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Query: UMLS:C0014118 (endocarditis)
 15,629 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The need to investigate novel dosing regimens and combinations is essential in combating poor treatment outcomes for Staphylococcus aureus bacteremia and endocarditis. We evaluated the impact of simulated standard- and high-dose daptomycin in combination with gentamicin or rifampin against daptomycin-susceptible and nonsusceptible matched strains of S. aureus. These strains were collected from the daptomycin bacteremia and endocarditis clinical trial and consisted of three susceptible strains (MIC, 0.25 mg/liter) and four nonsusceptible isolates (MICs, 2 to 4 mg/liter). Daptomycin regimens of 6 and 10 mg/kg of body weight daily alone and in combination with gentamicin at 5 mg/kg daily or rifampin at 300 mg every 8 h were evaluated using an in vitro model with simulated endocardial vegetations over 96 h. Rapid bactericidal activity, identified by time to 99.9% kill, was displayed in all regimens with the daptomycin-susceptible strains. Concentration-dependent activity was noted by more-rapid killing with the 10-mg/kg/day dose. The addition of gentamicin improved activity in the majority of susceptible isolates. Daptomycin 6-mg/kg/day monotherapy displayed bactericidal activity for only one of the nonsusceptible isolates and for only two isolates with increased doses of 10 mg/kg/day. Combination regimens demonstrated improvement with some but not all nonsusceptible isolates. Three isolates developed a reduction in daptomycin susceptibility with 6-mg/kg/day monotherapy, but this was suppressed with both combination therapy and high-dose daptomycin. These results suggest that high-dose daptomycin therapy and combination therapy may be reasonable treatment options for susceptible isolates; however, more investigations are needed to confirm the variability of these regimens with nonsusceptible isolates.
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PMID:Evaluation of daptomycin pharmacodynamics and resistance at various dosage regimens against Staphylococcus aureus isolates with reduced susceptibilities to daptomycin in an in vitro pharmacodynamic model with simulated endocardial vegetations. 1859 Dec 72

Gram-positive cocci are one of the leading causes of infections in clinical medicine. Since the invention of antibiotic substances, multidrug resistance is a major problem in the treatment of such infections. Methicillin-resistant Staphylococcus aureus (MRSA) is responsible for 60% of nosocomial infections in the US. The first-choice drug used in these cases is the glycopeptide vancomycin; however, vancomycin is associated with a significant number of adverse side effects, such as nephro- and ototoxicity. Thus, the discovery of new drugs against MRSA and other multidrug-resistant cocci is of utmost interest. Daptomycin, a lipopeptide, is one of these new drugs and has been successfully used in the treatment of complicated skin and skin-structure infections and right-sided endocarditis. Because of its potency and pharmacological profile, it is increasingly used for new indications not yet approved by the FDA. The purpose of this article is to provide an overview of daptomycin, with particular emphasis on potential new indications for which it could be used in the future.
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PMID:Daptomycin, a lipopeptide antibiotic in clinical practice. 1866 36

Traditionally, methicillin-resistant Staphylococcus aureus (MRSA) has been seen as an infection control problem in healthcare communities. It is now clear that antibiotic use is also an important factor in the control of MRSA, both in the treatment of infection and also, paradoxically perhaps, as a cause of the MRSA problem, in the same way that antibiotic use causes Clostridium difficile disease. At both levels, major improvements in the quality of our antibiotic use are required, particularly antibiotic stewardship to reduce the selection, maintenance and transmission of MRSA strains. In addition, new agents are required to reduce our reliance on glycopeptides for the treatment of serious MRSA infections. Daptomycin has great promise in this regard as its rapid bactericidal activity makes it particularly suitable for the treatment of bacteraemia and endocarditis.
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PMID:Who's winning the war? 1882 23

Daptomycin is the first new natural-product antibiotic launched in a generation. It was licensed first for skin and soft tissue infections (SSTIs) and, more recently, for staphylococcal bacteraemia and endocarditis. Further clinical trials are in progress, some investigating performance in subsets of SSTIs while others, more interestingly, are evaluating efficacy in enterococcal endocarditis and neutropenic fevers--settings where the compound's bactericidal activity is potentially advantageous. There is a need for further trials in bone and joint infections. On the negative side, there are several reports of mutational resistance emerging during the treatment of methicillin-resistant Staphylococcus aureus (MRSA) infections, mostly in settings with a heavy bacterial load, and there is a need to determine whether higher dosages or combination regimens will reduce this risk. A few patients have already been treated with doses of up to 12 mg/kg. Lastly, daptomycin is entering a market increasingly crowded with new anti-Gram-positive agents. More work is required to establish those settings where daptomycin and other new compounds offer real advantages over established glycopeptides and over each other. There is presently a paradox whereby vancomycin is agreed to be less than ideal, with outcomes impaired against MRSA with modestly raised MICs, but where new agents have yet to demonstrate unequivocal superiority.
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PMID:Future directions with daptomycin. 1882 25

