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BMC Infectious Diseases Dec 2014Linezolid, which has bacteriostatic activity, is approved for the treatment of vancomycin-resistant enterococci (VRE) infections. Meanwhile, daptomycin exerts... (Comparative Study)
Comparative Study Meta-Analysis Review
BACKGROUND
Linezolid, which has bacteriostatic activity, is approved for the treatment of vancomycin-resistant enterococci (VRE) infections. Meanwhile, daptomycin exerts bactericidal activity against VRE, but is not approved for the treatment of VRE bacteremia. Only a few studies with small sample sizes have compared the effectiveness of these drugs for treatment of VRE bacteremia.
METHODS
PubMed, EMBASE, and the Cochrane Library were searched for studies of VRE bacteremia treatment published before January 1, 2014. All studies reporting daptomycin and linezolid treatment outcomes simultaneously were included. The endpoints were mortality and microbiological cure. The adjusted odds ratios (aORs) of mortality in daptomycin- and linezolid-treated patients were extracted if available. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for all outcomes using a random-effects model.
RESULTS
Thirteen studies (532 patients receiving daptomycin, 656 patients receiving linezolid) met the selection criteria. All studies had retrospective cohort designs and relatively small sample sizes. Eight studies compared the aORs of mortality in daptomycin- and linezolid-treated patients. Four studies were published as conference papers and there was significant heterogeneity among these studies (I2 = 63%, p = 0.04). Daptomycin use was not associated with better microbiological cure (daptomycin vs. linezolid, OR: 0.67, 95% CI: 0.42-1.06, p = 0.09). However, mortality was higher in patients receiving daptomycin (OR: 1.43, 95% CI: 1.09-1.86, p = 0.009). Subgroup analysis of studies that reported aORs indicated that daptomycin was associated with higher mortality (OR: 1.59, 95% CI: 1.02-2.50, p = 0.04). There was no evidence of publication bias, but all enrolled studies were retrospective, had small sample sizes, and had substantial limitations.
CONCLUSIONS
Although limited data is available, the current meta-analysis shows that linezolid treatment for VRE bacteremia was associated with a lower mortality than daptomycin treatment. However, the results should be interpreted cautiously because of limitations inherent to retrospective studies and the high heterogeneity among studies. A large randomized trial is needed to confirm the present results.
Topics: Acetamides; Anti-Bacterial Agents; Bacteremia; Daptomycin; Humans; Linezolid; Oxazolidinones; Retrospective Studies; Treatment Outcome; Vancomycin; Vancomycin Resistance; Vancomycin-Resistant Enterococci
PubMed: 25495779
DOI: 10.1186/s12879-014-0687-9 -
The Permanente Journal May 2021Use of daptomycin at doses ≥ 6 mg/kg for treatment of osteomyelitis is increasing in clinical practice; unfortunately, limited data are available to guide optimal...
BACKGROUND
Use of daptomycin at doses ≥ 6 mg/kg for treatment of osteomyelitis is increasing in clinical practice; unfortunately, limited data are available to guide optimal dosing and duration. The objective of this study was to assess daptomycin dosing and duration regimens for osteomyelitis treatment.
METHODS
This was a retrospective, multi-site, cohort study conducted in an integrated healthcare delivery system. Nonpregnant patients ≥ 18 years of age with osteomyelitis diagnosed between November 1, 2003 and June 30, 2011, ≥ 2 weeks outpatient daptomycin therapy, and ≥ 1 month of follow-up were included. Daptomycin doses < 6 mg/kg and ≥ 6 mg/kg at durations of < 6 weeks and ≥ 6 weeks were examined with univariate and multivariate analyses to assess treatment success and all-cause mortality.
RESULTS
A total of 247 patients were included, with 39 (15.8%), 37 (15.0%), 107 (43.3%), and 64 (25.9%) receiving < 6 mg/kg and ≥ 6 weeks, < 6 mg/kg and < 6 weeks, ≥ 6 mg/kg and ≥ 6 weeks, and ≥ 6 mg/kg and < 6 weeks of daptomycin therapy, respectively. Patients had a mean age of 58 years and had received prior vancomycin therapy (65.6%). Patients receiving < 6 weeks of therapy were less likely to experience treatment success compared with ≥ 6 weeks (41.5% vs 25.3%, adjusted odds ratio = 0.55; 95% confidence interval = 0.31-0.98) independent of duration. There were no differences across groups in mortality after adjustment.
CONCLUSION
In a diverse clinical population, daptomycin for treatment of osteomyelitis of 6 weeks or longer duration was associated with success independent of dose. This finding supports longer treatment with daptomycin as a first-line agent in antimicrobial stewardship initiatives.
