Asociación entre infusión prolongada de vancomicina yconcentración valle en niños. Estudio retrospectivo / Association between prolonged vancomycin infusion and trough concentrations in children. Retrospective study

Introducción: Este estudio investigó la concentración plasmática de vancomicina en los niños, durante la infusión prolongada. Población y métodos: Estudio retrospectivo de una cohorte que incluyó pacientes pediátricos tratados con vancomicina desde junio de 2017 hasta junio de 2020, en un hospital de referencia de nivel III. Los pacientes se dividieron en dos grupos sogún el tipo de infusión: el grupo de infusión intermitente estándar (IIE) y el grupo de infusión prolongada (IP). Se registraron detalles demográficos, periodo de infusión, creatinina plasmática, duración del tratamiento con vancomicina, concentración valle de vancomicina y permanencia en la unidad de cuidados intensivos pediátricos (UCIP). Se midieron las diferencias entre concentraciones. Resultados: Se incluyeron 68 pacientes, 31 en el grupo IIE y 37 en el grupo IP. La concentración valle de vancomicina fue significativamente más alta en el grupo IP en comparación con el grupo IIE (11,2 mg/L [5,9-13,7] vs. 7 mg/L [3,5-9,3]; p = 0,02). La tasa de logro del objetivo fue más alta en el grupo IP que en el grupo IIE (59,4 % y 19,3 % respectivamente; p = 0,001). No hubo diferencias significativas entre ambos grupos en las concentraciones pico de vancomicina, valor de creatinina final, pico de creatinina, fracaso terapéutico, duración de la estadía en la UCIP y duración del tratamiento con vancomicina. El análisis multivariado mostró que la IP se asoció en forma significativa con concentraciones valle más altas de vancomicina (OR: 2,27, p = 0,005). Conclusión: En comparación con la estrategia de IIE, la infusión prolongada puede ser una opción optimizada para los niños con infección grave, porque puede alcanzar concentraciones valle más altas y mejorar la obtención de la concentración objetivo.

Introduction: This study investigated the serum concentration of vancomycin during prolonged infusion in children. Population and methods: This retrospective cohort study included pediatric patients who received vancomycin from June 2017 to June 2020 at a tertiary referral hospital. The patients were divided into two groups according to infusion strategy, the SII (standard intermittent infusion) group and the PI (prolonged infusion) group. Demographic details, infusion period, serum creatinine, duration of vancomycin therapy, trough concentration of vancomycin, and pediatric intensive care unit stay were reviewed. Differences of the concentrations were measured. Results: Sixty-eight patients were included: 31 in the SII group and 37 in the PI group. The trough concentration of vancomycin was significantly higher in the PI group than in SII group (11.2 mg/L [5.9-13.7] vs. 7 mg/L [3.5- 9.3]; p = 0.02). The target attainment rate was higher in the PI group than in the SII group (59.4% and 19.3%, respectively; p = 0.001). There were no significant differences between the SII and PI groups regarding the peak concentrations of vancomycin, final creatinine and peak creatinine. There were no differences between the SII and PI groups regarding the failure events, PICU stay and duration of vancomycin therapy. The multivariable analysis showed that PI was significantly associated with higher trough serum concentrations of vancomycin (OR = 2.27; p = 0.005). Conclusion: Compared to the SII strategy, the PI strategy may be an optimized option to children with severe infection, as it can achieve higher trough concentrations and target concentration attainment

Usabilidade de um aplicativo móvel de apoio aos profissionaisde saúde para cálculos de doses de vancomicina / Usability of a mobile application supporting healthprofessionals on vancomycin dosing calculation

O aplicativo móvel CalcVAN foi desenvolvido para auxiliar os profissionais de saúde para otimizar as doses de vancomicina em pacientes hospitalizados. Porém, é imprescindível avaliar a sua usabilidade antes de disponibilizá-lo para prática clínica. Assim, o objetivo do estudo é avaliar a usabilidade do aplicativo móvel na perspectiva dos profissionais de saúde. Trata-se de um estudo descritivo, de avaliação heurística da usabilidade de um aplicativo móvel. Foram convidados profissionais da área de saúde com expertise no tema de gerenciamento de antimicrobianos e vancomicina. O instrumento validado Smartphone Usability questionnaiRE (SURE) foi utilizado para mensuração da usabilidade por meio de um questionário on-line. Vinte e um especialistas participaram do estudo, com média de idade de 32,6 anos, sendo a maioria de mulheres (n = 14, 66,7%), profissionais farmacêuticos (n = 13, 61,9%), com pós-graduação lato sensu (n = 10, 47,6%), que trabalhavam em hospitais públicos ou privados (n = 15, 71,4%) e com média de experiência em 9,7 anos. Com base na interpretação dos resultados obtidos pelo instrumento SURE, a média de usabilidade geral do CalcVAN foi de 83 pontos, com escore menor de 78 e maior de 90 pontos. O teste de usabilidade foi enquadrado nos dois últimos níveis, 70 e 80, onde os profissionais de saúde passaram a concordar fortemente e totalmente, indicando que o aplicativo móvel apresenta uma usabilidade satisfatória. O CalcVAN atingiu uma usabilidade satisfatória e atende as necessidades e exigências dos profissionais de saúde, mostrando--se eficiente para realizar as funções propostas.

The CalcVAN app was developed to assist healthcare professionals in optimizing vancomycin doses for hospitalized patients. However, the usability test before making it available for clinical practice is essential. Therefore, the study aims to evaluate the usability of the app from the perspective of health professionals. A descriptive study, a heuristic evaluation of the usability of a mobile application was conducted. Healthcare professionals with expertise in antimicrobial management and vancomycin were invited to participate. The validated Smartphone Usability questionnaiRE (SURE) was used to measure usability through an online questionnaire. Twenty-one experts participated in the study, with a mean age of 32.6 years, mostly of them women (n = 14, 66.7%), pharmacists (n = 13, 61.9%), with postgraduate education (n = 10, 47.6%), working in private or public hospitals (n = 15, 71.4%), and a mean experience of 9.7 years. Overall usability score for CalcVAN was 83 points, ranging from a minimum of 78 to a maximum of 90 points. The usability test registered within the last two levels, 70 and 80, with users expressing strongly and fully agreed, indicating that the app demonstrates satisfactory usability. CalcVAN achieved satisfactory usability, fulfilling the needs and requirements of health professionals, proving to be efficient in performing the intended functions.

