Posts filed under ‘Resistencia bacteriana’

Early, Goal-Directed Therapy for Septic Shock — A Patient-Level Meta-Analysis

N Engl J Med  Mar 21, 2017

The PRISM Investigators*

BACKGROUND

After a single-center trial and observational studies suggesting that early, goal-directed therapy (EGDT) reduced mortality from septic shock, three multicenter trials (ProCESS, ARISE, and ProMISe) showed no benefit. This meta-analysis of individual patient data from the three recent trials was designed prospectively to improve statistical power and explore heterogeneity of treatment effect of EGDT.

METHODS

We harmonized entry criteria, intervention protocols, outcomes, resource-use measures, and data collection across the trials and specified all analyses before unblinding. After completion of the trials, we pooled data, excluding the protocol-based standard-therapy group from the ProCESS trial, and resolved residual differences. The primary outcome was 90-day mortality. Secondary outcomes included 1-year survival, organ support, and hospitalization costs. We tested for treatment-by-subgroup interactions for 16 patient characteristics and 6 care-delivery characteristics.

RESULTS

We studied 3723 patients at 138 hospitals in seven countries. Mortality at 90 days was similar for EGDT (462 of 1852 patients [24.9%]) and usual care (475 of 1871 patients [25.4%]); the adjusted odds ratio was 0.97 (95% confidence interval, 0.82 to 1.14; P=0.68). EGDT was associated with greater mean (±SD) use of intensive care (5.3±7.1 vs. 4.9±7.0 days, P=0.04) and cardiovascular support (1.9±3.7 vs. 1.6±2.9 days, P=0.01) than was usual care; other outcomes did not differ significantly, although average costs were higher with EGDT. Subgroup analyses showed no benefit from EGDT for patients with worse shock (higher serum lactate level, combined hypotension and hyperlactatemia, or higher predicted risk of death) or for hospitals with a lower propensity to use vasopressors or fluids during usual resuscitation.

CONCLUSIONS

In this meta-analysis of individual patient data, EGDT did not result in better outcomes than usual care and was associated with higher hospitalization costs across a broad range of patient and hospital characteristics. (Funded by the National Institute of General Medical Sciences and others; PRISM ClinicalTrials.gov number, NCT02030158.)

PDF

http://www.nejm.org/doi/pdf/10.1056/NEJMoa1701380

May 11, 2017 at 11:13 am

Ceftolozane/tazobactam activity against drug-resistant Enterobacteriaceae and Pseudomonas aeruginosa causing urinary tract and intraabdominal infections in Europe: report from an antimicrobial surveillance programme (2012–15)

Journal of Antimicrobial Chemotherapy May 2017 V.72 N.5

EDITOR’S CHOICE

Michael A. Pfaller; Matteo Bassetti; Leonard R. Duncan; Mariana Castanheira

Objectives:

To evaluate the in vitro activity of ceftolozane/tazobactam and comparators tested against European isolates of Enterobacteriaceae and Pseudomonas aeruginosa from hospitalized patients with urinary tract infection or intraabdominal infections.

Methods:

A total of 6553 Gram-negative organisms (603 P. aeruginosa and 5950 Enterobacteriaceae) were consecutively collected from 41 hospitals located in 17 European countries plus Israel and Turkey. The organisms were tested for susceptibility by broth microdilution methods and the results interpreted according to EUCAST and CLSI breakpoint criteria.

