Rapid Diagnostics of Orthopaedic-Implant-Associated Infections Using Nanopore Shotgun Metagenomic Sequencing on Tissue Biopsies.

Conventional culture-based diagnostics of orthopaedic-implant-associated infections (OIAIs) are arduous. Hence, the aim of this study was to evaluate a culture-independent, rapid nanopore-based diagnostic protocol with regard to (a) pathogen identification, (b) time to pathogen identification, and (c) identification of antimicrobial resistance (AMR). This prospective proof-of-concept study included soft tissue biopsies from 32 patients with OIAIs undergoing first revision surgery at Akershus University Hospital, Norway. The biopsies were divided into two segments. Nanopore shotgun metagenomic sequencing and pathogen and antimicrobial resistance gene identification using the EPI2ME analysis platform (Oxford Nanopore Technologies) were performed on one segment. Conventional culture-based diagnostics were performed on the other. Microbial identification matched in 23/32 OIAI patients (72%). Sequencing detected additional microbes in 9/32 patients. Pathogens detected by culturing were identified by sequencing within a median of 1 h of sequencing start [range 1-18 h]. Phenotypic AMR was explained by the detection of resistance genes in 11/23 patients (48%). Diagnostics of OIAIs using shotgun metagenomics sequencing are possible within 24 h from biopsy using nanopore technology. Sequencing outperformed culturing with respect to speed and pathogen detection where pathogens were at sufficient concentration, whereas culture-based methods had an advantage at lower pathogen concentrations. Sequencing-based AMR detection may not yet be a suitable replacement for culture-based antibiotic susceptibility testing.

Are conventional microbiological diagnostics sufficiently expedient in the era of rapid diagnostics? Evaluation of conventional microbiological diagnostics of orthopedic implant-associated infections (OIAI).

Background and purpose - In a time when rapid diagnostics are increasingly sought, conventional procedures for detection of microbes causing orthopedic implant-associated infections (OIAI) seem extensive and time-consuming, but how extensive are they? We assessed time to (a) pathogen identification, (b) antibiotic susceptibility patterns, and (c) targeted antibiotic treatment using conventional microbiological diagnostics of OIAI in a consecutive series of patients.Patients and methods - Consecutive patients aged ≥18 years undergoing first revision surgery for acute OIAI, including prosthetic joints, fracture, and osteotomy implants, in 2017-2018 at Akershus University Hospital (Ahus), Norway were included. Information regarding microbiological diagnostics and clinical data was collected retrospectively from the hospital's diagnostic and clinical databases.Results - 123 patients fulfilled the inclusion criteria. Median time to pathogen identification was 2.5 days and to antibiotic treatment recommendations was 3.5 days. The most common pathogens were S. aureus (52%) and S. epidermidis (15%). Cultures were inconclusive in 11% of the patients. Of the 109 patients with culture-positive results, antibiotic treatment was changed in 66 (61%) patients within a median of 4 days (0-24) after the recommendation was given.Interpretation - Conventional microbiological diagnostics of OIAI is time-consuming, taking days of culturing. Same-day diagnostics would vastly improve treatment efficacy, but is dependent on rapid implementation by clinicians of the treatment recommendations given by the microbiologist.

Increasing but levelling out risk of revision due to infection after total hip arthroplasty: a study on 108,854 primary THAs in the Norwegian Arthroplasty Register from 2005 to 2019.

