Linezolid resistance in a clinical isolate of Staphylococcus aureus
Sotirios TsiodrasHoward S. GoldGeorge SakoulasGeorge M. EliopoulosChristine WennerstenLata VenkataramanRobert C. MoelleringMary Jane Ferraro
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Post-antibiotic effect of linezolid and vancomycin against methicillin-resistant Staphyloccus aureus
Objective To investigate the post-antibiotic effect(PAE) of linezolid and vancomycin against methicillin-resistant Staphyloccus aureus(MRSA).Methods PAE of linezolid and vancomycin against MRSA was determined by plate colony counting at different concentrations(1×MIC,2×MIC,4×MIC,8×MIC) and different time points(1,2,3 h).The morphological changes of MRSA during the PAE period were observed by scanning electron microscopy.Results All strains were susceptible to linezolid and vancomycin.The PAE was greater at higher concentration and longer exposure time.There was no morphological change of MRSA during the PAE.Conclusion It was demonstrated that linezolid and vacomycin had a moderate in vitro PAE against MRSA.There was no morphological change of MRSA during the PAE.
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OBJECTIVE: To analyze the effectiveness of linezolid vs.vancomycin in the treatment of retention catheterization infection induced by methicillin-resistant staphylococcus aureus(MRSA) infections.METHODS: 53 patients with MRSA infection treated divided into linezolid group(27 cases) and vancomycin group(26 cases).Linezolid group was given linezolid 600 mg every 12 hours,and vancomycin group was given vancomycin 1 g every 12 hours.After 14 days treatment,microbiologic eradications of 2 groups of drugs were analyzed.RESULTS: After 14 days treatment,the cure rates of linezolid group and vancomycin group were 66.7% and 23.1%.There was statistical significance(P0.05).CONCLUSION: The effectiveness of linezolid are similar to those of vancomycin in the treatment of gram-positive bacterial infection,but the cure rate of linezolid is higher than vancomycin in 14 days.
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The present study was designed to compare in vitro antibacterial activities of linezolid and vancomycin against vancomycin-susceptible Enterococcus faecalis (VSEF) and vancomycin-resistant enterococci (VRE) isolated in Japan with those of quinupristin–dalfopristin, teicoplanin and minocycline, and the in vitro short time bactericidal activity and the in vivo activities of linezolid and vancomycin against vancomycin-susceptible and -resistant E. faecalis. The MIC90s of linezolid, quinupristin–dalfopristin, vancomycin, teicoplanin and minocycline for VSEF and VRE were both 2 mg/L, both 2 mg/L, 2 and >128 mg/L, 0.25 and >128 mg/L, and both 32 mg/L, respectively. The efficacy of linezolid for mice with bacteraemia caused by VSEF was similar to that of vancomycin, but the elimination ratio of viable organisms from the blood of mice treated with vancomycin was significantly higher than in linezolid-treated and untreated mice at 2 h post-administration, and those of the two groups at 4 and 6 h were significantly higher than in untreated mice. Moreover, linezolid was highly active in mice with bacteraemia caused by vancomycin-resistant E. faecalisbecause this drug had potent in vitro activity against the organisms. Our results indicate that linezolid is suitable for the treatment of VRE and VSEF bacteraemia, and vancomycin is suitable for VSEF bacteraemia.
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Enterococcus faecalis
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Methicillin resistant Staphylococcus aureus (MRSA) has emerged as one of the commonest cause of hospital acquired infections worldwide. Vancomycin is the antibiotic of choice for treatment of MRSA, but due to slow increase in vancomycin minimum inhibitory concentration (MIC) (vancomycin creep),Vancomycin has become a suboptimal therapeutic option in critically ill patients. Linezolid has emerged as an alternative drug in the treatment of such cases.
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The levels of effectiveness of linezolid, vancomycin, and the combination of linezolid and vancomycin were compared in the rabbit model of endocarditis caused by a clinical methicillin-resistant Staphylococcus aureus (MRSA) isolate. Vancomycin alone was more effective than either linezolid alone or the combination of linezolid and vancomycin for the treatment of endocarditis due to MRSA.
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In recent years,vancomycin resistant Staphycoloccus aureus has been increasing,which has brought a new challenge to anti-infective theraphy in clinic.It is very important for clinician and infection controlmen to have a correct understanding of vancomycin resistant Staphylococcus aureus.This article mainly reviews the epidemiology,detection,drug resistant mechanism and treatment of Staphylococcus aureus with reduced vancomycin susceptibility.
