460 research outputs found
Prevalence and mortality of ceftazidime/avibactam-resistant KPC-producing Klebsiella pneumoniae bloodstream infections (2018–2022)
No full textFunding Information: Open access funding provided by Università degli Studi di Torino within the CRUI-CARE Agreement. This research was supported by EU funding within the MUR PNRR Extended Partnership initiative on Emerging Infectious Diseases (Project no. PE00000007, INF-ACT). Publisher Copyright: © 2023, The Author(s).Introduction: Ceftazidime/avibactam-resistance in Klebsiella pneumoniae carbapenemase-producing Klebsiella pneumoniae (KPC-Kp) is a topic of great interest for epidemiological, diagnostic, and therapeutical reasons. However, data on its prevalence and burden on mortality in patients with bloodstream infection (BSI) are lacking. This study was aimed at identifying risk factors for mortality in patients suffering from ceftazidime/avibactam-resistant KPC-Kp BSI. Methods: An observational retrospective study (January 2018–December 2022) was conducted at a tertiary hospital including all consecutive hospitalized adult patients with a ceftazidime/avibactam-resistant KPC-Kp BSI. Data on baseline clinical features, management, and admission outcomes were analyzed. Results: Over the study period, among all the KPC-Kp BSI events recorded, 38 (10.5%) were caused by ceftazidime/avibactam-resistant KPC-Kp strains, 37 events being finally included. The ceftazidime/avibactam-resistant KPC-Kp strains revealed susceptibility restoration to at least one carbapenem in more than 60% of cases. In-hospital and 30-day all-cause mortality rates were 22% and 16.2%, respectively. Non-survivors suffered from more baseline comorbidities and experienced a more severe ceftazidime/avibactam-resistant KPC-Kp BSI presentation (i.e., both the Pitt Bacteremia and INCREMENT-CPE scores were significantly higher). Presenting with a higher Charlson Comorbidity Index, chronic kidney disease—KDIGO stage 3A or worse—having recently gone through renal replacement therapy, having suffered from an acute kidney injury following the ceftazidime/avibactam-resistant KPC-Kp BSI, and being admitted for cardiac surgery were the strongest predictors of mortality. Conclusion: Ceftazidime/avibactam resistance in KPC-Kp BSI easily emerged in our highly KPC-Kp endemic area with remarkable mortality rates. Our findings might provide physicians possibly actionable information when managing patients with a ceftazidime/avibactam-resistant KPC-Kp BSI.publishersversionpublishe
A simple phenotypic method for the differentiation of metallo-β-lactamases and class A KPC carbapenemases in Enterobacteriaceae clinical isolates
No full textBackground: The increasing frequency of class A KPC enzymes and class B metallo-β-lactamases (MBLs) among Enterobacteriaceae as well as their possible co-production makes their early differentiation urgent. Methods: A simple phenotypic algorithm employing three combined-disc tests consisting of meropenem alone and with phenylboronic acid (PBA), EDTA, or both PBA and EDTA was designed for the differentiation of KPC and MBL enzymes. Augmentation of the zone of inhibition by ≥5 mm was considered a positive combined-disc test result. A total of 141 genotypically confirmed carbapenemase-positive Enterobacteriaceae clinical isolates (63 KPC producers, 47 MBL producers, and 31 KPC and MBL producers) with various carbapenem MICs were examined. For comparison, 84 genotypically confirmed carbapenemase-negative Enterobacteriaceae clinical isolates [39 extended-spectrum β-lactamase (ESBL) producers, 22 AmpC producers, and 23 ESBL and AmpC producers] were also tested. Results: The phenotypic algorithm was able to differentiate MBL from KPC producers as well as to detect the possible co-production of both carbapenemases (positive result only with the combined-disc test using meropenem alone and with both PBA and EDTA). The method detected all KPC or MBL producers (sensitivity 100%) as well as 30 of the KPC and MBL producers (sensitivity 96.8%). All three combined-disc tests were negative for non-carbapenemase-producing isolates, except two ESBL and AmpC producers that gave positive combineddisc tests using meropenem alone and with PBA and both PBA and EDTA (specificity for KPC detection 98.8%). Conclusions: This phenotypic method is very helpful to detect carbapenemase production and provides a simple algorithm for the differentiation of KPC and MBL enzymes, especially in regions where KPC- and MBL-possessing Enterobacteriaceae are highly prevalent. © The Author 2010
Inhibitor-based methods for the detection of KPC carbapenemase- producing Enterobacteriaceae in clinical practice by using boronic acid compounds
