Effect of Molnupiravir on Biomarkers, Respiratory Interventions, and Medical Services in COVID-19 : A Randomized, Placebo-Controlled Trial.

BACKGROUND: In the MOVe-OUT trial, molnupiravir showed a clinically meaningful reduction in the risk for hospitalization or death in adults with mild to moderate COVID-19 and risk factors for progression to severe disease. OBJECTIVE: To identify other potential clinical benefits of molnupiravir versus placebo. DESIGN: Secondary analysis of the randomized, double-blind, placebo-controlled phase 3 component of MOVe-OUT. (ClinicalTrials.gov: NCT04575597). SETTING: 107 sites globally. PARTICIPANTS: 1433 nonhospitalized adults aged 18 years or older with mild to moderate COVID-19. INTERVENTION: Molnupiravir, 800 mg, or placebo every 12 hours for 5 days. MEASUREMENTS: Changes from baseline in C-reactive protein (CRP) concentration and oxygen saturation (Spo 2), need for respiratory interventions (including invasive mechanical ventilation), and need for medical services in all randomly assigned participants through day 29, and need for respiratory interventions and time to discharge in the subgroup of participants who were hospitalized after randomization. RESULTS: Participants receiving molnupiravir showed faster normalization of CRP and Spo 2, with improvements observed on day 3 of therapy, compared with placebo. Molnupiravir-treated participants had a decreased need for respiratory interventions versus placebo-treated participants (relative risk reduction [RRR], 34.3% [95% CI, 4.3% to 54.9%]), with similar findings in participants who were hospitalized after randomization (RRR, 21.3% [CI, 0.2% to 38.0%]). Hospitalized participants who received molnupiravir were discharged a median of 3 days before those who received placebo. Acute care visits (7.2% vs. 10.6%; RRR, 32.1% [CI, 4.4% to 51.7%]) and COVID-19-related acute care visits (6.6% vs. 10.0%; RRR, 33.8% [CI, 5.6% to 53.6%]) were less frequent in molnupiravir- versus placebo-treated participants. LIMITATIONS: Some analyses were performed post hoc. Longer-term benefits of molnupiravir therapy were not evaluated. Participants were not immunized against SARS-CoV-2. CONCLUSION: The findings suggest there are additional important clinical benefits of molnupiravir beyond reduction in hospitalization or death. PRIMARY FUNDING SOURCE: Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc.

Peritoneal tuberculosis in an immunocompetent patient: A case report.

Introduction: Tuberculosis is endemic in Colombia, the prevalence of its pulmonary form in immunocompetent hosts is high, and peritoneal compromise instead is rare and difficult to diagnose. Case presentation: A 24-year-old female patient living in a rural area presented to the emergency department with constitutional and gastrointestinal symptoms, including bloating, diarrhea, significant weight loss, nocturnal diaphoresis, and gradual onset of ascites with abdominal pain. Diagnostic workup, including paracentesis, a transvaginal ultrasound, and an abdominal CT scan, did not suggest malignancy or portal hypertension. However, diagnostic laparoscopy revealed a miliary pattern comprising the parietal and pelvic peritoneum, uterus, fallopian tubes, and major omentum suggestive of peritoneal tuberculosis. Anti-tuberculosis therapy was initiated with subsequent microbiological confirmation. Conclusion: Abdominal compromise by tuberculosis is a diagnostic challenge, especially in patients with no apparent risk factors. The clinical manifestations and paraclinical data may be unspecific or inconclusive, requiring peritoneal biopsy and empirical treatment before definitive confirmation.

Phase 2/3 Trial of Molnupiravir for Treatment of Covid-19 in Nonhospitalized Adults.

BACKGROUND: Safe and effective oral treatments are needed to improve clinical outcomes for nonhospitalized patients with Covid-19. Molnupiravir is an orally administered, small-molecule ribonucleoside prodrug shown to inhibit replication of severe acute respiratory syndrome coronavirus 2 in vitro and in animal models. METHODS: MOVe-OUT is an ongoing, phase 2/3, randomized, placebo-controlled, double-blind study evaluating the safety, efficacy, and pharmacokinetics of molnupiravir in nonhospitalized adults. In the phase 2 component, participants had mild or moderate, laboratory-confirmed Covid-19 with sign/symptom onset up to (and including) 7 days before randomization. Participants were randomly assigned 1:1:1:1 to receive 200, 400, or 800 mg of molnupiravir or placebo twice daily for 5 days, stratified by time since sign/symptom onset and by being at increased risk for severe illness from Covid-19. The primary efficacy end point was the proportion of participants who were hospitalized and/or died through day 29. RESULTS: The phase 2 component randomly assigned 302 participants to treatment; baseline characteristics were comparable across treatment groups. Molnupiravir had no apparent dose-related effect on adverse events, and no clinically meaningful abnormalities in laboratory test results were observed in relation to dose or treatment. Eleven participants were hospitalized or died through day 29. Of 225 participants in the combined molnupiravir group, 7 (3.1%) were hospitalized or died, compared with 4 of 74 participants (5.4%) in the placebo group. Subgroup analyses suggested lower incidences of hospitalization and/or death in the molnupiravir versus placebo groups in participants older than 60 years of age, those with increased risk for severe illness, those with symptom onset up to (and including) 5 days before randomization, and those with both symptom onset up to (and including) 5 days before randomization and increased risk for severe illness. CONCLUSIONS: These interim study results support further evaluation of molnupiravir as a potential treatment to reduce hospitalizations and/or death in nonhospitalized patients with Covid-19. (Funded by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.; ClinicalTrials.gov number, NCT04575597.)

