MPFL Reconstruction and Implant-Mediated Guided Growth in Skeletally Immature Patients With Patellar Instability and Genu Valgum.

BACKGROUND: There is a higher rate of failure of isolated MPFL reconstruction in skeletally immature patients with patellar instability compared to skeletally mature patients. Genu valgum is a known risk factor for patellar instability. There is potential for concomitant surgical correction of genu valgum to achieve better clinical outcomes and to decrease failure rates of MPFL reconstruction. PURPOSE: To evaluate outcomes of combined medial patellofemoral ligament (MPFL) reconstruction and implant-mediated guided growth (IMGG) in skeletally immature patients with patellar instability and genu valgum. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: In a multicenter study, all skeletally immature patients with recurrent patellar instability and genu valgum who underwent MPFL reconstruction using hamstring graft and IMGG using a transphyseal screw or tension band plate for the distal femur and/or proximal tibia were included. The knee valgus angle and mechanical axis were measured on full-length radiographs and anatomic risk factors were measured on MRI. Patients were followed until correction of their lower limb alignment and implant removal or until skeletal maturity. Clinical outcomes, including complications, were analyzed. RESULTS: A total of 31 patients (37 knees) were included in the study. The mean age and skeletal age of the cohort were 12.4 and 12.9 years, respectively. Simultaneous MPFL reconstruction and IMGG were performed in 26 of 37 knees; 11 underwent staged procedures. Twenty knees had transphyseal screws and 17 knees had tension band plates for IMGG. The knee valgus corrected from a mean of 12.4° to 5.1° in 12.1 months. Implants were removed from 22 of 37 knees once genu valgum was corrected. There was no significant difference (P = .65) in the correction rate between plates (0.7 deg/month) and screws (0.6 deg/month). Ten complications occurred in 4 patients (7 knees) and included 5 patellar redislocations, 2 rebound valgus, 1 varus overcorrection, 1 knee arthrofibrosis, and 1 implant loosening. For children <10 years of age, 3 of 6 (50%) knees had patellar redislocations and 5 of 6 knees had a complication. This was statistically significant (P = .003) compared with patients >10 years of age. Similarly, for patients with bilateral knee involvement, 5 of 12 (42%) knees had patellar redislocations and a total of 8 complications occurred in this subset. This was statistically significant (P < .001) compared with patients with unilateral involvement. CONCLUSION: IMGG with plates or screws in the setting of combined MPFL reconstruction improves genu valgum. Children <10 years of age and those with bilateral instability with genu valgum remain difficult subsets to treat with higher complication rates.

Integrated analysis of patient networks and plasmid genomes reveals a regional, multi-species outbreak of carbapenemase-producing Enterobacterales carrying both blaIMP and mcr-9 genes.

BACKGROUND: Carbapenemase-producing Enterobacterales (CPE) are challenging in healthcare, with resistance to multiple classes of antibiotics. This study describes the emergence of IMP-encoding CPE amongst diverse Enterobacterales species between 2016 and 2019 across a London regional network. METHODS: We performed a network analysis of patient pathways, using electronic health records, to identify contacts between IMP-encoding CPE positive patients. Genomes of IMP-encoding CPE isolates were overlayed with patient contacts to imply potential transmission events. RESULTS: Genomic analysis of 84 Enterobacterales isolates revealed diverse species (predominantly Klebsiella spp, Enterobacter spp, E. coli); 86% (72/84) harboured an IncHI2 plasmid carrying blaIMP and colistin resistance gene mcr-9 (68/72). Phylogenetic analysis of IncHI2 plasmids identified three lineages showing significant association with patient contacts and movements between four hospital sites and across medical specialities, which was missed on initial investigations. CONCLUSIONS: Combined, our patient network and plasmid analyses demonstrate an interspecies, plasmid-mediated outbreak of blaIMPCPE, which remained unidentified during standard investigations. With DNA sequencing and multi-modal data incorporation, the outbreak investigation approach proposed here provides a framework for real-time identification of key factors causing pathogen spread. Plasmid-level outbreak analysis reveals that resistance spread may be wider than suspected, allowing more interventions to stop transmission within hospital networks.