Topics: Anti-Bacterial Agents; Cohort Studies; Daptomycin; Humans; Middle Aged; Osteomyelitis; Outpatients; Retrospective Studies; Treatment Outcome
PubMed: 35348074
DOI: 10.7812/TPP/20.297 -
Antimicrobial Agents and Chemotherapy Oct 2021Exebacase is a lysin (cell wall hydrolase) with direct lytic activity against Staphylococcus aureus including methicillin-resistant S. aureus (MRSA). Time-kill analysis...
Exebacase is a lysin (cell wall hydrolase) with direct lytic activity against Staphylococcus aureus including methicillin-resistant S. aureus (MRSA). Time-kill analysis experiments illustrated bactericidal activity of exebacase-daptomycin against MRSA strains MW2 and 494. Furthermore, exebacase in addition to daptomycin (10, 6, and 4 mg/kg/day) in a two-compartment pharmacokinetic/pharmacodynamic simulated endocardial vegetation model with humanized doses resulted in reductions of 6.01, 4.99, and 2.81 log CFU/g (from initial inoculum) against MRSA strain MW2.
Topics: Anti-Bacterial Agents; Daptomycin; Endopeptidases; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests
PubMed: 34398668
DOI: 10.1128/AAC.00128-21 -
Joint Diseases and Related Surgery 2020This study aims to investigate the biocompatibility and cytotoxicity of daptomycin, gentamicin, vancomycin and teicoplanin at commonly-used dose intervals added to...
OBJECTIVES
This study aims to investigate the biocompatibility and cytotoxicity of daptomycin, gentamicin, vancomycin and teicoplanin at commonly-used dose intervals added to polymethylmethacrylate (PMMA) in vitro.
MATERIALS AND METHODS
This prospective study was conducted between February 2016 and June 2016. Antibiotics were added to PMMA at doses frequently used in clinical practice. The antibiotic doses added were teicoplanin (2 g, 3 g, 4 g), gentamicin (0.5 g, 0.75 g, 1 g), daptomycin (0.5 g.) and vancomycin (2 g, 3 g, 4 g). Standard cement balls (10 mm) were created. Activated L929 mouse fibroblast cell culture was used for incubation. Agar diffusion, Cell Proliferation Kit II (XTT) test and electron microscope investigations were performed to examine biocompatibility and cytotoxicity.
RESULTS
In the cytotoxicity test, teicoplanin at 4 g and daptomycin at 0.5 g doses were observed to cause reductions in viability percentages. The same doses caused 20% and 20-40% cell lysis indices during the agar diffusion test. On electron microscope images, cytotoxic effects in fibroblast cells and involvement with the surface of cement balls were observed.
CONCLUSION
Gentamicin, vancomycin and teicoplanin were observed to be non-toxic and biocompatible at commonly-used dose intervals. Teicoplanin at 4 g and daptomycin at 0.5 g doses were identified to be cytotoxic and not biocompatible. When selecting antibiotics to be added to bone cement, care should be taken that the antibiotic is non-toxic and biocompatible.
Topics: Animals; Anti-Bacterial Agents; Bone Cements; Cells, Cultured; Cytotoxicity Tests, Immunologic; Daptomycin; Dose-Response Relationship, Drug; Gentamicins; Materials Testing; Mice; Teaching Materials; Teicoplanin; Vancomycin
PubMed: 32584733
DOI: 10.5606/ehc.2020.74943 -
Revista Espanola de Quimioterapia :... Dec 2017Daptomycin is a cyclic lipopeptide active against multidrug-resistant Gram-positives, including methicillin-resistant Staphylococcus aureus (MRSA) and S. aureus with... (Review)
Review
Daptomycin is a cyclic lipopeptide active against multidrug-resistant Gram-positives, including methicillin-resistant Staphylococcus aureus (MRSA) and S. aureus with reduced susceptibility to vancomycin. It is 4-8 fold as active as vancomycin against methicillin-susceptible S. aureus (MSSA) and MRSA, and retains most of this activity against S. aureus with reduced susceptibility to vancomycin. The mechanism of action of daptomycin is not fully understood. Daptomycin binds to the bacterial cytoplasmic membrane, leading to depolarization due to the loss of potassium ions from the cytoplasm. Daptomycin non-susceptibility is unusual in the clinical setting. Different mechanisms have been proposed to explain daptomycin-resistance, most of them associated to changes in composition, charge and fluidity of the cell wall. The mprF mutations, which lead to an increase in the lysyl-phosphatidyl glycerol production, and rpoB and rpoC mutations (rpo genes encode for bacterial RNA polymerase subunits) have been proposed as associated to daptomycin-resistance, but a number of mutations in other genes ( walK, cls, ggrA…) have been proposed.
