vancomycin if cefazolin allergy). In the treatment group, the orthopaedic surgeon applied one gram vancomycin powder (500mg applied directly on the prosthesis and 500mg applied above the closed joint capsule). The incidence of acute surgical site infection was defined as positive deep cultures within 42 days of procedure. All patients with evidence of infection underwent joint aspiration for culture. After one year, 80 patients had received the topical vancomycin treatment and 85 patients had received the standard treatment. In the topical vancomycin group versus the controlled group, the average age was 64 vs 66, average BMI was 35.7 vs 33.4, number of males 33 vs 29, number of females 47 vs 56, and diabetic patients 16 vs 13. The number of infections in the topical vancomycin group was three vs zero in the post-operative IV antibiotic treatment group. One Tailed Z-test P Value = 0.03. This study statistically demonstrated inferiority of topical vancomycin in comparison to the use of IV antibiotics post-operatively in preventing deep wound infections in TKA. The authors would caution against the sole use of intra-operative vancomycin in TKA to prevent post-operative infection

The February 2024 Trauma Roundup³⁶⁰ looks at: Posterior malleolus fractures: what about medium-sized fragments?; Acute or delayed total hip arthroplasty after acetabular fracture fixation?; Intrawound antibiotics reduce the risk of deep infections in fracture fixation; Does the VANCO trial represent real world patients?; Can a restrictive transfusion protocol be effective beyond initial resuscitation?; What risk factors result in avascular necrosis of the talus?; Pre-existing anxiety and mood disorders have a role to play in complex regional pain syndrome; Three- and four-part proximal humeral fractures at ten years.

The August 2024 Trauma Roundup³⁶⁰ looks at: Does topical vancomycin prevent fracture-related infections in closed fractures undergoing open reduction and internal fixation? A randomized controlled trial; Is postoperative splinting advantageous after upper limb fracture surgery?; Does suprapatellar nailing resolve knee pain?; Locking versus non-locking plate fixation in comminuted talar neck fractures: a biomechanical study using cadaveric specimens; Revolutionizing recovery metrics: PROMIS versus SMFA in orthopaedic trauma care; Dorsal hook plating of patella fractures: reliable fixation and satisfactory outcomes; The impact of obesity on subtrochanteric femur fracture outcomes; Low-dose NSAIDs (ketorolac) and cytokine modulation in orthopaedic polytrauma: a detailed analysis.

The June 2023 Spine Roundup³⁶⁰ looks at: Characteristics and comparative study of thoracolumbar spine injury and dislocation fracture due to tertiary trauma; Sublingual sufentanil for postoperative pain management after lumbar spinal fusion surgery; Minimally invasive bipolar technique for adult neuromuscular scoliosis; Predictive factors for degenerative lumbar spinal stenosis; Lumbosacral transitional vertebrae and lumbar fusion surgery at level L4/5; Does recall of preoperative scores contaminate trial outcomes? A randomized controlled trial; Vancomycin in fibrin glue for prevention of SSI; Perioperative nutritional supplementation decreases wound healing complications following elective lumbar spine surgery: a randomized controlled trial.

Aims

Gram-negative periprosthetic joint infection (PJI) has been poorly studied despite its rapidly increasing incidence. Treatment with one-stage revision using intra-articular (IA) infusion of antibiotics may offer a reasonable alternative with a distinct advantage of providing a means of delivering the drug in high concentrations. Carbapenems are regarded as the last line of defense against severe Gram-negative or polymicrobial infection. This study presents the results of one-stage revision using intra-articular carbapenem infusion for treating Gram-negative PJI, and analyzes the characteristics of bacteria distribution and drug sensitivity.

Aims

Bacterial infection activates neutrophils to release neutrophil extracellular traps (NETs) in bacterial biofilms of periprosthetic joint infections (PJIs). The aim of this study was to evaluate the increase in NET activation and release (NETosis) and haemostasis markers in the plasma of patients with PJI, to evaluate whether such plasma induces the activation of neutrophils, to ascertain whether increased NETosis is also mediated by reduced DNaseI activity, to explore novel therapeutic interventions for NETosis in PJI in vitro, and to evaluate the potential diagnostic use of these markers.

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.