Characteristics of Gram-positive cocci infection and the therapeutic effect after liver transplantation / 中南大学学报(医学版)

OBJECTIVES@#Gram-positive cocci is the main pathogen responsible for early infection after liver transplantation (LT), posing a huge threat to the prognosis of liver transplant recipients. This study aims to analyze the distribution and drug resistance of Gram-positive cocci, the risk factors for infections and efficacy of antibiotics within 2 months after LT, and to guide the prevention and treatment of these infections.@*METHODS@#In this study, data of pathogenic bacteria distribution, drug resistance and therapeutic efficacy were collected from 39 Gram-positive cocci infections among 256 patients who received liver transplantation from donation after citizens' death in the Third Xiangya Hospital of Central South University from January 2019 to July 2022, and risk factors for Gram-positive cocci infection were analyzed.@*RESULTS@#Enterococcus faecium was the dominant pathogenic bacteria (33/51, 64.7%), followed by Enterococcus faecalis (11/51, 21.6%). The most common sites of infection were abdominal cavity/biliary tract (13/256, 5.1%) and urinary tract (10/256, 3.9%). Fifty (98%) of the 51 Gram-positive cocci infections occurred within 1 month after LT. The most sensitive drugs to Gram-positive cocci were teicoplanin, tigecycline, linezolid and vancomycin. Vancomycin was not used in all patients, considering its nephrotoxicity. Vancomycin was not administered to all patients in view of its nephrotoxicity.There was no significant difference between the efficacy of daptomycin and teicoplanin in the prevention of cocci infection (P>0.05). Univariate analysis indicated that preoperative Model for End-Stage Liver Disease (MELD) score >25 (P=0.005), intraoperative red blood cell infusion ≥12 U (P=0.013) and exposure to more than 2 intravenous antibiotics post-LT (P=0.003) were related to Gram-positive cocci infections. Multivariate logistic regression analysis revealed that preoperative MELD score >25 (OR=2.378, 95% CI 1.124 to 5.032, P=0.024) and intraoperative red blood cell transfusion ≥ 12 U (OR=2.757, 95% CI 1.227 to 6.195, P=0.014) were independent risk factors for Gram-positive cocci infections after LT. Postoperative Gram-positive cocci infections were reduced in LT recipients exposing to more than two intravenous antibiotics post-LT (OR=0.269, 95% CI 0.121 to 0.598, P=0.001).@*CONCLUSIONS@#Gram-positive cocci infections occurring early after liver transplantation were dominated by Enterococcus faecalis infections at the abdominal/biliary tract and urinary tract. Teicoplanin, tigecycline and linezolid were anti-cocci sensitive drugs. Daptomycin and teicoplanin were equally effective in preventing cocci infections due to Gram-positive cocci. Patients with high preoperative MELD score and massive intraoperative red blood cell transfusion were more likely to suffer Gram-positive cocci infection after surgery. Postoperative Gram-positive cocci infections were reduced in recipients exposing to more than two intravenous antibiotics post-LT.

Informe diário de evidências COVID-19: busca realizada em 17 de julho de 2020 / COVID-19 daily evidence report: search conducted on July 17, 2020

O Informe Diário de Evidências é uma produção do Ministério da Saúde que tem como objetivo acompanhar diariamente as publicações científicas sobre tratamento farmacológico e vacinas para a COVID-19. Dessa forma, são realizadas buscas estruturadas em bases de dados biomédicas, referentes ao dia anterior desse informe. Não são incluídos estudos pré-clínicos (in vitro, in vivo, in silico). A frequência dos estudos é demonstrada de acordo com a sua classificação metodológica (revisões sistemáticas, ensaios clínicos randomizados, coortes, entre outros). Para cada estudo é apresentado um resumo com avaliação da qualidade metodológica. Essa avaliação tem por finalidade identificar o grau de certeza/confiança ou o risco de viés de cada estudo. Para tal, são utilizadas ferramentas já validadas e consagradas na literatura científica, na área de saúde baseada em evidências. Cabe ressaltar que o documento tem caráter informativo e não representa uma recomendação oficial do Ministério da Saúde sobre a temática. Foram encontrados 14 artigos e 13 protocolos.