Background and purpose - Focus on prevention, surveillance, and treatment of infection after total hip arthroplasty (THA) in the last decade has resulted in new knowledge and guidelines. Previous publications have suggested an increased incidence of surgical revisions due to infection after THA. We assessed whether there have been changes in the risk of revision due to deep infection after primary THAs reported to the Norwegian Arthroplasty Register (NAR) over the period 2005-2019.Patients and methods - Primary THAs reported to the NAR from January 1, 2005 to December 31, 2019 were included. Adjusted Cox regression analyses with the first revision due to deep infection after primary THA were performed. We investigated changes in the risk of revision as a function of time of primary THA. Time was stratified into 5-year periods. We studied the whole population of THAs, and the subgroups: all-cemented, all-uncemented, reverse hybrid (cemented cup), and hybrid THAs (cemented stem). In addition, we investigated factors that were associated with the risk of revision, and changes in the time span from primary THA to revision.Results - Of the 108,854 primary THAs that met the inclusion criteria, 1,365 (1.3%) were revised due to deep infection. The risk of revision due to infection, at any time after primary surgery, increased through the period studied. Compared with THAs implanted in 2005-2009, the relative risk of revision due to infection was 1.4 (95% CI 1.2-1.7) for 2010-2014, and 1.6 (1.1-1.9) for 2015-2019. We found an increased risk for all types of implant fixation. Compared to 2005-2009, for all THAs, the risk of revision due to infection 0-30 days postoperatively was 2.2 (1.8-2.8) for 2010-2014 and 2.3 (1.8-2.9) for 2015-2019, 31-90 days postoperatively 1.0 (0.7-1.6) for 2010-2014 and 1.6 (1.0-2.5) for 2015-2019, and finally 91 days-1 year postoperatively 1.1 (0.7-1.8) for 2010-2014 and 1.6 (1.0-2.6) for 2015-2019. From 1 to 5 years postoperatively, the risk of revision due to infection was similar to 2005-2009 for both the subsequent time periodsInterpretation - The risk of revision due to deep infection after THA increased throughout the period 2005-2019, but appears to have levelled out after 2010. The increase was mainly due to an increased risk of early revisions, and may partly have been caused by a change of practice rather than a change in the incidence of infection.

Molecular characteristics of Staphylococcus aureus associated prosthetic joint infections after hip fractures treated with hemiarthroplasty: a retrospective genome-wide association study.

A retrospective study of Staphylococcus aureus isolates from orthopaedic patients treated between 2000 and 2017 at Akershus University Hospital, Norway was performed using a genome-wide association approach. The aim was to characterize and investigate molecular characteristics unique to S. aureus isolates from HHA associated prosthetic joint infections and potentially explain the HHA patients' elevated 1-year mortality compared to a non-HHA group. The comparison group consisted of patients with non-HHA lower-extremity implant-related S. aureus infections. S. aureus isolates from diagnostic patient samples were whole-genome sequenced. Univariate and multivariate analyses were performed to detect group-associated genetic signatures. A total of 62 HHA patients and 73 non-HHA patients were included. Median age (81 years vs. 74 years; p < 0.001) and 1-year mortality (44% vs. 15%, p < 0.001) were higher in the HHA group. A total of 20 clonal clusters (CCs) were identified; 75% of the isolates consisted of CC45, CC30, CC5, CC15, and CC1. Analyses of core and accessory genome content, including virulence, resistance genes, and k-mer analysis revealed few group-associated variants, none of which could explain the elevated 1-year mortality in HHA patients. Our findings support the premise that all S. aureus can cause invasive infections given the opportunity.

Virus transmission during orthopedic surgery on patients with COVID-19 - a brief narrative review.

Background and purpose - COVID-19 is among the most impactful pandemics that the society has experienced. Orthopedic surgery involves procedures generating droplets and aerosols and there is concern amongst surgeons that otherwise rational precautionary principles are being set aside due to lack of scientific evidence and a shortage of personal protective equipment (PPE). This narrative review attempts to translate relevant knowledge into practical recommendations for healthcare workers involved in orthopedic surgery on patients with known or suspected COVID-19.Patients and methods - We unsystematically searched in PubMed, reference lists, and the WHO's web page for relevant publications concerning problems associated with the PPE used in perioperative practice when a patient is COVID-19 positive or suspected to be. A specific search for literature regarding COVID-19 was extended to include publications from the SARS epidemic in 2002/3.Results - Transmission of infectious viruses from patient to surgeon during surgery is possible, but does not appear to be a considerable problem in clinical practice. Seal-leakage is a problem with surgical masks. Due to the lack of studies and reports, the possibility of transmission of SARS-CoV-2 from patient to surgeon during droplet- and aerosol-generating procedures is unknown.Interpretation - Surgical masks should be used only in combination with a widely covering visor and when a respirator (N95, FFP2, P3) is not made available. Furthermore, basic measures to reduce shedding of droplets and aerosols during surgery and correct and consistent use of personal protective equipment is important.