No full textEnterobacteriaceae clinical strains that produce the class A carbapenem-hydrolysing enzyme KPC (Klebsiella pneumoniae carbapenemase) are increasingly reported worldwide, and are already endemic in North and South America, China, Israel and Greece. The accurate detection of KPC enzymes is of utmost importance for containing the global spread of KPC producers. Currently, the detection of putative carbapenemase production is based on an initial phenotypic screen for carbapenem resistance followed by the modified Hodge test (MHT) as a confirmatory test. However, the MHT is often difficult to interpret, is not specific for carbapenemase activity due to KPC and there are reports of false-positive results with CTX-M-positive or AmpC-hyper-producing Enterobacteriaceae. Boronic acid compounds are serine-type β-lactamase inhibitors that were employed originally for the detection of class C plasmidic AmpCs in Enterobacteriaceae. Recently, they have also been evaluated for the differentiation of KPC-producing Enterobacteriaceae. In that respect, combined-disc tests using carbapenems with and without phenylboronic acid (PBA) have been proposed as the most accurate phenotypic tests for detecting KPC production. When these disc tests are extended to include carbapenem discs with EDTA or both PBA and EDTA on the same plate, the production of metallo-β-lactamase (MBL) or both KPC and MBL, respectively, can also be accurately detected. Phenotypic tests based on the inhibitory activity of boronic acid compounds are very easy to perform and interpret, and may be applied from the first day of isolation of the suspected resistant Enterobacteriaceae. We think that they could effectively replace MHT for the convenient and early detection of KPC carbapenemases in regions where these enzymes are common. © The Author 2010
Clonal spread of KPC-2 carbapenemase-producing Klebsiella pneumoniae strains in Greece
No full textObjectives: KPC-possessing Klebsiella pneumoniae have been found to be widespread in several regions but are still rarely detected in Europe. We describe the characteristics of an outbreak caused by KPC producers in a tertiary care Greek hospital. Methods: During a 12 month period (October 2007-September 2008), 47 patients in Hippokration University Hospital yielded K. pneumoniae isolates that exhibited reduced susceptibility to carbapenems and were phenotypically positive for carbapenemase production but negative for metallo-β-lactamase (MBL) production. Single patient isolates were tested by Vitek 2, Etest, agar dilution MICs, phenotypic assays and PFGE. Carbapenemase and other β-lactamase genes were identified by PCR and sequencing. Patient records were retrospectively reviewed to access co-morbidities, antibiotic exposure prior to infection and outcome. Results: The 47 K. pneumoniae isolates exhibited various susceptibilities to imipenem and meropenem; all were non-susceptible to ertapenem and several other antibiotics but most were susceptible to gentamicin, colistin and tigecycline. PFGE classified the isolates into two clonal types, with the predominant type, which was closely related to that of hyperepidemic strains from the USA and Israel, comprising three subtypes. All isolates carried the blaKPC-2 gene; 45 also carried blaSHV-12 and 29 blaTEM-1. Patients were hospitalized in nine different units. The median length of hospital stay prior to KPC isolation was 21 days; 38 patients (80.9%) had evidence of clinical infection due to a KPC producer and 16 (34%) had bacteraemia. The crude mortality rate was 27.7%. A β-lactam/ β-lactamase inhibitor combination was the most frequently administered antimicrobial prior to KPC isolation (20 patients; 42.5%), whereas only nine patients (19.1%) had prior carbapenem use. Conclusions: This study presents for the first time a wide intrahospital spread of KPC-producing K. pneumoniae clones in a European hospital. The KPC producers were rapidly disseminated in several units, indicating the difficulty in restraining such multidrug-resistant clones when they have been established in a hospital environment. © The Author 2009. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved
First occurrence of KPC-2-possessing Klebsiella pneumoniae in a Greek hospital and recommendation for detection with boronic acid disc tests
