JAC Advance Access originally published online on February 10, 2005
Journal of Antimicrobial Chemotherapy 2005 55(3):283-288; doi:10.1093/jac/dkh546
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
JAC vol.55 no.3 © The British Society for Antimicrobial Chemotherapy 2005; all rights reserved
Leading article |
Daptomycin: a lipopeptide antibiotic for the treatment of serious Gram-positive infections
Cubist Pharmaceuticals, Inc., 65 Hayden Avenue, Lexington, MA 02421, USA
* Corresponding author. Tel: +1-781-860-8434; Fax: +1-781-861-1164; Email: judith.steenbergen{at}cubist.com
 |
Abstract |
|---|
 Top Abstract IntroductionMechanism of actionMicrobiologyResistancePharmacologyPre-clinical studiesClinical studiesConclusionsReferences |
|---|
Infections caused by drug-resistant pathogens are on the rise. Daptomycin, a cyclic lipopeptide with activity against most Gram-positive pathogens, including vancomycin-resistant enterococci and methicillin-resistant Staphylococcus aureus, is a newly US-FDA approved antimicrobial for complicated skin and skin structure infections (cSSSI). Daptomycin has a unique mechanism of action that results in destruction of the membrane potential. The rapid bactericidal activity of daptomycin makes it an attractive antibiotic for serious Gram-positive infections.
Keywords: MRSA , cSSSI , vancomycin
|
Introduction |
|---|
|
TopAbstractIntroductionMechanism of actionMicrobiologyResistancePharmacologyPre-clinical studiesClinical studiesConclusionsReferences |
|---|
The increase in infections caused by Gram-positive pathogens and the rise in antibiotic-resistant bacterial strains have prompted the need for novel antibiotics.1,2 Recent reports indicate that more than 25% of Staphylococcus aureus infections in Europe are caused by methicillin-resistant S. aureus (MRSA), and the majority of these isolates are resistant to additional antibiotics.3 The incidence of MRSA varies greatly by country. Over 50% of S. aureus isolates in Portugal and Italy are methicillin-resistant, isolates in England, Greece, and France have MRSA rates around 25%, whereas the Netherlands and Switzerland have the lowest incidence of MRSA.3 Vancomycin has been an effective antibiotic against MRSA; however, the increased use of vancomycin has led to the development of isolates with reduced susceptibility. The mechanism of reduced susceptibility to vancomycin in S. aureus has not been fully elucidated and appears to be heterogeneous. Reduced susceptibility to vancomycin is correlated with alterations in the bacterial cell wall leading to significantly thicker and more disorganized cell walls.4 These thicker cell walls may sequester the vancomycin from reaching the target nascent cell wall precursors.4 Additional in vitro studies have linked development of vancomycin reduced susceptibility with phenotypic changes such as loss of haemolysis and the mecA gene, and genotypic changes such as the presence of either the group I or group II polymorphism in the agr gene locus.5–7
To date, three vancomycin-resistant S. aureus strains (VRSA) have been isolated in the United States.8–11 Both the Pennsylvania and the New York strains were isolated from patients not on vancomycin therapy.9,12 Therefore, the need for new potent antimicrobial agents with MRSA activity is essential.
|
Mechanism of action |
|---|
|
TopAbstractIntroductionMechanism of actionMicrobiologyResistancePharmacologyPre-clinical studiesClinical studiesConclusionsReferences |
|---|
Daptomycin, a fermentation product produced by Streptomyces roseosporus, is a cyclic lipopeptide antibiotic with potent bactericidal activity against most Gram-positive organisms including multiple antibiotic-resistant and -susceptible strains.13–21 Daptomycin was recently approved in the United States for the treatment of complicated skin and skin structure infections (cSSSI) associated with S. aureus (methicillin-susceptible, MSSA, and methicillin-resistant, MRSA), Streptococcus pyogenes, Streptococcus agalactiae, Streptococcus dysgalactiae subsp. equisimilis and Enterococcus faecalis (vancomycin-susceptible only). Below, we discuss the in vitro potency of daptomycin against a range of other organisms including vancomycin-resistant E. faecalis and Enterococcus faecium.
