Compassionate use of cefiderocol in a complex case of extensively drug-resistant Acinetobacter baumannii fracture-related infection: a comprehensive approach and multidisciplinary management.

PURPOSE: Fracture-related infections (FRI) pose a difficult management problem, as they require numerous surgical interventions and extended antibiotic treatments, especially when a multidrug-resistant organism is involved, with a paucity of available literature that provides guidance. RESULTS: A 42 year-old male presents an open diaphyseal tibia and fibula fracture, complicated by soft tissue necrosis and infections caused by extensively drug-resistant Acinetobacter baumannii (XDR-Ab). Initially treated with a damage control external fixator, the patient underwent multiple surgical procedures, including radical debridement, negative pressure wound therapy, external fixator revisions and reconstructive surgery using a latissimus dorsi free flap. The emergence of colistin resistance in the Acinetobacter baumannii strain led to the compassionate use of cefiderocol, finally achieving clinical cure. CONCLUSIONS: This case report is one of the firsts that highlights the potential efficacy of cefiderocol in treating challenging bone and joint infections sustained by XDR-Ab. The successful outcome also emphasizes the importance of a comprehensive, multidisciplinary approach in achieving favorable results in complex FRI.

Mid-Term Outcomes of a Short Modular Neck-Preserving Cementless Hip Stem: A Retrospective Study With a 6-Year Minimum Follow-Up.

Background: The neck-preserving cementless short stem represents a valid therapeutic option for total hip replacement in high-functional-demand patients, but few studies are available about the use of modularity in the last-generation short stem. The aim of the study was to evaluate the mid-term survival of a specific implant design that combines partial collum short hip stem with neck modularity; assessing the functional status was the second endpoint. Methods: A retrospective single-center cohort study was conducted on 75 patients aged 35 to 80 years, with a minimum 6-year follow-up. Patients with neurological/rheumatic pathologies and previous hip surgeries were excluded. All the patients underwent total hip replacement with a short modular neck-preserving cementless hip stem. Clinical outcomes, complications, revisions, and the Western Ontario and McMaster Universities Osteoarthritis Index, Harris hip score, and Short Form 12-Item Health Survey (SF-12) questionnaires were evaluated. The results were compared with healthy population's data extracted from the literature, stratified by age. Results: The Kaplan-Meier analysis revealed a 10-year implant survival rate of 96.7%, coupled with a revision rate of 1.3%. Results showed a Harris hip score and physical SF-12 significantly lower and a mental SF-12 higher when compared to healthy population. No statistically significant differences emerged when comparing groups based on neck modularity. Conclusions: The short modular neck-preserving cementless hip stem emerged as a reasonable choice for patients with elevated functional demands, ensuring good clinical outcomes while preserving bone integrity. The use of a modular neck in short stems didn't show any mechanical problems in the mid-term.

Hydrogel Coating versus Calcium Sulphate Beads as a Local Antibiotic Carrier for Debridement Procedures in Acute Periprosthetic Joint Infection: A Preliminary Study.

Periprosthetic joint infections (PJI) are among the most difficult complications to treat in orthopaedic surgery. Debridement, antibiotics, and implant retention (DAIR) represent an efficient strategy for acute PJI, especially when resorbable local antibiotic carriers and coatings are used. The aim of this pilot study was to evaluate the difference between using antibiotic-loaded hydrogel (ALH) and calcium sulphate (CS) beads in the DAIR procedure. We analysed 16 patients who had been treated since 2018 for acute PJI, namely eight patients with knee PJI (50%), seven with hip PJI (43.7%), and one with shoulder PJI (6.2%). Nine patients were treated with the Debridement, Antibiotic Coating and Retention of the Implant (DACRI) method, while seven were treated with the Debridement, Antibiotic Pearls, Retention of the Implant (DAPRI) method. We found no significant differences between the two groups in terms of age, sex, the American Society of Anesthesiologists risk score, Charlson Comorbidity Index, localisation, days from onset to diagnosis and pathogenesis. Furthermore, no differences were found between the DACRI and DAPRI groups in terms of infection control (15 patients, 93.75% with p = 0.36) and last C-Reactive Protein values (p = 0.26), with a mean follow-up of 26.1 ± 7.7 months. Treatment for one patient affected by knee Candida albicans PJI in the DACRI group was not successful. In conclusion, DAPRI and DACRI appear to be safe and effective treatments for PJIs. This evidence will encourage the development of new clinical research into local carriers and coatings for use in acute implant-associated infections.

Chronic Suppressive Antibiotic Treatment for Staphylococcal Bone and Joint Implant-Related Infections.

