Orthopedic Implant-associated Infections Research Articles

A Novel Bone-Targeting Enoxacin Delivery System to Eradicate Staphylococcus Aureus-Related Implantation Infections

Post-operative infections in orthopaedic implants are severe complications that require urgent solutions. Owing to the presence of implants and the formation of bacterial biofilms, the efficacy of antibiotics is limited. Furthermore, osteoclasts can become extremely active, accompanied by bone loss in the infected microenvironment. Therefore, implants often need to be removed. To improve the concentrations of antibiotics in bony tissues and enhance their effectiveness in preventing bacterial biofilm formation, the infection rate must be controlled to preserve the implants. Enoxacin exerts combined antibacterial and osteoclast inhibitory effects. It also plays a role in limiting infections and preventing bone loss. Aspartic acid octapeptide (ASP8) can also recognize and combine with hydroxyapatite crystals in bones and can be targeted to increase antibiotic concentrations in bones. Our previous research showed that preparing mesoporous nanomaterials resulted in optimal drug loading, releasing, and bone-targeting properties. Based on earlier research, a new bone-targeted antibiotic release system was developed. Enoxacin and ASP8 were loaded on mesoporous silica nanoparticles (MSNs) to increase antibiotic concentrations, prevent bacterial biofilm formation, inhibit aberrant osteoclast activities, and reduce bone loss. Enoxacin-loaded MSNs (Gen@MSN-D) were assessed using a variety of experimental methods, including rat models. We studied the in vitro antibacterial properties of the new drug delivery system. We found that these materials had antibacterial properties in vivo, inhibitory effects on osteoclasts, and can be used to prevent and treat post-implantation infections and bone loss. Therefore, we believe these materials will provide a new method for preventing and treating post-operative, orthopaedic implant-associated infections.

Efficacy of dalbavancin against MRSA biofilms in a rat model of orthopaedic implant-associated infection.

The aim of this study was to evaluate the efficacy of dalbavancin against MRSA biofilm-related infection in orthopaedic implants in vivo. One MRSA strain isolated from human osteomyelitis was used to promote biofilm formation on the surface of screws. The implants were inserted in the proximal tibia under general anaesthesia. Thirty-nine Wistar rats were divided into three groups [control group (no treatment), Group 1 (7 days of treatment) and Group 2 (14 days of treatment)]; both treatment groups were administered dalbavancin intraperitoneally and euthanized after treatment. cfu of bacteria present in both the tibia and the implant were quantified. The infection severity was assessed by histopathology and scored from 0 (no infection) to 4 (severe infection). The high number of cfu/g and cfu/mL present in the control group indicated a well-established infection. There was a significant reduction in cfu in rats treated with dalbavancin both in the tibia (2.8 × 105 cfu/g) and the implant (1.1 × 106 cfu/mL) in Group 1 (1.8 × 103 cfu/g and 2.4 × 105 cfu/mL, respectively) and in Group 2 (8.2 cfu/g and 8.2 × 103 cfu/mL, respectively). Most animals from the control group presented an infection scored as 3 (severe). At the end of the experiment, most rats from Groups 1 and 2 presented an infection scored as 2 (moderate) and 0 (no infection), respectively. Although there was a marked decrease in cfu number, signs of biofilm-induced infection prevailed after 14 days of treatment. Further studies should be carried out to evaluate the potential of dalbavancin in the treatment of bone and orthopaedic implant-associated MRSA infections.

Encapsulated bacteriophages in alginate-nanohydroxyapatite hydrogel as a novel delivery system to prevent orthopedic implant-associated infections

An innovative delivery system based on bacteriophages-loaded alginate-nanohydroxyapatite hydrogel was developed as a multifunctional approach for local tissue regeneration and infection prevention and control. Bacteriophages were efficiently encapsulated, without jeopardizing phage viability and functionality, nor affecting hydrogel morphology and chemical composition. Bacteriophage delivery occurred by swelling-disintegration-degradation process of the alginate structure and was influenced by environmental pH. Good tissue response was observed following the implantation of bacteriophages-loaded hydrogels, sustaining their biosafety profile. Bacteriophages-loaded hydrogels did not affect osteoblastic cells' proliferation and morphology. A strong osteogenic and mineralization response was promoted through the implantation of hydrogels system with nanohydroxyapatite. Lastly, bacteriophages-loaded hydrogel showed excellent antimicrobial activity inhibiting the attachment and colonization of multidrug-resistant E. faecalis surrounding and within femoral tissues. This new local delivery approach could be a promising approach to prevent and control bacterial contamination during implantation and bone integration.

