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Objective:To evaluate the antibacterial efficacy of ceftobiprole, vancomycin, linezolid, and daptomycin against Staphylococcus aureus (SAU) and coagulase-negative Staphylococcus (CNS) bloodstream infections, which can provide a reference for clinical medication. Methods:A total of 1 777 strains of staphylococci were isolated from blood culture of 51 hospitals within the Blood Bacterial Resistant Investigation Collaborative System (BRICS) from January to December in 2021. The dilution method was used to assess the minimum inhibitory concentrations (MIC) of ceftobiprole, vancomycin, linezolid and daptomycin on staphylococci. Additionally, the probability of target attainment (PTA) and cumulative fraction of response (CFR) of these medications in varied dosage regimens were predicted using Monte Carlo simulation.Results:Ceftobiprole demonstrated significant antibacterial activity against methicillin-resistant Staphylococcus aureus(MRSA), the MIC 50 and MIC 90 were 0.500 and 1.000 mg/L, respectively, and the MIC range was ≤0.060 to 4.000 mg/L.Meanwhile, the ceftobiprole-resistance rate of SAU was 0.1%(1/1 073), but the resistance rate of CNS was 7.7%(54/704). There was no evidence of staphylococcal resistance to daptomycin or vancomycin. Against methicillin-sensitive Staphylococcus aureus (MSSA), no resistance to the four drugs was observed. Monte Carlo simulation showed that standard drug regimens of ceftobiprole (500 mg once every eight hours) and daptomycin (6 mg·kg -1·d -1) achieved high PTA and CFR against staphylococcus.The current vancomycin and linezolid standard treatment for staphylococcal bloodstream infections had a low CFR. When vancomycin 1 000 mg once every eight hours was used, the CFRs of MRSA and MSSA were both≥90.0%, while the CFR of CNS was still less than 80.0%. CFR of linezolid against staphylococcus was ≥90.0% under the dosages of 600 mg once every eight hours. Conclusions:Ceftobiprole, vancomycin, linezolid and daptomycin all show strong antibacterial activity against staphylococcus.Ceftobiprole and daptomycin standard treatment represent adequate antibacterial efficacy against staphylococcal bloodstream infections. Furthermore, appropriate increase of the dosages of vancomycin and linezolid based on the MIC value and species of bacteria is necessary.
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AIM: To investigate the effect of extracorporeal membrane oxygenation (ECMO) on the pharmacokinetics/pharmacodynamics (PK/PD) of daptomycin in critically ill patients. METHODS: Twenty four patients with severe infection in our hospital were randomly selected and divided into ECMO group and non ECMO group. They were intravenously injected with daptomycin 500 mg qd. After the drug reached the stability statement, venous blood was collected at different time points before and after the infusion. The plasma drug concentration was measured and the pharmacokinetic parameters were calculated. The probability target acquisition (PTA) and the cumulative fraction response (CFR) were calculated by Monte Carlo simulation. RESULTS: After dosing, the main pharmacokinetic parameters in ECMO and non-ECMO group were calculated and listed as follows: C
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Objective:To predict and evaluate the antibacterial efficacy of linezolid, teicoplanin and daptomycin against Staphylococci bloodstream infections with Monte Carlo simulation, and to optimize the clinical administration program. Methods:A total of 1 847 Staphylococci strains isolated from blood samples between January 2018 to December 2019 were collected with the help of the Blood Bacterial Resistant Investigation Collaborative System (BRICS). Minimum inhibitory concentrations (MIC) of linezolid and daptomycin were detected by broth dilution method, while MIC of teicoplanin were detected by agar dilution method. The dosage regimens of linezolid were 800 mg once daily, 500 mg once every 12 hours, 600 mg once every 12 hours and 600 mg once every eight hours. The dosage regimens of teicoplanin were 400 mg once every 12 hours, 600 mg once every 12 hours, 800 mg once every 12 hours, and 1 000 mg once every 12 hours. The dosage regimens of daptomycin were 4 mg·kg -1·d -1, 6 mg·kg -1·d -1, 8 mg·kg -1·d -1, 10 mg·kg -1·d -1and 12 mg·kg -1·d -1. The probability of target attainment (PTA) and cumulative fraction of response (CFR) of three different dosage regimens were calculated by Monte Carlo simulation. A dosage regimen with CFR≥90.0% was a reasonable choice for empirical antimicrobial therapy. Results:PTA of