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.

Risk of acute kidney injury and cost-effectiveness analysis comparing vancomycin and linezolid for the treatment of pediatric patients infected with Gram-positive bacteria / Risco de lesão renal aguda e custo-efetividade comparando vancomicina e linezolida para o tratamento de pacientes pediátricos infectados por bactérias Gram-positivas

Objective: This study aimed to compare the occurrence of acute kidney injury (AKI) in pediatric patients who used vancomycin (VAN) or linezolid (LNZ) to treat Gram-positive coccus (GPC) infections and to assess which treatment (VAN or LNZ) is the most cost-effective considering a pediatric hospital perspective. Methods: A retrospective cohort was performed to evaluate the occurrence of nephrotoxicity in pediatric patients without previous AKI, with GPC infections that used LNZ, or VAN monitored by serum VAN levels. Initially, descriptive analysis and Fisher and chisquare test were performed for this comparison. Then, a cost-effectiveness analysis was conducted through a decision tree model. The outcomes of interest were the rate of AKI related to the drug and the rate of admission to the intensive care unit (ICU) and cure. Results: In patients without previous acute kidney injury (AKI), 20% developed nephrotoxicity associated with VAN versus 9.6% in the LNZ group (p = 0.241). As there was no difference in nephrotoxicity between VAN andlinezolid (LNZ), vancomycin (VAN) monitored by serum VAN levels can optimize and rationalize the treatment. The nephrotoxicity risk criterion should not guide the prescription for LNZ. Furthermore, the average global cost of treatment with VAN was approximately R$ 43,000, while for LNZ, it was R$ 71,000. Conclusion: VAN was considered dominant (lower cost and greater effectiveness) over LNZ for treating patients with GPC infection.

Objetivo: Este estudo objetivou comparar a ocorrência de lesão renal aguda (LRA) em pacientes pediátricos que usaram vancomicina (VAN) ou linezolida (LNZ) para tratar infecções por cocos Gram-positivos (CGP) e avaliar qual tratamento (VAN ou LNZ) é o mais custo-efetivo considerando a perspectiva de um hospital pediátrico. Métodos: Foi realizada uma coorte retrospectiva para avaliar a ocorrência de nefrotoxicidade em pacientes pediátricos sem LRA prévia, com infecções por CGP que utilizaram LNZ ou VAN, combinada com vancocinemia. Para essa comparação, inicialmente foram realizados análise descritiva e testes de Fisher e qui-quadrado. Em seguida, foi realizada uma análise de custo-efetividade por meio de um modelo de árvore de decisão. Os desfechos de interesse foram a taxa de LRA relacionada ao medicamento e a taxa de internação em unidade de terapia intensiva e cura. Resultados: Nos pacientes sem LRA prévia, 20% deles desenvolveram nefrotoxicidade associada à VAN versus 9,6% no grupo LNZ (p = 0,241). Como não houve diferença na nefrotoxicidade entre VAN e LNZ, a VAN combinada com a vancocinemia pode otimizar e racionalizar o tratamento, e a prescrição de LNZ não deve ser guiada pelo critério de risco de nefrotoxicidade. Além disso, o custo médio global do tratamento com VAN foi de aproximadamente R$ 43.000, enquanto para LNZ foi de R$ 71.000. Conclusão: Assim, a VAN foi considerada dominante (menor custo e maior eficácia) sobre a LNZ para o tratamento de pacientes com infecção por CGP.