Consensus-Based Guidelines for Management of First-Time Patellar Dislocation in Adolescents.

BACKGROUND: The management of first-time patellar dislocation remains variable, with limited evidence to support or compare different operative and nonoperative modalities. The primary aim was to establish consensus-based guidelines for different components of nonoperative treatment following a first-time patellar dislocation. The secondary aim was to develop guidelines related to management after failed nonoperative treatment. The tertiary aim was to establish consensus-based guidelines for the management of first-time patellar dislocation with a concomitant osteochondral fracture. METHODS: A 29-question, multiple-choice, case-based survey was developed by 20 members of the Patellofemoral Research Interest Group of the Pediatric Research in Sports Medicine Society. The survey consisted of questions related to demographic information, management of first-time patellar dislocation without an osteochondral fracture, and management of first-time patellar dislocation with a 2 cm osteochondral fracture. The survey underwent 2 rounds of iterations by Patellofemoral Research Interest Group members and the final survey was administered to Pediatric Research in Sports Medicine members, using REDCap. Consensus-based guidelines were generated when more than 66% of respondents chose the same answer. RESULTS: Seventy-nine of 157 (50%) eligible members responded. Sixty-one were orthopaedic surgeons and 18 were primary sports medicine physicians. Eleven consensus-based guidelines were generated based on survey responses. Those that met the criteria for consensus included initial knee radiographs (99% consensus), nonoperative treatment for first-time patellar dislocation without an osteochondral fracture (99%), physical therapy starting within the first month postinjury (99%), with return to sport after 2 to 4 months (68%) with a brace (75%) and further follow-up as needed (75%). Surgical treatment was recommended if there were patellar subluxation episodes after 6 months of nonoperative treatment (84%). Patellar stabilization should be considered for a first-time dislocation with an osteochondral fracture (81.5%). CONCLUSION: Consensus-based guidelines offer recommendations for the management of first-time patellar dislocation with or without an osteochondral fracture. Several changing trends and areas of disagreement were noted in clinical practice. CLINICAL RELEVANCE: In the absence of high-level evidence, consensus-based guidelines may aid in clinical decision-making when treating patients following a first-time patellar dislocation. These guidelines highlight the evolving trends in clinical practice for the management of first-time patellar dislocation. Areas not reaching consensus serve as topics for future research.

Discordance between different bioinformatic methods for identifying resistance genes from short-read genomic data, with a focus on Escherichia coli.

Several bioinformatics genotyping algorithms are now commonly used to characterize antimicrobial resistance (AMR) gene profiles in whole-genome sequencing (WGS) data, with a view to understanding AMR epidemiology and developing resistance prediction workflows using WGS in clinical settings. Accurately evaluating AMR in Enterobacterales, particularly Escherichia coli, is of major importance, because this is a common pathogen. However, robust comparisons of different genotyping approaches on relevant simulated and large real-life WGS datasets are lacking. Here, we used both simulated datasets and a large set of real E. coli WGS data (n=1818 isolates) to systematically investigate genotyping methods in greater detail. Simulated constructs and real sequences were processed using four different bioinformatic programs (ABRicate, ARIBA, KmerResistance and SRST2, run with the ResFinder database) and their outputs compared. For simulation tests where 3079 AMR gene variants were inserted into random sequence constructs, KmerResistance was correct for 3076 (99.9 %) simulations, ABRicate for 3054 (99.2 %), ARIBA for 2783 (90.4 %) and SRST2 for 2108 (68.5 %). For simulation tests where two closely related gene variants were inserted into random sequence constructs, KmerResistance identified the correct alleles in 35 338/46 318 (76.3 %) simulations, ABRicate identified them in 11 842/46 318 (25.6 %) simulations, ARIBA identified them in 1679/46 318 (3.6 %) simulations and SRST2 identified them in 2000/46 318 (4.3 %) simulations. In real data, across all methods, 1392/1818 (76 %) isolates had discrepant allele calls for at least 1 gene. In addition to highlighting areas for improvement in challenging scenarios, (e.g. identification of AMR genes at <10× coverage, identifying multiple closely related AMR genes present in the same sample), our evaluations identified some more systematic errors that could be readily soluble, such as repeated misclassification (i.e. naming) of genes as shorter variants of the same gene present within the reference resistance gene database. Such naming errors accounted for at least 2530/4321 (59 %) of the discrepancies seen in real data. Moreover, many of the remaining discrepancies were likely 'artefactual', with reporting of cut-off differences accounting for at least 1430/4321 (33 %) discrepants. Whilst we found that comparing outputs generated by running multiple algorithms on the same dataset could identify and resolve these algorithmic artefacts, the results of our evaluations emphasize the need for developing new and more robust genotyping algorithms to further improve accuracy and performance.

