Complication Of Orthopedic Surgery Research Articles

NSQIP data collection up to 30 postoperative days is sufficient to capture some complications in orthopedic surgeries

NSQIP data collection up to 30 postoperative days is sufficient to capture some complications in orthopedic surgeries

Do preoperative glucose levels predict risk of complications in orthopaedic surgery?

Post-operative hyperglycemia is a known risk factor for post-surgical complications. The predictive value of pre-operative blood glucose levels, however, is less understood. This study aimed to determine if pre-operative screening blood glucose levels affect the rate of post-operative infection or wound complications. We also investigated if case urgency or anatomic location alters this relationship. A single-institution retrospective chart review was performed to evaluate patients treated between 2018 and 2021. Subjects ≥ 18years with closed, non-infected orthopaedic diagnoses requiring surgery were included. Case urgency, demographics, comorbidities, blood glucose level within twelve h prior to surgery, and hemoglobin A1c level within 3months of surgery, were collected. Infections and wound complications were recorded as outcomes. A total of 775 subjects with a mean age of 61 (range 18-96) were identified, including 543 elective and 232 trauma patients, with a mean pre-operative fasting glucose value of 127.7mg/dL (range, 49-388mg/dL) and average HbA1c of 6.9%. The odds of infectious complications were increased by a factor of 1.01 for every 1-point increase in blood glucose (95% CI 1.01-1.02; p < 0.01). Pre-operative blood glucose levels greater than 137mg/dL were associated with an increase in wound complications, but not deep infections. Infection rates stratified by anatomic site and case urgency were not impacted by pre-operative glucose levels. The increased risk of poor wound healing in patients with pre-operative hyperglycemia demonstrates that day of surgery point-of-care blood glucose screening can be a useful risk stratification tool.

Long stem revision versus short stem revision with plate osteosynthesis for Vancouver type B2 periprosthetic femoral fracture: a comparative study of eighty five cases

PurposePeriprosthetic femoral fractures (PPFs) around the hip are challenging complications in orthopaedic surgery, particularly Vancouver type B2 (VTB2) fractures. The surgical management of these fractures is crucial and depends on various factors. Cementless short taper stem with plate osteosynthesis is an alternative surgical technique. This study aims to compare the outcomes of this surgical technique with revision arthroplasty (RA) with long stem in the treatment of VTB2 PPFs.MethodsThis retrospective study was conducted in a single medical institute from February 2010 to May 2019. Patients who had received either total hip arthroplasty or bipolar hemiarthroplasty and subsequently developed a VTB2 PPF were included; patients who sustained intra-operative fractures or received a cemented stem previously were excluded from the analysis. The patients were divided into two groups: group I received RA with cementless long stem, while group II underwent RA with cementless short taper stem with plate osteosynthesis. Demographic data, radiographic and functional outcomes, and complications were analyzed between the two groups.ResultsA total of 85 patients diagnosed with VTB2 PPFs were included in the study. There were no significant differences between the two groups in terms of demographic data, including age, gender, mean follow-up times, estimated blood loss, and operative times. The radiographic results showed that there was no significant difference in the incidence of subsidence and implant stability between the two groups. However, group II tended to have less subsidence and periprosthetic osteolysis. Patients in group II had significantly better functional scores (mean Harris hip score: post-operative: 60.2 in group I and 66.7 in group ii; last follow-up: 77.4 in group 1 and 83.2 in group II (both p < 0.05)). There were no significant differences in the overall complication rate, including infection, dislocation, re-fracture, and revision surgery, between the two groups.ConclusionsBoth surgical techniques, cementless long stem and cementless short taper stem with plate osteosynthesis, are effective in the treatment of Vancouver B2 PPFs, with no significant differences in outcomes or complications. However, patients in cementless short taper stem with plate osteosynthesis had better functional scores at both post-operative and the last follow-up.

Debridement, Antibiotic Pearls, and Retention of the Implant (DAPRI) in the Treatment of Early Periprosthetic Knee Joint Infections: A Literature Review.

