Seven-day antibiotic therapy for Enterobacterales bacteremia in high-risk neutropenic patients: toward a new paradigm.

PURPOSE: Data on short courses of antibiotic therapy for Enterobacterales bacteremia in high-risk neutropenic patients are limited. The aim of the study was to describe and compare the frequency of bacteremia relapse, 30-day overall and infection-related mortality, Clostridiodes difficile infection and length of hospital stay since bacteremia among those who received antibiotic therapy for 7 or 14 days. METHODS: This is a multicenter, prospective, observational cohort study in adult high-risk neutropenic patients with hematologic malignancies or hematopoietic stem cell transplant and monomicrobial Enterobacterales bacteremia. They received appropriate empirical antibiotic therapy, had a clinical response within 7 days, and infection source control. Clinical, epidemiological and outcomes variables were compared based on 7 or 14 days of AT. RESULTS: Two hundred patients were included (100, 7-day antibiotic therapy; 100, 14-day antibiotic therapy). Escherichia coli was the pathogen most frequently isolated (47.5%), followed by Klebsiella sp. (40.5%). Among those patients that received 7-day vs. 14-day antibiotic course, a clinical source of bacteremia was found in 54% vs. 57% (p = 0.66), multidrug-resistant Enterobacterales isolates in 28% vs. 30% (p = 0.75), and 40% vs. 47% (p = 0.31) received combined empirical antibiotic therapy. Overall mortality was 3% vs. 1% (p = 0.62), in no case related to infection; bacteremia relapse was 7% vs. 2% (p = 0.17), and length of hospital stay since bacteremia had a median of 9 days (IQR: 7-15) vs. 14 days (IQR: 13-22) (p = < 0.001). CONCLUSIONS: These data suggest that seven-day antibiotic therapy might be adequate for patients with high-risk neutropenia and Enterobacterales bacteremia, who receive appropriate empirical therapy, with clinical response and infection source control.

Ceftazidime-Avibactam Improves Outcomes in High-Risk Neutropenic Patients with Klebsiella pneumoniae Carbapenemase-Producing Enterobacterales Bacteremia.

Few studies have evaluated the efficacy of ceftazidime-avibactam (CA) for Klebsiella pneumoniae carbapenemase-producing Enterobacterales bacteremia (KPC-PEB) in high-risk neutropenic patients. This is a prospective multicenter observational study in high-risk neutropenic patients with multi-drug resistant Enterobacterales bacteremia. They were compared according to the resistance mechanism and definitive treatment provided: KPC-CPE treated with CA (G1), KPC-CPE treated with other antibiotics (G2), and patients with ESBL-producing Enterobacterales bacteremia who received appropriate definitive therapy (G3). Thirty-day mortality was evaluated using a logistic regression model, and survival was analyzed with Kaplan-Meier curves. A total of 238 patients were included: 18 (G1), 52 (G2), and 168 (G3). Klebsiella spp. (60.9%) and Escherichia coli (26.4%) were the Enterobacterales most frequently isolated, and 71% of the bacteremias had a clinical source. The resistance profile between G1 and G2 was colistin 35.3% vs. 36.5%, amikacin 16.7% vs. 40.4%, and tigeclycline 11.1% vs. 19.2%. The antibiotics prescribed in combination with G2 were carbapenems, colistin, amikacin, fosfomycin, tigecycline, and fluoroquinolones. Seven-day clinical response in G1 vs. G2 vs. G3 was 94.4% vs. 42.3% vs. 82.7%, respectively (p < 0.001). Thirty-day overall mortality in G1 vs. G2 vs. G3 was 22.2% vs. 53.8% vs. 11.9%, respectively (p < 0.001), and infection-related mortality was 5.5% vs. 51.9% vs. 7.7% (p < 0.001). The independent risk factors for mortality were Pitt score > 4: OR 3.63, 95% CI, 1.18-11.14 (p = 0.025) and KPC-PEB treated with other antibiotics: OR 8.85, 95% CI, 2.58-30.33 (p = 0.001), while 7-day clinical response was a protective factor for survival: OR 0.02, 95% CI, 0.01-0.08 (p < 0.001). High-risk neutropenic patients with KPC-CPE treated with CA had an outcome similar to those treated for ESBL-producing Enterobacterales, with higher 7-day clinical response and lower overall and infection-related mortality than those treated with other antibiotics. In view of these data, CA may be considered the preferred therapeutic option for KPC-PEB in high-risk neutropenic patients.