linezolid against Staphylococci when MIC≤0.500 mg/L at four dosage regimens (800 mg once daily, 500 mg once every 12 hours, 600 mg once every 12 hours and 600 mg once every eight hours) were all over 90.0%. When MIC was 1.000 mg/L, the PTA of linezolid against Staphylococci under the dosages of 500 mg once every 12 hours, 600 mg once every 12 hours and 600 mg once every eight hours were 92.2%, 96.6% and 97.6%, respectively. The CFR of the four dosage regimens of linezolid were 73.9%, 83.7%, 90.8% and 95.3%, respectively. When MIC≤1.000 mg/L, PTA of teicoplanin against Staphylococci were all 100.0% at four dosage regimens (400 mg once every 12 hours, 600 mg once every 12 hours, 800 mg once every 12 hours and 1 000 mg once every 12 hours). When MIC was 2.000 mg/L, the PTA of teicoplanin (800 mg once every 12 hours and 1 000 mg once every 12 hours) against Staphylococci were both 100.0%. The CFR of the four dosage regimens of teicoplanin were 90.8%, 92.8%, 93.5% and 94.6%, respectively. When MIC≤0.500 mg/L, PTA of daptomycin against Staphylococci under the five dosages of 4 mg·kg -1·d -1, 6 mg·kg -1·d -1, 8 mg·kg -1·d -1, 10 mg·kg -1·d -1 and 12 mg·kg -1·d -1 were all over 90.0%. When MIC was 1.000 mg/L, the PTA of daptomycin against Staphylococci under the three dosages of 8 mg·kg -1·d -1, 10 mg·kg -1·d -1 and 12 mg·kg -1·d -1were 96.9%, 100.0% and 100.0%, respectively. The CFR of the five dosage regimens of daptomycin against Staphylococci were 97.4%, 99.2%, 99.9%, 100.0% and 100.0%, respectively. Conclusions:Linezolid (600 mg once every 12 hours), teicoplanin (400 mg once every 12 hours) and daptomycin (4 mg·kg -1·d -1) can achieve satisfactory antibacterial activity for Staphylococci bloodstream infections.
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Resumen Introducción: Vancomicina ha sido considerada como el tratamiento de elección en especial para Staphylococcus aureus resistente a meticilina (SARM); pero su escasa penetración tisular, su toxicidad renal y el requerir monitoreo de su dosis, plantean la necesidad de nuevas alternativas de tratamiento, como daptomicina. Objetivos: Analizar la seguridad y efectividad de daptomicina en niños. Pacientes y Métodos: Se incluyeron, retrospectivamente, niños con infecciones microbiológicamente documentadas, tratados con daptomicina. Resultados: Las infecciones más frecuentes fueron endocarditis en 9 (32%), sepsis de la comunidad en 4 (14%), bacteriemia en 7 (asociada a catéter en 3) (25%), osteomielitis en 3 (10%), peritonitis asociada a diálisis en 3 (10%) y tromboflebitis supurativa en 2 pacientes (7%). Staphylococcus aureus resistente a meticilina fue el patógeno más común en 18 pacientes (64%), Daptomicina fue indicada por el fracaso del tratamiento convencional en 17 (61%), y la toxicidad o intolerancia a vancomicina en 11 pacientes (39%). La duración media de tratamiento fue de 19 días (RIC 95% 7-42 días). Cuatro pacientes (14%) completaron tratamiento ambulatorio. Tuvieron respuesta favorable 22 pacientes (79%) Se reportaron eventos adversos en tres pacientes: dos elevaciones de creatina-fosfocinasa) y una erupción cutánea grave. Conclusiones: Daptomicina demostró una eficacia y seguridad favorables en esta población pediátrica.
Abstract Background: Vancomycin has been considered the treatment of choice especially for methicillin-resistant Staphylococcus aureus (MRSA) infections; but its poor tissue penetration, renal toxicity, and requiring of dosages monitoring, raises the need for new treatment alternatives such as daptomycin. Aims: To analyze the safety and effectiveness of daptomycin in children. Methods: Children with microbiologically documented infections treated with daptomycin were retrospectively included. Results: The most frequent infections were endocarditis in 9 (32%), sepsis in 4 (14%), bacteremia in 7 (associated with catheter in 3) (25%), osteomyelitis in 3 (10%), peritonitis associated with dialysis in 3 (10%) and suppurative thrombophlebitis in 2 patients (p) (7%). Methicillin-resistant Staphylococcus aureus was the most common pathogen in 18 patients (64%). The indications for daptomycin were due to the failure of conventional treatment in 17 (61%), and the toxicity or intolerance to vancomycin in 11 patients (39%). The average duration of treatment was 19 days (95% ICR 7-42 days). Four patients (14%) completed outpatient treatment, 22 patients had a favorable response (79%). Adverse events were reported in 3 patients (2 creatinine-phosfo-kinase increase) and in one severe skin rash. Conclusions: Daptomycin demonstrated a favorable efficacy and safety in this pediatric population.
