Clinical outcomes of health-care-associated infections and antimicrobial resistance in patients admitted to European intensive-care units: a cohort study

Lambert, Marie‐Laurence; Suetens, Carl; Savey, Anne; Palomar, Mercedes; Hiesmayr, Michael; Moráles, Ingrid; Agodi, Antonella; Frank, Uwe; Mertens, Karl; Schumacher, Martin; Wolkewitz, Martin

doi:10.1016/s1473-3099(10)70258-9

Cited by 358 publications

(268 citation statements)

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“…Pseudomonas aeruginosa is a common nosocomial pathogen that causes a broad range of infections with a high mortality rate (Mahar et al, 2010; Iida et al, 2010;Lambert et al, 2011). A major factor in its prominence as a pathogen is, in part, its intrinsic resistance to a number of antibacterial agents (Poole et al, 1993;Hancock, 1998;Poole, 2002) and, particularly, the development of increased multidrug resistance in healthcare settings (Giamarellos-Bourboulis et al, 2006;Kirikae et al, 2008;Kallen et al, 2010;Keen et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

Primary mechanisms mediating aminoglycoside resistance in the multidrug-resistant Pseudomonas aeruginosa clinical isolate PA7

2012

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The multiresistant taxonomic outlier Pseudomonas aeruginosa PA7 possesses the conserved efflux genes, mexXY; however these are linked to a unique gene encoding an outer membrane channel, dubbed oprA, that is absent in most P. aeruginosa strains. Using genetic knockouts and single copy chromosomal complementation, we showed that aminoglycoside resistance in PA7 is mediated in part by the MexXY-OprA pump, and intriguingly that MexXY in this strain can utilize either the OprA or OprM outer membrane channel, linked to the mexAB efflux genes. We also identified a small portion of the oprA gene immediately downstream of the mexY gene in PAO1, suggesting that non-PA7 P. aeruginosa strains might have possessed, but lost, the intact mexXYoprA efflux pump locus. Consistent with this, most of a panel of serotype strains possessed the truncated oprA but the serotype O12 isolate had an intact mexXY-oprA locus, similar to PA7 and the related strain DSM 1128. We also showed that the mexZ repressor gene upstream of mexXYoprA in PA7 is mutated, leading to overexpression of mexXY-oprA, using sequencing, homologous replacement and real-time quantitative reverse transcriptase PCR. Finally we assessed the contribution of MexXY and aminoglycoside modifying enzymes AAC together to resistance in PA7 and the AAC(69)-Iae-mediated amikacin-resistant clinical isolate IMCJ2.S1, concluding that the effect of the modifying enzymes is enhanced by functional efflux, especially in the presence of divalent cations, to develop high-level aminoglycoside resistance in P. aeruginosa. INTRODUCTIONPseudomonas aeruginosa is a common nosocomial pathogen that causes a broad range of infections with a high mortality rate (Mahar et al., 2010; Iida et al., 2010;Lambert et al., 2011). A major factor in its prominence as a pathogen is, in part, its intrinsic resistance to a number of antibacterial agents (Poole et al., 1993;Hancock, 1998;Poole, 2002) and, particularly, the development of increased multidrug resistance in healthcare settings (Giamarellos-Bourboulis et al., 2006;Kirikae et al., 2008;Kallen et al., 2010;Keen et al., 2010). This organism readily acquires resistance via chromosomal mutations (e.g. overexpression of the efflux pump) and lateral gene transfer (e.g. acquisition of metallob-lactamase) (Lister et al., 2009;Poole, 2011). The emergence and spread of multidrug-, extensive drug-and pan-drug-resistant P. aeruginosa infections are very serious and of great concern, as few agents are effective against these organisms. In addition, antibiotic-resistant Gram-negative bacteria, including P. aeruginosa, increase the hospital costs and length of stay associated with healthcare-associated infections (Mauldin et al., 2010).Aminoglycosides such as amikacin, gentamicin and tobramycin are a vital component of antipseudomonal chemotherapy for a variety of infections, particularly pulmonary infections in cystic fibrosis (CF) patients (Poole, 2005(Poole, , 2011. Aminoglycoside resistance in P. aeruginosa has often arisen via acquired aminoglycoside-modifyi...

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Section: Introductionmentioning

confidence: 99%

Primary mechanisms mediating aminoglycoside resistance in the multidrug-resistant Pseudomonas aeruginosa clinical isolate PA7

2012

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“…10,13,14 Multistate models account for competing outcomes and time-dependent bias 11,15 and have not been used to evaluate the burden of infection by ESBL-positive organisms outside the intensive care context. 16 The primary aim of this study was to quantify the economic figure 1. Representation of the multistate model adopted for this analysis.…”

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confidence: 99%

Burden of Bloodstream Infection Caused by Extended-Spectrum β-Lactamase–Producing Enterobacteriaceae Determined Using Multistate Modeling at a Swiss University Hospital and a Nationwide Predictive Model

Stewardson

Fankhauser

Angelis

et al. 2013

Infect. Control Hosp. Epidemiol.

