Posts filed under ‘BIOMARCADORES’

REVIEW – Empiric therapy for hospital-acquired, Gram-negative complicated intra-abdominal infection and complicated urinary tract infections: a systematic literature review of current and emerging treatment options

BMC Infect Dis. August 2015 V.15 P.313. 



Empiric therapy for healthcare-associated infections remains challenging, especially with the continued development of Gram-negative organisms producing extended-spectrum β-lactamases (ESBLs) and the threat of multi-drug-resistant organisms. Current treatment options for resistant Gram-negative infections include carbapenems, tigecycline, piperacillin-tazobactam, cefepime, ceftazidime, and two recently approved therapies, ceftolozane-tazobactam and ceftazidime-avibactam.


This systematic literature review surveys the published clinical trial evidence available since 2000 in support of both current and emerging treatment options in the settings of complicated intra-abdominal infection (cIAI) and complicated urinary tract infection (cUTI). When available, clinical cure rates for patients with infections from ESBL-producing strains are provided, as is information about efficacy against Pseudomonas aeruginosa.


Clinical trial evidence to guide selection of empiric antibiotic therapy in patients with complicated, hospital-acquired, Gram-negative IAIs and UTIs is limited. Though most of the clinical trials explored in this overview enrolled patients with complicated infections, often patients with severe infections and multiple comorbidities were excluded.


Practitioners in the clinical setting who are treating patients with complicated, hospital-acquired, Gram-negative IAIs and UTIs need to consider the possibility of polymicrobial infections, antibiotic-resistant organisms, and/or severely ill patients with multiple comorbidities. There is a severe shortage of evidence-based research to guide the selection of empiric antibiotic therapy for many patients in this setting. New therapies recently approved or in late-stage development promise to expand the number of options available for empiric therapy of these hospital-acquired, Gram-negative infections.



July 14, 2020 at 5:34 pm

REVIEW – Treatment strategies for persistent methicillin-resistant Staphylococcus aureus bacteraemia

J Clin Pharm Ther. 2018;43:614–625

What is known and objective

Treatment of methicillin-resistant Staphylococcus aureus (MRSA) bacteraemia is a long-standing challenge to health care, often complicated by metastatic infections, treatment failure and mortality. When MRSA bacteraemia persists despite adequate initial treatment, current Infectious Diseases Society of America guidelines recommend evaluation and removal of possible sources of infection. In addition, a change in therapy may be considered. The objective of this review was to explore the therapeutic options for the treatment of persistent MRSA bacteraemia.


A literature search of PubMed, MEDLINE and Google Scholar was performed using the following search terms: [methicillin-resistant Staphylococcus aureus OR MRSA] AND [bacteraemia OR bloodstream infection] AND [persistent OR persistence OR refractory OR treatment failure OR salvage] AND treatment. We evaluated relevant, adult, English-language, peer-reviewed studies published between 1985 and May 2018. In vitro and animal studies were considered as supportive of in vivo data.

Results and discussion

Randomized, controlled trials are lacking. However, case series and case reports support multiple treatment options including high-dose daptomycin in combination with an antistaphylococcal β-lactam, ceftaroline, trimethoprim-sulfamethoxazole (TMP-SMX) or fosfomycin; ceftaroline alone or in combination with vancomycin or TMP-SMX; linezolid alone or in combination with a carbapenem, or telavancin.

What is new and conclusion

Given the heterogeneity of the data, a preferred regimen has not emerged. Prescribers must take into consideration recent exposure, source control, and available synergy and clinical data. Further comparative trials are needed to establish a preferred regimen and the creation of a universal treatment algorithm



July 13, 2020 at 3:55 pm

Prevalence and Etiology of Community-acquired Pneumonia in Immunocompromised Patients

Clin Infect Dis. April 24, 2019 V.68 N.9 P.1482-1493. 


The correct management of immunocompromised patients with pneumonia is debated. We evaluated the prevalence, risk factors, and characteristics of immunocompromised patients coming from the community with pneumonia.


We conducted a secondary analysis of an international, multicenter study enrolling adult patients coming from the community with pneumonia and hospitalized in 222 hospitals in 54 countries worldwide. Risk factors for immunocompromise included AIDS, aplastic anemia, asplenia, hematological cancer, chemotherapy, neutropenia, biological drug use, lung transplantation, chronic steroid use, and solid tumor.


