Orthopedic Infections Research Articles

Bilateral Obturator Osteotomy: A Novel Osteotomy for Bladder Exstrophy Closure

BackgroundAbdominal and pelvic closure remains a challenge during bladder exstrophy initial repair. We aimed to report on the feasibility and results of a novel technique of bilateral obturator osteotomy. MethodsRetrospective study of prospective collected data of children who underwent single-stage delayed bladder exstrophy closure combined with RSTM (Radical Soft Tissue Mobilization) for BEEC (Bladder Exstrophy Epispadias Complex) by the same team at different institutions between December 2017 and May 2021. When pubic approximation was not feasible at the end of the procedure, bilateral obturator osteotomy was performed through the same approach, consisting in bilateral divisions of the ilio-pubic rami, ischio-pubic rami, obturator membrane, and detachment of the internal obturator muscle. Pubic bone fragments were approximated together on the midline. Immobilization in a thermoformed posterior splint was indicated for 3 weeks. The main outcome criterion was the bladder dehiscence rate at 6 months, assessed by physical inspection. Secondary outcome criteria included neurovascular obturator pedicle injury, analyzed during orthopedic physical examination, wound or bone infections, gait acquisition, reported by parents and evaluated during medical examination, and vascular penile impairment, judged by penile and glans coloration. Results17 children (11 males, 6 females) were included, at a median age of 2 months [1–33]; and representing 29% (17/58) of the children with bladder exstrophy who underwent the same surgical approach during the time of study. There was no postoperative bladder dehiscence with a median follow-up of 34 months [6–47]. No complication was observed. Pelvic X-rays showed bilateral normal ossification process. Neither gait abnormality, nor clinical indication of obturator nerve deficiency was observed during follow-up. ConclusionWhen pubic bones approximation is not possible, bilateral obturator osteotomy is a useful adjunct in bladder exstrophy closure, feasible by the pediatric urologist through the same approach, and not requiring external fixator. Level of EvidenceIV.

Twelve-Year Dynamics of Leading Pathogens Spectrum Causing Orthopedic Infection: A Retrospective Study

Background. The number of surgeries on the musculoskeletal system is increasing every year. Along with the increasing access to orthopedic care, the number of patients with orthopedic infection, the etiological agents of which can be from various taxonomic groups, is also increasing. Staphylococcus aureus and different types of coagulase-negative staphylococci (CoNS), including S. epidermidis and S. lugdunensis, together are the causative agents in 70% of cases.
 Aim of the study — to analyze the dynamics of the microbial spectrum isolated from patients of the septic surgery department for the period from 2011 to 2022.
 Methods. We performed a retrospective analysis of the microbial spectrum isolated from patients who were treated in the septic surgery department from January 1, 2011 to December 31, 2022. The leading pathogens were microorganisms whose share in the spectrum exceeded 3.5%. Of the isolated pathogens, 48.8% were the only etiological agents, and microbial associations were detected in 51.2% of the isolated pathogens.
 Results. A total of 10,327 bacteria strains were identified over the 12-year period. The leading microorganisms causing orthopedic infection were Staphylococcus spp., Enterococcus spp., Propionibacterium spp., Pseudomonas aeruginosa, Corynebacterium spp., Streptococcus spp., Klebsiella spp. and Acinetobacter spp. In the dynamics of isolated pathogens during the analyzed period, several trends were determined: a decrease in the shares of S. aureus, Enterococcus spp., P. aeruginosa, Acinetobacter spp. and an increase in the shares of CoNS and Corynebacterium spp.
 Conclusion. During 12 years, in the microbial spectrum of orthopedic infection in patients of the septic surgery department of our Center, Gram-positive bacteria, in the majority representatives of the genus Staphylococcus, prevailed. At the same time, a significant decrease in the share of S. aureus strains and an increase in the frequency of isolation of various species of CoNS were registered. A significant decrease in the number of non-fermenting Gram-negative bacteria was also revealed.