Micrococcal-Nuclease-Triggered On-Demand Release of Vancomycin from Intramedullary Implant Coating Eradicates Staphylococcus aureus Infection in Mouse Femoral Canals.

Preventing orthopedic implant-associated bacterial infections remains a critical challenge. Current practices of physically blending high-dose antibiotics with bone cements is known for cytotoxicity while covalently tethering antibiotics to implant surfaces is ineffective in eradicating bacteria from the periprosthetic tissue environment due to the short-range bactericidal actions, which are limited to the implant surface. Here, we covalently functionalize poly(ethylene glycol) dimethacrylate hydrogel coatings with vancomycin via an oligonucleotide linker sensitive to Staphylococcus aureus (S. aureus) micrococcal nuclease (MN) (PEGDMA-Oligo-Vanco). This design enables the timely release of vancomycin in the presence of S. aureus to kill the bacteria both on the implant surface and within the periprosthetic tissue environment. Ti6Al4V intramedullary (IM) pins surface-tethered with dopamine methacrylamide (DopaMA) and uniformly coated with PEGDMA-Oligo-Vanco effectively prevented periprosthetic infections in mouse femoral canals inoculated with bioluminescent S. aureus. Longitudinal bioluminescence monitoring, μCT quantification of femoral bone changes, end point quantification of implant surface bacteria, and histological detection of S. aureus in the periprosthetic tissue environment confirmed rapid and sustained bacterial clearance by the PEGDMA-Oligo-Vanco coating. The observed eradication of bacteria was in stark contrast with the significant bacterial colonization on implants and osteomyelitis development found in the absence of the MN-sensitive bactericidal coating. The effective vancomycin tethering dose presented in this on-demand release strategy was >200 times lower than the typical prophylactic antibiotic contents used in bone cements and may be applied to medical implants and bone/dental cements to prevent periprosthetic infections in high-risk clinical scenarios. This study also supports the timely bactericidal action by MN-triggered release of antibiotics as an effective prophylactic method to bypass the notoriously harder to treat periprosthetic biofilms and osteomyelitis.

Growth detection of Cutibacterium acnes from orthopaedic implant-associated infections in anaerobic bottles from BACTEC and BacT/ALERT blood culture systems and comparison with conventional culture media

Cutibacterium acnes is a major etiologic agent of orthopaedic implant-associated infections (IAIs) and requires up to 14 days of incubation in an anaerobic atmosphere for growth detection. As blood culture (BC) systems are increasingly being used to monitor the growth of IAI specimens, we compared different BC media for growth detection of C. acnes. Non-duplicate C. acnes isolates (n = 99) obtained from sonicate-fluid cultures of orthopaedic IAIs from Slovenia (n = 54), conventional tissue samples of monomicrobial orthopaedic IAIs from France (n = 43) and two reference strains were inoculated to anaerobic BC bottles of two major BC systems and 3 conventional culture media types (thioglycolate broth, Schaedler and chocolate agar). Growth and time-to-detection (TTD) were recorded. Only Lytic (BACTEC) and SN (BacT/ALERT) bottles consistently detected growth of C. acnes within 14 days with 94% (n = 93) and 92% (n = 91) detection rates, respectively (p = 0.79). Lytic was superior to Plus BACTEC medium (p < 0.001), while SN was superior to all other BacT/ALERT media (p < 0.001). Mean TTD was 128 ± 43 h (61–336 h) for Lytic and 158 ± 65 h (77–336 h) for SN medium. Among the conventional media, 99% (n = 98) of the isolates grew on Schaedler agar, 96% (n = 95) in thioglycolate broth and 74% (n = 73) on chocolate agar. Inconsistent growth of C. acnes in different BC media can critically influence the detection of this major IAI pathogen. Only Lytic (BACTEC) and SN (BacT/ALERT) BC media types were consistently able to detect C. acnes within 14 days of incubation. However, visible growth was observed faster in thioglycolate broth and Schaedler agar media.

