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

Daptomycin (Cubicin; Cubist Pharmaceuticals, Inc., Lexington, MA) is a first-in-its-class cyclic lipopeptide approved for the treatment of patients with complicated skin and skin-structure infections due to susceptible gram-positive pathogens and recently approved for Staphylococcus aureus bloodstream infections including right-sided infective endocarditis. The clinical experience of patients registered in the Cubicin Outcomes Registry and Experience (CORE) 2004 database with daptomycin-treated infective endocarditis is described. The registry data were collected retrospectively by trained investigators to document real-world clinical experience. Study limitations included uncontrolled diagnostic criteria, noncomparative data, and lack of follow-up assessments. A total of 49 patients had a diagnosis of endocarditis: 38 with left-sided or both left-sided and right-sided endocarditis, and 11 with right-sided endocarditis alone. Renal failure was the most common comorbid condition. In all, 27 (55%) of the 49 patients had an initial creatinine clearance of < or =30 mL/min, and 14 (29%) were supported by dialysis. Staphylococcus aureus (59%; 83%, methicillin resistant) and enterococci (29%; 43%, vancomycin resistant) were the most commonly identified pathogens. In most instances, patients received gram-positive therapy before receiving daptomycin (43 of 49 [88%]). The median starting dose of daptomycin was 6 mg/kg (range, 4 to 7 mg/kg); 27 (55%) of the patients received a dose of > or =6 mg/kg. Daptomycin therapy was successful for 31 (63%) of the patients: cure was seen in 18 (37%) and improvement in 13 (27%). Therapy failed in 4 (8%) of the patients, and 14 (29%) of the cases were nonevaluable. The median duration of therapy in successful cases was 27 days. No differences in clinical response were observed based on baseline renal function, primary pathogen, or site of endocarditis. The results from the CORE 2004 database suggest that daptomycin should be considered a possible treatment for patients with right-sided infective endocarditis involving S aureus. Further studies are needed to extend daptomycin's experience in left-sided or enterococcal endocarditis.
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PMID:Daptomycin in the treatment of patients with infective endocarditis: experience from a registry. 1790 48

Most antibiotics with bactericidal activity require that the bacteria be actively dividing to produce rapid killing. However, in many infections, such as endocarditis, prosthetic joint infections, and infected embedded catheters, the bacteria divide slowly or not at all. Daptomycin is a lipopeptide antibiotic with a distinct mechanism of action that targets the cytoplasmic membrane of gram-positive organisms, including Staphylococcus aureus. Daptomycin is rapidly bactericidal against exponentially growing bacteria (a 3-log reduction in 60 min). The objectives of this study were to determine if daptomycin is bactericidal against nondividing S. aureus and to quantify the extent of the bactericidal activity. In high-inoculum methicillin-sensitive S. aureus cultures in stationary phase (10(10) CFU/ml), daptomycin displayed concentration-dependent bactericidal activity, requiring 32 micro/ml to achieve a 3-log reduction. In a study comparing several antibiotics at 100 microg/ml, daptomycin demonstrated faster bactericidal activity than nafcillin, ciprofloxacin, gentamicin, and vancomycin. In experiments where bacterial cell growth was halted by the metabolic inhibitor carbonyl cyanide m-chlorophenylhydrazone or erythromycin, daptomycin (10 microg/ml) achieved the bactericidal end point (a 3-log reduction) within 2 h. In contrast, ciprofloxacin (10 microg/ml) did not produce bactericidal activity. Daptomycin (2 microg/ml) remained bactericidal against cold-arrested S. aureus, which was protected from the actions of ciprofloxacin and nafcillin. The data presented here suggest that, in contrast to that of other classes of antibiotics, the bactericidal activity of daptomycin does not require cell division or active metabolism, most likely as a consequence of its direct action on the bacterial membrane.
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PMID:Bactericidal action of daptomycin against stationary-phase and nondividing Staphylococcus aureus cells. 1792 87

There is a clinical need for new treatment options as a result of continued increase in the expression of resistance among bacterial pathogens. A number of compounds currently in development show promise. However, in some cases, there is concern that resistance may develop quickly to new compounds that are based on existing antimicrobial agents. Therefore, daptomycin, a novel lipopeptide with a unique mode of action, is of particular interest. It has rapid bactericidal activity against growing and stationary-phase bacteria, once-daily dosing regimen, and has a low potential for the development of resistance. It has been approved for the treatment of complicated skin and soft tissue infections caused by Gram-positive bacteria, and registration for treatment of infective endocarditis and bacteraemia is anticipated. Daptomycin is a welcome addition to the antimicrobial armamentarium for the treatment of bacterial infections. Tigecycline is a new glycyclcycline antimicrobial recently approved for use in the USA, Europe and elsewhere. While related to the tetracyclines, tigecycline overcomes many of the mechanisms responsible for resistance to this class. It is a novel broad spectrum glycylcycline with good activity against Gram-positive, many Gram-negative, anaerobic, and some atypical pathogens that has been developed to address this need. It is efficacious in complicated skin and soft tissue infections and in intra-abdominal infections. This review aims to summarise the key clinical data of daptomycin and tigecycline which hold promise for widespread clinical use in the next decade.
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PMID:Daptomycin and tigecycline: a review of clinical efficacy in the antimicrobial era. 1792 83