Prosthetic joint infection (PJI) and fracture-related infection (FRI) are difficult-to-treat conditions in patients with severe comorbidity or significant surgical risk. In cases not eligible for standard strategy, debridement procedures with the retention of prosthesis or internal fixation device, combined with long-term antibiotic treatment and subsequent indefinite chronic oral antimicrobial suppression (COAS), can be the only reasonable choice. The aim of this study was to investigate the role of COAS and its follow-up in the management of these cases. We retrospectively analyzed a cohort of 16 patients with a follow-up of at least 6 months (mean age 75 yo, 9F, 7M, 11 PJI, 5 FRI). All microbiological isolates were tetracycline-susceptible staphylococci and for this reason a minocycline-based COAS was adopted after debridement and 3 months of antibiogram-guided antibiotic treatment. Patient monitoring was carried out on a clinical basis, with bimonthly execution of the inflammation indices and serial radiolabeled leukocyte scintigraphy (LS). The overall median time of COAS follow-up was 15 months (min 6-max 30). Moreover, 62.5% of patients were still taking COAS with no relapse after cure at the last evaluation available. Clinical failure with a relapse of the infection was observed in 37.5% of patients; interestingly, 50% of them had previously stopped COAS due to side effects of the antibiotic used. In the COAS follow-up, a combination of clinical, laboratory and LS evaluation seems to monitor the infection properly. COAS can be considered as an interesting approach in patients not suitable for standard treatments of PJI or FRI but it requires careful monitoring.

Antibiotic-Loaded Coatings to Reduce Fracture-Related Infections: Retrospective Case Series of Patients with Increased Infectious Risk.

Local antibiotic delivery strategies have been increasingly employed for the prevention of fracture-related infections (FRIs). The aim of this study is to evaluate the efficacy and safety of antibiotic-coated implants in the prevention of FRIs after surgical treatment in patients with increased infectious risk. A retrospective observational study has been conducted on patients with upper and lower limb fractures treated with internal fixation or prosthetic replacements, using a gentamicin coated nail (CN) and/or antibiotic-loaded hydrogel applied to the implant of choice (ALH). The study included 37 patients (20 M, 17 F), with a mean age of 63 years. The mean estimated preoperative infectious risk score was 6.4%. ALH was used in 27 cases, tibial CNs were implanted in 4 cases, and both were employed in 6 cases. The antibiotics used locally were gentamicin in 72.97% of cases (27 patients) and a combination of gentamicin + vancomycin in 27.03% of cases (10 patients). Mean follow-up was 32 months. Only one case (2.94%) showed onset of FRI at 5 months after surgery. Local antibiotic prophylaxis by coating resulted in a reduction in the incidence FRI, as compared to the estimated preoperative risk. The use of ALH allows for the choice of antibiotic; however, the application of antibiotics seems more nonuniform when applied to a nail.

Clinical Impact of Colonization with Carbapenem-Resistant Gram-Negative Bacteria in Critically Ill Patients Admitted for Severe Trauma.

Multidrug-resistant (MDR) Gram-negative bacteria (GNB) have raised concerns as common, frequent etiologic agents of nosocomial infections, and patients admitted to intensive care units (ICUs) present the highest risk for colonization and infection. The incidence of colonization and infection in trauma patients remains poorly investigated. The aim of this study was to assess the risk factors for Carbapenem-resistant (CR)-GNB colonization and the clinical impact of colonization acquisition in patients with severe trauma admitted to the ICU in a CR-GNB hyperendemic country. This is a retrospective observational study; clinical and laboratory data were extracted from the nosocomial infection surveillance system database. Among 54 severe trauma patients enrolled in the study, 28 patients were colonized by CR-GNB; 7 (12.96%) patients were already colonized at ICU admission; and 21 (38.89%) patients developed a new colonization during their ICU stay. Risk factors for colonization were the length of stay in the ICU (not colonized, 14.81 days ± 9.1 vs. colonized, 38.19 days ± 27.9; p-value = 0.001) and days of mechanical ventilation (not colonized, 8.46 days ± 7.67 vs. colonized, 22.19 days ± 15.09; p-value < 0.001). There was a strong statistical association between previous colonization and subsequent development of infection (OR = 80.6, 95% CI 4.5−1458.6, p-value < 0.001). Factors associated with the risk of infection in colonized patients also included a higher Charlson comorbidity index, a longer length of stay in the ICU, a longer duration of mechanical ventilation, and a longer duration of treatment with carbapenem and vasopressors (not infected vs. infected: 0(0−4) vs. 1(0−3), p = 0.012; 24.82 ± 16.77 vs. 47 ± 28.51, p = 0.016; 13.54 ± 15.84 vs. 31.7 ± 16.22, p = 0.008; 1.09 ± 1.14 vs. 7.82 ± 9.15, p = 0.008). The adoption of MDR-GNB colonization prevention strategies in critically ill patients with severe trauma is required to improve the quality of care and reduce nosocomial infections, length of hospital stay and mortality.