The unique structure of daptomycin consists of a 13-member amino acid cyclic lipopeptide with a decanoyl side-chain (Figure 1). This distinctive structure confers a novel mechanism of action.22 The proposed mechanism involves insertion of the lipophilic daptomycin tail into the bacterial cell membrane, causing rapid membrane depolarization and a potassium ion efflux. This is followed by arrest of DNA, RNA and protein synthesis resulting in bacterial cell death (Figure 2).22–24 The bactericidal effect of daptomycin is rapid with greater than 99.9% of both MRSA and MSSA bacteria dead in less than 1 h.25,26 This rapid cell death does not result in rapid bacterial cell lysis.24 Daptomycin also remains bactericidal (99.9% kill within 24 h) against stationary phase cultures of both MSSA and MRSA present at high density (109 cfu) in a simulated endocardial vegetation model.27
|
|
|
Microbiology |
|---|
|
TopAbstractIntroductionMechanism of actionMicrobiologyResistancePharmacologyPre-clinical studiesClinical studiesConclusionsReferences |
|---|
In vitro potency has been demonstrated for daptomycin against a range of aerobic and anaerobic Gram-positive bacteria including multidrug-resistant strains.13–21,28 MIC90 values along with MIC ranges for select pathogens can be found in Table 1. The table shows data from two recent studies illustrating the conserved MIC ranges and values for both European strains and isolates collected worldwide. Daptomycin's spectrum of activity encompasses the difficult to treat antibiotic-resistant organisms including methicillin-resistant and -susceptible Staphylococcus aureus (MRSA, MSSA), glycopeptide-intermediate S. aureus (GISA), methicillin-resistant coagulase-negative Staphylococcus spp. (CoNS), and vancomycin-resistant enterococci (VRE).13–21 Daptomycin demonstrated potency against the recently isolated vancomycin-resistant S. aureus as well as linezolid and quinupristin/dalfopristin-resistant S. aureus and E. faecium.14,17–20,24 Furthermore, daptomycin is also effective against a variety of streptococcal groups such as the ß-haemolytic streptococci including S. pyogenes (Group A) and S. agalactiae (Group B) as well as other Streptococcus spp.13–15,20,21 Along with the commonly isolated Gram-positive organisms, daptomycin is also potent against Corynebacterium jeikeium, and a variety of anaerobic species including Peptostreptococcus spp., Clostridium perfringens, Clostridium difficile, and Propionibacterium acnes (Table 1).28 Drug synergy with daptomycin has been described in vitro with aminoglycosides and rifampicin antibiotics.29
|
|
Resistance |
|---|
|
TopAbstractIntroductionMechanism of actionMicrobiologyResistancePharmacologyPre-clinical studiesClinical studiesConclusionsReferences |
|---|
Daptomycin's efficacy is enhanced by the near absence of antibiotic resistance as verified by both in vitro and clinical studies.30 Resistance to daptomycin has been difficult to generate in the laboratory both in single passage and serial passage experi ments.30 The emergence of resistance was <0.2% across the entire set of Phase II and III clinical trials with over 1000 daptomycin-treated patients. The reason for this decrease in susceptibility is unknown and no transferable elements conferring daptomycin resistance have been isolated.
|
Pharmacology |
|---|
|
TopAbstractIntroductionMechanism of actionMicrobiologyResistancePharmacologyPre-clinical studiesClinical studiesConclusionsReferences |
|---|
Analysis of daptomycin pharmacodynamics determined that a once-daily dosing regimen increases the efficacy and safety of daptomycin.31 In vitro and in vivo analysis established that daptomycin is effective in a concentration-dependent manner, has a long half-life (8 h), and demonstrates a prolonged post-antibiotic effect up to 6.8 h (Table 2).32 These findings resulted in a once a day dosing regimen recommendation of 4 mg/kg for complicated skin and skin structure infections (cSSSI) in the United States.
