Transmisión de Klebsiella pneumoniae resistente a carbapenemes en hospitales de EE.UU.

Antecedentes. La Klebsiella pneumoniae resistente a los carbapenemes (CRKp) es el Enterobacterales resistente a los carbapenemes más prevalente en los Estados Unidos. Se evaluó la agrupación de CRKp en pacientes de hospitales estadounidenses. Métodos. De abril de 2016 a agosto de 2017, 350 pacientes con grupo clonal 258 CRKp se inscribieron en el Consortium on Resistance Against Carbapenems in Klebsiella and other Enterobacteriaceae, un estudio de cohortes prospectivo y multicéntrico. Se construyó un árbol de máxima verosimilitud utilizando RAxML. Los conglomerados estáticos compartían ≤21 polimorfismos de un solo nucleótido (SNP) y un ancestro común más reciente. Los conglomerados dinámicos incorporaron la distancia SNP, el tiempo de cultivo y las tasas de acumulación y transmisión SNP utilizando el programa R TransCluster. Resultados. La mayoría de los pacientes ingresaron desde su domicilio (n=150, 43%) o desde centros de cuidados de larga duración (n=115, 33%). La orina (n=149, 43%) fue el lugar de aislamiento más común. En total, se identificaron 55 conglomerados estáticos y 47 dinámicos en 210 de 350 (60%) y 194 de 350 (55%) pacientes, respectivamente. Aproximadamente la mitad de los clusters estáticos eran idénticos a los dinámicos. Los conglomerados estáticos consistían en 33 (60%) conglomerados intrasistema y 22 (40%) conglomerados intersistema. Los conglomerados dinámicos estaban formados por 32 (68%) conglomerados intrasistema y 15 (32%) conglomerados intersistema y presentaban menos diferencias de SNP que los conglomerados estáticos (8 frente a 9; P=.045; intervalo de confianza [IC] del 95%: -4 a 0). Los conglomerados dinámicos intersistema contenían más pacientes que los conglomerados dinámicos intrasistema (mediana [intervalo intercuartílico], 4 [2, 7] frente a 2 [2, 2]; P=,007; IC del 95%: -3 a 0). Conclusiones. Se identificó una amplia transmisión intrasistémica e intersistémica de CRKp en pacientes estadounidenses hospitalizados. El uso de diferentes métodos para evaluar la similitud genética sólo dio lugar a diferencias menores en la interpretación.Background. Carbapenem-resistant Klebsiella pneumoniae (CRKp) is the most prevalent carbapenem-resistant Enterobacterales in the United States. We evaluated CRKp clustering in patients in US hospitals. Methods. From April 2016 to August 2017, 350 patients with clonal group 258 CRKp were enrolled in the Consortium on Resistance Against Carbapenems in Klebsiella and other Enterobacteriaceae, a prospective, multicenter, cohort study. A maximum likelihood tree was constructed using RAxML. Static clusters shared ≤21 single-nucleotide polymorphisms (SNP) and a most recent common ancestor. Dynamic clusters incorporated SNP distance, culture timing, and rates of SNP accumulation and transmission using the R program TransCluster. Results. Most patients were admitted from home (n=150, 43%) or long-term care facilities (n=115, 33%). Urine (n=149, 43%) was the most common isolation site. Overall, 55 static and 47 dynamics clusters were identified involving 210 of 350 (60%) and 194 of 350 (55%) patients, respectively. Approximately half of static clusters were identical to dynamic clusters. Static clusters consisted of 33 (60%) intrasystem and 22 (40%) intersystem clusters. Dynamic clusters consisted of 32 (68%) intrasystem and 15 (32%) intersystem clusters and had fewer SNP differences than static clusters (8 vs 9; P=.045; 95% confidence interval [CI]: −4 to 0). Dynamic intersystem clusters contained more patients than dynamic intrasystem clusters (median [interquartile range], 4 [2, 7] vs 2 [2, 2]; P=.007; 95% CI: −3 to 0). Conclusions. Widespread intrasystem and intersystem transmission of CRKp was identified in hospitalized US patients. Use of different methods for assessing genetic similarity resulted in only minor differences in interpretation

Scripts associated with 'Identifying Shared Pathways Across Multiple Muscle Groups of the Human Upper Limb'

This dataset contains the scripts used to conduct Chapter 3 and Chapter 4 of my PhD thesis 'Identifying Shared Pathways Across Multiple Muscle Groups of the Human Upper Limb'. In Chapter 3, I describe a pipeline which enables the time at peak response to stimulation to be marked in EMG data, and then measurements of instantaneous power spectral density to be taken at marked time points using the wavelet synchro-squeezed transform. In Chapter 4, I describe onset and offset marking of muscle bursts during isometric muscle contractions, calculation of intermuscular coherence in bands identified in Chapter 3, wavelet correlation analysis, and muscle synergy analysis using these data. Scripts are written in the CED Spike 2 script language, VBA, BASH, Matlab, and R. The scripts are subdivided into .zip files by the chapter in which they were used. There are associated README files in the .zip files for the appropriate chapter, as well as the subfolders containing the scripts for different steps of the analysis/processing

Kidney transplant in patients with abnormal bladder: Experience of tertiary care center in developing country-Is the outcome same?