Candida parapsilosis osteomyelitis following dog bite: a case report and review of the literature.

Candida osteomyelitis is uncommon, especially after dog bites. We describe a case of a 63-year-old man without significant comorbidities presenting progressing swelling of the distal interphalangeal joint (DIJ) of right index finger following a dog bite. Despite empiric antibiotic therapy and local medications, there were no clinical signs of improvement. Clinical examination revealed fistula with purulent drainage on the volar region. Even though laboratory data showed inflammatory markers on range, magnetic resonance imaging (MRI) demonstrated signs of osteomyelitis. The patient was taken to exploration and debridement of the bite wound. Culture of the bone biopsy showed growth of Candida parapsilosis. Therefore, the patient was diagnosed with isolated fungal osteomyelitis and was initiated on fluconazole therapy. The treatment was effective and all symptoms were resolved in 8 weeks after the surgery. There were no signs of recurrence after 20 months of follow-up. The patient had no cosmetic abnormalities or sequelae. Concurrently with the description of the case report a review of the literature was provided. According to the authors, there are three main etiopathogenesis for this infection. The first pathogenic mechanism is direct inoculation into the deep tissues through the dog bite. The second hypothesis is direct translocation of the pathogen from the skin to the deep tissue and to the bone. The last mode of transmission is hematogenous dissemination. Fungal osteomyelitis are really rare conditions, especially after dog bites, but nevertheless it should be considered as a possible diagnosis when there is no response to antibiotics.

Candida fracture-related infection: a systematic review.

Background: The aim of this study is to summarize and improve knowledge regarding a Candida fracture-related infection (CFRI) through a systematic review on the topic, accompanied by a case report. Methods: A systematic review and meta-analysis based on PRISMA statement were conducted on the CFRI topic. The following combined search terms were used to explore PubMed, Cochrane, and the Embase database: "fungal infection", "candida", "fracture related infection", "bone infection", "orthopedic infection", "internal fixation", "post-traumatic infection", and "osteomyelitis". Results: Out of 1514 records, only 5 case reports matched the selection criteria and were included. Moreover, a new case of CFRI, not previously described, was reported in this paper and reviewed. The main risk factors for CFRI were open wounds (three cases) and immunodeficiency (three cases). Initial improvement of clinical and laboratory signs of infection was noted in all cases. In the available short-term follow-up (mean 12.1 months; range 3-42), the reoperation rate was 33.3 %. Using a strategy based on extensive debridement/resection methods and prolonged systemic antifungal therapy (mean 8.8 weeks; range 6-18), four of six cases (66.6 %) were cured. Bone union occurred in three out of six cases. Conclusion: There is very low-quality evidence available regarding CFRI. Candida infections in surgically treated fractures are rare but difficult-to-treat events, with a slow onset, unspecific symptoms or signs, and a significant relapse risk; therefore, they still represent a current diagnostic challenge. The existing fracture-related infection treatment algorithm combined with long-term systemic antifungal therapy has an anecdotal value and needs more extensive studies to be validated.

Clinical Application of Antibacterial Hydrogel and Coating in Orthopaedic and Traumatology Surgery.

Implant related infection is one of the most frequent complications in orthopaedic and trauma surgery. Local antibiotic treatment strategies are becoming part of the prevention and treatment methodology for this fearful complication. To date, there are two coatings available on the market, both with a polylactic acid base. Current evidence supports the use of these types of coatings in the prophylaxis of periprosthetic infections and fracture-related infections. However, their therapeutic use has been less investigated. The purpose of this article is to summarise recent evidence relating to the clinical application of antibacterial hydrogels and coatings in orthopaedic and traumatology surgery and indicating which future applications may benefit from it.

The Aftermath of COVID-19 Lockdown on Daily Life Activities in Orthopaedic Patients.

