Ceftarolina como tratamiento de rescate para la bacteriemia complicada por Staphylococcus aureus sensible a la meticilina

Infections caused by methicillin-susceptible Staphylococcus aureus (MSSA) are still associated with significant morbidity and mortality. Treatment failures of cefazolin (CFZ) have been reported and probably related to the inoculum effect. New treatments for severe MSSA infections are needed and ceftaroline fosamil (CPT) could be an option. Our aim was to describe the clinical characteristics of five patients with complicated MSSA bacteremia failing CFZ and successfully treated with CPT. We performed a retrospective chart review in a Hospital in Buenos Aires, Argentina; in a 12-month period, five patients (24%) of 21 with MSSA bacteremia experienced CFZ failure and were salvaged with CPT. The median time of CFZ therapy was 10 days before changing to CPT; four patients had evidence of metastatic spread and 2 had endocarditis. All patients experienced microbiological and clinical cure with CPT, which was used as monotherapy in 4 and in combination with daptomycin in another. One patient discontinued CPT due to neutropenia on day 23 of treatment. In patients with MSSA BSI failing current therapy, CPT could be a good therapeutic option.Las infecciones causadas por Staphylococcus aureus sensible a la meticilina (SASM) todavía se asocian con una morbilidad y mortalidad significativas. Se han informado fallas en el tratamiento de cefazolina (CFZ) probablemente relacionadas con efecto inóculo. Nuevos tratamientos son necesarios para estas infecciones y ceftarolina fosamil (CPT) podría ser una opción. Nuestro objetivo fue describir las características clínicas de cinco pacientes con bacteriemia por SASM complicada con falla a CFZ y que fueron exitosamente tratados con CPT. Realizamos una revisión retrospectiva de historias clínicas en un hospital de Buenos Aires, Argentina; en un período de 12 meses, cinco pacientes (24%) de 21 con bacteriemia por SASM experimentaron falla a CFZ y fueron tratados con CPT. La mediana de tiempo de la terapia con CFZ fue de 10 días antes de cambiar a CPT; cuatro pacientes presentaban evidencia de diseminación metastásica y 2 tenían endocarditis. Todos los pacientes experimentaron curación microbiológica y clínica con CPT, que se utilizó como monoterapia en 4 y en combinación con daptomicina en otro. Un paciente interrumpió CPT debido a neutropenia el día 23 de tratamiento. En enfermos con infecciones graves por SASM que fallan en la terapia actual, CPT podría ser una buena opción terapéutica.Fil: Obed, Mora N.. Instituto Medico Platense.; ArgentinaFil: Toresani, Ines. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas.; ArgentinaFil: Mykietiuk, Analía. Instituto Medico Platense.; ArgentinaFil: Nannini, Esteban. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Inmunología Clinica y Experimental de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Médicas. Instituto de Inmunología Clinica y Experimental de Rosario; Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Médicas. Escuela de Ciencias Médicas; Argentina. Sanatorio Británico; Argentin

Ceftarolina como tratamiento de rescate para la bacteriemia complicada por Staphylococcus aureus sensible a la meticilina