Transição de via de linezolida endovenosa para via oral: uma análise de custo-minimização / Switching from intravenous to oral linezolid therapy: a cost-minimization analysis

Objetivo: Comparar custos da terapia endovenosa exclusiva com linezolida com os custos da terapia iniciada por via endovenosa com transição para via oral após 72 horas, como estratégia de intervenção em programas de gestão de antimicrobianos. Métodos: Avaliação econômica de custo-minimização comparando custos diretos da terapia endovenosa exclusiva com linezolida com a terapia endovenosa seguida de transição para via oral em cenário simulado, sob a perspectiva do Sistema Único de Saúde (SUS), com árvore de decisão como modelo para tomada de decisão. Resultados: A alternativa englobando a transição de via mostrou-se a mais econômica em todos os cenários analisados. Para 28 dias de tratamento com linezolida, houve redução de 22% nos custos, considerando o paciente internado. Ao considerar alta após o sexto dia de tratamento, a redução de custos variou de 26%, com financiamento pelo SUS do restante do tratamento, a 84%, com financiamento do tratamento pós-alta pelo paciente. Conclusão: Conclui-se que a transição de via de linezolida é uma importante estratégia nos programas de gerenciamento de antimicrobianos, capaz de gerar economia significativa para a instituição. As avaliações econômicas de custo-minimização, nesse contexto, são uma importante ferramenta para demonstrar o aspecto econômico com potencial para sensibilizar gestores e tomadores de decisão.

Objective: To compare the direct costs of linezolid intravenous therapy with the costs of intravenous therapy switching to oral therapy after 72 hours as an intervention strategy in antimicrobial stewardship programs. Methods: Economic evaluation cost-minimization comparing direct costs of exclusive linezolid intravenous therapy with intravenous therapy for 72 hours and after switching to oral therapy in a simulated scenario, from the perspective of the National Health Service, with a decision tree as a decision modeling. Results: The alternative encompassing the therapy transition proved to be the most economical in all analyzed scenarios. For 28 days of treatment with linezolid, there was a 22% reduction in costs, considering the hospitalized patient. When considering discharge after the sixth day of treatment, the cost reduction ranged from 26%, with funding from the National Health Service for the rest of the treatment, to 84%, with funding for the post-discharge treatment by the patient. Conclusion: It was concluded that the linezolid therapy transition is an important strategy in antimicrobial management programs, capable of generating significant savings for the institution. In this context, economic cost-minimization assessments are an important tool to demonstrate the economic aspect with the potential to raise awareness among managers and decision-makers.

Linezolid-resistant Enterococcus casseliflavus and Enterococcus gallinarum isolated from poultry farms in Kelantan, Malaysia

Aims@#Linezolid has become a decisive therapy in treating infections with vancomycin-resistant Enterococcus (VRE). Currently, the emergence of linezolid-resistant Enterococcus further complicates the therapeutic options and leads to global health threat not only in hospital setting but in the community. The study aimed at antimicrobial pattern of Enterococcus isolated from 6 poultry farms in Kelantan, Malaysia.@*Methodology and results@#Between February and December 2019, 300 broiler cloacal swab sample (Gallus gallus domesticus) were collected and screened for linezolid-resistant enterococci (LRE) using a standard biochemical and antimicrobial susceptibility tests. Among all the samples, 32.3% (n=97/300) grew Enterococcus, 71.1% (n=69/97) of it were identified Enterococcus casseliflavus by molecular identification, whilst remaining isolates 28.9% (n=28/97) were further identified as Enterococcus gallinarum by 16S rRNA sequencing. None of the isolates were found to exhibit high-level resistance to vancomycin. However, 3/97 (3.1%) were exhibit resistance to high-level gentamicin based on Kirby-Bauer disk diffusion test. Whereas 48/97 (49.5%) of isolates were observed to be resistant to ampicillin, 28/97 (28.9%) were resistant to penicillin. Surprisingly, among the two strains isolated, 18.6% (n=18/97) of it were resistant to linezolid. Isolates showed resistance to linezolid by disk diffusion test were verified by VITEK-2 automated system (bioMérieux, USA) with MIC ≥8 µg/mL. All antimicrobial susceptibility test and minimal inhibitory concentration (MIC) results were interpreted according to Clinical and Laboratory Standard Institute (CLSI). @*Conclusion, significance and impact of study@#In conclusion, this study has reported the prevalence of linezolid resistant Enterococcus (LRE) in highly intrinsic antibiotic resistant of E. casseliflavus and E. gallinarum in Malaysia poultry farms, alongside with the truancy of vanA strains. The emergence of LRE strains is an alarming problem to the animal husbandry and healthcare setting worldwide. This could lead to potentially untreatable and life-threatening enterococcal infections. Even more worrying is the spread of LRE to geographical regions where these strains were previously unreported, which may pose a global health threat. Antimicrobial surveillance in poultry husbandry is thus, dimly necessary to prevent wide spread of multidrug-resistant bacteria.