Relationship Between Age and Pathology With Treatment of Pediatric and Adolescent Discoid Lateral Meniscus: A Report From the SCORE Multicenter Database.

BACKGROUND: Surgical treatment options of discoid lateral meniscus in pediatric patients consist of saucerization with or without meniscal repair, meniscocapular stabilization, and, less often, subtotal meniscectomy. PURPOSE: To describe a large, prospectively collected multicenter cohort of discoid menisci undergoing surgical intervention, and further investigate corresponding treatment of discoid menisci. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: A multicenter quality improvement registry (16 institutions, 26 surgeons), Sports Cohort Outcomes Registry, was queried. Patient characteristics, discoid type, presence and type of intrasubstance meniscal tear, peripheral rim instability, repair technique, and partial meniscectomy/debridement beyond saucerization were reviewed. Discoid meniscus characteristics were compared between age groups (<14 and >14 years old), based on receiver operating characteristic curve, and discoid morphology (complete and incomplete). RESULTS: In total, 274 patients were identified (mean age, 12.4 years; range, 3-18 years), of whom 55.6% had complete discoid. Meniscal repairs were performed in 55.1% of patients. Overall, 48.5% of patients had rim instability and 36.8% had >1 location of peripheral rim instability. Of the patients, 21.5% underwent meniscal debridement beyond saucerization, with 8.4% undergoing a subtotal meniscectomy. Patients <14 years of age were more likely to have a complete discoid meniscus (P < .001), peripheral rim instability (P = .005), and longitudinal tears (P = .015) and require a meniscal repair (P < .001). Patients ≥14 years of age were more likely to have a radial/oblique tear (P = .015) and require additional debridement beyond the physiologic rim (P = .003). Overall, 70% of patients <14 years of age were found to have a complete discoid meniscus necessitating saucerization, and >50% in this young age group required peripheral stabilization/repair. CONCLUSION: To preserve physiological "normal" meniscus, a repair may be indicated in >50% of patients <14 years of age but occurred in <50% of those >14 years. Additional resection beyond the physiological rim may be needed in 15% of younger patients and 30% of those aged >14 years.

IS1-related large-scale deletion of chromosomal regions harbouring the oxygen-insensitive nitroreductase gene nfsB causes nitrofurantoin heteroresistance in Escherichia coli.

