scholarly journals Impact of KPC Production and High-Level Meropenem Resistance on All-Cause Mortality of Ventilator-Associated Pneumonia in Association with Klebsiella pneumoniae

2020 ◽  
Vol 64 (6) ◽  
Author(s):  
Francisco Rivera-Espinar ◽  
Isabel Machuca ◽  
Rocio Tejero ◽  
Jorge Rodríguez ◽  
Ana Mula ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Retrospective Cohort ◽  
Cox Regression ◽  
University Hospital ◽  
Ventilator Associated Pneumonia ◽  
Content Type ◽  
Appropriate Treatment ◽  
All Cause Mortality ◽  
High Level ◽  
Level Resistance

ABSTRACT Carbapenemase-producing Enterobacterales and specifically Klebsiella pneumoniae carbapenemase (KPC)-producing Klebsiella pneumoniae (KPC-Kp) are rapidly spreading worldwide. The prognosis of ventilator-associated pneumonia (VAP) caused by KPC-Kp is not well known. Our study tries to assess whether ventilator-associated pneumonia caused by a KPC-Kp strain is associated with higher all-cause mortality than that caused by carbapenem-susceptible isolates. This is a retrospective cohort study of patients with VAP due to K. pneumoniae from a 35-bed polyvalent intensive care unit in a university hospital (>40,000 annual admissions) between January 2012 and December 2016. Adjusted multivariate analysis was used to study the association of KPC-Kp with 30-day all-cause mortality (Cox regression). We analyze 69 cases of K. pneumoniae VAP, of which 39 were produced by a KPC-Kp strain with high-level resistance to meropenem (MIC > 16 mg/ml). All-cause mortality at 30 days was 41% in the KPC-Kp group (16/39) and 33.3% in the carbapenem-susceptible cases (10/30). KPC-Kp etiology was not associated with higher mortality when controlled for confounders (adjusted hazard ratio [HR], 1.25; 95% confidence interval [CI], 0.46 to 3.41). Adequate targeted therapy (HR, 0.03; 95% CI, <0.01 to 0.23) was associated with all-cause mortality. Assuming the limitations due to the available sample size, the prognosis of VAP caused by KPC-Kp is similar to VAPs caused by carbapenem-susceptible K. pneumoniae when appropriate treatment is used.

scholarly journals A Novel Complex Mutant β-Lactamase, TEM-68, Identified in a Klebsiella pneumoniae Isolate from an Outbreak of Extended-Spectrum β-Lactamase-Producing Klebsiellae

2000 ◽  
Vol 44 (6) ◽  
pp. 1499-1505 ◽  
Author(s):  
Janusz Fiett ◽  
Andrzej Pałucha ◽  
Beata Mia˛czyńska ◽  
Maria Stankiewicz ◽  
Hanna Przondo-Mordarska ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
University Hospital ◽  
Pediatric Hospitals ◽  
Extended Spectrum ◽  
Novel Complex ◽  
High Level ◽  
Inhibitor Resistance ◽  
The University ◽  
Level Resistance

ABSTRACT Twenty-two Klebsiella pneumoniae and two K. oxytoca extended-spectrum β-lactamase (ESBL)-producing isolates were collected in 1996 from patients in two pediatric wards of the University Hospital in Wrocław, Poland. Molecular typing has revealed that the K. pneumoniae isolates represented four different epidemic strains. Three kinds of enzymes with ESBL activity (pI values of 5.7, 6.0, and 8.2) were identified. The pI 6.0 β-lactamases belonged to the TEM family, and sequencing of thebla TEM genes amplified from representative isolates revealed that these enzymes were TEM-47, previously identified in K. pneumoniae isolates from pediatric hospitals in Łódź and Warsaw. One of the TEM-47-producing strains from Wrocław was very closely related to the isolates from the other cities, and this indicated countrywide spread of the epidemic strain. The pI 5.7 β-lactamase was produced by a single K. pneumoniae isolate for which, apart from oxyimino-β-lactams, the MICs of β-lactam–inhibitor combinations were also remarkably high. Sequencing revealed that this was a novel TEM β-lactamase variant, TEM-68, specified by the following combination of mutations: Gly238Ser, Glu240Lys, Thr265Met, and Arg275Leu. The new enzyme has most probably evolved from TEM-47 by acquiring the single substitution of Arg275, which before was identified only twice in enzymes with inhibitor resistance (IR) activity. TEM-68 was shown to be a novel complex mutant TEM β-lactamase (CMT-2) which combines strong ESBL activity with relatively weak IR activity and, when expressed inK. pneumoniae, is able to confer high-level resistance to a wide variety of β-lactams, including inhibitor combinations. This data confirms the role of the Arg275Leu mutation in determining IR activity and documents the first isolation of K. pneumoniae producing the complex mutant enzyme.