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Humanos , Criança , Daptomicina/uso terapêutico , Hospitais Pediátricos/estatística & dados numéricos , Infecções Bacterianas/tratamento farmacológico , Estudos Retrospectivos , Resultado do Tratamento , Antibacterianos/uso terapêuticoRESUMO
To evaluate the clinical outcomes of daptomycin therapy and adherence to treatment recommendations, a retrospective cohort study was conducted with patients that received daptomycin during the period of the study. The adherence and nonadherence to clinical guidelines were assessed through organism identification, dose and time of treatment, management of bacteremia, and vancomycin treatment failure. A multiple logistic regression model analyzed the association between independent variables and clinical success (dependent variable), considering 5% of statistical significance. The study presented 52 patients who received daptomycin for the treatment of bacteremia (21.1%) or infections (osteomyelitis [63.5%], synovial fluid [15.4%]). Most patients (86.5%) received daptomycin as the second line of treatment, and 51.9% achieved clinical success. The patients had a better chance of clinical success when they followed the guideline indications (OR = 16.86; 95% CI = 1.45-195.88) and the medication was prescribed by a specialist in infectious diseases (OR = 4.84; 95% CI = 1.11-21.09). The study demonstrated lower clinical success than that described in the literature because of patients who were not eligible according to the clinical guidelines. Adherence to recommendations and appropriate prescription of reserve antibiotics is important in limiting early resistance, and avoiding clinical failure and unnecessary expenditure.
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Estudos de Coortes , Falha de Tratamento , Daptomicina/análise , Antibacterianos/efeitos adversos , Pacientes/classificação , Vigilância de Produtos Comercializados , Organização Mundial da Saúde , Doenças Transmissíveis/complicações , Infecções por Bactérias Gram-Positivas/classificação , Dosagem/efeitos adversosRESUMO
ABSTRACT Backgroud: Daptomycin has been used in bone and joint infections (BJI) and prosthesis joint infections (PJI) considering spectrum of activity and biofilm penetration. However, the current experience is based on case reports, case series, cohorts, and international surveys. The aim of this systematic review was to evaluate studies about daptomycin treatment efficacy in BJI/PJI compared to other antibiotic regimens. Methods: PubMed, LILACS, Scielo and Web of Science databases were searched for articles about daptomycin and treatment of BJI and PJI from inception to March 2018. Inclusion criteria were any published researches that included patients with BJI treated with daptomycin. Diagnosis of BJI was based on clinical, laboratory and radiological findings according to IDSA guidelines. Results: From 5107 articles, 12 articles were included. Only three studies described the outcomes of patients with BJI treated with daptomycin with comparator regimen (vancomycin, teicoplanin and oxacillin). Studies presented large heterogeneity regarding device related infections, surgical procedures, and daptomycin regimens (varied from 4 mg/kg to 10 mg/kg). A total of 299 patients have been included in all studies (184 infections associated with orthopedic disposal and 115 osteomyelitis/septic arthritis). Two hundred and thirty-three patients were treated with daptomycin. The clinical cure rates on device related and non-device related infections (i.e. osteomyelitis) were 70% and 78%, respectively. Compared to all regimens evaluated, daptomycin group outcomes were non-inferior. Conclusion: Although a randomized clinical trial is needed, this systematic review tends to support daptomycin usage for bone and joint infections.