|
Once-daily dosing of daptomycin results in linear pharmacokinetics with minimal drug accumulation.31 Daptomycin distributes primarily in the plasma, with penetration to vascular tissues (Table 3). Daptomycin does not cross the blood–brain barrier and does not penetrate the cerebrospinal fluid of normal individuals. However, there was a 5% penetration (relative to serum) of daptomycin into the cerebrospinal fluid of rabbits with Streptococcus pneumoniae meningitis, resulting in clearance of the infection in this model.33 Daptomycin is primarily renally excreted, with the majority of the drug remaining intact in the urine.31 Since daptomycin is excreted through the kidneys, the dosing interval is increased to every 48 h in patients with severe renal impairment defined as a creatinine clearance of <30 mL/min. Because of daptomycin's unique mechanism of action and because it is not metabolized by cytochrome p450 or other hepatic enzymes, no antagonistic drug interactions have been observed.
|
|
Pre-clinical studies |
|---|
|
TopAbstractIntroductionMechanism of actionMicrobiologyResistancePharmacologyPre-clinical studiesClinical studiesConclusionsReferences |
|---|
In pre-clinical studies, daptomycin treatment has been linked to fully reversible skeletal muscle toxicity with no effect on smooth or cardiac muscle. Animal studies determined that both degenerative and regenerative changes are observed in skeletal muscle with no rhabdomyolysis.31 These effects, which can be associated with elevated creatine phosphokinase (CPK) levels, are fully reversible after cessation of daptomycin use and were not statistically significant when compared with comparator.31 The numbers of side effects for patients receiving daptomycin were comparable to standard therapy and less than 2% of patients receiving daptomycin discontinued therapy.34 The most common adverse events from the Phase III cSSSI clinical trials for daptomycin and comparator drugs are listed in Table 4.
|
2% of patients in either daptomycin or comparator treatment groups in Phase III cSSSI studiesThe efficacy of daptomycin against a range of infections has been demonstrated in animal studies. Using a variety of antibiotic-resistant and -sensitive Gram-positive bacteria, daptomycin eradicated infections in the blood, muscle, kidney, heart and bone tissues of animals.35–41 These results show promise for daptomycin therapy for further clinical indications. An ongoing Phase III clinical trial is in progress to determine the efficacy of 6 mg/kg daptomycin once a day for endocarditis and bacteraemia caused by S. aureus.
|
Clinical studies |
|---|
|
TopAbstractIntroductionMechanism of actionMicrobiologyResistancePharmacologyPre-clinical studiesClinical studiesConclusionsReferences |
|---|
Daptomycin was evaluated in two large investigator-blinded, randomized, multicentre cSSSI studies in Europe, South Africa and the United States.34 Adults with cSSSI of known or suspected Gram-positive aetiology were enrolled. The predominant cSSSI infections studied included wound infections, major abscesses and ulcer infections. Daptomycin was compared with conventional therapy of a semi-synthetic penicillin (e.g. nafcillin, oxacillin, cloxacillin, or flucloxacillin) or vancomycin (for suspected MRSA). The clinical success rates for each treatment group (intent to treat, modified intent to treat, clinically evaluable, and microbiologically evaluable) are shown in Table 5.34 The study was designed to determine whether daptomycin was comparable to standard therapy and was not powered to show superiority. Therefore, statistical analysis determined that in the clinical trails, daptomycin was non-inferior to comparator therapy leading to daptomycin approval by the FDA in the United States.34 Results of the microbiologically evaluable population are detailed by pathogen in Table 6.34 Over 1000 patients were evaluated, and the following pathogens were the predominant organisms isolated; MSSA, MRSA, S. pyogenes, S. agalactiae, S. dysgalactiae subsp. equisimilis, and E. faecalis. The results from these Phase III trials confirmed the efficacy and safety of daptomycin.
|
|
|
Conclusions |
|---|
|
TopAbstractIntroductionMechanism of actionMicrobiologyResistancePharmacologyPre-clinical studiesClinical studiesConclusionsReferences |
|---|
In summary, daptomycin is a rapidly bactericidal antibiotic that is active against clinically relevant Gram-positive bacteria including antibiotic-resistant strains. Clinical data demonstrate that daptomycin is highly effective against cSSSI and ongoing clinical trials including infectious endocarditis caused by S. aureus, should expand treatment indications. The low occurrence of side effects, low resistance rates, and high potency demonstrate that daptomycin has significant clinical utility in the treatment of Gram-positive infections, including those caused by MRSA.