scholarly journals High-Level Resistance to Colistin Mediated by Various Mutations in the crrB Gene among Carbapenemase-Producing Klebsiella pneumoniae

2017 ◽  
Vol 61 (11) ◽  
Author(s):  
Aurélie Jayol ◽  
Patrice Nordmann ◽  
Adrian Brink ◽  
Maria-Virginia Villegas ◽  
Véronique Dubois ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Wild Type ◽  
Content Type ◽  
Resistance Phenotype ◽  
Two Component ◽  
Genes Encoding ◽  
High Level ◽  
Type Strains ◽  
Level Resistance

ABSTRACT Mutations in crrAB genes encoding a two-component regulator involved in modifications of lipopolysaccharide were searched for among a collection of colistin-resistant Klebsiella pneumoniae isolates. Four isolates, respectively, producing carbapenemases NDM-1, OXA-181, or KPC-2 showed mutated CrrB proteins compared with those in wild-type strains. Complementation assays with a wild-type CrrB protein restored the susceptibility to colistin in all cases, confirming the involvement of the identified substitutions in the resistance phenotype.

scholarly journals Emergence of KPC-2-Producing Pseudomonas aeruginosa Sequence Type 463 Isolates in Hangzhou, China

2015 ◽  
Vol 59 (5) ◽  
pp. 2914-2917 ◽  
Author(s):  
Yan-yan Hu ◽  
Dan-xia Gu ◽  
Jia-chang Cai ◽  
Hong-wei Zhou ◽  
Rong Zhang
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Klebsiella Pneumoniae ◽  
Molecular Epidemiology ◽  
Clonal Expansion ◽  
Sequence Type ◽  
Environment Analysis ◽  
Content Type ◽  
Genetic Environment ◽  
High Level ◽  
Level Resistance

ABSTRACTThirty-nineKlebsiella pneumoniaecarbapenemase (KPC)-producingPseudomonas aeruginosaisolates, all exhibiting high-level resistance to carbapenems and other β-lactam antibiotics, were isolated in Hangzhou, China. Molecular epidemiology analysis indicated the presence of two dominant clones, namely, clones A and B, both of which belong to sequence type 463 (ST463). A genetic environment analysis demonstrated that both clones harbor an ISKpn8transposase,blaKPC-2, and an ISKpn6-like transposase. These findings depict the features of clonal expansion and transmission of KPC-2-producingP. aeruginosastrains in Hangzhou, China.

scholarly journals Mortality Associated with Bacteremia Due to Colistin-Resistant Klebsiella pneumoniae with High-Level Meropenem Resistance: Importance of Combination Therapy without Colistin and Carbapenems

2017 ◽  
Vol 61 (8) ◽  
Author(s):  
Isabel Machuca ◽  
Belén Gutiérrez-Gutiérrez ◽  
Irene Gracia-Ahufinger ◽  
Francisco Rivera Espinar ◽  
Ángela Cano ◽  
...  
Keyword(s):  
Septic Shock ◽  
Regression Analysis ◽  
Combination Therapy ◽  
Klebsiella Pneumoniae ◽  
Cox Regression ◽  
Lower Mortality ◽  
Content Type ◽  
Cox Regression Analysis ◽  
High Level ◽  
The Impact

