Daptomycin antimicrobial activity tested against methicillin-resistant staphylococci and vancomycin-resistant enterococci isolated in European medical centers (2005)

JMI Laboratories, North Liberty, Iowa, USA.
BMC Infectious Diseases (Impact Factor: 2.61). 02/2007; 7(1):29. DOI: 10.1186/1471-2334-7-29
Source: PubMed


Daptomycin is a cyclic lipopeptide with potent activity and broad spectrum against Gram-positive bacteria currently used for the treatment of complicated skin and skin structure infections and bacteremia, including right sided endocarditis. We evaluated the in vitro activity of this compound and selected comparator agents tested against clinical strains of staphylococci and enterococci collected in European medical centers in 2005.
A total of 4,640 strains from 23 medical centers located in 10 European countries, Turkey and Israel (SENTRY Program platform) were tested for susceptibility by reference broth microdilution methods according to Clinical and Laboratory Standards Institute guidelines and interpretative criteria. Mueller-Hinton broth was supplemented to 50 mg/L Ca++ for testing daptomycin. Results for oxacillin (methicillin)-resistant staphylococci and vancomycin-resistant enterococci were analyzed separately.
Oxacillin resistance rates among Staphylococcus aureus varied from 2.1% in Sweden to 42.5% in the United Kingdom (UK) and 54.7% in Ireland (29.1% overall), while vancomycin resistance rates varied from 0.0% in France, Sweden and Switzerland to 66.7% in the UK and 71.4% in Ireland among Enterococcus faecium (17.9% overall). All S. aureus strains were inhibited at daptomycin MIC of 1 mg/L (MIC50/90, 0.25/0.5 mg/L; 100.0% susceptible) and only one coagulase-negative staphylococci strain (0.1%) showed an elevated (>1 mg/L) daptomycin MIC value (4 mg/L). Among E. faecalis (MIC50/90, 0.5/1 mg/L; 100% susceptible) the highest daptomycin MIC value was 2 mg/L; while among E. faecium (MIC50/90, 2/4 mg/L; 100% susceptible) the highest MIC result was 4 mg/L.
Daptomycin showed excellent in vitro activity against staphylococci and enterococci collected in European medical centers in 2005 and resistance to oxacillin, vancomycin or quinupristin/dalfopristin did not compromise its activity overall against these pathogens. Based on these results and those of previous publications, daptomycin appears to be an excellent therapeutic option for serious infections caused by oxacillin-resistant staphylococci and vancomycin-resistant enterococci in Europe.