Nitrofurantoin is a broad-spectrum first-line antimicrobial used for managing uncomplicated urinary tract infection (UTI). Loss-of-function mutations in chromosomal genes nfsA, nfsB and ribE of Escherichia coli are known to reduce nitrofurantoin susceptibility. Here, we report the discovery of nitrofurantoin heteroresistance in E. coli clinical isolates and a novel genetic mechanism associated with this phenomenon. Subpopulations with lower nitrofurantoin susceptibility than major populations (hereafter, nitrofurantoin-resistant subpopulations) in two E. coli blood isolates (previously whole-genome sequenced) were identified using population analysis profiling. Each isolate was known to have a loss-of-function mutation in nfsA. From each isolate, four nitrofurantoin-resistant isolates were derived at a nitrofurantoin concentration of 32 mg l-1, and a comparator isolate was obtained without any nitrofurantoin exposure. Genomes of derived isolates were sequenced on Illumina and Nanopore MinION systems. Genetic variation between isolates was determined based on genome assemblies and read mapping. Nitrofurantoin minimum inhibitory concentrations (MICs) of both blood isolates were 64 mg l-1, with MICs of major nitrofurantoin-susceptible populations varying from 4 to 8 mg l-1. Two to 99 c.f.u. per million demonstrated growth at the nitrofurantoin concentration of 32 mg l-1, which is distinct from that of a homogeneously susceptible or resistant isolate. Derived nitrofurantoin-resistant isolates had 11-66 kb deletions in chromosomal regions harbouring nfsB, and all deletions were immediately adjacent to IS1-family insertion sequences. Our findings demonstrate that the IS1-associated large-scale genetic deletion is a hitherto unrecognized mechanism of nitrofurantoin heteroresistance and could compromise UTI management. Further, frequencies of resistant subpopulations from nitrofurantoin-heteroresistant isolates may challenge conventional nitrofurantoin susceptibility testing in clinical settings.

Treatment of proximal tibial buckle fractures: removable knee immobilizer versus long leg cast.

The purpose of this study was to compare outcomes and management of patients with buckle fractures of the proximal tibia treated with either a knee immobilizer or a long leg cast (LLC). A retrospective review was performed of pediatric patients with a buckle fracture of the proximal tibia over a 5-year period. Two cohorts were included, those treated with a LLC versus a removable knee immobilizer. Data collected included immobilization type, fracture laterality, length of immobilization, number of clinic visits, fracture displacement, and complications. Differences in complications and management between the cohorts were evaluated. In total, 224 patients met inclusion criteria (58% female, mean age 3.1 years ± 1.7 years). Of these patients, 187 patients (83.5%) were treated with a LLC. No patients in either group were found to have interval fracture displacement during treatment. Seven patients (3.1%) demonstrated skin complications, all in the LLC cohort. Mean length of immobilization was shorter for those treated in a knee immobilizer at 25.9 days versus 27.9 days for the LLC cohort (P = 0.024). Total number of clinic visits was also less at 2.2 (SD ±â€…0.4 days) for the knee immobilizer and 2.6 (SD ±â€…0.7 days) for the LLC (P = 0.001) cohorts. Pediatric patients with proximal tibial buckle fractures can be safely managed with a knee immobilizer. This treatment method is associated with a shorter duration of immobilization and fewer clinic visits without incidence of fracture displacement. In addition, knee immobilizers can lessen skin issues associated with cast immobilization and cast-related office visits. This is a Level III evidence, retrospective comparative study.

Variability in Pain Management Practices for Pediatric Anterior Cruciate Ligament Reconstruction.

BACKGROUND: The opioid epidemic in the United States is a public health crisis. Pediatric orthopaedic surgeons must balance adequate pain management with minimizing the risk of opioid misuse or dependence. There is limited data available to guide pain management for anterior cruciate ligament reconstruction (ACLR) in the pediatric population. The purpose of this study was to survey current pain management practices for ACLR among pediatric orthopaedic surgeons. METHODS: A cross-sectional survey study was conducted, in which orthopaedic surgeons were asked about their pain management practices for pediatric ACLR. The voluntary survey was sent to members of the Pediatric Orthopaedic Society of North America. Inclusion criteria required that the surgeon perform anterior cruciate ligament repair or reconstruction on patients under age 18. Responses were anonymous and consisted of surgeon demographics, training, practice, and pain management strategies. Survey data were assessed using descriptive statistics. RESULTS: Of 64 included responses, the average age of the survey respondent was 48.9 years, 84.4% were males, and 31.3% practiced in the southern region of the United States. Preoperative analgesia was utilized by 39.1%, 90.6% utilized perioperative blocks, and 89.1% prescribed opioid medication postoperatively. For scheduled non-narcotic medications postoperatively 82.8% routinely advocated and 93.8% recommended cryotherapy postoperatively.Acetaminophen was the most used preoperative medication (31.3%), the most common perioperative block was an adductor canal block (81.0%), and the most common postoperative analgesic medication was ibuprofen (60.9%). Prior training or experience was more frequently reported than published research as a primary factor influencing pain management protocols. CONCLUSIONS: Substantial variability exists in pain management practices in pediatric ACLR. There is a need for more evidence-based practice guidelines regarding pain management. LEVEL OF EVIDENCE: Level V.

