FREE NEJM E-TOC    HOME   |   SUBSCRIBE   |   CURRENT ISSUE   |   PAST ISSUES   |   COLLECTIONS   |   Search Term  Advanced Search

Sign in | Get NEJM's E-Mail Table of Contents — Free | Subscribe

Previous Volume 355:653-665 August 17, 2006 Number 7 Next

Abstract PDF PDA Full Text PowerPoint Slide Set Supplementary Material Editorial by Grayson, M. L. Letters Add to Personal Archive Add to Citation Manager Notify a Friend E-mail When Cited E-mail When Letters Appear PubMed Citation

ABSTRACT

Background Alternative therapies for Staphylococcus aureus bacteremia and endocarditis are needed.

Methods We randomly assigned 124 patients with S. aureus bacteremia with or without endocarditis to receive 6 mg of daptomycin intravenously per kilogram of body weight daily and 122 to receive initial low-dose gentamicin plus either an antistaphylococcal penicillin or vancomycin. The primary efficacy end point was treatment success 42 days after the end of therapy.

Results Forty-two days after the end of therapy in the modified intention-to-treat analysis, a successful outcome was documented for 53 of 120 patients who received daptomycin as compared with 48 of 115 patients who received standard therapy (44.2 percent vs. 41.7 percent; absolute difference, 2.4 percent; 95 percent confidence interval, –10.2 to 15.1 percent). Our results met prespecified criteria for the noninferiority of daptomycin. The success rates were similar in subgroups of patients with complicated bacteremia, right-sided endocarditis, and methicillin-resistant S. aureus. Daptomycin therapy was associated with a higher rate of microbiologic failure than was standard therapy (19 vs. 11 patients, P=0.17). In 6 of the 19 patients with microbiologic failure in the daptomycin group, isolates with reduced susceptibility to daptomycin emerged; similarly, a reduced susceptibility to vancomycin was noted in isolates from patients treated with vancomycin. As compared with daptomycin therapy, standard therapy was associated with a nonsignificantly higher rate of adverse events that led to treatment failure due to the discontinuation of therapy (17 vs. 8, P=0.06). Clinically significant renal dysfunction occurred in 11.0 percent of patients who received daptomycin and in 26.3 percent of patients who received standard therapy (P=0.004).

Conclusions Daptomycin (6 mg per kilogram daily) is not inferior to standard therapy for S. aureus bacteremia and right-sided endocarditis. (ClinicalTrials.gov number, NCT00093067 [ClinicalTrials.gov] .)

Daptomycin is a cyclic lipopeptide antibiotic that is rapidly bactericidal in vitro against most clinically relevant gram-positive bacteria, including S. aureus.^11,12,13,14 Daptomycin is approved for the treatment of complicated skin and skin-structure infections attributable to gram-positive organisms at a dose of 4 mg per kilogram of body weight intravenously per day,¹⁵ but its efficacy in the treatment of S. aureus bacteremia and endocarditis and its safety at higher doses have not been established. We assessed the efficacy and safety of daptomycin as compared with standard therapy for S. aureus bacteremia and endocarditis.

Methods

Study Design

This open-label, randomized trial was conducted between August 28, 2002, and February 16, 2005. The institutional review board at each site approved the protocol, and all patients or their authorized representatives provided written informed consent. Eligible patients were 18 years of age or older and had one or more blood cultures that were positive for S. aureus within two calendar days before initiating study medication. Patients were ineligible if they had a creatinine clearance of less than 30 ml per minute, known osteomyelitis, polymicrobial bacteremia, or pneumonia. Full exclusion criteria are listed in the Supplementary Appendix, available with the full text of this article at www.nejm.org.

The adjudication committee of five infectious-disease experts (Drs. Abrutyn, Corey, Cosgrove, Fowler, and Karchmer) reviewed the data from each patient to establish the diagnosis and outcome. The committee was unaware of patients' treatment assignments.