Shortened tuberculosis treatment regimens: what is new? / Esquemas mais curtos de tratamento da tuberculose: o que há de novo?

ABSTRACT Given the global burden of tuberculosis, shortened treatment regimens with existing or repurposed drugs are needed to contribute to tuberculosis control. The long duration of treatment of drug-susceptible tuberculosis (DS-TB) is associated with nonadherence and loss to follow up, and the treatment success rate of multidrug-resistant tuberculosis (MDR-TB) is low (approximately 50%) with longer regimens. In this review article, we report recent advances and ongoing clinical trials aimed at shortening regimens for DS-TB and MDR-TB. We discuss the role of high-dose rifampin, as well as that of clofazimine and linezolid in regimens for DS-TB. There are at least 5 ongoing clinical trials and 17 observational studies and clinical trials evaluating shorter regimens for DS-TB and MDR-TB, respectively. We also report the results of observational studies and clinical trials evaluating a standardized nine-month moxifloxacin-based regimen for MDR-TB. Further studies, especially randomized clinical trials, are needed to evaluate regimens including newer drugs, drugs proven to be or highly likely to be efficacious, and all-oral drugs in an effort to eliminate the need for injectable drugs.

RESUMO Em virtude da carga global da tuberculose, esquemas mais curtos de tratamento com medicamentos já existentes ou reaproveitados são necessários para contribuir para o controle da doença. A longa duração do tratamento da tuberculose sensível (TBS) está relacionada com não adesão e perda de seguimento, e a taxa de sucesso do tratamento da tuberculose multirresistente (TBMR) é baixa (de aproximadamente 50%) com esquemas mais longos. Neste artigo de revisão, relatamos avanços recentes e ensaios clínicos em andamento cujo objetivo é encurtar os esquemas de tratamento de TBS e TBMR. Discutimos o papel da rifampicina em altas doses, assim como o da clofazimina e linezolida em esquemas de tratamento de TBS. Relatamos também os resultados de estudos observacionais e ensaios clínicos de avaliação de um esquema padronizado de nove meses à base de moxifloxacina para o tratamento de TBMR. Mais estudos, especialmente ensaios clínicos randomizados, são necessários para avaliar esquemas que incluam medicamentos mais novos, medicamentos comprovadamente ou provavelmente eficazes e medicamentos exclusivamente orais na tentativa de dispensar o uso de medicamentos injetáveis.

Blefarite: epidemiologia, etiologia, apresentações clínicas, tratamento e evolução de nossos pacientes / Blepharitis: epidemiology, etiology, clinical presentations, treatment and evolution of our patients

Resumo Objetivo: A blefarite é uma das condições mais comumente encontradas na prática oftalmológica e se constitui em uma causa frequente de irritação e desconforto ocular. Por ser uma doença de difícil tratamento, os autores buscaram compreender melhor a epidemiologia, etiologia, apresentações clínicas, tratamento e evolução de seus pacientes, visando maior sucesso terapêutico. Métodos: Foram avaliados retrospectivamente e transversalmente o prontuário de 124 pacientes do Centro de Oftalmologia Tadeu Cvintal, os quais apresentavam blefarite e foram submetidos à classificação de gravidade e coleta de secreções palpebrais para cultura bacteriana e antibiograma. Resultados: A media da idade dos pacientes foi de 67,4 anos, o sexo feminino foi responsável por 70 (56,4%) casos e o masculino por 54 (43,5%). Quanto à gravidade da doença, constatou-se 71 casos de blefarite leve (56,8%), 52 (41,6%) com intensidade moderada e 2 (1,6%) casos graves. Avaliando o seguimento do tratamento da doença, foi observado que 103 (82,4%) pacientes não retornaram para avaliar o resultado do tratamento e apenas 22 (17,6%) retornaram. Em relação às culturas realizadas, 82 (66,1%) não apresentaram crescimento microbiano. Dentre as 42 (33,8%) amostras positivas, os Staphylococcus coagulase negativo foram os mais prevalentes, sobretudo os Staphylococcus epidermidis, responsável por 35 (83,3%) delas. Quanto à sensibilidade aos antibióticos, os agentes de nossa amostra demonstraram maior resistência à Penicilina, Eritromicina e Ciprofloxacino e 100% de sensibilidade à Linezolida, Vancomicina e Daptomicina. Conclusão: Conhecendo melhor as características epidemiológicas da blefarite e a sensibilidade antimicrobiana das bactérias envolvidas, é possível oferecer tratamentos mais eficazes.