No full textObjectives: To investigate the first KPC carbapenemase-producing Klebsiella pneumoniae isolate from a Greek hospital, including phenotypic methods to aid recognition of this resistance type. Methods: A carbapenem-resistant clinical isolate of K. pneumoniae was recovered from a hospitalized Greek patient. Detailed susceptibility testing was carried out by the agar dilution method. The isolate was screened by phenotypic and genotypic assays for the presence of various β-lactamases. Boronic acid disc tests were performed to show the ability of these tests to detect production of the KPC enzymes. The potential for conjugal transfer of carbapenem resistance was examined by biparental matings, plasmid analysis and PCR studies. Results: The isolate possessed on the same self-transferable plasmid the KPC-2 carbapenemase and the SHV-12 extended-spectrum β-lactamase. Although the isolate did not produce an AmpC-type enzyme, the production of KPC-2 was associated with positive boronic acid disc tests using cephamycins and cefotaxime as well as cefepime and carbapenems as substrates. Discussion KPC-2-possessing K. pneumoniae clinical isolates seem to have been introduced in our region. Boronic acid disc tests using boronic acid in combination with carbapenems or cefepime may help the phenotypic detection of KPC enzymes and their distinction from plasmid-mediated AmpC enzymes. © The Author 2008. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved
Reversion to susceptibility of a carbapenem-resistant clinical isolate of klebsiella pneumoniae producing KPC-3
No full textObjectives:We report the case of a kidney-transplant patient, suffering an intra-abdominal abscess at the surgical site caused by a carbapenem-resistant ST258 Klebsiella pneumoniae clone, producing the KPC-3 carbapenemase. Under tigecycline treatment, the patient developed a sepsis caused by a carbapenem-susceptible ST258 K. pneumoniae strain. Complete DNA sequences of the plasmids carried by the resistant and susceptible strains from this patient were determined. Methods: The complete DNA sequences of plasmids were obtained by applying the 454 Genome Sequencer FLXPLUSprocedure onalibrary constructed of total plasmidDNApurified fromthe carbapenem-resistantand-susceptible strains. Results: In the carbapenem-resistant strain, four plasmids encoding 24 resistance genes, including blaKPC-3, and two putative virulence clusters were detected. In the susceptible strain, large rearrangements occurred in the KPC-carrying plasmid, causing the deletion of the entire Tn4401::blaKPC-3 transposon, with the consequent reversion of the strain to carbapenem susceptibility. The patient was successfully treated with carbapenems and fully recovered. Conclusions: The description of the plasmid content in these two strains gives interesting insights into the plasticity of KPC-carrying plasmids in K. pneumoniae. © The Author 2013. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved
The Milky Way's rotation curve out to 100 kpc and its constraint on the Galactic mass distribution
No full textThe rotation curve (RC) of the Milky Way out to similar to 100 kpc has been constructed using similar to 16 000 primary red clump giants (PRCGs) in the outer disc selected from the LAMOST Spectroscopic Survey of the Galactic Anti-centre (LSS-GAC) and the Sloan Digital Sky Survey (SDSS)-III/APOGEE survey, combined with similar to 5700 halo K giants (HKGs) selected from the SDSS/SEGUE survey. To derive the RC, the PRCG sample of the warm disc population and the HKG sample of halo stellar population are, respectively, analysed using a kinematical model allowing for the asymmetric drift corrections and re-analysed using the spherical Jeans equation along with measurements of the anisotropic parameter beta currently available. The typical uncertainties of RC derived from the PRCG and HKG samples are, respectively, 5-7 km s(-1) and several tens km s(-1). We determine a circular velocity at the solar position, V-c(R-0) = 240 +/- 6 km s(-1) and an azimuthal peculiar speed of the Sun, V-circle dot = 12.1 +/- 7.6 km s(-1), both in good agreement with the previous determinations. The newly constructed RC has a generally flat value of 240 km s(-1) within a Galactocentric distance r of 25 kpc and then decreases steadily to 150 km s(-1) at r similar to 100 kpc. On top of this overall trend, the RC exhibits two prominent localized dips, one at r similar to 11 kpc and another at r similar to 19 kpc. From the newly constructed RC, combined with other constraints, we have built a parametrized mass model for the Galaxy, yielding a virialmass of the Milky Way's dark matter halo of 0.90(-0.08)(+0.07) x 10(12) M-circle dot and a local dark matter density, rho(circle dot, dm) = 0.32(-0.02)(+0.02) GeV cm(-3).National Key Basic Research Program of China [2014CB845700]; National Natural Science Foundation of China [11473001, 11233004]; National Development and Reform CommissionSCI(E)[email protected]; [email protected]