Infections caused by methicillin-susceptible Staphylococcus aureus (MSSA) are still associated with significant morbidity and mortality. Treatment failures of cefazolin (CFZ) have been reported and probably related to the inoculum effect. New treatments for severe MSSA infections are needed and ceftaroline fosamil (CPT) could be an option. Our aim was to describe the clinical characteristics of five patients with complicated MSSA bacteremia failing CFZ and successfully treated with CPT. We performed a retrospective chart review in a Hospital in Buenos Aires, Argentina; in a 12-month period, five patients (24%) of 21 with MSSA bacteremia experienced CFZ failure and were salvaged with CPT. The median time of CFZ therapy was 10 days before changing to CPT; four patients had evidence of metastatic spread and 2 had endocarditis. All patients experienced microbiological and clinical cure with CPT, which was used as monotherapy in 4 and in combination with daptomycin in another. One patient discontinued CPT due to neutropenia on day 23 of treatment. In patients with MSSA BSI failing current therapy, CPT could be a good therapeutic option.Las infecciones causadas por Staphylococcus aureus sensible a la meticilina (SASM) todavía se asocian con una morbilidad y mortalidad significativas. Se han informado fallas en el tratamiento de cefazolina (CFZ) probablemente relacionadas con efecto inóculo. Nuevos tratamientos son necesarios para estas infecciones y ceftarolina fosamil (CPT) podría ser una opción. Nuestro objetivo fue describir las características clínicas de cinco pacientes con bacteriemia por SASM complicada con falla a CFZ y que fueron exitosamente tratados con CPT. Realizamos una revisión retrospectiva de historias clínicas en un hospital de Buenos Aires, Argentina; en un período de 12 meses, cinco pacientes (24%) de 21 con bacteriemia por SASM experimentaron falla a CFZ y fueron tratados con CPT. La mediana de tiempo de la terapia con CFZ fue de 10 días antes de cambiar a CPT; cuatro pacientes presentaban evidencia de diseminación metastásica y 2 tenían endocarditis. Todos los pacientes experimentaron curación microbiológica y clínica con CPT, que se utilizó como monoterapia en 4 y en combinación con daptomicina en otro. Un paciente interrumpió CPT debido a neutropenia el día 23 de tratamiento. En enfermos con infecciones graves por SASM que fallan en la terapia actual, CPT podría ser una buena opción terapéutica.Fil: Obed, Mora N.. Instituto Medico Platense.; ArgentinaFil: Toresani, Ines. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas.; ArgentinaFil: Mykietiuk, Analía. Instituto Medico Platense.; ArgentinaFil: Nannini, Esteban. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Inmunología Clinica y Experimental de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Médicas. Instituto de Inmunología Clinica y Experimental de Rosario; Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Médicas. Escuela de Ciencias Médicas; Argentina. Sanatorio Británico; Argentin

Arenas ferrotitaníferas y circoníferas del litoral de la provincia de Buenos Aires

Las acumulaciones de hierro, titanio y circón, de origen detrítico, conocidas desde hace décadas, se encuentran ubicadas en el sector costero sudoriental de la provincia de Buenos Aires. En la zona de la bahía San Blas, partido de Carmen de Patagones, es donde históricamente se han realizado estudios, debido a que es ahí donde se presentan las mayores concentraciones de minerales opacos del litoral bonaerense. Estas acumulaciones ferrotitaníferas (circoníferas) se desarrollan, en el área mencionada, a lo largo de 30 km del área costera, tanto en las arenas de playa como en los principales cordones de médanos. Cabe destacar la presencia de médanos ferrotitaníferos y circoníferos en otros parajes costeros de la provincia de Buenos Aires, tales como los de Necochea, Miramar y Claromecó.Instituto de Recursos MineralesConsejo Nacional de Investigaciones Científicas y Técnica

Effect of statin use on outcomes of adults with candidemia

Background: Statins have immunomodulatory properties and hinder Candida growth. However, it is unknown whether they may improve prognosis in patients with candidemia. We sought to determine the effect of prior statin use on the clinical outcomes of patients suffering candidemia. Methods and Findings: Multicenter cohort study of hospitalized adults with candidemia between 2005 and 2011 in six hospitals in Spain, Brazil and Argentina. Of 326 candidemias, 44 (13.5%) occurred in statin users and 282 (86.5%) in statin non-users. The median value of APACHE II at candidemia diagnosis was similar between groups (18 vs. 16; p=.36). Candida albicans was the most commonly isolated species, followed by C. parapsilosis, C. tropicalis, C. glabrata, and C. krusei. There were no differences regarding appropriate empirical antifungal treatment. Statin users had a lower early (5 d) case-fatality rate than non-users (4.5 vs. 17%; p=.031). This effect was not observed with other cardiovascular drugs (aspirin, beta blockers and ACE inhibitors). Independent factor related to early case-fatality rate was APACHE II score (AOR, 1.08; 95% CI, 1.03-1.14; p=.002). An appropriate empirical antifungal therapy (AOR, 0.11; 95% CI, 0.04-0.26; p=<.001) and prior statin use were independently associated with lower early case-fatality (AOR, 0.17; 95% CI, 0.03-0.93; p=.041). Fourteen days (14d) and overall (30d) case-fatality rates were similar between groups (27% vs. 29%; p=0.77 and 40% vs. 44%; p=.66). Conclusions: The use of statins might have a beneficial effect on outcomes of patients with candidemia. This hypothesis deserves further evaluation in randomized trials

Understanding the treatment benefit of hyperimmune anti-influenza intravenous immunoglobulin (Flu-IVIG) for severe human influenza

