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Zhouyang Hu,1,2,* Xiaobing Yin,3,* Guoxin Fan,1,2 Xiang Liao1,2 1Department of Pain Medicine, Huazhong University of Science and Technology Union Shenzhen Hospital, Shenzhen, People’s Republic of China; 2Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, National-Regional Key Technology Engineering Laboratory for Medical Ultrasound, School of Biomedical Engineering, Shenzhen University Medical School, Shenzhen, 518060, People’s Republic of China; 3Nursing Department, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Guoxin Fan; Xiang Liao, Department of Pain Medicine, Huazhong University of Science and Technology Union Shenzhen Hospital, Shenzhen, People’s Republic of China, Tel +86-18529093630 ; +86-13725595056, Email fan06309@163.com; liaoxiang75@email.szu.edu.cnObjective: Bibliometric analysis is commonly used to visualize the knowledge foundation, trends, and patterns in a specific scientific field by performing a quantitative evaluation of the relevant literature. The purpose of this study was to perform a bibliometric analysis of recent studies in the field of orthopedic biofilm research and identify its current trends and hotspots.Methods: Research studies were retrieved from the Web of Science Core Collection and Scopus databases and analyzed in bibliometrix with R package (4.2.2).Results: A total of 2426 literature were included in the study. Journal of orthopaedic research and Clinical orthopaedics and related research ranked first in terms of productivity and impact, with 57 published articles and 32 h-index, respectively. Trampuz A, Ohio State Univ and the United States ranked as the most productive authors, institutions, and countries. Biofilm formation, role of sonication, biomaterial mechanism and antibiotic loading have been investigated as the trend and hotspots in the field of orthopedic biofilm research.Conclusion: This study provides a thorough overview of the state of the art of current orthopedic biofilm research and offers valuable insights into recent trends and hotspots in this field.Keywords: biofilm, orthopedic infection, bibliometric analysis, hotspot, research trend

Sifeng Shi, Weiran Shi, Bing Zhou, Shang Qiu Department of Orthopedic Surgery, the Affiliated Hospital of Xuzhou Medical University, Xuzhou, People’s Republic of ChinaCorrespondence: Sifeng Shi, Email shisifeng20071@163.com; Shang Qiu, Email shangqiu20132@163.comAbstract: Orthopedic infection is one of the most intractable orthopedic problems. Bacteria resistant to antibiotics also develop gradually. Chitosan is widely used in the Biomedical field because of its high biocompatibility, biodegradability, and antibacterial activity. Chitosan-based drug delivery systems are frequently utilized to produce controlled medication release. When combined with antibiotics, synergistic antibacterial effects can be achieved. Chitosan-based nanoparticles are one of the most widely used applications in drug delivery systems. The focus of this review is to provide information on new methods being developed for chitosan-based nanoparticles in the field of bone infection treatment, including chitosan nanoparticles for antibacterial purposes, Ch-loaded with antibiotics, Ch-loaded with metal, and used as immune adjuvants. It may Provide ideas for the fundamental research and the prospects of future clinical applications of orthopedic infections.Keywords: chitosan nanoparticles, orthopedic infection, chitosan-based nanoparticles, staphylococcus aureus