Diagnostic accuracy of 99mTc-antigranulocyte SPECT/CT in patients with osteomyelitis and orthopaedic device-related infections: A retrospective analysis

ObjectivesConventional imaging techniques are routinely used in the diagnostic work-up of patients with suspected osteomyelitis or orthopaedic implant-associated infections. Hybrid nuclear medicine imaging techniques are a suitable alternative to routine imaging modalities as they provide anatomical and functional information within one procedure. Our study investigated the performance of anti-granulocyte SPECT/CT using 99mTc-labelled monoclonal antibodies in the diagnosis of osteomyelitis and orthopaedic implant-associated infections. MethodsIn this retrospective analysis, we included patients with 99mTc-antigranulocyte SPECT/CT acquired in the context of a suspected bone and joint infection. All patients underwent routine diagnostics and/or had a clinical follow-up of at least 12months. Results26 episodes were included. Fifteen exams were performed for suspected osteomyelitis, and 11 for suspected orthopaedic implant-associated infection. SPECT/CT was ordered most often if standard diagnostic tests or conventional imaging modalities remained inconclusive. The overall sensitivity and specificity for the diagnosis of an infection were 77.8% and 94.1%, respectively. The positive predictive value was 87.5% and the negative predictive value 88.9%. Diagnostic accuracy was 88.5%. Conclusions99mTc-antigranulocyte SPECT/CT imaging has a high accuracy in the diagnosis of osteomyelitis and orthopaedic implant-associated infections and is a suitable non-invasive diagnostic tool if standard diagnostic examinations are inconclusive or not applicable.

Lytic bacteriophages against multidrug-resistant Staphylococcus aureus, Enterococcus faecalis and Escherichia coli isolates from orthopaedic implant-associated infections

Orthopaedic implant-associated infections are a devastating complication of orthopaedic surgery with a significant impact on patients and healthcare systems. The aims of this work were to describe the patterns of antimicrobial resistance, pathogenicity and virulence of clinical bacterial isolates from orthopaedic implant-associated infections and to further isolate and characterise bacteriophages that are efficient in controlling these bacteria. Staphylococcus aureus, Enterococcus faecalis and Escherichia coli isolated from orthopaedic infections showed multiresistance patterns to the most frequently used antibiotics in clinical settings. The presence of mobile genetic elements (mecA, Tn916/Tn1545 and intl1) and virulence determinants (icaB, cna, hlb, cylLs, cylM, agg, gelE, fsr and fimA) highlighted the pathogenicity of these isolates. Moreover, the isolates belonged to clonal complexes associated with the acquisition of pathogenicity islands and antimicrobial resistance genes by recombination and horizontal gene transfer. Bacteriophages vB_SauM_LM12, vB_EfaS_LM99 and vB_EcoM_JB75 were characterised and their ability to infect clinical isolates of S. aureus, E. faecalis and E. coli, respectively, was assessed. Morphological and genomic analyses revealed that vB_EfaS_LM99 and vB_EcoM_JB75 belong to the Siphoviridae and Myoviridae families, respectively, and no genes associated with lysogeny were found. The bacteriophages showed low latent periods, high burst sizes, broad host ranges and tolerance to several environmental conditions. Moreover, they showed high efficiency and specificity to infect and reduce clinical bacteria, including methicillin-resistant S. aureus and vancomycin-resistant enterococci. Therefore, the results obtained suggest that the bacteriophages used in this work are a promising approach to control these pathogens involved in orthopaedic implant-associated infections.

Chitosan sponges as a sustained release carrier system for the prophylaxis of orthopedic implant-associated infections