Definitions

The diagnosis at baseline was determined with the use of the modified Duke criteria.¹⁶ The adjudication committee determined final diagnoses (Table 1). Uncomplicated bacteremia was defined by the isolation of S. aureus from enrollment blood cultures in patients without endocarditis and without evidence of hematogenous spread. Patients with such infections received medication for a minimum of 10 to 14 days. In patients without definite endocarditis, complicated bacteremia was defined by the isolation of S. aureus from blood cultures on at least two days through study day 5, the presence of spread of infection, or infection involving prostheses not removed within four days. Such patients received medication for a minimum of 28 to 42 days. Uncomplicated right-sided endocarditis was defined as definite or possible¹⁶ methicillin-susceptible S. aureus (MSSA) endocarditis in the absence of predisposing abnormalities or active infection of the mitral or aortic valve in a patient with active injection-drug use, a serum creatinine level of less than 2.5 mg per deciliter (221 µmol per liter), and no evidence of extrapulmonary sites of infection. Patients with uncomplicated MSSA right-sided endocarditis received medication for a minimum of 14 to 28 days. Complicated right-sided endocarditis was defined as definite or possible¹⁶ endocarditis in the absence of predisposing abnormalities or active infection of the mitral or aortic valve, with extrapulmonary sites of infection, a serum creatinine level of at least 2.5 mg per deciliter, MRSA bacteremia, or the absence of injection-drug use. Patients with such infections were treated for a minimum of 28 to 42 days. Left-sided endocarditis was defined according to the criteria of Li et al.¹⁶ Patients with such infections received medication for a minimum of 28 to 42 days.

View this table: [in this window] [in a new window]   Table 1. Characteristics of Patients in the Modified Intention-to-Treat Population.

 
The intention-to-treat population included all randomized patients. All patients in the intention-to-treat group who received at least one dose of the study medication were included in the safety analyses. The modified intention-to-treat population included all randomized patients who received at least one dose of study medication except those with a high likelihood of left-sided endocarditis who were enrolled before a protocol amendment allowing their inclusion. The per-protocol population included all patients in the modified intention-to-treat group with documented adherence to the protocol (Figure 1 of the Supplementary Appendix). Unless otherwise specified, all results presented are based on the modified intention-to-treat population, the primary efficacy population.

Patients were considered to have clinical failure if they had no response to the study drug on the basis of ongoing signs and symptoms of infection. Patients were considered to have microbiologic failure if they had persistent or relapsing S. aureus infection, defined as either ongoing positive cultures leading to discontinuation of the study drug or subsequent isolation of S. aureus of the same strain type after apparent clinical improvement.

Randomization, Treatment, and Monitoring

Patients were randomly assigned with the use of a block randomization schedule to receive either daptomycin or standard therapy; this centralized computer-generated schedule was designed to achieve a 1:1 ratio of patients, stratified according to investigative site.

Patients received daptomycin (Cubicin, Cubist Pharmaceuticals) (6 mg per kilogram of body weight intravenously once daily) or standard therapy with either vancomycin (1 g every 12 hours with appropriate dose adjustment) or an antistaphylococcal penicillin (nafcillin, oxacillin, or flucloxacillin) (2 g every 4 hours), depending on the susceptibility of the causative strain to methicillin. The duration of therapy was determined by the investigator on the basis of the working diagnosis. All patients who were randomly assigned to standard treatment and patients with left-sided endocarditis who were assigned to daptomycin were to receive gentamicin (1 mg per kilogram intravenously every eight hours or adjusted on the basis of renal function) for the first four days.

The investigators evaluated patients at baseline, at the end of therapy, and 42 days after the end of therapy (at the test-of-cure visit). Blood cultures were obtained daily until they were negative, as well as at the end of therapy and 42 days after the end of therapy (Figure 1 of the Supplementary Appendix). Patients were required to undergo transesophageal echocardiography within five days after starting the study medication. All echocardiograms were reviewed by an independent expert unaware of the patient's treatment assignment; these results were used in all analyses.