Daptomycin is the first approved member of a new class of antibiotics, namely the cyclic lipopeptides. Daptomycin has rapid bactericidal activity against Gram-positive pathogens. It acts by penetrating into the bacterial cell wall with consecutive formation of pores, loss of electrical membrane potential and inhibition of peptidoglycan synthesis. As the mode of action of daptomycin is 'concentration-dependent', the pharmacokinetic/pharmacodynamic indices that correlate best with its activity are the ratios of the peak concentration (C(max)) to minimum inhibitory concentration (MIC) or the area under the curve (24-hour AUC) to MIC. Daptomycin should be administered intravenously once daily, because adverse effects on skeletal muscle associated with an increase in plasma levels of creatine phosphokinase and myopathy were observed more frequently at shorter dosing intervals. Overall, the rate of adverse events during daptomycin therapy is comparable to that of other standard regimens. Daptomycin was shown to be not inferior to antimicrobial standard therapy and therefore was approved for complicated skin and skin structure infections at a dose of 4 mg/kg, for Staphylococcus aureus bacteremia and right-sided endocarditis at a dose of 6 mg/kg. Dosage regimens remain a matter of discussion, and an increase in the currently approved doses from 4-6 to 6-8 mg/kg per day for severe infections seems promising. Though not approved up to now, daptomycin appears to be a treatment alternative for Gram-positive bone and joint infections based on clinical observations. Large international studies showed high susceptibility of relevant Gram-positive pathogens to daptomycin, even in multidrug-resistant strains. Thus, treatment of infections caused by Gram-positive cocci resistant to other antimicrobial drugs is a potential indication of daptomycin. Since glycopeptides and daptomycin have the same target site, there appears to be a risk of reduced susceptibility to both drugs after consecutive use. Therefore, daptomycin should be used with caution for treatment of vancomycin-resistant isolates or after prior vancomycin (glycopeptide) therapy. This review describes the history, mechanism of action, susceptibility, recent discoveries and clinical experience regarding daptomycin, discussing its current role in the field of infectious diseases.
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PMID:Daptomycin: a review 4 years after first approval. 1794 Mar 48

Daptomycin is the first of a new class of antibiotics, the cyclic lipopeptides, for which a novel mechanism of action is hypothesised. Owing to its mode of action, daptomycin is rapidly bactericidal without being bacteriolytic, is active against static- and growing-phase bacteria, and has a low resistance rate in vitro. Phase III clinical trials have demonstrated that daptomycin is as effective as standard therapy for the treatment of complicated skin and soft-tissue infections associated with Gram-positive infections, and daptomycin-treated patients benefited from a reduced time to clinical resolution. Daptomycin has also been shown to be as effective as standard therapy in the treatment of bacteraemia associated with Staphylococcus aureus, with or without endocarditis. These results indicate that daptomycin is a useful therapeutic option for treating Gram-positive infections, particularly those caused by S. aureus.
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PMID:Treatment of staphylococcal infections with cyclic lipopeptides. 1822 85

Daptomycin is a novel bactericidal antibiotic with excellent activity against gram-positive organisms. It is a large cyclic lipopeptide with a unique mechanism of action. Daptomycin is given once a day and is renally cleared, requiring dose adjustment in patients with impaired renal function. Unfortunately, there have been case reports of resistant gram-positive organisms. Daptomycin is generally well tolerated, though myopathy has been reported. 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors should be stopped in patients on daptomycin. Daptomycin shows promise in experimental models of endocarditis, meningitis, ventriculitis, and peritonitis, and is currently approved for use in skin and soft-tissue infections. Daptomycin is a welcome newcomer to the gram-positive antimicrobial arsenal.
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PMID:A review of daptomycin for injection (Cubicin) in the treatment of complicated skin and skin structure infections. 1836 May 90

The proliferation of methicillin-resistant Staphylococcus aureus (MRSA) and the severity of nosocomial critical care infections necessitate the development of viable alternative therapies. An increase in the tolerance of MRSA to the activity of vancomycin and to the associated suboptimal therapeutic measures is of particular concern. Daptomycin, the first of a new class of antimicrobials known as the lipopeptides, is indicated for the treatment of S aureus, including MRSA, in bacteremia, right-sided endocarditis, and complicated skin and skin structure infections. Daptomycin has a novel mechanism of action, rapid bactericidal activity, and a lack of cross resistance with other antibiotic classes. Daptomycin has also demonstrated efficacy in case studies involving the treatment of osteomyelitis and involving complicated persistent infections associated with indwelling medical devices. Because of its efficacy and safety in a variety of infectious conditions and because of its rapid bactericidal activity, daptomycin is well suited as a viable alternative for patients in the critical care setting.
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PMID:The use of daptomycin for Staphylococcus aureus infections in critical care medicine. 1836 50

