The Association Between Mental Health, Substance Use Disorder, and Outcomes After Total Joint Arthroplasty.

BACKGROUND: Prior studies suggest that distressed patients or those who have poor mental health have inferior postoperative outcomes when compared to nondistressed patients. However, these studies typically do not account for substance use or other comorbidities often found in this population, which can independently contribute to postoperative complications. This study sought to control for these factors and assess if a diagnosis of a mental health condition is directly associated with worse outcomes after total joint arthroplasty. METHODS: A retrospective chart review was performed for 3,182 patients who underwent a total hip arthroplasty and 4,430 patients who underwent a total knee arthroplasty. Diagnosis of the mental health disorders included depression, anxiety disorder, adjustment disorder, bipolar disorder, trauma, stressor-related disorder, and schizophrenia or schizoaffective disorder. Multivariable analyses were performed to control for alcohol use, drug use, tobacco use, body mass index, and a comorbidity index. RESULTS: When controlling for body mass index and Charlson comorbidity index, no statistically significant associations were found between a diagnosis of any mental health condition or a specific diagnosis of depression or anxiety, and 90-day readmission, reoperation, or 1 year mortality for patients undergoing total knee arthroplasty or total hip arthroplasty. CONCLUSIONS: When accounting for confounding factors, there does not appear to be a direct association between diagnosis of any of the psychiatric conditions we studied and outcomes after primary total joint arthroplasty. While prior studies suggest addressing the mental health condition may improve outcomes, this study suggests that preoperative medical optimization and potentially addressing substance use may be more effective strategies.

Inpatient Hospital Costs, Emergency Department Visits, and Readmissions for Revision Hip and Knee Arthroplasty.

BACKGROUND: Revision total hip arthroplasty (THA) and total knee arthroplasty (TKA) tremendously burden hospital resources. This study evaluated factors influencing perioperative costs, including emergency department (ED) visits, readmissions, and total costs-of-care within 90 days following revision surgery. METHODS: A retrospective analysis of 772 revision TKAs and THAs performed on 630 subjects at a single center between January 2007 and December 2019 was conducted. Cost data were available from January 2015 to December 2019 for 277 patients. Factors examined included comorbidities, demographic information, preoperative Anesthesia Society of Anesthesiologists score, implant selection, and operative indication using mixed-effects linear regression models. RESULTS: Among 772 revisions (425 THAs and 347 TKAs), 213 patients required an ED visit, and 90 required hospital readmission within 90 days. There were 22.6% of patients who underwent a second procedure after their initial revision. Liver disease was a significant predictor of ED readmission for THA patients (multivariable odds ratio [OR]: 3.473, P = .001), while aseptic loosening, osteolysis, or instability significantly reduced the odds of readmission for TKA patients (OR: 0.368, P = .014). In terms of ED visits, liver disease increased the odds for THA patients (OR: 1.845, P = .100), and aseptic loosening, osteolysis, or instability decreased the odds for TKA patients (OR: 0.223, P < .001). Increased age was associated with increased costs in both THA and TKA patients, with significant cost factors including congestive heart failure for TKA patients (OR: $7,308.17, P = .004) and kidney disease for THA patients. Revision surgeries took longer than primary ones, with TKA averaging 3.0 hours (1.6 times longer) and THA 2.8 hours (1.5 times longer). CONCLUSIONS: Liver disease increases ED readmission risk in revision THA, while aseptic loosening, osteolysis, or instability decreases it in revision TKA. Increased age and congestive heart failure are associated with increased costs. These findings inform postoperative care and resource allocation in revision arthroplasty. LEVEL OF EVIDENCE: Economic and Decision Analysis, Level IV.

Morbidity and Mortality Following Total Hip and Knee Arthroplasty With Spinal Versus General Anesthesia: A Retrospective Analysis.