An independent data and safety monitoring committee was established to regularly review the data and make recommendations regarding continuation of the study.

Clinical Outcomes

The primary outcome was the clinical success rate in each of the two treatment groups in the modified intention-to-treat population at the visit 42 days after the end of therapy. Failure at this visit was defined as clinical failure, microbiologic failure, death, failure to obtain blood culture, receipt of potentially effective nonstudy antibiotics, or premature discontinuation of the study medication because of clinical failure, microbiologic failure, or an adverse event.

Microbiologic Methods

The species of all isolates was identified, and each isolate was tested for antimicrobial susceptibility by a central laboratory with the use of accepted interpretative criteria.¹⁷ A minimal inhibitory concentration (MIC) of at least 2 µg of daptomycin per milliliter was considered to indicate a nonsusceptible isolate of S. aureus. S. aureus isolates from patients with persistent or recurrent infection were evaluated with repeated susceptibility testing and pulsed-field gel electrophoresis.

Statistical Analysis

            Efficacy Assessments

In this noninferiority trial, the 95 percent confidence interval for the difference in success rates (daptomycin minus standard therapy) was calculated on the basis of the normal approximation to the binomial distribution. The noninferiority test was based on the lower bound of the confidence intervals being within the prespecified noninferiority margin of 20 percent and the upper bounds containing 0 percent. Assuming 65 percent efficacy in both treatment groups, a statistical power of 80 percent, and a one-sided significance level of 0.025, we estimated that 90 patients would need to be enrolled in each treatment group in the modified intention-to-treat population in order to test the null hypothesis (that the treatments differed by at least 20 percent). All reported P values were two-sided and not adjusted for multiple analyses.

            Safety Assessments

The incidence of adverse events was compared between treatment groups with the use of Fisher's exact test. Changes in laboratory values, in particular, changes in serum creatine kinase and creatinine clearance, were evaluated. Creatinine clearance was calculated at baseline and at regular intervals thereafter according to the Cockcroft–Gault formula.¹⁸

The study was designed by the sponsor (Cubist Pharmaceuticals) with the assistance of Drs. Chambers, Fowler, and Karchmer. Data were held and analyzed by the sponsor. However, the authors had complete and unfettered access to the data and vouch for the veracity and completeness of the data and analyses used for this article.

Results

Patients

Of the 246 randomized patients, 10 (6 assigned to daptomycin and 4 assigned to standard therapy) did not receive the study drug (Figure 1 of the Supplementary Appendix); thus, 236 — 120 assigned to daptomycin and 116 assigned to standard therapy — were treated at 44 sites in four countries and represent the population used in the safety analyses. These 10 patients plus 1 patient who was treated with standard therapy and who enrolled before the amendment to allow patients with a high likelihood of left-sided endocarditis were excluded from the modified intention-to-treat population (120 assigned to daptomycin and 115 assigned to standard therapy). Risk factors for S. aureus infection were similar in the two groups (Table 1). Clinical evidence of the systemic inflammatory response syndrome was present in 89 of 120 patients treated with daptomycin (74.2 percent) and in 87 of 115 patients treated with standard therapy (75.7 percent). The median duration of therapy was 14 days for daptomycin and 15 days for standard therapy (including early discontinuations). Gentamicin was administered to 107 of 115 patients in the standard-therapy group (93.0 percent) and to 1 patient in the daptomycin group (0.8 percent) for a median of four days. At entry, 75.0 percent of the daptomycin group and 79.1 percent of the standard-therapy group met modified Duke criteria for definite or possible endocarditis. The final diagnoses were distributed similarly in the treatment groups (Table 1). MRSA was isolated from 45 of 120 patients who were treated with daptomycin (37.5 percent) and 44 of 115 patients who were treated with standard therapy (38.3 percent).