Daptomycin is a lipopeptide antibiotic with potent in vitro activity against gram-positive cocci, including Staphylococcus aureus. This study evaluated the in vitro and in vivo efficacies of daptomycin against two clinical isolates: methicillin-resistant S. aureus (MRSA) 277 (vancomycin MIC, 2 microg/ml) and glycopeptide-intermediate S. aureus (GISA) ATCC 700788 (vancomycin MIC, 8 microg/ml). Time-kill experiments demonstrated that daptomycin was bactericidal in vitro against these two strains. The in vivo activity of daptomycin (6 mg/kg of body weight every 24 h) was evaluated by using a rabbit model of infective endocarditis and was compared with the activities of a high-dose (HD) vancomycin regimen (1 g intravenously every 6 h), the recommended dose (RD) of vancomycin regimen (1 g intravenously every 12 h) for 48 h, and no treatment (as a control). Daptomycin was significantly more effective than the vancomycin RD in reducing the density of bacteria in the vegetations for the MRSA strains (0 [interquartile range, 0 to 1.5] versus 2 [interquartile range, 0 to 5.6] log CFU/g vegetation; P = 0.02) and GISA strains (2 [interquartile range, 0 to 2] versus 6.6 [interquartile range, 2.0 to 6.9] log CFU/g vegetation; P < 0.01) studied. In addition, daptomycin sterilized more MRSA vegetations than the vancomycin RD (13/18 [72%] versus 7/20 [35%]; P = 0.02) and sterilized more GISA vegetations than either vancomycin regimen (12/19 [63%] versus 4/20 [20%]; P < 0.01). No statistically significant difference between the vancomycin HD and the vancomycin RD for MRSA treatment was noted. These results support the use of daptomycin for the treatment of aortic valve endocarditis caused by GISA and MRSA.
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PMID:Daptomycin is effective in treatment of experimental endocarditis due to methicillin-resistant and glycopeptide-intermediate Staphylococcus aureus. 1842

Staphylococcus aureus bacteremia is a common disease with a high risk of mortality and complications. An increasing proportion of cases are methicillin-resistant S.aureus (MRSA), and methicillin-resistance is being observed from both community-acquired bacteremias and in healthcare-associated infections. The duration of bacteremia and transesophageal echocardiographic findings are useful in predicting the likelihood of complications including endocarditis. Therapy with vancomycin has been the mainstay in the treatment of MRSA bacteremias, but is associated with a long duration of bacteremia on therapy and relapses. Loss of susceptibility to vancomycin, due to thickened cell walls and through the acquisition of the vanA gene, has been described. Daptomycin is newly approved lipopeptide that is highly bactericidal against most strains of MRSA. In a randomized trial, daptomycin was demonstrated to be effective in the treatment of S. aureus bacteremia and right-sided endocarditis. However treatment failures associated with isolates with daptomycin non-susceptibility are reported, and there is a correlation between isolates with reduced vancomycin susceptibility and reduced daptomycin susceptibility. Daptomycin is a useful alternative to vancomycin in the therapy of MRSA bacteremia and endocarditis. However the appropriate role of daptomycin in optimizing therapy with MRSA bacteremia and endocarditis remains to be elucidated.
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PMID:Bacteremia and endocarditis due to methicillin-resistant Staphylococcus aureus: the potential role of daptomycin. 1847 90

Daptomycin is a clinically important antibiotic approved for the treatment of complicated skin and skin structure infections caused by Gram-positive pathogens, and for the treatment of bacteremia and endocarditis caused by Staphylococcus aureus. Daptomycin and related acidic cyclic lipopeptide antibiotics have ten amino acids in the ring, and exocyclic tails containing one or three amino acids. The N-termini of the exocyclic amino acids are generally coupled to long chain fatty acids. Biosynthesis is initiated by the coupling of fatty acids to the N-terminal amino acids, followed by the coupling of the remaining amino acids by nonribosomal peptide synthetase (NRPS) mechanisms, then cyclization and release of the lipopeptides. The biosynthetic genes for daptomycin, calcium dependent antibiotic (CDA), A54145 and friulimicin have been cloned, sequenced, analyzed bioinformatically, and in some cases genetically or biochemically. The information on the organization and expression of the NRPS and other genes has been exploited to generate combinatorial libraries of hybrid lipopeptide antibiotics related to daptomycin, including several compounds with very good antibacterial activities.
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PMID:Biosynthesis and genetic engineering of lipopeptide antibiotics related to daptomycin. 1847 88


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