BACKGROUND: The optimal anesthetic mode in total joint arthroplasty (TJA) has yet to be clearly identified. Patients undergoing TJA may recieve spinal anesthesia (SA) or general anesthesia (GA). While arthroplasty literature indicates differences in postoperative morbidity, hip fracture literature does not show clear superiority of SA or GA. The purpose of this study was to further investigate this relationship and determine if there is a significant difference in morbidity and mortality between GA and SA in patients undergoing primary total joint arthroplasty. METHODS: Patients undergoing primary THA or TKA from February 2007 to February 2021 were retrospectively reviewed, creating four cohorts: THA/GA (n = 1,266), THA/SA (n = 1,084), TKA/GA (n = 882), and THA/SA (n = 2,067). Readmission within 90 days, mortality within 365 days, and thromboembolic events within 30 days postoperatively were compared using logistic regression, controlling for age, body mass index, and Charlson Comorbidity Index. RESULTS: The odds of experiencing a deep venous thrombosis within 30 days postoperatively were elevated in the analysis of both the THA/GA (odds ratio (OR) = 3.1; 95% confidence interval (CI): 1.5 to 7.0; P = .004) and the TKA/GA (OR = 1.9; 95% CI: 1.2 to 3.0; P = .005) groups. Similarly, the risk of pulmonary embolism as higher in the THA/GA cohort (OR = 3.9; 95% CI: 1.2 to 17.3; P = .04). There were also higher odds of mortality within 365 days postoperatively in THA/GA patients (OR = 4.3; 95% CI: 1.7 to 13.0; P = .004). No other differences existed among TKA patients. CONCLUSIONS: Based upon these data, both SA and GA are reasonable options for primary TKA with similar risk profiles. However, GA may be associated with higher rates of deep venous thrombosis in TJA and pulmonary embolism in THA. General anesthesia (GA) was also loosely associated with increased mortality within 1 year of THA, but this result should be considered with caution.

Risk Factors for Trochanteric Bursitis Following Total Hip Arthroplasty: A Radiographic Analysis.

BACKGROUND: Trochanteric bursitis (TB) is a prevalent complication following total hip arthroplasty (THA), with increased offset hypothesized as a potential risk factor. This study investigated potential TB predictors in THA patients, including radiographic measurements of offset and leg length, comorbidities, and patient characteristics. METHODS: In this retrospective cohort study, all THA patients from a single academic tertiary care center between 2005 and 2021 were reviewed. Exclusion criteria included less than one-year follow-up, osteonecrosis, or fracture. Manual radiographic measurements of offset (acetabular, femoral, and total) and leg length from preoperative and postoperative AP (antero-posterior) pelvis X-rays were taken, with scaling using femoral cortical diameter. Univariable and multivariable Cox proportional hazard models were employed to estimate TB risk. RESULTS: Of 1,094 patients, 103 (9.4%) developed trochanteric bursitis, with a median (Q1, Q3) time to presentation of 41.8 weeks (25.5, 66.9). In univariable models, only sex was associated with increased TB risk, with women exhibiting a 1.79 times increased risk (HR [hazard ratio]: 1.79 (1.16, 2.76), P = 0.009). Changes in acetabular offset, femoral offset, total offset, and leg length between preoperative and postoperative radiographs were not associated with an increased risk of developing TB in the univariate or multivariate models. Furthermore, various offset thresholds were evaluated, with no amount of increased offset showing increased TB risk. CONCLUSION: This study found no relationship between femoral, acetabular, or total offset and trochanteric bursitis following THA. These findings suggest that surgeons may consider adding offset for increased prosthetic stability in high-risk cases. However, given that this is a retrospective study, the authors are not advocating for the routine use of increased offset. The study identified women as a risk factor with a 1.79 times higher TB risk, highlighting the importance of counseling women patients on this heightened risk.

A2B-COVID: A Tool for Rapidly Evaluating Potential SARS-CoV-2 Transmission Events.

Identifying linked cases of infection is a critical component of the public health response to viral infectious diseases. In a clinical context, there is a need to make rapid assessments of whether cases of infection have arrived independently onto a ward, or are potentially linked via direct transmission. Viral genome sequence data are of great value in making these assessments, but are often not the only form of data available. Here, we describe A2B-COVID, a method for the rapid identification of potentially linked cases of COVID-19 infection designed for clinical settings. Our method combines knowledge about infection dynamics, data describing the movements of individuals, and evolutionary analysis of genome sequences to assess whether data collected from cases of infection are consistent or inconsistent with linkage via direct transmission. A retrospective analysis of data from two wards at Cambridge University Hospitals NHS Foundation Trust during the first wave of the pandemic showed qualitatively different patterns of linkage between cases on designated COVID-19 and non-COVID-19 wards. The subsequent real-time application of our method to data from the second epidemic wave highlights its value for monitoring cases of infection in a clinical context.