Emergent Escherichia coli of the highly virulent B2-ST1193 clone producing KPC-2 carbapenemase in ready-to-eat vegetables
No full textABSTRACT: Objectives: Critical priority carbapenem-resistant pathogens constitute a worldwide public health problem. Escherichia coli (E. coli) ST1193 is an emerging high-risk clone that demonstrates prolonged gut persistence, and association with community-onset urinary and bloodstream infections. The purpose of this study is to report microbiological and genomic data on the emergence of KPC-2-producing E. coli ST1193 in ready-to-eat (RTE) vegetables. Methods: RTE vegetables were purchased from markets in southeastern Brazil. Epiphytic and endophytic Gram-negative bacteria displaying resistance to broad-spectrum beta-lactams were identified by matrix-assisted laser desorption ionization-time of flight mass spectrometry. Whole-genome sequence was conducted using the Illumina NextSeq platform. Antimicrobial susceptibility, conjugation, and acid tolerance assays were performed. Virulence behaviour was evaluated using the Galleria mellonella (G. mellonella) infection model. Results: Epiphytic KPC-2-producing E. coli belonging to pandemic ST1193 was identified in RTE arugula. Genomic analysis predicted clinically relevant genes conferring resistance to β-lactams, fluoroquinolones, hazardous heavy metals, pesticides, disinfectants, and chlorine sanitizer. The blaKPC-2 gene was carried by a conjugative IncF plasmid. Acid tolerance of E. coli KPC-2/ST1193 during exposure to pH 2.0 was confirmed, being associated with gadWX and ibaG pH tolerance genes, supporting survival to stomach acid prior to reaching the small intestine, and potential for a dietary mode of host colonization. Virulent behaviour was supported by wide virulome of the highly virulent phylogroup B2, whereas single nucleotide polymorphisms of core genes (cgSNP)-based phylogenomics revealed clonal relationship with healthcare-associated lineages circulating in the United States, China, Mexico, France, and Brazil. Conclusions: We report the occurrence of KPC-2-producing E. coli of the highly virulent B2-ST1193 clone in RTE vegetables, highlighting a possible route of dissemination of the World Health Organization (WHO) priority pathogens to humans. © 2024 The Author(s). Published by Elsevier Ltd on behalf of International Society for Antimicrobial Chemotherapy
CHANG-ES. XXX. 10 kpc Radio Lobes in the Sombrero Galaxy
No full textWe report the discovery of the 10 kpc scale radio lobes in the Sombrero galaxy (NGC 4594), using data from the Continuum Halos in Nearby Galaxies—an Expanded Very Large Array Survey project. We further examine the balance between the magnetic pressure inside the lobes and the thermal pressure of the ambient hot gas. At the radii r of ∼(1–10) kpc, the magnetic pressure inside the lobes and the thermal pressure of the ambient hot gas are generally in balance. This implies that the jets could expand into the surroundings to at least r ∼ 10 kpc. The feedback from the active galactic nucleus jet responsible for the large-scale lobes may help to explain the unusually high X-ray luminosity of this massive quiescent isolated disk galaxy, although more theoretical work is needed to further examine this possibility. © 2024. The Author(s). Published by the American Astronomical Society.Y.Y. acknowledges support from the National Natural Science Foundation of China (NSFC) through grant No. 12203098 and the Shanghai Sailing Program (19YF1455500). Both Y.Y. and J.T.L. acknowledge the support from the NSFC through grants No. 12273111 and No. 12321003, and also the science research grants from the China Manned Space Project. Z.L. acknowledges support from the National Key Research and Development Program of China (No. 2022YFF0503402) and the National Natural Science Foundation of China (grant No. 12225302). T.W. acknowledges financial support from the grant CEX2021-001131-S funded by MCIU/AEI/ 10.13039/501100011033, from the coordination of the participation in SKA-SPAIN, funded by the Ministry of Science, Innovation and Universities (MCIU). F.G. is thankful for the support from the Chinese Academy of Sciences under grant No. YSBR-061 and Shanghai Pilot Program for Basic Research—Chinese Academy of Science, Shanghai Branch (JCYJ-SHFY-2021-013). Research in this field at AIRUB is supported by Deutsche Forschungsgemeinschaft SFB1491.With funding from the Spanish government through the "Severo Ochoa Centre of Excellence" accreditation (CEX2021-001131-S).Peer reviewe
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