Dengue Virus Infection in Solid Organ Transplant Recipients: A Case Series and Literature Review.

Dengue fever is the most prevalent arbovirus infection among humans, and tropical regions are hyperendemic for this infection. The number of solid organ transplant recipients is continuously increasing, and there are few data regarding the clinical course and outcomes of dengue infection among this population. We report on a retrospective case series of solid organ transplant recipients with dengue virus infection from 2001 to 2018 at Fundación Valle del Lili in Cali, Colombia. A total of 20 patients were included. The median age was 50.5 years (interquartile range [IQR] = 31-63.5 years) and 65% were female. Regarding the clinical course, 75% of patients had at least one warning sign, 45% were managed in the intensive care unit, and 30% had severe dengue. The median of time from transplant and dengue infection was 27.6 months (IQR = 3.82-59.12 months), and three patients had the disease in the first month after the transplant. All patients were discharged, and none of them had graft rejection. Dengue is an endemic disease in our region and represents a threat among solid organ transplantation recipients. All patients had a full recovery after the infection, suggesting that timely and effective management of patients and the access to high-complexity services could prevent fatal cases.

Emerging carbapenem-resistant Aeromonas spp. infections in Cali, Colombia.

INTRODUCTION: Aeromonas species are renowned enteric pathogens with virulence determinants linked to human diseases, such as gastroenteritis, skin, soft-tissue and muscle infections, and septicemia. A recent concern of resistance in this organism has emerged, especially the presence carbapenemases. Herein we describe a case series of emerging carbapenem-resistant Aeromonas species infection in our hospital in Cali, Colombia. MATERIALS AND METHODS: Cases from 2012 to 2018 are reported. Clinical data was abstracted from the clinical charts and laboratory information. Phenotypic detection of resistance was identified using the VITEK®2 system (BioMérieux) and broth microdilution MicroScan WalkAway plus System (Beckman Coulter). CARBA NP-test and multiplex qPCR assay was performed in 11 isolates to identify genes encoding carbapenemases (blaKPC, blaVIM, blaIMP and blaNDM). RESULTS: 21 cases of Aeromonas infection in hospitalized patients with phenotypic resistance to carbapenems were studied. The median age was 50 years, 55% (12/21) were male, and 67% (14/21) were healthcare-associated infections (HAI). Aeromonas hydrophila was the most common species (19/21). Forty-three percent (9/21) of the patients were immunocompromised. The mortality was 33% (7/21), and in patients with bacteremia was 100%. Most patients received empirical treatment with meropenem and failed to this treatment. PCR amplification tests showed negative results for the carbapenemases analyzed. CONCLUSION: Emerging phenotypic carbapenem-resistant infection has been seen in our hospital, most as HAI. High mortality was found, especially in immunocompromised patients and in those who failled empirical treatment with carbapenems. As the main carbapenemases tested were negative, carbapenem-resistant could be attributed to an intrinsic metallo-ß-lactamase, CphA encoded by the cphA gene, possible hyperproduction of ampC ß-lactamase and/or porins expression.

Infección por Aspergillus flavus y Rhizopus oryzae complex en paciente con diabetes mellitus / Infection due to Aspergillus flavus and Rhizopus oryzae complex in a patient with diabetes mellitus