Topics: Anti-Bacterial Agents; Daptomycin; Drug Resistance, Bacterial; Humans; Staphylococcal Infections; Staphylococcus aureus
PubMed: 29082727
DOI: No ID Found -
Antimicrobial Agents and Chemotherapy Jan 2019Daptomycin is a calcium-dependent lipodepsipeptide antibiotic clinically used to treat serious infections caused by Gram-positive pathogens. Its precise mode of action...
Daptomycin is a calcium-dependent lipodepsipeptide antibiotic clinically used to treat serious infections caused by Gram-positive pathogens. Its precise mode of action is somewhat controversial; the biggest issue is daptomycin pore formation, which we directly investigated here. We first performed a screening experiment using propidium iodide (PI) entry to cells and chose the optimum and therapeutically relevant conditions (10 µg/ml daptomycin and 1.25 mM CaCl) for the subsequent analyses. Using conductance measurements on planar lipid bilayers, we show that daptomycin forms nonuniform oligomeric pores with conductance ranging from 120 pS to 14 nS. The smallest conductance unit is probably a dimer; however, tetramers and pentamers occur in the membrane most frequently. Moreover, daptomycin pore-forming activity is exponentially dependent on the applied membrane voltage. We further analyzed the membrane-permeabilizing activity in cells using fluorescence methods [PI and DiSC(5)]. Daptomycin most rapidly permeabilizes cells with high initial membrane potential and dissipates it within a few minutes. Low initial membrane potential hinders daptomycin pore formation.
Topics: Anti-Bacterial Agents; Bacillus subtilis; Biological Transport; Cell Membrane Permeability; Daptomycin; Membrane Potentials; Microbial Sensitivity Tests; Pore Forming Cytotoxic Proteins
PubMed: 30323037
DOI: 10.1128/AAC.01589-18 -
Antimicrobial Agents and Chemotherapy Sep 2021and species are fastidious organisms, representing the causative agents of ∼1% to 3% of cases of infective endocarditis (IE). Little is known about the optimal...
and species are fastidious organisms, representing the causative agents of ∼1% to 3% of cases of infective endocarditis (IE). Little is known about the optimal antibiotic treatment for these species, and daptomycin has been suggested as a therapeutic option. We describe the antimicrobial profiles of and IE isolates, investigate high-level daptomycin resistance (HLDR) development, and evaluate daptomycin activity in combination therapy. studies with 16 IE strains (6 Abiotrophia defectiva strains, 9 Granulicatella adiacens strains, and 1 G. elegans strain) were performed using microdilution to determine MICs and time-kill methodology to evaluate combination therapy. Daptomycin nonsusceptibility (DNS) (MIC ≥ 2 mg/liter) and HLDR (MIC ≥ 256 mg/liter) were based on existing Clinical and Laboratory Standards Institute (CLSI) breakpoints for viridans group streptococci. All isolates were susceptible to vancomycin: G. adiacens was more susceptible to penicillin and ampicillin than A. defectiva (22% versus 0% and 67% versus 33%) but less susceptible to ceftriaxone and daptomycin (56% versus 83% and 11% versus 50%). HLDR developed in both A. defectiva (33%) and (78%) after 24 h of exposure to daptomycin. Combination therapy did not prevent the development of daptomycin resistance with ampicillin (2/3 strains), gentamicin (2/3 strains), ceftriaxone (2/3 strains), or ceftaroline (2/3 strains). Once developed, HLDR was stable for a prolonged time (>3 weeks) in , whereas in A. defectiva, HLDR reversed to the baseline MIC at day 10. This study is the first to demonstrate rapid HLDR development in and species . Resistance was stable, and most combination therapies did not prevent it.
Topics: Abiotrophia; Anti-Bacterial Agents; Carnobacteriaceae; Daptomycin; Endocarditis, Bacterial; Humans
PubMed: 34252304
DOI: 10.1128/AAC.02522-20 -
Clinical Microbiology and Infection :... Mar 2006In the face of increasing resistance to currently available antibiotics, there is a continued interest in the development of new drugs to treat Gram-positive infections.... (Review)
Review
In the face of increasing resistance to currently available antibiotics, there is a continued interest in the development of new drugs to treat Gram-positive infections. One such agent is the cyclic lipopeptide daptomycin-licensed in the USA for treatment of Gram-positive complicated skin and skin structure infections (cSSSIs) in 2003 and currently awaiting European approval for a similar indication (complicated skin and soft tissue infections). Daptomycin exerts its rapid bactericidal effect through insertion into and subsequent depolarisation of the bacterial cell membrane, a mode of action unlike that of any other available antibiotic. This novel mechanism of action makes the development of cross-resistance between daptomycin and other antibiotic classes unlikely. Daptomycin is highly active in vitro against a range of Gram-positive pathogens, including both susceptible and multidrug-resistant staphylococci and enterococci. Bactericidal activity has also been demonstrated against both growing and stationary-phase organisms, suggesting potential utility in the treatment of deep-seated infections. Two pivotal clinical studies comparing daptomycin 4 mg/kg per day intravenously with vancomycin or oxacillin-class antibiotics demonstrated the efficacy of daptomycin for treatment of cSSSIs. Daptomycin was well tolerated, with most adverse events considered to be unrelated to study medication, of mild-to-moderate intensity, and with a frequency and distribution similar to those associated with comparator antibiotics. The favourable clinical profile and low potential for development of resistance combine to make daptomycin a promising alternative to current agents for treatment of Gram-positive bacterial infections.