Boyong Wang,1,* Qiaojie Wang,1,* Mingzhang Li,1 Jinlong Yu,1 Feng Jiang,1 Yujie Hu,1 Geyong Guo,1 Xiaohua Chen,2 Jin Tang,3 Pei Han,1 Hao Shen1 1Department of Orthopedics, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200233, People’s Republic of China; 2Department of Infectious Diseases, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200233, People’s Republic of China; 3Clinical Laboratory, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200233, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hao Shen, Department of Orthopedics, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200233, People’s Republic of China, Email shenhao7212@sina.comObjective: The diagnosis of tubercular orthopedic implant-associated infection (TB-IAI) is challenging. This study evaluated the value of metagenomic next-generation sequencing (mNGS) for the diagnosis of TB-IAI and developed a standardized diagnostic procedure for TB-IAI.Methods: The records of all patients with TB-IAI diagnosed and treated at our institution between December 2018 and September 2022 were retrospectively reviewed. Patient demographic characteristics, medical history, laboratory test, microbial culture, histopathology, and mNGS results, and time to diagnosis were recorded. The diagnostic efficiency of mNGS for TB-IAI was assessed by comparing the results and diagnostic time with that of other diagnostic modalities.Results: Ten patients were included in the analysis, including eight with prosthetic joint infections and two with fracture-related infections. The mNGS positivity rate was 100% (10/10), which was higher than that of TB-antibody (11%, 1/9), real-time quantitative polymerase chain reaction (22%, 2/9), T-SPOT.TB (25%, 2/8), purified protein derivative (50%, 4/8), microbial culture (50%, 5/10), and histopathology (20%, 2/10). mNGS shortened the time to diagnosis of TB-IAI. A standardized diagnostic procedure for TB-IAI was developed based on the findings.Conclusion: mNGS is useful for the diagnosis of TB-IAI. mNGS is recommended in cases where it is difficult to identify a pathogen using routine diagnostic tests. The standardized diagnostic procedure might improve TB-IAI diagnosis.Importance: TB-IAI is a rare infection, which occurs after orthopedic surgery and hard to diagnose microbiologically. mNGS is a new detection technique not yet discussed in current literature as a means for TB-IAI diagnostics. Here we describe a cohort of patients with TB-IAI diagnosed by mNGS show high efficiency of mNGS for detection of this pathology and present a clinical algorithm supplementing conventional methods for TB-IAI assessment.Keywords: metagenomic next-generation sequencing, implant-associated infection, Mycobacterium tuberculosis complex, orthopedic infection, diagnosis

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.

IntroductionAccurate identification of the etiology of orthopedic infection is very important for correct and timely clinical management, but it has been poorly studied. In the current study we explored the association of multiple bacterial pathogens with orthopedic infection.MethodsHospitalized orthopedic patients were enrolled in a rural hospital in Qingdao, China. Wound or exudate swab samples were collected and tested for twelve bacterial pathogens with both culture and multiplex real time PCR.Results and discussionA total of 349 hospitalized orthopedic patients were enrolled including 193 cases presenting infection manifestations upon admission and 156 with no sign of infection. Orthopedic infection patients were mainly male (72.5%) with more lengthy hospital stay (median 15 days). At least one pathogen was detected in 42.5% (82/193) of patients with infection while 7.1% (11/156) in the patients without infection (P < 0.001). S. aureus was the most prevalent causative pathogen (15.5%). Quantity dependent pathogen association with infection was observed, particularly for P. aeruginosa and K. pneumoniae, possibly indicating subclinical infection. Most of the patients with detected pathogens had a previous history of orthopedic surgery (odds ratio 2.8, P = 0.038). Pathogen specific clinical manifestations were characterized. Multiplex qPCR, because of its high sensitivity, superior specificity, and powerful quantification could be utilized in combination with culture to guide antimicrobial therapy and track the progression of orthopedic infection during treatment.

