Daptomycin resistance

For many antibiotics, the mechanism of antibiotic resistance can help establish the mechanism of action. Therefore, it may be instructive to determine the mechanism(s) of daptomycin resistance to see if it yields insights into the mechanism of action. The incidence of reduced susceptibility to daptomycin in clinical isolates is very low and resistant strains are usually associated with deep-seated infections in compromised patients.2,9,36,37... 

If the isolate is determined to be vancomycin-resistant, it is most important to know the exact species because some of the treatment options, such as quinupristin/dalfopristin, are not active against E. faecalis. Currently, the treatment options for vancomycin-resistant enterococci (VRE) are not well established by clinical studies or patient experience. The treatment recommendations for vancomycin-resistant E. faecium include linezolid or quinupristin/dalfopristin for a minimum of 8 weeks. However, newer agents, such as daptomycin, may provide another option for treatment for either enterococci species (E. faecium and E. faecalis). Additionally, guidelines suggest the use of imipenem-cilistatin plus ampicillin or ceftriaxone plus ampicillin for the treatment of E. faecalis with a minimum of 8 weeks of therapy. Consultation with an infectious diseases specialist is recommended. 

Methicillin-resistant Staphylococcus aureus (MRSA) is a common hospital-acquired pathogen and is also increasing in the community. MRSA has presented a problem in the past because it required treatment with vancomycin. Community-acquired MRSA presents a major therapeutic challenge. MRSA can cause pneumonia, cellulitis, and other infections. Clinicians should be aware of the rate of hospital and community MRSA in your geographic area. New treatment options are available for MRSA. They include linezolid, tigecycline, and daptomycin. Prospective clinical trials have not demonstrated benefits of these agents over vancomycin.36-37... 

Vancomycin, linezolid, and daptomycin should be used to treat serious infections caused by methicillin-resistantS. aureus. 

Initial therapy with trimethoprim-sulfamethoxazole appears to be effective for CA-MRSA and should be considered in geographic areas in which CA-MRSA are commonly encountered. Alternative agents for documented infections with resistant gram-positive bacteria such as methicil-lin-resistant staphylococci and vancomycin-resistant enterococci include linezolid, quinupristin/dalfopristin, daptomycin, and tigecycline. 

Vancomycin is used frequently in severe infections with gram-positive pathogens. With increasing staphylococcal resistance, linezolid, quinupris-tin/dalfopristin, daptomycin, and tigecycline are alternatives. 

Daptomycin has a unique mechanism of action it disrupts the bacterial membrane of Gram-positive organisms by forming channels across it. These channels permit the leakage of intracellular ions, eventually leading to cell death. Resistance to daptomycin is rare, at least so far. 

It is clear that we need more novel antibacterials such as linezolid and daptomycin to counter resistance development and appearance of new pathogeiuc bacteria. These will not be easy to come by but continued control of infectious diseases requires them. It is also clear that we need a continuous flow of effective vaccines as a means to protect us from infections in the first place. 

Dhawan B, Gadepalli R, Kapil A. (2009) In vitro activity of daptomycin against Staphylococcus Aureus and vancomycin-resistant Enterococcus Faecium isolates associated with skin and soft tissue infections First results from India. Diagn Microbiol Infect Dis 65 196-198. 

Carpenter CF, Chambers HF Daptomycin Another novel agent for treating infections due to drug-resistant gram-positive pathogens. Clin Infect Dis 2004 38 994. [PMID 15034832]... 

Methicillin-resistant Vancomycin TMP-SMZ,1 minocycline, linezolid, daptomycin, tigecycline... 

There is no regimen that is reliably bactericidal for vancomycin-resistant enterococcus for which there is extensive clinical experience daptomycin has bactericidal activity in vitro. Regimens that have been reported to be efficacious include nitrofurantoin (for urinary tract infection) potential regimens for bacteremia include daptomycin, linezolid, and dalfopristin/quinupristin. 

Cellulitis S aureus, group A streptococcus Penicillinase-resistant penicillin, cephalosporin (first-generation)2 Vancomycin, clindamycin, linezolid, daptomycin... 

Vancomycin, daptomycin or linezolid (to cover staphylococci including methicillin-resistant Staphylococcus aureus (MRSA), streptococci and enterococci) plus metronidazole (to cover anaerobes) plus gentamicin, ciprofloxacin, ceftazidime or aztreonam (to cover Gram-negative organisms including Pseudomonas). 

Daptomycin is an important antibiotic approved for the treatment of complicated skin and skin structure infections caused by Gram-positive pathogens1 and for treatment of bacteraemia, including right-sided endocarditis caused by Staphylococcus aureus strains, including those resistant to methicillin (MRSA).2... 

Daptomycin has proven efficacy in a number of in vivo animal models, including soft tissue infections by MRSA, bacteraemia caused by S. aureus or vancomycin-resistant enterococci (VRE), Enterococcus faecalis pyelonephritis, MRSA osteomyelitis, MRSA and Bacillus anthracis pulmonary infections, Gram-positive endocarditis, Clostridium difficile colitis and S. pneumoniae and S. aureus meningitis.9,64 66... 

Daptomycin is a novel lipopeptide antibiotic, an inhibitor of lipoteichoic acid synthesis, with potent bactericidal activity against most clinically important Gram-positive bacteria, including resistant strains (1,2). 

The activity of daptomycin against both vancomycin-sensitive and vancomycin-resistant Enterococcus faecalis was greater than that of quinupristin + dalfopristin (5). Daptomycin was as active as quinupristin + dalfopristin but more active than linezolid. At concentrations four times the MIC, daptomycin and vancomycin achieved 99.9% killing of methicillin-resistant Staphylococcus aureus after 8 hours, which was greater than the killing seen with linezolid and quinupristin + dalfopristin. However, the antibacterial activity of daptomycin strongly depended on the calcium concentration of the medium. 

In vitro activities of daptomycin, vancomycin, linezolid, and quinupristin-dalfopristin against staphylococci and enterococci, including vancomycin-intermediate and -resistant strains. Antimicrob Agents Chemother... 

HMR 1043, discovered by the Aventis group, exhibits good antimicrobial activity against susceptible and resistant gram-positive bacteria. The activity of HMR 1043 in vitro is less influenced by the presence of calcium ions than that of daptomycin l... 

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