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.

Perfil fenotípico de resistência à colistina e tigeciclina em um hospital público no Brasil / Phenotypical profile of colistin and tigecycline resistance in a public hospital in Brazil / Perfil fenotípico de resistencia a la colistina y tigeciclina en un hospital público de Brasil

Justificativa e objetivos: Infecções Relacionadas à Assistência à Saúde (IRAS) causadas por bacilos Gram negativos multirresistentes (BGN-MDR) são consideradas um problema de saúde pública e um impacto nas taxas de mortalidade nas Unidades de Terapia Intensiva (UTI). O objetivo deste estudo foi verificar o perfil fenotípico de resistência à colistina e à tigeciclina, consideradas como último recurso terapêutico aos BGN-MDR. Métodos: Os dados foram coletados nas fichas de busca ativa do serviço de controle de infecções e prontuários médicos de pacientes internados em duas UTIs de um hospital público de Joinville, entre janeiro de 2016 e junho de 2017. Resultados: Ocorreram 256 IRAS por BGN, acometendo principalmente o gênero masculino (62%), com mediana de idade de 65 anos. Entre os BGN, 37% expressaram MDR; sendo as espécies mais frequentes: Klebsiella pneumoniae e (47%), Acinetobacter baumannii (23%) e Stenotrophomonas maltophilia (11%). A resistência de BGN-MDR à colistina e tigeciclina foi de 5% e de 12%, respectivamente; 5% dos isolados foram resistentes aos dois antibióticos. A taxa de óbito entre os pacientes com IRAS por BGN-MDR resistentes à colistina foi mais alta (60%) que aquelas à tigeciclina (45%). Conclusão: K. pneumoniae e A. baumannii produtores de carbapenemases, resistentes a colistina e tigeciclina prevaleceram entre os BGN-MDR, e estiveram associadas a maioria dos óbitos. Essas observações, junto com o alto uso de carbapenêmicos na terapia empírica, mostra a necessidade do uso racional de antimicrobianos.(AU)

Background and objectives: Healthcare-associated Infections (HAIs) caused by multidrug-resistant Gram-negative bacilli (GNB-MDR) are considered a public health problem and have an impact on mortality rates in Intensive Care Units (ICU). The aim of this study was to verify the phenotypic profile of resistance to colistin and tigecycline, considered as the last antimicrobial choice to treat BGNMDR infections. Methods: Data were collected on the active search records of the infection control service and medical records of patients admitted to two ICUs at a public hospital in Joinville between January 2016 and June 2017. Results: There were 256 HAIs caused by GNB, mainly affecting males (62%), with a median age of 65 years. Among GNBs, 37% expressed MDR; the most frequent species were: Klebsiella pneumoniae (47%), Acinetobacter baumannii (23%) and Stenotrophomonas maltophilia (11%). The resistance of GNB-MDR to colistin and tigecycline was 5% and 12%, respectively; 5% of the isolates were resistant to both antibiotics. The death rate among patients with HAIs caused by colistin-resistant GNB-MDR was higher (60%) than those to tigecycline (45%). Conclusion: Carbapenemase-producing K. pneumoniae and A. baumannii, resistant to colistin and tigecycline, prevailed among GNB-MDRs, and were associated with most deaths. These observations, coupled with the high use of carbapenems in empirical therapy, show the need for rational use of antimicrobials.(AU)

Justificación y objetivos: Las Infección nosocomial (IHs) causadas por bacilos Gram negativos multirresistentes (BGN-MDR) se consideran un problema de salud pública y un impacto en las tasas de mortalidad en las Unidades de Terapia Intensiva (UTI). El objetivo de este estudio fue verificar el perfil fenotípico de resistencia a la colistina ya la tigeciclina, consideradas como último recurso terapéutico a los BGN-MDR. Métodos: Los datos fueron recolectados en las fichas de búsqueda activa del servicio de control de infecciones y prontuarios médicos de pacientes internados en dos UTIs de un hospital público de Joinville, entre enero de 2016 y junio de 2017. Resultados: Ocurrieron 256 IHs por BGN, que afectan principalmente al género masculino (62%), con mediana de edad de 65 años. Entre los BGN, el 37% expresó MDR; siendo las especies más frecuentes: Klebsiella pneumoniae (47%), Acinetobacter baumannii (23%) y Stenotrophomonas maltophilia (11%). La resistencia de BGN-MDR a la colistina y tigeciclina fue del 5% y del 12%, respectivamente; 5% de los aislados fueron resistentes a los dos antibióticos. La tasa de muerte entre los pacientes con IH causadas por los BGN-MDR resistentes la colistina fue más alta (60%) que aquellas a tigeciclina (45%). Conclusión: K. pneumoniae y A. baumannii productoras de carbapenemases, resistentes la colistina y la tigeciclina, fueron más frecuentes entre los BGN-MDR y su asociación estuvo presente en la mayoría de las muertes. Estas observaciones, junto con el alto uso de carbapenems en la terapia empírica, muestran la necesidad de un uso racional de los antimicrobianos.(AU)