At least 1 risk factor for immunocompromise was recorded in 18% of the 3702 patients enrolled. The prevalences of risk factors significantly differed across continents and countries, with chronic steroid use (45%), hematological cancer (25%), and chemotherapy (22%) the most common. Among immunocompromised patients, community-acquired pneumonia (CAP) pathogens were the most frequently identified, and prevalences did not differ from those in immunocompetent patients. Risk factors for immunocompromise were independently associated with neither Pseudomonas aeruginosa nor non-community-acquired bacteria. Specific risk factors were independently associated with fungal infections (odds ratio for AIDS and hematological cancer, 15.10 and 4.65, respectively; both P = .001), mycobacterial infections (AIDS; P = .006), and viral infections other than influenza (hematological cancer, 5.49; P < .001).


Our findings could be considered by clinicians in prescribing empiric antibiotic therapy for CAP in immunocompromised patients. Patients with AIDS and hematological cancer admitted with CAP may have higher prevalences of fungi, mycobacteria, and noninfluenza viruses.




July 13, 2020 at 3:53 pm

Summary of the international clinical guidelines for the management of hospital-acquired and ventilator-acquired pneumonia

ERJ Open Res. Jube 26, 2018 V.4 N.2 



July 13, 2020 at 3:49 pm

The Cefazolin Inoculum Effect Is Associated With Increased Mortality in Methicillin-Susceptible Staphylococcus aureus Bacteremia

Open Forum Infect Dis. May 23, 2018 V.5 N.6 


Recent studies have favored the use of cefazolin over nafcillin for the treatment of methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia. The clinical influence of the cefazolin inoculum effect (CzIE) in the effectiveness of cephalosporins for severe MSSA infections has not been evaluated.


We prospectively included patients from 3 Argentinian hospitals with S. aureus bacteremia. Cefazolin minimum inhibitory concentrations (MICs) were determined at standard (105 colony-forming units [CFU]/mL) and high (107 CFU/mL) inoculum. The CzIE was defined as an increase of MIC to ≥16 µg/mL when tested at high inoculum. Whole-genome sequencing was performed in all isolates.


A total of 77 patients, contributing 89 MSSA isolates, were included in the study; 42 patients (54.5%) had isolates with the CzIE. In univariate analysis, patients with MSSA exhibiting the CzIE had increased 30-day mortality (P = .034) and were more likely to have catheter-associated or unknown source of bacteremia (P = .033) compared with patients infected with MSSA isolates without the CzIE. No statistically significant difference between the groups was observed in age, clinical illness severity, place of acquisition (community vs hospital), or presence of endocarditis. The CzIE remained associated with increased 30-day mortality in multivariate analysis (risk ratio, 2.65; 95% confidence interval, 1.10-6.42; P = .03). MSSA genomes displayed a high degree of heterogeneity, and the CzIE was not associated with a specific lineage.


In patients with MSSA bacteremia where cephalosporins are used as firstline therapy, the CzIE was associated with increased 30-day mortality. Clinicians should be cautious when using cefazolin as firstline therapy for these infections.



July 13, 2020 at 3:47 pm

International ERS/ESICM/ESCMID/ALAT guidelines for the management of hospital-acquired pneumonia and ventilator-associated pneumonia

Eur Respir J. September 10, 2017 V.50 N.3 

Guidelines for the management of hospital-acquired pneumonia (HAP)/ventilator-associated pneumonia (VAP) of the European Respiratory Society (ERS), European Society of Intensive Care Medicine (ESICM), European Society of Clinical Microbiology and Infectious Diseases (ESCMID) and Asociación Latinoamericana del Tórax (ALAT)

The most recent European guidelines and task force reports on hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP) were published almost 10 years ago. Since then, further randomised clinical trials of HAP and VAP have been conducted and new information has become available. Studies of epidemiology, diagnosis, empiric treatment, response to treatment, new antibiotics or new forms of antibiotic administration and disease prevention have changed old paradigms. In addition, important differences between approaches in Europe and the USA have become apparent.The European Respiratory Society launched a project to develop new international guidelines for HAP and VAP. Other European societies, including the European Society of Intensive Care Medicine and the European Society of Clinical Microbiology and Infectious Diseases, were invited to participate and appointed their representatives. The Latin American Thoracic Association was also invited.A total of 15 experts and two methodologists made up the panel. Three experts from the USA were also invited (Michael S. Niederman, Marin Kollef and Richard Wunderink).Applying the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) methodology, the panel selected seven PICO (population-intervention-comparison-outcome) questions that generated a series of recommendations for HAP/VAP diagnosis, treatment and prevention.