Rapid diagnostics of orthopedic implant-associated infections using Unyvero ITI implant and tissue infection application is not optimal for Staphylococcus species identification.

OBJECTIVES: This pilot study aimed to compare the commercial Unyvero ITI multiplex PCR application (U-ITI, Curetis GmbH) with conventional culturing concerning (a) detection of pathogens, (b) time to detection of pathogens and (c) time to and quality of antibiotic treatment recommendation in diagnostics of orthopedic implant-associated infections (OIAI). RESULTS: 72 tissue biopsies from 15 consecutive patients with deep OIAI infections were analyzed with conventional culturing including phenotypic antibiotic susceptibility testing and the U-ITI. U-ITI showed lower sensitivity than conventional culturing concerning detection of pathogens (73% vs 93%). 4/15 patients would have been given false negative results by U-ITI, all of which were culture-positive for Staphylococcus species. Median time to detection of pathogens was 47 h and antibiotic resistance 89 h by conventional methods compared to 13.5 h with the U-ITI. The U-ITI did not detect antibiotic resistance, whereas conventional culturing showed resistance to antibiotics covered by the U-ITI panel in 2 patients. Time to detection of pathogens was improved, but the detection limit for staphylococci was unsatisfactory. Although the time to antibiotic treatment recommendation was significantly reduced, the U-ITI would have resulted in incorrect antibiotic recommendation in 2 patients. Our data do not support use of this assay in diagnostics.

Infeksjon i operasjonsområdet.

BACKGROUND: All Norwegian hospitals must submit data to the Norwegian Surveillance System for Antibiotic Consumption and Healthcare-Associated Infections (NOIS) regarding surgical site infections following coronary artery bypass graft, caesarean section, hip arthroplasty, cholecystectomy and colonic surgery. The purpose of our study was to identify the proportion of patients undergoing surgery in 2016 who developed a surgical site infection, and the consequences in the form of prolonged postoperative hospitalisation, readmission or revision surgery. MATERIAL AND METHOD: All patients who underwent one of the five surgical procedures registered in NOIS in 2016 were included and followed up for 30 days after the surgery. The criteria set out by the European Centre for Disease Prevention and Control were used to define infections. RESULTS: From among the 31 401 patients included, a total of 1 225 surgical site infections were recorded. The incidence was highest following colonic surgery (10.9 %) and lowest following total hip arthroplasty (1.8 %). Median postoperative length of hospitalisation was three days for those with no infection, and six days for the 544 patients with a deep infection or an infection in an organ or cavity. The infections resulted in the need for revision surgery in 308 patients and readmission for 323 patients. INTERPRETATION: A total of 3.9 % of patients registered with a surgical procedure included in NOIS developed a surgical site infection. Consequences such as increased hospitalisation time, and more readmissions as well as revision procedures serve to highlight the importance of preventing such infections.

Surgical Site Infections in Orthopaedic Surgery Demonstrate Clones Similar to Those in Orthopaedic Staphylococcus aureus Nasal Carriers.