Safety and efficacy of vancomycin therapy in a tertiary care hospital: A prospective observational study

Background: Vancomycin is widely used to treat infections caused by Gram-positive organisms. However, its use results in several clinically significant side effects in human beings. This study focuses on the safety and clinical outcomes of vancomycin therapy and its judicious use in hospitalized patients. Materials and Methods: A prospective observational study was conducted over a period of 6 months in Lourdes Hospital, Ernakulam. Demographic and clinical details, including pertinent laboratory values of patients prescribed with vancomycin during hospitalization, were documented and analyzed using a specifically designed data collection form. Results: Positive clinical outcomes were observed in a study of 60 patients treated with vancomycin for various infections, although two died within 30 days. The average duration of therapy was 6.86 days, and the average length of hospital stay was 12.23 days. Nephrotoxicity was observed in 5% of patients, with 11.6% developing acute kidney injury network (AKIN) Stage 1 and 5% progressing to Stage 2. Laboratory results demonstrated recovery from infection (reflected by reduced neutrophil and erythrocyte sedimentation rate levels) alongside a slight increase in creatinine levels and a significant decrease in urea levels. Adverse drug reactions were reported in 19 patients (31.7%). Conclusion: This study assessed the safety and efficacy of vancomycin, highlighting nephrotoxicity in 16.6% of patients. Despite some adverse reactions, there were favorable responses in 90% of the cases. Doses were administered according to standard guidelines. The study’s findings contributed to developing proposed guidelines for vancomycin use in collaboration with the Nephrology Department.

Linezolid and vancomycin for nosocomial infections in pediatric patients: a systematic review

Abstract Objective: To investigate the effectiveness of linezolid and vancomycin for the treatment of nosocomial infections in children under 12 years old. Data sources: This is a systematic review in which five randomized clinical trials about the effectiveness of linezolid and vancomycin, involving a total of 429 children with nosocomial infections, were evaluated. They were searched in scientific databases: PubMed, Bvs, and SciELO. Summary of findings: The main nosocomial infections that affected children were bacteremia, skin, and soft tissue infections followed by nosocomial pneumonia. Most infections were caused by Gram-positive bacteria, which all studies showed infections caused by Staphylococcus aureus, with methicillin-resistant S. aureus (MRSA) and methicillin-resistant coagulase-negative staphylococci strains being isolated. Both linezolid and vancomycin showed high therapeutic efficacy against different types of nosocomial infections, ranging from 84.4% to 94% for linezolid and 76.9% to 90% for vancomycin. Patients receiving linezolid had lower rates of rash and red man syndrome compared to those receiving vancomycin. However, despite the adverse reactions, antimicrobials can be safely administered to children to treat nosocomial infections caused by resistant Gram-positive bacteria. Conclusion: Both linezolid and vancomycin showed good efficacy in the treatment of bacterial infections caused by resistant Gram-positive bacteria in hospitalized children. However, linezolid stands out regarding its pharmacological safety. Importantly, to strengthen this conclusion, further clinical trials are needed to provide additional evidence.

Characterization of vancomycin resistance mechanisms in Enterococcus faecium isolates from a Brazilian tertiary hospital / Caracterização dos mecanismos de resistência à vancomicina em isolados de Enterococcus faecium de um hospital terciário brasileiro / Caracterización de los mecanismos de resistencia a la vancomicina en aislamientos de Enterococcus faecium de un hospital terciario brasileño

Background and Objectives: Vancomycin-resistant Enterococcus faecium (VREf) is an opportunistic pathogen responsible for hospital infections, characterized by increasing prevalence and a lack of comprehensive epidemiological studies. We aimed to assess the occurrence of VREf and vancomycin resistance genetic elements vanA and vanB in strains isolated from clinical samples of patients treated at a tertiary hospital in Brazil. Methods: The isolates were obtained from convenience sampling according to routine medical requests for nine months. Enterococcus faecium strains were identified by routine biochemical tests, BD Phoenix® Automated Microbiology System and confirmed by MALDI-TOF Mass Spectrometry. The antimicrobial sensitivity profile was determined by disk-diffusion method and BD Phoenix® Automated Microbiology System. Vancomycin resistance was specially assessed and confirmed by the conventional microdilution technique. Molecular detection of vanA and vanB resistance genes was investigated by polymerase chain reaction (PCR) and confirmed by Sanger DNA sequencing. Results: A total of 8,376 cultures was performed, of which 19 (0.22%) were identified as Enterococcus sp. and nine (47%) as vancomycin-resistant E. faecium. The antimicrobial susceptibility testing analysis of E. faecium showed high resistance to antimicrobial agents. The analysis to determine the genetic profile of E. faecium isolates by PCR showed that all of them carried the vanA gene associated with vancomycin resistance. Conclusion: During the study period, there was low occurrence of Enterococcus species observed. However, all VREf isolates carried the vanA gene associated with vancomycin resistance and showed resistance to commonly used antimicrobial agents, highlighting concerns about the effectiveness of available antimicrobial treatments for infections caused by these isolates.(AU)