Outcome

A successful outcome was documented 42 days after the end of therapy for 53 of 120 patients in the daptomycin group, as compared with 48 of 115 patients in the standard-therapy group (44.2 percent vs. 41.7 percent; absolute difference, 2.4 percent; 95 percent confidence interval for the difference, –10.2 to 15.1 percent). The lower limit of the 95 percent confidence interval was within the prespecified margin of –20 percent; thus, daptomycin was not inferior to standard therapy. Differences in success rates were similar across all of the prespecified analyses (Table 2 and Figure 1). Success rates favored daptomycin over vancomycin among patients who were infected with MRSA (44.4 percent for daptomycin vs. 31.8 percent for standard therapy, P=0.28) but were higher among patients receiving standard therapy for MSSA infection (44.6 percent for daptomycin vs. 48.6 percent for standard therapy, P=0.74). At the end of therapy, the success rates were 61.7 percent in the daptomycin group, as compared with 60.9 percent in the standard-therapy group (74 of 120 patients vs. 70 of 115 patients; absolute difference, 0.8 percent; 95 percent confidence interval, –11.7 to 13.3 percent). Eighty-five percent of patients treated with daptomycin and 84 percent of patients treated with standard therapy survived to the end of the study (P=0.98).

View this table: [in this window] [in a new window]   Table 2. Outcomes 42 Days after the End of Therapy, According to Prespecified Diagnostic Categories.

 

View larger version (47K): [in this window] [in a new window]   Figure 1. Comparison of the Rates of Success of Daptomycin and Standard Therapy for Staphylococcus aureus Bacteremia and Endocarditis. Horizontal bars represent 95 percent confidence intervals.

 
Nine patients in each treatment group had a final diagnosis of left-sided endocarditis. Three patients had a successful outcome; one received daptomycin and two received standard therapy. Therapy failed in all nine patients with left-sided endocarditis caused by MRSA.

The median length of time to clearance of MRSA bacteremia (eight days and nine days, respectively; P=0.25) and MSSA bacteremia (four days and three days, respectively; P=0.28) did not differ significantly between the daptomycin and standard-therapy groups.

Reasons for Treatment Failure

The overall rates of failure of daptomycin and standard therapy were similar (55.8 percent and 58.3 percent, respectively) (Table 3). The reasons for failure, however, were different. Failure of daptomycin treatment was more frequently attributable to persistent or relapsing S. aureus infection (19 of 120 patients [15.8 percent] vs. 11 of 115 patients [9.6 percent] in the standard-therapy group, P=0.17). In contrast, failure of standard therapy was somewhat, but not significantly more frequently, associated with treatment-limiting adverse events (occurring in 17 patients [14.8 percent] vs. 8 patients [6.7 percent] in the daptomycin group, P=0.06).

View this table: [in this window] [in a new window]   Table 3. Reasons for Treatment Failure According to the Adjudication Committee.

 
Nineteen patients who were given daptomycin and 11 patients who were given standard therapy (9 were given vancomycin, and 2 were given an antistaphylococcal penicillin) had persistent or relapsing infection (P=0.17). Microbiologic failure occurred after a mean of 12 to 13 days of therapy in both groups. Among patients with microbiologic failure, more patients who were treated with daptomycin (63.2 percent) than who were treated with standard therapy (45.5 percent) had a diagnosis of complicated bacteremia. The MIC of daptomycin of the S. aureus isolates increased from baseline values in seven patients who were treated with daptomycin; six of these patients had microbiologic failure. Five of these six patients had isolates that were MRSA. In six patients with microbiologic failure, the baseline MIC was 0.25 µg of daptomycin per milliliter in five isolates and 0.5 µg per milliliter in one isolate and rose to 2 µg per milliliter in five isolates and 4 µg per milliliter in one isolate. In the central microbiology laboratory, the isolates from one of the nine patients treated with vancomycin who had microbiologic failure had an increase in the MIC of vancomycin to 2 µg per milliliter. An additional three of these nine isolates demonstrated similar rises in the MIC of vancomycin in the local microbiology laboratory only. Most patients whose treatment failed because of persistent or relapsing S. aureus infection had deep-seated infection and did not receive the necessary surgical intervention. No significant association was found between levels of plasma daptomycin or vancomycin and the occurrence of microbiologic treatment failure.