(1) Background: Periprosthetic joint infections (PJIs) are severe and frightening complications in orthopaedic surgery, and they are generally divided into three categories: early infections (those occurring within the first 4-6 weeks), delayed infections (those occurring between 3 and 24 months), and late infections (those occurring more than 2 years after surgery). PJI treatment comprises "debridement, antibiotics, and implant retention" (DAIR), single-stage revision, and double-stage revision. Nowadays, to improve the chances of retaining an infected implant and to improve the traditional DAIR method, a modified surgical technique has been developed, named DAPRI (debridement, antibiotic pearls, and retention of the implant). Our study aims to present an up-to-date concept evaluation of the DAPRI technique and its success rate. (2) Methods: Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) standards were followed, applying a protocol defined by the authors: a total of 765 articles were identified, and at the end of the screening process only 7 studies were included. (3) Results: Currently, the DAPRI procedure can be performed only on patients who have had PJI symptoms for less than 4 weeks, and in order to achieve the highest success rate, indications are quite strict: it is appropriate in patients with acute, superficial infections without sinus tract presence, and well-fixed implants with known sensitive bacteria. The DAPRI surgical method follows a step-by-step process consisting of a first phase of biofilm identification with intra-articular injection of methylene blue, followed by biofilm removal (thermic, mechanical, and chemical aggression), and a last step consisting of prevention of PJI recurrence by using calcium sulphate antibiotic-added beads. (4) Conclusions: The DAPRI approach improves the traditional DAIR technique. It is a correct treatment for acute and early haematogenous PJI, and improves the DAIR success rate.

Nanomaterials for Anti-Infection in Orthopedic Implants: A Review

Postoperative implant infection is a severe complication in orthopedic surgery, often leading to implant failure. Current treatment strategies mainly rely on systemic antibiotic therapies, despite contributing to increasing bacterial resistance. In recent years, nanomaterials have gained attention for their potential in anti-infection methods. They exhibit more substantial bactericidal effects and lower drug resistance than conventional antimicrobial agents. Nanomaterials also possess multiple bactericidal mechanisms, such as physico-mechanical interactions. Additionally, they can serve as carriers for localized antimicrobial delivery. This review explores recent applications of nanomaterials with different morphologies in post-orthopedic surgery infections and categorizes their bactericidal mechanisms.

Nanoadjuvant-triggered STING activation evokes systemic immunotherapy for repetitive implant-related infections

Repetitive implant-related infections (IRIs) are devastating complications in orthopedic surgery, threatening implant survival and even the life of the host. Biofilms conceal bacterial-associated antigens (BAAs) and result in a "cold tumor"-like immune silent microenvironment, allowing the persistence of IRIs. To address this challenge, an iron-based covalent organic framed nanoadjuvant doped with curcumin and platinum (CFCP) was designed in the present study to achieve efficient treatment of IRIs by inducing a systemic immune response. Specifically, enhanced sonodynamic therapy (SDT) from CFCP combined with iron ion metabolic interference increased the release of bacterial-associated double-stranded DNA (dsDNA). Immunogenic dsDNA promoted dendritic cell (DC) maturation through activation of the stimulator of interferon gene (STING) and amplified the immune stimulation of neutrophils via interferon-β (IFN-β). At the same time, enhanced BAA presentation aroused humoral immunity in B and T cells, creating long-term resistance to repetitive infections. Encouragingly, CFCP served as neoadjuvant immunotherapy for sustained antibacterial protection on implants and was expected to guide clinical IRI treatment and relapse prevention.

Utility of the modified 5-item frail index to predict complications and reoperations after hallux valgus surgery

IntroductionThe modified 5-item frailty index (mFI-5) has been recently proposed as a useful tool for predicting postoperative complications in orthopedic surgery. We aimed to analyze the utility of this score in predicting complications and reoperations after hallux valgus (HV) deformity surgery. Methods551 patients undergoing percutaneous HV corrective surgery were retrospectively reviewed. The mFI-5 was calculated based and patients were categorized in three groups: (1) non-frail: patients without any of the 5 comorbidities, (2) pre-frail: patients with one comorbidity and (3) frail: patients with two or more comorbidities. Complications and surgical reoperations were recorded. ResultsIn the study period 772 percutaneous surgeries were performed to correct hallux valgus deformity, 551 patients were included with a median age of 60 (IQR 48–70). 389 patients were non-frail (70.6%), 132 were pre-frail (23.9%) and 30 were frail (5.4%). 75 patients suffered complications (13.6%). Even though the rate of complications was higher in frailty patients (23.3%) compared with pre-frail (13.6%) and non frail (12.8%), no significant differences were observed among groups. 48 patients required reoperation (8.7%) but the rate of reoperations among frailty groups was not significantly different (p=0.11). Frailty patients had worse AOFAS scores at final follow up (p=0.011). ConclusionThe mFI-5 was not useful to predict postoperative complications and reoperations after hallux valgus corrective surgery. Therefore, other factors should be considered when analyzing the risk of complications after HV corrective surgery.