Topics: Anti-Bacterial Agents; Clinical Trials as Topic; Daptomycin; Drug Resistance, Bacterial; Drug Synergism; Drug-Related Side Effects and Adverse Reactions; Gram-Positive Bacteria; Gram-Positive Bacterial Infections; Humans; Staphylococcal Infections; Staphylococcus aureus; Treatment Outcome
PubMed: 16445721
DOI: 10.1111/j.1469-0691.2006.01342.x -
Japanese Journal of Infectious Diseases May 2021We previously reported the emergence and high prevalence of group B streptococci (GBS) with reduced penicillin susceptibility (PRGBS) clinical isolates in Japan. PRGBS...
We previously reported the emergence and high prevalence of group B streptococci (GBS) with reduced penicillin susceptibility (PRGBS) clinical isolates in Japan. PRGBS tend to be non-susceptible to macrolides and fluoroquinolones. In our previous study, we found that the minimum inhibitory concentration (MIC) of daptomycin for one clinical isolate of GBS was above the susceptible breakpoint settled by the Clinical and Laboratory Standards Institute (CLSI). This suggests the possibility of the unrecognized spread of daptomycin-non-susceptible clinical GBS isolates in Japan. This study aimed to analyze the daptomycin susceptibility in 1,046 clinical GBS isolates that were recovered after the approval of daptomycin in Japan. MICs of daptomycin for the 1,046 clinical isolates were determined by the microdilution method recommended by the CLSI. The MIC range was 0.12-1 µg/mL, and the MIC and MIC were 0.5 µg/mL and 1 µg/mL, respectively. All the GBS isolates evaluated in this study were susceptible to daptomycin. Therefore, at present, daptomycin might be considered as a new option to treat GBS infections, especially multidrug-resistant PRGBS infections.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Child; Child, Preschool; Daptomycin; Drug Resistance, Bacterial; Female; Humans; Infant; Japan; Male; Middle Aged; Streptococcal Infections; Streptococcus; Young Adult
PubMed: 32999183
DOI: 10.7883/yoken.JJID.2020.371 -
Scientific Reports Dec 2019Staphylococcus epidermidis infections are a common occurrence in hospitals, particularly in catheter-related bloodstream and surgical site infections and infective...
Staphylococcus epidermidis infections are a common occurrence in hospitals, particularly in catheter-related bloodstream and surgical site infections and infective endocarditis. Higher daptomycin minimum inhibitory concentration (MIC) values may be associated with daptomycin treatment failure among patients with S. epidermidis infections. We therefore conducted a retrospective cohort study to determine the predictive value of daptomycin susceptibility. A retrospective study was undertaken in 1,337 patients with S. epidermidis infections. Data were collected from 1 January 2013 to 31 December 2016 at Ehime University Hospital, and included the following clinicopathological factors for evaluation: age, sex, resistance to vancomycin or teicoplanin, and history of antimicrobial therapy. Multiple analysis was performed using logistic regression to identify factors that independently and significantly affected the daptomycin resistance. Daptomycin-resistant S. epidermidis was identified in 38 (2.8%) patients. According to the multiple analysis, only higher MIC values (≥16 mg/L) for teicoplanin (P < 0.0001) were independently associated with an increased risk of developing daptomycin resistance. In conclusion, higher teicoplanin MIC values may predict resistance to daptomycin treatment in S. epidermidis infections.
Topics: Aged; Anti-Bacterial Agents; Catheter-Related Infections; Daptomycin; Dose-Response Relationship, Drug; Drug Resistance, Bacterial; Endocarditis, Bacterial; Female; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Predictive Value of Tests; Retrospective Studies; Staphylococcal Infections; Staphylococcus epidermidis; Surgical Wound Infection; Teicoplanin; Treatment Failure
PubMed: 31811214
DOI: 10.1038/s41598-019-55149-z