Background: Antibody-based therapies for respiratory viruses are of increasing importance. The INSIGHT 006 trial administered anti-influenza hyperimmune intravenous immunoglobulin (Flu-IVIG) to patients hospitalized with influenza. Flu-IVIG treatment improved outcomes in patients with influenza B but showed no benefit for influenza A. Methods: To probe potential mechanisms of Flu-IVIG utility, sera collected from patients hospitalized with influenza A or B viruses (IAV or IBV) were analyzed for antibody isotype/subclass and Fcγ receptor (FcγR) binding by ELISA, bead-based multiplex, and NK cell activation assays. Results: Influenza-specific FcγR-binding antibodies were elevated in Flu-IVIG–infused IBV- and IAV-infected patients. In IBV-infected participants (n = 62), increased IgG3 and FcγR binding were associated with more favorable outcomes. Flu-IVIG therapy also improved the odds of a more favorable outcome in patients with low levels of anti-IBV Fc-functional antibody. Higher FcγR-binding antibody was associated with less favorable outcomes in IAV-infected patients (n = 50), and Flu-IVIG worsened the odds of a favorable outcome in participants with low levels of anti-IAV Fc-functional antibody. Conclusion: These detailed serological analyses provide insights into antibody features and mechanisms required for a successful humoral response against influenza, suggesting that IBV-specific, but not IAV-specific, antibodies with Fc-mediated functions may assist in improving influenza outcome. This work will inform development of improved influenza immunotherapies

Predictors of inhospital mortality and re-hospitalization in older adults with community-acquired pneumonia: a prospective cohort study

<p>Abstract</p> <p>Background</p> <p>A better understanding of potentially modifiable predictors of in-hospital mortality and re-admission to the hospital following discharge may help to improve management of community-acquired pneumonia in older adults. We aimed to assess the associations of potentially modifiable factors with mortality and re-hospitalization in older adults hospitalized with community-acquired pneumonia.</p> <p>Methods</p> <p>A prospective cohort study was conducted from July 2003 to April 2005 in two Canadian cities. Patients aged 65 years or older hospitalized for community-acquired pneumonia were followed up for up to 30 days from initial hospitalization for mortality and these patients who were discharged alive within 30 days of initial hospitalization were followed up to 90 days of initial hospitalization for re-hospitalization. Separate logistic regression analyses were performed identify the predictors of mortality and re-hospitalization.</p> <p>Results</p> <p>Of 717 enrolled patients hospitalized for community-acquired pneumonia, 49 (6.8%) died within 30 days of hospital admission. Among these patients, 526 were discharged alive within 30 days of hospitalization of whom 58 (11.2%) were re-hospitalized within 90 days of initial hospitalization. History of hip fracture (odds ratio (OR) = 4.00, 95% confidence interval (CI) = (1.46, 10.96), P = .007), chronic obstructive pulmonary disease (OR = 2.31, 95% CI = (1.18, 4.50), P = .014), cerebrovascular disease (OR = 2.11, 95% CI = (1.03, 4.31), P = .040) were associated with mortality. Male sex (OR = 2.35, 95% CI = (1.13, 4.85), P = .022) was associated with re-hospitalization while vitamin E supplementation was protective (OR = 0.37 (0.16, 0.90), P = .028). Lower socioeconomic status, prior influenza and pneumococcal vaccinations, appropriate antibiotic prescription upon admission, and lower nutrition risk were not significantly associated with mortality or re-hospitalization.</p> <p>Conclusion</p> <p>Chronic comorbidities appear to be the most important predictors of death and re-hospitalization in older adults hospitalized with community-acquired pneumonia while vitamin E supplementation was protective.</p

Abatacept, Cenicriviroc, or Infliximab for Treatment of Adults Hospitalized With COVID-19 Pneumonia: A Randomized Clinical Trial