The present investigation aims to study the chitosan sponge as a carrier matrix for the sustained antibiotic release system for the prophylaxis of orthopedic implant-associated infections (OIAIs). We have prepared sponges of three broad-spectrum antibiotics, namely vancomycin, ciprofloxacin and cefuroxime possessing different physicochemical properties. The blank, vancomycin, ciprofloxacin and cefuroxime loaded chitosan sponges were denoted as Blank-CH, CH-VAN, CH-CIP, and CH-CEF sponges. Chitosan sponges were assessed for morphology, drug-release, antibacterial potential, and preclinical evaluation using a rat subcutaneous implantation model. The results revealed that the physicochemical properties of the drug incorporated into the chitosan matrix play an important role in the morphology, degradation and drug release profile. Due to the highly hydrophilic properties of vancomycin, the CH-VAN sponge showed the highest swelling and fastest degradation profile. The CH-VAN sponge demonstrated the short-term release in contrast with the CH-CEF and CH-CIP sponges, which showed sustained release along with sustainable antibacterial activity. The preclinical evaluation proved that the CH-CIP and CH-CEF sponges were biodegradable, non-toxic and biocompatible. Further, the CH-CIP and CH-CEF sponges were able to maintain minimum plasma concentration with higher local tissue antibiotic concentration. Therefore, the CH-CIP and CH-CEF sponges could be promising candidates for the long-term prophylaxis of OIAIs.

Sonication of Extracted Implants Improves Microbial Detection in Patients With Orthopedic Implant-Associated Infections

BackgroundWe assessed whether combining the conventional culture and implant sonicate fluid culture (SFC) methods increased the diagnostic accuracy of orthopedic implant-associated infection (OIAI). MethodsConsecutive patients (n = 66) undergoing implant removal (OIAI, 17; non-OIAI, 49) were evaluated prospectively. We analyzed 493 samples (39 preoperative joint aspirates, 243 peri-implant tissue specimens, 124 implant sonication, 67 controls, and 20 water bath samples). OIAI was preoperatively evaluated based on clinical evidence of infection or aspirate culture (AC). Conventional methods required positive results in either preoperative ACs or intraoperative tissue cultures (TCs), whereas the combination method required at least 1 positive culture among 3 sources (AC, TC, or SFC). The application of SFC and the detection rate, sensitivity, and specificity of the diagnostic methods were assessed. ResultsNo controls or water bath samples harbored bacteria. Three patients (18%) were detected by SFC only and Peptostreptococcus and Corynebacterium species were isolated by SFC only. The OIAI detection rate attributable to SFC was significantly higher than that of TC (61% vs 36%; P = .02). The sensitivities of AC, TC, and SFC at a cutoff point of 1 colony-forming unit/plate and 1 positive culture were 60%, 59%, and 71%, respectively. At a cutoff point of 2 positive cultures, the combination (vs conventional) method showed significantly greater sensitivity (71% vs 47%; P = .008). ConclusionBy incorporating SFCs into conventional culture methods, the diagnostic accuracy in the context of OIAI was significantly improved.

Orthopedic Implant-Associated Infection by Multidrug Resistant Enterobacteriaceae

Introduction: Orthopedic implant-associated infections caused by multidrug-resistant Enterobacteriaceae are a growing challenge for healthcare providers due to their increasing incidence and the difficulties of medical and surgical treatment. Material and Methods: A retrospective observational study of all cases of multidrug resistant Enterobacteriaceae orthopedic implant-associated infection diagnosed in a tertiary European hospital from December 2011 to November 2017 was carried out. Clinical records were reviewed using a previously designed protocol. Data analysis was performed with IBM® SPSS®, version 22. Results: 25 patients met inclusion criteria. The infected implants included 10 prosthetic joints, seven osteosyntheses, six combinations of prosthetic joint and osteosynthesis material, and two spacers. Of the multidrug resistant Enterobacteriaceae obtained on culture, 12 were extended-spectrum beta-lactamase-producing Escherichia coli, three OXA-48-producing Klebsiella pneumoniae, nine extended-spectrum beta-lactamase-producing Klebsiella pneumoniae, and one extended-spectrum beta-lactamase-producing Proteus mirabilis. Combination antimicrobial therapy was employed in all cases but two. Overall, 16 (64%) patients underwent implant removal. The rate of infection control in the overall implant removal group was 100% compared to 33% in the implant retention group. A strong relationship between implant removal and infection control was observed (p = 0.001). Discussion: Implant removal is strongly associated with infection control. However, in some cases, patient age and comorbidity contraindicate hardware extraction. Potential objectives for future studies should be geared towards targeting the population in which debridement, antibiotic therapy, and implant retention can be used as a first-line therapeutic strategy with a reasonable probability of achieving infection control.

Same Organism, Different Phenotype - Are Phenotypic Criteria Adequate In Coagulase-Negative Staphylococcal Orthopaedic Implant-Associated Infections?