Síndrome serotoninérgico como reacción adversa infrecuente ante la sinergia entre Linezolid y Fentanilo: presentación de caso / Serotonin syndrome as an infrequent adverse reaction to synergy between Linezolid and Fentanyl: case presentation

Resumen El síndrome serotoninérgico es una condición potencialmente mortal causada por medicamentos que afectan el metabolismo de la serotonina o que actúan como agonistas directos del receptor de esta o una combinación de ambos. El síndrome da lugar a una variedad de manifestaciones mentales, autonómicas y neuromusculares, que pueden variar desde leves hasta potencialmente mortales. Se reporta el caso clínico de un paciente el cual desarrolló este síndrome por la coadministración y sinergismo de linezolid y fentanilo, con una gran variedad de características clínicas, desde las más sutiles, como cifras tensionales altas de difícil manejo mientras se encontraba bajo el efecto de sedoanalgesia, hasta las manifestaciones más floridas del síndrome posterior a la suspensión de esta. La asociación de estos medicamentos representa una etiología poco informada que puede favorecer la aparición del síndrome, mientras que el uso de benzodiazepinas puede enmascarar el cuadro dificultando su diagnóstico. MÉD.UIS.2020;33(3): 59-66

Abstract Serotonin syndrome is a life-threatening condition caused by medications that affect serotonin metabolism or that act as direct agonists for serotonin receptor or a combination of both. The syndrome gives rise to a variety of mental, autonomic, and neuromuscular manifestations, which can range from mild to life-threatening. We report a clinical case of a patient who developed this syndrome due to the co-administration and synergism of linezolid and fentanyl, with a wide variety of clinical characteristics, from the most subtle, such as high blood pressure levels difficult to manage while under the effect of sedoanalgesia, to the most florid manifestations of the syndrome after 48 hours of its suspension. The association of these drugs represents a poorly reported etiology that may favor the appearance of the syndrome, while the use of benzodiazepines may mask the condition, making its diagnosis difficult. MÉD.UIS.2020;33(3): 59-66

A retrospective cohort study to screen linezolid-induced thrombocytopenia in adult patients hospitalized in the Midwestern Region of Brazil

ABSTRACT Background: Thrombocytopenia (TP) is the major event associated with linezolid (LZD) therapy. We investigated the incidence and risk factors for thrombocytopenia in hospitalized adults who received LZD (1200 mg/day) between 2015 and 2017. HIV-positive, death during follow-up and those with a baseline platelet count ≤100 × 103/mm3 were excluded. Method: TP was defined as a decrease in platelet count of ≥20% from the baseline level at the initiation of linezolid therapy and a final count of <100 × 103/mm3. The odds ratios (OR) for thrombocytopenia were obtained using multivariate stepwise logistic regression analysis. Main results: A total of 66 patients were included (mean age [SD] 62 [18], male gender [%], 37 [56]). LZD-associated TP was identified in 12 patients (18.2%). For TP, the adjusted OR [95% CI] of the platelet count ≤200 × 103/mm3, serum creatinine and renal impairment at baseline were 5.66 [1.15-27.9], 4.57 [1.26-16.5] and 9.41 [1.09-80.54], respectively. Male gender and dosage per weight per day (DPWD) >20 mg/kg/day were not risk factors. Conclusion: The results showed that the incidence of linezolid-induced thrombocytopenia was lower in patients with normal renal function and higher in those with platelet counts ≤200 × 103/mm3 or serum creatinine >1.5 mg/dL at the start of the treatment.