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Humanos , Doenças Ósseas/tratamento farmacológico , Infecções Relacionadas à Prótese/tratamento farmacológico , Daptomicina/uso terapêutico , Artropatias/tratamento farmacológico , Antibacterianos/uso terapêutico , Osteomielite/tratamento farmacológico , Artrite Infecciosa/tratamento farmacológico , Prótese Articular/efeitos adversosRESUMO
ABSTRACT Introduction: This study aimed to characterize Staphylococcus aureus isolates from bloodstream infections in patients attending a teaching hospital, between 2011 and 2015. Methods: The minimum inhibitory concentration for daptomycin, linezolid, oxacillin, teicoplanin, vancomycin, and trimethoprim/sulfamethoxazole was accessed by broth microdilution. SCCmec type and clonal profile were determined by molecular tests. Vancomycin heteroresistance was evaluated using screening tests and by population analysis profile/area under the curve. Results: Among 200 S. aureus isolates, 55 (27.5%) were MRSA, carrying SCCmec II (45.5%) or IV (54.5%). The most frequent MRSA lineages were USA100 (ST5-II) (45.5%) and USA800 (ST5-IV) (30.9%). Six isolates were confirmed as vancomycin heteroresistant, showing area under the curve ratio 1.1, 1.2 or 1.3 (four USA100, one USA800 and one USA1100 isolates). Conclusions: Daptomycin and vancomycin non-susceptible MRSA clonal lineages were found in bloodstream infections over five years, highlighting the importance of continuous surveillance of multiresistant bacteria in hospitals.
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Humanos , Vancomicina/farmacologia , Bacteriemia/microbiologia , Daptomicina/farmacologia , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Antibacterianos/farmacologia , Infecções Estafilocócicas/microbiologia , Brasil , Testes de Sensibilidade Microbiana , Infecção Hospitalar/microbiologia , Hospitais de EnsinoRESUMO
Objective To detect the plasma concentrations of daptomycin in the left ventricle and right ventricle of rats by high-performance liquid chromatography-mass spectrometry(LC-MS/MS), and evaluate the therapeutic effect of daptomycin on left ventricular endocarditis. Methods Thirty-five healthy Sprague-Dawley (SD) rats were divided into a normal saline group (5 rats) and a daptomycin group (30 rats) according to the random number table method. The daptomycin group was subdivided into 6 subgroups according to the times of blood collection (0.25, 0.5, 1, 2, 4, 8 hours), with 5 rats in each subgroup. The normal saline group was given 4 mL/kg normal saline; the daptomycin group was injected with 50 mg/kg daptomycin into the tail vein. The blood samples from left ventricle and right ventricle were extracted at the corresponding time points, the plasma concentrations of daptomycin group were determined by high performance liquid chromatography-mass spectrometry (HPLC-MS) and the differences of left ventricular and right ventricular plasma concentrations were compared at different time points. The plasma in normal saline group was the blank plasma that was used for HPLC-MS methodological evaluation. Results There were no statistical significant differences between the left ventricle and right ventricle in plasma concentrations of daptomycin at 0.25, 0.5, 1, 2, 4, and 8 hours after administration (g/L: 2.67±0.30 vs. 2.77±0.31, 1.77±1.27 vs. 1.64±0.55, 1.35±0.40 vs. 1.36±0.41, 0.97±0.07 vs. 0.92±0.09, 0.73±0.16 vs. 0.65±0.18, 0.07±0.06 vs. 0.06±0.05, respectively all P > 0.05). Conclusion There are no significant differences between the left ventricle and right ventricle in plasma concentrations of daptomycin. It is speculated that daptomycin may have the same therapeutic effect on left endocarditis.
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Due to potent bactericidal activity and low rate of drug-resistance, daptomycin is recognized as first line antibiotic to treat serious infections caused by drug-resistant Gram-positive pathogens. However, the incidence of daptomycin resistance is increasing due to its widespread application. Alteration of cell wall homeostasis and membrane phospholipid metabolism is involved in daptomycin resistance. The unique mode of action underlying daptomycin resistance in important pathogens, including Staphylococcus aureus and Enterococci, is presented in this paper.
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Objective To evaluate the efficacy of daptomycin in the treatment of left-sided infective endocarditis after failing to respond to vancomycin.Methods A retrospective analysis was conducted for 6 cases of infective endocarditis.Results Five of the six infective endocarditis patients were complicated with paravalvular abscess (artificial valve in 3 cases,native valve in 2 cases).Their disease deteriorated even under vancomycin treatment.Four of these patients received emergency valve replacement surgery but still febrile after operation.The antimicrobial therapy was switched to daptomycin at dose of 6 mg/kg daily for 2 to 4 weeks.The patients responded satisfactorily to daptomycin.The infection was controlled to some extent in the fifth patient after switching to daptomycin,but recurred later,and died suddenly on day 21 after reoperation.The sixth patient had infective endocarditis of native valve,and had treated with piperacillin-tazobactam for 2 weeks and vancomycin for 3 weeks,but responded poorly.The patient still had fever and enlarged vegetation.Switching to daptomycin reduced the body temperature and vegetation.Serum creatine kinase elevated moderately in one patient,and normal in the other 5 patients.No other apparent adverse reaction was reported.One patient died and the other five patient survived well for 18 months to 5 years.Conclusions Preliminary observation demonstrates the efficacy of daptomycin salvage treatment in a few cases of left-sided infective endocarditis after failing to respond to vancomycin therapy.