Results:

Ceftolozane/tazobactam [MIC50/90 0.25/1 mg/L; 93.5%/91.3% susceptible (S) (CLSI/EUCAST criteria)] and meropenem [MIC50/90 ≤0.06/≤0.06 mg/L; 98.1%/98.3% S (CLSI/EUCAST)] were the most active compounds tested against Enterobacteriaceae. Among the Enterobacteriaceae isolates, 1.9% were carbapenem resistant (CRE), 15.2% exhibited an ESBL non-CRE phenotype, 14.6% were MDR, 2.2% were XDR and <0.1% were pan-drug resistant (PDR). Whereas ceftolozane/tazobactam showed activity against ESBL non-CRE phenotype isolates (MIC50/90 0.5/8 mg/L), it lacked useful activity against strains with a CRE (MIC50/90 >32/>32 mg/L; 3.6% S) or PDR (MIC50 >32 mg/L; 0.0% S) phenotype. Ceftolozane/tazobactam was the most potent (MIC50/90 0.5/4 mg/L) β-lactam agent tested against P. aeruginosa isolates, inhibiting 91.7% at an MIC of ≤4 mg/L. P. aeruginosa exhibited high rates of resistance to cefepime (20.6%), ceftazidime (23.1%), meropenem (9.0%) and piperacillin/tazobactam (26.9%) (EUCAST criteria). Among these four P. aeruginosa resistant phenotypes, 61.3%–70.4% were susceptible to ceftolozane/tazobactam.

Conclusions:

Ceftolozane/tazobactam was the most active β-lactam agent tested against P. aeruginosa and demonstrated higher in vitro activity than currently available cephalosporins and piperacillin/tazobactam when tested against Enterobacteriaceae.

PDF

https://oup.silverchair-cdn.com/oup/backfile/Content_public/Journal/jac/72/5/10.1093_jac_dkx009/1/dkx009.pdf?Expires=1494290906&Signature=PwSqO0ia77fjFIGKAD-W7rdRM5XjqvpROnT0K-LohId~LiUbAxo0px11Dxre1WTGBWhaMlZq5X6G180jhdj-NtSzi1Iu~6KARm~e8UGTBuVzV0X-Xb5iQrejbrdikp-krcYo967o99FoG~-XOpVwEuORM95fqKgqUQpG-0Afn-X6ceMYzUfT4A5sKJxR0uDL7Kghjz4KxfBo6FS8y-NsbwIblUMmNl-m35sUsB2hyztQnKcMDeCS3TCeo3djHeI07MIUOHBFKsheiiCmCN6EbOj1FnV0NJ1HuhNE1l7sr4Jggny0sNk90PitwHXRkrodP3JL-PwETe0Ywihi4qT0dQ__&Key-Pair-Id=APKAIUCZBIA4LVPAVW3Q

May 7, 2017 at 8:00 pm

In vitro activity of cefepime/zidebactam (WCK 5222) against Gram-negative bacteria

Journal of Antimicrobial Chemotherapy May 2017 V.72 N.5

EDITOR’S CHOICE

David M. Livermore; Shazad Mushtaq; Marina Warner; Anna Vickers; Neil Woodford

Objectives:

Diazabicyclooctanes (DBOs) inhibit class A, class C and some class D β-lactamases. A few also bind PBP2, conferring direct antibacterial activity and a β-lactamase-independent ‘enhancer’ effect, potentiating β-lactams targeting PBP3. We tested a novel DBO, zidebactam, combined with cefepime.

Methods:

CLSI agar dilution MICs were determined with cefepime/zidebactam in a chequerboard format. Bactericidal activity was also measured.

Results:

Zidebactam MICs were ≤2 mg/L (mostly 0.12–0.5 mg/L) for most Escherichia coli, Klebsiella, Citrobacter and Enterobacter spp., but were >32 mg/L for Proteeae, most Serratia and a few E. coli, Klebsiella and Enterobacter/Citrobacter. The antibacterial activity of zidebactam dominated chequerboard studies for Enterobacteriaceae, but potentiation of cefepime was apparent for zidebactam-resistant isolates with class A and C enzymes, illustrating β-lactamase inhibition. Overall, cefepime/zidebactam inhibited almost all Enterobacteriaceae with AmpC, ESBL, K1, KPC and OXA-48-like β-lactamases at 1 + 1 mg/L and also 29 of 35 isolates with metallo-carbapenemases, including several resistant to zidebactam alone. Zidebactam MICs for 36 of 50 Pseudomonas aeruginosa were 4–16 mg/L, and the majority of AmpC, metallo-β-lactamase-producing and cystic fibrosis isolates were susceptible to cefepime/zidebactam at 8 + 8 mg/L. Zidebactam MICs for Acinetobacter baumannii and Stenotrophomonas maltophilia were >32 mg/L; potentiation of cefepime was frequent for S. maltophilia, but minimal for A. baumannii. Kill curve results largely supported MICs.