Introduction Polymethyl methacrylate (PMMA) is a common depot system in the treatment of chronic osteomyelitis. However, a lot of its shortcomings do not allow us to consider it ideal. Purpose of the work was to study in vivo the effectiveness of a polymer hydrogel containing an antibiotic for chronic osteomyelitis of the tibia in a rabbit model and compare it with PMMA Materials and methods The study was performed on the lower leg of 25 mature Chinchilla rabbits. A model of chronic osteomyelitis of the tibia was created. A methicillin-sensitive strain of Staphylococcus aureus (MSSA), highly active against cefazolin, was chosen as an infectious agent. Surgical debridement started 21 days after the clinical, laboratory, radiological and microbiological confirmation of the diagnosis, the technique for all animals was the same. The experimental group (n = 11) was treated by implantation of a polymer hydrogel, the comparison group (n = 11) with PMMA, and the control group (n = 3) had no implanted substance. In the postoperative period, monitoring of the local status, weight and body temperature of the animals, microbiological and radiological studies were carried out. Animals were taken out of the experiment by stages. Biopsies were sent for bacteriological and histomorphometric studies. Statistical comparison of the groups was performed using the Mann ‑ Whitney, Kruskell ‑ Wallis and Tukey criteria, descriptive statistics were used for the control group. Results In the experimental group, in all cases, postoperative wounds healed in a timely manner, the levels of WBC and CRP significantly (p = 0.040) decreased from 14 and 21 days, respectively. Microbiologically, the growth of microflora from the wound discharge and biopsy specimens was not detected; radiographic progression of chronic osteomyelitis was not observed; histomorphometry revealed a significant (p = 0.002) effective relief of the inflammatory process. In the comparison group, systemic antibiotic therapy was required from postoperative day 7. Levels of inflammatory markers decreased less effectively than in the experimental group. MSSA was verified from wound discharge and biopsy specimens at almost every follow-up time-point. X-rays and histomorphometry (p = 0.001), on average, detected exacerbation of osteomyelitis. In the control group, systemic therapy did not give positive dynamics. Discussion A comparative analysis showed that the hydrogel impregnated with an antibacterial agent, unlike PMMA, reliably arrests chronic osteomyelitis without auxiliary systemic antibiotic therapy and does not cause material-associated bone resorption. The clinical and laboratory picture is fully consistent with the data of microbiology, radiology and histomorphometry. Conclusion Hydrogel impregnated with an antibiotic reliably and effectively stops chronic osteomyelitis compared to PMMA.

Introduction Mycobacterium abscessus species belongs to the group of non-tuberculosis mycobacteria responsible for chronic infections in people with weakened immunity. M. abscessus exist in various ecological niches and are able to colonize artificial surfaces, including medical and surgical instruments/ devices. Due to the low incidence of M. abscessus as a causative agent of orthopedic infection, a rare clinical case of periprosthetic infection caused by M. abscessus would interest practitioners. The aim is to present a clinical case of periprosthetic infection caused by M. abscessus. Materials and methods From the medical records and discharge documents, it was known that female patient X. underwent total hip replacement at her residence hospital. Signs of acute infection of the postoperative wound appeared in the early postoperative period. Results Three months later, the patient was hospitalized in a specialized institution with a diagnosis of chronic deep periprosthetic infection. During the examination, the mycobacterial etiology of the process was established. During two hospitalizations, the patient underwent 4 consecutive revision surgeries (including muscle plastic surgery and installation of an antimicrobial spacer) and massive parenteral antibiotic therapy for 8 months, including at the outpatient stage, using at least 3 antibacterial agents. After 4 years, the patient does not complain of the infectious process. Postoperative scar is 45 cm. The residual shortening of the right lower limb of 3 cm was compensated by orthopedic shoes. Discussion Treatment of infection caused by M. abscessus is challenging due to the natural resistance of the pathogen to a wide range of antibacterial drugs. The literature describes separate cases of orthopedic infections caused by this pathogen. All authors agree that the key to successful treatment is a combination of radical surgical debridement and antibacterial therapy using at least three antimicrobial drugs. Conclusion A rare clinical case of periprosthetic infection caused by Mycobacterium abscessus after primary hip replacement is presented. This infectious agent is a rare pathogen, for which there is no proven therapeutic algorithm. Long-term aggressive antibiotic therapy in combination with stage-by-stage surgical treatment was successful.