Risk Factors Associated With Postoperative Cardiac Events Following Total Hip and Knee Arthroplasty

BackgroundThis study investigated the prevalence of adverse cardiac events following a total joint arthroplasty and subsequently analyzed risk factors that may increase the likelihood of these events. MethodsData for this study were extracted from a large national database. Chi-squared analyses and multivariate modelings were performed to determine the risk factors associated with 30-day perioperative troponin elevation, myocardial infarction (MI), and heart failure. We identified 80,544 total hip arthroplasty (THA) patients and 112,531 total knee arthroplasty (TKA) patients and analyzed the following cardiac risk factors: diabetes, renal insufficiency, prior MI, hypertension, and cerebrovascular disease. ResultsThere were 34% of THA patients and 52% of TKA patients who had at least one of the studied risk factors. At-risk THA patients had 2.2, 5.9, and 5.3 times the odds of troponin elevation, MI, and postoperative heart failure, respectively, within 1 month compared to the control group (P < .0001). The TKA group had 2.9, 5.3, and 5.9 times the odds of troponin elevation, MI, and postoperative heart failure within 1 month compared to the control group (P < .0001). For both procedures, prior MI had the highest odds of resulting in perioperative troponin elevation and MI. Renal insufficiency had the highest odds of resulting in perioperative heart failure. ConclusionsRisk stratification for postoperative complications in orthopedic surgery is important to minimize adverse outcomes. This study highlights the need for consideration of risk factors prior to joint arthroplasty surgery. Level of EvidenceLevel III, Prognostic.

Host bone microstructure for enhanced resistance to bacterial infections

Postoperative bacterial infection is a serious complication of orthopedic surgery. Not only infections that develop in the first few weeks after surgery but also late infections that develop years after surgery are serious problems. However, the relationship between host bone and infection activation has not yet been explored. Here, we report a novel association between host bone collagen/apatite microstructure and bacterial infection. The bone-mimetic-oriented micro-organized matrix structure was obtained by prolonged controlled cell alignment using a grooved-structured biomedical titanium alloy. Surprisingly, we have discovered that highly aligned osteoblasts have a potent inhibitory effect on Escherichia coli adhesion. Additionally, the oriented collagen/apatite micro-organization of the bone matrix showed excellent antibacterial resistance against Escherichia coli. The proposed mechanism for realizing the antimicrobial activity of the micro-organized bone matrix is by the controlled secretion of the antimicrobial peptides, including β-defensin 2 and β-defensin 3, from the highly aligned osteoblasts. Our findings contribute to the development of anti-infective strategies for orthopedic surgeries. The recovery of the intrinsically ordered bone matrix organization provides superior antibacterial resistance after surgery.

Anti-Staphylococcal Activity of Ligilactobacillus animalis SWLA-1 and Its Supernatant against Multidrug-Resistant Staphylococcus pseudintermedius in Novel Rat Model of Acute Osteomyelitis.

Osteomyelitis caused by staphylococcal infection is a serious complication of orthopedic surgery. Staphylococcus pseudintermedius is the main causative agent of osteomyelitis in veterinary medicine. Methicillin-resistant S. pseudintermedius (MRSP) has been reported in companion animals, especially dogs. Multidrug-resistant S. pseudintermedius is an emerging pathogen and has acquired antibiotic resistance against various commercial antimicrobial agents. New antimicrobial compounds are urgently needed to address antibiotic resistance, and the development of novel agents has become an international research hotspot in recent decades. Antimicrobial compounds derived from probiotics, such as bacteriocins, are promising alternatives to classical antibiotics. In this study, the antibacterial activities of Ligilactobacillus animalis SWLA-1 and its concentrated cell-free supernatant (CCFS) were evaluated in vitro and in vivo. The CCFS of this bacterium showed no toxicity against osteoblast and myoblast cells in vitro, while significantly inhibiting the multidrug-resistant S. pseudintermedius KUVM1701GC strain in a newly established rat model. The CCFS significantly inhibited multidrug-resistant staphylococci both in vitro and in vivo. This suggests that CCFS derived from L. animalis SWLA-1 has potential as an alternative to classic antibiotics for staphylococcal infections in dogs.