ABSTRACT Combination therapy including colistin and a carbapenem has been found to be associated with lower mortality in the treatment of bloodstream infections (BSI) due to KPC-producing Klebsiella pneumoniae when the isolates show a meropenem or imipenem MIC of <16 mg/liter. However, the optimal treatment of BSI caused by colistin- and high-level carbapenem-resistant KPC-producing K. pneumoniae is unknown. A prospective cohort study including episodes of bacteremia caused by colistin-resistant and high-level meropenem-resistant (MIC ≥ 64 mg/liter) KPC-producing K. pneumoniae diagnosed from July 2012 to February 2016 was performed. The impact of combination therapy on crude 30-day mortality was analyzed by Cox regression using a propensity score as a covariate to control for indication bias and in an inverse probability of treatment weighting (IPTW) cohort. The study sample comprised 104 patients, of which 32 (30.8%) received targeted monotherapy and 72 (69.2%) received targeted combination therapy; none of them received either colistin or a carbapenem. The 30-day crude mortality rate was 30.8% (43.8% in patients treated with monotherapy and 25% in patients receiving combination therapy). In the Cox regression analysis, 30-day mortality was independently associated with septic shock at BSI onset (hazard ratio [HR], 6.03; 95% confidence interval [CI], 1.65 to 21.9; P = 0.006) and admission to the critical care unit (HR, 2.87; 95% CI, 0.99 to 8.27; P = 0.05). Targeted combination therapy was associated with lower mortality only in patients with septic shock (HR, 0.14; 95% CI, 0.03 to 0.67; P = 0.01). These results were confirmed in the Cox regression analysis of the IPTW cohort. Combination therapy is associated with reduced mortality in patients with bacteremia due to colistin-resistant KPC-producing K. pneumoniae with high-level carbapenem resistance in patients with septic shock.

scholarly journals First Outbreak of a Plasmid-Mediated Carbapenem-Hydrolyzing OXA-48 β-Lactamase in Klebsiella pneumoniae in Spain

2011 ◽  
Vol 55 (9) ◽  
pp. 4398-4401 ◽  
Author(s):  
Cristina Pitart ◽  
Mar Solé ◽  
Ignasi Roca ◽  
Anna Fàbrega ◽  
Jordi Vila ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Sequence Type ◽  
Conjugative Plasmid ◽  
Content Type ◽  
Low Level ◽  
High Level ◽  
Level Resistance

ABSTRACTTwentyKlebsiella pneumoniaeisolates producing OXA-48 were collected from April 2009 to September 2010. Strains were clonally related and coproduced a CTX-M-15 β-lactamase. A conjugative plasmid of circa 70 kb carryingblaOXA-48was identified. Eleven isolates showed low-level resistance to carbapenems, whereas nine showed high-level resistance. Decreased expression of OmpK36 was related to high-level resistance to carbapenems. The isolates belonged to sequence type 101 (ST101). This is the first outbreak caused by an OXA-48-producingK. pneumoniaestrain in Spain.

scholarly journals KPC-53, a KPC-3 Variant of Clinical Origin Associated with Reduced Susceptibility to Ceftazidime-Avibactam

2020 ◽  
Vol 65 (1) ◽  
pp. e01429-20
Author(s):  
Vincenzo Di Pilato ◽  
Noemi Aiezza ◽  
Valentina Viaggi ◽  
Alberto Antonelli ◽  
Luigi Principe ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Whole Genome Sequencing ◽  
Clinical Isolate ◽  
Genome Sequencing ◽  
Whole Genome ◽  
Mechanisms Of Resistance ◽  
Content Type ◽  
High Level ◽  
Level Resistance

ABSTRACTThis study reports on the characterization of a Klebsiella pneumoniae clinical isolate showing high-level resistance to ceftazidime-avibactam associated with the production of KPC-53, a KPC-3 variant exhibiting a Leu167Glu168 duplication in the Ω-loop and a loss of carbapenemase activity. Whole-genome sequencing (WGS) revealed the presence of two copies of blaKPC-53, located on a pKpQIL-like plasmid and on a plasmid prophage of the Siphoviridae family, respectively. The present findings provide new insights into the mechanisms of resistance to ceftazidime-avibactam.