Background: Fifteen percent of adults and 20%–30% of pediatric patients develop renal failure, results from structural urological abnormalities. Successful renal transplantation depends partly on a bladder which has adequate capacity, good compliance, and efficient voluntary emptying. Urinary bladder rehabilitation with augmentation or diversion is necessary before transplant in these patients to achieve good graft outcome. We, hereby report our last 10 years' experience of such patients undergoing kidney transplant in abnormal bladder. Materials and Methods: A total of 14 patients underwent renal transplantation in rehabilitated bladder from 2006 to 2016. Demographic details, prereconstruction bladder and urodynamic findings, and type of pretransplant reconstruction were recorded. Posttransplant creatinine levels, graft survival at 7 days, 3 months, 1 year, and 3 years were recorded. Results: Mean (± standard deviation) serum creatinine posttransplant at 7 days, 3 months, 1 year, and 3 years was 0.9 (±0.20), 1.58 (±0.65), 1.92 (±1.02), and 2.47 (1.17) mg/dl, respectively. Four patients developed rejection within 6 months of transplant. Kidney biopsy was suggestive of acute cellular rejection in all cases, which was treated successfully. At three years follow-up, four patients who had rejection-have rising creatinine levels and diminishing renal functions. No patient needed dialysis support till last follow-up. All these four patients had rejection, urinary tract infection (UTI) episodes and pyelonephritis in the past. Conclusion: Native bladder is the best reservoir for urinary storage and drainage. The main cause of graft dysfunction in rehabilitated bladder is UTI as a result of poor hygiene, contamination during clean intermittent self-catheterization (CISC) and noncompliance for CISC leading to high residual urine. Controlling frequent attacks of UTI posttransplant is essential, otherwise long-term graft survival and function will deteriorate faster and might trigger rejection

Enhancing Image Characteristics of Retinal Images of Aggressive Posterior Retinopathy of Prematurity Using a Novel Software, (RetiView)

Purpose. To report pilot data from a novel image analysis software “RetiView,” to highlight clinically relevant information in RetCam images of infants with aggressive posterior retinopathy of prematurity (APROP). Methods. Twenty-three imaging sessions of consecutive infants of Asian Indian origin with clinically diagnosed APROP underwent three protocols (Grey Enhanced (GE), Color Enhanced (CE), and “Vesselness Measure” (VNM)) of the software. The postprocessed images were compared to baseline data from the archived unprocessed images and clinical exam by the retinopathy of prematurity (ROP) specialist for anterior extent of the vessels, capillary nonperfusion zones (CNP), loops, hemorrhages, and flat neovascularization. Results. There was better visualization of tortuous loops in the GE protocol (56.5%); “bald” zones within the CNP zones (26.1%), hemorrhages (13%), and edge of the disease (34.8%) in the CE images; neovascularization on both GE and CE protocols (13% each); clinically relevant information in cases with poor pupillary dilatation (8.7%); anterior extent of vessels on the VNM protocol (13%) effecting a “reclassification” from zone 1 to zone 2 posterior. Conclusions. RetiView is a noninvasive and inexpensive method of customized image enhancement to detect clinically difficult characteristics in a subset of APROP images with a potential to influence treatment planning

Clinical and laboratory evaluation of patients with SARS-CoV-2 pneumonia treated with high-titer convalescent plasma

Here, we report on a phase IIa study to determine the intubation rate, survival, viral clearance, and development of endogenous Abs in patients with COVID-19 pneumonia treated with convalescent plasma (CCP) containing high levels of neutralizing anti–SARS-CoV-2 Abs. Radiographic and laboratory evaluation confirmed all 51 treated patients had COVID-19 pneumonia. Fresh or frozen CCP from donors with high titers of neutralizing Abs was administered. The nonmechanically ventilated patients (n = 36) had an intubation rate of 13.9% and a 30-day survival rate of 88.9%, and the overall survival rate for a comparative group based on network data was 72.5% (1625/2241). Patients had negative nasopharyngeal swab rates of 43.8% and 73.0% on days 10 and 30, respectively. Patients mechanically ventilated had a day-30 mortality rate of 46.7%; the mortality rate for a comparative group based on network data was 71.0% (369/520). All evaluable patients were found to have neutralizing Abs on day 3 (n = 47), and all but 1 patient had Abs on days 30 and 60. The only adverse event was a mild rash. In this study on patients with COVID-19 disease, we show therapeutic use of CCP was safe and conferred transfer of Abs, while preserving endogenous immune response