Staphylococcus aureus planktonic but not biofilm environment induces an IFN-β macrophage immune response via the STING/IRF3 pathway

ABSTRACT Chronic implant-related bone infections are a severe complication in orthopaedic surgery. Biofilm formation on the implant impairs the immune response, leading to bacterial persistence. In a previous study, we found that Staphylococcus aureus (SA) induced interferon regulatory factor 3 (IRF3) activation and Ifnb expression only in its planktonic form but not in the biofilm. The aim of this study was to clarify the role of the stimulator of interferon genes (STING) in this process. We treated RAW 264.7 macrophages with conditioned media (CM) generated from planktonic or biofilm cultured SA in combination with agonists or inhibitors of the cyclic GMP-AMP synthase (cGAS)/STING pathway. We further evaluated bacterial gene expression of planktonic and biofilm SA to identify potential mediators. STING inhibition resulted in the loss of IRF3 activation and Ifnb induction in SA planktonic CM, whereas STING activation induced an IRF3 dependent IFN-β response in SA biofilm CM. The expression levels of virulence-associated genes decreased during biofilm formation, but genes associated with cyclic dinucleotide (CDN) synthesis did not correlate with Ifnb induction. We further observed that cGAS contributed to Ifnb induction by SA planktonic CM, although cGAS activation was not sufficient to induce Ifnb expression in SA biofilm CM. Our data indicate that the different degrees of virulence associated with SA planktonic and biofilm environments result in an altered induction of the IRF3 mediated IFN-β response via the STING pathway. This finding suggests that the STING/IRF3/IFN-β axis is a potential candidate as an immunotherapeutic target for implant-related bone infections.

Comparative analysis of venous thromboembolic complications in diverse groups of orthopaedic patients.

Venous thromboembolism (VTE) is one of the most important and life-threatening complications in orthopaedic surgery. According to current scientific reports, there are several variables that can affect the severity of CVD, including the site of the pathology or the type of treatment implemented. The aim of the study was to analyze the risk of VTE depending on the location of the pathology, as well as to evaluate the impact of surgical treatment compared to conservative management. Analysis of laboratory results and clinical picture of 276 patients hospitalized for orthopaedic reasons, admitted between January 2008 - December 2019, with suspected pulmonary embolism (PE). Among patients diagnosed with PE, the most common location of the disease was in the lower limb 59/116 (50.9%), followed by the pelvis location - 22/116 (19.0%), the spine - 19/116 (16.4%), disseminated lesions in oncological patients - 12/116 (10.3%), and a group of pathologies in the upper limb - 4/116 (3.5%). Significant statistical differences were found between the incidence of PE and the diagnosis of pathology in the lower limb and the pelvis. In the group of patients, there was no statistically significant relationship between the incidence of PE associated with surgical treatment, compared to conservative management. The group with the highest risk of VTE were lower limb and pelvic pathologies. The results are largely consistent with numerous reports treating the risk of CVD among orthopaedic patient populations.

Hydrogel delivery of DNase I and liposomal vancomycin to eradicate fracture-related methicillin-resistant staphylococcus aureus infection and support osteoporotic fracture healing.