Justificativa e Objetivos: Enterococcus faecium resistente à vancomicina (VREf) é um patógeno oportunista responsável por infecções hospitalares, caracterizado por crescente prevalência e falta de estudos epidemiológicos abrangentes. O objetivo foi avaliar a ocorrência de VREf e dos elementos genéticos de resistência à vancomicina vanA e vanB em cepas isoladas de pacientes atendidos em um hospital terciário no Brasil. Métodos: Os isolados foram obtidos por amostragem de conveniência de acordo com as solicitações médicas de rotina durante nove meses. As cepas foram identificadas por testes bioquímicos, Sistema de Microbiologia Automatizada BD Phoenix®, e confirmadas por MALDI-TOF. O perfil de sensibilidade aos antimicrobianos foi determinado por difusão em disco e pelo BD Phoenix®. A resistência à vancomicina foi avaliada e confirmada pela técnica de microdiluição. A detecção molecular dos genes de resistência vanA e vanB foi investigada por reação em cadeia da polimerase (PCR) e sequenciamento de DNA. Resultados: Um total de 8.376 culturas foi realizado, sendo 19 (0.22%) identificadas como Enterococcus sp., e nove (47%), como Enterococcus faecium resistente à vancomicina. A análise do teste de sensibilidade aos antimicrobianos do E. faecium mostrou alta resistência aos antimicrobianos. A análise para determinar o perfil genético dos isolados de E. faecium por PCR mostrou que todos eles carregavam o gene vanA associado à resistência à vancomicina. Conclusão: Durante o período de estudo, observou-se baixa ocorrência de espécies de Enterococcus. No entanto, todos os isolados de VREf apresentaram o gene vanA associado à resistência à vancomicina e mostraram resistência aos antimicrobianos comumente utilizados, alertando sobre a eficácia dos tratamentos antimicrobianos disponíveis para infecções causadas por esses isolados.(AU)

Justificación y Objetivos: Enterococcus faecium resistente a vancomicina (VREf) es un patógeno oportunista responsable de infecciones hospitalarias, caracterizado por su creciente prevalencia y la falta de estudios epidemiológicos exhaustivos. El objetivo fue evaluar la ocurrencia de VREf y los elementos genéticos de resistencia a vancomicina vanA y vanB en cepas aisladas de muestras clínicas de pacientes tratados en un hospital terciario en Brasil. Métodos: Los aislamientos se obtuvieron mediante muestreo de conveniencia según las solicitudes médicas de rutina durante nueve meses. Las cepas fueron identificadas mediante pruebas bioquímicas, utilizando el BD Phoenix® y MALDI-TOF. El perfil de sensibilidad a los antimicrobianos se determinó mediante difusión en disco y el BD Phoenix®. La resistencia a vancomicina se evaluó mediante microdilución. La detección molecular de los genes de resistencia vanA y vanB se investigó mediante reacción en cadena de la polimerasa (PCR) y secuenciación de ADN. Resultados: Se realizaron un total de 8,376 cultivos, identificándose 19 (0.22%) como Enterococcus sp., de las cuales 9 (47%) fueron VREf. El análisis de la sensibilidad a los antimicrobianos mostró una alta resistencia. El análisis para determinar el perfil genético de los aislados de E. faecium mediante PCR mostró que todos portaban el gen vanA asociado a la resistencia a la vancomicina. Conclusión: Durante el período de estudio, se observó una baja incidencia de especies de Enterococcus. Sin embargo, todos los aislamientos de VREf presentaron el gen vanA asociado con resistencia a la vancomicina y mostraron resistencia a los antimicrobianos comúnmente utilizados, lo cual alerta sobre la eficacia de los tratamientos antimicrobianos disponibles para infecciones causadas por VREf.(AU)

Evaluation of antibiotic resistance and quorum sensing assay of Enterococcus faecalis isolates from the urine samples

The Gram-positive Enterococci found in the normal flora of the gastrointestinal tract (GIT) and urinary tract infection (UTI) were characterized by high resistance to antibiotics and large virulence. The aim of our study was to evaluate the diversity of antibiotic-resistant and quorum-sensing assays of Enterococcus faecalis isolated from urine samples of children aged between 11 and 15 with UTI. A total of 155 samples were collected from hospitals and diagnostic centers of Kalaburagi region. The E. faecalis isolates were screened on bile esculin azide agar media. Antibiotic susceptibility test was performed using different antibiotics as per Clinical and Laboratory Standards Institute guidelines. Minimum inhibitory concentrations (MICs) for gentamycin and vancomycin were determined by the method of broth dilution. Quorum sensing assay of E. faecalis was determined by a bioluminescence-based method. The species-level identification of E. faecalis isolates was determined by 16S rRNA polymerase chain reaction amplification. The incidence of E. faecalis in urine samples was found to be 47.74% (74/155). Antimicrobial susceptibility test (AST) indicates that 27% of isolates were multi-drug resistant, showing increased resistance to gentamycin and vancomycin (54.05%). MIC results show that 23 isolates were resistant to gentamycin with concentration of 128 ?g/ml and 17 isolates were resistant to vancomycin with concentration of 1024 ?g/ml. The quorum sensing assay has shown that the normalized relative light units range from 0.4 to 1.2. According to the 16srRNA gene amplification, out of 10 isolates, seven were identified as Enterococcus faecalis and three isolates were Streptococcus gallolyticus. This study emphasizes the development of increased vancomycin resistance of E. faecalis and indicates the presence of the virulence factors through the autoinducer assay. It is been suggested that major precaution measures should be implemented in the eradication of VRE in UTI infection.

Vancomicina contra metronidazol en infección por Clostridioides difficile leve-moderada de manejo ambulatorio / Vancomycin or metronidazole in the outpatient treatment of mild-moderate Clostridioides difficile infection

INTRODUCCIÓN: En la diarrea asociada a Clostridioides dfficile (DACD) leve-moderada se recomienda tratar con vancomicina por sobre metronidazol, a pesar de su difícil acceso y poca evidencia en el medio ambulatorio. OBJETIVO: Comparar la tasa de cura clínica y recurrencia entre vancomicina y metronidazol en adultos chilenos con primer episodio leve-moderado de DACD de manejo ambulatorio. MÉTODOS: Cohorte retrospectiva entre enero 2015 y diciembre 2020 en centros de una red de salud universitaria de pacientes de ≥ 18 años con DACD tratados ambulatoriamente. RESULTADOS: Se obtuvieron 161 pacientes, 59% mujeres, edad promedio de 53 años (entre 18 y 94 años). De ellos, 109 (67,7%) usaron metronidazol y 52 (32,3%) vancomicina. En el análisis multivariado ajustado por edad y comorbilidades se obtuvo un OR 3,00 (IC 95% 1,12-9,59) para cura clínica y 0,27 (IC 95% 0,06-0,88) para recurrencia a ocho semanas, ambos a favor de vancomicina, sin diferencias en recurrencia a 12 meses, necesidad de hospitalización o mortalidad. CONCLUSIÓN: La terapia con vancomicina comparada contra metronidazol en el tratamiento ambulatorio de la infección leve-moderada por C. dfficile se asocia a mayor cura clínica y menor tasa de recurrencia a corto plazo, sin diferencias en desenlaces a largo plazo.

