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

The Purinergic P2X7 Receptor Is Not Required for Control of Pulmonary Mycobacterium tuberculosis Infection

The importance in vivo of P2X7 receptors in control of virulent Mycobacterium tuberculosis was examined in a low-dose aerosol infection mouse model. P2X7(−/−) mice controlled infection in lungs as well as wild-type mice, suggesting that the P2X7 receptor is not required for control of pulmonary M. tuberculosis infection

Environmental Contamination with Candida Species in Multiple Hospitals Including a Tertiary Care Hospital with a Candida auris Outbreak

Environmental sources have been implicated as a potential source for exogenous acquisition of species, particularly the emerging multidrug-resistant . However, limited information is available on environmental reservoirs of species in healthcare facilities. During a 6-month period, cultures for species were collected from high-touch surfaces in patient rooms and from portable equipment in 6 US acute care hospitals in 4 states. Additional cultures were collected from sink drains and floors in one of the hospitals and from high-touch surfaces, portable equipment, and sink drains in a hospital experiencing an outbreak due to species were identified using matrix-assisted laser desorption/ionization time-of-flight mass spectometry. species were recovered from patient rooms in 4 of the 6 hospitals. Seven of 147 patient room cultures (4.8%) and 1 of 57 (1.8%) portable equipment cultures were positive, with the most common species being For the hospital where additional sites were sampled, species were recovered from 8 of 22 (36.4%) hospital room floors and 4 of 17 (23.5%) sink drains. In the facility with a outbreak, species were frequently recovered from sink drains (20.7%) and high-touch surfaces (15.4%), but recovery of was uncommon (3.8% of high-touch surfaces, 3.4% of sink drains, and 0% of portable equipment) and only present in rooms that currently or recently housed a patient with . species often contaminate surfaces in hospitals and may be particularly common on floors and in sink drains. However, contamination was uncommon in a facility experiencing an outbreak, suggesting that current cleaning and disinfection practices can be effective in minimizing environmental contamination

Carbapenem-Resistant Enterobacteriaceae Infections in Patients on Renal Replacement Therapy

Abstract Background: Patients on chronic intermittent renal replacement therapy (RRT) are at risk for infection with carbapenem-resistant Enterobacteriaceae (CRE). However, the impact of RRT on outcomes after CRE infections remains to be defined. Here we perform a comparison of outcomes for CRE-infected patients with preserved renal function compared with CRE-infected patients on RRT. Methods: Cases and controls were defined from a prospective cohort of CRE-infected patients from the Consortium on Resistance against Carbapenems in Klebsiella and other Enterobacteriaceae (CRACKLE). Cases were defined as CRE-infected patients on RRT at hospital admission, while controls were defined as CRE-infected patients with serum creatinine <2 mg/dL and not receiving RRT at admission. Risk factors for 28-day in-hospital mortality were assessed using multivariable logistic regression. An ordinal ranking of outcomes by desirability analysis was performed. Results: Patients on RRT were more likely to have diabetes mellitus and cardiac disease than controls. Urinary sources of infection were less common in the RRT group. In RRT patients, 28-day in-hospital mortality was increased as compared with controls: 22/71 (31%) vs 33/295 (11%). RRT remained significantly associated with 28-day in-hospital mortality after adjustment for source of infection, prehospitalization origin, and severity of illness (adjusted odds ratio, 2.27; 95% confidence interval [CI], 1.09–4.68; P = .03). Using univariable desirability of outcome ranking analysis, RRT status was associated with a 68% (95% CI, 61%–74%) chance of a worse disposition outcome. Conclusions: Chronic RRT in CRE-infected patients is associated with increased in-hospital mortality and worse disposition outcomes at 28 days

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