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Vancomycin intermediate Staphylococcus aureus; Heterogeneous vancomycin intermediate Staphylococcus aureus; Vancomycin; Minimal inhibitory concentration
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Vancomycin is the mainstay of treatment for methicillin-resistant Staphylococcus aureus (MRSA) meningitis. However, successful outcomes with linezolid have not been reported in a large series of patients. We conducted a single-center retrospective cohort study to compare vancomycin with linezolid in the treatment of MRSA meningitis.We extracted data and outcomes for all adult patients (age >18 years) with culture-proved MRSA meningitis who received vancomycin or linezolid between January 2006 and June 2011. A definite diagnosis of meningitis was based on the isolation of MRSA in at least one cerebrospinal fluid (CSF) culture and findings in CSF that are typical of the infection. Linezolid was given intravenously (IV) at a dosage of 600 mg q12h and vancomycin IV at 500 mg q6h.A total of 8 patients with MRSA meningitis (5 male, 3 female; age [mean±SD] 61.6±13.2 years) received vancomycin and 9 patients (7 male, 2 female; age 59.1±15.6 years) received linezolid. All isolated strains of MRSA were susceptible to both vancomycin and linezolid. The rates of microbiologic success with linezolid or vancomycin, in terms of clearance of MRSA from CSF on day 5, were 7/9 and 2/8 (p=0.044, Fisher exact test). No severe adverse events occurred in either treatment arm of the study. One-month survival of the patients in whom treatment was successful microbiologically was 2/2 in the vancomycin-treated group and 4/7 in the linezolid-treated group. Minimum inhibitory concentration (MIC) data for vancomycin were available for 5/6 treatment failures with vancomycin, and vancomycin MIC values of these five strains were 2 mg/L.Analysis of the findings in the limited cohorts in our study suggests that linezolid is superior to vancomycin for treating MRSA meningitis, especially in cases in which there is a high MIC (2 mg/L) for vancomycin. A clinical study involving larger cohorts may increase the evidence available in relation to this question.
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[Objective]The paper aims to explore the difference of vancomycin,teicoplanin and linezolid in the inducing resistance of MRSA by measuring MIC before and after drug inducing.[Methods]The MIC of Nine MRSA to vancomycin,teicoplanin and linezolid are identified by two-fold agar dilution method,and then two MRSA which are sensitive to the three drugs are found out.The two MRSA are induced separately by vancomycin,teicoplanin and linezolid for 25 generations.At last,the MIC of MRSA which have been induced to vancomycin,teicoplanin and linezolid are identified.The data is analyzed by SPSS 19.0.[Results]After vancomycin,teicoplanin and linezolid inducing MRSA for 25 generations respectively,the MIC of vancomycin and linezolid increased 2 times and teicoplanin increased 2.67 times compared with those before drug induction.However,there was no difference of the change of MIC among the 3 groups.Additionally,no resistant strains were generated.The MIC of 3 drugs to MRSA strains in control groups in drug-free plates did not change after passage.[Conclusions]The comparison of the three drugs at inducing resistance have no significant difference.
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Endocarditis, and prosthetic valve endocarditis in particular, is a serious disease with high morbidity and mortality. We investigate the effects of tigecycline, linezolid and vancomycin on biofilms of viridans group streptococci (VGS) isolated from patients with definite native or prosthetic valve endocarditis.Ten of 20 VGS blood stream isolates from patients with endocarditis formed biofilms in the microtiter plate biofilm model. The minimal inhibitory concentrations (MIC) for tigecycline, linezolid and vancomycin were determined using the microdilution broth method. Biofilms were grown for 24 hours and were incubated with tigecycline, linezolid and vancomycin at increasing concentrations from 1-128x MIC of the isolate being tested. Biofilm thickness was quantified by measuring the optical density (OD) after dyeing it with crystal violet. The incubation of the biofilms with tigecycline, linezolid or vancomycin resulted in a significant reduction of OD compared to the control biofilm without antibiotic (p<0.05). The optical density ratio (Odr) decreased significantly at 2x MIC for tigecycline, and at 8x MIC for linezolid and vancomycin (p<0.05). Although biofilms persisted even at the highest antibiotic concentrations of 128x MIC, bacterial growth was eradicated starting at concentrations of 16x MIC for vancomycin and of 32x MIC for linezolid, but not for tigecycline, up to a concentration of 128x MIC.In the present study on viridans streptococci isolated from patients with endocarditis, tigecycline and linezolid reduced the density of the biofilms as effectively as vancomycin. However, linezolid and vancomycin were bactericidal at higher concentrations. Linezolid and vancomycin at very high doses may be useful in the treatment of biofilm-associated diseases caused by VGS infections.
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Linezolid
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Vancomycin serum levels (VSL) were measured to prevent dose-dependent side effects. However, the cost of VSL is high, therefore in some cases alternative antibacterial treatments, such as linezolid, can be used. The aim of this study was to perform an economic analysis of the cost of linezolid compared to vancomycin plus therapeutic drug monitoring. This is an ecological, retrospective, quantitative study, conducted in a Brazilian public university hospital. The study period was from January 2018 to January 2019. First part from January/18 - July/18 based on pre-linezolid data (T1) and another after the introduction of linezolid from August/18 - January/19 (T2). A breakeven analysis to vancomycin substitution was performed following 3 scenarios: (i) in all patients, (ii) in critically ill patients with renal failure or (iii) only in patients in hemodialysis. The DDD/1000-patients day, MRSA incidence, costs with VSL, as well as the costs of drugs (vancomycin and linezolid) and infusion kits were evaluated. Vancomycin was substituted in critically ill patients with renal failure from T1 to T2. The incidence of MRSA infections did not vary between T1 and T2. Vancomycin consume maintained constant (p=0.157); while linezolid consuming increased (0 DDD/1000PD versus 33.4 DDD/1000PD; p=0.002). Vancomycin and linezolid costs was lower in T1 than T2 (USD 9202,00 versus 11331,00; p=0.015). Linezolid implementation as a strategy to avoid vancomycin plus VSL was not cost-effective in critically ill patients with renal failure. More studies are needed to understand if linezolid implementation may be cost-effective in different scenarios.
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Therapeutic Drug Monitoring
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