A sensitivity analysis was performed to define the relative contribution of individual reasons for failure. This analysis demonstrated similar success rates in the two groups when each reason for failure was considered, including failure of efficacy (e.g., microbiologic failure, death, or clinical failure) (Table 4). In addition, the overall success rates for daptomycin (49.2 percent) and standard therapy (48.7 percent) were similar when treatments that failed only because of treatment-limiting adverse events were classified as successes (absolute difference, 0.5 percent; 95 percent confidence interval, –12.3 to 13.3 percent) or were excluded from the analysis (data not shown).

View this table: [in this window] [in a new window]   Table 4. Sensitivity Analyses of Success Rates 42 Days after the End of Therapy, According to the Reported Reasons for Failure as Determined by the Adjudication Committee.

 
Safety and Tolerability

The overall incidence of adverse events in the two treatment groups was similar (Table 5). Most events were considered by the investigators to be unrelated to study treatment and were mild to moderate in severity. Of the 120 patients who received daptomycin, 62 (51.7 percent) had a serious adverse event, as did 52 of 116 patients who received standard therapy (44.8 percent). Adverse events that occurred in at least 5 percent of patients in either treatment group are listed in Table 2 of the Supplementary Appendix. All differences in the rates of adverse events between groups reaching a significance level of P0.05 are provided in Table 3 of the Supplementary Appendix. No statistical adjustments for multiple comparisons were made.

View this table: [in this window] [in a new window]   Table 5. Results of the Safety Analysis.

 
Creatine kinase elevations were significantly more common in the daptomycin group than the standard-therapy group (6.7 percent vs. 0.9 percent, P=0.04). Among patients with normal baseline levels of creatine kinase, elevations of creatine kinase were noted in 23 of 92 patients who received daptomycin, as compared with 12 of 96 patients who received standard therapy (25.0 percent vs. 12.5 percent, P=0.04). Among patients with data that could be evaluated, 2 of 111 patients who received standard therapy had elevations in creatine kinase to more than 500 IU per liter, as compared with 11 of 116 patients who received daptomycin (1.5 percent vs. 9.5 percent, P=0.02). Four of the 11 patients who received daptomycin had elevations that were greater than 10 times the upper limit of normal. Elevation of creatine kinase led to the discontinuation of treatment in 3 of 120 patients treated with daptomycin (2.5 percent). For 20 of the 24 patients who received daptomycin and who had increased levels of creatine kinase at baseline (83.3 percent), the level of creatine kinase returned to the normal range during treatment (18 patients) or after treatment (2 patients). Three patients had low-level elevations of creatine kinase (range, 114 to 451 U per liter) throughout the course of daptomycin therapy (one of whom had no follow-up data after treatment and two of whom had follow-up data approximately six weeks after treatment, with levels of creatine kinase of 215 and 389 U per liter). The fourth patient, who died on day 4, had a decrease in the creatine kinase level from 1004 U per liter on day 1 to 466 U per liter on day 4.

Eleven of 120 patients who received daptomycin had adverse events related to the peripheral nervous system (e.g., paresthesias, dysesthesias, and peripheral neuropathies) (9.2 percent), as compared with 2 of 116 patients who received standard therapy (1.7 percent, P=0.02). All of the events were classified as mild to moderate in severity; most were short-lived and resolved during continued treatment.