Tigeciclina en infecciones de piel y tejidos blandos complicadas / Tigecycline in complicated skin and soft-tissue infection

Objetivo: evaluar la mejor evidencia actual disponible para generar recomendaciones con respecto a la efectividad y seguridad del uso de tigeciclina en adultos con infección de piel y tejidos blandos (IPTB). Materiales y métodos: se realizó una revisión sistemática de la literatura, seleccionando los metaanálisis y experimentos clínicos controlados (ECCs), los cuales se valoraron utilizando la herramienta SIGN (Scottish Intercollegiate Guidelines Network.), con el fin de generar tablas de evidencia según GRADE de los estudios de tigeciclina en la indicación de IPTB, para posteriormente utilizar un proceso Delphi modificado para calificar las diferentes recomendaciones. Resultados: la revisión sistemática se incluyeron 9 metaanálisis que incluyeron 5 estudios clínicos aleatorizados con 1873 pacientes, y de ellos 952 asignados al brazo de tigeciclina, no mostró inferioridad frente a los comparadores en curación clínica (RR= 0.76 IC95% 0,57 - 1.03), curación microbiológica (RR= 0.92 IC95% 0,61 - 1.38), eventos adversos serios RR 1,41 (IC95%0,97 a 2,35), ni mortalidad RR 1,9 (IC95%0,84 a 4,3). La tigeciclina puede relacionarse con mayor frecuencia de eventos adversos leves de origen gastrointestinal. Conclusión: en pacientes adultos con IPTB, se considera que el uso de tigeciclina en monoterapia en pacientes no críticamente enfermos es equivalente en eficacia a otras opciones terapéuticas antimicrobianas. Se debe considerar especialmente como terapia de ajuste en pacientes con infecciones polimicrobianas.

Objective: To assess current best evidence available to generate recommendations regarding the effectiveness and safety of tigecycline use in adults with skin and soft-tissue infections (SSTIs). Materials and methods: A systematic review of the literature was conducted by selecting meta-analyzes and controlled clinical trials (CCTs), which were assessed using the SIGN tool (Scottish Intercollegiate Guidelines Network) in order to generate evidence tables according to GRADE of studies of tigecycline in the SSTIs indication, and then using a modified Delphi Method to score the different recommendations. Results: Nine meta-analyzes were included compounded by five randomized clinical trials with a sample size of 1873 patients, where 952 patients were assigned to tigecycline. The group of patients with tigecycline showed no inferiority to the comparator in clinical cure (RR = 0.76 95% CI 0.57 - 1.03), microbiologic cure (RR = 0.92 95% CI 0.61 - 1.38), serious adverse events RR 1, 41 (95% CI 0.97 to 2.35) or mortality RR 1.9 (95% CI 0.84 to 4.3). Tigecycline may be related to increased frequency of minor adverse events of gastrointestinal origin. Conclusion: In adult patients with SSTIs, it is considered that the use of tigecycline in monotherapy in non-critically ill patients is equivalent in effectiveness to other antimicrobial treatment options. It should be especially considered as an adjustment therapy in patients with polymicrobial infections.

Tigeciclina en infecciones intraabdominales complicadas / Tigecycline in complicated intra-abdominal infections

Objetivo: evaluar la mejor evidencia actual disponible para generar recomendaciones, con respecto a la efectividad y seguridad del uso de tigeciclina en adultos con infección intraabdominal complicada. Materiales y métodos: se realizó una revisión sistemática de la literatura, seleccionando los metaanálisis y experimentos clínicos controlados, los cuales se valora- ron utilizando la herramienta SIGN, con el fin de generar tablas de evidencia según GRADE de los estudios de tigeciclina en la indicación infección intraabdominal complicada, para posteriormente utilizar un proceso Delphi modificado para calificar las diferentes recomendaciones con el fin de generar un consenso. Resultados: se analizaron los resultados basados en la revisión sistemática de la literatura en la que se incluyeron 5 metaanálisis que cumplieron los criterios de selección comparando tigeciclina con otros tratamientos antibióticos en infección intraabdominal complicada; de los cuales, 2711 pacientes recibieron al menos una dosis del antibiótico (1382 tigeciclina y 1389 el comparador) y en los que no se observaron diferencias estadísticamente significativas en los desenlaces evaluados al comparar tigeciclina con otros antibióticos. Conclusión: en pacientes adultos con infección intraabdominal complicada, se considera que el uso de tigeciclina en monoterapia es equivalente en eficacia y seguridad a otras opciones terapéuticas antimicrobianas y no representa un exceso de mortalidad en comparación a otros antibióticos