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Due to the potent bactericidal activity and low incidence of drug resistance, the novel cyclic lipopeptide antibiotic - daptomycin has emerged as one of the first line antimicrobial agents in the treatment of serious infections caused by gram-positive resistant pathogens. This review summarizes the research advances of daptomycin in recent years, mainly including spectrum of antimicrobial activity, biosynthesis, mode of action, mechanism of drug resistance, structure-activity relationships, surotomycin and siderophore-daptomycin conjugate to kill multidrug resistant Acinetobacter baumannii. The findings summarized in this review highlight the directions of next-generation of daptomycin derivatives.
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Abstract Introduction Treatment of multidrug-resistant Gram-positive infections caused by Staphylococcus aureus remains as a clinical challenge due to emergence of new resistance mechanisms. Tedizolid is a next-generation oxazolidinone, recently approved for skin and soft tissues infections. We conducted a study to determine in vitro susceptibility to vancomycin, daptomycin, linezolid and tedizolid in MRSA clinical isolates from adult patients with skin and soft tissue infections. Material and methods Methicillin-resistant S. aureus isolates were collected in three tertiary-care hospitals of Medellin, Colombia, from February 2008 to June 2010 as part of a previous study. Clinical characteristics were assessed by medical records and MIC values were determined by Epsilometer test. Genotypic analysis included spa typing, MLST, and SCCmec typing. Results A total of 150 MRSA isolates were evaluated and tedizolid MIC values obtained showed higher in vitro activity than other antimicrobials, with MIC values ranging from 0.13 µg/mL to 0.75 µg/mL and lower values of MIC50 and MIC90 (0.38 µg/mL and 0.5 µg/mL). In contrast, vancomycin and linezolid had higher MIC values, which ranged from 0.5 µg/mL to 2.0 µg/mL and from 0.38 µg/mL to 4.0 µg/mL, respectively. Tedizolid MICs were 2- to 5-fold lower than those of linezolid. Clinical characteristics showed high previous antimicrobial use and hospitalization history. The majority of the strains belong to the CC8 harboring the SCCmec IVc and were associated with the spa t1610 (29.33%, n = 44). Conclusion In vitro effectiveness of tedizolid was superior for isolates from skin and soft tissue infections in comparison with the other antibiotics evaluated. The above added to its less toxicity, good bioavailability, daily dose and unnecessity of dosage adjustment, make tedizolid in a promising alternative for the treatment of infections caused by MRSA.
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Humanos , Masculino , Feminino , Infecções Estafilocócicas/microbiologia , Infecções dos Tecidos Moles/microbiologia , Antibacterianos/farmacologia , Oxazóis/farmacologia , Organofosfatos/farmacologia , Vancomicina/farmacologia , Testes de Sensibilidade Microbiana , Daptomicina/farmacologia , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Linezolida/farmacologiaRESUMO
Introducción: Para el tratamiento de las infecciones por Enterococcus resistente a vancomicina (ERV) se emplean fármacos de segunda línea como daptomicina y linezolid. Objetivo: hacer una revisión sistemática para evaluar el tratamiento de la bacteriemia por ERV, con daptomicina o linezolid. Metodología: búsqueda electrónica en las bases de datos de Pubmed, Embase, Scopus, ScienceDirect, CENTRAL, Lilacs y Google Académico, para identificar estudios anteriores a julio de 2015 que hayan comparado los tratamientos con daptomicina o linezolid de pacientes infectados por ERV. Resultados: se incluyeron 15 estudios de 1307 registros. No hubo diferencias entre daptomicina y linezolid con respecto a la mortalidad a 30 días. Con la daptomicina se logró más tempranamente el control microbiológico (OR: 0,64; IC95 %: 0,45-0,92). No hubo diferencias entre los dos antibióticos en cuanto a la mejoría clínica, la necesidad de admisión a la UCI o la aparición de efectos adversos como trombocitopenia, neutropenia e insuficiencia renal. Conclusiones: no encontramos diferencias entre daptomicina y linezolid en cuanto a la mortalidad de pacientes infectados por ERV, aunque con la daptomicina se logró una cura microbiológica más rápida.