|
References |
|---|
|
TopAbstractIntroductionMechanism of actionMicrobiologyResistancePharmacologyPre-clinical studiesClinical studiesConclusionsReferences |
|---|
1 . Bell, J. M. & Turnidge, J. D. (2002). High prevalence of oxacillin-resistant Staphylococcus aureus isolates from hospitalized patients in Asia-Pacific and South Africa: results from SENTRY antimicrobial surveillance program, 1998–1999. Antimicrobial Agents and Chemotherapy 46, 879–81.
2 . Stefani, S. & Varaldo, P. E. (2003). Epidemiology of methicillin-resistant staphylococci in Europe. Clinical Microbiology and Infection 9, 1179–86.[CrossRef][Web of Science][Medline]
3
.
Fluit, A. C., Wielders, C. L., Verhoef, J. et al. (2001). Epidemiology and susceptibility of 3,051 Staphylococcus aureus isolates from 25 university hospitals participating in the European SENTRY study. Journal of Clinical Microbiology 39, 3727–32.
4
.
Cui, L., Ma, X., Sato, K. et al. (2003). Cell wall thickening is a common feature of vancomycin resistance in Staphylococcus aureus. Journal of Clinical Microbiology 41, 5–14.
5
.
Verdier, I., Reverdy, M. E., Etienne, J. et al. (2004). Staphylococcus aureus isolates with reduced susceptibility to glycopeptides belong to accessory gene regulator group I or II. Antimicrobial Agents and Chemotherapy 48, 1024–7.
6 . Sakoulas, G., Eliopoulos, G. M., Moellering, R. C. et al. (2003). Staphylococcus aureus accessory gene regulator (agr) group II: is there a relationship to the development of intermediate-level glycopeptide resistance? Journal of Infectious Diseases 187, 929–38.[CrossRef][Web of Science][Medline]
7
.
Adhikari, R. P., Scales, G. C., Kobayashi, K. et al. (2004). Vancomycin-induced deletion of the methicillin resistance gene mecA in Staphylococcus aureus. Journal of Antimicrobial Chemotherapy 54, 360–3.
8 . Centers for Disease Control and Prevention. (2002). Staphylococcus aureus resistant to vancomycin—United States, 2002. In Morbidity and Mortality Weekly Report, pp. 565–7.
9 . Centers for Disease Control and Prevention. (2002). Public Health Dispatch: vancomycin-resistant Staphylococcus aureus—Pennsylvania, 2002. In Morbidity and Mortality Weekly Report 902.
10 . Centers for Disease Control and Prevention. (2004). Brief report: vancomycin-resistant Staphylococcus aureus—New York, 2004. In Morbidity and Mortality Weekly Report 322.
11 . Mutnick, A. H., Biedenbach, D. J. & Jones, R. N. (2003). Geographic variations and trends in antimicrobial resistance among Enterococcus faecalis and Enterococcus faecium in the SENTRY Antimicrobial Surveillance Program (1997–2000). Diagnostic Microbiology and Infectious Disease 46, 63–8.[CrossRef][Web of Science][Medline]
12 . Kacica, M. A., Scott, C., Johnson, G. et al. (2004). Vancomycin-resistant Staphylococcus aureus (VRSA) in a resident of a long-term care facility (LTCF). In Program and Abstracts of the 42nd Annual Meeting of the Infectious Diseases Society of America, Boston, MA, USA. Abstract 530, p. 143. Infectious Diseases Society of America, Alexandria, VA, USA.
13
.
Barry, A. L., Fuchs, P. C. & Brown, S. D. (2001). In vitro activities of daptomycin against 2,789 clinical isolates from 11 North American medical centers. Antimicrobial Agents and Chemotherapy 45, 1919–22.
14
.