scholarly journals Mutations in fbiD (Rv2983) as a Novel Determinant of Resistance to Pretomanid and Delamanid in Mycobacterium tuberculosis

2020 ◽  
Vol 65 (1) ◽  
pp. e01948-20
Author(s):  
Dalin Rifat ◽  
Si-Yang Li ◽  
Thomas Ioerger ◽  
Keshav Shah ◽  
Jean-Philippe Lanoix ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Clinical Evidence ◽  
Clinical Samples ◽  
Loss Of Function ◽  
Wild Type ◽  
Content Type ◽  
Solid Media ◽  
High Level ◽  
Level Resistance

ABSTRACTThe nitroimidazole prodrugs delamanid and pretomanid comprise one of only two new antimicrobial classes approved to treat tuberculosis (TB) in 50 years. Prior in vitro studies suggest a relatively low barrier to nitroimidazole resistance in Mycobacterium tuberculosis, but clinical evidence is limited to date. We selected pretomanid-resistant M. tuberculosis mutants in two mouse models of TB using a range of pretomanid doses. The frequency of spontaneous resistance was approximately 10−5 CFU. Whole-genome sequencing of 161 resistant isolates from 47 mice revealed 99 unique mutations, of which 91% occurred in 1 of 5 genes previously associated with nitroimidazole activation and resistance, namely, fbiC (56%), fbiA (15%), ddn (12%), fgd (4%), and fbiB (4%). Nearly all mutations were unique to a single mouse and not previously identified. The remaining 9% of resistant mutants harbored mutations in Rv2983 (fbiD), a gene not previously associated with nitroimidazole resistance but recently shown to be a guanylyltransferase necessary for cofactor F420 synthesis. Most mutants exhibited high-level resistance to pretomanid and delamanid, although Rv2983 and fbiB mutants exhibited high-level pretomanid resistance but relatively small changes in delamanid susceptibility. Complementing an Rv2983 mutant with wild-type Rv2983 restored susceptibility to pretomanid and delamanid. By quantifying intracellular F420 and its precursor Fo in overexpressing and loss-of-function mutants, we provide further evidence that Rv2983 is necessary for F420 biosynthesis. Finally, Rv2983 mutants and other F420H2-deficient mutants displayed hypersusceptibility to some antibiotics and to concentrations of malachite green found in solid media used to isolate and propagate mycobacteria from clinical samples.

scholarly journals ArmA Methyltransferase in a Monophasic Salmonella enterica Isolate from Food

2011 ◽  
Vol 55 (11) ◽  
pp. 5262-5266 ◽  
Author(s):  
Sophie A. Granier ◽  
Laura Hidalgo ◽  
Alvaro San Millan ◽  
Jose Antonio Escudero ◽  
Belen Gutierrez ◽  
...  
Keyword(s):  
16S Rrna ◽  
Salmonella Enterica ◽  
Multidrug Resistant ◽  
Broad Host Range ◽  
En Bloc ◽  
Content Type ◽  
Route Of Transmission ◽  
Amoxicillin Clavulanate ◽  
High Level ◽  
Level Resistance

ABSTRACTThe 16S rRNA methyltransferase ArmA is a worldwide emerging determinant that confers high-level resistance to most clinically relevant aminoglycosides. We report here the identification and characterization of a multidrug-resistantSalmonella entericasubspecies I.4,12:i:− isolate recovered from chicken meat sampled in a supermarket on February 2009 in La Reunion, a French island in the Indian Ocean. Susceptibility testing showed an unusually high-level resistance to gentamicin, as well as to ampicillin, expanded-spectrum cephalosporins and amoxicillin-clavulanate. Molecular analysis of the 16S rRNA methyltransferases revealed presence of thearmAgene, together withblaTEM-1,blaCMY-2, andblaCTX-M-3. All of these genes could be transferreden blocthrough conjugation intoEscherichia coliat a frequency of 10−5CFU/donor. Replicon typing and S1 pulsed-field gel electrophoresis revealed that thearmAgene was borne on an ∼150-kb broad-host-range IncP plasmid, pB1010. To elucidate howarmAhad integrated in pB1010, a PCR mapping strategy was developed for Tn1548, the genetic platform forarmA.The gene was embedded in a Tn1548-like structure, albeit with a deletion of the macrolide resistance genes, and an IS26was inserted within themelgene. To our knowledge, this is the first report of ArmA methyltransferase in food, showing a novel route of transmission for this resistance determinant. Further surveillance in food-borne bacteria will be crucial to determine the role of food in the spread of 16S rRNA methyltransferase genes worldwide.