Clinical challenges and advancements in diagnosing Staphylococcus aureus-associated musculoskeletal infections

Musculoskeletal infections (MSKI) present a significant health challenge, with a rising incidence linked to the aging population and advancements in orthopedic surgical care. Staphylococcus aureus is the most prevalent pathogen associated with orthopedic infections. The conventional culture method for identification of pathogen frequently lacks accuracy and is challenged by false-positive or false-negative results. Inflammatory markers such as the erythrocyte sedimentation rate and C-reactive protein are not site-specific or accurate, as they can be confounded by other medical conditions. Identifying the dominant pathogen and monitoring treatment response following surgical debridement and antibiotics therapy continues to pose challenges. Understanding the pathogenesis of MSKI is crucial for the development of innovative diagnostics and alternative therapeutics. S. aureus immune evasion stands out as a key component of the pathogenic mechanism, complicating clinical decisions. Other unique mechanisms such as biofilm and abscess formation, as well as osteocyte-lacuno canalicular network invasion, underscore the need for aggressive debridement and the complete removal of infected implants and bone tissues. Ongoing efforts focus on exploring and developing innovative diagnostics, such as serum immunoassays, next-generation sequencing of infected tissue, transcriptomics of peripheral blood mononuclear cells, and serum proteomics. These endeavors offer promising avenues for improved diagnostics, medical management, and innovative therapeutics for MSKI.

Current updates in MSK infection imaging: A narrative review

This article presents a comprehensive overview of the diagnostic utility of existing imaging techniques including radiography, computed tomography, ultrasonography, magnetic resonance imaging (MRI), and radionuclide imaging in the context of the most common orthopaedic or musculoskeletal infections. It also includes illustrative images showcasing significant findings in various musculoskeletal infections including osteomyelitis, cellulitis, septic arthritis, necrotising infections and peri-prosthetic joint infections and their associated complications.

Next Generation Sequencing in orthopaedic infections – Where is the road headed?

Next-generation sequencing (NGS) has emerged as a game changer in the field of orthopaedic diagnostics, notably in the detection and management of infections associated with prosthetic joints and implants. This paper conducts an exhaustive examination of the pivotal role, outcomes, and prospective future uses of NGS in diagnosing orthopaedic infections. In comparison to conventional culture-based methods, NGS offers a marked improvement in sensitivity thereby facilitating prompt and comprehensive identification of pathogens. This encompasses the ability to detect polymicrobial infections, antibiotic-resistant strains, and previously imperceptible microorganisms. Furthermore, this article delves into the technology's contribution to advancing personalized medicine and promoting judicious antibiotic use. Nonetheless, the seamless integration of NGS into routine clinical practice is impeded by challenges such as substantial financial outlays, the requisite for specialized equipment and expertise, and the intricacy associated with data analysis. Notwithstanding these impediments, the potential for NGS to revolutionize orthopaedic diagnostics remains substantial, with ongoing advancements poised to address current limitations and broaden its scope within clinical applications.

Porous versus solid shoulder implants in humeri of different bone densities: A finite element analysis.

Porous metallic prosthesis components can now be manufactured using additive manufacturing techniques, and may prove beneficial for promoting bony ingrowth, for accommodating drug delivery systems, and for reducing stress shielding. Using finite element modeling techniques, 36 scenarios (three porous stems, three bone densities, and four held arm positions) were analysed to assess the viability of porous humeral stems for use in total shoulder arthroplasty, and their resulting mechanobiological impact on the surrounding humerus bone. All three porous stems were predicted to experience stresses below the yield strength of Ti6Al4V (880 MPa) and to be capable of withstanding more than 10 million cycles of each loading scenario before failure. There was an indication that within an 80 mm region of the proximal humerus, there would be a reduction in bone resorption as stem porosity increased. Overall, this study shows promise that these porous structures are mechanically viable for incorporation into permanent shoulder prostheses to combat orthopedic infections.

Role of Dithiothreitol in Detection of Orthopaedic Implant-Associated Infections.

Orthopaedic implant-associated infections (OIAIs) represent a notable complication of contemporary surgical procedures, exerting a considerable impact on patient outcomes and escalating healthcare expenditures. Prompt diagnosis holds paramount importance in managing OIAIs, with sonication widely acknowledged as the preferred method for detecting biofilm-associated infections. Recently, dithiothreitol (DTT) has emerged as a potential substitute for sonication, owing to its demonstrated ability to impede biofilm formation. This study aimed to compare the efficacy of DTT with sonication in identifying microorganisms within implants. Conducted as a prospective cohort investigation, the study encompassed two distinct groups: patients with suspected infections undergoing implant removal (Group A) and those slated for hardware explantation (Group B). Hardware segments were assessed for biofilm-related microorganisms using both sonication and DTT, with a comparative analysis of the two methods. A total of 115 patients were enrolled. In Group A, no statistically significant disparity was observed between DTT and sonication. DTT exhibited a sensitivity of 89.47% and specificity of 96.3%. Conversely, in Group B, both DTT and sonication fluid cultures yielded negative results in all patients. Consequently, this investigation suggests that DTT holds comparable efficacy to sonication in detecting OIAIs, offering a novel, cost-effective, and readily accessible diagnostic modality for identifying implant-associated infections.