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Available from: Helio S Sader, Apr 13, 2015
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    • "These infections are often indolent and unresponsive to antimicrobials [5], and frequently result in the removal of the adulterated device. In clinical samples, rates of methicillin resistance in intensive care unit settings have been reported to be 55–77%, or even 86% [6-8]. "
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    ABSTRACT: Background Staphylococcus epidermidis is a common pathogen in medical device-associated infections and have an ability to form adherent slime. We aimed to study the effects of icaA and icaD genes on the slime formation of Staphylococcus epidermidis associated with catheter-associated infections. Methods S. epidermidis isolates from the central venous catheter blood of patients with catheter-associated infections, and from the nasal vestibules of healthy volunteers, intensive care unit hospital staff, and patients, were collected. Slime phenotype was determined by Congo red agar test. The icaA/D was detected by polymerase chain reaction. Slime was examined using scanning electron microscopy. Results A total of 82 S. epidermidis isolates were collected. We found a statistically significant difference with regards to slime production between the clinical isolates from the catheter blood specimens and those from the nasal vestibules (p<0.05). All S. epidermidis slime positive strains isolated were icaA positive. There was a greater correlation between the presence of both icaA and icaD and the slime production than the single expression of icaA or icaD and the presence of slime in all groups. The co-expression of mecA and icaD was associated with enhanced resistance to antibiotics. Conclusion S. epidermidis bacteria are significant nosocomial pathogens, and icaA/D can clarify the adhesion mechanism in the pathogenesis of infections associated with medical devices. This study result could be useful for the development of rapid diagnosis for slime producing and methicillin resistant S. epidermidis strains.
    BMC Infectious Diseases 05/2013; 13(1):242. DOI:10.1186/1471-2334-13-242 · 2.61 Impact Factor
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    • "Of all the antibacterial agents tested for susceptibility against the MRSA isolates detected at screening, daptomycin showed potent antibacterial activity, with a MIC90 of 0.5 μg/ml. The susceptibility of MRSA isolates in Japan seems similar to that reported elsewhere [6, 7, 17]. Patients with baseline pathogens with a higher MIC tended to show less favorable clinical responses to daptomycin. "
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    ABSTRACT: Daptomycin is a lipopeptide antibiotic active against gram-positive organisms and recently approved for marketing in Japan. This study investigates the efficacy and safety of daptomycin in Japanese patients with skin and soft tissue infections (SSTIs) caused by methicillin-resistant Staphylococcus aureus (MRSA) for regulatory filing in Japan. Overall, 111 Japanese patients with SSTI were randomized in this open-label, randomized, active-comparator controlled, parallel-group, multicenter, phase III study. Patients received intravenous daptomycin 4 mg/kg once daily or vancomycin 1 g twice daily for 7-14 days. Efficacy was determined by a blinded Efficacy Adjudication Committee. Among patients with SSTIs caused by MRSA, 81.8 % (95 % CI, 69.1-90.9) of daptomycin recipients and 84.2 % (95 % CI, 60.4-96.6) of vancomycin recipients achieved a successful clinical response at the test-of-cure (TOC) visit. The microbiological success rate against MRSA at the TOC visit was 56.4 % (95 % CI, 42.3-69.7) with daptomycin and 47.4 % (95 % CI, 24.4-71.1) with vancomycin. Daptomycin was generally well tolerated; most adverse events were of mild to moderate severity. The measurement of daptomycin concentration in plasma revealed that patients with mild or moderate impaired renal function showed similar pharmacokinetics profiles to patients with normal renal function. Clinical and microbiological responses, stratified by baseline MRSA susceptibility, suggested that patients infected with MRSA of higher daptomycin MIC showed a trend of lower clinical success with a P value of 0.052 by Cochran-Armitage test. Daptomycin was clinically and microbiologically effective for the treatment of MRSA-associated SSTIs in Japanese patients.
    Journal of Infection and Chemotherapy 10/2012; 19(3). DOI:10.1007/s10156-012-0501-9 · 1.49 Impact Factor
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    • "Additional reports have documented that enterococci are frequently also resistant to antibiotics other than vancomycin. In the 2005 SENTRY antimicrobial surveillance programme, which evaluated 953 enterococci isolates from medical centres in 10 European countries, Turkey and Israel, 49.5% and 29.2% of the isolates were resistant to ciprofloxacin and ampicillin, respectively.44 This could possibly be a consequence of CC17 E. faecium expansion.28 "
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    ABSTRACT: Nosocomial infections caused by enterococci present a challenge for clinicians because treatment options are often limited due to the widespread occurrence of strains resistant to multiple antibiotics, including vancomycin. Daptomycin is a first-in-class cyclic lipopeptide that has proven efficacy for the treatment of Gram-positive infections. Although methicillin-resistant Staphylococcus aureus has been the most prominent target in the clinical development of daptomycin, this agent has demonstrated potent bactericidal activity in enterococcal infection models and has been used for the treatment of enterococcal infections in humans. In recent years, large-scale susceptibility studies have shown that daptomycin is active against >98% of enterococci tested, irrespective of their susceptibility to other antibacterial agents. This lack of cross-resistance reflects the fact that daptomycin has a mode of action distinct from those of other antibiotics, including glycopeptides. While there are limited data available from randomized controlled trials, extensive clinical experience with daptomycin in enterococcal infections (including bacteraemia, endocarditis, skin and soft tissue infections, bone and joint infections and urinary tract infections) has been reported. This growing body of evidence provides useful insights regarding the efficacy of daptomycin against enterococci in clinical settings.
    Journal of Antimicrobial Chemotherapy 04/2010; 65(6):1126-36. DOI:10.1093/jac/dkq087 · 5.31 Impact Factor
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