BACKGROUND: Staphylococcus aureus is the main microbial pathogen in orthopaedic infections, and it adds considerable extra costs to the national health-care system each year. Nasal carriers of Staphylococcus aureus have an increased risk of invasive disease, including surgical site infection. The purpose of the present study was to investigate whether the Staphylococcus aureus carrier clones found in patients undergoing elective orthopaedic surgery were the same as the clones found in isolates from orthopaedic patients with Staphylococcus aureus surgical site infections. METHODS: Patients admitted for elective orthopaedic surgery underwent nasal cultures for Staphylococcus aureus. Further, orthopaedic patients with a deep surgical site infection caused by Staphylococcus aureus were characterized using the same genotyping methods: multilocus sequence typing and staphylococcal protein A typing. RESULTS: Multilocus sequence typing revealed a large number of genotypes in the two populations. However, 85% of nasal carriers and 90% of surgical site infection isolates could be classified into the same four multilocus sequence typing clonal complexes. The risk of Staphylococcus aureus surgical site infection in nasal carriers compared with non-carriers was 5.8 times higher (95% confidence interval, 1.5 to 23.1 times). Of the nasal carriers, 6.3% (95% confidence interval, 1.7% to 10.9% [seven of 111 patients]) developed a deep Staphylococcus aureus surgical site infection, and all but one patient had identical genotypes in the nasal and surgical site infection isolates. CONCLUSIONS: Staphylococcus aureus isolates from nasal carriers and patients with surgical site infection clustered into the same few multilocus sequence typing clonal complexes. This finding confirms the existence of some commonly occurring Staphylococcus aureus clones in different population groups within a geographically restricted area. The almost complete individual concordance between Staphylococcus aureus genotypes in carriers who developed a deep surgical site infection strongly supports transmission from the nose, skin surfaces, and other endogenous body regions as a possible route. CLINICAL RELEVANCE: Surgical site infections might be more frequently caused by endogenous transmission than was previously assumed. Perioperative preventive efforts must focus more on this route to further decrease the risk of postoperative orthopaedic infections.

Time-dependent improvement in functional outcome following Oxford medial unicompartmental knee arthroplasty. A prospective longitudinal multicenter study involving 96 patients.

BACKGROUND AND PURPOSE: 10-year survival rates after unicompartmental knee replacement (UKR) have been up to 97% in single-center studies, but they have been as low as 80% in studies from arthroplasty registers. Few studies have evaluated short-term functional outcome and its improvement with time. We determined the time course of functional outcome as evaluated by the knee injury and osteoarthritis outcome score (KOOS) over the first 2 years after Oxford medial UKR. PATIENTS AND METHODS: In a prospective multicenter study, we included 99 unselected knees (96 patients, mean age 65 (51-80) years, 57 women) operated with Oxford medial UKR at 3 hospitals in the southeast of Norway between November 2003 and October 2006. Data were collected by independent investigators preoperatively and at 6 weeks, 3 months, 6 months, 1 year, and 2 years postoperatively. KOOS and range of motion (ROM) were determined at all follow-ups. RESULTS: Mean KOOS values for pain and activities of daily living were improved already after 6 weeks, and increased between each time point up to 2 years postoperatively. However, no statistically significant improvements were seen after 6 months. Mean active and passive ROM gradually improved up to 2 years after UKR, and were then better than before surgery. INTERPRETATION: Most of the expected improvements in pain and function after UKR are achieved within 6 months of surgery. Only minimal improvement can be expected beyond this time.

Infection after primary hip arthroplasty: a comparison of 3 Norwegian health registers.