PURPOSE: Following the 2019 coronavirus (COVID-19) pandemic, many reports have investigated the psychosocial effects of the lockdown. The aim of our study was to investigate the effects of the lockdown on the daily life habits of orthopaedic patients. PATIENTS AND METHODS: Around 30 days after the start of the Italian lockdown, from April 17th to the end of the containment measures on May 18th, the Sapienza University of Rome carried out a 19-item survey on the effects the lockdown caused in patients suffering from an orthopaedic pathology (with regard to changes in lifestyle, pain, treatment) by stratifying the sample by age, sex, profession, pain location, pathogenesis and prior surgeries. RESULTS: A total of 292 subjects with orthopaedic pathologies took part in the survey. Taking into consideration the totality of the sample, physical activity was significantly reduced (p <0.001). The increase of a sedentary lifestyle was statistically significant (p <0.001), as well as an increase in pain (p <0.001) and the need to adjust the pharmacological treatment (p <0.001). The increase in pain was particularly significant in the 50-70 age group, among workers, and in polyarthralgic patients. About 55.48% stated that the lockdown period worsened their underlying pathological condition and 53.77% expressed the need to undergo a new clinical evaluation at the end of the lockdown. CONCLUSION: The impact of the COVID-19 pandemic lockdown and resulting sudden changes in lifestyle led to a change in patient perception of orthopedic pathology including a worsening of musculoskeletal pain requiring an adjustment or change in pharmacological and physical therapy.

A novel approach for the isolation and long-term expansion of pure satellite cells based on ice-cold treatment.

Satellite cells (SCs) are muscle stem cells capable of regenerating injured muscle. The study of their functional potential depends on the availability of methods for the isolation and expansion of pure SCs with preserved myogenic properties after serial passages in vitro. Here, we describe the ice-cold treatment (ICT) method, which is a simple, economical, and efficient method for the isolation and in vitro expansion of highly pure mouse and human SCs. It involves a brief (15-30 min) incubation on ice (0 °C) of a dish containing a heterogeneous mix of adherent muscle mononuclear cells, which leads to the detachment of only the SCs, and gives rise to cultures of superior purity compared to other commonly used isolation methods. The ICT method doubles up as a gentle passaging technique, allowing SC expansion over extended periods of time without compromising their proliferation and differentiation potential. Moreover, SCs isolated and expanded using the ICT method are capable of regenerating injured muscle in vivo. The ICT method involves minimal cell manipulation, does not require any expertise or expensive reagents, it is fast, and highly reproducible, and greatly reduces the number of animals or human biopsies required in order to obtain sufficient number of SCs. The cost-effectiveness, accessibility, and technical simplicity of this method, as well as its remarkable efficiency, will no doubt accelerate SC basic and translational research bringing their therapeutic use closer to the clinic.

A Simple Method for the Isolation and in vitro Expansion of Highly Pure Mouse and Human Satellite Cells.

Satellite cells (SCs) are muscle stem cells capable of regenerating injured muscle. The study of their functional potential depends on the availability of methods for the isolation and expansion of pure SCs, which retain myogenic properties after serial passages in vitro. Here, we describe a protocol for the isolation and in vitro expansion of highly pure mouse and human SCs based on ice-cold treatment (ICT). The ICT is carried out by briefly incubating the dish containing a heterogeneous mix of adherent muscle mononuclear cells on ice for 15-30 min, which leads to the detachment only of the SCs, and gives rise to SC cultures with 95-100% purity. This approach can also be used to passage the cells, allowing SC expansion over extended periods of time without compromising their proliferation or differentiation potential. Overall, the ICT method is cost-effective, accessible, technically simple, reproducible, and highly efficient. Graphic abstract: Figure 1.Satellite cell isolation using the ice-cold treatment method.

Gentamicin-Coated Tibia Nail in Fractures and Nonunion to Reduce Fracture-Related Infections: A Systematic Review.

The incidence of a fracture-related infection (FRI) can reach 30% of open tibia fractures (OTF). The use of antibiotic-coated implants is one of the newest strategies to reduce the risk of infection in orthopedic surgery. The aim of this study was to investigate the efficacy and safety of a gentamicin-coated tibia nail in primary fracture fixation (FF) and revision surgery (RS) of nonunion cases in terms of FRI incidence. We conducted a systematic review according to the PRISMA checklist on Pub-Med, Cochrane, and EMBASE. Of the 32 studies, 8 were included, for a total of 203 patients treated: 114 were FF cases (63% open fractures) and 89 were RS cases, of which 43% were infected nonunion. In the FF group, four FRI were found (3.8%): three OTF (Gustilo-Anderson III) and one closed fracture; bone healing was achieved in 94% of these cases. There were four relapses of infection and one new onset in the RS group; bone healing occurred in 88% of these cases. No side effects were found. There were no significant differences in terms of FRI, nonunion, and healing between the two groups. Gentamicin-coated tibia nail is an effective therapeutic option in the prophylaxis of high-risk fracture infections and in complex nonunion cases.