Staphylococcus aureus (S. aureus) has the ability to invade human cortical bones and cause intracellular infections in osteoblasts, which may lead to a long-term infection that is difficult to eliminate. It is critical to identify the underlying mechanisms of the osteoblast response to the intracellular S. aureus. More recently, multiple circular RNA (circRNA) functions have been identified, including serving as protein scaffolds or miRNA sponges and being translated into polypeptides. The role that circRNAs play in intracellular S. aureus infection of osteoblasts has not, to our knowledge, been investigated. Here, we established an intracellular infection model of S. aureus in osteoblasts and compared the circRNA expression of osteoblasts between the infected and control groups using RNA sequencing technology, by which a significant difference was found. In total, 117 upregulated and 125 down-regulated differentially expressed circRNAs (DEcircRNAs) were identified, and reverse transcription-quantitative PCR was employed to validate the results of RNA sequencing. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses demonstrated that DEcircRNAs were enriched in processes associated with macromolecule modification, cellular component organization or biogenesis, and intracellular non-membrane-bound organelles. Finally, a potentially important network of circRNA-miRNA-mRNA based on the DEcircRNAs was constructed. Overall, this study revealed the circRNA expression profile of human osteoblasts infected by intracellular S. aureus for the first time, and identified the circRNAs that may contribute to the pathogenesis of infectious diseases caused by intracellular S. aureus infection in human osteoblasts.

Osteoarticular infections (OAI) are a significant cause of morbidity and mortality. Cultures and serology are some of the gold standards for identifying infection but are often unable to provide a timely diagnosis or a diagnosis at all. Genetic testing offers capabilities that other modalities lack. Polymerase chain reaction has multiple versions with various costs and turnaround times. This technology has become implemented in multiple pediatric center OAI diagnostic protocols. There is sufficient literature documenting effectiveness in certain clinical situations, especially with fastidious organism diagnosis, but significant limitation still exists. Metagenomic next-generation sequencing is an unbiased or hypothesis-free modality with the capability to detect the genetic material of bacteria, viruses, parasites, fungi, and humans from a single sample. Potential benefits include pathogen identification unaffected by antimicrobial administration, detection of fastidious organisms more quickly, delineation of pathogens in polymicrobial infections, antimicrobial susceptibility, and avoidance of invasive procedures. It is a resource-intensive modality with little standardization of the complex processes. Appropriate use and definitive clinical impact have yet to be determined.

The widespread use of orthopedic implants to support or replace bones is increasingly threatened by the risk of incurable bacterial infections, impenetrable microbial biofilms, and irreversible antibiotic resistance. In the past, the development of anti-infective biomaterials focused solely on direct antibacterial properties while ignoring the host's immune response. Inspired by the clearance of infection by the innate neutrophil response and participation in anti-infectious immunity of Zn ions, we report an innovative neutrophil extracellular traps (NETs) strategy, induced by biodegradable pure Zn, which achieved therapeutic efficacy toward biomaterial-related infections. Our in vitro and in vivo data showed that pure Zn was favorable for NETs formation by promoting the release of DNA fibers and granule proteins in a reactive oxygen species (ROS)-dependent manner, thereby retraining and degrading bacteria with an efficiency of up to 99.5%. Transcriptome analysis revealed that cytoskeletal rearrangement and toll-like receptor (TLR) signaling pathway were also involved in Zn-induced NETs formation. Furthermore, the in vivo results of a Staphylococcus aureus (S. aureus)-infected rat model verified that pure Zn potentiated the bactericidal capability of neutrophils around implants, and promoted osseointegration in S. aureus-infected rat femurs. This antibacterial immunity concept lays a foundation for the development of other antibacterial biomaterials and holds great promise for treating orthopedic infections.