Clinical outcomes and bacterial characteristics of carbapenem-resistant Klebsiella pneumoniae complex among patients from different global regions (CRACKLE-2): a prospective, multicentre, cohort study

BackgroundCarbapenem-resistant Klebsiella pneumoniae (CRKP) is a global threat. We therefore analysed the bacterial characteristics of CRKP infections and the clinical outcomes of patients with CRKP infections across different countries.MethodsIn this prospective, multicentre, cohort study (CRACKLE-2), hospitalised patients with cultures positive for CRKP were recruited from 71 hospitals in Argentina, Australia, Chile, China, Colombia, Lebanon, Singapore, and the USA. The first culture positive for CRKP was included for each unique patient. Clinical data on post-hospitalisation death and readmission were collected from health records, and whole genome sequencing was done on all isolates. The primary outcome was a desirability of outcome ranking at 30 days after the index culture, and, along with bacterial characteristics and 30-day all-cause mortality (a key secondary outcome), was compared between patients from China, South America, and the USA. The desirability of outcome ranking was adjusted for location before admission, Charlson comorbidity index, age at culture, Pitt bacteremia score, and anatomical culture source through inverse probability weighting; mortality was adjusted for the same confounders, plus region where relevant, through multivariable logistic regression. This study is registered at ClinicalTrials.gov, NCT03646227, and is complete.FindingsBetween June 13, 2017, and Nov 30, 2018, 991 patients were enrolled, of whom 502 (51%) met the criteria for CRKP infection and 489 (49%) had positive cultures that were considered colonisation. We observed little intra-country genetic variation in CRKP. Infected patients from the USA were more acutely ill than were patients from China or South America (median Pitt bacteremia score 3 [IQR 2-6] vs 2 [0-4] vs 2 [0-4]) and had more comorbidities (median Charlson comorbidity index 3 [IQR 2-5] vs 1 [0-3] vs 1 [0-2]). Adjusted desirability of outcome ranking outcomes were similar in infected patients from China (n=246), South America (n=109), and the USA (n=130); the estimates were 53% (95% CI 42-65) for China versus South America, 50% (41-61) for the USA versus China, and 53% (41-66) for the USA versus South America. In patients with CRKP infections, unadjusted 30-day mortality was lower in China (12%, 95% CI 8-16; 29 of 246) than in the USA (23%, 16-30; 30 of 130) and South America (28%, 20-37; 31 of 109). Adjusted 30-day all-cause mortality was higher in South America than in China (adjusted odds ratio [aOR] 4·82, 95% CI 2·22-10·50) and the USA (aOR 3·34, 1·50-7·47), with the mortality difference between the USA and China no longer being significant (aOR 1·44, 0·70-2·96).InterpretationGlobal CRKP epidemics have important regional differences in patients' baseline characteristics and clinical outcomes, and in bacterial characteristics. Research findings from one region might not be generalisable to other regions.FundingThe National Institutes of Health

Clinical Outcomes and Bacterial Characteristics of Carbapenem-Resistant Acinetobacter baumannii Among Patients from Different Global Regions

Abstract Background Carbapenem-resistant Acinetobacter baumannii (CRAb) is one of the most problematic antimicrobial-resistant bacteria. We sought to elucidate the international epidemiology and clinical impact of CRAb. Methods In a prospective observational cohort study, 842 hospitalized patients with a clinical CRAb culture were enrolled at 46 hospitals in five global regions between 2017 and 2019. The primary outcome was all-cause mortality at 30 days from the index culture. The strains underwent whole-genome analysis. Results Of 842 cases, 536 (64%) represented infection. By 30 days, 128 (24%) of the infected patients died, ranging from 1 (6%) of 18 in Australia-Singapore to 54 (25%) of 216 in the United States and 24 (49%) of 49 in South-Central America, whereas 42 (14%) of non-infected patients died. Bacteremia was associated with a higher risk of death compared with other types of infection (40 [42%] of 96 vs. 88 [20%] of 440). In a multivariable logistic regression analysis, bloodstream infection and higher age-adjusted Charlson comorbidity index were independently associated with 30-day mortality. Clonal group 2 (CG2) strains predominated except in South-Central America, ranging from 216 (59%) of 369 in the United States to 282 (97%) of 291 in China. Acquired carbapenemase genes were carried by 769 (91%) of the 842 isolates. CG2 strains were significantly associated with higher levels of meropenem resistance, yet non-CG2 cases were over-represented among the deaths compared with CG2 cases. Conclusions CRAb infection types and clinical outcomes differed significantly across regions. While CG2 strains remained predominant, non-CG2 strains were associated with higher mortality. ClinicalTrials.gov #NCT0364622