As compared with patients who received daptomycin, significantly more patients who received standard therapy had renal impairment as an adverse event, defined by the investigators as interstitial nephritis, toxic nephropathy, acute prerenal failure, acute or chronic renal failure, renal impairment, or renal tubular necrosis (18.1 percent vs. 6.7 percent, P=0.009) or on the basis of worsening creatinine clearance (46.8 percent vs. 19.8 percent, P<0.001). The incidence of renal impairment was similar among patients who received gentamicin and vancomycin (20.4 percent) and patients who received gentamicin and an antistaphylococcal penicillin (18.6 percent). In the safety analysis, renal impairment resulted in the discontinuation of treatment in 5 of 116 patients in the standard-therapy group (4.3 percent) and in 1 of 120 patients in the daptomycin group (0.8 percent). The proportion of patients with clinically significant decreases in renal function during treatment (a decrease in the creatinine clearance to less than 50 ml per minute or a decrease of more than 10 ml per minute from a baseline creatinine clearance of less than 50 ml per minute) was significantly higher in the standard-therapy group than in the daptomycin group by day 7 (14.2 percent vs. 5.2 percent, P=0.03) and through the end of the study (26.3 percent vs. 11.0 percent, P=0.004). Among patients who had clinically significant decreases in renal function, these decreases were reversible (defined by a final creatinine clearance within 10 ml per minute of the baseline value) in 5 of 13 patients who received daptomycin (38.5 percent) and 14 of 30 patients who received standard therapy (46.7 percent; 10 of 19 patients received an antistaphylococcal penicillin [52.6 percent], and 4 of 11 patients received vancomycin [36.4 percent]).

Discussion

Our findings demonstrate that daptomycin is not inferior to standard therapy for the treatment of S. aureus bacteremia and right-sided endocarditis caused by MSSA or MRSA. Our findings were consistent among all efficacy populations and at assessments at both the end of therapy and 42 days after the end of therapy. The study population had high rates of complicated infections, coexisting conditions, and MRSA bacteremia.^3,4,5,6

The growing problem of MRSA bacteremia and endocarditis is magnified by reports of clinical failure^19,20 and resistance^21,22,23,24 to vancomycin. The similar success rates among patients with MRSA bacteremia and right-sided endocarditis treated with daptomycin and such patients who were treated with vancomycin suggest that daptomycin may be considered an alternative to vancomycin in the management of these serious infections.

Although elevations of creatine kinase were documented in one quarter of the patients in the daptomycin group who had normal levels of creatine kinase at baseline, only three patients withdrew from the study for this reason. In our study, clinically significant daptomycin-associated elevations of creatine kinase occurred in 6.7 percent of recipients. Patients who are taking daptomycin should be monitored for elevations in creatine kinase and skeletal-muscle dysfunction.

Patients in the standard-therapy group may have had significantly greater increases in serum creatinine because of the addition of gentamicin to the treatment regimen.²⁵ This observation suggests that even a few days of low-dose gentamicin may result in considerable renal dysfunction in this high-risk population. Our findings provide support for the position of recent guidelines²⁶ that the use of gentamicin in the treatment of native-valve S. aureus endocarditis should be considered optional. However, our study was not designed to examine the contribution of gentamicin to the efficacy or toxicity of standard treatment.

Nineteen of 120 patients who received daptomycin (15.8 percent) had microbiologic failure, defined as persistent or relapsing S. aureus infection. In six of these patients, S. aureus isolated during or after treatment became less susceptible to daptomycin. In contrast, 11 of 115 patients (9.6 percent) who received standard therapy had microbiologic failure, including 9 of 53 patients who received vancomycin and 2 of 62 patients who received an antistaphylococcal penicillin. In four of these nine patients who received vancomycin, the MIC of vancomycin increased to 2 µg per milliliter from baseline values of 0.5 or 1 µg per milliliter. Most patients with persistent or relapsing infection had complicated bacteremia associated with osteomyelitis or indwelling prostheses. Given the complicated nature of these infections, the contribution of decreased antimicrobial susceptibility to clinical failure is difficult to determine. However, these observations, as well as reports of clinical failures associated with reduced susceptibility to vancomycin²⁰ and daptomycin,²⁷ underscore the importance of adjunctive therapy, especially surgical intervention, in optimizing outcomes.