Fracture-related infection (FRI) is a devastating complication in orthopedic surgery. A recent study showed that FRI causes more severe infection and further delays healing in osteoporotic bone. Moreover, bacterial biofilm formed on implants cannot be eradicated by systemic antibiotics, warranting novel treatments.Here, we developed a DNase I and Vancomycin hydrogel delivery vehicle to eradicate Methicillin-resistant Staphylococcus aureus (MRSA) infection in vivo. Vancomycin was encapsulated in liposomes, and DNase I and Vancomycin/liposomal-Vancomycin was loaded on thermosensitive hydrogel. In vitro drug release test showed a burst release of DNase I (77.2%) within 72h and sustained release of Vancomycin (82.6%) up to day 14. The in vivo efficacy was evaluated in a clinically relevant ovariectomy (OVX) induced osteoporotic metaphyseal fracture model with MRSA infection, and a total of 120 Sprague Dawley rats were used. In the OVX with infection group, biofilm development caused a drastic inflammatory response, trabecular bone destruction, and non-union. In the DNase I and Vancomycin co-delivery hydrogel group (OVX-Inf-DVG), bacteria on bone and implant were eradicated. X-ray and micro-CT showed preservation of trabecular bone and bone union. HE staining showed the absence of inflammatory necrosis, and fracture healing was restored. The local elevation of TNF-α and IL-6 and increased number of osteoclasts were prevented in the OVX-Inf-DVG group. Our findings suggest that dual release of DNase I and Vancomycin initially followed by Vancomycin only later up to 14 days effectively eliminates MRSA infection, prevents biofilm development and provides a sterile environment to promote fracture healing in osteoporotic bone with FRI. STATEMENT OF SIGNIFICANCE: The biofilm on implants are difficult to eradicate, causing recurrent infection and non-union in fracture-related infection (FRI). Here we developed a hydrogel therapy with high in vivo efficacy to eliminate MRSA biofilm infection in a clinically-relevant FRI model in osteoporotic bone. By loading DNase I and vancomycin/liposomal-vancomycin on thermosensitive poly-(DL-lactic acidco-glycolic acid) (PLGA)-polyethylene glycol (PEG)-PLGA hydrogel, a dual release of DNase I and Vancomycin was achieved whilst preserving enzyme activity. In this model, the progressive development of infection caused a drastic inflammatory response, osteoclastogenesis, trabecular bone destruction, and non-union of fracture. These pathological changes were successfully prevented by the dual delivery of DNase I and vancomycin. Our findings provide a promising strategy for FRI in osteoporotic bone.

Are self-reported anthropometric data reliable enough to meet antibiotic prophylaxis guidelines in orthopedic surgery?

BackgroundSurgical site infection is a serious complication in orthopedic surgery. The use of antibiotic prophylaxis (AP) combined with other prevention strategies has been shown to reduce this risk to 1% for hip arthroplasty and 2% for knee arthroplasty. The French Society of Anesthesia and Intensive Care Medicine (SFAR) recommends doubling the dose when the patient's weight is greater than or equal to 100 kg, and the body mass index (BMI) is greater than or equal to 35 kg/m2. Similarly, patients with a BMIgreater than40 kg/m2 orlesser than18 kg/m2 are ineligible for surgery in our hospital. Self-reported anthropometric measurements are commonly used in clinical practice to calculate BMI, but their validity has not been assessed in the orthopedic literature. Therefore, we conducted a study comparing self-reported with systematically measured values and observed the impact these differences may have on perioperative AP regimens and contra-indications to surgery. HypothesisThe hypothesis of our study was that self-reported anthropometric values differed from those measured during preoperative orthopedic consultations. Materials and methodsThis single-center retrospective study with prospective data collection was conducted between October and November 2018. The patient-reported anthropometric data were first collected and then directly measured by an orthopedic nurse. Weight was measured with a precision of 500 g and height was measured with a precision of 1 cm. ResultsA total of 370 patients (259 women and 111 men) with a median age of 67 years (17–90) were enrolled. The data analysis found significant differences between the self-reported and measured height [166 cm (147–191) vs. 164 cm (141–191) (p<0.0001)], weight [72.9 kg (38–149) vs. 73.1 kg (36–140) (p<0.0005)] and BMI [26.3 (16.2–46.4) vs. 27 (16–48.2) (p<0.0001)]. Of these patients, 119 (32%) reported an accurate height, 137 (37%) an accurate weight, and 54 (15%) an accurate BMI. None of the patients had two accurate measurements. The maximum underestimation was 18 kg for weight, 9 cm for height, and 6.15 kg/m2 for BMI. The maximum overestimation was 28 kg for weight, 10 cm for height, and 7.2 kg/m2 for BMI. The verification of the anthropometric measurements identified another 17 patients who had contra-indications to surgery (12 with a BMI>40 kg/m2 and 5 with a BMI<18 kg/m2) and who would not have been detected based on the self-reported values. ConclusionsAlthough patients underestimated their weight and overestimated their height in our study, these had no impact on the perioperative AP regimens. However, this misreporting failed to detect potential contraindications to surgery. Level of evidenceIV; retrospective study with prospective data collection and no control group.