La sinusitis micótica es una condición patológica que puede presentarse en pacientes con diabetes mellitus y estar asociada a una crisis hiperglucémica. Es una entidad agresiva con complicaciones locales que incluyen afectación de la órbita y el sistema nervioso central, y compromiso vascular. A pesar del tratamiento quirúrgico y antimicótico, la mortalidad es de hasta el 75 %. Se describe el caso de una paciente con diagnóstico de cetoacidosis diabética y signos de oftalmoplejía unilateral que llevaron al estudio con resonancia magnética del sistema nervioso central; se encontraron signos de sinusitis, meningitis y cerebritis. Los estudios microbiológicos iniciales fueron negativos, y los biomarcadores galactomanano sérico y el antígeno de Cryptococcus también fueron negativos. Tras el manejo quirúrgico, se llegó a la identificación de Aspergillus flavus y Rhizopus spp. en el tejido de los senos paranasales. La paciente recibió tratamiento con posaconazol y, tras dos meses de seguimiento, había presentado mejoría clínica. La infección fúngica dual y la infección por A. flavus son entidades poco frecuentes y de relevancia clínica, sin casos presentados previamente en nuestro país por lo que este corresponde a un caso de interés clínico.

Fungal sinusitis is a pathology that can occur in patients with diabetes mellitus and be associated with a hyperglycemic crisis. It is an aggressive entity with local complications that include involvement of the orbit or the central nervous system, and vascular involvement. Despite surgical and antifungal treatment, mortality raises up to 75%. We report the case of a female patient with a diagnosis of diabetic ketoacidosis and signs of unilateral ophthalmoplegia, which led to the study with magnetic resonance imaging of the central nervous system, finding signs of sinusitis, meningitis, and cerebritis. Initial microbiological studies were negative, and biomarkers such as serum galactomannan and Cryptococcus antigen were also negative. After surgical management and the identification of Aspergillus flavus and Rhizopus spp. in sinus tissue, the patient received treatment with posaconazole and after two months of follow-up she presented clinical improvement. Dual fungal infection and infection by A. flavus are uncommon and clinically relevant entities, with no cases previously reported in our country, therefore this corresponds to a case of clinical interest.

Infección invasiva por Candida spp. En pacientes inmunocomprometidos: Descripción de curso clínico experiencia diagnóstica, manejo y seguimiento en centro de alta complejidad / Invasive infection by Candida spp. in immunocompromised patients: A description of clinical, diagnostics, therapeutic and follow up experience in high complexity healthcare center

Introducción: Candida spp. Es la principal causa de fungemia, cuya incidencia ha aumentado en los últimos años. Existen datos locales insuficientes sobre este tipo de infecciones. Materiales y métodos: Este fue un estudio observacional retrospectivo de 44 pacientes diagnosticados con candidiasis invasiva hospitalizados en la Fundación Valle del Lili, el cual es un centro de cuarto nivel afiliado a la Universidad Icesi en el Suroccidente Colombiano, entre los años 2012 a 2017. Resultados: Se identificaron 44 pacientes con candidiasis invasiva, 27 de ellos mujeres (61%). La mediana de edad fue de 56 años (36 - 70). Más del 50% tenían una enfermedad crónica subyacente, uso de antibióticos (84%), catéter venoso central (80%), ventilación mecánica (68%) y nutrición enteral (66%) El 80% requirió manejo en unidad de cuidados intensivos (UCI) donde debutaron con sepsis (68%) y falla respiratoria (61%). En el 90% de los casos se aisló alguna especie de Candida spp. A partir de hemocultivo y sólo al 22% se le realizó prueba de sensibilidad. El tratamiento de elección fue con fluconazol (80%), asociado a caspofungina (70%). La tasa de mortalidad fue del 49%, con una mediana de 33 (22-49,5) días desde el ingreso hasta el fallecimiento. C. albicans fue el principal microorganismo aislado. La resistencia a azoles en especies no albicans existe en nuestro medio. Conclusión: La candidiasis se presenta como candidemia asociada a infección bacteriana concomitante, que cobra mayor importancia en el contexto del paciente inmunosuprimido asociado a elevadas tasas de mortalidad.

Introduction: Candida spp. is the main cause of fungemia, whose incidence has increased in recent years. There are insufficient local data about this pathology. Materials and methods: This was an observational, retrospective chart review of 44 patients diagnosed with invasive candida who were hospitalized at Fundación Valle del Lili, which is a fourth level center affiliated to Icesi university between 2012 and 2017. Results: We identified 44 patients with invasive candidiasis, 27 of them women (61%). The median age was 56 years (36 - 70). More than 50% had an underlying chronic disease, use of antibiotics (84%), central venous catheter (80%), mechanical ventilation (68%) and enteral nutrition (66%). 80% required management in an intensive care unit. Sepsis (68%) and respiratory failure (61%) were the most common clinical presentation. Almost 90% of the cases, had positive blood cultures, but only 22% presented susceptibility tests. The treatment was mainly fluconazole (80%), associated with caspofungin (70%). The mortality rate was 49%, median of 33 (22-49.5) days from admission to death. Candida albicans was the main isolated organism. Azole resistance in non-albicans species was observed. Conclusion: Candidiasis presents as bacterial infection associated candidemia, which becomes more important in the context of the immunosuppressed patient with high mortality rates.