BACKGROUND AND PURPOSE: The aim of the present study was to assess incidence of and risk factors for infection after hip arthroplasty in data from 3 national health registries. We investigated differences in risk patterns between surgical site infection (SSI) and revision due to infection after primary total hip arthroplasty (THA) and hemiarthroplasty (HA). MATERIALS AND METHODS: This observational study was based on prospective data from 2005-2009 on primary THAs and HAs from the Norwegian Arthroplasty Register (NAR), the Norwegian Hip Fracture Register (NHFR), and the Norwegian Surveillance System for Healthcare-Associated Infections (NOIS). The Norwegian Patient Register (NPR) was used for evaluation of case reporting. Cox regression analyses were performed with revision due to infection as endpoint for data from the NAR and the NHFR, and with SSI as the endpoint for data from the NOIS. RESULTS: The 1-year incidence of SSI in the NOIS was 3.0% after THA (167/5,540) and 7.3% after HA (103/1,416). The 1-year incidence of revision due to infection was 0.7% for THAs in the NAR (182/24,512) and 1.5% for HAs in the NHFR (128/8,262). Risk factors for SSI after THA were advanced age, ASA class higher than 2, and short duration of surgery. For THA, the risk factors for revision due to infection were male sex, advanced age, ASA class higher than 1, emergency surgery, uncemented fixation, and a National Nosocomial Infection Surveillance (NNIS) risk index of 2 or more. For HAs inserted after fracture, age less than 60 and short duration of surgery were risk factors of revision due to infection. INTERPRETATION: The incidences of SSI and revision due to infection after primary hip replacements in Norway are similar to those in other countries. There may be differences in risk pattern between SSI and revision due to infection after arthroplasty. The risk patterns for revision due to infection appear to be different for HA and THA.

Nasal carriage of Staphylococcus aureus: frequency and molecular diversity in a randomly sampled Norwegian community population.

A randomly selected, healthy Norwegian community population was studied for nasal carriage of Staphylococcus aureus (S. aureus) to describe frequency and molecular diversity in a non-hospital cohort (n = 95). Multilocus sequence typing revealed 31 sequence types (STs) belonging to 15 clonal complexes (CCs). The majority of isolates (71%) were classified as CC 15, 30 or 45. This clustering was confirmed by spa typing. There was no statistically significant difference in the distribution of CCs between this community population and a previously studied group of orthopaedic health care workers from a hospital in the same community. The study may indicate that microbial and host factors may be stronger determinants for S. aureus colonization than exposures associated with the hospital environment.

The need for better analysis of observational studies in orthopedics. A retrospective study of elbow fractures in children.

BACKGROUND AND PURPOSE: The conventional statistical methods employed in observational studies in orthopedics require the fundamental assumption that the outcomes are independent. However, fractures treated by the same surgeon cannot be regarded as being independent of each other and should be nested in the statistical analysis. If the effect on outcome of early rather than delayed surgery depends on the severity of the fracture, we have a case of interaction. This is rarely considered in orthopedic research, but could affect the conclusions drawn. The aim of this paper is to describe the concepts of multilevel modeling and interaction in orthopedics. PATIENTS AND METHODS: In a cohort of 112 patients with single supracondylar humerus fractures, 78 patients were examined clinically on average 4 years after surgery. The range of motion was measured and the global satisfaction was assessed. The results were used to compare traditional least-squares regression analysis with a 2-level model with interactions. RESULTS: We found that 25% of the variance in outcome could be attributed to between-surgeon variance. We identified an interaction between the surgeons' experience and the severity of the fractures that influenced the conclusions. The variable "number of pins" was not significant in the 2-level model (p = 0.07), while the ordinary least-squares analysis gave a result that was statistically significant (p = 0.01). INTERPRETATION: Researchers should consider the need for a 2-level model and the presence of interactions. Standard statistical methods might lead to wrong conclusions.

Nasal carriage of Staphylococcus aureus: which sequence types do orthopedic surgical healthcare workers carry?

Using sequence typing methods, we found that healthcare workers on our orthopedic surgery unit were persistent carriers of a limited number of sequence types of Staphylococcus aureus for a limited time. Multilocus sequence typing characterized 3 clonal complexes that accounted for more than 80% of the clonal complexes identified.

Infectious tenosynovitis and osteomyelitis caused by Mycobacterium nonchromogenicum.

Infections due to Mycobacterium terrae complex are rare. We report a severe case of chronic tenosynovitis and osteomyelitis of the hand caused by Mycobacterium nonchromogenicum requiring second ray finger amputation.