Because of the strict definition for success based on findings 42 days after the completion of therapy, treatment in many cases failed for reasons other than lack of efficacy. For example, not having blood cultures drawn at the visit 42 days after the end of therapy, despite a lack of evidence of persistent or relapsing S. aureus infection, contributed to the high failure rates seen in both groups. In addition, gentamicin therapy may have contributed to the likelihood of both microbiologic success and treatment failure associated with adverse effects in the patients who received standard therapy. However, the overall success rates 42 days after the end of therapy in both groups were similar when treatments that failed only because of treatment-limiting adverse events were classified as successes and when outcomes were assessed according to measures of efficacy (e.g., microbiologic failure, death, or clinical failure).

The open-label nature of the study might have led to bias if investigators were more likely to withdraw a patient in one of the treatment groups than in the other.²⁸ The effect of this potential bias was minimized by including an objective microbiologic end point as part of the assessment and by the use of a blinded adjudication committee to establish the final outcome. Another limitation was the small number of patients with left-sided S. aureus endocarditis and the poor clinical outcome among these patients in both treatment groups. Additional studies are required to optimize medical and surgical therapies in the management of this life-threatening infection.

In conclusion, our results suggest that daptomycin at a dose of 6 mg per kilogram once daily is not inferior to standard therapy for the treatment of bacteremia and right-sided endocarditis caused by MSSA or MRSA.

Supported by Cubist Pharmaceuticals.

Drs. Fowler, Boucher, Corey, Abrutyn, Karchmer, Rupp, Levine, Chambers, Cabell, Link, Price, and Cosgrove report having served as consultants for Cubist Pharmaceuticals. Drs. Tally and Vigliani are employees of Cubist Pharmaceuticals. Dr. Fowler reports having received grant support from Inhibitex, Merck, Nabi, and Theravance; Dr. Corey, from Inhibitex, Merck, and Theravance; Dr. Abrutyn, from Tenet Healthcare Foundation; Dr. Karchmer, from Cubist, Merck, Theravance, and Pfizer; Dr. Rupp, from Becton Dickinson and 3M; Dr. Levine, from Cubist; Dr. Chambers, from Cubist and Ortho-McNeil; Dr. Filler, from Amgen; Dr. Zervos, from Merck and Elan; Dr. Parsonnet, from Procter & Gamble; Dr. Bernstein, from Theravance, Cubist, and Peninsula; Dr. Price, from Denver Health Medical Center, Fujisawa, GlaxoSmithKline, and Cubist; Dr. Rehm, from Cubist; Dr. Tice, from Cubist, Roche, and Merck; and Dr. Cosgrove, from Merck. Dr. Fowler reports having received lecture fees from Cubist, Nabi, and Pfizer; Dr. Boucher, from Pfizer, Schering-Plough, and Cubist; Dr. Karchmer, from Cubist; Dr. Rupp, from Aventis, Ortho-McNeil, Cubist, Schering-Plough, and Bayer; Dr. Levine, from Cubist; Dr. Chambers, from Basilea and Pfizer; Dr. Link, from Cubist; Dr. Zervos, from Pfizer, Aventis, Cubist, and Wyeth; Dr. Bernstein, from Cubist and Ortho-McNeil; Dr. Price, from Ortho-McNeil; Dr. Forrest, from AdvanDx; Dr. Rehm, from Wyeth and Cubist; and Dr. Tice, from Cubist. No other potential conflict of interest relevant to this article was reported.