Development of a Clinical Score to Stratify the Risk for Carbapenem-Resistant Enterobacterales Bacteremia in Patients with Cancer and Hematopoietic Stem Cell Transplantation.

Identifying the risk factors for carbapenem-resistant Enterobacterales (CRE) bacteremia in cancer and hematopoietic stem cell transplantation (HSCT) patients would allow earlier initiation of an appropriate empirical antibiotic treatment. This is a prospective multicenter observational study in patients from 12 centers in Argentina, who presented with cancer or hematopoietic stem-cell transplant and developed Enterobacterales bacteremia. A multiple logistic regression model identified risk factors for CRE bacteremia, and a score was developed according to the regression coefficient. This was validated by the bootstrap resampling technique. Four hundred and forty-three patients with Enterobacterales bacteremia were included: 59 with CRE and 384 with carbapenem-susceptible Enterobacterales (CSE). The risk factors that were identified and the points assigned to each of them were: ≥10 days of hospitalization until bacteremia: OR 4.03, 95% CI 1.88-8.66 (2 points); previous antibiotics > 7 days: OR 4.65, 95% CI 2.29-9.46 (2 points); current colonization with KPC-carbapenemase-producing Enterobacterales: 33.08, 95% CI 11.74-93.25 (5 points). With a cut-off of 7 points, a sensitivity of 35.59%, specificity of 98.43%, PPV of 77.7%, and NPV of 90.9% were obtained. The overall performance of the score was satisfactory (AUROC of 0.85, 95% CI 0.80-0.91). Finally, the post-test probability of CRE occurrence in patients with none of the risk factors was 1.9%, which would virtually rule out the presence of CRE bacteremia.

[Refractory colitis by Clostridium difficile treated with fecal microbiota transplant]. / Colitis refractaria por Clostridium difficile tratada con trasplante de microbiota fecal.

Clostridium difficile infection is an increasingly recognized cause of diarrhea in inpatients, frequently associated to high mortality. Vancomycin is the treatment of choice for all Clostridium difficile- associated diarrheas, with different degrees of severity. However, some patients develop refractory forms to that treatment and there are no alternative antibiotic schemes recommended for these cases. Fecal microbiota transplantation has been shown to be successful in a series of cases of severe diarrhea associated with this organism. We present a case of refractory C. difficile infection successfully treated with fecal microbiota transplantation.

La diarrea por Clostridium difficile es reconocida de manera creciente en pacientes hospitalizados y se asocia con alta mortalidad. La vancomicina por vía enteral es el tratamiento antibiótico recomendado para las diferentes formas, incluso las más graves. Sin embargo, un grupo pequeño de pacientes desarrolla formas refractarias a ese tratamiento y no existen esquemas antibióticos alternativos recomendados para estos casos. El trasplante de microbiota fecal ha demostrado ser exitoso en una serie de casos de diarrea grave asociada a este microorganismo. Presentamos un caso de diarrea refractaria por C. difficile que fue tratada con éxito con una infusión de microbiota fecal.

Colitis refractaria por Clostridium difficile tratada con trasplante de microbiota fecal / Refractory colitis by Clostridium difficile treated with fecal microbiota transplant

La diarrea por Clostridium difficile es reconocida de manera creciente en pacientes hospitalizados y se asocia con alta mortalidad. La vancomicina por vía enteral es el tratamiento antibiótico recomendado para las diferentes formas, incluso las más graves. Sin embargo, un grupo pequeño de pacientes desarrolla formas refractarias a ese tratamiento y no existen esquemas antibióticos alternativos recomendados para estos casos. El trasplante de microbiota fecal ha demostrado ser exitoso en una serie de casos de diarrea grave asociada a este microorganismo. Presentamos un caso de diarrea refractaria por C. difficile que fue tratada con éxito con una infusión de microbiota fecal.

