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.

[Severe Staphylococcus aureus infections: clinical characteristics, antibiotic susceptibility and use of antimicrobials. Case series]. / Infecciones graves por Staphylococcus aureus: características clínicas, sensibilidad antibiótica y uso de antimicrobianos. Serie de casos.

Infectious due to methicillin-resistant community acquired Staphylococcus aureus is a public health problem of varying magnitude in different geographical areas of the world, representing a major burden on health systems. The debate on the initial empiric antibiotic therapy remains open. We present a case series of hospitalized patients with severe Staphylococcus aureus infections admitted to the pediatric intermediate care unit of Hospital El Cruce. Between May 2008 and December 2010, 43 patients were admitted. Sixty nine percent of isolated Staphylococcus aureus were methicillin-resistant. Although the difference was not statistically significant, methicillin-resistant Staphylococcus aureus infections required more days of hospitalization in critical care unit and developed more secondary sites of infection. Vancomycin, rifampicin and clindamycin were the most commonly prescribed antibiotics. There was a high resistance of Staphylococcus aureus to p-lactams in the series.

Infecciones graves por Staphylococcus aureus: características clínicas, sensibilidad antibiótica y uso de antimicrobianos. Serie de casos / Severe Staphylococcus aureus infections: clinical characteristics, antibiotic susceptibility and use of antimicrobials. Case series

La aparición de infecciones por Staphylococcus aureus (SA) meticilino-resistente (MR) de la comunidad es un problema de salud pública de variable magnitud en diferentes áreas geográficas del mundo. El debate acerca del tratamiento antibiótico empírico inicial permanece abierto. Nuestro objetivo es presentar una serie de pacientes hospitalizados con infecciones graves por Staphyloccocus aureus en la Unidad de Cuidados Intermedios Pediátricos del Hospital El Cruce. Entre mayo de 2008 y diciembre de 2010, se internaron 43 pacientes. El 69,8% de los SA aislados fueron MR. Aunque la diferencia no fue estadísticamente significativa, las infecciones por SAMR requirieron mayor cantidad de días de internación en terapia intensiva y desarrollaron más focos secundarios de infección. Vancomicina, rifampicina y clindamicina fueron los antibióticos más comúnmente prescritos. Existió una alta resistencia de los SA a los ß-lactámicos en la serie estudiada

Infectious due to methicillin-resistant community acquired Staphylococcus aureus is a public health problem of varying magnitude in different geographical areas of the world, representing a major burden on health systems. The debate on the initial empiric antibiotic therapy remains open. We present a case series of hospitalized patients with severe Staphylococcus aureus infections admitted to the pediatric intermediate care unit of Hospital El Cruce. Between May 2008 and December 2010, 43 patients were admitted. Sixty nine percent of isolated Staphylococcus aureus were methicillin-resistant. Although the difference was not statistically significant, methicillin-resistant Staphylococcus aureus infections required more days of hospitalization in critical care unit and developed more secondary sites of infection. Vancomycin, rifampicin and clindamycin were the most commonly prescribed antibiotics. There was a high resistance of Staphylococcus aureus to p-lactams in the series.