scholarly journals Integrative and Conjugative Element-Mediated Azithromycin Resistance in Multidrug-Resistant Salmonella enterica Serovar Albany

2021 ◽  
Vol 65 (5) ◽  
Author(s):  
Yu-Ping Hong ◽  
Ying-Tsong Chen ◽  
You-Wun Wang ◽  
Bo-Han Chen ◽  
Ru-Hsiou Teng ◽  
...  
Keyword(s):  
Vibrio Cholerae ◽  
Salmonella Enterica ◽  
Multidrug Resistant ◽  
Content Type ◽  
Human Salmonellosis ◽  
High Level ◽  
Azithromycin Resistance ◽  
Level Resistance ◽  
Integrative And Conjugative Element

ABSTRACT We identified an erm42-carrying integrative and conjugative element, ICE_erm42, in 26.4% of multidrug-resistant Salmonella enterica serovar Albany isolates recovered from cases of human salmonellosis between 2014 and 2019 in Taiwan. ICE_erm42-carrying strains displayed high-level resistance to azithromycin, and the element could move into the phylogenetically distant species Vibrio cholerae via conjugation.

P6209Relationship between skin autofluorescence levels and clinical outcomes in heart failure patients undergoing cardiac rehabilitation

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
M Kunimoto ◽  
K Shimada ◽  
M Yokoyama ◽  
A Honzawa ◽  
M Yamada ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cardiac Rehabilitation ◽  
Cox Regression ◽  
Left Ventricular ◽  
University Hospital ◽  
Left Ventricular Ejection ◽  
Skin Autofluorescence ◽  
Ventricular Ejection Fraction ◽  
All Cause Mortality

Abstract Background Advanced glycation end-products, indicated by skin autofluorescence (SAF) levels, could be prognostic predictors of all-cause and cardiovascular mortality in patients with diabetes mellitus (DM) and renal disease. However, the clinical usefulness of SAF levels in patients with heart failure (HF) who underwent cardiac rehabilitation (CR) remains unclear. Purpose The purpose of this study was to investigate the prognostic value of SAF levels in patients with HF who underwent CR. Methods This study enrolled 204 consecutive patients with HF who had undergone CR at our university hospital between November 2015 and October 2017. Clinical characteristics and anthropometric data were collected at the beginning of CR. SAF levels were noninvasively measured with an autofluorescence reader. The major adverse cardiovascular event (MACE) was a composite of all-cause mortality and unplanned hospitalization for HF. Follow-up data concerning primary endpoints were collected until November 2018. Results Patients' mean age was 68.1 years, and 61% were males. Patients were divided into two groups according to the median SAF levels (high and low SAF groups). Patients in the high SAF group were significantly older, had a higher prevalence of chronic kidney disease, and histories of coronary artery bypass surgery; however, there were no significant between-group differences in sex, prevalence of DM, left ventricular ejection fraction, and physical function. During a median follow-up period of 623 days, 25 patients experienced all-cause mortality and 34 were hospitalized for HF. Kaplan–Meier analysis showed that patients in the high SAF group had a higher incidence of MACE (log-rank P<0.05), whereas when patients were divided into two groups according to the median hemoglobin A1c level, no significant between-group difference was observed for the incidence of MACE (Figure). After adjusting for confounding factors, Cox regression multivariate analysis revealed that SAF levels were independently associated with the incidence of MACE (hazard ratio: 1.74, 95% confidence interval: 1.12–2.65, P<0.05). Figure 1 Conclusion SAF levels were significantly associated with the incidence of MACE in patients with HF and may be useful for risk stratification in patients with HF who undergo CR.

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