Abstract Objective: Blepharitis is one of the most commonly encountered conditions in ophthalmic practice and is a frequent cause of eye irritation and discomfort. Being a difficult to treat disease, the authors sought to better understand the epidemiology, etiology, clinical presentations, treatment and evolution of their patients, aiming at greater therapeutic success. Methods: The medical records of 124 patients of Centro de Oftalmologia Tadeu Cvintal who had blepharitis were retrospectively and cross-sectionally evaluated and underwent severity classification and collection of eyelid secretions for bacterial culture and antibiogram. Results: The mean age of the patients was 67.4 years, females accounted for 70 (56.4%) cases and males for 54 (43.5%). Regarding the severity of the disease, there were 71 cases of mild blepharitis (56.8%), 52 (41.6%) with moderate intensity and 2 (1.6%) severe cases. Evaluating the follow-up of treatment of the disease, it was observed that 103 (82.4%) patients did not return to evaluate the treatment outcome and only 22 (17.6%) returned. In respect of the cultures performed, 82 (66.1%) did not show microbial growth. Among the 42 (33.8%) positive samples, coagulase-negative staphylococci were the most prevalent, especially Staphylococcus epidermidis, responsible for 35 (83.3%) of them. As for antibiotic sensitivity, the agents in our sample showed greater resistance to Penicillin, Erythromycin and Ciprofloxacin and 100% sensitivity to Linezolid, Vancomycin and Daptomycin. Conclusion: By better understanding the epidemiological characteristics of blepharitis and the antimicrobial sensitivity of the bacteria involved, it is possible to offer more effective treatments.

Avances en el tratamiento de la tuberculosis multirresistente / Advances in the treatment of multi-drug resistant tuberculosis

Resumen El tratamiento de las tuberculosis multidrogorresistentes (TBC-MDR) se basa en esquemas de fármacos con diseños muy variables, en pacientes con patrones de resistencia heterogéneos y seguimientos no estandarizados, lo que hace dificil plantear recomendaciones con fuerte nivel de evidencia. Además, sólo una minoría de estos enfermos recibe tratamiento a nivel mundial y con los actuales esquemas menos del 50% de los que logran ser tratados curan. Afortunadamente, durante los últimos años han aparecido nuevos medicamentos, (bedaquilina, delamanid y pretomanid), que están demostrando ser de real utilidad para estos pacientes en ensayos con mejor diseño y seguimiento, donde se puede establecer con mayor precisión la eficacia, toxicidad y grado de recaídas. Además, algunos fármacos ya conocidos, (fluoroquinolonas, linezolid, clofazimina) están siendo introducidos dentro de los nuevos esquemas de tratamiento.

Abstract Therapy of multi-drug resistant tuberculosis (MDR TB) is based on trials with drugs with highly variable patterns of resistance and non-standardized follow-ups that make it difficult to provide recommendations with strong levels of evidence. Also, the vast majority of MDR-TB patients fail to receive therapy and those who receive it, only achieve around 50% of good results. Fortunately new drugs have emerged (bedaquiline, delamanid, pretomanid) that are being useful for these patients with better designed trials and monitoring, in which the efficacy, toxicity and degree of relapses can be evaluated more accurately. Some drugs already known (fluorquinolones, linezolid and clofazimine) are also being introduced in new schemes of therapy.

Efficacy, safety, tolerability and population pharmacokinetics of tedizolid, a novel antibiotic, in Latino patients with acute bacterial skin and skin structure infections