Conclusions:

Zidebactam represents a second triple-action DBO following RG6080, with lower MICs for Enterobacteriaceae and P. aeruginosa. Clinical evaluation of cefepime/zidebactam must critically evaluate the reliance that can be placed on this direct antibacterial activity and on the enhancer effect as well as β-lactamase inhibition.

PDF

https://oup.silverchair-cdn.com/oup/backfile/Content_public/Journal/jac/72/5/10.1093_jac_dkw593/1/dkw593.pdf?Expires=1494290748&Signature=LS~WEfmC9yA22ZLeOO5MTEq-ovySpA8AANP0PAy9zm08YHIwrxp8VusV4iNC1RrwaCWsl5l3jHVkhY9q1Fihfm9uoMoVGno7tlEQeBvNriPMi8KQ~lqtQ0hkuMVKEs5j7CHcSJMHLTrK7DOIcJq9ZkhKUVg32kF8So6ywsULYbCoIk~iQ0cPTM5Ic2iHso5T6-c82mCP8R~5gaAMy4KFRSuhgEYLhlY~lPXt8I3d89UukOF4eg2sFGzVRlmSv7CNLRul~d4Z2cMrwyHJ6FcqE5MdcMq0Jv6oEq6NMMBVAwNl8DzrOdd9DOkPnVhgJhkYvuqvf6z-2tmZrWptHyHjcw__&Key-Pair-Id=APKAIUCZBIA4LVPAVW3Q

 

May 7, 2017 at 7:58 pm

REVIEW – DNA replication proteins as potential targets for antimicrobials in drug-resistant bacterial pathogens

Journal of Antimicrobial Chemotherapy May 2017 V.72 N.5

Erika van Eijk; Bert Wittekoek; Ed J. Kuijper; Wiep Klaas Smits

With the impending crisis of antimicrobial resistance, there is an urgent need to develop novel antimicrobials to combat difficult infections and MDR pathogenic microorganisms. DNA replication is essential for cell viability and is therefore an attractive target for antimicrobials. Although several antimicrobials targeting DNA replication proteins have been developed to date, gyrase/topoisomerase inhibitors are the only class widely used in the clinic. Given the numerous essential proteins in the bacterial replisome that may serve as a potential target for inhibitors and the relative paucity of suitable compounds, it is evident that antimicrobials targeting the replisome are underdeveloped so far. In this review, we report on the diversity of antimicrobial compounds targeting DNA replication and highlight some of the challenges in developing new drugs that target this process.

PDF

https://oup.silverchair-cdn.com/oup/backfile/Content_public/Journal/jac/72/5/10.1093_jac_dkw548/1/dkw548.pdf?Expires=1494290559&Signature=GYN2zJuKzTFrD1-qf7~UeFD0AvUDxmml1T9pnLClF3C1j6nTJ4nWxf9-SEIF3r5Y4CqK13zu7xAyz~viPDamtEKDAyFxqmaKg-xjsqK0gYKgkfkA-oX5i7vtwhG35aLCm3sZTPwPWrnHJwoLIJpvMUaXwWjqq69PxnCLWhMZ6pJ9WTMTC1oT-W-XZzax3V1NLcALEF7z8J7zQPSTKXugB030HYwnSUr8JrqEgyHEkh6FeuLYbhzr2IWI8ZzA1jj8UL0Dw1WS4s5coys-A7fiu1pOe0Y32gH5oLAFOgXISaPvBiK8NRSu3X1zJ7G68jpyJAF9Bvbx0GFF68O9~W0rIQ__&Key-Pair-Id=APKAIUCZBIA4LVPAVW3Q

