Comparative Efficacy of a High-Dose vs Standard-Dose Hepatitis B Revaccination Schedule Among Patients With HIV: A Randomized Clinical Trial.

Importance: Active immunization for hepatitis B virus (HBV) infection is recommended in patients living with HIV. Limited evidence is available about the most appropriate regimen of HBV vaccination among those who have not responded to an initial schedule. Objective: To determine the efficacy of a high-dose schedule compared with a standard dose of HBV vaccination. Design, Setting, and Participants: This double-masked, parallel-group, randomized controlled trial included patients living with HIV at a single outpatient HIV and hepatology clinic in Chile for whom previous HBV vaccination had failed. Patients with hepatitis B surface antibody (anti-HBs) titers less than 10 IU/L after an initial HBV vaccination regimen were included. Consecutive patients were recruited between December 2013 and March 2018. Data were analyzed in June 2018 using intention-to-treat analysis. Intervention: The high-dose HBV vaccination group consisted of 3 doses of 40 µg recombinant hepatitis B vaccine at 0, 1, and 2 months. The standard-dose group received 3 doses 20 µg each at 0, 1, and 2 months. Main Outcomes and Measures: Primary outcome was the serologic response to HBV vaccination (anti-HBs greater than 10 IU/L) 4 to 8 weeks after completion of the schedule. Secondary outcomes were anti-HBs greater than 100 IU/L and seroprotective anti-HBs at 1 year follow up. Results: A total of 107 patients underwent randomization (55 to the standard-dose group, 52 to the high-dose group); 81 (75.7%) were men, and the mean (SD) patient age was 47.0 (13.3) years. Nearly all patients were receiving antiretroviral therapy (105 patients [98%]) and 92 patients (86%) had an undetectable HIV viral load. Mean (SD) CD4 count was 418 (205) cells/mm3. There were no differences in baseline characteristics between groups. Serological response in the high-dose group was found in 36 of 50 patients (72%; 95% CI, 56.9%-82.9%) compared with 28 of 55 patients in the standard-dose group (51%; 95% CI, 37.1%-64.6%) (odds ratio, 2.48; 95% CI, 1.02-6.10; P = .03). Mean (SD) anti-HB levels were 398.0 (433.4) IU/L in the high-dose group and 158.5 (301.4) IU/L in the standard-dose group (P < .001). Of patients with a serological response in the high-dose group, 29 of 36 (80.6%) had anti-HBs titers greater than 100 IU/L compared with 14 of 28 responders (50.0%) in the standard-dose group (P = .02). At 1-year follow-up, 20 of 25 patients (80.0%) with a serological response in the high-dose group had protective anti-HBs vs 9 of 23 patients (39.1%) in the standard-dose group (P = .01). Conclusions and Relevance: The results of this randomized clinical trial suggest that use of a high-dose regimen for HBV revaccination for patients with HIV achieves a higher and longer-lasting serological response as compared with a standard-dose regimen. Trial Registration: ClinicalTrials.gov Identifier: NCT02003703.

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 .).

Presence of anti-HBc is associated to high rates of HBV resolved infection and low threshold for Occult HBV Infection in HIV patients with negative HBsAg in Chile.

HBV-HIV coinfection is prevalent. Frequently, anti-HBc is the only serological marker of HBV, which can be indicative of HBV resolved infection, when found together with anti-HBs reactivity; or present as "isolated anti-HBc," related to HBV occult infection with presence of detectable DNA HBV, more prevalent in HIV-positive individuals. Regional data about this condition are scarce. Anti-HBc rapid test has been used as screening, but its performance has not been described in HIV-positive patients. The aim of this study was determine prevalence of anti-HBc in HIV-positive patients, serological pattern of HBV resolved infection and isolated anti-HBc, evaluating presence of HBV occult infection. Assess anti-HBc rapid test compared to ECLIA. Methods included measurement of anti-HBc and anti-HBs in HIV-positive patients with negative HBsAg. Serum HBV DNA quantification and HBV booster vaccination to "isolated anti-HBc" individuals. Detection of anti-HBc by rapid test and ECLIA. In 192 patients, prevalence of anti-HBc was 42.7% (82/192); associated to male gender, drug use, men-sex-men, positive-VDRL, and longer time HIV diagnosis. 34.4% (66/192) had presence of anti-HBs, mean titers of 637 ui/ml. Isolated anti-HBc in 8.3% (16/192), associated to detectable HIV viral load and no-use of HAART; in them, HBV DNA was undetectable, and 60% responded to HBV vaccination booster. Anti-HBc rapid test showed low sensibility (32.9%) compared to ECLIA. These results show that prevalence of anti-HBc in HIV-positive individuals is high, in most cases accompanied with anti-HBs as HBV resolved infection. Low prevalence of "isolated anti-HBc," with undetectable HBV DNA, and most had anamnestic response to HBV vaccination; suggest low possibility of occult HBV infection. Anti-HBc rapid test cannot be recommended as screening method for anti-HBc.