Daptomycin is a broad-spectrum, bactericidal agent active against Gram-positive bacteria, acting largely and unusually through membrane depolarization. Activity is markedly affected in vitro by the availability of calcium ions, and its high molecular weight with associated poor diffusion means that conventional disc diffusion testing is not reliable (and as a consequence not available). In order to allow susceptibility categorization, it is recommended that the MIC be determined in the presence of a defined calcium concentration. The activity of daptomycin is concentration-dependent with a prolonged post-antibiotic effect. It has linear pharmacokinetics, with a half-life of 8-9 h, the primary route of excretion is renal, it exhibits serum protein binding of approximately 92% and there is no interaction with the P450 cytochrome. Daptomycin is inactivated by surfactant in the lung and, in consequence, is not recommended for the treatment of respiratory infections. Daptomycin is currently licensed for the treatment of complicated skin and soft tissue infections and for bacteraemia and right-sided endocarditis due to methicillin-susceptible and -resistant Staphylococcus aureus. To date, daptomycin-resistant bacteria have rarely been isolated from patients, although increases in vancomycin MIC may be linked to reduced susceptibility to daptomycin. Close monitoring of resistance is essential to maintain the clinical utility of the drug. Using once-daily dosing, daptomycin has been generally well tolerated; however, weekly monitoring of creatinine phosphokinase is recommended, as myopathy in skeletal muscles has been seen, albeit rarely. The rapid bactericidal action of daptomycin makes it a useful addition to the therapeutic armamentarium for the treatment of Gram-positive infections, providing a valuable alternative to vancomycin when it is inappropriate or resistance is a problem.
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PMID:Pre-clinical experience with daptomycin. 1882 26

Daptomycin is approved for treatment of Staphylococcus aureus bacteremia and right-sided endocarditis. Increases in daptomycin MICs have been associated with failure. A rabbit model of aortic valve endocarditis was used to determine whether MIC correlates with activity in vivo and whether a higher daptomycin dose can improve efficacy. Two related clinical S. aureus strains, one with a daptomycin MIC of 0.5 microg/ml and the other with a MIC of 2 microg/ml, were used to establish aortic valve endocarditis in rabbits. Daptomycin was administered once a day for 4 days at 12 mg/kg of body weight or 18 mg/kg to simulate doses in humans of 6 mg/kg and 10 mg/kg, respectively. Endocardial vegetations, spleens, and kidneys were harvested and quantitatively cultured. The strain with a MIC of 2 microg/ml had a survival advantage over the strain with a MIC of 0.5 microg/ml with >100 times more organisms of the former in endocardial vegetations at the 12-mg/kg dose in a dual-infection model. Both the 12-mg/kg dose and the 18-mg/kg dose completely eradicated the strain with a MIC of 0.5 from vegetations, spleens, and kidneys. The 12-mg/kg dose was ineffective against the strain with a MIC of 2 in vegetations; the 18-mg/kg dose produced a reduction of 3 log(10) units in CFU in vegetations compared to the controls, although in no rabbit were organisms completely eliminated. Increasing the dose of daptomycin may improve its efficacy for infections caused by strains with reduced daptomycin susceptibility.
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PMID:Relationship between susceptibility to daptomycin in vitro and activity in vivo in a rabbit model of aortic valve endocarditis. 1917 3

Enterococcal infections are a common cause of nosocomial bloodstream infections. Vancomycin resistance and the emergence of linezolid resistance necessitate alternative therapies. Studies in vitro as well as animal and case studies suggest that daptomycin may be effective in enterococcal infections. Patients with positive blood cultures for enterococci in the Cubicin((R)) Outcomes Registry and Experience (CORE) 2005-2006 were identified. Patients with endocarditis, intracardiac foreign body infections or non-speciated enterococci were excluded. Outcome was assessed using protocol-defined criteria. Of 159 patients included in the efficacy population, Enterococcus faecium and Enterococcus faecalis were isolated in 120 (75.5%) and 39 (24.5%) patients, respectively. Vancomycin resistance was detected in 91% and 23% of patients with E. faecium and E. faecalis infections, respectively. Prior to daptomycin, 94/159 (59.1%) and 35/159 (22.0%) patients had received vancomycin and linezolid, respectively. Daptomycin was first-line therapy in 27/159 cases (17%). Success was observed in 139/159 patients (87%) and in 104/120 (87%) and 35/39 (90%) patients with E. faecium and E. faecalis infections, respectively. Among the safety population (n=211), 20 (9.5%) experienced 28 adverse events possibly related to daptomycin, 8 of which were considered serious. Daptomycin may be a useful agent for treating enterococcal bacteraemia caused by E. faecium or E. faecalis. Further studies are warranted.
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PMID:Daptomycin for the treatment of enterococcal bacteraemia: results from the Cubicin Outcomes Registry and Experience (CORE). 1920 Nov 65