IMPORTANCE: Immune dysregulation contributes to poorer outcomes in COVID-19. OBJECTIVE: To investigate whether abatacept, cenicriviroc, or infliximab provides benefit when added to standard care for COVID-19 pneumonia. DESIGN, SETTING, AND PARTICIPANTS: Randomized, double-masked, placebo-controlled clinical trial using a master protocol to investigate immunomodulators added to standard care for treatment of participants hospitalized with COVID-19 pneumonia. The results of 3 substudies are reported from 95 hospitals at 85 clinical research sites in the US and Latin America. Hospitalized patients 18 years or older with confirmed SARS-CoV-2 infection within 14 days and evidence of pulmonary involvement underwent randomization between October 2020 and December 2021. INTERVENTIONS: Single infusion of abatacept (10 mg/kg; maximum dose, 1000 mg) or infliximab (5 mg/kg) or a 28-day oral course of cenicriviroc (300-mg loading dose followed by 150 mg twice per day). MAIN OUTCOMES AND MEASURES: The primary outcome was time to recovery by day 28 evaluated using an 8-point ordinal scale (higher scores indicate better health). Recovery was defined as the first day the participant scored at least 6 on the ordinal scale. RESULTS: Of the 1971 participants randomized across the 3 substudies, the mean (SD) age was 54.8 (14.6) years and 1218 (61.8%) were men. The primary end point of time to recovery from COVID-19 pneumonia was not significantly different for abatacept (recovery rate ratio [RRR], 1.12 [95% CI, 0.98-1.28]; P = .09), cenicriviroc (RRR, 1.01 [95% CI, 0.86-1.18]; P = .94), or infliximab (RRR, 1.12 [95% CI, 0.99-1.28]; P = .08) compared with placebo. All-cause 28-day mortality was 11.0% for abatacept vs 15.1% for placebo (odds ratio [OR], 0.62 [95% CI, 0.41-0.94]), 13.8% for cenicriviroc vs 11.9% for placebo (OR, 1.18 [95% CI 0.72-1.94]), and 10.1% for infliximab vs 14.5% for placebo (OR, 0.59 [95% CI, 0.39-0.90]). Safety outcomes were comparable between active treatment and placebo, including secondary infections, in all 3 substudies. CONCLUSIONS AND RELEVANCE: Time to recovery from COVID-19 pneumonia among hospitalized participants was not significantly different for abatacept, cenicriviroc, or infliximab vs placebo. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04593940

Bezlotoxumab for Prevention of Recurrent Clostridium difficile Infection

BACKGROUND Clostridium difficile is the most common cause of infectious diarrhea in hospitalized patients. Recurrences are common after antibiotic therapy. Actoxumab and bezlotoxumab are human monoclonal antibodies against C. difficile toxins A and B, respectively. METHODS We conducted two double-blind, randomized, placebo-controlled, phase 3 trials, MODIFY I and MODIFY II, involving 2655 adults receiving oral standard-of-care antibiotics for primary or recurrent C. difficile infection. Participants received an infusion of bezlotoxumab (10 mg per kilogram of body weight), actoxumab plus bezlotoxumab (10 mg per kilogram each), or placebo; actoxumab alone (10 mg per kilogram) was given in MODIFY I but discontinued after a planned interim analysis. The primary end point was recurrent infection (new episode after initial clinical cure) within 12 weeks after infusion in the modified intention-to-treat population. RESULTS In both trials, the rate of recurrent C. difficile infection was significantly lower with bezlotoxumab alone than with placebo (MODIFY I: 17% [67 of 386] vs. 28% [109 of 395]; adjusted difference, −10.1 percentage points; 95% confidence interval [CI], −15.9 to −4.3; P<0.001; MODIFY II: 16% [62 of 395] vs. 26% [97 of 378]; adjusted difference, −9.9 percentage points; 95% CI, −15.5 to −4.3; P<0.001) and was significantly lower with actoxumab plus bezlotoxumab than with placebo (MODIFY I: 16% [61 of 383] vs. 28% [109 of 395]; adjusted difference, −11.6 percentage points; 95% CI, −17.4 to −5.9; P<0.001; MODIFY II: 15% [58 of 390] vs. 26% [97 of 378]; adjusted difference, −10.7 percentage points; 95% CI, −16.4 to −5.1; P<0.001). In prespecified subgroup analyses (combined data set), rates of recurrent infection were lower in both groups that received bezlotoxumab than in the placebo group in subpopulations at high risk for recurrent infection or for an adverse outcome. The rates of initial clinical cure were 80% with bezlotoxumab alone, 73% with actoxumab plus bezlotoxumab, and 80% with placebo; the rates of sustained cure (initial clinical cure without recurrent infection in 12 weeks) were 64%, 58%, and 54%, respectively. The rates of adverse events were similar among these groups; the most common events were diarrhea and nausea. CONCLUSIONS Among participants receiving antibiotic treatment for primary or recurrent C. difficile infection, bezlotoxumab was associated with a substantially lower rate of recurrent infection than placebo and had a safety profile similar to that of placebo. The addition of actoxumab did not improve efficacy. (Funded by Merck; MODIFY I and MODIFY II ClinicalTrials.gov numbers, NCT01241552 and NCT01513239.