Caracterización de los pacientes con diarrea asociada a clostridium difficile en el hospital dr. Gustavo Fricke entre los años 2003-2008 / Characterization of patients with clostridium difficile associated diarrhea in hospital dr. Gustavo Fricke between the years 2003-2008

Introducción: la mayoría de las diarreas nosocomiales en la población adulta son producidas por Clostridium diffícile. Suele asociarse con terapia antimocrobiana previa al cuadro clínico, en especial Clindamicina. Objetivo: caracterizar el cuadro de diarrea por C. diffícile, en pacientes hospitalizados en el Hospital Gustavo Fricke (HGF). Material y Método: se consideró el registro de exámenes del Laboratorio de Microbiología del Hospital para la detección de toxina A de C. diffícile desde Junio de 2003 a Marzo de 2008, debiendo excluirse 57 casos de 169 por registro incompleto. Se procedió a revisar fichas, tomando en cuenta 22 variables que se analizaron con el programa estadístico SPSS. Se define caso como aquel en que se detectó la toxina A en una muestra de deposiciones de un paciente con diarrea; resolución al cese de la diarrea a los 5 días de terapia con metronidazol oral en dosis convencionales; fracaso como la persistencia de diarrea luego de 5 días con metronidazol oral; recaída a la reaparición de diarrea con un nuevo examen de toxina A positiva luego de al menos una semana de evolucionar con deposiciones normales. Resultados: del total de 112 casos, 52,6 por ciento eran sexo masculino. El promedio de edad fue de 59,9 años. Un 45 por ciento del total de pacientes era diabético tipo 2 y un 41 por ciento hipertenso. Los diagnósticos de ingreso más frecuentes fueron neumonía adquirida en la comunidad (14,2 por ciento) y pie diabético complicado (12 por ciento). Se analizó el número de casos por servicio en relación a sus egresos durante el período en estudio, siendo el servicio más afectado la Unidad de Cuidados Intensivos con 0,45 por ciento casos por cada 100 egresos. Un 98 por ciento del total de pacientes tenía el antecedente de uso de antibiótico previo al inicio de síntomas, ya sea terapia antimicrobiana asociada o monoterapia. En ambos casos las cefalosporinas fueron los mas involucrados, destacando Ceftriaxona.

Introduction: the majority of nosocomial diarrhea in adults ar caused by Clostridium difficile. Often it is associated with antimicrobial therapy prior to clinical symptoms, especially clindamycin. Objective: to characterize C. difficile associated diarrhea in patients hospitalized in the Hospital Gustavo Fricke (HGF). Patients and Methods: we considered the record of examinations of the Laboratory of Microbiology of the detection of C. difficile toxin A from June 2003 to March 2008, with 57 cases excluded for incomplete record. We reviewed medical records, including 22 variables, analyzed with the statistical program SPSS. Case is defined as one in which the toxin A was detected in a stool sample from a patient with diarrhea, resolution as the cessation of diarrhea within 5 days of therapy with conventional-dose of oral metronidazole; failure as the persistence of diarrhea after 5 days with oral metronidazole; relapse as a recurrence of diarrhea with a new examination of toxin A positive after at least a week to move with normal stools. Results: a total of 112 cases were studied, 52,6 percent were male. The average age was 59.9 years. 45 percent of patients hay Type 2 Diabetes and 41 percent hypertension. The most frequent diagnosis on admission was community-acquired pseumonia (14.2 percent) and complicated diabetic foot (12 percent). We analyzed the number of cases by service in relation to their expenditures during the period under review, the most affected was the Intensive Care Unit with 0.45 cases per 100 discharges; 98 percent patients had a history of antibiotic use prior to onset of symptoms, either alone or associated with antimicrobial therapy. In both cases cepthalosporins were the most involved, including ceftriaxone.