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.

Microorganismos más frecuentes en infecciones cutáneas en el Hospital Provincial General Ambato / Most frequent microorganisms in skin infections at the General Provincial Hospital "Ambato"

Las infecciones cutáneas producidas por microorganismos afectan directamente a la piel, partes blandas y tejidos, donde proliferan y ocasionan graves alteraciones. Estas infecciones constituyen un problema de salud pública, ya que muchos microorganismos muestran resistencia a antimicrobianos comunes y no comunes, lo cual incide directamente en la aplicación del tratamiento adecuado al paciente. El objetivo de este estudio fue identificar los microorganismos más frecuentes en infecciones cutáneas, su sensibilidad y resistencia a los antibióticos en los pacientes con infección que acudieron al Hospital Provincial General "Ambato" en el período mayo 2017 ­ junio 2018. La metodología empleada en esta investigación se basa en un estudio descriptivo, de corte transversal y enfoque cuali-cuantitativo, empleando la técnica documental y el reporte de resultados como instrumento. La información se tabuló y analizó mediante el paquete operativo Microsoft 2010. Se encontró que en el 29% de las muestras procesadas se aisló Staphylococcus aureus como el más frecuente en este tipo de infecciones, con mayor sensibilidad a Clindamicina, Doxacilina y Linezolid (100%) y resistencia a Penicilinas y Oxacilina (47,82%). Es importante destacar que el 47,83 % de las cepas de S. aureus aisladas expresaron fenotípicamente el gen mecA. La entidad clínica más frecuente asociada a este tipo de infección fue el ectima con un 55%. En conclusión, se comprobó la resistencia de cepas a diversos antibióticos presentando las más relevantes como meticilino resistentes, vancomicina resistentes y Klebsiella pneumoniae carbapenemasas

The skin infections caused by microorganisms directly alter the skin, soft tissues and tissues cause serious damage and the proliferation of them, which is a problem for health centers and hospitals, since these microorganisms are often resistant to antibacterial which are not very common is a problem for the treatment of the patient. The objective of this study was to identify the most frequent microorganisms in cutaneous infections, their sensitivity and resistance to antibiotics in the patients with infection who when to the General Provincial Hospital "Ambato", in the period May 2017 - June 2018 the methodology used in this investigation is based on a descriptive cutting study cross-section and qualitative-quantitative approach, using the documentary technique and the report of results as an instrument. The information was tabulated and analyzed using the Microsoft 2010 operating package. It was found that 29% of the samples processed were isolated Staphylococcus aureus as the most frequent in this type of infections, with greater sensitivity to Clindamycin, Doxacillin and Linezolid (100%) and resistance to Penicillins and Oxacillin (47,82%). It is important to note that 47,82% of strains of S. aureus were expressly phenotypically expressed in the mecA gene. The most frequent clinical entity associated with this type of infection was efficacy with 55%. In conclusion, the resistance of strains in several antibiotics was proved, presenting the most relevant ones as methicillin resistant, vancomycin resistant and Klebsiella pneumoniae carbapenemasas.

Molecular detection of chloramphenicol-florfenicol resistance (cfr) genes among linezolid resistant MRSA isolates in Sokoto State, Nigeria / Detecção molecular de genes de resistência ao cloranfenicol-florfenicol (cfr) entre isolados de MRSA resistentes a linezolida no estado de Sokoto, Nigéria