Local delivery of linezolid in the treatment of complex orthopedic bone and joint infections in patients with vancomycin allergy: a case series.

Introduction: Osteomyelitis is a challenging bone infection associated with ischemia, trauma, or various surgical procedures (e.g., joint reconstruction). Treatment involves eradicating infected bone and soft tissue, local antibiotic delivery, and a 6-week course of antibiotics. Methicillin-resistant Staphylococcus aureus (MRSA) infections are common, and vancomycin is the standard treatment, but alternatives like linezolid are needed in vancomycin-resistant and vancomycin-allergic patients. Methods: A retrospective chart review was conducted on patients treated by the senior author between 2013 and 2021. The study included patients who received local delivery of linezolid for bone and/or joint infection with documented evidence of vancomycin allergy. Patient demographics, surgical details, linezolid delivery method, and outcomes were recorded. Clinical outcomes and subsequent procedures leading to infection eradication were documented. Results: A total of 13 patients were treated with linezolid-antibiotic-laden spacers with polymethyl methacrylate (PMMA) carrier. Nine patients were successfully treated using limb-salvage techniques and were still infection-free after a mean follow-up of 55.5 months. Conclusions: Linezolid-loaded bone cement is an option for managing chronic bone and joint infections, particularly MRSA, in patients with vancomycin allergy.

Outpatient parenteral antimicrobial therapy (OPAT) in Germany: insights and clinical outcomes from the K-APAT cohort study

PurposeOutpatient parenteral antimicrobial therapy (OPAT) offers several key advantages, including enhanced patient quality of life, reduced healthcare costs, and a potential reduction of nosocomial infections. It is acknowledged for its safety and effectiveness. This study provides the first systematic clinical data for Germany, where OPAT has not yet been widely adopted. The aim is to establish a foundational reference point for further research and integration of OPAT into the German healthcare system.MethodsThis prospective observational study descriptively analyses data obtained from a cohort of patients receiving OPAT. Both in- and outpatients from all medical specialties could be recruited. Patients administered the anti-infective medications themselves at home using elastomeric pumps.Results77 patients received OPAT, with a median duration of 15 days and saving 1782 inpatient days. The most frequently treated entities were orthopaedic infections (n = 20, 26%), S. aureus bloodstream infection (n = 16, 21%) and infectious endocarditis (n = 11, 14%). The most frequently applied drugs were flucloxacillin (n = 18, 23%), penicillin G (n = 13, 17%) and ceftriaxone (n = 10; 13%). Only 5% of patients (n = 4) reported to have missed more than one outpatient dose (max. 3 per patient). Only one catheter-related adverse event required medical intervention, and there were no catheter-related infections.ConclusionThe study demonstrates that OPAT can be safely conducted in Germany. In preparation for its broader implementation, crucial next steps include creating medical guidelines, fostering interdisciplinary and inter-sectoral communication, as well as creating financial and structural regulations that facilitate and encourage the adoption of OPAT.Trial registration numberNCT04002453.

Recent Advances in Antibacterial Coatings to Combat Orthopedic Implant-Associated Infections.

Implant-associated infections (IAIs) represent a major health burden due to the complex structural features of biofilms and their inherent tolerance to antimicrobial agents and the immune system. Thus, the viable options to eradicate biofilms embedded on medical implants are surgical operations and long-term and repeated antibiotic courses. Recent years have witnessed a growing interest in the development of robust and reliable strategies for prevention and treatment of IAIs. In particular, it seems promising to develop materials with anti-biofouling and antibacterial properties for combating IAIs on implants. In this contribution, we exclusively focus on recent advances in the development of modified and functionalized implant surfaces for inhibiting bacterial attachment and eventually biofilm formation on orthopedic implants. Further, we highlight recent progress in the development of antibacterial coatings (including self-assembled nanocoatings) for preventing biofilm formation on orthopedic implants. Among the recently introduced approaches for development of efficient and durable antibacterial coatings, we focus on the use of safe and biocompatible materials with excellent antibacterial activities for local delivery of combinatorial antimicrobial agents for preventing and treating IAIs and overcoming antimicrobial resistance.