Critchley, I. A., Draghi, D. C., Sahm, D. F. et al. (2003). Activity of daptomycin against susceptible and multidrug-resistant Gram-positive pathogens collected in the SECURE study (Europe) during 2000–2001. Journal of Antimicrobial Chemotherapy 51, 639–49.
15 . Fluit, A. C., Schmitz, F. J., Verhoef, J. et al. (2004). Daptomycin in vitro susceptibility in European Gram-positive clinical isolates. International Journal of Antimicrobial Agents 24, 59–66.[CrossRef][Web of Science][Medline]
16
.
Fluit, A. C., Schmitz, F. J., Verhoef, J. et al. (2004). In vitro activity of daptomycin against Gram-positive European clinical isolates with defined resistance determinants. Antimicrobial Agents and Chemotherapy 48, 1007–11.
17
.
Petersen, P. J., Bradford, P. A., Weiss, W. J. et al. (2002). In vitro and in vivo activities of tigecycline (GAR-936), daptomycin, and comparative antimicrobial agents against glycopeptide-intermediate Staphylococcus aureus and other resistant gram-positive pathogens. Antimicrobial Agents and Chemotherapy 46, 2595–601.
18
.
Richter, S. S., Kealey, D. E., Murray, C. T. et al. (2003). The in vitro activity of daptomycin against Staphylococcus aureus and Enterococcus species. Journal of Antimicrobial Chemotherapy 52, 123–7.
19
.
Rybak, M. J., Hershberger, E., Moldovan, T. et al. (2000). In vitro activities of daptomycin, vancomycin, linezolid, and quinupristin–dalfopristin against staphylococci and enterococci, including vancomycin-intermediate and -resistant strains. Antimicrobial Agents and Chemotherapy 44, 1062–6.
20
.
Snydman, D. R., Jacobus, N. V., McDermott, L. A. et al. (2000). Comparative in vitro activities of daptomycin and vancomycin against resistant Gram-positive pathogens. Antimicrobial Agents and Chemotherapy 44, 3447–50.
21
.
Streit, J. M., Jones, R. N. & Sader, H. S. (2004). Daptomycin activity and spectrum: a worldwide sample of 6737 clinical Gram-positive organisms. Journal of Antimicrobial Chemotherapy 53, 669–74.
22
.
Silverman, J. A., Perlmutter, N. G. & Shapiro, H. M. (2003). Correlation of daptomycin bactericidal activity and membrane depolarization in Staphylococcus aureus. Antimicrobial Agents and Chemotherapy 47, 2538–44.
23
.
Canepari, P., Boaretti, M., del Mar Lleo, M. et al. (1990). Lipoteichoic acid as a new target for activity of antibiotics: mode of action of daptomycin (LY146032). Antimicrobial Agents and Chemotherapy 34, 1220–6.
24 . Silverman, J., Harris, B., Cotroneo, N., et al. (2003). Daptomycin (DAP) treatment induces membrane and cell wall alterations in Staphylococcus aureus. In Interscience Conference on Antimicrobial Agents and Chemotherapy, Chicago, IL. Abstract C1–2135, p. 103. American Society for Microbiology, Washington, DC, USA.
25
.
Cha, R. & Rybak, M. J. (2004). Influence of protein binding under controlled conditions on the bactericidal activity of daptomycin in an in vitro pharmacodynamic model. Journal of Antimicrobial Chemotherapy 54, 259–62.
26
.
Fuchs, P. C., Barry, A. L. & Brown, S. D. (2002). In vitro bactericidal activity of daptomycin against staphylococci. Journal of Antimicrobial Chemotherapy 49, 467–70.
27 . Tedesco, K. L. & Rybak, M. J. (2003). Impact of high inoculum Staphylococcus aureus on the activities of nafcillin (NAF), vancomycin (VAN), linezolid (LZD), gentamicin (GEN), and daptomycin (DAP) in an in vitro pharmacodynamic model (IVD). In Interscience Conference on Antimicrobial Agents and Chemotherapy, Chicago, IL. Abstract A-1151, p. 14. American Society for Microbiology, Washington, DC, USA.
28
.