BACKGROUND: Recommended treatment against mild cases of Clostridioides difficile associated diarrhea is vancomycin despite the difficulties of access compared to metronidazole. AIM: To compare the effectiveness of vancomycin and metronidazole in Chilean adults with first mild-moderate episode of Clostridiodes difficile infection (CDI). METHODS: Retrospective cohort of patients with CDI between January 2015 and December 2020 treated in centers of a university health network. The patients were adults treated for C. difficile infection on an outpatient basis. Recurrent and severe cases were excluded. Outcomes included clinical cure and recurrence rate. RESULTS: Data from 161 patients was recovered. Fifty-nine percent were women and average age was 53 (18-94). One hundred and nine patients were treated with metronidazole (67.7%) and 52 (32.3%) used vancomycin. Multivariate analysis adjusted by age and comorbidities showed an Odds Ratio of 3.00 (IC 95% 1.12-9.59) for clinical cure and 0.27 (IC 95% 0.06-0.88) for 8-week recurrence rate, both in favor of vancomycin, without differences in 12-month recurrence rate, hospitalization rate nor mortality. CONCLUSIONS: Vancomycin is associated with better short-term outcomes in the treatment of outpatient mild-moderate first episode C. difficile infection, without differences in long term recurrence or mortality when compared with metronidazole.

The association between vancomycin trough concentrations and nephrotoxicity in the paediatric intensive care unit / A associação entre concentrações no vale de vancomicina e nefrotoxicidade em uma unidade de terapia intensiva pediátrica

Objective: To analyze and describe the pharmacokinetic aspects of vancomycin usage in a cohort of critically ill children and to construct a pharmacokinetic model for this population. Method: We conducted an observational study in a pediatric intensive care unit from September 2017 to March 2019. Children receiving vancomycin with at least one serum measurement were included. Variables with a p-value lower than 0.2 in univariate analysis, and biologically plausible for inducing nephrotoxicity and not correlated with other predictors, were incorporated into logistic regression. Additionally, pharmacokinetic modeling was performed using the PMETRICS® package for patients with creatinine clearance (CLCR) > 30 mL/min. Result: The study included 70 children, with an average vancomycin dose of 60 mg/kg/day. Only eleven children achieved vancomycin levels within the target range (15-20 mg/L). No significant differences in doses/mg/kg/day were observed among children above, within, or below the vancomycin target range. In the multivariate model, children above the recommended serum range had an odds ratio of 4.6 [95% CI 1.4 ­ 17.2] for nephrotoxicity. A pharmacokinetic model was proposed using data from 15 children, estimating PK parameters for CLCR and V as 0.94 L/h and 5.71 L, respectively. Conclusion: Nephrotoxicity was associated with vancomycin plasma concentrations equal to or exceeding 15 mg/L. The developed model enhanced understanding of the drug's behavior within this population, potentially aiding clinical practice in dose calculations and estimation of the area under the curve ­ a recommended parameter for vancomycin monitoring.

Objetivo: Analisar e descrever os aspectos farmacocinéticos do uso de vancomicina em uma coorte de crianças sob cuidados intensivos e elaborar um modelo farmacocinético para essa população. Método: Estudo observacional em uma unidade de terapia intensiva pediátrica conduzido entre setembro de 2017 a março de 2019. Inclui-se crianças em uso de vancomicina com pelo menos uma mensuração sérica desse antimicrobiano. As variáveis com valor de p < 0,2 na análise univariada e com plausibilidade biológica para propiciar nefrotoxicidade, não correlacionadas com outras preditoras, foram incluídas na regressão logística. Adicionalmente, uma modelagem farmacocinética foi realizada usando o programa PMETRICS® para pacientes com clearance de creatinina (CLCR) > 30 mL/min. Resultado: Foram incluídas 70 crianças no estudo. A dose média de vancomicina foi de 60 mg/kg/dia. Apenas onze crianças apresentaram vancocinemia dentro da faixa alvo (15-20 mg/L). Não foram observadas diferenças significativas entre as doses administradas e a observação de vancocinemia acima, dentro ou abaixo da faixa preconizada. No modelo multivariado, crianças acima da faixa sérica preconizada apresentaram odd ratio de 4,6 [IC 95% 1,4 ­ 17,2] para nefrotoxicidade. Um modelo farmacocinético com os dados de 15 crianças foi proposto, no qual os parâmetros de PK estimados para CLCR e Volume de distribuição foram de 0,94 L/h e 5,71 L, respectivamente. Conclusão: A nefrotoxicidade mostrou-se associada às concentrações plasmáticas de vancomicina iguais ou maiores a 15 mg/L. O modelo desenvolvido permitiu entender o comportamento do fármaco nessa população e pode ser útil na prática clínica para o monitoramento do uso de vancomicina.

Repair of infected osteochondral defect with sustained release vancomycin three-dimensional scaffold in rabbits / 中国组织工程研究