July 13, 2020 at 3:45 pm

Magnetic Resonance Imaging in Differentatial Diagnosis of Pyogenic Spondylodiscitis and Tuberculous Spondylodiscitis

Pol J Radiol. February 2017 V.82 P.71-87.


La espondilodiscitis infecciosa se caracteriza por la participación de dos vértebras adyacentes y el disco intermedio.

La tasa de incidencia de la enfermedad se estima en 0.4-2 casos por 100000 por año.

Staphylococcus aureus es el agente infeccioso más común que causa espondilodiscitis piógena.

Las infecciones no piógenas de la columna vertebral son causadas con mayor frecuencia por Mycobacterium tuberculosis y hongos.

Los síntomas clínicos son inespecíficos.

El diagnóstico temprano y el tratamiento adecuado pueden evitar secuelas irreversibles desfavorables para el paciente.

Los desarrollos significativos en las técnicas de imagen de tejidos patológicos aumentaron las expectativas entre los médicos con respecto a la posibilidad de distinguir entre la espondilodiscitis tuberculosa y la espondilodiscitis piógena en las imágenes de RM.

El objetivo de este estudio fue identificar y diferenciar las características de la espondilodiscitis tuberculosa y piógena en las imágenes de RM.


Realizamos un análisis retrospectivo de imágenes de RM obtenidas de 34 pacientes con espondilodiscitis confirmada (18 con espondilodiscitis piógena y 16 con espondilodiscitis tuberculosa). La adquisición de datos se realizó utilizando escáneres de resonancia magnética de 1,5 T, donde se obtuvieron imágenes utilizando protocolos similares. T2 TIRM y las imágenes ponderadas en T1 con y sin realce de contraste fueron sujetas a evaluación en planos coronal, axial y sagital.


Las características de la espondilodiscitis piógena incluyen: afectación de la columna lumbar, aumento del contraste anormal paraespinal mal definido, aumento del contraste difuso / homogéneo de los cuerpos vertebrales, destrucción de grado bajo de los cuerpos vertebrales, señal hiperintensa / homogénea de los cuerpos vertebrales en las imágenes T2 TIRM . Las características predominantes de la espondilodiscitis tuberculosa incluyeron: afectación de la columna torácica, afectación de 2 o más cuerpos vertebrales adyacentes, destrucción severa del cuerpo vertebral, realce de contraste focal / heterogéneo de los cuerpos vertebrales, señal heterogénea de los cuerpos vertebrales en imágenes T2 TIRM, bien Mejora de contraste anormal paraespinal -definido, abscesos paraespinales y epidurales, realce meníngeo a nivel de la columna afectada.


La comparación de imágenes de RM de pacientes diagnosticados con espondilodiscitis piógena y espondilodiscitis tuberculosa permitió la identificación de características individuales para la diferenciación preliminar entre TB y espondilodiscitis infecciosa y, por lo tanto, permitió un tratamiento adecuado.


July 12, 2020 at 1:39 pm

Magnetic Resonance Imaging of Bacterial and Tuberculous Spondylodiscitis With Associated Complications and Non-Infectious Spinal Pathology Mimicking Infections: A Pictorial Review

BMC Musculoskelet Disord. June 5, 2017 V.18 N.1 P.244.

La resonancia magnética (RM) desempeña un papel importante en la evaluación de la espondilodiscitis bacteriana y tuberculosa y las complicaciones asociadas.

Debido a su alta sensibilidad y especificidad, es una poderosa herramienta de diagnóstico en el diagnóstico precoz de infecciones en curso y, por lo tanto, proporciona ayuda para el inicio inmediato de una terapia adecuada, que puede ser médica o quirúrgica, al definir el alcance de la participación y la detección de complicaciones. tales como abscesos epidurales y paraespinales.