Halicin remains active against Staphylococcus aureus in biofilms grown on orthopaedically relevant substrates.

Biofilm infections are among the most challenging complications in orthopaedics, as bacteria within the biofilms are protected from the host immune system and many antibiotics. Halicin exhibits broad-spectrum activity against many planktonic bacteria, and previous studies have demonstrated that halicin is also effective against Staphylococcus aureus biofilms grown on polystyrene or polypropylene substrates. However, the effectiveness of many antibiotics can be substantially altered depending on which orthopaedically relevant substrates the biofilms grow. This study, therefore, evaluated the activity of halicin against less mature and more mature S. aureus biofilms grown on titanium alloy, cobalt-chrome, ultra-high molecular weight polyethylene (UHMWPE), devitalized muscle, or devitalized bone. S. aureus-Xen36 biofilms were grown on the various substrates for 24 hours or seven days. Biofilms were incubated with various concentrations of halicin or vancomycin and then allowed to recover without antibiotics. Minimal biofilm eradication concentrations (MBECs) were defined by CFU counting and resazurin reduction assays, and were compared with the planktonic minimal inhibitory concentrations (MICs). Halicin continued to exert significantly (p < 0.01) more antibacterial activity against biofilms grown on all tested orthopaedically relevant substrates than vancomycin, an antibiotic known to be affected by biofilm maturity. For example, halicin MBECs against both less mature and more mature biofilms were ten-fold to 40-fold higher than its MIC. In contrast, vancomycin MBECs against the less mature biofilms were 50-fold to 200-fold higher than its MIC, and 100-fold to 400-fold higher against the more mature biofilms. Halicin is a promising antibiotic that should be tested in animal models of orthopaedic infection.

Mechanobiology of bacterial biofilms: Implications for orthopedic infection.

Postoperative bacterial infections are prevalent complications in both human and veterinary orthopedic surgery, particularly when a biofilm develops. These infections often result in delayed healing, early revision, permanent functional loss, and, in severe cases, amputation. The diagnosis and treatment pose significant challenges, and bacterial biofilm further amplifies the therapeutic difficulty as it confers protection against the host immune system and against antibiotics which are usually administered as a first-line therapeutic option. However, the inappropriate use of antibiotics has led to the emergence of numerous multidrug-resistant organisms, which largely compromise the already imperfect treatment efficiency. In this context, the study of bacterial biofilm formation allows to better target antibiotic use and to evaluate alternative therapeutic strategies. Exploration of the roles played by mechanical factors on biofilm development is of particular interest, especially because cartilage and bone tissues are reactive environments that are subjected to mechanical load. This review delves into the current landscape of biofilm mechanobiology, exploring the role of mechanical factors on biofilm development through a multiscale prism starting from bacterial microscopic scale to reach biofilm mesoscopic size and finally the macroscopic scale of the fracture site or bone-implant interface.

Silver carboxylate-TiO2/polydimethyl siloxane is a safe and effective antimicrobial with significant wound care potential.

With the rise in antibiotic resistance, new methodologies are needed to combat musculoskeletal infections. Silver is an antimicrobial that can be synthesized in different forms, but its pharmacokinetics are difficult to control. This study details the antibacterial efficacy and cellular cytotoxicity of a formulation consisting of silver carboxylate (AgCar) released through a titanium dioxide/polydimethylsiloxane matrix with a predictable release profile on Pseudomonas aeruginosa, Acinetobacterium baumannii, and human-derived primary osteoblasts. Through an Institutional Animal Care and Use Committee and IRB-approved protocol, AgCar was applied to live Yucatan porcine skin and histologically analyzed for skin penetration. Graphite Furnace Atomic Absorption Spectroscopy (GFAAS) was used to measure elution of AgCar. Dose-response curves were generated through optical density to assess potency. Finally, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was used to quantify the cellular cytotoxicity of the novel formulation. The results were subject to statistical analysis using analysis of variance and post hoc Tukey tests. The silver carboxylate coating demonstrated deep penetration into the epithelium at the level of the deep pilosebaceous glands in animal models. GFAAS testing demonstrated the extended elution profile of silver carboxylate over 96 hours, while 100% silver with no titanium dioxide-polydimethylsiloxane matrix fully eluted within 48 hours. 10x silver carboxylate demonstrated superior antimicrobial activity to antibiotics and other silver formulations and showed minimal cytotoxicity compared with other silver formulations. Current antimicrobial therapies in wound care and surgical antisepsis, such as chlorhexidine gluconate, have pitfalls including poor skin penetration and short duration of efficacy. The broad antimicrobial activity, extended elution, and deep skin penetration of this AgCar formulation show great promise for surgical site infection and wound care treatment. Novel technology to fight the growing threat of microbial resistance should be at the forefront of orthopaedic surgical site infection prevention and treatment.