Prevention Techniques Have Had Minimal Impact on the Population Rate of Prosthetic Joint Infection for Primary Total Hip and Knee Arthroplasty: A National Database Study.

BACKGROUND: Several studies over the years have offered modalities that may greatly decrease the rate of periprosthetic joint infection when implemented. As a result, one would expect a drastic decrease in infection rate among the implementing population with its widespread use. The purpose of this study was to assess whether there exists a decrease in infection rate over time, after accounting for available confounding variables, within a large national database. METHODS: A large national database from 2005 to 2019 was queried for primary total hip arthroplasty (THA) and total knee arthroplasty (TKA). In total, 221,416 THAs and 354,049 TKAs were performed over the study period. Differences in 30-day infection rate were assessed with time and available preoperative risk factors using multinominal logistic regressions. RESULTS: Rate of infection overall trended downward for both THA and TKA. After accounting for confounding variables, odds of THA infection marginally decreased over time (odds ratio 0.968 [0.952-0.985], P < .0001), while the odds of a TKA infection marginally increased with time (odds ratio 1.037 [1.020-1.054], P < .0001). CONCLUSION: Individual peer-reviewed publications have presented infection control modalities demonstrating dramatic decreases in infection rate while analysis at a population level shows almost no changes in infection rate over a 15-year time period. This study supports continued investigation for influential modalities in preventing periprosthetic joint infection and care in patient selection for primary hip and knee arthroplasty.

Artificial Intelligence Autonomously Measures Cup Orientation, Corrects for Pelvis Orientation, and Identifies Retroversion From Antero-Posterior Pelvis Radiographs.

BACKGROUND: Measuring cup orientation is time consuming and inaccurate, but orientation influences the risk of impingement and dislocation following total hip arthroplasty (THA). This study designed an artificial intelligence (AI) program to autonomously determine cup orientation, correct for pelvis orientation, and identify cup retroversion from an antero-posterior pelvic radiographs. METHODS: There were 2,945 patients between 2012 and 2019 identified to have 504 computed tomographic (CT) scans of their THA. A 3-dimensional (3D) reconstruction was performed on all CTs, where cup orientation was measured relative to the anterior pelvic plane. Patients were randomly allocated to training (4,000 x-rays), validation (511 x-rays), and testing (690 x-rays) groups. Data augmentation was applied to the training set (n = 4,000,000) to increase model robustness. Statistical analyses were performed only on the test group in their accuracy with CT measurements. RESULTS: AI predictions averaged 0.22 ± 0.03 seconds to run on a given radiograph. Pearson correlation coefficient was 0.976 and 0.984 for AI measurements with CT, while hand measurements were 0.650 and 0.687 for anteversion and inclination, respectively. The AI measurements more closely represented CT scans when compared to hand measurements (P < .001). Measurements averaged 0.04 ± 2.21°, 0.14 ± 1.66°, -0.31 ± 8.35°, and 6.48° ± 7.43° from CT measurements for AI anteversion, AI inclination, hand anteversion, and hand inclination, respectively. AI predictions identified 17 radiographs as retroverted with 100.0% accuracy (total retroverted, n = 45). CONCLUSION: The AI algorithms may correct for pelvis orientation when measuring cup orientation on radiographs, outperform hand measurements, and may be implemented in a timely fashion. This is the first method to identify a retroverted cup from a single AP radiograph.

Artificial Intelligence for Automated Implant Identification in Total Hip Arthroplasty: A Multicenter External Validation Study Exceeding Two Million Plain Radiographs.