In current diagnostic criteria for implant-associated bone- and joint infections, phenotypically identical low-virulence bacteria in two intraoperative cultures are usually required. Using whole-genome sequencing, we have further characterized three phenotypically different Staphylococcus capitis isolated from one prosthetic joint infection, highlighting the challenges in defining microbiological criteria for low-virulence prosthetic joint infections.

Biodegradable Electrosprayed NPs as Drug Carriers for Optimal Treatment of Orthopaedic Infections

Abstract The possibility of replacing the damaged joint by an artificial (hip replacement) is one of the most important achievements of the orthopaedic science because it enables the person suffering from osteoarthritis to regain a normal life. However, infections that can be created after an implantation are one of the major complications that can lead to implant failure. Therefore, a preliminary study of vancomycin drug loaded Polycaprolactone (PCL) nanoparticles were created via Electrospraying Process, making it a promising nanovehicle to prevent and treat orthopedic implant-associated infections. Scanning Electron Microscopy (SEM) measurements confirmed the successful fabrication of these structures. Finally, drug release kinetics was established to observe the sustained release of the drug and degradation studies were performed in order to evaluate the mass loss of polymers.

Improving the Diagnosis of Orthopedic Implant-Associated Infections: Optimizing the Use of Tools Already in the Box

With the increasing number of prosthetic joints replaced annually worldwide, orthopedic implant-associated infections (OIAI) present a considerable burden. Accurate diagnostics are required to optimize surgical and antimicrobial therapy. Sonication fluid cultures have been shown in multiple studies to improve the microbiological yield of OIAIs, but uptake of sonication has not been widespread in many routine clinical microbiology laboratories. In this issue, M. Dudareva and colleagues (J Clin Microbiol 56:e00688-18, 2018, https://doi.org/10.1128/JCM.00688-18) describe their unit's experience with OIAI diagnosis using periprosthetic tissue inoculated into an automated blood culture system and sonication fluid culture.

Orthopedic implant-associated infections caused by Cutibacterium spp. - A remaining diagnostic challenge.

BackgroundThe definition criteria and clinical characteristics of implant-associated infection (IAI) caused by Cutibacterium (formerly Propionibacterium) spp. are poorly known. We analyzed microbiologically proven Cutibacterium orthopedic IAI in a prospective cohort.MethodsPatients with periprosthetic joint infections (PJI) and fixation device–associated infections (FDAI) caused by Cutibacterium spp. were prospectively included. IAI was defined by significant growth of Cutibacterium spp. and presence of at least one non-microbiological criterion for infection. The McNemar’s chi-squared or binomial test was used to compare the performance of diagnostic tests.ResultsOf 121 patients with Cutibacterium IAI, 62 patients (51%) had PJI and 59 (49%) had FDAI. 109 infections (90%) were caused by C. acnes and 12 (10%) by C. avidum. The median time from implantation until diagnosis of infection was 15.7 months (interquartile range, 5–46.5 months). Clinical local signs were present in 30 patients (28%) and radiological implant loosening in 64 patients (63%). Culture sensitivity of sonication fluid was 84%, of peri-implant tissue 84% and of synovial or peri-implant fluid 56% after 14 days of incubation.ConclusionCutibacterium IAI was diagnosed late in the disease course and presented with subtle signs. Prolonged culture incubation and implant sonication improved the poor performance of conventional microbiological tests. Due to lack of reliable diagnostic tests, Cutibacterium remains difficult to detect making the diagnosis challenging.

Chitosan nanoparticles and povidone iodine containing alginate gel for prevention and treatment of orthopedic implant associated infections

Orthopedic Implant associated infections (OIAIs) are the most serious complications in the orthopedic surgery. Such complications are of major concern unless encountered during initial stages of contamination due to the bacterial biofilm formation. Thus, our aim is to eradicate bacteria at the early stages of infection. Herein, we develop a vancomycin-loaded chitosan nanoparticles (CNPs) and povidone-iodine (PI) containing in situ alginate (CNPs-PI-Alg) gel for antibacterial and antibiofilm activity, respectively. The CNPs were synthesized by ionic gelation method and the processing parameters were optimized to attain nanoparticles of 200–250 nm size and 37.13 ± 3.18 mV charge. A PI-loaded in situ alginate (PI-Alg) gel served as a carrier wherein, the CNPs were incorporated to attain sustained release of an antibacterial agent. The CNPs-PI-Alg gel showed more stability and mechanical properties compared to the Blank-Alg gel. The CNPs-PI-Alg gel exhibited sustained release of vancomycin and PI over a period of 10–15 days. The hemolysis and cytocompatibility studies demonstrated the safety and biocompatibility of CNPs-PI-Alg gel. Furthermore, significant antibacterial and antibiofilm effect against Staphylococcus aureus showed that the CNPs-PI-Alg in situ gel has a potential for the prevention of OIAIs.