Clostridium difficile infection is an increasingly recognized cause of diarrhea in inpatients, frequently associated to high mortality. Vancomycin is the treatment of choice for all Clostridium difficile- associated diarrheas, with different degrees of severity. However, some patients develop refractory forms to that treatment and there are no alternative antibiotic schemes recommended for these cases. Fecal microbiota transplantation has been shown to be successful in a series of cases of severe diarrhea associated with this organism. We present a case of refractory C. difficile infection successfully treated with fecal microbiota transplantation.

Staphylococcus aureus meticilino resistente adquirido en la comunidad: una nueva amenaza / Community acquired methicillin-resistant Staphylococcus: A new threat

Objetivos: Conocer la frecuencia de Staphylococcus aureus meticilino resistente adquirido en la comunidad (SAMR-AC) en neumonía adquirida en la comunidad (NAC); examinar sus características clínicas - evolutivas y analizar factores de riesgo. Pacientes, material y métodos: Estudio retrospectivo, descriptivo, observacional, realizado en una unidad de cuidados intensivos respiratorios entre 2006 y 2012. Resultados: Se evaluaron 180 pacientes con NAC con diagnóstico etiológico. Etiologías más frecuentes: Streptococcus pneumoniae (50.5%), Haemophillus influenzae (18.3%) ySAMR-AC (12.2%, 22 casos). La neumonía por SAMR-AC se presentó en individuos jóvenes, mayoritariamente hombres. En el 81.8% de los casos el foco primario fue infección de piel y estructuras relacionadas (IPER), 95.4% presentó criterios clínicos de sepsis, 72.7% tuvo compromiso radiológico bilateral y 45.5% desarrolló derrame pleural. El 40.9% requirió ventilación mecánica y el 45.4% utilizó drogas vasoactivas. El 81.8% de los pacientes no alcanzó criterios de estabilidad clínica al cabo de la primer semana y la mortalidad fue del 36.3%, significativamente superior al resto de los microorganismos (8.8%, p<0,001). Los factores clínicos asociados con mayor riesgo de SAMR-AC fueron la presencia de IPER concomitante, compromiso radiológico bilateral, presencia de criterios clínicos de sepsis, edad inferior a 30 años y requerimiento de drogas vasoactivas. Los factores que se asociaron con mortalidad en NAC fueron la etiología por SAMR-AC y el compromiso radiológico bilateral. Conclusiones: La neumonía por SAMR-AC es una patología emergente, asociada a elevada morbimortalidad. Debe ser considerada en pacientes jóvenes, con presencia concomitante de IPER, compromiso radiológico bilateral, criterios clínicos de sepsis o necesidad de drogas vasoactivas.

Objectives: To know the incidence of Community Acquired Pneumonia (CAP) caused by Methicillin Resistant Sthaphylococcus aureus (MRSA), to examine their clinical and developmental characteristics and to analyze risk factors. Materials and Methods: Retrospective, descriptive and observational study carried out at a Respiratory Intensive Care Unit, between 2006 and 2012. Results: 180 patients with etiologic diagnosis of CAP were evaluated. The most common causes were Streptococcus pneumoniae (50.5%), Haemophillus influenzae (18.3%) and MRSA (12.2%, 22 cases). Community Acquired MRSA (CA-MRSA) pneumonia was present in young people, especially in male. In 81.8% of the cases, skin and related structure infections (SRSI) were the primary focus, 95.4% presented clinical criteria of sepsis, 72.7% had bilateral radiology involvement and 45.5% developed pleural effusion. 40.9% needed mechanical ventilation and 45.4% used vasoactive drugs. Clinical stability at the first week was not reached in 81.8% and mortality rate was 36.6%, significantly higher than for pneumonia caused by other microorganisms (8.8% p<0,001). Clinical factors related with high risk of CA-MRSA pneumonia were the concomitant presence of SRSI, bilateral radiology involvement, clinical criteria of sepsis, age <30 years old and need for vasoactive drugs. Factors related to CAP mortality were CA-MRSA aetiology and bilateral radiology involvement. Conclusions: CA-MRSA pneumonia is an emergent disease with high morbidity and mortality. It must be considered in young patients, with SRSI, bilateral radiology involvement, clinical criteria of sepsis or intake of vasoactive drugs.