BACKGROUND: The surgical management of complications after total hip arthroplasty (THA) necessitates accurate identification of the femoral implant manufacturer and model. Automated image processing using deep learning has been previously developed and internally validated; however, external validation is necessary prior to responsible application of artificial intelligence (AI)-based technologies. METHODS: We trained, validated, and externally tested a deep learning system to classify femoral-sided THA implants as one of the 8 models from 2 manufacturers derived from 2,954 original, deidentified, retrospectively collected anteroposterior plain radiographs across 3 academic referral centers and 13 surgeons. From these radiographs, 2,117 were used for training, 249 for validation, and 588 for external testing. Augmentation was applied to the training set (n = 2,117,000) to increase model robustness. Performance was evaluated by area under the receiver operating characteristic curve, sensitivity, specificity, and accuracy. Implant identification processing speed was calculated. RESULTS: The training and testing sets were drawn from statistically different populations of implants (P < .001). After 1,000 training epochs by the deep learning system, the system discriminated 8 implant models with a mean area under the receiver operating characteristic curve of 0.991, accuracy of 97.9%, sensitivity of 88.6%, and specificity of 98.9% in the external testing dataset of 588 anteroposterior radiographs. The software classified implants at a mean speed of 0.02 seconds per image. CONCLUSION: An AI-based software demonstrated excellent internal and external validation. Although continued surveillance is necessary with implant library expansion, this software represents responsible and meaningful clinical application of AI with immediate potential to globally scale and assist in preoperative planning prior to revision THA.

Artificial Intelligence for Automated Implant Identification in Knee Arthroplasty: A Multicenter External Validation Study Exceeding 3.5 Million Plain Radiographs.

BACKGROUND: Surgical management of complications following knee arthroplasty demands accurate and timely identification of implant manufacturer and model. Automated image processing using deep machine learning has been previously developed and internally validated; however, external validation is essential prior to scaling clinical implementation for generalizability. METHODS: We trained, validated, and externally tested a deep learning system to classify knee arthroplasty systems as one of the 9 models from 4 manufacturers derived from 4,724 original, retrospectively collected anteroposterior plain knee radiographs across 3 academic referral centers. From these radiographs, 3,568 were used for training, 412 for validation, and 744 for external testing. Augmentation was applied to the training set (n = 3,568,000) to increase model robustness. Performance was determined by the area under the receiver operating characteristic curve, sensitivity, specificity, and accuracy. Implant identification processing speed was calculated. The training and testing sets were drawn from statistically different populations of implants (P < .001). RESULTS: After 1,000 training epochs by the deep learning system, the system discriminated 9 implant models with a mean area under the receiver operating characteristic curve of 0.989, accuracy of 97.4%, sensitivity of 89.2%, and specificity of 99.0% in the external testing dataset of 744 anteroposterior radiographs. The software classified implants at a mean speed of 0.02 seconds per image. CONCLUSION: An artificial intelligence-based software for identifying knee arthroplasty implants demonstrated excellent internal and external validation. Although continued surveillance is necessary with implant library expansion, this software represents a responsible and meaningful clinical application of artificial intelligence with immediate potential to globally scale and assist in preoperative planning prior to revision knee arthroplasty.

Detection of vancomycin-resistant Enterococcus faecium hospital-adapted lineages in municipal wastewater treatment plants indicates widespread distribution and release into the environment.

Vancomycin-resistant Enterococcus faecium (VREfm) is a leading cause of healthcare-associated infection. Reservoirs of VREfm are largely assumed to be nosocomial although there is a paucity of data on alternative sources. Here, we describe an integrated epidemiological and genomic analysis of E. faecium associated with bloodstream infection and isolated from wastewater. Treated and untreated wastewater from 20 municipal treatment plants in the East of England, United Kingdom was obtained and cultured to isolate E. faecium, ampicillin-resistant E. faecium (AREfm), and VREfm. VREfm was isolated from all 20 treatment plants and was released into the environment by 17/20 plants, the exceptions using terminal ultraviolet light disinfection. Median log10 counts of AREfm and VREfm in untreated wastewater from 10 plants in direct receipt of hospital sewage were significantly higher than 10 plants that were not. We sequenced and compared the genomes of 423 isolates from wastewater with 187 isolates associated with bloodstream infection at five hospitals in the East of England. Among 481 E. faecium isolates belonging to the hospital-adapted clade, we observed genetic intermixing between wastewater and bloodstream infection, with highly related isolates shared between a major teaching hospital in the East of England and 9/20 plants. We detected 28 antibiotic resistance genes in the hospital-adapted clade, of which 23 were represented in bloodstream, hospital sewage, and municipal wastewater isolates. We conclude that our findings are consistent with widespread distribution of hospital-adapted VREfm beyond acute healthcare settings with extensive release of VREfm into the environment in the East of England.

