Dataset Information

Molecular and clinical epidemiology of carbapenem-resistant Enterobacterales in the USA (CRACKLE-2): a prospective cohort study.

ABSTRACT:

Background

Carbapenem-resistant Enterobacterales (CRE) are a global threat. We aimed to describe the clinical and molecular characteristics of Centers for Disease Control and Prevention (CDC)-defined CRE in the USA.

Methods

CRACKLE-2 is a prospective, multicentre, cohort study. Patients hospitalised in 49 US hospitals, with clinical cultures positive for CDC-defined CRE between April 30, 2016, and Aug 31, 2017, were included. There was no age exclusion. The primary outcome was desirability of outcome ranking (DOOR) at 30 days after index culture. Clinical data and bacteria were collected, and whole genome sequencing was done. This trial is registered with ClinicalTrials.gov, number NCT03646227.

Findings

1040 patients with unique isolates were included, 449 (43%) with infection and 591 (57%) with colonisation. The CDC-defined CRE admission rate was 57 per 100 000 admissions (95% CI 45-71). Three subsets of CDC-defined CRE were identified: carbapenemase-producing Enterobacterales (618 [59%] of 1040), non-carbapenemase-producing Enterobacterales (194 [19%]), and unconfirmed CRE (228 [22%]; initially reported as CRE, but susceptible to carbapenems in two central laboratories). Klebsiella pneumoniae carbapenemase-producing clonal group 258 K pneumoniae was the most common carbapenemase-producing Enterobacterales. In 449 patients with CDC-defined CRE infections, DOOR outcomes were not significantly different in patients with carbapenemase-producing Enterobacterales, non-carbapenemase-producing Enterobacterales, and unconfirmed CRE. At 30 days 107 (24%, 95% CI 20-28) of these patients had died.

Interpretation

Among patients with CDC-defined CRE, similar outcomes were observed among three subgroups, including the novel unconfirmed CRE group. CDC-defined CRE represent diverse bacteria, whose spread might not respond to interventions directed to carbapenemase-producing Enterobacterales.

Funding

National Institutes of Health.

SUBMITTER: van Duin D

PROVIDER: S-EPMC7473597 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Publications

Molecular and clinical epidemiology of carbapenem-resistant Enterobacterales in the USA (CRACKLE-2): a prospective cohort study.

van Duin David D Arias Cesar A CA Komarow Lauren L Chen Liang L Hanson Blake M BM Weston Gregory G Cober Eric E Garner Omai B OB Jacob Jesse T JT Satlin Michael J MJ Fries Bettina C BC Garcia-Diaz Julia J Doi Yohei Y Dhar Sorabh S Kaye Keith S KS Earley Michelle M Hujer Andrea M AM Hujer Kristine M KM Domitrovic T Nicholas TN Shropshire William C WC Dinh An A Manca Claudia C Luterbach Courtney L CL Wang Minggui M Paterson David L DL Banerjee Ritu R Patel Robin R Evans Scott S Hill Carol C Arias Rebekka R Chambers Henry F HF Fowler Vance G VG Kreiswirth Barry N BN Bonomo Robert A RA

The Lancet. Infectious diseases 20200306 6

<h4>Background</h4>Carbapenem-resistant Enterobacterales (CRE) are a global threat. We aimed to describe the clinical and molecular characteristics of Centers for Disease Control and Prevention (CDC)-defined CRE in the USA.<h4>Methods</h4>CRACKLE-2 is a prospective, multicentre, cohort study. Patients hospitalised in 49 US hospitals, with clinical cultures positive for CDC-defined CRE between April 30, 2016, and Aug 31, 2017, were included. There was no age exclusion. The primary outcome was des ...[more]