Goldstein, E. J., Citron, D. M., Merriam, C. V. et al. (2003). In vitro activities of daptomycin, vancomycin, quinupristin–dalfopristin, linezolid, and five other antimicrobials against 307 gram-positive anaerobic and 31 Corynebacterium clinical isolates. Antimicrobial Agents and Chemotherapy 47, 337–41.
29
.
Rand, K. H. & Houck, H. (2004). Daptomycin synergy with rifampicin and ampicillin against vancomycin-resistant enterococci. Journal of Antimicrobial Chemotherapy 53, 530–2.
30
.
Silverman, J. A., Oliver, N., Andrew, T. et al. (2001). Resistance studies with daptomycin. Antimicrobial Agents and Chemotherapy 45, 1799–802.
31
.
Oleson, F. B., Jr, Berman, C. L., Kirkpatrick, J. B. et al. (2000). Once-daily dosing in dogs optimizes daptomycin safety. Antimicrobial Agents and Chemotherapy 44, 2948–53.
32
.
Safdar, N., Andes, D. & Craig, W. A. (2004). In vivo pharmacodynamic activity of daptomycin. Antimicrobial Agents and Chemotherapy 48, 63–8.
33
.
Cottagnoud, P., Pfister, M., Acosta, F. et al. (2004). Daptomycin is highly efficacious against penicillin-resistant and penicillin- and quinolone-resistant pneumococci in experimental meningitis. Antimicrobial Agents and Chemotherapy 48, 3928–33.
34 . Arbeit, R. D., Maki, D., Tally, F. P. et al. (2004). The safety and efficacy of daptomycin for the treatment of complicated skin and skin-structure infections. Clinical Infectious Diseases 38, 1673–81.[CrossRef][Web of Science][Medline]
35
.
Alder, J., Li, T., Yu, D. et al. (2003). Analysis of daptomycin efficacy and breakpoint standards in a murine model of Enterococcus faecalis and Enterococcus faecium renal infection. Antimicrobial Agents and Chemotherapy 47, 3561–6.
36
.
Cha, R., Grucz, R. G., Jr & Rybak, M. J. (2003). Daptomycin dose–effect relationship against resistant gram-positive organisms. Antimicrobial Agents and Chemotherapy 47, 1598–603.
37
.
Dandekar, P. K., Tessier, P. R., Williams, P. et al. (2003). Pharmacodynamic profile of daptomycin against Enterococcus species and methicillin-resistant Staphylococcus aureus in a murine thigh infection model. Journal of Antimicrobial Chemotherapy 52, 405–11.
38
.
Kaatz, G. W., Seo, S. M., Reddy, V. N. et al. (1990). Daptomycin compared with teicoplanin and vancomycin for therapy of experimental Staphylococcus aureus endocarditis. Antimicrobial Agents and Chemotherapy 34, 2081–5.
39
.
Louie, A., Kaw, P., Liu, W. et al. (2001). Pharmacodynamics of daptomycin in a murine thigh model of Staphylococcus aureus infection. Antimicrobial Agents and Chemotherapy 45, 845–51.
40
.
Mader, J. T. & Adams, K. (1989). Comparative evaluation of daptomycin (LY146032) and vancomycin in the treatment of experimental methicillin-resistant Staphylococcus aureus osteomyelitis in rabbits. Antimicrobial Agents and Chemotherapy 33, 689–92.
41 . Smith, K., Cobbs, G., Dill, R. et al. (1990). Daptomycin versus vancomycin treatment for Staphylococcus aureus bacteremia in a murine model. Chemotherapy 36, 428–34.[Web of Science][Medline]
42
.
Wise, R., Gee, T., Andrews, J. M. et al. (2002). Pharmacokinetics and inflammatory fluid penetration of intravenous daptomycin in volunteers. Antimicrobial Agents and Chemotherapy 46, 31–3.
43 . Michiels, M. J. & Bergeron, M. G. (1996). Differential increased survival of staphylococci and limited ultrastructural changes in the core of infected fibrin clots after daptomycin administration. Antimicrobial Agents and Chemotherapy 40, 203–11.[Abstract]
44
.