Descending thoracic aortic homograft for superior vena caval translocation in the Warden procedure: Report of six cases.

BACKGROUND: Warden procedure has been described for repair of partial anomalous pulmonary venous connections inserted high into the superior vena cava. In the current report, we describe a new modification. METHODS: A total of six patients (five females, 83%) with a mean age of 18.8 ± 10.8 years, underwent a modified Warden procedure with a descending thoracic aortic (DTA) homograft connected to the free wall of the right atrium, rather than to the right atrial appendage in the period between June 2021 and July 2022. RESULTS: All patients had evidence of enlarged right-sided cardiac chambers. Two patients had intact interatrial septum (33.3%), while three patients had sinus venosus (50%) and one had secundum atrial septal defects (16.7%). The procedure was performed via minimally invasive right thoracotomy in half of the patients. Patients were extubated in the operating room or soon after. No early mortality or reoperation. One patient required concomitant aortic root replacement and one needed repair of anomalous left upper pulmonary vein connection to the left innominate vein. Follow-up was complete in all patients with a mean of 6.2 ± 4.6 months. No late mortality or reoperation. All patients were discharged on antiplatelet therapy. Follow-up imaging studies showed satisfactory repair with widely patent superior vena caval and pulmonary venous pathways. CONCLUSIONS: The use of DTA homograft to facilitate superior vena caval translocation in the modified Warden procedure appears to be beneficial as it decreases tension on the anastomosis and avoids the need for anticoagulation.

Predictors of Success With Chronic Antibiotic Suppression for Prosthetic Joint Infections.

BACKGROUND: Management of recurrent prosthetic joint infection (PJI) after attempted surgical eradication remains a challenge. Chronic antibiotic suppression (CAS) is regarded as a reasonable treatment option for select patients with persistent infection or multiple comorbidities. The study seeks to compare cohorts who succeed and fail with CAS. METHODS: This retrospective cohort study assesses patients who were treated with CAS for a PJI. Patients were included if they had a culture-proven PJI and received chronic suppressive antibiotics. Failure of suppression was defined as reoperation after initiating CAS or death occurring as result of infection. A Cox proportional hazards multivariate regression model was used to estimate risk of reoperation as a function of risk factors related to patient comorbidities, surgical history, affected joint, and infecting organism. RESULTS: We identified 45 PJIs (31 knees, 14 hips) managed with CAS with a median follow-up of 50 (95% confidence interval [CI] 33.61-74.02) months. The overall success rate of managing PJI with CAS was 67% (30/45). Controlling for body mass index and Gram status of the organism, total hip arthroplasty patients were less likely than total knee arthroplasty patients to require reoperation (hazard ratio 0.18, 95% CI 0.01-0.96, P = .04). Patients with Gram-positive infections were less likely than those with a Gram-negative infections to require reoperation (hazard ratio 0.22, 95% CI 0.05-0.88, P = .03). Severe antibiotic side effects were rare. Patients who experienced multiple changes to their antibiotic regimen were more likely to fail with CAS. CONCLUSION: CAS is a reasonable strategy in patients with PJI who lack or refuse further surgical treatment options. Most hips and Gram-positive infections treated with CAS successfully avoided reoperation in this cohort.

Demographic Data Reliably Predicts Total Hip Arthroplasty Component Size.