Purpose To evaluate the results of a comparative analysis of the in vitro antimicrobial activity of polymer hydrogels and PMMA impregnated with antibiotics against test cultures of the leading pathogens of bone infection. Materials and methods A comparative analysis of the antimicrobial activity of the polymer hydrogel and PMMA impregnated with antibiotics was carried out. The bactericidal efficacy and prolongation of action of the following microbe-antibiotic pairs were assessed: MSSA – gentamicin, MSSE – cefazolin, MRSA and MRSE – vancomycin, A. baumannii – tobramycin. The duration of the study is 7 days. Statistical comparison of groups was carried out using the Mann-Whitney and Wilcoxon tests; the median and 95 % CI were used to describe the data. Results The obtained indicators of the zone of inhibition of the growth of microorganisms around the polymer hydrogel were several times higher than the results of PMMA (p < 0.05 for all periods). The antimicrobial activity of hydrogels in all cases lasted more than 7 days. Hydrogels impregnated with vancomycin showed the lowest rate of contraction of the inhibition zone. The best antimicrobial effect was demonstrated by the compared samples with cefazolin in relation to MSSE, the maximum index of the zone of suppression of which, on average, for the hydrogel was 29.3 mm, PMMA – 22.3 mm. Discussion Samples from polymer hydrogel impregnated with antibiotics demonstrated prolonged pronounced effective antimicrobial activity against the leading pathogens of orthopedic infections in comparison with PMMA. The bactericidal efficacy of the polymer hydrogel significantly exceeded the activity of PMMA already from the first day of the study (p = 0.002). The action of the hydrogel throughout the study was uniform without abrupt changes or dips (p > 0.05), in contrast to bone cement, whose activity against all test cultures significantly decreased (p = 0.042) on the 2nd day of the study. Conclusion Polymeric biodegradable hydrogels impregnated with antibiotics have a greater antimicrobial potential compared to PMMA. Uniform, slow and controlled release of the drug and effective inhibition of the growth of microorganisms, as well as prolonged action show that these properties may turn hydrogels into an effective depot system.

Objective. To study effects of bacteriophages on biofilm formation and formed biofilm by S. aureus isolated from patients with orthopedic infection. Materials and Methods. A total of 50 clinical strains of S. aureus were tested. Species identification was performed by MALDI-TOF MS, antibiotic susceptibility – in accordance with the EUCAST v21. Isolates susceptibility to bacteriophages «Sextafag» (Microgen, Russia) was determined by MPA medium. The antibacterial activity of phages against S. aureus ATCC 29213 and S. aureus ATCC 43300 was evaluated by growth kinetic curves. Biofilms of bacteriophage-sensitive S. aureus strains were formed according to the protocol described by O’Toole. Isolates were divided into categories in accordance with the Stepanovic criteria. The effects of bacteriophages on the formation of S. aureus biofilm were studied by co-incubation of phages and bacteria followed by calculation of the percentage inhibition relative to the control without the introduction of the phages. The effect of phages on 24-hour biofilms formed by staphylococci was also evaluated in comparison with the control. Results. Out of 50 clinical S. aureus strains studied, 43 isolates (86%) were susceptible to phages, including 22 MSSA and 21 MRSA. All phage-susceptible cultures were characterized by biofilm-forming ability of varying degree: 28% – weak biofilm producer, 35% – moderate, 37% – strong. Inhibition of biofilm formation was determined in all tested MRSA strains, while in 73% of isolates the index of biofilm formation inhibition was more than 80%, which exceeded this indicator for MSSA by 2.5 times. In turn, the destruction of the formed biofilm under the action of the bacteriophage was 72% for all S. aureus. In 57% of MSSA strains, the decrease in biofilm biomass in comparison with the control was more than 80%, while this indicator was 2 times higher than for MRSA. Conclusions. The results demonstrated a high in vitro efficacy of bacteriophages against biofilm formation in S. aureus.

Background: Multispecies biofilm orthopedic infections are more challenging to treat than mono-species infections. In this in-vitro study, we aimed to determine if a multispecies biofilm, consisting of Gram positive and negative species with different antibiotic susceptibilities could be treated more effectively using high purity antibiotic-loaded calcium sulfate beads (HP-ALCSB) containing vancomycin (VAN) and tobramycin (TOB) in combination than alone. Methods: Three sets of species pairs from bioluminescent strains of Pseudomonas aeruginosa (PA) and Staphylococcus aureus (SA) and clinical isolates, Enterococcus faecalis (EF) and Enterobacter cloacae were screened for compatibility. PA + EF developed intermixed biofilms with similar cell concentrations and so were grown on 316L stainless steel coupons for 72 h or as 24 h agar lawn biofilms and then treated with HP-ALCSBs with single or combination antibiotics and assessed by viable count or bioluminescence and light imaging to distinguish each species. Replica plating was used to assess viability. Results: The VAN + TOB bead significantly reduced the PA + EF biofilm CFU and reduced the concentration of surviving antibiotic tolerant variants by 50% compared to single antibiotics. Conclusions: The combination of Gram-negative and positive targeted antibiotics released from HP-ALCSBs may be more effective in treating multispecies biofilms than monotherapy alone.