Rate of concomitant cellulitis and osteoarticular infections in a pediatric population.

Concern for infection is a common presentation in pediatric emergency departments. Clinical signs of cellulitis in pediatric patients often lead to a workup for osteoarticular infection despite a lack of evidence to suggest that the two entities commonly co-exist. With this in mind, we asked: (1) What is the rate of concomitant cellulitis and osteoarticular infections in the pediatric population? (2) What factors are associated with concomitant cellulitis and osteoarticular infections? This is a retrospective study of 482 pediatric patients who underwent MRI to evaluate for either cellulitis or an osteoarticular infection at a single tertiary care children's hospital. Data were analyzed to assess the prevalence of osteomyelitis concomitant with cellulitis in our sample population. Concomitant cellulitis and osteoarticular infection were present in 11% of all cases (53/482). Of the concomitant infections, 92% percent (49/53) were present in distal locations (Group 1) and 8% (4/53) were present in proximal locations (Group 2). Bivariate analysis showed that concomitant infections on the distal extremities were significantly more common than concomitant infections on the proximal extremities ( P < 0.001). We found that concomitant cellulitis and osteoarticular infection were (1) uncommon and (2) significantly less common when clinical signs of cellulitis were present in the proximal extremities (proximal to ankle or wrist). This suggests that advanced imaging is most appropriate for patients who present with cellulitis on the distal extremities and can be used more judiciously in patients presenting with cellulitis on the proximal extremities. Level of Evidence - Level III.

A Broad-Host-Range Plasmid Outbreak: Dynamics of IncL/M Plasmids Transferring Carbapenemase Genes.

IncL/M broad-host-range conjugative plasmids are involved in the global spread of blaOXA-48 and the emergence of blaNDM-1. The aim of this study was to evaluate the transmission potential of plasmids encoding the emergent NDM-1 carbapenemase compared to the pandemic OXA-48. The conjugation rate and fitness cost of IncM2 and IncL plasmids encoding these carbapenemase genes were tested using a variety of host bacteria. Genomic analysis of uropathogenic Escherichia coli SAP1756 revealed that blaNDM-1 was encoded on an IncM2 plasmid, which also harboured blaTEM-1, bleMBL and sul1 and was highly similar to plasmids isolated from the same geographical area. Conjugation experiments demonstrated that NDM-1 and OXA-48-carrying plasmids transfer successfully between different Enterobacterales species, both in vitro and in vivo. Interestingly, E. coli isolates tested as recipients belonging to phylogroups A, B1, D and F were able to receive IncM2 plasmid pSAP1756, while phylogroups B2, C, E and G were not permissive to its acquisition. In general, the IncL OXA-48-carrying plasmids tested transferred at higher rates than IncM2 harbouring NDM-1 and imposed a lower burden to their host, possibly due to the inactivation of the tir fertility inhibition gene and reflecting their worldwide dissemination. IncM2 plasmids carrying blaNDM-1 are considered emergent threats that need continuous monitoring. In addition to sequencing efforts, phenotypic analysis of conjugation rates and fitness cost are effective methods for estimating the pandemic potential of antimicrobial resistance plasmids.

Diversity of carbapenemase-producing Enterobacterales in England as revealed by whole-genome sequencing of isolates referred to a national reference laboratory over a 30-month period.