Objective: we investigated previous literatures for documentation of the trend in Sokoto, Nigeria and found none. We deemed it fit to determine the frequency of linezolid resistance mediated by cfr gene among MRSA isolates from Sokoto State-owned hospitals. Methods: Bacterial species identification was carried out with Microgen™ Staph-ID System kit (Microgen, Surrey, UK). Disc agar diffusion method (Modified Kirby-Bauer's) following Clinical and Laboratory Standards Institute (CLSI 2018) guidelines was used in antimicrobial susceptibility testing. The results were interpreted and managed using WHONET 5.6 software (WHO, Switzerland). Oxacillin resistant screening agar base (ORSAB) culture was used to determine phenotypic methicillin resistance. Polymerase chain reaction (PCR) was carried out to determine the presence of cfr-gene. Results: A total of 81 S. aureus isolates were phenotypically identified. Of this number, 46.91% (38/81) were MRSA; Healthcare workers (39.5%), Outpatient (28.9%), In patient (21%), Security men and Cleaners (5.3% each). Importantly linezolid resistance rate among the MRSA isolates was 44.7%. Analysis of antimicrobial susceptibility profile also showed a multiple antibiotics resistance burden of MDR (5.9%), possible XDR (47.1%), XDR (41.1%) and PDR (5.9%) amongst LR-MRSA. About 52.9% (9/17) of LR-MRSA harbored the cfr gene. Conclusions: This is the first report to document cfr gene in LR-MRSA strains in Sokoto. The cfr gene was found among the studied LR-MRSA strains and if cfr-mediated linezolid resistance is not properly checked, its phenotypic expression may result in an outbreak of multiple antibiotic resistant strains.

Objetivo: avaliar a incidência de resistência linezolida cfr-mediada entre os isolados de MRSA dos hospitais do Estado de Sokoto. Métodos: A identificação das espécies bacterianas foi realizada com Microgen™ Staph-ID System kit (Microgen, Surrey, UK). Método de difusão em ágar de disco (Kirby-Bauer modificado) seguindo as diretrizes do Clinical and Laboratory Standards Institute (CLSI 2018). O resultado foi interpretado e gerido com WHONET 5.6 (OMS, Suíça) software. A cultura ORSAB (Oxacillin resistant screening agar) foi utilizada para determinar a resistência fenotípica à meticilina. A PCR foi realizada para determinar a presença de cfr-gene. Resultados: um total de 81 isolados de S. aureus foi identificada fenotipicamente. Desse número, 46,91% (38/81) eram de MRSA; Profissionais de saúde (39,5%), Ambulatoriais (28,9%), Em paciente (21%), Homens de segurança e Limpadores (5,3% cada). A taxa de resistência linezolida entre os isolados de MRSA foi de 44,7%. A análise do perfil de sensibilidade antimicrobiana também mostrou uma carga de resistência a antibióticos múltiplos de MDR (5,9%), possível XDR (47,1%), XDR (41,1%) e PDR (5,9%) entre LR-MRSA. Um total de, 52,9% (9/17) da LR-MRSA abrigava o gene cfr. Conclusões: Este é o primeiro relatório a documentar o cfr-gen nas estirpes LR-MRSA em Sokoto. O gene cfr está presente entre as cepas estudadas de LR-MRSA, e se a resistência cfr-mediated linezolida não for adequadamente verificada, sua expressão fenotípica pode resultar em um surto de múltiplas cepas resistentes a antibióticos.

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.

Culture-Positive Spontaneous Ascitic Infection in Patients with Acute Decompensated Cirrhosis: Multidrug-Resistant Pathogens and Antibiotic Strategies

Linezolid Resistance in Methicillin-Resistant Staphylococcus aureus in Korea: High Rate of False Resistance to Linezolid by the VITEK 2 System