May 7, 2017 at 7:57 pm

Daptomicina: características farmacológicas y aporte en el tratamiento de infecciones por cocos gram positivos

Revista Chilena de Infectología Abril 2012 V.29 N.2

Daptomycin: pharmacological characteristics and its role in the treatment of gram positive infections

Rafael Araos, Patricia García, Leonardo Chanqueo y Jaime Labarca

Facultad de Medicina Clínica Alemana/Universidad del Desarrollo, Santiago, Chile. Departamento de Medicina Interna (RA).

Pontificia Universidad Católica de Chile. Departamento de Laboratorios Clínicos (PG).

Pontificia Universidad Católica de Chile. Departamento de Medicina Interna (JL).

Hospital San Juan de Dios de Santiago. Laboratorio de Microbiología (LCh).

Daptomicina es un anti-infeccioso de reciente introducción en Chile, miembro exclusivo de una nueva familia de antimicrobianos conocida como lipopéptidos cíclicos. Tiene un mecanismo de acción único que le confiere un potente efecto bactericida sobre los microorganismos susceptibles. Su especto antimicrobiano comprende cocáceas grampositivas de importancia clínica como Staphylococcus aureus y Enterococcus spp., incluyendo cepas resistentes a antimicrobianos habituales. Está aprobada para el uso clínico en infecciones de piel y tejidos blandos y bacteriemia complicada y no complicada por S. aureus, en adultos. Estudios en curso sugieren que será una alternativa útil en otras infecciones frecuentes como osteomielitis, infecciones asociadas a dispositivos ortopédicos, infecciones asociadas a biopelículas e infecciones en hospederos inmunosuprimidos, en particular en pacientes onco-hematológicos. El principal efecto adverso asociado al uso de daptomicina es la toxicidad muscular, observándose miopatía reversible, la mayoría de las veces asintomática, en aproximadamente 3% de los pacientes que utilizan el fármaco.

PDF

http://www.scielo.cl/pdf/rci/v29n2/art01.pdf

May 6, 2017 at 7:10 pm

Yersinia enterocolitica: patogénesis, virulencia y resistencia a antibióticos

Enferm Infecc Microbiol Clin 2012;30:24-32

Anna Fàbrega, Jordi Vila

Department of Microbiology, Hospital Clínic, School of Medicine, University of Barcelona, Spain

Y. enterocolitica es un grupo heterogéneo de cepas clasificadas en 6 biogrupos y en más de 57 serogrupos O. Las cepas patógenas humanas más frecuentemente aisladas pertenecen a los serogrupos O:3, O:5,27, O:8 y O:9.

La transmisión de la infección es principalmente a través de alimentos o agua contaminados. La etapa esencial de la patogénesis es la colonización del tracto intestinal, donde ocurren la mayoría de los efectos patológicos y manifestaciones clínicas.

La temperatura y la concentración de calcio regulan la expresión de los factores de virulencia que guían al patógeno durante la invasión, supervivencia y diseminación. Normalmente las infecciones gastrointestinales son autolimitadas y no necesitan tratamiento antimicrobiano.

Las fluoroquinolonas y cefalosporinas de tercera generación son los tratamientos más eficaces en casos de enterocolitis en immunodeprimidos, septicemia o infección invasiva, situaciones en las que la mortalidad puede alcanzar el 50%.

Se presenta una revisión de la patogénesis, virulencia y resistencia antimicrobiana.

PDF del artículo completo hacer CLIC a la derecha en OPCIONES donde dice “DESCARGAR PDF”

http://www.elsevier.es/es-revista-enfermedades-infecciosas-microbiologia-clinica-28-articulo-yersinia-enterocolitica-pathogenesis-virulence-antimicrobial-S0213005X11002655?referer=buscador

May 6, 2017 at 5:35 pm

Complex Routes of Nosocomial Vancomycin-Resistant Enterococcus faecium Transmission Revealed by Genome Sequencing.