PMID: 32151332

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Project description:BackgroundCarbapenem-resistant Enterobacterales (CRE) is a global threat. Enterobacterales develops carbapenem resistance through several mechanisms, including the production of carbapenemases. We aim to describe the prevalence of Carbapenem-resistant Enterobacterales (CRE) with and without carbapenemase production and distribution of carbapenemase-producing (CP) genes in Thailand using 2016-2018 data from a national antimicrobial resistance surveillance system developed by the Thailand National Institute of Health (NIH).MethodsCRE was defined as any Enterobacterales resistant to ertapenem, imipenem, or meropenem. Starting in 2016, 25 tertiary care hospitals from the five regions of Thailand submitted the first CRE isolate from each specimen type and patient admission to Thailand NIH, accompanied by a case report form with patient information. NIH performed confirmatory identification and antimicrobial susceptibility testing and performed multiplex polymerase chain reaction testing to detect CP-genes. Using 2016-2018 data, we calculated proportions of CP-CRE, stratified by specimen type, organism, and CP-gene using SAS 9.4.ResultsOverall, 4,296 presumed CRE isolates were submitted to Thailand NIH; 3,946 (93%) were confirmed CRE. Urine (n = 1622, 41%) and sputum (n = 1380, 35%) were the most common specimen types, while blood only accounted for 323 (8%) CRE isolates. The most common organism was Klebsiella pneumoniae (n = 2660, 72%), followed by Escherichia coli (n = 799, 22%). The proportion of CP-CRE was high for all organism types (range: 85-98%). Of all CRE isolates, 2909 (80%) had one CP-gene and 629 (17%) had > 1 CP-gene. New Delhi metallo-beta-lactamase (NDM) was the most common CP-gene, present in 2392 (65%) CRE isolates. K. pneumoniae carbapenemase (KPC) and Verona integron-encoded metallo-β-lactamase (VIM) genes were not detected among any isolates.ConclusionCP genes were found in a high proportion (97%) of CRE isolates from hospitals across Thailand. The prevalence of NDM and OXA-48-like genes in Thailand is consistent with pattern seen in Southeast Asia, but different from that in the United States and other regions. As carbapenemase testing is not routinely performed in Thailand, hospital staff should consider treating all patients with CRE with enhanced infection control measures; in line with CDC recommendation for enhanced infection control measures for CP-CRE because of their high propensity to spread.

Project description: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.

Project description:BackgroundCarbapenem-resistant Pseudomonas aeruginosa (CRPA) is a global threat, but the distribution and clinical significance of carbapenemases are unclear. The aim of this study was to define characteristics and outcomes of CRPA infections and the global frequency and clinical impact of carbapenemases harboured by CRPA.MethodsWe conducted an observational, prospective cohort study of CRPA isolated from bloodstream, respiratory, urine, or wound cultures of patients at 44 hospitals (10 countries) between Dec 1, 2018, and Nov 30, 2019. Clinical data were abstracted from health records and CRPA isolates were whole-genome sequenced. The primary outcome was 30-day mortality from the day the index culture was collected. We compared outcomes of patients with CRPA infections by infection type and across geographic regions and performed an inverse probability weighted analysis to assess the association between carbapenemase production and 30-day mortality.FindingsWe enrolled 972 patients (USA n=527, China n=171, south and central America n=127, Middle East n=91, Australia and Singapore n=56), of whom 581 (60%) had CRPA infections. 30-day mortality differed by infection type (bloodstream 21 [30%] of 69, respiratory 69 [19%] of 358, wound nine [14%] of 66, urine six [7%] of 88; p=0·0012) and geographical region (Middle East 15 [29%] of 52, south and central America 20 [27%] of 73, USA 60 [19%] of 308, Australia and Singapore three [11%] of 28, China seven [6%] of 120; p=0·0002). Prevalence of carbapenemase genes among CRPA isolates also varied by region (south and central America 88 [69%] of 127, Australia and Singapore 32 [57%] of 56, China 54 [32%] of 171, Middle East 27 [30%] of 91, USA ten [2%] of 527; p<0·0001). KPC-2 (n=103 [49%]) and VIM-2 (n=75 [36%]) were the most common carbapenemases in 211 carbapenemase-producing isolates. After excluding USA patients, because few US isolates had carbapenemases, patients with carbapenemase-producing CRPA infections had higher 30-day mortality than those with non-carbapenemase-producing CRPA infections in both unadjusted (26 [22%] of 120 vs 19 [12%] of 153; difference 9%, 95% CI 3-16) and adjusted (difference 7%, 95% CI 1-14) analyses.InterpretationThe emergence of different carbapenemases among CRPA isolates in different geographical regions and the increased mortality associated with carbapenemase-producing CRPA infections highlight the therapeutic challenges posed by these organisms.FundingNational Institutes of Health.

Dataset Information

Molecular and clinical epidemiology of carbapenem-resistant Enterobacterales in the USA (CRACKLE-2): a prospective cohort study.

Background

Methods

Findings

Interpretation

Funding

Publications

Molecular and clinical epidemiology of carbapenem-resistant Enterobacterales in the USA (CRACKLE-2): a prospective cohort study.

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