As various linezolid resistance mechanisms have been identified in methicillin-resistant Staphylococcus aureus (MRSA), we investigated the molecular characteristics of MRSA with elevated linezolid minimum inhibitory concentrations (MICs), using the VITEK 2 system (bioMérieux, Marcy-l'Étoile, France). Twenty-seven MRSA isolates from 14 patients exhibiting linezolid MICs ≥8 µg/mL were examined by broth microdilution (BMD) test as well as by sequencing for mutations in the 23S rRNA gene or ribosomal proteins (L3, L4, and L22) and the presence of the optrA, cfr, and cfr(B) genes. Of the 27 isolates, four (14.8%) from one patient were confirmed as linezolid resistant by BMD and harbored a 23S rRNA T2500A mutation. The remaining 23 were confirmed as linezolid susceptible, indicating that the linezolid-resistant results were major errors generated by VITEK 2. The most commonly detected mutation (19/27, 70.4%), L3 Gly152Asp, was detected in only linezolid-susceptible isolates. No isolates contained optrA, cfr, or cfr(B) or any L4 or L22 protein alterations. Our results show that the 23S rRNA T2500A mutation was mainly associated with linezolid resistance, while the L3 Gly152Asp mutation was not related to linezolid resistance. A confirmatory test is recommended for VITEK 2 linezolid-resistant results owing to the high probability of false resistant results.

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.

Molecular Epidemiology and Mechanisms of 43 Low-Level Linezolid-Resistant Enterococcus faecalis Strains in Chongqing, China

BACKGROUND: Enterococcus faecalis strains with low-level resistance to linezolid (an oxazolidinone antibiotic) have become common. No large-scale study has examined the underlying mechanisms in linezolid-resistant E. faecalis (LRE) strains. We investigated these mechanisms and molecular characteristics in Chongqing, China. METHODS: A total of 1,120 non-duplicated E. faecalis strains collected from August 2014 to June 2017 underwent drug susceptibility testing. LRE strains were screened for optrA, cfr, and mutations in the 23S rRNA and ribosomal proteins L3 and L4 by PCR amplification and sequencing. Multi-locus sequence typing (MLST) and pulsed-field gel electrophoresis (PFGE) were used for epidemiological analysis. RESULTS: All 43 low-level LRE strains (minimum inhibitory concentration: 8–16 mg/L) harbored optrA; cfr and 23S rRNA mutations were not detected. Novel mutations in the ribosomal proteins L3 and L4—one deletion (Q103del) and four substitutions (S113L, T35A, I98V, and N79D)—were identified. Novel amino acid substitutions at positions E60K, G197D, and T285P of the OptrA protein were observed. MLST revealed 20 types of LRE strains; the most common type was ST16 (32.6%). PFGE showed 14 strains of ST16 with unique banding patterns. Eight novel sequence types (ST823 to ST830) and one allele (gki95) were identified for the first time in China. CONCLUSIONS: optrA plays an important role in linezolid resistance and may serve as a marker for resistance screening. Since the L3 and L4 mutations did not simultaneously occur in the same strain, they play a negligible role in linezolid resistance. Epidemiological investigation suggested that the LRE cases were sporadic.

Toxicité hématologique sévère du linezolide au cours du traitement de la tuberculose pharmacorésistante : A propos de deux(2) cas au service de Pneumo-Phtisiologie du CHU de Conakry

Introduction : Le linezolide est un médicament potentiellement efficace pour le traitement des patients atteints de tuberculose pharmaco-résistante. En dépit de son efficacité et sa bonne biodisponibilité, il présente des toxicités, dont celle hématologique demeure l'une des plus graves. Nous rapportons deux cas de toxicité hématologique du linézolide au cours du traitement de la tuberculose pharmacorésistante. Le premier cas concernait un patient de 65 ans traité pour une tuberculose multi-résistante avec un schéma thérapeutique contenant du linézolide. L'évolution fut marquée par la survenue d'une pancytopénie avec anémie sévère à 5,4 g et un tableau d'insuffisance rénale. L'issue fut favorable après arrêt du médicament et transfusion sanguine. Le second cas concernait un patient de 33 ans, pré XDR qui lutte contre la tuberculose depuis 10 ans avec cinq cures de chimiothérapie antituberculeuse qui se sont soldées par des échecs et résistances. Au cours de son suivi, il a présenté une bonne évolution clinique et bactériologique initiale mais rapidement était survenue une anémie sévère à 5g/dl, à cette anémie était associées des neuropathies périphériques. Le Linezolide avait été retiré du schéma thérapeutique, suivi de transfusions sanguines. La suite avait été favorable sous traitement antituberculeux et le patient fut guéri de sa tuberculose. Conclusion Le linézolide est efficace dans le traitement de la tuberculose pharmacorésistante mais présente une toxicité hématologique