Abstract Acute bacterial skin and skin structure infections are caused mainly by Gram-positive bacteria which are often treated with intravenous vancomycin, daptomycin, or linezolid, with potential step down to oral linezolid for outpatients. Tedizolid phosphate 200 mg once daily treatment for six days demonstrated non-inferior efficacy, with a favourable safety profile, compared with linezolid 600 mg twice daily treatment for 10 days in the Phase 3 ESTABLISH-1 and -2 trials. The objective of the current post-hoc analysis of the integrated dataset of ESTABLISH-1 and -2 was to evaluate the efficacy and safety of tedizolid (N = 182) vs linezolid (N = 171) in patients of Latino origin enrolled into these trials. The baseline demographic characteristics of Latino patients were similar between the two treatment groups. Tedizolid demonstrated comparable efficacy to linezolid at 48–72 h in the intent-to-treat population (tedizolid: 80.2% vs linezolid: 81.9%). Sustained clinical success rates were comparable between tedizolid- and linezolid-treated Latino patients at end-of-therapy (tedizolid: 86.8% vs linezolid: 88.9%). Tedizolid phosphate treatment was well tolerated by Latino patients in the safety population with lower abnormal platelet counts at end-of-therapy (tedizolid: 3.4% vs linezolid: 11.3%, p = 0.0120) and lower incidence of gastrointestinal adverse events (tedizolid: 16.5% vs linezolid: 23.5%). Population pharmacokinetic analysis suggested that estimated tedizolid exposure measures in Latino patients vs non-Latino patients were similar. These findings demonstrate that tedizolid phosphate 200 mg, once daily treatment for six days was efficacious and well tolerated by patients of Latino origin, without warranting dose adjustment.

Nocardia asteroides peritoneal dialysis-related peritonitis: first case in pediatrics, treated with protracted linezolid

Nocardia asteroides is a rare pathogen in peritoneal dialysis-related peritonitis. We report on a 13-year-old female with Nocardia asteroides peritonitis complicated by an intra-abdominal abscess. Linezolid was administered intravenously for 3 months and followed by oral therapy for an additional 5 months with close monitoring for adverse effects. The patient was discharged after 3 months of hospitalization on hemodialysis. The diagnosis and management of such cases can be problematic due to the slow growth and difficulty of identifying Nocardia species. The optimal duration of treatment for Nocardia peritonitis is not known. Linezolid can be used for prolonged periods in cases of trimethoprim/sulfamethoxazole-resistant cases with close monitoring for adverse effects

The challenge of managing extensively drug-resistant tuberculosis at a referral hospital in the state of São Paulo, Brazil: a report of three cases / O desafio do tratamento da tuberculose extensivamente resistente em um hospital de referência no estado de São Paulo: um relato de três casos

ABSTRACT Here, we report the cases of three patients diagnosed with extensively drug-resistant tuberculosis and admitted to a referral hospital in the state of São Paulo, Brazil, showing the clinical and radiological evolution, as well as laboratory test results, over a one-year period. Treatment was based on the World Health Organization guidelines, with the inclusion of a new proposal for the use of a combination of antituberculosis drugs (imipenem and linezolid). In the cases studied, we show the challenge of creating an acceptable, effective treatment regimen including drugs that are more toxic, are more expensive, and are administered for longer periods. We also show that treatment costs are significantly higher for such patients, which could have an impact on health care systems, even after hospital discharge. We highlight the fact that in extreme cases, such as those reported here, hospitalization at a referral center seems to be the most effective strategy for providing appropriate treatment and increasing the chance of cure. In conclusion, health professionals and governments must make every effort to prevent cases of multidrug-resistant and extensively drug-resistant tuberculosis.

RESUMO Relatamos aqui os casos de três pacientes portadores de tuberculose extensivamente resistente, internados em um hospital de referência no estado de São Paulo, e mostramos sua evolução clínica, radiológica e laboratorial pelo período de um ano. O tratamento instituído foi baseado nas diretrizes da Organização Mundial da Saúde, com a inclusão de uma nova proposta de uso de uma associação de drogas antituberculose (linezolida e imipenem). Nos casos estudados, demonstrou-se o desafio de construir um esquema terapêutico aceitável e eficiente com drogas mais tóxicas, mais dispendiosas e que foram utilizadas por períodos mais prolongados. Mostramos também o importante acréscimo nos custos do tratamento desses pacientes, com possíveis impactos no sistema de saúde mesmo após a alta hospitalar. Ressaltamos que, em casos extremos como os apresentados neste estudo, a hospitalização em centros de referência mostrou-se o caminho mais efetivo para oferecer tratamento adequado com possibilidade de cura. Em conclusão, todos os esforços dos profissionais da saúde e do poder público devem ser direcionados a evitar casos de tuberculose multirresistente e extensivamente resistente.