Abstract Background Staphylococcus aureus is a primary pathogen of orthopedic infections. By mediating antimicrobial resistance, S. aureus biofilm plays an important role in the recalcitrance of orthopedic infections, especially for the intractable osteomyelitis (OM). This study investigated the relationship between biofilm production and various genetic or phenotypic characteristics among orthopedic S. aureus strains. Methods A total of 137 orthopedic S. aureus isolates were enrolled and divided into OM and non-OM groups. Biofilm production was evaluated using the crystal violet assay. Genetic and phenotypic characteristics including MRSA identification, MLST and spa typing, carriage of virulence genes, drug resistance, and patients’ inflammatory responses indicators were characterized. The relationship between biofilm production and above-mentioned features was respectively analyzed among all isolates and compared between OM and non-OM isolates. Results Biofilm production presented no significant difference between OM (including 9 MRSA isolates) and non-OM (including 21 MRSA isolates) strains. We found that ST88, t377 and ST630-MSSA-t377 strains produced very strong biofilms, while MLST types of ST15, ST25, ST398, ST5, ST59 and spa types of t002, t2325, t437 tended to produce weaker biofilms. Strains with the following profiles produced stronger biofilms: fib(+)-hlgv(+)-lukED(+)-sei(-)-sem(-)-seo(-) for all isolates, sei(-)-sem(-)-seo(-) for OM isolates, and cna (+)-fib (+)-hlgv (+)-lukED (+)-seb(-)-sed(-) for non-OM isolates. In addition, not any single drug resistance was found to be related to biofilm production. We also observed that, among OM patients, strains with stronger biofilms caused weaker inflammatory responses. Conclusion Some genetic or phenotypic characteristics of orthopedic strains were associated with biofilm production, and this association could be different among OM and non-OM strains. The results are of great significance for better understanding, evaluating and managing different kinds of biofilm-associated orthopedic infections, and provide potential targets for biofilm clearance.

Objective. To evaluate the resistance rate and production of carbapenemases in Klebsiella pneumoniae with phenotypic resistance to carbapenems isolated from patients with orthopedic infection. Materials and Methods. The materials for the study were tissue samples, aspirates and removed orthopedic devices of patients with orthopedic infection at the Vreden Russian Research Institute of Traumatology and Orthopedics, between 2017 and 2019. K. pneumoniae strains were identified in Microlatest by iEMS ReaderMF. These strains were tested for susceptibility to 15 antimicrobial agents by disk diffusion methods, as described by the EUCAST. The carbapenemase genes were investigated by RT-PCR. Results. Of 858 isolated cultures, 6.8% were resistant to carbapenems. Molecular genetic analysis showed that 43.1% of the cultures had blaNDM gene and 24.1% blaOXA-48. All isolates of K. pneumoniae were characterized by resistance to cefotaxime, moxifloxacin and ciprofloxacin. OXA-48-strains were MDR in 50.0% of cases, XDR in 42.9%, PDR in 7.1%. Strains with NDM-carbapenemases were XDR in 68.0% and PDR in 32.0% of cases. The most effective antibiotic was fosfomycin. Thus, 66.7% of NDM-isolates demonstrated sensitivity to fosfomycin. One isolate was PDR with both NDM and OXA-48. Conclusions. Over the period of three years, carbapenemase-producing K. pneumoniae were isolated in the orthopedic hospital. These isolates were not only resistant to carbapenems, but also to a number of other antimicrobial agents. Isolates differed in resistance phenotypes depending on the presence of carbapenemases group, while strains with gene blaNDM were more resistant than those with blaOXA-48.