Clin Infect Dis. 2017 Apr 1;64(7):886-893.

Raven KE1, Gouliouris T1,2,3, Brodrick H1, Coll F4, Brown NM2,3, Reynolds R5,6, Reuter S1, Török ME1,2,3, Parkhill J7, Peacock SJ1,3,4,7.

Author information

1 Department of Medicine, University of Cambridge.

2 Public Health England, Clinical Microbiology and Public Health Laboratory, Addenbrooke’s Hospital, and.

3 Cambridge University Hospitals NHS Foundation Trust, Cambridge.

4 London School of Hygiene and Tropical Medicine.

5 British Society for Antimicrobial Chemotherapy, Birmingham.

6 North Bristol NHS Trust, Southmead Hospital, Bristol; and.

7 Wellcome Trust Sanger Institute, Hinxton, Cambridge, United Kingdom.

Abstract

BACKGROUND:

Vancomycin-resistant Enterococcus faecium (VREfm) is a leading cause of nosocomial infection. Here, we describe the utility of whole-genome sequencing in defining nosocomial VREfm transmission.

METHODS:

A retrospective study at a single hospital in the United Kingdom identified 342 patients with E. faecium bloodstream infection over 7 years. Of these, 293 patients had a stored isolate and formed the basis for the study. The first stored isolate from each case was sequenced (200 VREfm [197 vanA, 2 vanB, and 1 isolate containing both vanA and vanB], 93 vancomycin-susceptible E. faecium) and epidemiological data were collected. Genomes were also available for E. faecium associated with bloodstream infections in 15 patients in neighboring hospitals, and 456 patients across the United Kingdom and Ireland.

RESULTS:

The majority of infections in the 293 patients were hospital-acquired (n = 249) or healthcare-associated (n = 42). Phylogenetic analysis showed that 291 of 293 isolates resided in a hospital-associated clade that contained numerous discrete clusters of closely related isolates, indicative of multiple introductions into the hospital followed by clonal expansion associated with transmission. Fine-scale analysis of 6 exemplar phylogenetic clusters containing isolates from 93 patients (32%) identified complex transmission routes that spanned numerous wards and years, extending beyond the detection of conventional infection control. These contained both vancomycin-resistant and -susceptible isolates. We also identified closely related isolates from patients at Cambridge University Hospitals NHS Foundation Trust and regional and national hospitals, suggesting interhospital transmission.

CONCLUSIONS:

These findings provide important insights for infection control practice and signpost areas for interventions. We conclude that sequencing represents a powerful tool for the enhanced surveillance and control of nosocomial E. faecium transmission and infection

PDF

https://oup.silverchair-cdn.com/oup/backfile/Content_public/Journal/cid/64/7/10.1093_cid_ciw872/1/ciw872.pdf?Expires=1493989314&Signature=PWsoHk4ZslYHxHMhvNbpngwvfxGkVif–DIxIYk7GJ9EKlIKOeczfr1QNsV~Neh79GNdopZ4oYseQAFN5ZZevQ5wV26yFb3WlZrhe5XWWHK45XvTEZIRMnF~XT1IBzk2TWlG-8eWaVliA9lOwV6Ips8eFOS7zet~NxFrhqYm~egD6oqYG4VdqYQU6CfywYx58wdNsM5FNgQd~VGdFaTOsdgH-VF4LS6z~CvXiM50YcyE1A-RWeZLx34m6OHbN389~GKP2dk0TEa9IMP4yU51q7ZTYpzlzPyMWu-33JN5lVhywnHk0AREZfP8AIgHrFl0qgJWO47z8J8Ea8NTrfwe5A__&Key-Pair-Id=APKAIUCZBIA4LVPAVW3Q

 

May 4, 2017 at 8:51 am

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