Posts filed under ‘Infecciones respiratorias’

Intrapulmonary Pharmacokinetics of Relebactam, a Novel β-Lactamase Inhibitor, Dosed in Combination with Imipenem-Cilastatin in Healthy Subjects.

Antimicrob Agents Chemother. February 23, 2018 V.62 N.3

Rizk ML1, Rhee EG2, Jumes PA2, Gotfried MH3, Zhao T2, Mangin E2, Bi S2, Chavez-Eng CM2, Zhang Z2, Butterton JR2.

Abstract

This phase I study assessed the intrapulmonary pharmacokinetic profiles of relebactam (MK-7655), a novel β-lactamase inhibitor, and imipenem. Sixteen healthy subjects received 250 mg relebactam with 500 mg imipenem-cilastatin, given intravenously every 6 h for 5 doses, and were randomized to bronchoscopy/bronchoalveolar lavage at 0.5, 1, 1.5, or 3 h after the last dose (4 subjects per time point). Both drugs penetrated the epithelial lining fluid (ELF) to a similar degree, with the profiles being similar in shape to the corresponding plasma profiles and with the apparent terminal half-lives in plasma and ELF being 1.2 and 1.3 h, respectively, for relebactam and 1.0 h in both compartments for imipenem. The exposure (area under the concentration-time curve from time zero to infinity) in ELF relative to that in plasma was 54% for relebactam and 55% for imipenem, after adjusting for protein binding. ELF penetration for relebactam was further analyzed by fitting the data to a two-compartment pharmacokinetic model to capture its behavior in plasma, with a partitioning coefficient capturing its behavior in the lung compartment. In this model, the time-invariant partition coefficient for relebactam was found to be 55%, based on free drug levels. These results support the clinical evaluation of relebactam with imipenem-cilastatin for the treatment of bacterial pneumonia.

PDF

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5826112/pdf/e01411-17.pdf

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July 21, 2019 at 2:45 pm

Efficacy and accuracy of qSOFA and SOFA scores as prognostic tools for community-acquired and healthcare-associated pneumonia

International Journal of Infectious Diseases July 2019 V.84 P.89-96

Nobuhiro Asai, Hiroki Watanabe, Arufumi Shiota, Hideo Kato, Daisuke Sakanashi, Mao Hagihara, Yusuke Koizumi, Yuka Yamagishi, Hiroyuki Suematsu, Hiroshige Mikamo

Highlights

  • The Japanese Respiratory Society recently updated the prognostic guidelines for pneumonia in 2017.
  • The new guidelines recommend that pneumonia severity be evaluated using the sequential organ failure assessment (SOFA) and the quick SOFA (qSOFA) scoring systems in a therapeutic strategy flowchart.
  • The combination of qSOFA and SOFA score could be an independent prognostic factor for 30-day mortality among patients with community-onset pneumonia.

Background

The Japanese Respiratory Society recently updated its prognostic guidelines for pneumonia, recommending that pneumonia severity be evaluated using the sequential organ failure assessment (SOFA) and quick SOFA (qSOFA) scoring systems in a therapeutic strategy flowchart. However, the efficacy and accuracy of these tools are still unknown.

Methods

All patients with community-acquired pneumonia (CAP) and healthcare-associated pneumonia (HCAP) who were admitted to the study institution between 2014 and 2017 were enrolled in this study. Pneumonia severity on admission was evaluated by A-DROP, CURB-65, PSI, I-ROAD, qSOFA, and SOFA scoring systems. Prognostic factors for 30-day mortality were also analyzed.

Results

This study included 406 patients, 257 male (63%) and 149 female (37%). The median age was 79 years (range 19–103 years). The 30-day and in-hospital mortality rates were both 5%. With respect to the diagnostic value of the predictive assessments for 30-day mortality, the area under the receiver operating characteristic curve (AUROC) value for the SOFA score was 0.769 for CAP patients and 0.774 for HCAP patients. Further, the AUROC values for the SOFA score in CAP and HCAP patients with a qSOFA score ≥2 were 0.829 and 0.784, respectively, for 30-day mortality.

Conclusions

qSOFA and SOFA scores were able to correctly evaluate the severity of CAP and HCAP.