This study evaluated the activity of daptomycin combined with either gentamicin or rifampin against three methicillin-resistant Staphylococcus aureus (MRSA) clinical isolates in vitro and one isolate in vivo against a representative strain (MRSA-572). Time-kill experiments showed that daptomycin was bactericidal against these strains at concentrations over the MIC. Daptomycin at sub-MIC concentrations plus gentamicin at 1x and 2x the MIC yielded synergy, while the addition of rifampin at 2 to 4 microg/ml resulted in indifference (two strains) or antagonism (one strain). The in vivo activity of daptomycin (6 mg/kg of body weight once a day) was evaluated +/- gentamicin (1 mg/kg intravenously [i.v.] every 8 h [q8h]) or rifampin (300 mg i.v. q8h) in a rabbit model of infective endocarditis by simulating human pharmacokinetics. Daptomycin plus gentamicin (median, 0 [interquartile range, 0 to 2] log10 CFU/g vegetation) was as effective as daptomycin alone (0 [0 to 2] log10 CFU/g vegetation) in reducing the density of bacteria in valve vegetations (P = 0.83), and both were more effective than daptomycin plus rifampin (3 [2 to 3.5] log10 CFU/g vegetation; P < 0.05) for the strain studied. In addition, daptomycin sterilized a ratio of vegetations that was similar to that of daptomycin plus gentamicin (10/15 [67%] versus 9/15 [60%]; P = 0.7), and both regimens did so more than daptomycin plus rifampin (3/15 [20%]; P = 0.01 and P = 0.02, respectively). No statistical difference was noted between daptomycin plus gentamicin and daptomycin alone for MRSA treatment. In the combination arm, all isolates from vegetations remained susceptible to daptomycin, gentamicin, and rifampin. Sixty-one percent of the isolates (8/13) acquired resistance to rifampin during monotherapy. In the daptomycin arm, resistance was detected in only one case, in which the daptomycin MIC rose to 2 microg/ml among the recovered bacteria. In conclusion, the addition of gentamicin or rifampin does not enhance the effectiveness of daptomycin in the treatment of experimental endocarditis due to MRSA.
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PMID:Addition of gentamicin or rifampin does not enhance the effectiveness of daptomycin in treatment of experimental endocarditis due to methicillin-resistant Staphylococcus aureus. 1962 Mar 26

The complications from S. aureus bacteremia (SAB) and infective endocarditis (SAIE) are higher in patients with diabetes. We summarize the characteristics and outcome of diabetic patients enrolled in a multicenter trial of daptomycin vs. standard therapy for SAB and SAIE. Adult patients with SAB were randomized to daptomycin 6 mg/kg/day or standard therapy (vancomycin 1 g every 12 h or antistaphylococcal penicillin 2 g every 4 h, both with gentamicin 1 mg/kg every 8 h for 4 days). Clinical success was defined as survival, resolution of S. aureus infection, and clinical outcome of cure or improved 6 weeks after end of therapy. Diabetic patients (86/235) were older, more overweight, and were more likely to present with systemic inflammatory response syndrome (SIRS) and to have complicated SAB. Clinical success rates were similar (67.4% in diabetics and 70.5% in non-diabetics). The mortality rate was significantly higher among diabetic patients (22.1% vs. 11.4%, p = 0.038). In the diabetes subgroup, the clinical success and mortality rates were comparable between the daptomycin and the standard therapy arms. The presence of diabetes is associated with significantly higher mortality in patients with SAB and SAIE. Daptomycin is an alternative therapeutic option in diabetic patients with these serious staphylococcal infections.
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PMID:Clinical characteristics and outcomes of diabetic patients with Staphylococcus aureus bacteremia and endocarditis. 1973 Sep

Epidemiology of infectious endocarditis has changed in last decades, endocarditis associated to hospital practices, sustained by multiresistant pathogens being highly increased. In particular, methicillin-resistant staphylococci (MRSA), almost resistant to a number of other antimicrobial classes, often exhibit a reduced susceptibility to vancomycin (h-VISA) with MICs' values more e than 1 mg/l, leading to suppose a reduced therapeutic efficacy of this drug. Thirty-one percent of MRSA strains in the ICE study, which prospectively collected more than 5000 endocarditis, were h-VISA. Daptomycin shows a rapid bactericidal activity against both methicillin-susceptible staphylococcci (MSSA) and MRSA, included those strains with reduced susceptibility to vancomycin. Daptomycin shows a good therapeutic efficacy in staphylococcal endocarditis: MRSA 71%, MSSA 75%. These data suggest the use of daptomycin as initial therapy for treatment of staphylococcal endocarditis, independently from methcillin susceptibility. Some experimental data showed that daptomycin efficacy can diminish, if it is used as a rescue therapy after vancomycin failure. The thickness of bacterial cell-wall recognized in h-VISA strains can represent a physical and electrical barrier to reach both the vancomycin and daptomycin target site. However, the reduced efficacy of daptomycin following vancomycin exposure is an extremely rare event in the clinical practice. It is preferrable to use daptomycin as first line therapy, at a proper dosage. As far as endocarditis is concerned, recent data proved the excellent daptomycin tolerability, with dosages up to 8-10 mg/kg/die. During the treatment, CPK values must be always monitored. For endocarditis sustained by vancomycin-resistant enterococci, therapeutic choices are based on linezolid or ampicillin-ceftriaxone combination therapy. Daptomycin alone, or in association with gentamycin and rifampin, can represent a promising therapeutic alternative.
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PMID:[Treatment of multiresistant Gram positive endocarditis]. 1983 95


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