Effects of high antibiotic concentrations applied to continuous local antibiotic perfusion on human bone tissue-derived cells.

Continuous local antibiotic perfusion (CLAP) has recently attracted attention as a new drug delivery system for orthopaedic infections. CLAP is a direct continuous infusion of high-concentration gentamicin (1,200 μg/ml) into the bone marrow. As it is a new system, its influence on the bone marrow is unknown. This study aimed to examine the effects of high-concentration antibiotics on human bone tissue-derived cells. Cells were isolated from the bone tissue grafts collected from six patients using the Reamer-Irrigator-Aspirator system, and exposed to different gentamicin concentrations. Live cells rate, apoptosis rate, alkaline phosphatase (ALP) activity, expression of osteoblast-related genes, mineralization potential, and restoration of cell viability and ALP activity were examined by in vitro studies. The live cells rate (the ratio of total number of cells in the well plate to the absorbance-measured number of live cells) was significantly decreased at ≥ 500 μg/ml of gentamicin on day 14; apoptosis rate was significantly increased at ≥ 750 μg/ml, and ALP activity was significantly decreased at ≥ 750 μg/ml. Real-time reverse transcription-polymerase chain reaction results showed no significant decrease in the ALP and activating transcription factor 4 transcript levels at ≥ 1,000 μg/ml on day 7. Mineralization potential was significantly decreased at all concentrations. Restoration of cell viability was significantly decreased at 750 and 1,000 μg/ml on day 21 and at 500 μg/ml on day 28, and ALP activity was significantly decreased at 500 μg/ml on day 28. Our findings suggest that the exposure concentration and duration of antibiotic administration during CLAP could affect cell functions. However, further in vivo studies are needed to determine the optimal dose in a clinical setting.

Enhanced osteogenic and bactericidal performance of premixed calcium phosphate cement with photocrosslinked alginate thin film.

The increasing prevalence of implant-associated infections (IAI) in orthopedics remains a public health challenge. Calcium phosphates (CaPs) are critical biomaterials in dental treatments and bone regeneration. It is highly desirable to endow CaPs with antibacterial properties. To achieve this purpose, we developed a photocrosslinked methacrylated alginate co-calcium phosphate cement (PMA-co-PCPC) with antibacterial properties, using α-tricalcium phosphate (α-TCP) powders with 16% amorphous contents as solid phase, liquid phases containing CuCl2 and SrCl2 as an inhibitor, and CaCl2 as an activator to construct PCPC. When CaCl2 started to activate the hydration reaction, Sr2+ or Cu2+ ions were exchanged with Ca2+, and α-TCP dissolution was restarted and gradually hydrated to form calcium-deficient hydroxyapatite (CDHA). PMA was added to crosslink with Cu/Sr ions and form gel-layer-wrapped hydrated CDHA. This study explored the binding mechanism of PMA and PCPC and the ion release rule of Ca2+ → Sr2+/Cu2+, optimized the construction of several antibacterial PMA-co-PCPC materials, and analyzed the physical, chemical, and biological properties. Because of the combined effect of Cu and Sr ions, the scaffold exhibited a potential antibacterial activity, promoting bone formation and vascular regeneration. This work provides a basis for designing antibacterial calcium phosphate biomaterials with controllable treatment, which is an important characteristic for preventing IAI of biomaterials.

Emerging Issues and Initial Insights into Bacterial Biofilms: From Orthopedic Infection to Metabolomics.

