Monica Maria Gomes da Silva

BACKGROUND: New treatments are needed to reduce the risk of progression of coronavirus disease 2019 (Covid-19). Molnupiravir is an oral, small-molecule antiviral prodrug that is active against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: We conducted a phase 3, double-blind, randomized, placebo-controlled trial to evaluate the efficacy and safety of treatment with molnupiravir started within 5 days after the onset of signs or symptoms in nonhospitalized, unvaccinated adults with mild-to-moderate, laboratory-confirmed Covid-19 and at least one risk factor for severe Covid-19 illness. Participants in the trial were randomly assigned to receive 800 mg of molnupiravir or placebo twice daily for 5 days. The primary efficacy end point was the incidence hospitalization or death at day 29; the incidence of adverse events was the primary safety end point. A planned interim analysis was performed when 50% of 1550 participants (target enrollment) had been followed through day 29. RESULTS: A total of 1433 participants underwent randomization; 716 were assigned to receive molnupiravir and 717 to receive placebo. With the exception of an imbalance in sex, baseline characteristics were similar in the two groups. The superiority of molnupiravir was demonstrated at the interim analysis; the risk of hospitalization for any cause or death through day 29 was lower with molnupiravir (28 of 385 participants [7.3%]) than with placebo (53 of 377 [14.1%]) (difference, -6.8 percentage points; 95% confidence interval [CI], -11.3 to -2.4; P = 0.001). In the analysis of all participants who had undergone randomization, the percentage of participants who were hospitalized or died through day 29 was lower in the molnupiravir group than in the placebo group (6.8% [48 of 709] vs. 9.7% [68 of 699]; difference, -3.0 percentage points; 95% CI, -5.9 to -0.1). Results of subgroup analyses were largely consistent with these overall results; in some subgroups, such as patients with evidence of previous SARS-CoV-2 infection, those with low baseline viral load, and those with diabetes, the point estimate for the difference favored placebo. One death was reported in the molnupiravir group and 9 were reported in the placebo group through day 29. Adverse events were reported in 216 of 710 participants (30.4%) in the molnupiravir group and 231 of 701 (33.0%) in the placebo group. CONCLUSIONS: Early treatment with molnupiravir reduced the risk of hospitalization or death in at-risk, unvaccinated adults with Covid-19. (Funded by Merck Sharp and Dohme; MOVe-OUT ClinicalTrials.gov number, NCT04575597.).

OBJECTIVES: To assess a bundled Antimicrobial Stewardship Program and its effect on mortality. DATA: Eight months of clinical electronic medical records and Antimicrobial Stewardship Program registries were used as source of data. METHOD: This is a historical cohort study conducted in a Brazilian University Hospital. Eligible patients were admitted to general wards or intensive care units and had an antimicrobial therapy prescribed and assessed by different strategies: Bundled Antimicrobial Stewardship Program (bundled intervention consisted of clinical pharmacist chart review, discussion with microbiologist and infectious disease physicians, local education and continuous follow-up) or Conventional Antimicrobial Stewardship Program (clinical pharmacist chart review and discussion with infectious disease physician). Primary outcome from this study was 30-day mortality, which was compared between groups, by using Kaplan-Meier survival curve and log-rank test. Other outcomes included Defined Daily Doses per 1000 patient-days and occurrence of resistant bacteria. RESULTS: From 533 patients, 491 were eligible for the study, of which 191 patients were included to Antimicrobial Stewardship Program and 300 to Conventional strategy. In general, they were likely to be male and age was similar in groups (58.9 vs 55.5 years, p=0.38). Likewise, Charlson Comorbidity Index was not statistically different between groups (2.6 vs 2.7, p=0.2). Bloodstream site infections were frequently diagnosed in both groups (30.89% vs 26%, p=0.24). Other less common sites of infections were central nervous system and lungs. The ASP group had higher survival rates (p<0.01) and the risk difference was 10.8% (95% CI: 2.41-19.14). There were less Defined Daily Doses per 1000 patient-days (417 vs 557.2, p<0.05) and higher rates of resistant bacteria identified in the ASP group (83% vs 17%). CONCLUSION: Bundled ASP was the most effective strategy, with reduced mortality and Defined Daily Doses per 1000 patient-days.

There is a lack of formal economic analysis to assess the efficiency of antimicrobial stewardship programs. Herein, we conducted a cost-effectiveness study to assess two different strategies of Antimicrobial Stewardship Programs. A 30-day Markov model was developed to analyze how cost-effective was a Bundled Antimicrobial Stewardship implemented in a university hospital in Brazil. Clinical data derived from a historical cohort that compared two different strategies of antimicrobial stewardship programs and had 30-day mortality as main outcome. Selected costs included: workload, cost of defined daily doses, length of stay, laboratory and imaging resources used to diagnose infections. Data were analyzed by deterministic and probabilistic sensitivity analysis to assess model's robustness, tornado diagram and Cost-Effectiveness Acceptability Curve. Bundled Strategy was more expensive (Cost difference US$ 2119.70), however, it was more efficient (US$ 27,549.15 vs 29,011.46). Deterministic and probabilistic sensitivity analysis suggested that critical variables did not alter final Incremental Cost-Effectiveness Ratio. Bundled Strategy had higher probabilities of being cost-effective, which was endorsed by cost-effectiveness acceptability curve. As health systems claim for efficient technologies, this study conclude that Bundled Antimicrobial Stewardship Program was more cost-effective, which means that stewardship strategies with such characteristics would be of special interest in a societal and clinical perspective.