The First Case of Otitis in Korea Caused by Brevibacterium otitidis

Brevibacterium spp. are gram-positive rods that are considered to be strictly nonpathogenic, and a very few cases of their infection in humans have been reported. In this study, we report a case of otitis caused by Brevibacterium otitidis. A 53-year-old woman, who visited the hospital, complained of symptoms, such as otorrhea from both ears, ear fullness, tinnitus, and hearing impairment, for several months. Ear discharge was cultured on blood agar for pathogen identification. Bacteria from the isolated colony were initially identified as Actinomyces odontolyticus by VITEK 2 (bioMerieux, France), whereas VITEK® MS (bioMerieux, France) identified them as Brevibacterium luteolum. Subsequently, bacteria from the isolated colony were confirmed as B. otitidis by 16S rRNA sequencing. Antimicrobial susceptibility testing confirmed their sensitivity to vancomycin and linezolid and resistance to clindamycin and penicillin. To our knowledge, this is the first reported case of otitis caused by B. otitidis in Korea.

Treatment of Mycobacterium Abscessus Pulmonary Disease / 대한내과학회지

Mycobacterium abscessus is the second most important pathogen in pulmonary disease caused by nontuberculous mycobacteria (NTM), following Mycobacterium avium. Mycobacterium abscessus is classified into three subspecies: M. abscessus subsp. abscessus, M. abscessus subsp. massiliense, and M. abscessus subsp. bolletii. Mycobacterium abscessus is the most difficult to treat NTM due to its resistance to many antibiotics. Treatment should include an initial regimen of 2–3 injectable and oral antibiotics for several weeks or months, followed by inhaled amikacin and 1–3 oral antibiotics, depending on the subspecies and drug susceptibility patterns, including macrolide susceptibility. The continuation phase should be continued for a minimum of 12 months after culture conversion. Suitable injectable antibiotics include amikacin, imipenem, cefoxitin, and tigecycline, while oral antibiotics include macrolides (azithromycin or clarithromycin), clofazimine, linezolid, and moxifloxacin. Surgery can be a useful adjunctive therapy for some patients with refractory disease. However, the overall treatment prognosis is still unsatisfactory. Therefore, novel and more effective interventions are required for the treatment of M. abscessus pulmonary disease.

Multiplex PCR analysis of virulence genes and their influence on antibiotic resistance in Enterococcus spp. isolated from broiler chicken

Enterococcus spp. are opportunistic pathogens that cause lameness in broiler chickens, resulting in serious economic losses worldwide. Virulence of Enterococcus spp. is associated with several putative virulence genes including fsr, efm, esp, cylA, cad1, ace, gelE, and asa1. In this study, multiplex polymerase chain reaction (PCR) for the simultaneous detection of these virulence genes in Enterococcus spp. was developed, and detection limits for E. faecium, E. faecalis, and E. hirae were 64.0 pg/µL, 320.0 pg/µL, and 1.6 ng/µL DNA, respectively. Among 80 Enterococcus isolates tested, efm and cad1 were detected in all 26 E. faecium samples, and only cad1 was observed in E. hirae. Additionally, the presence of virulence genes in 25 E. faecalis isolates were 100% for cad1, 88.0% for gelE, 64.0% for fsr, 44.0% for asa1, 16.0% for cylA, and 4.0% for esp. No virulence genes were found in E. gallinarum isolates. A total of 49 isolates were resistant to tigecycline and to at least 2 different classes of antibiotics. The most prevalent resistance was to ciprofloxacin (73.5%), quinupristin/dalfopristin (55.1%), and tetracycline (49.0%). No strains were resistant to vancomycin or linezolid. This is the first multiplex PCR assay to simultaneously detect eight virulence genes in Enterococcus spp., and the method provides diagnostic value for accurate, rapid, and convenient detection of virulence genes. Additionally, we report the prevalence of virulence genes and antimicrobial resistance in Enterococcus isolates from commercial broiler chickens suffering lameness.