Introduction: Second-line drugs such as linezolid and daptomycin are used for treatment of vancomycin-resistant Enterococcus (VRE) infections. Objective: A systematic review to evaluate treatment of VRE bacteremia with linezolid versus daptomycin. Methods: A search was done in the databases of Pubmed, Embase, Scopus, ScienceDirect, CENTRAL, Lilacs and Google Scholar to identify studies comparing treatment with daptomycin or linezolid of patients infected by VRE up to July 2015. Result: Only 15 studies were included of a total of 1.307 records. There were no differences between daptomycin and linezolid with respect to mortality at 30 days. Microbiological cure was better with daptomycin (OR: 0.64; 95 % CI: 0.45-0.92), whereas there was no difference between the two antibiotics with respect to clinical cure, need to ICU admission, and the occurrence of adverse effects such as thrombocytopenia, neutropenia and renal failure. Conclusions: No significant differences were observed between daptomycin and linezolid in reference to mortality of patients infected with VRE, although daptomycin treatment produced a faster microbiological cure.
Introdução: Para o tratamento das infecções por Enterococcusresistente a vancomicina (ERV) se empregam fármacos de segunda linha como daptomicina e linezolida. Objetivo: fazer uma revisão sistemática para avaliar o tratamento da bacteriemia por ERV, com daptomicina o linezolida. Metodologia: busca eletrônica nas bases de dados de Pubmed, Embase, Scopus, ScienceDirect, CENTRAL, Lilacs e Google Acadêmico, para identificar estudos anteriores a julho de 2015 que foram comparados os tratamentos com daptomicina ou linezolida de pacientes infectados por ERV. Resultados: se incluíram 15 estudos de 1.307 registros. Não houve diferenças entre daptomicina e linezolida com respeito à mortalidade a 30 dias. Com a daptomicina se conseguiu mais precoce o controle microbiológico (OR: 0,64; IC95 %: 0,45-0,92). Não houve diferenças entre os dois antibióticos em quanto à melhoria clínica, a necessidade de admissão à UTI ou a aparição de efeitos adversos como trombocitopenia, neutropenia e insuficiência renal. Conclusões: não encontramos diferenças entre daptomicina e linezolida em quanto à mortalidade de pacientes infectados por ERV, embora com a daptomicina se conseguiu uma cura microbiológica mais rápida.
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Humanos , Adulto , Antibacterianos , Bacteriemia , Daptomicina , Enterococcus , Vancomicina , InfecçõesRESUMO
Objective To investigate the effect of daptomycin on the serum levels of proclacitonin (PCT) and copeptin in septicopyemia patients induced by methicillin-resistant Staphylococcus aureus (MRSA). Methods 54 cases septicopyemia patients induced by MRSA were selected and divided into two groups, 27 cases in each group. The two groups received fluid replacement therapy and nutrition support, the control group received vancomycin (0.5g per times, three times daily) with intravenous drip, and the study group received daptomycin (6mg/kg, once daily) with intravenous drip. The serum PCT, proclacitonin levels pre-and post-treatment in two groups were detected, the acute physiology and chronic health evaluationⅡ (APACHEⅡ) and sepsis-related organ failure assessment (SOFA) were used to evaluate the patients' condition, the clearance time of pathogenic bacteria was recorded and the clinical efficacy was compared between two groups. Results Compared with before treatment, serum PCT, C-reactive protein (CRP), interleukin-1β(IL-1β) and IL-6 in two groups decreased(P<0.01), the count of WBC, NE% and copeptin decreased (P<0.01), the APACHEⅡ and SOFA score were lower(P<0.05); compared with the control group, the PCT, CRP, IL-1 beta and IL-6 in study group were lower(P<0.05), the count of WBC, NE% and copeptin level were lower(P<0.05), APACHEⅡ and SOFA score were lower(P<0.05), the pathogen clearance rate was higher(P<0.05), clearance time was shorter(P<0.05), the total efficiency was higher(P<0.05). Conclusion Daptomycin can reduce serum PCT and copeptin in patients with septicopyemia induced by MRSA, and remove pathogenic bacteria rapidly, inhibit the inflammatory reaction, safe and reliable.