FULL TEXT

https://www.ijidonline.com/article/S1201-9712(19)30190-0/fulltext

PDF

https://www.ijidonline.com/article/S1201-9712(19)30190-0/pdf

June 30, 2019 at 9:25 pm

A Therapeutic Strategy for All Pneumonia Patients: A 3-Year Prospective Multicenter Cohort Study Using Risk Factors for Multidrug-resistant Pathogens to Select Initial Empiric Therapy

Clinical Infectious Diseases April 1, 2019 V.68 N.7 P.1080-1088 

EDITOR’S CHOICE

We applied a single algorithm to all forms of pneumonia, which was followed in 82.5% of a cohort of 1089 patients. Only 4.3% received inappropriate therapy; in multivariate analysis, site of pneumonia acquisition was not predictive of 30-day mortality.

Background

Empiric therapy of pneumonia is currently based on the site of acquisition (community or hospital), but could be chosen, based on risk factors for multidrug-resistant (MDR) pathogens, independent of site of acquisition.

Methods 

We prospectively applied a therapeutic algorithm based on MDR risks, in a multicenter cohort study of  1089 patients with 656 community-acquired pneumonia (CAP), 238 healthcare-associated pneumonia (HCAP), 140 hospital-acquired pneumonia (HAP), or 55 ventilator-associated pneumonia (VAP).

Results

Approximately 83% of patients were treated according to the algorithm, with 4.3% receiving inappropriate therapy. The frequency of MDR pathogens varied, respectively, with VAP (50.9%), HAP (27.9%), HCAP (10.9%), and CAP (5.2%). Those with ≥2 MDR risks had MDR pathogens more often than those with 0–1 MDR risk (25.8% vs 5.3%, P < .001). The 30-day mortality rates were as follows: VAP (18.2%), HAP (13.6%), HCAP (6.7%), and CAP (4.7%), and were lower in patients with 0–1 MDR risks than in those with ≥2 MDR risks (4.5% vs 12.5%, P < .001). In multivariate logistic regression analysis, 5 risk factors (advanced age, hematocrit <30%, malnutrition, dehydration, and chronic liver disease), as well as hypotension and inappropriate therapy were significantly correlated with 30-day mortality, whereas the classification of pneumonia type (VAP, HAP, HCAP, CAP) was not.

Conclusions

Individual MDR risk factors can be used in a unified algorithm to guide and simplify empiric therapy for all pneumonia patients, and were more important than the classification of site of pneumonia acquisition in determining 30-day mortality.

FULL TEXT

https://academic.oup.com/cid/article/68/7/1080/5063558

PDF (CLIC en PDF)

May 4, 2019 at 12:14 pm

Clinical Practice Guidelines by the Infectious Diseases Society of America: 2018 Update on Diagnosis, Treatment, Chemoprophylaxis, and Institutional Outbreak Management of Seasonal Influenza.

Clinical Infectious Diseases March 5, 2019 V.68 N.6 P.e1-e47.   

Clinical Practice Guidelines by the Infectious Diseases Society of America: 2018 Update on Diagnosis, Treatment, Chemoprophylaxis, and Institutional Outbreak Management of Seasonal Influenza.

Uyeki TM1, Bernstein HH2, Bradley JS3,4, Englund JA5, File TM6, Fry AM1, Gravenstein S7, Hayden FG8, Harper SA9, Hirshon JM10, Ison MG11, Johnston BL12, Knight SL13, McGeer A14, Riley LE15, Wolfe CR16, Alexander PE17,18, Pavia AT19.

Abstract

These clinical practice guidelines are an update of the guidelines published by the Infectious Diseases Society of America (IDSA) in 2009, prior to the 2009 H1N1 influenza pandemic. This document addresses new information regarding diagnostic testing, treatment and chemoprophylaxis with antiviral medications, and issues related to institutional outbreak management for seasonal influenza. It is intended for use by primary care clinicians, obstetricians, emergency medicine providers, hospitalists, laboratorians, and infectious disease specialists, as well as other clinicians managing patients with suspected or laboratory-confirmed influenza. The guidelines consider the care of children and adults, including special populations such as pregnant and postpartum women and immunocompromised patients.

Published by Oxford University Press for the Infectious Diseases Society of America 2018.

FULL TEXT

https://academic.oup.com/cid/article/68/6/e1/5251935

PDF (CLIC en PDF)

May 1, 2019 at 6:23 pm

Clinical Practice Guidelines by the Infectious Diseases Society of America: 2018 Update on Diagnosis, Treatment, Chemoprophylaxis, and Institutional Outbreak Management of Seasonal Influenza.

Clinical Infectious Diseases March 2019 V.68  N.6 e1–e47

Uyeki TM, Bernstein HH, Bradley JS, Englund JA, File TM Jr, Fry AM, et al.

