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Query: UMLS:C0014118 (endocarditis)
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Daptomycin, a novel lipopeptide, is bactericidal against a broad range of gram-positive strains, including methicillin- (MRSA) and vancomycin-resistant Staphylococcus aureus. Daptomycin is approved at 4 mg/kg of body weight given intravenously once daily for the treatment of complicated skin and skin structure infections and at 6 mg/kg for the treatment of S. aureus bloodstream infections (bacteremia), including right-sided endocarditis caused by methicillin-susceptible S. aureus and MRSA. The present study was designed to evaluate the multiple-dose pharmacokinetics and safety of daptomycin at doses of 6 to 12 mg/kg in healthy volunteers. Three cohorts of 12 subjects each were given daptomycin (10 mg/kg) or placebo once daily for 14 days, daptomycin (12 mg/kg) or placebo once daily for 14 days, or daptomycin (6 or 8 mg/kg) once daily for 4 days. Daptomycin produced dose-proportional increases in the area under the plasma concentration-time curve and in trough daptomycin levels and nearly dose-proportional increases in peak daptomycin concentrations. Other pharmacokinetic parameters measured on day 1 and at steady state were independent of the dose, including the half-life (approximately 8 h), weight-normalized plasma clearance (9 to 10 ml/h/kg), and volume of distribution (approximately 100 ml/kg). Plasma protein binding was 90% to 93% and was independent of the daptomycin concentration. Daptomycin did not produce electrocardiographic abnormalities or electrophysiological evidence of muscle or nerve toxicity. Daptomycin was well tolerated in subjects dosed with up to 12 mg/kg intravenously for 14 days. Doses of daptomycin higher than 6 mg/kg once daily may be considered in further studies to evaluate the safety and efficacy of daptomycin in difficult-to-treat infections.
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PMID:Pharmacokinetics and tolerability of daptomycin at doses up to 12 milligrams per kilogram of body weight once daily in healthy volunteers. 1700 1

Daptomycin, a cyclic lipopeptide produced by Streptomyces roseosporus, is the active ingredient of Cubicin (daptomycin-for-injection), a first-in-class antibiotic approved for treatment of skin and skin-structure infections caused by Gram-positive pathogens and bacteremia and endocarditis caused by Staphylococcus aureus, including methicillin-resistant strains. Genetic engineering of the nonribosomal peptide synthetase (NRPS) in the daptomycin biosynthetic pathway was exploited for the biosynthesis of novel active antibiotics. lambda-Red-mediated recombination was used to exchange single or multiple modules in the DptBC subunit of the NRPS to modify the daptomycin cyclic peptide core. We combined module exchanges, NRPS subunit exchanges, inactivation of the tailoring enzyme glutamic acid 3-methyltransferase, and natural variations of the lipid tail to generate a library of novel lipopeptides, some of which were as active as daptomycin against Gram-positive bacteria. One compound was more potent against an Escherichia coli imp mutant that has increased outer membrane permeability. This study established a robust combinatorial biosynthesis platform to produce novel peptide antibiotics in sufficient quantities for antimicrobial screening and drug development.
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PMID:Combinatorial biosynthesis of novel antibiotics related to daptomycin. 1709 Jun 67

We present a case of drug-induced eosinophilic pneumonia resulting from intravenous daptomycin being used as therapy for recurrent methicillin-sensitive Staphlococcus aureus endocarditis. The patient developed hypoxic respiratory failure requiring intubation and mechanical ventilation. Daptomycin therapy was discontinued immediately, and the patient improved significantly after the administration of intravenous corticosteroids allowing for extubation 3 days later.
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PMID:Eosinophilic pneumonia induced by daptomycin. 1720 58