Vaudaux, P., Francois, P., Bisognano, C. et al. (2003). Comparative efficacy of daptomycin and vancomycin in the therapy of experimental foreign body infection due to Staphylococcus aureus. Journal of Antimicrobial Chemotherapy 52, 89–95.
45 . Alder, J., Arbeit, R., Eisenstein, B., et al. (2004). Pulmonary epithelial lining fluid (ELF) as a privileged site: daptomycin in pulmonary infections. In International Congress of Infectious Diseases, Cancun, Mexico. 11th ICID Abstracts, Abstract 60.005, p. S195. International Society for Infectious Diseases, Brighton, UK.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  A.-K. John, D. Baldoni, M. Haschke, K. Rentsch, P. Schaerli, W. Zimmerli, and A. Trampuz Efficacy of Daptomycin in Implant-Associated Infection Due to Methicillin-Resistant Staphylococcus aureus: Importance of Combination with Rifampin Antimicrob. Agents Chemother., July 1, 2009; 53(7): 2719 - 2724. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Schoen, C. Unzicker, G. Stuhler, J. Elias, H. Einsele, G. U. Grigoleit, M. Abele-Horn, and S. Mielke Life-Threatening Infection Caused by Daptomycin-Resistant Corynebacterium jeikeium in a Neutropenic Patient J. Clin. Microbiol., July 1, 2009; 47(7): 2328 - 2331. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. M. Hawkey Pre-clinical experience with daptomycin J. Antimicrob. Chemother., November 1, 2008; 62(suppl_3): iii7 - iii14. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. M. Amsler, T. A. Davies, W. Shang, M. R. Jacobs, and K. Bush In Vitro Activity of Ceftobiprole against Pathogens from Two Phase 3 Clinical Trials of Complicated Skin and Skin Structure Infections Antimicrob. Agents Chemother., September 1, 2008; 52(9): 3418 - 3423. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. I. Hidron, A. N. Schuetz, F. S. Nolte, C. V. Gould, and M. K. Osborn Daptomycin resistance in Enterococcus faecalis prosthetic valve endocarditis J. Antimicrob. Chemother., June 1, 2008; 61(6): 1394 - 1396. [Full Text] [PDF]
|
|
|
|
|
|
L. Spanjaard and C. M. J. E. Vandenbroucke-Grauls Activity of Daptomycin against Listeria monocytogenes Isolates from Cerebrospinal Fluid Antimicrob. Agents Chemother., May 1, 2008; 52(5): 1850 - 1851. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. L. Baltch, W. J. Ritz, L. H. Bopp, P. Michelsen, and R. P. Smith Activities of Daptomycin and Comparative Antimicrobials, Singly and in Combination, against Extracellular and Intracellular Staphylococcus aureus and Its Stable Small-Colony Variant in Human Monocyte-Derived Macrophages and in Broth Antimicrob. Agents Chemother., May 1, 2008; 52(5): 1829 - 1833. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Shea, E. Hilburger, A. Baroco, and E. Oldfield Successful Treatment of Vancomycin-Resistant Enterococcus faecium Pyelonephritis with Daptomycin During Pregnancy Ann. Pharmacother., May 1, 2008; 42(5): 722 - 725. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y.-T. Huang, C.-H. Hsiao, C.-H. Liao, C.-W. Lee, and P.-R. Hsueh Bacteremia and Infective Endocarditis Caused by a Non-Daptomycin-Susceptible, Vancomycin-Intermediate, and Methicillin-Resistant Staphylococcus aureus Strain in Taiwan J. Clin. Microbiol., March 1, 2008; 46(3): 1132 - 1136. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. P. Zavascki, L. Z. Goldani, J. Li, and R. L. Nation Polymyxin B for the treatment of multidrug-resistant pathogens: a critical review J. Antimicrob. Chemother., December 1, 2007; 60(6): 1206 - 1215. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. A Mergenhagen and M. T Pasko Daptomycin Use After Vancomycin-Induced Neutropenia in a Patient with Left-Sided Endocarditis Ann. Pharmacother., September 1, 2007; 41(9): 1531 - 1535. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. H. Rand, H. J. Houck, and J. A. Silverman Daptomycin-reversible rifampicin resistance in vancomycin-resistant Enterococcus faecium J. Antimicrob. Chemother., May 1, 2007; 59(5): 1017 - 1020. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Credito, G. Lin, and P. C. Appelbaum Activity of Daptomycin Alone and in Combination with Rifampin and Gentamicin against Staphylococcus aureus Assessed by Time-Kill Methodology Antimicrob. Agents Chemother., April 1, 2007; 51(4): 1504 - 1507. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. L. Baltch, W. J. Ritz, L. H. Bopp, P. B. Michelsen, and R. P. Smith Antimicrobial Activities of Daptomycin, Vancomycin, and Oxacillin in Human Monocytes and of Daptomycin in Combination with Gentamicin and/or Rifampin in Human Monocytes and in Broth against Staphylococcus aureus Antimicrob. Agents Chemother., April 1, 2007; 51(4): 1559 - 1562. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Vouillamoz, P. Moreillon, M. Giddey, and J. M. Entenza Efficacy of daptomycin in the treatment of experimental endocarditis due to susceptible and multidrug-resistant enterococci J. Antimicrob. Chemother., December 1, 2006; 58(6): 1208 - 1214. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. L. French Bactericidal agents in the treatment of MRSA infections--the potential role of daptomycin J. Antimicrob. Chemother., December 1, 2006; 58(6): 1107 - 1117. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. A. DeRyke, C. Sutherland, B. Zhang, D. P. Nicolau, and J. L. Kuti Serum Bactericidal Activities of High-Dose Daptomycin with and without Coadministration of Gentamicin against Isolates of Staphylococcus aureus and Enterococcus species Antimicrob. Agents Chemother., November 1, 2006; 50(11): 3529 - 3534. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Makovitzki, D. Avrahami, and Y. Shai Ultrashort antibacterial and antifungal lipopeptides PNAS, October 24, 2006; 103(43): 15997 - 16002. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. M. Citron and M. D. Appleman In Vitro Activities of Daptomycin, Ciprofloxacin, and Other Antimicrobial Agents against the Cells and Spores of Clinical Isolates of Bacillus Species. J. Clin. Microbiol., October 1, 2006; 44(10): 3814 - 3818. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. A. Jevitt, G. M. Thorne, M. M. Traczewski, R. N. Jones, J. E. McGowan Jr., F. C. Tenover, and S. D. Brown Multicenter Evaluation of the Etest and Disk Diffusion Methods for Differentiating Daptomycin-Susceptible from Non-Daptomycin-Susceptible Staphylococcus aureus Isolates. J. Clin. Microbiol., September 1, 2006; 44(9): 3098 - 3104. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. Denis, A. Deplano, C. Nonhoff, M. Hallin, R. De Ryck, R. Vanhoof, R. De Mendonca, and M. J. Struelens In Vitro Activities of Ceftobiprole, Tigecycline, Daptomycin, and 19 Other Antimicrobials against Methicillin-Resistant Staphylococcus aureus Strains from a National Survey of Belgian Hospitals. Antimicrob. Agents Chemother., August 1, 2006; 50(8): 2680 - 2685. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. K. English, E. M. Maryniw, A. J. Talati, and E. A. Meals Diminished Macrophage Inflammatory Response to Staphylococcus aureus Isolates Exposed to Daptomycin versus Vancomycin or Oxacillin. Antimicrob. Agents Chemother., June 1, 2006; 50(6): 2225 - 2227. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. M. Marty, W. W. Yeh, C. B. Wennersten, L. Venkataraman, E. Albano, E. P. Alyea, H. S. Gold, L. R. Baden, and S. K. Pillai Emergence of a Clinical Daptomycin-Resistant Staphylococcus aureus Isolate during Treatment of Methicillin-Resistant Staphylococcus aureus Bacteremia and Osteomyelitis J. Clin. Microbiol., February 1, 2006; 44(2): 595 - 597. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. J. Skiest Treatment Failure Resulting from Resistance of Staphylococcus aureus to Daptomycin J. Clin. Microbiol., February 1, 2006; 44(2): 655 - 656. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||