Microbiología y resistencia a antimicrobianos de urocultivos: en el Hospital Dr. Gustavo Fricke / Microbiology and antimicrobial resistance in urinary cultures: at Dr. Gustavo Fricke Hospital

Introducción: La terapia antibiótica, muchas veces empírica, es el eje fundamental del tratamiento de las infecciones del tracto urinario. Esto hace necesario conocer la flora bacteriana local y su patrón de resistencia para optimizar el tratamiento. Objetivo: Determinar frecuencia y resistencia de microorganismos en cultivos urinarios de pacientes adultos ambulatorios y pacientes críticos de nuestro medio hospitalario. Materiales y Método: Se realizó un estudio descriptivo retrospectivo de los urocultivos del año 2007 del Hospital Dr. Gustavo Fricke. Se utilizaron frecuencias, porcentajes, y prueba de Ji2 o Fisher para el análisis de los datos. Resultados: Se obtuvo un total de 11185 urocultivos, resultando 3500 positivos (31,29 por ciento), y de éstos 1247 polimicrobianos (39,06 por ciento). Se obtuvo 830 muestras correspondientes a pacientes ambulatorios, siendo el microorganismo más frecuentemente aislado Escherichia coli (Ec) (72,53 por ciento) seguido por Klebsiella pneumonías (Kp) (5,78 por ciento). Ec presenta una resistencia de 20,43 por ciento a ciprofloxacino, 49,5 por ciento a ampicilina, y 29 por ciento a cotrimoxazol. Se obtuvo 129 urocultivos correspondientes a unidades de pacientes críticos, aislándose más frecuentemente Ec (24,03 por ciento), Kp (20,93 por ciento), Candida albicans (16,28 por ciento) y Pseudomonas aeruginosa (13,95 por ciento). Se encontró una diferencia significativa al comparar las frecuencias de cada microorganismo entre pacientes ambulatorios y críticos (p=0,001), y al comparar los patrones de resistencia de Ec para diferentes antibacterianos entre ambos grupos. Conclusiones: La microbiología se ajusta a lo descrito en la literatura, aunque se observa mayor resistencia por parte de Ec a antimicrobianos de uso común en nuestro medio. Se observan además poblaciones microbiológicas diferentes entre el medio ambulatorio y el de pacientes críticos.

The antibiotic therapy, often empirical, is the fundamental axis in treatment of urinary tract infections. This makes necessary to know the local bacterial flora and its pattern of resistance to optimize the treatment. Aim: To determine the frequency and resistance of microorganisms in urinary cultures of adult ambulatory patients and critical units patients of our hospital. Materials and method: We conducted a descriptive retrospective study of the urinary cultures of 2007 at Dr. Gustavo Fricke Hospital. Frequencies, percentages, and 312 or Fisher test the data analysis. Results: A total of 11185 urinary cultures was obtained, with 3500 positives (31,29 per cent), and of these 1247 polymicrobial (39,06 per cent). There were 830 samples corresponding to ambulatory patients, and the most frequently isolated microorganism was Escherichia coli (Ec) (72,53 per cent) followed by klebsiella pneumoniae (Kp) (5,78 per cent). Ec presents a resistance of 20,43 per cent to ciprofloxacine, 49,5 per cent to ampicillin, and 29 per cent to cotrimoxazole. There were 129 urinary cultures from critical care patients, isolating more frequently Ec (24,03 per cent), Kp (20,93 per cent), Candida albicans (16,28 per cent) and Pseudomonas aeruginosa (13,95 per cent). There was a significant diffence when comparing the frequencies of every microorganism among ambulatory and critical units patients (p=0,001), and when comparing the pattern of drug resistence of Ec for different antibacterial agents between both groups. Conclusions: The microbiology of this sample adjusts to that described in the literature, although higher resistance is observed of Ec to antimicrobial agents of common use in our hospital. Microbiological different populations are observed among the ambulatory and critical units patients.