Introdução: Vancomicina é um antibiótico glicopeptídico utilizado no tratamento de infecções causadas por microrganismos gram-positivos, especialmente no tratamento de MRSA. Objetivos: Monitorar os níveis séricos de vancomicina nos pacientes internados na UTI do Hospital de Clínicas/UFPR, contribuindo para o ajuste individual da terapia. Métodos: Os pacientes incluídos no protocolo foram divididos em três grupos: função renal normal, disfunção renal e sob terapia de substituição renal. Resultados: foram incluídos 27 pacientes com idade média de 56,2 ± 14,1 anos. Seis pacientes (27,3%) apresentaram infecção causada por MRSA e 16 pacientes (59,2%) foram a óbito. A insuficiência renal foi observada em dez pacientes (37,1%), destes, seis (22,2%) necessitaram de terapia de substituição renal. Neste grupo foram realizadas doze dosagens (17,9%), sendo uma (8,3%) dentro da faixa adequada. Nos dezessete pacientes com função renal normal foram realizadas 36 dosagens, sendo que dez (27,8%) estavam dentro da faixa adequada de 15-20 µg/mL. Nos seis pacientes submetidos a terapia de substituição renal foram realizadas dezenove mensurações (28,4%), sendo que duas (10,5%) estavam dentro dos níveis desejados. Nos pacientes com infecção por MRSA e nos pacientes que foram a óbito, 17 (25,4%) e 36 (53,7%) dosagens foram realizadas e destas, três (17,6%) e quatro (11,1%) estavam dentro da faixa de 15-20 µg/mL, respectivamente. Conclusão: A monitorização sérica da vancomicina é necessária para o controle do processo infeccioso, devido ao estado crítico dos pacientes internados na UTI e a grande variedade de fatores que podem influenciar a sua farmacocinética.Introdução: Vancomicina é um antibiótico glicopeptídico utilizado no tratamento de infecções causadas por microrganismos gram-positivos, especialmente no tratamento de MRSA. Objetivos: Monitorar os níveis séricos de vancomicina nos pacientes internados na UTI do Hospital de Clínicas/UFPR, contribuindo para o ajuste individual da terapia. Métodos: Os pacientes incluídos no protocolo foram divididos em três grupos: função renal normal, disfunção renal e sob terapia de substituição renal. Resultados: foram incluídos 27 pacientes com idade média de 56,2 ± 14,1 anos. Seis pacientes (27,3%) apresentaram infecção causada por MRSA e 16 pacientes (59,2%) foram a óbito. A insuficiência renal foi observada em dez pacientes (37,1%), destes, seis (22,2%) necessitaram de terapia de substituição renal. Neste grupo foram realizadas doze dosagens (17,9%), sendo uma (8,3%) dentro da faixa adequada. Nos dezessete pacientes com função renal normal foram realizadas 36 dosagens, sendo que dez (27,8%) estavam dentro da faixa adequada de 15-20 µg/mL. Nos seis pacientes submetidos a terapia de substituição renal foram realizadas dezenove mensurações (28,4%), sendo que duas (10,5%) estavam dentro dos níveis desejados. Nos pacientes com infecção por MRSA e nos pacientes que foram a óbito, 17 (25,4%) e 36 (53,7%) dosagens foram realizadas e destas, três (17,6%) e quatro (11,1%) estavam dentro da faixa de 15-20 µg/mL, respectivamente. Conclusão: A monitorização sérica da vancomicina é necessária para o controle do processo infeccioso, devido ao estado crítico dos pacientes internados na UTI e a grande variedade de fatores que podem influenciar a sua farmacocinética.

OBJECTIVE: Analyze patients with HIV infection from Curitiba, Paraná, their epidemiological characteristics and HIV RAM. METHODS: Patients regularly followed in an ID Clinic had their medical data evaluated and cases of virological failure were analyzed with genotypic report. RESULTS: Patients with complete medical charts were selected (n = 191). Demographic and clinical characteristics were compared. One hundred thirty two patients presented with subtype B infection (69.1%), 41 subtype C (21.5%), 10 subtype F (5.2%), 7 BF (3.7%) and 1 CF (0.5%). Patients with subtype B infection had been diagnosed earlier than patients with subtype non-B. Also, subtype B infection was more frequent in men who have sex with men, while non-B subtypes occurred more frequently in heterosexuals and women. Patients with previous history of three classes of ARVs (n = 161) intake were selected to evaluate resistance. For RT inhibitors, 41L and 210W were more frequently observed in subtype B than in non-B strains. No differences between subtypes and mutations were observed to NNTRIs. Mutations at 10, 32 and 63 position of protease were more observed in subtype B viruses than non-B, while positions 20 and 36 of showed more amino acid substitutions in subtype non-B viruses. Patients with history of NFV intake were evaluated to resistance pathway. The 90M pathway was more frequent in subtypes B and non-B. Mutations previously reported as common in non-B viruses, such as 65R and 106M, were uncommon in our study. Mutations 63P and 36I, previously reported as common in HIV-1 subtypes B and C from Brazil, respectively, were common. CONCLUSION: There is a significant frequency of HIV-1 non-B infections in Paraná state, with isolates classified as subtypes C, F, BF and BC. Patients with subtype C infection were more frequently female, heterosexual and had a longer average time of HIV diagnosis.