Characterisation of aerobic bacteria isolated from orthopaedic implant-associated infections

BACKGROUND AND OBJECTIVES: Orthopaedic implant-associated infections (OAIs) are challenging to treat, as it may result in high chances of implant removal and causes huge financial burden due to absenteeism, disability, hospital stay and cost of treatment. Early detection of the infection and prompt antimicrobial therapy is very important. The study was undertaken to identify the pathogens causing OAI and their antibiogram and to formulate the antibiotic policy accordingly. METHODOLOGY: It was a prospective observational study carried out for a period of one year (January 2016 to December 2016) in the Department of Microbiology and Orthopaedics in a tertiary care centre. All patients with suspected OAI, who were admitted to the hospital, were included in the study. The pus or wound swab from these patients was tested for the pathogens and their antibiogram. RESULTS: A total of 1628 implant surgeries were conducted during the study period, of which 136 patients suspected to have OAI, amongst them 81 (59.55%) had bacterial growth. The Orthopaedic implant infection rate was 4.9%. The most common pathogen isolated was Staphylococcus aureus and of which 30.43% were methicillin-resistant strains. The most common site affected was tibia (41.97%). The majority (27.16%) of the patients had developed implant-associated infection within six months of the implant surgery. CONCLUSIONS: The OAIs it greatly affects the quality of life of the individual. Early suspicion, prompt investigation and timely treatment can reduce the morbidity caused by the OAI. Since the pathogens causing OAI can vary in hospital, the local bacterial profile of the pathogen causing OAI and their antibiogram needs to be monitored to treat the patients effectively for better outcome.

Finegoldia magna Isolated from Orthopedic Joint Implant-Associated Infections.

The anaerobic Gram-positive coccus Finegoldia magna is a rare cause of infections of bone and joints. The aim of this study was to describe the microbiological and clinical characteristics of orthopedic implant-associated infections caused by F. magna We retrospectively analyzed samples consisting of anaerobic Gram-positive cocci and samples already identified as F. magna from patients with orthopedic infections. The isolates found were determined to the species level using matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS). The antibiotic susceptibility pattern was determined by Etest. Whole-genome sequencing (WGS) was performed. Clinical data were extracted from each patient's journal. In nine patients, orthopedic joint implant-associated infections were identified as being caused by F. magna The isolates were susceptible to most of the antibiotics tested, with the exception of rifampin and moxifloxacin in a few cases. Five of the nine infections were monomicrobial. The most common antibiotic used to treat the infection was penicillin V, but five of the nine patients received a combination of antibiotics. Eight patients underwent surgical treatment, with extraction of the implant performed in seven cases and reimplantation in only two cases. The WGS showed a relatively small core genome, with 126,647 single nucleotide polymorphisms identified within the core genome. A phylogenomic analysis revealed that the isolates clustered into two distinct clades. Orthopedic implant-associated infections caused by F. magna are rare, but the bacteria are generally susceptible to antibiotics. Despite this, surgical treatment combined with long-term antibiotics is often necessary. The WGS analysis revealed a high heterogeneity and suggested the existence of at least two different Finegoldia species.

Bacteria antibiotic resistance: New challenges and opportunities for implant-associated orthopedic infections.