BACKGROUND: Preoperative radiographic templating for total hip arthroplasty (THA) has been shown to be inaccurate, although essential for streamlining operating room efficiency. Although demographic data have shown to predict total knee arthroplasty component sizes, the unique contour and design among femoral stem implants have limited a similar application for hip arthroplasty. The purpose of this study was to determine whether demographic data may predict cementless THA size independent of the stem design. METHODS: A consecutive series of 1,653 index cementless metaphyseal-fitting THAs were reviewed between 2007 and 2019. This included 12 unique femoral component designs, 6 acetabular component designs, 60 femur size-design combinations, and 23 acetabular size-design combinations. Implanted component sizes and patient demographic data were collected, including gender, height, weight, laterality, age, race, and ethnicity. Multivariate linear regressions were formulated to predict implanted femur and acetabular component sizes from the demographic data. RESULTS: There was a significant linear correlation between gender, implant model, age, height, and weight for femur (R2 = 0.778; P < .001) and acetabular (R2 = 0.491; P < .001) sizes. Calculated femur and acetabular component sizes averaged within 0.97 and 0.95 sizes of those implants, respectively. Femur and acetabular sizes were predicted within 1 size 79.1% and 78.2% and within 2 sizes 94.3% and 94.6% of the time, respectively. CONCLUSIONS: Multivariate regression models were created based on specific demographics data to predict femur and acetabular component sizes. The model allows for simplified preoperative planning and potential cost savings implementation. A free phone application named EasyTJA was constructed for ease of implementation.

A Multivariate Analysis to Predict Total Hip Arthroplasty Dislocation With Preoperative Diagnosis, Surgical Approach, Spinal Pathology, Cup Orientation, and Head Size.

BACKGROUND: There are several risk factors for dislocation after total hip arthroplasty (THA), but few studies include radiographic assessment of implants, with spine pathology and patient characteristics. This study estimates the rate of dislocation by patient gender, age, race/ethnicity, body mass index, Charlson Comorbidity Index, spine pathology, prior spine fusion, levels affected, radiographic Kellgren-Lawrence score of spine osteoarthritis, THA indication, surgical approach, and femoral head size. METHODS: Seventy-six primary THA patients between January 2007 and 2020 with a dislocation were matched on age and gender to subjects without a known history of dislocation using a 2:1 allocation. Univariable and multivariable survival models that account for matched strata were used to estimate the rate of dislocation. RESULTS: Median follow-up of patients at risk for dislocation was 26.48 months (95% confidence interval [CI] 23.75-36.40). On multivariable analysis, patients with an indication other than primary osteoarthritis were 3.69 (95% CI 2.22-6.13, P < .001) times more likely to dislocate than those with osteoarthritis. Patients with a spine pathology were also nominally more likely to dislocate (hazard ratio 1.76, 95% CI 0.97-3.18, P = .06), and patients receiving a posterior surgical approach were 2.74 (95% CI 1.11-6.76, P = .03) times more likely than those receiving a non-posterior approach to dislocate. CONCLUSION: Patients with THA indication other than primary osteoarthritis and receiving a posterior surgical approach, and to a lesser degree spinal pathology, were identified as affecting the rate of dislocation. After correcting for other variables, femoral head size, cup orientation, and patient factors were not predictive. LEVEL OF EVIDENCE: Level IV, case-control study.

Treatment of methicillin-resistant Staphylococcus aureus (MRSA): updated guidelines from the UK.

The UK guidelines for the treatment of infections caused by MRSA have been updated and are published in JAC-Antimicrobial Resistance. The update reviews new evidence published since the previous UK guidelines were published over 10 years ago. It includes evidence relating to antimicrobial agents that have been licensed since then for the treatment of Gram-positive bacterial infections including MRSA. It also considers the impact on treatment of the changing epidemiology of MRSA in the UK, especially relating to circulating community strains. A striking finding from the current literature review was the paucity of good quality evidence. The current guidelines therefore represent a hybrid of varying degrees of evidence and expert opinion. Where there was no new published evidence, we have retained some of the existing recommendations. We were unable to find strong evidence of the superior efficacy of newer agents compared with that of vancomycin.

A prospective surveillance study to determine the prevalence of 16S rRNA methyltransferase-producing Gram-negative bacteria in the UK.