Introduction. Increasing numbers of carbapenemase-producing Enterobacterales (CPE), which can be challenging to treat, have been referred to the national reference laboratory in England since the early 2000s.Gap Statement/Aim. Previous studies on CPE in the UK have focussed on localized outbreaks. We applied whole-genome sequencing (WGS) to isolates referred to the national reference laboratory over 30 months to inform our understanding of CPE epidemiology in England.Methodology. The first confirmed CPE from each new patient referred by an English diagnostic laboratory between 1 January 2014 and 30 June 2016 was sequenced on an Illumina HiSeq 2500. Multiple isolates from the same patient were included from either different species or the same species with different carbapenemase genes. The data were analysed using an in-house bioinformatics pipeline that determines species identification, multi-locus sequence typing (MLST) profile and antimicrobial resistance gene content.Results. A total of 2658 non-duplicate CPE were sequenced amongst which three host organisms belonging to diverse sequence types (STs) predominated: Klebsiella pneumoniae (1380/2658, 51.9 %; 177 STs), Escherichia coli (723/2658, 27.2 %; 133 STs) and Enterobacter cloacae (294/2658, 11.1 %; 88 STs). Thirty different carbapenemase gene variants were identified, although bla OXA-48-like (1122/2658, 42.2%), bla NDM (692/2658, 26.0 %), bla KPC (571/2658, 21.5 %), bla VIM (100/2658, 3.8 %) and bla IMP (33/2658, 1.2 %) predominated. ST/carbapenemase gene pairings represented widely distributed high-risk clones or clusters at a regional or hospital level.Conclusion. CPE referred to the national reference laboratory are diverse, suggesting multiple introductions to England and a role for horizontal transfer of carbapenemase genes in English CPE epidemiology.

Bacterial genotypic and patient risk factors for adverse outcomes in Escherichia coli bloodstream infections: a prospective molecular epidemiological study.

OBJECTIVES: Escherichia coli bloodstream infections have shown a sustained increase in England, for reasons that are unknown. Furthermore, the contribution of MDR lineages such as ST131 to overall E. coli disease burden and outcome is undetermined. METHODS: We genome-sequenced E. coli blood isolates from all patients with E. coli bacteraemia in north-west London from July 2015 to August 2016 and assigned MLST genotypes, virulence factors and AMR genes to all isolates. Isolate STs were then linked to phenotypic antimicrobial susceptibility, patient demographics and clinical outcome data to explore relationships between the E. coli STs, patient factors and outcomes. RESULTS: A total of 551 E. coli genomes were analysed. Four STs (ST131, 21.2%; ST73, 14.5%; ST69, 9.3%; and ST95, 8.2%) accounted for over half of cases. E. coli genotype ST131-C2 was associated with phenotypic non-susceptibility to quinolones, third-generation cephalosporins, amoxicillin, amoxicillin/clavulanic acid, gentamicin and trimethoprim. Among 300 patients from whom outcome was known, an association between the ST131-C2 lineage and longer length of stay was detected, although multivariable regression modelling did not demonstrate an association between E. coli ST and mortality. Several unexpected associations were identified between gentamicin non-susceptibility, ethnicity, sex and adverse outcomes, requiring further research. CONCLUSIONS: Although E. coli ST was associated with defined antimicrobial non-susceptibility patterns and prolonged length of stay, E. coli ST was not associated with increased mortality. ST131 has outcompeted other lineages in north-west London. Where ST131 is prevalent, caution is required when devising empiric regimens for suspected Gram-negative sepsis, in particular the pairing of ß-lactam agents with gentamicin.

Emergence of methicillin resistance predates the clinical use of antibiotics.

The discovery of antibiotics more than 80 years ago has led to considerable improvements in human and animal health. Although antibiotic resistance in environmental bacteria is ancient, resistance in human pathogens is thought to be a modern phenomenon that is driven by the clinical use of antibiotics1. Here we show that particular lineages of methicillin-resistant Staphylococcus aureus-a notorious human pathogen-appeared in European hedgehogs in the pre-antibiotic era. Subsequently, these lineages spread within the local hedgehog populations and between hedgehogs and secondary hosts, including livestock and humans. We also demonstrate that the hedgehog dermatophyte Trichophyton erinacei produces two ß-lactam antibiotics that provide a natural selective environment in which methicillin-resistant S. aureus isolates have an advantage over susceptible isolates. Together, these results suggest that methicillin resistance emerged in the pre-antibiotic era as a co-evolutionary adaptation of S. aureus to the colonization of dermatophyte-infected hedgehogs. The evolution of clinically relevant antibiotic-resistance genes in wild animals and the connectivity of natural, agricultural and human ecosystems demonstrate that the use of a One Health approach is critical for our understanding and management of antibiotic resistance, which is one of the biggest threats to global health, food security and development.