Validity and reliability of the Unified Classification System applied to periprosthetic femur fractures: a comparison with the Vancouver system.

Objective: The Unified Classification System (UCS) presents itself as an evolution of the Vancouver Classification (VCS) for the evaluation of periprosthetic fractures of the proximal femur (PPF). The aim of our study was to highlight any loss of reproducibility or validity of the new classification system, compared to the previous one.Material and methods: We tested the interobserver and intraobserver agreement using 40 PPF clinical cases. Each classifying subtype of the UCS and VCS was present in at least two cases. Six experienced hip surgeons (Senior Surgeon, SS) and 5 surgeons in training (Junior Surgeon, JS) classified the clinical cases, using VCS and UCS. The validity of both classifications was then tested with intraoperative surveys.Results: The mean κ value for interobserver agreement for the VCS in the JS group was 0.65 and 0.81 for the SS group. The mean κ value for interobserver agreement for the UCS in the JS group was 0.63 and 0.65 for the SS group. The mean κ value for intraobserver agreement for the VCS in the JS group was 0.71 and 0.73 for the SS group. The mean κ value for intraobserver agreement for the UCS in the JS group was 0.72 and 0.7 for the SS group. Validity analysis showed a moderate agreement for the VCS and a good agreement for the UCS.Conclusion: The UCS completes the Vancouver classification, expanding it. It is reliable, despite the increase in classification categories and number of parameters to evaluate, with a slightly higher validity.

Is postoperative hyponatremia a real threat for total hip and knee arthroplasty surgery?

Postoperative hyponatremia (POH) is thought to be a fearsome complication of orthopedic surgery. Primary aim of this cohort study was to evaluate the incidence of POH and its clinical relevance in elective surgery, outlining differences between total knee arthroplasty (TKA) and total hip arthroplasty, looking for the presence of any risk factor commonly related to POH.Four hundred two patients that underwent total hip arthroplasty and total knee arthroplasty performed between 2016 and 2017 were retrospectively examined. Serum electrolytes, hemoglobin, hematocrit, glucose, and creatinine were evaluated preoperatively and at day 0-I-II from surgery. Age, sex, body mass index, comorbidities, drugs, surgery data, transfusions, postoperative symptoms, and length of stay (LOS) were determined. All surgeries were performed by the same equipe. Patients had the same perioperative management, excluded those that took thiazides, already at risk of POH.Patients were divided in 2 groups: group A, patients with normal postoperative natremia (294 patients) and group B, patients who developed POH (108, 26.9%); 66.7% of these developed POH within 24 hours postoperatively. In group B mean postoperative natremia was 133.38 (127.78-134.85) mmol/L. Two patients (1.8%) developed moderate hyponatremia, no severe hyponatremia was documented. Type of surgery, operation time, LOS, and presence of postoperative symptoms did not show statistically significant differences within groups. At multivariate logistic analysis chronic use of thiazides was the only variable associated to a decreased risk of developing POH (OR = 0.39; P = .03). Hemoglobin postoperative values (OR = 1.22; P = .03), the need of postoperative transfusion (OR = 2.50; P = .02) and diabetes (OR = 2.70; P = .01) were associated to an increased risk of POH.Although 26.9% of our patients exhibited POH, the onset of this disorder had no implication on postoperative symptoms and on LOS. Diabetes and transfusion are factors most often associated to POH.

Antibiotic-Loaded Hydrogel Coating to Reduce Early Postsurgical Infections in Aseptic Hip Revision Surgery: A Retrospective, Matched Case-Control Study.

Periprosthetic joint infections (PJIs) are a cause of frequent implant failure in revision hip replacement surgery. The purpose of this study is to evaluate the onset of early postoperative infections in patients who underwent hip surgery with cementless prostheses treated with an antibiotic loaded hydrogel on their surface, in addition to systemic prophylaxis, and compare them to a control group. The secondary objective was to evaluate the onset of any local and systemic adverse effects and interference with bone ingrowth processes and functional recovery. A retrospective observational study was conducted on patients who underwent revision hip surgery by performing a 1:1 match between patients treated with an antibiotic hydrogel (ALH) and the control patients. The incidence of PJIs was assessed with a minimum of six months follow-up. Seventeen patients treated with the ALH were compared with 17 patients from the control group. No PJIs were reported in the ALH group versus the six cases encountered in the control group (p < 0.0001). No significant differences were reported with regard to prosthetic osseointegration and functional results, nor were there side effects in the ALH group. Despite the low sample size, the use of on-site prophylaxis with ALH has proven effective and safe in reducing the risk of PJIs in patients with a high risk for infections. Further studies are needed to validate these results in other implant-related surgeries.