Antibiotic resistance among Gram-positive bacteria has increased in recent years, thereby compromising the use of traditional therapies. Reducing the spread of antimicrobial resistance is mandatory and requires worldwide cooperation. Complementary to such measures in the management of infectious diseases is the development of novel therapeutic agents. Daptomycin is the first in a new class of antibiotics, the cyclic lipopeptide with a potent and bactericidal activity against Gram-positive pathogens and, due to its in vitro and in vivo characteristics, demonstrates to be an exciting option for the treatment of Gram-positive infections. It has very good pharmacokinetics properties with a long half-life which allows a single intravenous daily dose and is currently approved for treatment of complicated skin and soft tissue infections at the dosage of 4 mg/kg/die and for treatment of bacteremia and endocarditis at the dosage of 6 mg/kg/die. Its favourable clinical profile together with its bactericidal activity and low potential for development of resistance makes daptomycin a good alternative to currently used agents for treatment of Gram positive infections.
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PMID:[Daptomycin, the first cydal antibiotic of a new class active against Gram positive pathogens]. 1738 85

Antimicrobial resistance among Gram-positive organisms continues to increase and has reached epidemic proportions in a number of countries and within medical centers worldwide. Daptomycin is a new lipopeptide antibiotic with rapid bactericidal activity against Staphylococcus aureus. It is also active against coagulase-negative staphylococci, enterococci and streptococci. It exerts its effect through cell membrane disruption that results in dissipation of the membrane potential. Daptomycin exhibits a prolonged postantibiotic effect and is well tolerated. In Phase III clinical trials, daptomycin was found to be similar in efficacy to standard therapy in complicated skin and skin structure infections. More recently, it was approved for the treatment of S. aureus bacteremia and right-sided endocarditis. Daptomycin is not indicated for pulmonary infections. Preliminary data suggest that daptomycin may be effective in urinary tract, bone and joint infections. However, randomized clinical trials are needed to confirm these findings. Daptomycin is an effective antimicrobial agent for the treatment of various serious Gram-positive infections, especially those caused by methicillin-resistant S. aureus.
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PMID:Daptomycin: a rapidly bactericidal lipopeptide for the treatment of Gram-positive infections. 1740 33

Daptomycin (Cubicin) is the first of a new class of antibacterials, the cyclic lipopeptides, and is approved for use in the treatment of complicated skin and soft-tissue or skin-structure infections (hereafter referred to as cSSTI) caused by Gram-positive bacteria and Staphylococcus aureus bacteraemia including right-sided infective endocarditis.Daptomycin has activity in vitro against a wide variety of Gram-positive bacteria, including meticillin-resistant S. aureus (MRSA) and vancomycin-resistant enterococci. When administered as a once-daily intravenous infusion, daptomycin was not inferior to standard parenteral therapy (vancomycin or semi-synthetic penicillins) in terms of clinical and microbiological efficacy in patients with cSSTI or S. aureus bacteraemia with or without infective endocarditis (including MRSA infection) and was well tolerated. With the advantage of once-daily administration and a low potential for drug interactions, daptomycin is a useful addition to the range of parenteral antibacterial agents available for the treatment of patients with cSSTI or S. aureus bacteraemia with or without right-sided infective endocarditis. Efficacy against both meticillin-susceptible S. aureus (MSSA) and MRSA infections makes daptomycin suitable for empirical therapy in patients with serious Gram-positive infections.
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PMID:Daptomycin: a review of its use in the management of complicated skin and soft-tissue infections and Staphylococcus aureus bacteraemia. 1760 Mar 94

There has been a steady rise in the prevalence of resistant Gram-positive pathogens and concerns about the clinical effectiveness of glycopeptides in treating infections due to Staphylococcus aureus. Daptomycin is a novel lipopeptide antimicrobial agent with activity against Gram-positive organisms, including multi-resistant strains. It is licensed in the USA and Europe for the treatment of complicated skin and soft tissue infections caused by Gram-positive organisms at a dose of 4mg/kg once daily. It has also been licensed in the USA for the treatment of S. aureus bacteraemia and right-sided endocarditis at 6mg/kg once daily. It is a safe and well-tolerated antibiotic, particularly at the current dosing regimen. Antimicrobial resistance, whilst being increasingly reported, still remains relatively rare. Further studies are required to determine the role of daptomycin for the treatment of osteomyelitis and septic arthritis, as well as its use in combination therapy.
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PMID:Daptomycin. 1762 67