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This study is aimed to make a comprehensive introduction to the anti-MRSA drugs,and also to compare the safety and efficacy among a variety of anti-MRSA drugs.Finally,it is pointed that we should select the anti-MRSA drugs precisely according to different situation of disease when treating the infection with MRSA.Then we can make the individualized treatment for patients and provide a basis for the disease when treatment of patients as well.
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Objective: To prepare daptomycin liposomes and investigate the in vitro drug release.Methods: Daptomycin liposomes were prepared by an active loading method.The distribution of particle size and zeta potential of liposomes were determined by a laser particle size analyzer.The encapsulation efficiency and in vitro drug release were determined by HPLC.Results: The particle size of daptomycin liposomes was 109.5 nm, the heterogeneous dispersion coefficient was 0.042 and the zeta potential was-6.48 mV.The entrapment efficiency determined by gel column and centrifugation was 50.8% and 50.3%, respectively.The result of in vitro drug release showed that daptomycin liposomes had a good sustained-release effect when compared with daptomycin for injection.Conclusion: Daptomycin liposomes have uniform particle size, which can release drug slowly to reduce administration frequency.
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Abstract INTRODUCTION: Methicillin-resistant Staphylococcus aureus (MRSA) is a nosocomial pathogen in community settings. MRSA colonized individuals may contribute to its dissemination; the risk of MRSA infection is increased in human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS) patients, although the prevalence of colonization in this group is not well established. The present study addressed this issue by characterizing MRSA isolates from HIV/AIDS patients and their healthcare providers (HCPs) to determine whether transmission occurred between these two populations. METHODS: A total of 24 MRSA isolates from HIV-infected patients and five from HCPs were collected between August 2011 and May 2013. Susceptibility to currently available antimicrobials was determined. Epidemiological typing was carried out by pulsed-field gel electrophoresis, multilocus sequence typing, and Staphylococcus cassette chromosome (SCCmec) typing. The presence of heterogeneous vancomycin-intermediate Staphylococcus aureus (hVISA) and heterogeneous daptomycin-resistant Staphylococcus aureus (hDRSA) was confirmed by population analysis profile. Isolates characterized in this study were also compared to isolates from 2009 obtained from patients at the same hospital. RESULTS: A variety of lineages were found among patients, including ST5-SCCmecII and ST30-SCCmecIV. Two isolates were Panton-Valentine leukocidin-positive, and hVISA and hDRSA were detected. MRSA isolates from two HCPs were not related to those from HIV/AIDS patients, but clustered with archived MRSA from 2009 with no known relationship to the current study population. CONCLUSIONS: ST105-SCCmecII clones that colonized professionals in 2011 and 2012 were already circulating among patients in 2009, but there is no evidence that these clones spread to or between HIV/AIDS patients up to the 7th day of their hospitalization.
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Humanos , Infecções Estafilocócicas , Infecções por HIV/microbiologia , Infecção Hospitalar/transmissão , Transmissão de Doença Infecciosa do Profissional para o Paciente/estatística & dados numéricos , Staphylococcus aureus Resistente à Meticilina/genética , Antibacterianos/farmacologia , Infecções Estafilocócicas/microbiologia , Testes de Sensibilidade Microbiana , Infecção Hospitalar/microbiologia , Técnicas de Tipagem Bacteriana , Eletroforese em Gel de Campo Pulsado , Epidemiologia Molecular , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Tipagem de Sequências Multilocus , Centros de Atenção TerciáriaRESUMO
Background: Multidrug-resistant Enterococci are major problem and are increasingly reported worldwide. Enterococcal infections have been associated with higher hospitalization costs and a higher number of related deaths. Treatment of multidrug-resistant enterococci has become a challenge in hospitals around the world due to the lack of reliable therapeutic options. So the present study was undertaken with the aim to know the antimicrobial resistantpattern of enterococcus to newer antibiotic. Methodology: 22 isolates of enterococcus resistant to the entire routinely tested antibiotic were further tested for newer antimicrobial agent linezolid, daptomycin, rifampin, synercid, teicoplanin, telavancin, vancomycin, gentamicin (HLG). Results: Among these 22 enterococci isolated none of our isolates showed resistance to vancomycin, teicoplanin, telavancin, tigecycline and linezolid. But one isolate of E.faecalis showed resistance to daptomcyin. This daptomycinnonsusceptible isolate was found susceptible to ceftaroline. E. faecalis showed higher resistance to Gentamicin (HLG) and Synercid as compared to E.faecium. Specimen-wise higher distribution of enterococci (resistant to routinely tested antimicrobial agents) was observed in Urine 11(50%) followed by Pus 4(18.18%) and Miscellaneous 4(18.18%) and from Blood 3(13.64%). Conclusion: In our study none of the isolates showed resistance to vancomycin, tigecycline, telavancin, linezolid and ceftaroline but thepresence of daptomycin non-susceptible enterococci 1(4.55%) in our rural set-up is cause of concern.