There has been a dramatic increase in the emergence of antibiotic-resistant bacterial strains, which has made antibiotic choices for infection control increasingly limited and more expensive. In the U.S. alone, antibiotic-resistant bacteria cause at least 2 million infections and 23,000 deaths a year resulting in a $55-70 billion per year economic impact. Antibiotics are critical to the success of surgical procedures including orthopedic prosthetic surgeries, and antibiotic resistance is occurring in nearly all bacteria that infect people, including the most common bacteria that cause orthopedic infections, such as Staphylococcus aureus (S. aureus). Most clinical cases of orthopedic surgeries have shown that patients infected with antibiotic-resistant bacteria, such as methicillin-resistant S. aureus (MRSA), are associated with increased morbidity and mortality. This paper reviews the severity of antibiotic resistance at the global scale, the consequences of antibiotic resistance, and the pathways bacteria used to develop antibiotic resistance. It highlights the opportunities and challenges in limiting antibiotic resistance through approaches like the development of novel, non-drug approaches to reduce bacteria functions related to orthopedic implant-associated infections. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:22-32, 2018.

Orthopedic-Implant Associated Infection due to Gram-Negative Bacilli: The Worrisome Impact of Acinetobacter baumannii Multidrug Resistance in a Brazilian Center

Background Orthopedic implant-associated surgical site infection (SSI) is a severe complication presenting a treatment challenge. Recently, Gram-negative bacteria orthopedic infections have become a global concern.Objectives:To describe the bacterial profile of orthopedic implant-associated Gram-negative infections and specific outcome of Acinetobacter baumannii infections.Methods A single-center, retrospective cohort study analyzing the infection control database on the year 2016. Cases selected were those osteosynthesis or prosthetic joint, which evolved with SSI and Gram-negative bacterial growth in bone tissue or periprosthetic cultures.ResultsIn 2016, 4001 clean surgeries with orthopedic implant placement were performed; of which 84 fulfillled the criteria for SSI, according to CDC/NHSH definitions (54 cases of open fracture reduction, 24 of hip arthroplasty, five of knee arthroplasty). Main agent of infections was Staphylococcus aureus (29.9%); Gram-negative bacteria however were responsible for 57.3% of infections (Enterobacter ssp. 22.4%; Acinetobacter baumannii 14.9%; Klebsiella pneumoniae 10%; Pseudomonas aeruginosa 10%). Among them, 100% Enterobacter ssp. were sensitive to carbapenems and 75% to ciprofloxacin. Klebsiella pneumoniae showed sensitivity to carbapenems in 85.7%, Pseudomonas aeruginosa showed sensitivity in 85.7% to carbapenems and 100% to ciprofloxacin. However, Acinetobacter baumannii showed the least favorable profile amongst Gram-negatives since only 12.5% of strains were sensitive to carbapenems, 28.6% to Ampicilin-sulbactam, 22.2% to ciprofloxacin, while showing 100% sensitivity to polymyxins. From 13 patients in whom Acinetobacter baumannii was isolated, none presented sepsis related to this infection, yet four of them died as result of hospitalization-related complications (30.7% mortality rate). Among these deaths, two were related to total hip arthroplasty, one to knee arthroplasty and one to open fracture fixation. Among the survivors, two remain in antimicrobial use and seven showed remission/cure.Conclusion SSI caused by carbepenem-resistant Acinetobacter baumannii represents great impact on morbi-mortality in patients who undergo surgery with placement of orthopedic implants.Disclosures All authors: No reported disclosures.

An Embedded Wireless Temperature Sensor for Orthopedic Implants

A wireless and passive (battery free) temperature sensor that can be embedded inside an orthopedic implant, such as an interference screw, was developed. The sensor is based on an inductive-capacitive-resistive resonant circuit that is inductively powered so the temperature at the implant can be measured wirelessly. A potential application of this sensor is to monitor internal wound temperature for the diagnosis of local infection at the implant site. Infections pose a significant risk to patients, who receive orthopedic implants, often lead to adverse conditions including implant failure, tissue necrosis, and amputation. Current approaches for diagnosing orthopedic implant-associated infections, such as blood tests, radiographic imaging, and histological study are slow, tedious, and nonspecific. In recent years, thermographic imaging has been used to monitor local temperature at the external surgical site as a means to detect infection, but its applications are limited to surface or near-surface wounds. The described sensor will serve as an useful research tool to investigate using temperature as an indication of deep-tissue orthopedic implant infection. When fully developed, this sensor may also improve orthopedic care by allowing simple, early detection of infection at an implant site. This paper describes the design and fabrication of the sensor, as well as characterizes its performance. Experimental results indicate the temperature response of the sensor is reproducible within the tested range of 30-42 °C.