BACKGROUND:A large number of studies have confirmed that tissue engineering scaffolds can almost completely repair osteochondral defects.However,when osteochondral defects are complicated with infection,even after thorough debridement in the early stage,the repair effect of simple osteochondral tissue engineering scaffolds is often unsatisfactory. OBJECTIVE:To prepare fibroin/chitosan/nano-hydroxyapatite scaffold loaded with vancomycin hydrochloride sustained release microspheres,and to investigate the repair effect on infected osteochondral defect in distal femur of rabbit. METHODS:(1)Vancomycin hydrochloride sustained release microspheres were prepared by emulsified solvent evaporation method.The sustained-release microspheres of different weights(7.5,10,and 12.5 mg)were mixed with fibroin protein-chitosan nanohydroxyapatite solution,and the scaffolds of fibroin protein/chitosan/nano-hydroxyapatite were prepared by chemical crosslinking method.The porosity,water absorption and expansion rate,hot water loss rate of the scaffolds,and drug sustained-release in vitro were characterized.(2)Forty-five New Zealand white rabbits were randomly divided into blank group,control group,and experimental group,with 15 rabbits in each group.The osteochondral defect and infection model of the distal femur of the right hind limb was established in both groups.The blank group was not treated,and the control group was implanted with fibroin protein-chitosan-nano-hydroxyapatite scaffold.Vancomycin hydrochloride sustained-release microspheres(10 mg)of fibroin/chitosan/nano-hydroxyapatite scaffold were implanted in the defect of the experimental group.The levels of C-reactive protein and leukocytes in blood samples were detected 1 week after operation.At 4,8 and 12 weeks after operation,the tissue of the operative area was taken for gross observation and pathological observation. RESULTS AND CONCLUSION:(1)With the increase of sustained-release microspheres content,the porosity of scaffolds decreased,and there was significant difference among groups(P＜0.05).There were no significant differences in the pore size,water absorption expansion rate and hot water loss rate among the three groups(P＞0.05).Vancomycin hydrochloride was released sustainably in vitro for more than 30 days in all three groups of scaffolds.(2)The levels of C-reactive protein and leukocytes in blood samples of the experimental group were lower than those of the blank group and control group(P＜0.05).The repair of gross cartilage in the experimental group was significantly better than that in the blank group and the control group.Hematoxylin-eosin,Masson,Alcian blue and type Ⅱ collagen immunohistochemical stainings showed that the osteochondral repair effect of the experimental group was significantly better than that of the blank group and the control group at each time point.(3)The results showed that fibroin/chitosan/nano-hydroxyapatite scaffolds loaded with vancomycin hydrochloride sustained-release microspheres could effectively promote the repair of open osteochondral defects.

Topical application of vancomycin in prevention of early incision infection in total knee arthroplasty / 中国组织工程研究

BACKGROUND:The use of vancomycin in total knee arthroplasty is a controversial strategy for the prevention of incisional infection.At present,there is little evidence to evaluate the efficacy of this preventive measure in China. OBJECTIVE:To evaluate the efficacy of local vancomycin in the prevention of early postoperative incision infection during total knee arthroplasty. METHODS:120 patients with osteoarthritis of the knee who received unilateral total knee arthroplasty for the first time at Department of Joint Surgery of First Affiliated Hospital of Anhui Medical University from March to June 2022 were included in this study.They were randomly divided into the observation group and the control group,with 60 cases in each group.All patients gave informed consent to the treatment plan.In the observation group,1 g of vancomycin was applied intraoperatively;in the control group,no vancomycin was applied intraoperatively.Erythrocyte sedimentation rate,C-reactive protein,fever rate on seven consecutive days after surgery,degree of knee joint swelling,cumulative drainage volume,and incidence of periprosthetic joint infection were recorded in two groups of patients on days 1,3,and 5 after surgery so as to evaluate the efficacy of topical vancomycin in total knee arthroplasty for the prevention of incision infection in the early postoperative period. RESULTS AND CONCLUSION:(1)The differences in erythrocyte sedimentation rate and C-reactive protein between the two groups on days 1,3,and 5 after surgery were not significant(P>0.05).(2)The difference in fever rate between the two groups for 7 consecutive days after surgery was not significant(P>0.05).(3)There was no significant difference in the degree of postoperative knee swelling and cumulative drainage flow between the two groups(P>0.05).(4)The difference in the incidence of periprosthetic joint infection one year after surgery was not significant between the two groups(P>0.05).(5)The results suggest that the local use of vancomycin in total knee arthroplasty has not shown significant efficacy in preventing incision infection in the early postoperative period.

Clinical Efficacy of Clostridium Difficile Infection in Children / 医学研究杂志

Objective To analyze the clinical characteristics and treatment of clostridium difficile infection(CDI)in children.Methods The clinical data of 159 children with CDI admitted to the Department of Gastroenterology and Hepatology,Shanghai Children's Hospital,School of Medicine,Shanghai Jiao Tong University from September 2014 to October 2022 were retrospectively analyzed.All ini-tial CDI patients were divided into vancomycin treatment group and metronidazole treatment group according to different treatment meth-ods,Children with recurrent CDI(RCDI)were divided into two groups according to vancomycin or FMT treatment.Results A total of 159 children with initial CDI were included,including 93 males and 66 females,the age of these children was 4.3(1.7,8.0)years.109 children(68.55％)were treated with metronidazole,and 50 children(31.45％)were treated with vancomycin.Recurrence occurred in 51 children after antibiotic treatment,37 children(33.94％)of them treated with metronidazole,and 14 children(28.00％)of them treated with vancomycin,there was no significant difference(P＞0.05).Among RCDI children,21 cases were treated with vancomycin and 30 were treated with FMT.The cure rate of FMT was 90.00％,and the cure rate of vancomycin was 57.14％.The cure rate of FMT was significantly higher than that of vancomycin.There were no serious adverse events reported after two months of FMT treatment.Conclusion Metronidazole can be used as the drug of choice for initial CDI in children.The cure rate of FMT for RCDI is superior to vancomycin treatment.