OBJECTIVES: To determine the prevalence of 16S rRNA methyltransferase- (16S RMTase-) producing Gram-negative bacteria in patients in the UK and to identify potential risk factors for their acquisition. METHODS: A 6 month prospective surveillance study was conducted from 1 May to 31 October 2016, wherein 14 hospital laboratories submitted Acinetobacter baumannii, Enterobacterales and Pseudomonas aeruginosa isolates that displayed high-level amikacin resistance according to their testing methods, e.g. no zone of inhibition with amikacin discs. Isolates were linked to patient travel history, medical care abroad, and previous antibiotic exposure using a surveillance questionnaire. In the reference laboratory, isolates confirmed to grow on Mueller-Hinton agar supplemented with 256 mg/L amikacin were screened by PCR for 16S RMTase genes armA, rmtA-rmtH and npmA, and carbapenemase genes (blaKPC, blaNDM, blaOXA-48-like and blaVIM). STs and total antibiotic resistance gene complement were determined via WGS. Prevalence was determined using denominators for each bacterial species provided by participating hospital laboratories. RESULTS: Eighty-four isolates (44.7%), among 188 submitted isolates, exhibited high-level amikacin resistance (MIC >256 mg/L), and 79 (94.0%) of these harboured 16S RMTase genes. armA (54.4%, 43/79) was the most common, followed by rmtB (17.7%, 14/79), rmtF (13.9%, 11/79), rmtC (12.7%, 10/79) and armA + rmtF (1.3%, 1/79). The overall period prevalence of 16S RMTase-producing Gram-negative bacteria was 0.1% (79/71 063). Potential risk factors identified through multivariate statistical analysis included being male and polymyxin use. CONCLUSIONS: The UK prevalence of 16S RMTase-producing Gram-negative bacteria is low, but continued surveillance is needed to monitor their spread and inform intervention strategies.

Ventilator-associated pneumonia in critically ill patients with COVID-19.

BACKGROUND: Pandemic COVID-19 caused by the coronavirus SARS-CoV-2 has a high incidence of patients with severe acute respiratory syndrome (SARS). Many of these patients require admission to an intensive care unit (ICU) for invasive ventilation and are at significant risk of developing a secondary, ventilator-associated pneumonia (VAP). OBJECTIVES: To study the incidence of VAP and bacterial lung microbiome composition of ventilated COVID-19 and non-COVID-19 patients. METHODS: In this retrospective observational study, we compared the incidence of VAP and secondary infections using a combination of microbial culture and a TaqMan multi-pathogen array. In addition, we determined the lung microbiome composition using 16S RNA analysis in a subset of samples. The study involved 81 COVID-19 and 144 non-COVID-19 patients receiving invasive ventilation in a single University teaching hospital between March 15th 2020 and August 30th 2020. RESULTS: COVID-19 patients were significantly more likely to develop VAP than patients without COVID (Cox proportional hazard ratio 2.01 95% CI 1.14-3.54, p = 0.0015) with an incidence density of 28/1000 ventilator days versus 13/1000 for patients without COVID (p = 0.009). Although the distribution of organisms causing VAP was similar between the two groups, and the pulmonary microbiome was similar, we identified 3 cases of invasive aspergillosis amongst the patients with COVID-19 but none in the non-COVID-19 cohort. Herpesvirade activation was also numerically more frequent amongst patients with COVID-19. CONCLUSION: COVID-19 is associated with an increased risk of VAP, which is not fully explained by the prolonged duration of ventilation. The pulmonary dysbiosis caused by COVID-19, and the causative organisms of secondary pneumonia observed are similar to that seen in critically ill patients ventilated for other reasons.

Genomic Surveillance of Methicillin-resistant Staphylococcus aureus: A Mathematical Early Modeling Study of Cost-effectiveness.