NDM-1 carbapenemase resistance gene vehicles emergent on distinct plasmid backbones from the IncL/M family.

OBJECTIVES: To assess the genetic contexts surrounding blaNDM-1 genes carried on IncM plasmids harboured by six carbapenemase-producing Enterobacterales (CPE) isolates referred to the UK Health Security Agency's Antimicrobial Resistance and Healthcare Associated Infections (AMRHAI) Reference Unit. METHODS: Between 2014 and 2018, the AMRHAI Reference Unit undertook WGS of CPE isolates using Illumina NGS. Nanopore sequencing was used for selected isolates and publicly available plasmid references were downloaded. Analysis of incRNA, which encodes the antisense RNA regulating plasmidic repA gene expression, was performed and bioinformatics tools were used to analyse whole plasmid sequences. RESULTS: Of 894 NDM-positive isolates of Enterobacterales, 44 NDM-1-positive isolates of five different species (Citrobacter spp., Enterobacter cloacae, Escherichia coli, Klebsiella pneumoniae and Klebsiella oxytoca) encoded the IncRNA locus of IncM2 plasmids. Long-read sequencing of six diverse isolates revealed related IncM2, NDM-1-encoding plasmids. Plasmid 'backbone' areas were conserved and contrasted with highly variable resistance regions. Sub-groupings of IncM2 plasmids encoding blaNDM-1 were detected; one sub-group occurred in five different health regions of England in every year. The diversity of NDM-1-encoding resistance gene integrons and transposons and their insertions sites in the plasmids indicated that NDM-1 has been acquired repeatedly by IncM2 variants. CONCLUSIONS: The use of sequencing helped inform: (i) a wide geographical distribution of isolates encoding NDM-1 on emergent IncM2 plasmids; (ii) variant plasmids have acquired NDM-1 separately; and (iii) dynamic arrangements and evolution of the resistance elements in this plasmid group. The geographical and temporal distribution of IncM2 plasmids that encode NDM-1 highlights them as a public health threat that requires ongoing monitoring.

Migration of Escherichia coli and Klebsiella pneumoniae Carbapenemase (KPC)-Producing Enterobacter cloacae through Wastewater Pipework and Establishment in Hospital Sink Waste Traps in a Laboratory Model System.

Sink waste traps and drains are a reservoir for multi-drug resistant Gram-negative bacteria in the hospital environment. It has been suggested that these bacteria can migrate through hospital plumbing. Hospital waste traps were installed in a laboratory model system where sinks were connected through a common wastewater pipe. Enterobacterales populations were monitored using selective culture, MALDI-TOF identification and antibiotic resistance profiling before and after a wastewater backflow event. When transfer between sinks was suspected, isolates were compared using whole-genome sequencing. Immediately after the wastewater backflow, two KPC-producing Enterobacter cloacae were recovered from a waste trap in which Carbapenemase-producing Enterobacterales (CPE) had not been detected previously. The isolates belonged to ST501 and ST31 and were genetically indistinguishable to those colonising sinks elsewhere in the system. Following inter-sink transfer, KPC-producing E. cloacae ST501 successfully integrated into the microbiome of the recipient sink and was detected in the waste trap water at least five months after the backflow event. Seven weeks and three months after the backflow, other inter-sink transfers involving Escherichia coli ST5295 and KPC-producing E. cloacae ST501 were also observed.

What's New in Pain Management for Pediatric Orthopaedic Surgery.