Therapeutic Drug Monitoring of 1 106 Cases of Vancomycin Therapy and Analysis of Risk Factors / 医药导报

Objective To analyze the achievement of target vancomycin concentration and the risk factors affecting the concentration to reach the target,providing a reference for the rational use of vancomycin and the implementation of therapeutic drug monitoring(TDM).Methods Patients who were hospitalized and received vancomycin TDM from January 2016 to June 2019 at Zhongshan Hospital,Fudan University were selected.Clinical data,vancomycin blood concentrations,and occurrences of acute kidney injury(AKI)during the hospitalization were collected.Factors affecting the attainment of target vancomycin concentrations were analyzed using logistic regression and grouped according to whether the target concentrations were attained.The correlation between drug concentration and the occurrence of AKI was analyzed.Results A total of 1 106 patients were included,with 70.7％being males and a median age of 60.0(IQR=20)years.Surgical departments accounted for 76.4％of the distribution.The median duration of vancomycin therapy was 10.8 d(IQR=9.0).A total of 21.6％of patients had their first concentration monitored before administration of doses 4 and 5.The drug concentration monitoring results of 46.8％(518/1 106)of patients were in the range between 10-20 μg·mL-1,reaching the target concentration range.The incidence of vancomycin-associated AKI was 25.9％.The incidence of AKI varied among patients with different vancomycin concentrations:when the concentrations are＜10,10-＜15,15-20,and＞20 μg·mL-1,the AKI rates are 15.8％,20.5％,25.8％,and 39.4％,respectively.Multivariate logistic regression analysis showed that target concentrations were more likely to be reached with a dosing course of＞7-14 d(OR=1.688,P=0.001)and＞14 d(OR=1.744,P=0.002)than with a dosing course of ≤7 d.Patients receiving conventional daily doses were more likely to achieve target concentrations than those receiving the non-conventional daily dose(OR=1.540,P=0.003).Conclusion The current status of vancomycin TDM in China still suffers from deficiencies,such as delayed timing of monitoring and low rate of target concentration attainment.Higher vancomycin concentrations are significantly associated with AKI,and the factors affecting the vancomycin concentration to reach the target mainly include treatment duration and the complexity of the dosing regimen.

Drug Resistance and Prognosis of 150 Cases of Peritoneal Dialysis-associated Peritonitis / 医药导报

Objective To analyze the pathogenic bacteria and drug resistance of peritoneal dialysis-associated peritonitis(PDAP),and provide a clinical reference for the rational use of antibiotics.Methods The demographic data of PDAP patients admitted to the peritoneal dialysis(PD)Center of the First Affiliated Hospital of Soochow University from July 1,2015 to December 30,2021 were collected,and the pathogens,drug resistance and prognosis were retrospectively analyzed.Results A total of 150 episodes of PDAP occurred in 92 patients.The positive rate of PD fluid culture was 61.33％,including 65 cases(70.65％)of Gram-positive(G+)bacteria,mainly Staphylococcus and Streptococcus.Gram-negative(G-)bacteria were in 16 cases(17.39％),mainly Escherichia coli and Enterobacter cloacae.There were 11 cases(11.96％)of multiple infections,including 5 cases of combined fungal infection.From 2016 to 2021,the incidence of G+bacteria-related PDAP decreased from 14 to 8 cases.G+strains were resistant to methicillin(35.00％),and were sensitive to linezolid(100.00％),teicoplanin(100.00％)and rifampicin(100.00％).The sensitivity rate to vancomycin was 98.59％.G-strains were sensitive to ceftazidime(86.36％),ceftizoxime(88.89％)and amikacin(100.00％).The MIC of vancomycin against Staphylococcus showed an upward trend in 2019-2021.The overall cure rate of PDAP was 81.33％in patients who responded to antibiotic treatment,and the cure rate of G+bacteria was higher than that of multiple infections(89.23％vs.36.36％,P＜0.01).The outcome of patients with multiple infections,especially those with concurrent fungal infection was poor.Conclusion The incidence of PDAP in the PD center has shown a decreasing trend in recent years.G+bacteria are still the main pathogenic bacteria causing PDAP,and they are highly resistant to methicillin,so vancomycin should be used as empirical therapy.For G-bacteria,cefotaxime and amikacin can be chosen as empirical therapy.There is a drift in the MIC values of vancomycin against Staphylococcus in the study period,so it is necessary to monitor the MIC of vancomycin against Staphylococcus and its changing trend.

Analysis of influencing factors and prediction models of vancomycin AUC0-24h in postoperative orthopedic patients / 中国药师

Objective To investigate the influencing factors of vancomycin in the area under curve for 24 h(AUC0-24h)in patients after orthopedic surgery,and to predictive and analyze a good pharmacokinetic model for AUC0-24h Methods Patients who underwent orthopedic surgery and used vancomycin in The Sixth Affiliated Hospital of Xinjiang Medical University from January 2018 to December 2022 were included,and the basic information,the medication,the blood and biochemical indexes of the patients were collected to analyze the factors affecting postoperative vancomycin AUC0-24h in orthopedic surgery.The AUC0-24h was calculated using the first-level pharmacokinetic formula,the JavaPK? for Desktop(JPKD)and the vancomycin daily dose elimination rate formula.Results 91 patients were finally included,and the cystatin C(OR=189.168,P=0.005)and the single dose(OR=19.160,P＜0.001)were independent protective factors for vancomycin AUC0 24 h in postoperative orthopedic patients,and the retinol binding protein was an independent risk factor for vancomycin AUC0-24h(OR=0.910,P＜0.05).By predicting and analyzing the model of vancomycin AUC0 24h in postoperative orthopedic patients,the absolute percentage error of both JPKD software and vancomycin daily dose elimination rate formula were lower than 30％.The intraclass correlation efficient between the AUC0 24h of the JPKD software and vancomycin daily dose elimination rate formula,and the AUC0 24h of the first-level pharmacokinetic formula were 0.781 and 0.524,respectively.Conclusion Cystatin C is an important factor influencing vancomycin AUC0-24h in postoperative orthopedic patients,and JPKD software is more suitable for predicting vancomycin AUC0-24h after orthopedic surgery than the vancomycin daily dose elimination rate formula method.