Risks of Immunosuppressive Therapy in Patients Undergoing Open Reduction Internal Fixation for Ankle Fractures

Chronic steroid and immunosuppressant use have been shown to increase the risk for postoperative complications in orthopedic surgery. Further understanding of the risks of immunosuppression is necessary to aid in risk stratification and patient counseling. However, these risks have not yet been explored in ankle fracture patients. Thus, the purpose of this study is to determine whether patients taking immunosuppressives are at an increased risk for morbidity and mortality following open reduction and internal fixation (ORIF) of ankle fractures. Patients undergoing operative treatment for ankle fractures from 2006 to 2018 were identified in the National Surgical Quality Improvement Program database. Patients were categorized based on their use of immunosuppressive medications. Postoperative outcomes assessed included superficial surgical site infections, deep surgical site infections, organ space infections, wound dehiscence, pneumonia, unplanned intubation, pulmonary embolism, urinary tract infection, renal failure, blood transfusion requirement, deep vein thrombosis, sepsis, cardiac arrest, extended length of hospital stay, readmission, reoperation, and mortality. Univariate and multivariate analyses were performed. In total, 10,331 patients underwent operative treatment for ankle fracture. Total 10,153 patients (98.3%) were not taking immunosuppressants and 178 (1.7%) were taking these medications. In multivariate analysis, patients taking immunosuppressants were at increased risk of pulmonary embolism (odds ratio [OR] 4.382; p=.041) and hospital readmission (OR 2.131; p=.021). Use of immunosuppressive medications is an independent risk factor for pulmonary embolism and readmission following ORIF for ankle fractures. Notably, no association with wound complications, infections, or sepsis was identified.

Smart Trap‐Capture‐Kill Antibacterial System for Infected Microenvironment Improvement and Vascularized Bone Regeneration via Magnetic Thermotherapy

AbstractInfected bone defect has gradually become a disastrous complication in orthopedic surgery because of the bacterial biofilm formation both on the surface of the implants and surrounding tissues, which will cause antibiotic resistance and weak postoperative osseointegration. Herein, drug‐loaded hollow mesoporous ferrite nanoparticles coated by gelatin (GM/HMFNs) with pomegranate structure are prepared and compounded into calcium magnesium phosphate cement (MCPC) as a Trap‐Capture‐Kill system to kill bacteria and inhibit biofilm formation efficiently. Under the action of alternating magnetic field (AMF), MCPC/GM/HMFNs/Drug composites exhibit acute magnetic hyperthermal capacity and recruit the free bacteria. Then, the permeability of bacterial cell membrane is increased via reactive oxygen species (ROS) damage of nano‐MgO and HMFNs, providing channels through which vancomycin (Van) and ciprofloxacin (CPFX) encapsulated in GM/HMFNs can penetrate. Subsequently, the bacteria are efficiently killed under the synergetic cooperation of magnetothermal effect, ROS damage, and adsorption damage of nano‐MgO, and the bioactive ions and drugs. The antibacterial system also presents outstanding pro‐osteogenesis and pro‐angiogenic capacity in vitro. And it promotes the vascularized bone regeneration of infective femoral defect in SD rats in vivo, providing promising potential for the treatment of infected bone defects through magnetothermal therapy.

Host Immune Regulation in Implant-Associated Infection (IAI): What Does the Current Evidence Provide Us to Prevent or Treat IAI?

The number of orthopedic implants for bone fixation and joint arthroplasty has been steadily increasing over the past few years. However, implant-associated infection (IAI), a major complication in orthopedic surgery, impacts the quality of life and causes a substantial economic burden on patients and societies. While research and study on IAI have received increasing attention in recent years, the failure rate of IAI has still not decreased significantly. This is related to microbial biofilms and their inherent antibiotic resistance, as well as the various mechanisms by which bacteria evade host immunity, resulting in difficulties in diagnosing and treating IAIs. Hence, a better understanding of the complex interactions between biofilms, implants, and host immunity is necessary to develop new strategies for preventing and controlling these infections. This review first discusses the challenges in diagnosing and treating IAI, followed by an extensive review of the direct effects of orthopedic implants, host immune function, pathogenic bacteria, and biofilms. Finally, several promising preventive or therapeutic alternatives are presented, with the hope of mitigating or eliminating the threat of antibiotic resistance and refractory biofilms in IAI.