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JSTOR is a not-for-profit service that helps scholars, researchers, and students discover, use, and build upon a wide range of content in a trusted digital archive. We use information technology and tools to increase productivity and facilitate new forms of scholarship. For more information about JSTOR, please contact support@jstor.org.. results. Thirty ESBL-positive and 96 ESBL-negative BSI cases were included. The excess LOS attributable to ESBL-positive and ESBLnegative BSI was 9.4 (95% confidence interval [CI], 0.4-18.4) and 2.6 (95% CI, 0.7-5.9) days, respectively. ESBL positivity was therefore associated with 6.8 excess days and CHF 9,473 per BSI. The adjusted end-of-LOS HRs for ESBL-positive and ESBL-negative BSI were 0.62 (95% CI, 0.43-0.89) and 0.90 (95% CI, 0.74-1.10), respectively. After reimbursement, the average financial loss per acute care episode in ESBL-positive BSI, ESBL-negative BSI, and control cohorts was CHF 48,674, 48,131, and 13,532, respectively. Our predictive model estimated that the nationwide cost of third-generation cephalosporin resistance would increase from CHF 2,084,000 in 2010 to CHF 3,526,000 in 2015.conclusions. This is the first hospital-wide analysis of excess LOS attributable to ESBL positivity determined using multistate modeling to avoid time-dependent bias. These results may inform health-economic evaluations of interventions targeting ESBL control.

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“…There are conflicting reports in the literature concerning the outcomes of ICU patients with bacteraemia; for example, a Canadian study demonstrated that patients presenting to the ICU with bacteraemia did not have increased mortality compared to those without (OR 1.1 95% CI 0.7-1.8) [3]. This contrasts with studies by Prowle et al and Lambert et al which found that bacteraemia was independently associated with an increase in mortality rate in ICU patients of three and two-four fold respectively [4,5].…”

Section: Introductionmentioning

confidence: 84%

“…Several other authors have also investigated this, with some finding that bacteraemia does not increase mortality [3,14,18] and others concluding it does [4,5,19]. This may be because the observed impact of bacteraemia varies with study population and setting.…”

Section: Discussionmentioning

confidence: 99%

“…Because the United Kingdom has the smallest number of ICU beds/population in developed world [21] a smaller percentage of the hospital population will accommodated there and as such may be sicker at baseline and more susceptible to the effects of bacteraemia. Previous investigations have predominantly taken place outside the UK [7,15,18] or have been limited tonosocomial acquired infection [5,19] or specific organisms [4] and thus their results may not be applicable to this population. These results, including all patients with bacteraemia in a general ICU population provide up-to-date knowledge of the impact bacteraemia.…”

Section: Discussionmentioning

confidence: 99%

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Mortality in intensive care: The impact of bacteremia and the utility of systemic inflammatory response syndrome

Brooks

Smith

Young

et al. 2016

American Journal of Infection Control

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Mortality in intensive care: The impact of bacteremia and the utility of systemic inflammatory response syndrome. American Journal of Infection Control, 44(11), pp. 1291Control, 44(11), pp. -1295Control, 44(11), pp. . (doi:10.1016Control, 44(11), pp. /j.ajic.2016 This is the author's final accepted version.There may be differences between this version and the published version. You are advised to consult the publisher's version if you wish to cite from it. TitleMortality in intensive care -the impact of bacteremia and the utility of SIRS. 2 Abstract ObjectiveTo determine the impact of bacteraemia on ICU mortality and develop a bacteremia prediction tool using Systemic Inflammatory Response Syndrome (SIRS) criteria. ParticipantsPatients aged >18 who had blood cultures taken in the ICU 1 st January 2011-31 st December 2013. DesignAll patients meeting the above criteria were identified from microbiology department records of Glasgow Royal Infirmary, Scotland. Clinical and outcome data were gathered from ICU records. Patients with clinically significant bacteraemia were matched to controls using propensity scores. SIRS criteria were gathered and used to create decision rules to predict the absence of bacteraemia. Main outcome measuresMortality at ICU discharge. Sensitivity and accuracy of prediction of blood culture status by SIRS decision rule. ResultsOne hundred patients had a clinically significant positive blood culture and were matched to 100 controls. Bacteraemic patients had higher ICU mortality (OR 2.35 p=0.001) and longer ICU stay (17.0 vs. 7.8 days, p=<0.001). Of 1548 blood culture episodes, 1274 met ≥2 SIRS criteria (106 significant positive cultures, 1168 negative cultures). There was no association between SIRS criteria and positive blood cultures (p=0.11). A decision rule using three SIRS criteria had optimal predictive performance (sensitivity 56%; specificity 50%) but had low accuracy. ConclusionICU patients with bacteraemia have increased mortality and length of ICU stay. SIRS criteria cannot be used to identify patients at low risk of bacteraemia.

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Clinical outcomes of health-care-associated infections and antimicrobial resistance in patients admitted to European intensive-care units: a cohort study

Cited by 358 publications

References 28 publications

Primary mechanisms mediating aminoglycoside resistance in the multidrug-resistant Pseudomonas aeruginosa clinical isolate PA7

Primary mechanisms mediating aminoglycoside resistance in the multidrug-resistant Pseudomonas aeruginosa clinical isolate PA7

Burden of Bloodstream Infection Caused by Extended-Spectrum β-Lactamase–Producing Enterobacteriaceae Determined Using Multistate Modeling at a Swiss University Hospital and a Nationwide Predictive Model

Mortality in intensive care: The impact of bacteremia and the utility of systemic inflammatory response syndrome

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