Más específicamente, la resonancia magnética ayuda a diferenciar las infecciones bacterianas de las tuberculosas y permite el seguimiento de la progresión o resolución después del tratamiento adecuado.

Sin embargo, otra patología no infecciosa puede demostrar apariencias similares de imágenes de RM y uno debe ser consciente de estos posibles imitadores al interpretar imágenes de RM.

Los radiólogos y otros médicos deben ser conscientes de estas posibles imitaciones, que incluyen patologías tales como cambios degenerativos tipo I, trauma, enfermedad metastásica y amiloidosis.

En esta revisión pictórica, describiremos e ilustraremos los hallazgos de imágenes de la espondilodiscitis bacteriana y tuberculosa, sus complicaciones y patologías no infecciosas que imitan estas infecciones espinales.



July 12, 2020 at 1:38 pm

The Rheumatologist’s Role in COVID-19.

J Rheumatol. May 1, 2020 V.47 N.5 P.639-642.

Cron RQ1, Chatham WW2.

Author information

1 University of Alabama at Birmingham, Department of Pediatrics, Division of Rheumatology;

2 University of Alabama at Birmingham, Department of Medicine, Division of Clinical Immunology and Rheumatology, Birmingham, Alabama, USA.

La nueva pandemia de SARS-CoV-2 se ha extendido rápidamente por todo el planeta. Se cree que se originó en la provincia china de Wuhan, pero este virus respiratorio altamente contagioso se ha extendido a más de 140 países en 6 continentes a mediados de marzo 2020, según la OMS.

A nivel mundial, se han identificado más de 164,000 casos y más de 6500 muertes atribuidas a la infección viral.

A mediados de marzo de 2020, hay más de 3700 casos confirmados y 68 muertes atribuidas a la enfermedad por coronavirus 2019 (COVID-19; la enfermedad causada por el SARS-CoV-2) en los Estados Unidos ( updates-united-states.html).

Estos números solo continuarán creciendo a nivel mundial.

Basado principalmente en datos de China, aproximadamente el 80% de las personas infectadas con SARS-CoV-2 experimentan un “resfriado” relativamente leve, como se observa con las infecciones por coronavirus más comunes.

Sin embargo, el 20% de los infectados requieren hospitalización, con un 5–15% en general que requieren cuidados intensivos.

Como todavía no se conoce el verdadero denominador de los infectados, no está claro cuál es la tasa de mortalidad general asociada con COVID-19, pero las estimaciones oscilan entre 1% y 4% 2.

Aunque la tasa de mortalidad es más baja que la reportada para epidemias previas de coronavirus como el SARS y el MERS, el número absoluto mucho mayor de individuos infectados con SARS-CoV-2 dará como resultado un número sustancial de muertes en todo el mundo.



May 18, 2020 at 8:11 pm

Infectious Diseases Society of America Guidelines on the Treatment and Management of Patients with COVID-19.

Clin Infect Dis. April 27, 2020.

Bhimraj A1, Morgan RL2, Shumaker AH3, Lavergne V4, Baden L5, Cheng VC6, Edwards KM7, Gandhi R8, Muller WJ9, O’Horo JC10, Shoham S11, Murad MH12, Mustafa RA13, Sultan S14, Falck-Ytter Y3.



There are many pharmacologic therapies that are being used or considered for treatment of COVID-19. There is a need for frequently updated practice guidelines on their use, based on critical evaluation of rapidly emerging literature.


Develop evidence-based rapid guidelines intended to support patients, clinicians and other health-care professionals in their decisions about treatment and management of patients with COVID-19.


IDSA formed a multidisciplinary guideline panel of infectious disease clinicians, pharmacists, and methodologists with varied areas of expertise. Process followed a rapid recommendation checklist. The panel prioritized questions and outcomes. Then a systematic review of the peer-reviewed and grey literature was conducted. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to assess the certainty of evidence and make recommendations.


The IDSA guideline panel agreed on 7 treatment recommendations and provided narrative summaries of other treatments undergoing evaluations.


The panel expressed the overarching goal that patients be recruited into ongoing trials, which would provide much needed evidence on the efficacy and safety of various therapies for COVID-19, given that we could not make a determination whether the benefits outweigh harms for most treatments.


May 18, 2020 at 8:09 pm

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