Staphylococcus aureus meticilino resistente adquirido en la comunidad: una nueva amenaza / Community acquired methicillin-resistant Staphylococcus: A new threat

Objetivos: Conocer la frecuencia de Staphylococcus aureus meticilino resistente adquirido en la comunidad (SAMR-AC) en neumonía adquirida en la comunidad (NAC); examinar sus características clínicas - evolutivas y analizar factores de riesgo. Pacientes, material y métodos: Estudio retrospectivo, descriptivo, observacional, realizado en una unidad de cuidados intensivos respiratorios entre 2006 y 2012. Resultados: Se evaluaron 180 pacientes con NAC con diagnóstico etiológico. Etiologías más frecuentes: Streptococcus pneumoniae (50.5%), Haemophillus influenzae (18.3%) ySAMR-AC (12.2%, 22 casos). La neumonía por SAMR-AC se presentó en individuos jóvenes, mayoritariamente hombres. En el 81.8% de los casos el foco primario fue infección de piel y estructuras relacionadas (IPER), 95.4% presentó criterios clínicos de sepsis, 72.7% tuvo compromiso radiológico bilateral y 45.5% desarrolló derrame pleural. El 40.9% requirió ventilación mecánica y el 45.4% utilizó drogas vasoactivas. El 81.8% de los pacientes no alcanzó criterios de estabilidad clínica al cabo de la primer semana y la mortalidad fue del 36.3%, significativamente superior al resto de los microorganismos (8.8%, p<0,001). Los factores clínicos asociados con mayor riesgo de SAMR-AC fueron la presencia de IPER concomitante, compromiso radiológico bilateral, presencia de criterios clínicos de sepsis, edad inferior a 30 años y requerimiento de drogas vasoactivas. Los factores que se asociaron con mortalidad en NAC fueron la etiología por SAMR-AC y el compromiso radiológico bilateral. Conclusiones: La neumonía por SAMR-AC es una patología emergente, asociada a elevada morbimortalidad. Debe ser considerada en pacientes jóvenes, con presencia concomitante de IPER, compromiso radiológico bilateral, criterios clínicos de sepsis o necesidad de drogas vasoactivas. (AU)

Objectives: To know the incidence of Community Acquired Pneumonia (CAP) caused by Methicillin Resistant Sthaphylococcus aureus (MRSA), to examine their clinical and developmental characteristics and to analyze risk factors. Materials and Methods: Retrospective, descriptive and observational study carried out at a Respiratory Intensive Care Unit, between 2006 and 2012. Results: 180 patients with etiologic diagnosis of CAP were evaluated. The most common causes were Streptococcus pneumoniae (50.5%), Haemophillus influenzae (18.3%) and MRSA (12.2%, 22 cases). Community Acquired MRSA (CA-MRSA) pneumonia was present in young people, especially in male. In 81.8% of the cases, skin and related structure infections (SRSI) were the primary focus, 95.4% presented clinical criteria of sepsis, 72.7% had bilateral radiology involvement and 45.5% developed pleural effusion. 40.9% needed mechanical ventilation and 45.4% used vasoactive drugs. Clinical stability at the first week was not reached in 81.8% and mortality rate was 36.6%, significantly higher than for pneumonia caused by other microorganisms (8.8% p<0,001). Clinical factors related with high risk of CA-MRSA pneumonia were the concomitant presence of SRSI, bilateral radiology involvement, clinical criteria of sepsis, age <30 years old and need for vasoactive drugs. Factors related to CAP mortality were CA-MRSA aetiology and bilateral radiology involvement. Conclusions: CA-MRSA pneumonia is an emergent disease with high morbidity and mortality. It must be considered in young patients, with SRSI, bilateral radiology involvement, clinical criteria of sepsis or intake of vasoactive drugs. (AU)