These clinical practice guidelines are an update of the guidelines published by the Infectious Diseases Society of America (IDSA) in 2009, prior to the 2009 H1N1 influenza pandemic.

This document addresses new information regarding diagnostic testing, treatment and chemoprophylaxis with antiviral medications, and issues related to institutional outbreak management for seasonal influenza.

It is intended for use by primary care clinicians, obstetricians, emergency medicine providers, hospitalists, laboratorians, and infectious disease specialists, as well as other clinicians managing patients with suspected or laboratory-confirmed influenza.

The guidelines consider the care of children and adults, including special populations such as pregnant and postpartum women and immunocompromised patients.

FULL TEXT

https://academic.oup.com/cid/article/68/6/e1/5251935

PDF (CLIC en PDF)

March 20, 2019 at 3:42 pm

Correlación entre criterios clínicos y de laboratorio de casos notificados por sospecha de hantavirosis y el resultado de la técnica de referencia.

Rev. Chil. Infectol. Junio 2016 V.33 N.3 P.275-281

Actualmente en Chile, debido a la elevada sospecha clínica de enfermedad por hantavirus y el alto impacto en salud pública que esto provoca, se hace necesario reforzar al equipo de salud, los criterios de sospecha clínica y epidemiológica de hantavirosis.

Objetivo:

Analizar la información contenida en las notificaciones de sospecha de infección por hantavirus versus la técnica de referencia para el diagnóstico confirmatorio de casos sospechosos, ELISA IgM de captura anti-hantavirus.

Material y Método:

Mediante cálculo de precisión diagnóstica se analizó la correlación que existe entre la información entregada en las notificaciones versus el resultado de la confirmación mediante la técnica de referencia.

Resultados:

De 1.566 pacientes estudiados 3,4% (53 casos) fue confirmado para SCPH. De las notificaciones analizadas 58,6% estaban con datos incompletos. Los porcentajes de positividad de la técnica de referencia asociada a fiebre, mialgia y cefalea, fueron de 80-85%. Destaca que la presencia de inmunoblastos (> 10%), presenta: S: 25%, E: 98%, VPP: 37%, VPN: 97%. Paratrombocitopenia se obtuvo: S: 98%, E: 74%, VPP: 16%, VPN: 100%.

Conclusión:

Se hace necesario reiterar a nivel del sistema sanitario chileno la importancia de contar con datos completos en los formularios de notificación. La presencia de trombocitopenia e inmunoblastos (> 10%) fue altamente sensible y especifica, respectivamente, en la detección de pacientes con SCPH. Con el fin de optimizar la sospecha de infección por hantavirus, según la definición de caso sospechoso, se plantea la necesidad de desarrollar programas de capacitación para la sospecha clínica y lectura de parámetros de laboratorio, tales como presencia de inmunoblastos en el hemograma, así como incluir un algoritmo con el fin de optimizar la sospecha y el uso adecuado de los recursos sanitarios.

PDF

https://scielo.conicyt.cl/pdf/rci/v33n3/art04.pdf

 

January 20, 2019 at 8:05 pm

1er caso de SCPH diagnosticado en la Región de Antofagasta, Chile. 

Rev. Chil. Infectol. Agosto 2012 V.29 N.4 P.477-477

En Chile, desde 1995 se han confirmado casos del SCPH desde Valparaíso hasta Aysén, correspondiendo la mayor incidencia a las regiones de Aysén, Los Lagos, Araucanía y Bío Bío. El agente etiológico del SCPH es un virus ARN del género hantavirus, familia Bunyaviridae, variedad Andes.

El reservorio es el “ratón de cola larga” (Oligoryzomis longicaudatus) el cual se distribuye desde la Región de Atacama hasta la Región de Magallanes (XII°). El virus es eliminado por el ratón a través de sus secreciones (saliva, orina y heces) e ingresa al hombre por vía digestiva, cutánea o aérea, siendo esta última la más frecuente1. La transmisión de persona a persona está documentada, pero se considera excepcional.

El SCPH es un cuadro agudo grave con alta letalidad (30-55%) y sin tratamiento específico. El período de incubación puede durar hasta 45 días. Los primeros síntomas son fiebre, mialgias, cefalea y ocasionalmente diarrea; días después aparece la fase de compromiso respiratorio, con disnea progresiva e insuficiencia respiratoria grave. Es indispensable la terapia de soporte hemodinámico y manejo de la falla respiratoria en una UCI.

PDF

https://scielo.conicyt.cl/pdf/rci/v29n4/art22.pdf

January 20, 2019 at 8:02 pm

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