Bacteriologic profile, antibiotics resistance pattern, and outcomes of patients admitted to Lancet General Hospital from June 2022 to June 2023: A retrospective cohort study

Background Prior studies indicated increased antimicrobial resistance in Ethiopia, with related health, economic, and environmental costs. Knowing an institutions and population microbiologic profile allows for proper antibi-otic treatment, which substantially impact patients' outcomes such as healthcare related costs, morbidity, and mortality. The current study assessed the bacteriologic profile, resistance pattern, and treatment outcome in Lancet General Hospital. Method A retrospective cohort study on the bacteriologic profile, antibiotics resistance pattern, and outcome of patients was done on 128 eligible patients who were admitted to Lancet General Hospital from June 2022 to June 2023. Data from all hospitalized patients with culture-confirmed infection were analyzed. SPSS version 26.0 was used to analyze the data. Association between independent and dependent variables was analyzed using binary logistic regression model. Results Gram-negative bacteria were recovered in 77% of the cases. Extended-spectrum beta-lactamase producing Enterobacteriaceae was found in 37.5% (54) isolates and carbapenem resistant bacteria were identified in 27.8% of patients. In-hospital mortality from multidrug resistant bacterial infection was 14.8%. Age ≥ 65 years, presence of septic shock, and presence of carbapenem-resistant bacteria were independently associated with in-creased in-hospital mortality. Conclusion High number of resistant microorganisms was isolated, and increased mortality was documented from infections caused by carbapenem-resistant bacteria. Multi-center studies should be done to determine the extent of resistant organisms in health facilities throughout the country. epidemiology, and the findings should be factored into clinical decision making and program design for disease prevention, screening, and treatment. It also calls for further prospective research to learn more about the conditions in the context of additional relevant personal and clinical characteristics

El desarrollo y los complejos mecanismos de resistencia de S. aureus: una amenaza persistente en la era de los antibióticos

Introducción: S. aureus ha emergido como una amenaza persistente, demostrando una notable habilidad para desarrollar resistencia a lo largo de la evolución de los antibióticos. Desde los primeros enfrentamientos con la penicilina hasta los desafíos actuales con cepas resistentes a la vancomicina y la daptomicina, el estudio de los mecanismos de resistencia de este patógeno ha adquirido una importancia crítica. Objetivos: documentar los cambios en los patrones de resistencia de S. aureus a lo largo del tiempo, además de identificar las etapas críticas en el desarrollo de la resistencia a diferentes antibióticos. Materiales y métodos: el proceso de selección de artículos revisados se llevó a cabo identificando artículos publicados entre 2010 y 2023. Se utilizaron varias bases de datos relevantes, incluyendo PubMed, Scopus, Embase, Cochrane Library y Scielo. Se incluyeron estudios observacionales, artículos de revisión y guías clínicas. Se desarrollaron estrategias de búsqueda específicas para cada base de datos utilizando palabras clave y términos de búsqueda relacionados con S. aureus y su resistencia antimicrobiana, así como los tipos de estudios de interés. Se extrajeron datos relevantes de los estudios seleccionados, incluyendo información sobre los patrones de resistencia, mecanismos de resistencia, impacto clínico y estrategias terapéuticas. Los datos recopilados se analizaron y sintetizaron para documentar los cambios en los patrones de resistencia de S. aureus a lo largo del tiempo y para identificar las etapas críticas en el desarrollo de la resistencia a diferentes antibióticos. Resultados: se incluyeron 100 artículos donde se evidencia una evolución temporal de la resistencia, desde las primeras cepas resistentes a la penicilina hasta las actuales cepas resistentes a la vancomicina y la daptomicina. Estos estudios proporcionaron un análisis detallado de los mecanismos moleculares clave que impulsan la resistencia antimicrobiana, tales como la producción de beta-lactamasas, las alteraciones en las proteínas de unión a penicilina y las modificaciones en la membrana celular. Los hallazgos destacan una evolución significativa en la capacidad de S. aureus para adaptarse a diferentes antibióticos a lo largo del tiempo, subrayando la complejidad y la diversidad de los mecanismos de resistencia desarrollados por esta bacteria. Conclusiones: la evolución de la resistencia de S. aureus ha seguido un patrón marcado por etapas críticas, desde la aparición de cepas productoras de penicilinasa tras la introducción de la penicilina, hasta el surgimiento de MRSA con la meticilina y de VISA y VRSA con la vancomicina. Estos cambios destacan la capacidad de adaptación de S. aureus a nuevas presiones antibióticas. La revisión subraya la necesidad urgente de desarrollar estrategias antimicrobianas innovadoras y sostenibles para controlar esta creciente amenaza. Comprender los mecanismos de resistencia es crucial para desarrollar enfoques más efectivos y personalizados en el tratamiento de las infecciones por este germen.

Introduction: S. aureus has emerged as a persistent threat, demonstrating a remarkable ability to develop resistance throughout the evolution of antibiotics. From the first confrontations with penicillin to the current challenges with strains resistant to vancomycin and daptomycin, the study of the resistance mechanisms of this pathogen has acquired critical importance. Objectives: To document changes in S. aureus resistance patterns over time and identify critical stages in the development of resistance to different antibiotics. Materials and methods: The reviewed articles were selected by identifying articles published between 2010 and 2023. Several relevant databases were used, including PubMed, Scopus, Embase, Cochrane Library, and SciELO. Observational studies, review articles, and clinical guidelines were included. Specific search strategies were developed for each database using keywords and search terms related to S. aureus and its antimicrobial resistance as well as the types of studies of interest. Relevant data were extracted from the selected studies, including information on resistance patterns, resistance mechanisms, clinical impact, and therapeutic strategies. The collected data were analyzed and synthesized to document changes in S. aureus resistance patterns over time and identify critical stages in the development of resistance to different antibiotics. Results: One hundred articles were included where a temporal evolution of resistance is evident, from the first strains resistant to penicillin to the current strains resistant to vancomycin and daptomycin. These studies provided a detailed analysis of the key molecular mechanisms driving antimicrobial resistance, such as beta-lactamase production, alterations in penicillin-binding proteins, and cell membrane modifications. The findings highlight a significant evolution in the ability of S. aureus to adapt to different antibiotics over time, underscoring the complexity and diversity of resistance mechanisms developed by this bacterium. Conclusions: The evolution of S. aureus resistance has followed a pattern marked by critical stages, from the appearance of penicillinase-producing strains after the introduction of penicillin to the emergence of MRSA with methicillin and of VISA and VRSA with vancomycin. These changes highlight the ability of S. aureus to adapt to new antibiotic pressures. The review highlights the urgent need to develop innovative and sustainable antimicrobial strategies to control this growing threat. Understanding resistance mechanisms is crucial to developing more effective and personalized approaches for the treatment of infections caused by this germ.