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Considering that some antibacterial agents can identify the outer structure of pathogens like cell wall and/or cell membrane, we explored a self-enhanced targeted delivery strategy by which a small amount of the antibiotic molecules were modified on the surface of carriers as targeting ligands of certain bacteria while more antibiotic molecules were loaded inside the carriers, and thus has the potential to improve the drug concentration at the infection site, enhance efficacy and reduce potential toxicity. In this study, a novel targeted delivery system against methicillin-resistant Staphylococcus aureus (MRSA) pneumonia was constructed with daptomycin, a lipopeptide antibiotic, which can bind to the cell wall of S. aureus via its hydrophobic tail. Daptomycin was conjugated with N-hydroxysuccinimidyl-polyethylene glycol-1,2-distearoyl-sn-glycero-3-phosphoethanolamine to synthesize a targeting compound (Dapt-PEG-DSPE) which could be anchored on the surface of liposomes, while additional daptomycin molecules were encapsulated inside the liposomes. These daptomycin-modified, daptomycin-loaded liposomes (DPD-L[D]) showed specific binding to MRSA as detected by flow cytometry and good targeting capabilities in vivo to MRSA-infected lungs in a pneumonia model. DPD-L[D] exhibited more favorable antibacterial efficacy against MRSA than conventional PEGylated liposomal daptomycin both in vitro and in vivo. Our study demonstrates that daptomycin-modified liposomes can enhance MRSA-targeted delivery of encapsulated antibiotic, suggesting a novel drug delivery approach for existing antimicrobial agents.
RESUMO
abstract Daptomycin (DPT) was the first lipopeptide antibiotic available for commercialization. It is active against gram-positive bacteria, including resistant strains. This work aimed to develop and validate a turbidimetric microbiologic assay to determine daptomycin in an injectable form. A 3x3 design was employed, at concentrations of 1, 2 and 4.0 µg/mL. The microorganism test used was Staphylococcus aureus ATCC 6538p, and Antibiotic Medium 3 was used as the culture medium. Method validation demonstrated that the bioassay was linear (r=0.9995), precise (RSD=2.58%), accurate (recovery 100.48± 2.11%), and robust. Degradation kinetics was also performed in an alkaline medium, indicating that daptomycin degradation follows first order kinetics under these conditions. The analyses of degraded solutions showed that daptomycin degradation products do not possess bactericidal activity. The bioassay was compared to HPLC method that was previously developed and no significant difference was found between them (p>0.05). The method proved to be appropriate for daptomycin injection quality control.
resumo A daptomicina (DPT) é o primeiro lipopeptídeo cíclico disponível para comercialização. Possui atividade frente a bactérias gram-positivas, incluindo cepas resistentes. O objetivo deste trabalho foi desenvolver e validar um ensaio microbiológico turbidimétrico para quantificar a daptomicina na forma injetável. Empregou-se delineamento 3x3, nas concentrações de 1,0; 2,0 e 4,0 µg/mL. Como micro-organismo teste foi usado Staphylococcus aureus ATCC 6538p, e Meio para Antibióticos nº 3 foi empregado como meio de cultura. A validação do método demonstrou que o ensaio foi linear (r=0,9995), preciso (RSD=2,55%), exato (recuperação de 100,48 ± 2,11%) e robusto. A cinética de degradação em meio alcalino foi avaliada, indicando que a daptomicina segue cinética de primeira ordem nessa condição. A análise das soluções degradadas mostrou que os produtos de degradação da daptomicina não possuem atividade antimicrobiana. O bioensaio foi comparado com o método por CLAE previamente desenvolvido e não houve diferença significativa entre ambos (p<0,05). O método mostrou-se apropriado para o controle de qualidade da daptomicina injetável.