Application of Phage Therapy in a Case of a Chronic Hip-Prosthetic Joint Infection due to Pseudomonas aeruginosa: An Italian Real-Life Experience and In Vitro Analysis.

Prosthetic joint infection (PJI) caused by Pseudomonas aeruginosa represents a severe complication in orthopedic surgery. We report the case of a patient with chronic PJI from P. aeruginosa successfully treated with personalized phage therapy (PT) in combination with meropenem. A 62-year-old woman was affected by a chronic right hip prosthesis infection caused by P. aeruginosa since 2016 . The patient was treated with phage Pa53 (I day 10 mL q8h, then 5 mL q8h via joint drainage for 2 weeks) in association with meropenem (2gr q12h iv) after a surgical procedure. A 2-year clinical follow up was performed. An in vitro bactericidal assay of the phage alone and in combination with meropenem against a 24-hour-old biofilm of bacterial isolate was also carried out. No severe adverse events were observed during PT. Two years after suspension, there were no clinical signs of infection relapse, and a marked leukocyte scan showed no pathological uptake areas. In vitro studies showed that the minimum biofilm eradicating concentration of meropenem was 8 µg/mL. No biofilm eradication was observed at 24 hours incubation with phages alone (108 plaque-forming units [PFU]/mL). However, the addition of meropenem at suberadicating concentration (1 µg/mL) to phages at lower titer (103 PFU/mL) resulted in a synergistic eradication after 24 hours of incubation. Personalized PT, in combination with meropenem, was found to be safe and effective in eradicating P. aeruginosa infection. These data encourage the development of personalized clinical studies aimed at evaluating the efficacy of PT as an adjunct to antibiotic therapy for chronic persistent infections.

Development and Characterization of a Subcutaneous Implant-Related Infection Model in Mice to Test Novel Antimicrobial Treatment Strategies.

Orthopedic-device-related infection is one of the most severe complications in orthopedic surgery. To reduce the associated morbidity and healthcare costs, new prevention and treatment modalities are continuously under development. Preclinical in vivo models serve as a control point prior to clinical implementation. This study presents a mouse model of subcutaneously implanted titanium discs, infected with Staphylococcus aureus, to fill a gap in the early-stage testing of antimicrobial biomaterials. Firstly, three different inocula were administered either pre-adhered to the implant or pipetted on top of it following implantation to test their ability to reliably create an infection. Secondly, the efficacy of low-dose (25 mg/kg) and high-dose (250 mg/kg) cefazolin administered systemically in infection prevention was assessed. Lastly, titanium implants were replaced by antibiotic-loaded bone cement (ALBC) discs to investigate the efficacy of local antibiotics in infection prevention. The efficacy in infection prevention of the low-dose perioperative antibiotic prophylaxis (PAP) depended on both the inoculum and inoculation method. Bacterial counts were significantly lower in animals receiving the high dose of PAP. ALBC discs with or without the additional PAP proved highly effective in infection prevention and provide a suitable positive control to test other prevention strategies.

Use of a Novel Anti-Infective Noble Metal Alloy-Coated Titanium Orthopedic Nail in Patients with Open Fractures: A Case Series from Malaysia.

Fracture-related infection is a serious complication in orthopedic surgery with severe consequences for the patient. We evaluated whether a novel noble metal nail-coating technology can prevent bacterial adhesion and biofilm formation without interfering with bony union. In this retrospective, single-center case series, we described the incidence of fracture-related infections and bony union achievement in patients who had Gustilo type IIIa or IIIb femoral or tibial fractures treated with noble metal alloy-coated titanium nails. Patients were treated between January 2017 and January 2019 at the Sultanah Aminah Hospital, Johor Bahru, Malaysia. Information on fracture-related infections and bone healing assessments was collected from patient records. Additionally, three independent experts retrospectively reviewed patient X-ray images from follow-up visits to further evaluate bony union achievement. Thirty-five patients were included. Infection developed in 3/35 (8.6%) patients; all cases were resolved by antibiotic therapy. Radiographs were available for 32 patients; these confirmed the presence of bone healing in 30/32 (93.8%) patients. However, according to patient records, bony union was achieved in all patients. No safety issues were recorded. This case series suggests that a noble metal alloy-coated titanium nail can prevent infection and facilitate bony union achievement in patients undergoing surgery for severe open fractures.