Comparison of vancomycin assays in patients undergoing hemodialysis

Abstract Vancomycin is a glycopeptide antibiotic mainly excreted by glomerular filtration. Therefore, patients undergoing hemodialysis tend to accumulate its crystalline degradation product, which has been associated with cross-reaction in commercial immunoassays. The aim of this study was to assess the performance of two commercial immunoassays for measuring vancomycin levels in patients undergoing hemodialysis. This method-comparison study enrolled patients undergoing hemodialysis at two hospitals in Porto Alegre, Brazil. Vancomycin serum concentrations measured by Chemiluminescent Microparticle Assay (CMIA) and measured by Kinetic Interaction of Microparticles in Solution (KIMS) were compared with Liquid Chromatography coupled with Tandem Mass Spectrometry (LC-MS/MS). A total of 64 samples from 42 patients and 54 samples from 23 patients were included in CMIA and KIMS groups. Both measurements were highly correlated with LC-MS/MS, with Spearman rank correlation coefficient r = 0.840 (p < 0.001) and r = 0.926 (p < 0.001), respectively. No deviation of linearity was observed (p = 0.81 and p = 0.49, respectively). The mean difference between CMIA and LC-MS/MS was -1.19 μg/mL and between KIMS and LC-MS/MS was -2.28 μg/mL. LC-MS/MS measured levels were, on average, 2.64 % higher than CMIA and 8.81 % higher than KIMS. CMIA and KIMS revealed accurate commercial methods to measure vancomycin serum concentrations in patients undergoing hemodialysis.

Evaluation of diagnostic accuracy of latex agglutination test and E-test for the detection of methicillin-resistant Staphylococcus aureus

Background: This study was undertaken to compare the phenotypic methods of latex agglutination test and e-test with polymerase chain reaction for the detection of methicillin-resistant Staphylococcus aureus. Methods: Two hundred pus samples obtained from different clinical disciplines were subjected to the latex agglutination test and minimum inhibitory concentration by e-test (Oxacillin and Vancomycin) as per the standard guidelines. The comparison was made with polymerase chain reaction as the reference test. The diagnostic accuracy of each method was reported in terms of sensitivity, specificity, positive predictive value, and negative predictive value. Results: The sensitivity of latex agglutination test was found to be 100% whereas e-test for Oxacillin was found to be 96.67% sensitive. Higher specificity for e-test was reported (99.41%) when compared to the latex agglutination test (97.65%). Conclusions: Latex agglutination and e-tests are tests are relatively simpler, rapid, and easy-to-perform methods when compared to polymerase chain reaction. The present study reported high sensitivity and specificity values for both the tests, and therefore supports usage of the stated methods as screening tools for methicillin-resistant S. aureus. However, more multi-centric studies are recommended to precisely determine the diagnostic accuracy of these phenotypic methods.

PREVALENCE OF VANCOMYCIN RESISTANT ENTEROCOCCI FROM URINARY TRACT INFECTED PATIENTS

Urinary tract infections (UTIs) are one of the infectious diseases affecting humankind. The microbial agents that infect the tissues of the urinary tract from the renal cortex to the urethral meatus Enterococci are opportunistic pathogens that are found in the normal gut flora. Enterococci are the second leading cause of UTIs, accounting for 10% of all nosocomial UTIs. This species has become a major pathogen in the United States, Iran, Europe, and other parts of the world, including India. Antibiotic resistance is increasing, which slows the rate of progress in practical therapies, making susceptibility testing necessary. So, enterococci were isolated from urine samples of patients with UTI that were subjected to morphological characterization, biochemical assays, etc., The main aim of the study was to help in identifying resistance patterns and the dispersal of Enterococcus strains from various samples of urine to antibiotic agents like Penicillin G, Tetracycline, Teicoplanin, Norfloxacin, high-level Gentamycin, Linezolid, Nitrofurantoin, and with special emphasis on Vancomycin antibiotic. The greatest threat posed by Vancomycin-Resistant Enterococci (VRE) is its ability to transfer resistance genes to more dangerous gram-positive bacteria, potentially leading to truly terrifying pathogens in the future. A long stay in the hospital and the use of Vancomycin were connected to VRE-UTI and colonisation. Renal dialysis, renal failure, previous aminoglycoside, and third-generation cephalosporin use were all relevant hazard factors for VRE from UTI. The paper also underlines the importance of screening clinical samples for VRE and proposes that control measures be implemented to limit the spread of VRE.

Clinical Evaluation of a Vancomycin Dosage Strategy Based on a Serum Trough Concentration Model in Elderly Patients with Severe Pneumonia / 生物医学与环境科学（英文）

OBJECTIVE@#This study aimed to evaluate the clinical benefits of a vancomycin dosage strategy based on a serum trough concentration model in elderly patients.@*METHODS@#This prospective single-center, open-label, randomized controlled trial categorized 66 elderly patients with severe pneumonia into study and control groups. The control group received vancomycin using a regimen decided by the attending physician. Meanwhile, the study group received individualized vancomycin therapy with a dosing strategy based on a serum trough concentration model. The primary endpoint was the proportion of patients with serum trough concentrations reaching the target values. The secondary endpoints were clinical response, vancomycin treatment duration, and vancomycin-associated acute kidney injury (VA-AKI) occurrence.@*RESULTS@#All patients were at least 60 years old (median age = 81 years). The proportion of patients with target trough concentration achievement (≥ 15 mg/L) with the initial vancomycin regimen was significantly higher in the study group compared to the control group (75.8% vs. 42.4%, P = 0.006). Forty-five patients (68.2%) achieved clinical success, the median duration of vancomycin therapy was 10.0 days, and VA-AKI occurred in eight patients (12.1%). However, there were no significant differences in these parameters between the two groups. The model for predicting vancomycin trough concentrations was upgraded to: serum trough concentration (mg/L) = 17.194 - 0.104 × creatinine clearance rate (mL/min) + 0.313 × vancomycin daily dose [(mg/(kg∙d)].@*CONCLUSION@#A vancomycin dosage strategy based on a serum trough concentration model can improve the proportion of patients achieving target trough concentrations in elderly patients with severe pneumonia.