Bacterial biofilms, enigmatic communities of microorganisms enclosed in an extracellular matrix, still represent an open challenge in many clinical contexts, including orthopedics, where biofilm-associated bone and joint infections remain the main cause of implant failure. This study explores the scenario of biofilm infections, with a focus on those related to orthopedic implants, highlighting recently emerged substantial aspects of the pathogenesis and their potential repercussions on the clinic, as well as the progress and gaps that still exist in the diagnostics and management of these infections. The classic mechanisms through which biofilms form and the more recently proposed new ones are depicted. The ways in which bacteria hide, become impenetrable to antibiotics, and evade the immune defenses, creating reservoirs of bacteria difficult to detect and reach, are delineated, such as bacterial dormancy within biofilms, entry into host cells, and penetration into bone canaliculi. New findings on biofilm formation with host components are presented. The article also delves into the emerging and critical concept of immunometabolism, a key function of immune cells that biofilm interferes with. The growing potential of biofilm metabolomics in the diagnosis and therapy of biofilm infections is highlighted, referring to the latest research.

In-label, off-label prescription, efficacy and tolerability of dalbavancin: report from a National Registry

PurposeAlthough dalbavancin is currently approved for the treatment of ABSSIs, several studies suggest its efficacy and tolerance as long-term therapy for other off-label indications requiring prolonged intravenous antibiotic administration.MethodsWe conducted a prospective nationwide study of dalbavancin use in real-life settings for both approved and off-label indications analysing for each case the clinical and microbiological characteristics of infection the efficacy and safety of treatments.ResultsDuring the study period (from December 2018 to July 2021), the ID specialists from 14 different centres enrolled 223 patients treated with dalbavancin [141 males (63%) and 82 females (37%); male/female ratio 1.72; mean age 59 (SD 17.2) years, (range 15–96). Most patients in the study population (136/223; 61.0%) came from community rather than health care facilities and most of them were visited in Infectious Diseases wards (93/223; 41.7%) and clinics (55/223; 24.7%) even though some patients were cured in other settings, such as surgery wards (18/223; 8.1%), orthopaedic wards (11/223; 4.9%), Emergency Rooms (7/223; 3.1%) and non-surgical other than ID wards (6/223; 2.7%). The most common ID diagnoses were osteomyelitis (44 cases/223; 19.7%; of which 29 acute and 15 chronic osteomyelitis), cellulitis (28/223; 12.5%), cutaneous abscess (23/223; 10.3%), orthopaedic prosthesis-associated infection (22/223; 9.9%), surgical site infection (20/223; 9.0%) and septic arthritis (15/223; 6.7%).ConclusionIn conclusion, by virtue of its PK/PD properties, dalbavancin represents a valuable option to daily in-hospital intravenous or outpatient antimicrobial regimens also for off-label indications requiring a long-term treatment of Gram-positive infections.

Prevalence of Infective Endocarditis among Patients with Staphylococcus aureus Bacteraemia and Bone and Joint Infections.

We aimed to evaluate the occurrence of infective endocarditis (IE) among patients with bone and joint infections (BJIs) and Staphylococcus aureus bacteraemia. This observational study was conducted at Lausanne University Hospital, Switzerland, from 2014 to 2023, and included episodes involving BJI, S. aureus bacteraemia, and cardiac imaging studies. The endocarditis team defined IE. Among the 384 included episodes, 289 (75%) involved native BJI (NBJI; 118 septic arthritis, 105 acute vertebral or non-vertebral osteomyelitis, 101 chronic osteitis), and 112 (29%) involved orthopedic implant-associated infection (OIAI; 78 prosthetic joint infection and 35 osteosynthesis/spondylodesis infection). Fifty-one episodes involved two or more types of BJI, with 17 episodes exhibiting both NBJI and OIAI. IE was diagnosed in 102 (27%) episodes. IE prevalence was 31% among patients with NBJI and 13% among patients with OIAI (p < 0.001). The study revealed a high prevalence of IE among S. aureus bacteraemic patients with NBJI, with notably lower prevalence among those with OIAI.