Una aproximación a la tuberculosis resistente a isoniazida: ¿un problema subestimado en Colombia? / An appraisal of the isoniazid resistant tuberculosis in Colombia: a underestimated problem in Colombia?

Objetivo: Describir las características clínicas y desenlaces al tratamiento de los pacientes con tuberculosis resistente a isoniazida (Hr-TB) en una institución del suroccidente colombiano. Materiales y métodos: Se realizó un estudio observacional retrospectivo. Se incluyeron pacientes con confirmación diagnóstica, aislamiento microbiológico, pruebas de susceptibilidad a fármacos y evidencia de Hr-TB. Resultados: Se incluyeron 32 pacientes con Hr-TB entre 2006-2018 que corresponden al 6% (32/528) de resistencia del total de casos. El 78% (n=25) fueron casos nuevos, resistencia primaria, y el 22% (n=7) previamente tratados, resistencia adquirida. La comorbilidad más frecuente fue infección por VIH (n=9). El patrón de Hr-TB mostró en 23 (72%) casos con alto nivel, 4 (12%) de bajo nivel y 5 (16%) con bajo y alto nivel. El análisis de resultados al tratamiento se realizó a 22 pacientes, presentando el 50% cura, el 41% tratamiento completo y 9% muerte relacionada con la tuberculosis. Conclusiones: La Hr-TB predomina en los casos nuevos, lo que supone un obstáculo al tratamiento donde no se realizan las pruebas de susceptibilidad de forma rutinaria.

Objective: To describe the clinical characteristics and outcomes to the treatment of patients with isoniazid-resistant tuberculosis (Hr-TB) in an institution in southwest Colombia. Materials and methods: A retrospective observational study was conducted. Patients with diagnostic confirmation, microbiological isolation, drug susceptibility tests, and evidence of Hr-TB were included. Results: Thirty-two patients with Hr-TB were included between 2006-2018, corresponding to 6% (32/528) of resistance in total cases. 78% were new cases, primary resistance, and 22% previously treated, acquired resistance. The most frequent comorbidity was HIV infection (n = 9). The pattern of Hr-TB showed in 23 (72%) cases with high level, 4 (12%) of low level and 5 (16%) with low and high level. The analysis of treatment results was performed on 22 patients, presenting 50% cure, 41% completed treatment, and 9% death related to tuberculosis. Conclusions: Hr-TB predominates in new cases, which is an obstacle to treatment where susceptibility tests are not performed routinely.

Curso clínico de pacientes de trasplante autógeno de médula ósea portadores del virus linfotrópico humano / Clinical evolution of carriers of human T-lymphotropic virus 1 after autologous hematopoietic stem cell transplantation

La infección por virus linfotrópico humano 1 es frecuente en la costa pacífica colombiana y se ha relacionado con leucemia/linfoma de células T del adulto y mielopatía en una proporción baja de los seropositivos. En pacientes con trasplante de órganos sólidos pareciera que estas patologías se desarrollan más rápidamente que en los otros escenarios pero se desconoce el curso de la infección por virus linfotrópico humano 1 en trasplante de médula ósea por lo cual describimos 3 casos de pacientes seropositivos y linfoma que fueron llevados a trasplante autógeno. Uno de ellos tuvo recaída de su patología hematológica y falleció a consecuencia de la misma, otra paciente presentó un cuadro compatible con mielopatía asociada al virus linfotrópico humano 1 y la última, una enfermedad injerto contra hospedero. En las personas seropositivas y que necesitan un trasplante de células hematopoyéticas se requiere una búsqueda activa de este virus para hacer seguimientos y evaluar su impacto real en los desenlaces y saber si el curso de la infección podría cambiar con el régimen condicionante del trasplante.

Human T-lymphotropic virus 1 infection is common in Colombia´s Pacific coast and has been linked to adult T-cell leukemia/lymphoma and human T-lymphotropic virus 1-associated myelopathy in a low percentage of cases. In patients with solid organ transplantation, these diseases occur more quickly than in other scenarios but in bone marrow transplantation the true impact is unknown. We describe 3 seropositive patients with lymphoma who underwent autologous stem cell transplantation; in one case there was relapse of the hematologic malignancy and death occurred as a result. Another patient had symptoms compatible with human T-lymphotropic virus 1-associated myelopathy and the last patient had a graft vs. host disease. In seropositive people who need hematopoietic cell transplantation, an active search for this virus is required to be able to follow and assess the virus´s impact on outcomes, as well as to assess whether the evolution could change according to the transplant conditioning regimen.