The most common pathologic manifestation of Rhodococcus equi, a gram-positive, facultative intracellular bacterium, is pyogranulomatous pneumonia in foals and weanlings. Hematogenous spread of bacteria may subsequently occur, resulting in joint sepsis, osteomyelitis, or subcutaneous abscessation. Medical records from horses presenting to the Cornell University Equine Hospital from 1998 to 2018 were reviewed for cases diagnosed with R. equi joint and/or bone infection, and information about case progression and outcome were analyzed. We hypothesized that, despite advances in diagnostic imaging, antimicrobials and antimicrobial delivery methods, the prognosis for R. equi joint sepsis and osteomyelitis remains grave for athletic activity and poor for survival. The 12 cases that met the review criteria had a mortality rate of 84% (10/12), with one case lost to follow up after discharge and one case discharged with a grave prognosis for athleticism.

ABSTRACT Periprosthetic joint infection (PJI) develops clinically, even with antibiotic treatment, and methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa are predominant causes of these infections. Due to biofilm formation, antibiotic treatment for patients with PJI can perpetuate resistance, further complicating the use of noninvasive treatments. This study evaluated cathodic-voltage-controlled electrical stimulation (CVCES) of titanium, in combination with a clinically relevant antibiotic, to synergistically prevent MRSA and P. aeruginosa PJIs by inhibiting bacterial adherence or as a treatment for eradicating established biofilms. CVCES of −1.0 V, −1.5 V, or −1.8 V (versus Ag/AgCl), with or without vancomycin for MRSA or gentamicin for P. aeruginosa, was applied to sterile titanium incubated with cultures to evaluate prevention of attachment or eradication of preestablished biofilms. Treatments were 24 h long and included open-circuit potential controls, antibiotic alone, CVCES, and CVCES plus antibiotic. Biofilm-associated and planktonic CFU were enumerated. In general, CVCES at −1.8 V alone or with antibiotic completely eradicated biofilm-associated CFU for both strains, and these parameters were also highly effective against planktonic bacteria, resulting in a >6-log reduction in MRSA and no detectable planktonic P. aeruginosa. All CFU were reduced ∼3 to 5 logs from controls for prevention CVCES plus antibiotics at −1.0 V and −1.5 V against MRSA. Remarkably, there were no detectable P. aeruginosa CFU following prevention CVCES at −1.0 V or −1.5 V with gentamicin. Our results suggest that CVCES in combination with antibiotics may be an effective approach for prevention and treatment of PJI. IMPORTANCE Periprosthetic joint infections (PJIs) develop clinically in the presence of antibiotic therapies and are responsible for increased patient morbidity and rising health care costs. Many of these infections involve bacterial biofilm formation on orthopedic hardware, and it has been well established that these biofilms are refractory to most antibiotic treatments. Recent studies have focused on novel methods to prevent and eradicate infection. Cathodic-voltage-controlled electrical stimulation (CVCES) has previously been shown to be effective as a method for prevention and eradication of Gram-positive and Gram-negative infections. The present study revealed that the utility of CVCES for prevention and eradication of methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa is enhanced in the presence of clinically relevant antibiotics. The synergistic effects of CVCES and antibiotics are effective in a magnitude-dependent manner. The results of this study indicate a promising alternative method to current PJI mitigation techniques.

Fungal osteomyelitis has been difficult to treat, with first-line treatments consisting of implant excision, radical debridement, and local release of high-dose antifungal agents. Locally impregnated antifungal beads are another popular treatment option. This study aimed to develop biodegradable antifungal-agent-loaded Poly(d,l-lactide-co-glycolide) (PLGA) beads and evaluate the in vitro/in vivo release patterns of amphotericin B and fluconazole from the beads. Beads of different sizes were formed using a compression-molding method, and their morphology was evaluated via scanning electron microscopy. Intrabead incorporation of antifungal agents was evaluated via Fourier-transform infrared spectroscopy, and in vitro fluconazole liberation curves of PLGA beads were inspected via high-performance liquid chromatography. When we implanted the drug-incorporated beads into the bone cavity of rabbits, we found that a high level of fluconazole (beyond the minimum therapeutic concentration [MTC]) was released for more than 49 d in vivo. Our results indicate that compression-molded PLGA/fluconazole beads have potential applications in treating bone infections.