Objective: To assess current best evidence available to generate recommendations regarding the effectiveness and safety of tigecycline use in adults with complicated intra-abdominal infection (cIAIs). Materials and methods: We conducted a systematic review of published meta-analysis that evaluated tigecycline compared to other antimicrobials and included the indication of cIAI. Quality of the evidence was evaluated by using the SIGN tool (Scottish Intercollegiate Guidelines Network) according to GRADE, and final recommendations were assessed by a modified Delphi Method in order to develop a consensus. Results: Five meta-analyzes met the selection criteria comparing tigecycline with other antibiotic treatments in complicated intra-abdominal infection. Five randomized clinical trials comprised in these meta-analysis included 2711 patients that received at least one dose of antibiotic (1382 tigecycline and 1389 the comparator regimen), We found no statistically significant differences in the evaluated outcomes by comparing tigecycline with other antibiotics, including clinical and microbiologic efficacy, safety and drug related mortality Conclusion: In adult patients with cIAIs, the use of tigecycline as monotherapy is equivalent in effectiveness to other antimicrobial therapeutic options and does not represent an increase in mortality compared to other antibiotics.

La experiencia clínica con tigeciclina: Una breve revisión / Clinical experience with tygecicline: A brief review

The available clinical experience with tigecycline is analyzed under the perspective of a systematic review of the hterature, related to the already approved indications reported in the recent hterature. The safety profile is checked in the above mentioned clinical trials. The available information allows supporting tigecycline efficiency in the managing of complicated skin and soft tissues infections, complicated intrabdominales infections and in community acquired pneumonias.

Se analiza, bajo la perspectiva de una revisión sistemática de la literatura médica, la experiencia clínica con tigeciclina, en las indicaciones ya aprobadas por las entidades reguladoras reportadas en la literatura reciente. Se revisa el perfil de seguridad y tolerabilidad en dichos ensayos clínicos. La información disponible permite avalar su eficacia en el manejo de infecciones de piel y tejidos blandos complicadas, infecciones intra-abdominales complicadas y neumonías adquiridas en la comunidad.

Tigeciclina versus vancomycin más aztreonam en el tratamiento de infecciones complicadas de piel y tejidos blandos: Experiencia en Latinoamérica / Tigecycline as effective as vancomycin plus aztreonam in the treatment of complicated skin and skin structure infections: Experience in Latin America

BACKGROUND: Treating complicated skin and skin structure infections (cSSSIs) can be challenging. Tigecycline was compared to vancomycin/aztreonam in patients with cSSSIs in a multinational trial; this article reports on the Latin American (LA) population. METHODS: Patients were randomly assigned to receive tigecycline or vancomycin/ aztreonam. Primary endpoint was clinical cure rate at test-of-cure (TOC). Several secondary endpoints and safety were also assessed. RESULTS: A subtotal of 167 LA patients from the multinational trial (N = 573) received ≥ 1 dose of study drug. At TOC, cure rates were similar between tigecycline and vancomycin/aztreonam in the clinically evaluable population.) Noninferiority of tigecycline could not be demonstrated (insufficient sample sizes). Tigecycline-treated patients had higher incidences of nausea, vomiting, anorexia; vancomycin/aztreonam-treated patients had higher incidences of pruritus and rash. CONCLUSIONS: Efficacy results in the LA population were consistent with the multinational study suggesting that tigecycline is noninferior to vancomycin/aztreonam in treating patients with cSSSI.

INTRODUCCIÓN: El tratamiento de infecciones complicadas de piel y tejidos blandos (ICPTB) puede representar un desafío. Se comparó la eficacia de tigeciclina versus vancomicina/aztreonam en pacientes con ICPTB en un estudio multicéntrico; este artículo se refiere a la experiencia en Latinoamérica (LA). MÉTODO: Se asignaron, en forma randomizada, los pacientes a dos grupos de tratamiento: tigeciclina o vancomicina/aztreonam. La meta a evaluar (outcome) primaria fue la curación clínica, denominada test de curación (TC). Se establecieron, además, metas secundarias y la evaluación de seguridad del fármaco. RESULTADOS: Un subtotal de 167 pacientes procedentes de LA, de un estudio multinacional que incluyó 573 pacientes, recibieron ≥ 1 dosis del fármaco en estudio. Al TC, los porcentajes de curación fueron similares entre tigeciclina y vanco-micina/aztreonam en los pacientes clínicamente evaluables). La no inferioridad de tigeciclina no pudo ser demostrada (tamaño de muestra insuficiente). Los pacientes tratados con tigeciclina tuvieron mayor incidencia de náuseas, vómitos y anorexia; los pacientes que recibieron vancomicina/aztreonam tuvieron mayor incidencia de prurito y rash. CONCLUSIONES: Los resultados de eficacia en LA fueron consistentes con el estudio multinacional sugiriendo que tigeciclina no es inferior a vancomicina/aztreonam en el tratamiento de pacientes con ICPTB.