Synergistic use of anti-inflammatory ketorolac and gentamicin to target staphylococcal biofilms

BackgroundWhile antibiotics remain our primary tools against microbial infection, increasing antibiotic resistance (inherent and acquired) is a major detriment to their efficacy. A practical approach to maintaining or reversing the efficacy of antibiotics is the use of other commonly used therapeutics, which show synergistic antibacterial action with antibiotics. Here, we investigated the extent of antibacterial synergy between the antibiotic gentamicin and the anti-inflammatory ketorolac regarding the dynamics of biofilm growth, the rate of acquired resistance, and the possible mechanism of synergy.MethodsControl (ATCC 12600, ATCC 35984) and clinical strains (L1101, L1116) of Staphylococcus aureus and Staphylococcus epidermidis with varying antibiotic susceptibility profiles were used in this study to simulate implant-material associated low-risk and high-risk biofilms in vitro. The synergistic action of gentamicin sulfate (GS) and ketorolac tromethamine (KT), against planktonic staphylococcal strains were determined using the fractional inhibitory concentration measurement assay. Nascent (6 h) and established (24 h) biofilms were grown on 316L stainless steel plates and the synergistic biofilm eradication activity was determined and characterized using adherent bacteria count, minimum biofilm eradication concentration (MBEC) measurement for GS, visualization by live/dead imaging, scanning electron microscopy, gene expression of biofilm-associated genes, and bacterial membrane fluidity assessment.ResultsGentamicin-ketorolac (GS-KT) combination demonstrated synergistic antibacterial action against planktonic Staphylococci. Control and clinical strains showed distinct biofilm growth dynamics and an increase in biofilm maturity was shown to confer further resistance to gentamicin for both ‘low-risk’ and ‘high-risk’ biofilms. The addition of ketorolac enhanced the antibiofilm activity of gentamicin against acquired resistance in staphylococcal biofilms. Mechanistic studies revealed that the synergistic action of gentamicin–ketorolac interferes with biofilm morphology and subverts bacterial stress response altering bacterial physiology, membrane dynamics, and biofilm properties.ConclusionThe results of this study have a significant impact on the local administration of antibiotics and other therapeutic agents commonly used in the prevention and treatment of orthopaedic infections. Further, these results warrant the study of synergy for the concurrent or sequential administration of non-antibiotic drugs for antimicrobial effect.

Factors affecting risk of recurrence with periprosthetic infection in shoulder arthroplasty

BackgroundThe goal of treating periprosthetic infection, beside its eradication, is to avoid recurrence. The purpose of this study was to evaluate the impacts of increasing Infection Severity (IS) score (based on the 2018 International Committee on Orthopedic Infection Consensus statement), single-stage revision and the pathogenicity of the infective organism have on the risks of infection recurrence. MethodsA database of 790 revisions performed by a single surgeon from 2004-2020 was reviewed for patients with minimum 2-year follow-up and at least 1 positive culture and/or pathology result from that revision surgery. One hundred fifty-seven cases performed in 144 patients met inclusion criteria. Cases were then categorized by infection probability (IS score) according to the 2018 consensus statement. Forty-six of 157 (29%) cases were classified as definite/probable, 25/157 (16%) were classified as possibly infected, and 86/157 (55%) were classified as unlikely to be infected. Additionally, patients were grouped by single-stage surgery, and pathogenicity of infective organism. ResultsA recurrence in this study was classified as any patient requiring revision surgery that grew the same organism. The 86 cases in the unlikely group had a recurrence rate of 2.3%. The 25 cases in the possibly infected group had a recurrence rate of 12%. The 46 cases in the definite/probable group had a recurrence rate of 17.4%. Patients in the definite/probable group had a higher rate of recurrence than the possible and unlikely groups (p=0.009). The IS score was higher in the recurrence group than the non-recurrence group (7.5±4.3 vs 3.9±3.4; p<0.001). Overall, one-stage revision had a 5.0% recurrence rate, but of the 34 patients with an infection classification of definite/probable who underwent a one-stage revision, the recurrence rate was 5.9%. Highly virulent methicillin-resistant Staphylococcus aureus (MRSA) also had a recurrence rate of 30.8% compared to 4.0% and 5.9% in C. acnes and Coagulase-negative staphylococci, respectively (p=0.005). ConclusionRecurrent infection after treating a periprosthetic infection is associated with increasing severity scores as defined in 2018 consensus statement and more aggressive microorganisms. However, a single-stage surgery, even in patients with a higher IS score, did not impart a significant increased risk of recurrence.