Evaluation of in vitro antimicrobial susceptibility of Bacillus anthracis strains isolated during anthrax outbreaks in Italy from 1984 to 2017

Anthrax, caused by Bacillus anthracis, is a non-contagious infectious disease that affects a wide range of animal species (primarily ruminants) including humans. Due to the often-fatal outcome in humans, quick administration of definitely effective antimicrobials is crucial either as prophylaxis or as a clinical case therapy. In this study, 110 B. anthracis strains, temporally, geographically, and genetically different, isolated during anthrax outbreaks in Italy from 1984 to 2017, were screened using a broth microdilution method to determine their susceptibility to 16 clinically relevant antimicrobial agents. The strains were isolated from various matrices (human, animal, and environmental samples) and were representative of thirty distinct genotypes previously identified by 15-loci multiple-locus variable-number of tandem repeats analysis. The antimicrobials tested were gentamicin, ceftriaxone, streptomycin, penicillin G, clindamycin, chloramphenicol, vancomycin, linezolid, cefotaxime, tetracycline, erythromycin, rifampin, amoxicillin, ciprofloxacin, doxycycline, and trimethoprim. All isolates were susceptible to most of the tested antimicrobials, with the exception of trimethoprim for which all of them showed high minimal inhibitory concentration values. An intermediate level of susceptibility was recorded for ceftriaxone and cefotaxime. Although the Centers for Disease Control and Prevention recommend the use of doxycycline, ciprofloxacin, penicillin G, and amoxicillin for treatment of human cases and for post-exposure prophylaxis to anthrax spores, this study shows a high degree of in vitro susceptibility of B. anthracis to many other antimicrobials, suggesting the possibility of an alternative choice for prophylaxis and therapy.

Delamanid, Bedaquiline, and Linezolid Minimum Inhibitory Concentration Distributions and Resistance-related Gene Mutations in Multidrug-resistant and Extensively Drug-resistant Tuberculosis in Korea

BACKGROUND: Delamanid, bedaquiline, and linezolid have recently been approved for the treatment of multidrug- and extensively drug-resistant (MDR and XDR, respectively) tuberculosis (TB). To use these drugs effectively, drug susceptibility tests, including rapid molecular techniques, are required for accurate diagnosis and treatment. Furthermore, mutation analyses are needed to assess the potential for resistance. We evaluated the minimum inhibitory concentrations (MICs) of these three anti-TB drugs for Korean MDR and XDR clinical strains and mutations in genes related to resistance to these drugs. METHODS: MICs were determined for delamanid, bedaquiline, and linezolid using a microdilution method. The PCR products of drug resistance-related genes from 420 clinical Mycobacterium tuberculosis strains were sequenced and aligned to those of M. tuberculosis H37Rv. RESULTS: The overall MICs for delamanid, bedaquiline, and linezolid ranged from ≤0.025 to >1.6 mg/L, ≤0.0312 to >4 mg/L, and ≤0.125 to 1 mg/L, respectively. Numerous mutations were found in drug-susceptible and -resistant strains. We did not detect specific mutations associated with resistance to bedaquiline and linezolid. However, the Gly81Ser and Gly81Asp mutations were associated with resistance to delamanid. CONCLUSIONS: We determined the MICs of three anti-TB drugs for Korean MDR and XDR strains and identified various mutations in resistance-related genes. Further studies are needed to determine the genetic mechanisms underlying resistance to these drugs.