Daptomycin is a lipopeptide antibiotic that exhibits bactericidal activity against a range of Gram-positive bacterial pathogens including strains resistant to other antibiotics, such as methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci. Daptomycin is licensed both in the USA and Europe for the treatment of complicated skin and skin-structure infections and in the USA this has recently been expanded to include bacteremia and right-sided endocarditis due to Staphylococcus aureus. A marketing authorization application for this indication is currently under consideration by the European Medicines Agency. The pharmacokinetic and pharmacodynamic properties of daptomycin allow for once-daily dosing, although it is recommended that the dosing interval be increased to 2 days in patients with renal impairment. Clinical data generally indicate that daptomycin is well tolerated, but nonetheless concerns persist regarding potential muscle toxicity. Emergence of resistance to daptomycin has been reported, highlighting the need for prospective surveillance to determine the extent of this potential problem.
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PMID:Daptomycin in the treatment of skin, soft-tissue and invasive infections due to Gram-positive bacteria. 1766 38

Methicillin-resistant Staphylococcus aureus infections are becoming more frequent and less easily treated by means of currently recommended agents. Vancomycin has been associated with decreased susceptibility in staphylococci and with treatment failures. Daptomycin is rapidly bactericidal; a dosage of 4 mg/kg daily is approved for treatment of skin and soft-tissue infections, and a dosage of 6 mg/kg daily is approved for treatment of patients with S. aureus bacteremia and right-sided endocarditis. Findings of in vitro studies suggest a correlation between the minimum inhibitory concentrations of daptomycin and vancomycin. Clinical failure was associated with increasing minimum inhibitory concentrations in case reports and in a randomized study of persons with S. aureus bacteremia and endocarditis. Patients who did not respond to therapy had deep-seated infections that required but could not be or were not managed with adjunctive surgical therapy. No definitive resistance mechanism has been identified, although genetic mutations have been described. Clinically, prior vancomycin therapy has not been associated with failure of daptomycin therapy. Although clinical practitioners must monitor for daptomycin resistance, the available data support the use of daptomycin in the treatment of methicillin-resistant S. aureus bacteremia and endocarditis.
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PMID:Perspectives on Daptomycin resistance, with emphasis on resistance in Staphylococcus aureus. 1768 96

Vancomycin- and methicillin-resistant gram-positive cocci have emerged as an increasingly problematic cause of hospital-acquired infections. We conducted a literature review of newer antibiotics with activity against vancomycin-resistant and methicillin-resistant gram-positive cocci. Quinupristin/dalfopristin, linezolid, daptomycin, and tigecycline have in vitro activity for methicillin-resistant staphylococci and are superior to vancomycin for vancomycin-resistant isolates. Dalbavancin, telavancin, and oritavancin are new glycopeptides that have superior pharmacodynamic properties compared to vancomycin. We review the antibacterial spectrum, clinical indications and contraindications, pharmacologic properties, and adverse events associated with each of these agents. Daptomycin has rapid bactericidal activity for Staphylococcus aureus and is approved for use in bacteremia and right-sided endocarditis. Linezolid is comparable to vancomycin in patients with methicillin-resistant S. aureus (MRSA) pneumonia and has pharmacoeconomic advantages given its oral formulation. Quinupristin/dalfopristin is the drug of choice for vancomycin-resistant Enterococcus faecium infections but has no activity against Enterococcus faecalis. Tigecycline has activity against both enterococcus species and MRSA; it is also active against Enterobacteriaceae and anaerobes which allows for use in intra-abdominal and diabetic foot infections. A review of numerous in vitro and animal model studies shows that interaction between these newer agents and other antistaphylococcal agents for S. aureus are usually indifferent (additive).
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PMID:New antimicrobial agents as therapy for resistant gram-positive cocci. 1789 28


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