BACKGROUND: Improving pain control and decreasing opioid prescription and usage continue to be emphasized across both pediatric and adult populations. The purpose of this review is to provide a comprehensive assessment of recent literature and highlight new advancements pertaining to pain control in pediatric orthopaedic surgery. METHODS: An electronic search of the PubMed database was performed for keywords relating to perioperative pain management of pediatric orthopaedic surgery. Search results were filtered by publication date for articles published between January 1, 2015 and December 1, 2020 and yielded 404 papers. RESULTS: A total of 32 papers were selected for review based upon new findings and significant contributions in the following categories: risk factors for increased opioid usage, opioid overprescribing and disposal, nonpharmacologic interventions, nonsteroidal anti-inflammatory drugs, peripheral nerve blocks, spine surgery specific considerations, surgical pathway modifications, and future directions. CONCLUSIONS: There have been many advances in pain management for pediatric patients following orthopaedic surgery. Rapid recovery surgical care pathways are associated with shorter length of stay and improved pain control in pediatric spine surgery. Opioid overprescribing continues to be common and information regarding safe opioid disposal practices should be routinely provided for pediatric patients undergoing surgery. LEVEL OF EVIDENCE: Level IV-literature review.

Optimizing antimicrobial use: challenges, advances and opportunities.

An optimal antimicrobial dose provides enough drug to achieve a clinical response while minimizing toxicity and development of drug resistance. There can be considerable variability in pharmacokinetics, for example, owing to comorbidities or other medications, which affects antimicrobial pharmacodynamics and, thus, treatment success. Although current approaches to antimicrobial dose optimization address fixed variability, better methods to monitor and rapidly adjust antimicrobial dosing are required to understand and react to residual variability that occurs within and between individuals. We review current challenges to the wider implementation of antimicrobial dose optimization and highlight novel solutions, including biosensor-based, real-time therapeutic drug monitoring and computer-controlled, closed-loop control systems. Precision antimicrobial dosing promises to improve patient outcome and is important for antimicrobial stewardship and the prevention of antimicrobial resistance.

Interrater and Intrarater Reliability and Discriminant Validity of a Pediatric Lower Extremity Physical Therapy Clearance Test.

BACKGROUND: Few studies have validated when an athlete can safely return to sports, and even fewer have identified when he or she no longer requires physical therapy after surgery. Discontinuing physical therapy is often dictated by insurance restrictions, but most studies have suggested that the decision should be multifactorial, stemming from patient-derived subjective outcome questionnaires, clinical examination, and isokinetic and functional testing. PURPOSE/HYPOTHESIS: The purpose of this study was to establish discriminant validity and reliability of an objective physical therapy clearance (PTC) test in a clinical setting. The hypotheses were that the PTC test (1) will demonstrate different scores between normal and postoperative cohorts and (2) will have acceptable inter- and intraobserver reliability. STUDY DESIGN: Cohort study (diagnosis); Level of evidence, 3. METHODS: Four cohorts (27 total participants; age range, 12-18 years) underwent the PTC test: 9 adolescents 6 months after anterior cruciate ligament reconstruction, 4 adolescents 6 weeks after partial meniscectomy, 5 adolescents with nonstructural knee pain, and 9 control/healthy participants without any lower extremity complaint. The PTC test included a dynamic warm-up, objective measures (knee range of motion, thigh girth, and muscle motor tone), functional strength tests (heel raises, single-leg dips, hop tests, tuck jumps), and agility tests (shuffle and sprint T-test). Each testing session was videotaped and scored live by the physical therapist administering the test, and then scored via the video recording by an independent physical therapist and 2 orthopaedic surgeons. RESULTS: The PTC test was found to have discriminant validity between the control cohort and both cohorts with previous surgery. The single-leg dip, single-leg hop, and vertical tuck jump were the most discriminatory components. The PTC test had moderate to almost perfect intrarater reliability (κ = 0.57-1), but only fair to moderate interrater reliability among video graders (κ = 0.29-0.58) and slight to substantial reliability between video graders and the live PT rater (κ = 0.19-0.63). CONCLUSION: The PTC test was found to have moderate inter- and intraobserver agreement, with the ability to discriminate between postoperative and control patients.