BACKGROUND: Genomic surveillance of methicillin-resistant Staphylococcus aureus (MRSA) identifies unsuspected transmission events and outbreaks. Used proactively, this could direct early and highly targeted infection control interventions to prevent ongoing spread. Here, we evaluated the cost-effectiveness of this intervention in a model that compared whole-genome sequencing plus current practice versus current practice alone. METHODS: A UK cost-effectiveness study was conducted using an early model built from the perspective of the National Health Service and personal social services. The effectiveness of sequencing was based on the relative reduction in total MRSA acquisitions in a cohort of hospitalized patients in the year following their index admissions. A sensitivity analysis was used to illustrate and assess the level of confidence associated with the conclusions of our economic evaluation. RESULTS: A cohort of 65 000 patients were run through the model. Assuming that sequencing would result in a 90% reduction in MRSA acquisition, 290 new MRSA cases were avoided. This gave an absolute reduction of 28.8% and avoidance of 2 MRSA-related deaths. Base case results indicated that the use of routine, proactive MRSA sequencing would be associated with estimated cost savings of over £728 290 per annual hospitalized cohort. The impact in total quality-adjusted life years (QALYs) was relatively modest, with sequencing leading to an additional 14.28 QALYs gained. Results were most sensitive to changes in the probability of a MRSA-negative patient acquiring MRSA during their hospital admission. CONCLUSIONS: We showed that proactive genomic surveillance of MRSA is likely to be cost-effective. Further evaluation is required in the context of a prospective study.

A One Health Study of the Genetic Relatedness of Klebsiella pneumoniae and Their Mobile Elements in the East of England.

BACKGROUND: Klebsiella pneumoniae is a human, animal, and environmental commensal and a leading cause of nosocomial infections, which are often caused by multiresistant strains. We evaluate putative sources of K. pneumoniae that are carried by and infect hospital patients. METHODS: We conducted a 6-month survey on 2 hematology wards at Addenbrooke's Hospital, Cambridge, United Kingdom, in 2015 to isolate K. pneumoniae from stool, blood, and the environment. We conducted cross-sectional surveys of K. pneumoniae from 29 livestock farms, 97 meat products, the hospital sewer, and 20 municipal wastewater treatment plants in the East of England between 2014 and 2015. Isolates were sequenced and their genomes compared. RESULTS: Klebsiella pneumoniae was isolated from stool of 17/149 (11%) patients and 18/922 swabs of their environment, together with 1 bloodstream infection during the study and 4 others over a 24-month period. Each patient carried 1 or more lineages that was unique to them, but 2 broad environmental contamination events and patient-environment transmission were identified. Klebsiella pneumoniae was isolated from cattle, poultry, hospital sewage, and 12/20 wastewater treatment plants. There was low genetic relatedness between isolates from patients/their hospital environment vs isolates from elsewhere. Identical genes encoding cephalosporin resistance were carried by isolates from humans/environment and elsewhere but were carried on different plasmids. CONCLUSION: We identified no patient-to-patient transmission and no evidence for livestock as a source of K. pneumoniae infecting humans. However, our findings reaffirm the importance of the hospital environment as a source of K. pneumoniae associated with serious human infection.

Systematic longitudinal survey of invasive Escherichia coli in England demonstrates a stable population structure only transiently disturbed by the emergence of ST131.

Escherichia coli associated with urinary tract infections and bacteremia has been intensively investigated, including recent work focusing on the virulent, globally disseminated, multidrug-resistant lineage ST131. To contextualize ST131 within the broader E. coli population associated with disease, we used genomics to analyze a systematic 11-yr hospital-based survey of E. coli associated with bacteremia using isolates collected from across England by the British Society for Antimicrobial Chemotherapy and from the Cambridge University Hospitals NHS Foundation Trust. Population dynamics analysis of the most successful lineages identified the emergence of ST131 and ST69 and their establishment as two of the five most common lineages along with ST73, ST95, and ST12. The most frequently identified lineage was ST73. Compared to ST131, ST73 was susceptible to most antibiotics, indicating that multidrug resistance was not the dominant reason for prevalence of E. coli lineages in this population. Temporal phylogenetic analysis of the emergence of ST69 and ST131 identified differences in the dynamics of emergence and showed that expansion of ST131 in this population was not driven by sequential emergence of increasingly resistant subclades. We showed that over time, the E. coli population was only transiently disturbed by the introduction of new lineages before a new equilibrium was rapidly achieved. Together, these findings suggest that the frequency of E. coli lineages in invasive disease is driven by negative frequency-dependent selection occurring outside of the hospital, most probably in the commensal niche, and that drug resistance is not a primary determinant of success in this niche.