Source Information

From Duke University Medical Center, Durham, N.C. (V.G.F., G.R.C., C.H.C.); Tufts New England Medical Center (H.W.B.) and Beth Israel Deaconess Medical Center (A.W.K.) — both in Boston; Drexel University College of Medicine, Philadelphia (E.A.); University of Nebraska Medical Center, Omaha (M.E.R.); Wayne State University School of Medicine, Detroit (D.P.L.); San Francisco General Hospital, San Francisco (H.F.C.); Cubist Pharmaceuticals, Lexington, Mass. (F.P.T., G.A.V.); Forsyth Medical Center, Winston-Salem, N.C. (A.S.L.); Onze Lieve Vrouw Ziekenhuis, Aalst, Belgium (I.D.); Harbor–UCLA Medical Center, Torrance, Calif. (S.G.F.); William Beaumont Hospital, Royal Oak, Mich. (M.Z.); East Carolina University, Greenville, N.C. (P.C.); Dartmouth–Hitchcock Medical Center, Lebanon, N.H. (J.P.); Veterans Affairs Medical Center, Dayton, Ohio (J.M.B.); Denver Health Medical, Denver (C.S.P.); University of Maryland School of Medicine (G.N.F.), Johns Hopkins University School of Medicine (S.E.C.) — both in Baltimore; Klinikum, University of Cologne, Cologne, Germany (G.F.); Lehigh Valley Hospital Trauma and Critical Care Research, Allentown, Pa. (M.G.); Cleveland Clinic Foundation, Cleveland (S.J.R.); Johann Wolfgang Goethe Universität, Frankfurt, Germany (H.R.B.); and University of Hawaii, and Queens Medical Center — both in Honolulu (A.T.).

Address reprint requests to Dr. Fowler at Box 3281, Division of Infectious Diseases, Duke University Medical Center, Durham, NC 27710, or at vance.fowler{at}duke.edu.

References

1. Fluit AC, Jones ME, Schmitz FJ, Acar J, Gupta R, Verhoef J. Antimicrobial susceptibility and frequency of occurrence of clinical blood isolates in Europe from the SENTRY Antimicrobial Surveillance Program, 1997 and 1998. Clin Infect Dis 2000;30:454-460. [CrossRef][Web of Science][Medline]
2. Wisplinghoff H, Bischoff T, Tallent SM, Seifert H, Wenzel RP, Edmond MB. Nosocomial bloodstream infections in US hospitals: analysis of 24,179 cases from a prospective nationwide surveillance study. Clin Infect Dis 2004;39:309-317. [Erratum, Clin Infect Dis 2004;39:1093.] [CrossRef][Web of Science][Medline]
3. Fowler VG Jr, Miro JM, Hoen B, et al. Staphylococcus aureus endocarditis: a consequence of medical progress. JAMA 2005;293:3012-3021. [Erratum, JAMA 2005;294: 900.] [Free Full Text]
4. Miro JM, Anguera I, Cabell CH, et al. Staphylococcus aureus native valve infective endocarditis: report of 566 episodes from the International Collaboration on Endocarditis Merged Database. Clin Infect Dis 2005;41:507-514. [Erratum, Clin Infect Dis 2005;41:1075-7.] [CrossRef][Web of Science][Medline]
5. Chang FY, MacDonald BB, Peacock JE Jr, et al. A prospective multicenter study of Staphylococcus aureus bacteremia: incidence of endocarditis, risk factors for mortality, and clinical impact of methicillin resistance. Medicine (Baltimore) 2003;82:322-332. [Medline]
6. Fowler VG Jr, Olsen MK, Corey GR, et al. Clinical identifiers of complicated Staphylococcus aureus bacteremia. Arch Intern Med 2003;163:2066-2072. [Free Full Text]
7. Chang FY, Peacock JE Jr, Musher DM, et al. Staphylococcus aureus bacteremia: recurrence and the impact of antibiotic treatment in a prospective multicenter study. Medicine (Baltimore) 2003;82:333-339. [Medline]
8. Fowler VG Jr, Kong LK, Corey GR, et al. Recurrent Staphylococcus aureus bacteremia: pulsed-field gel electrophoresis findings in 29 patients. J Infect Dis 1999;179:1157-1161. [CrossRef][Web of Science][Medline]
9. Levine DP, Fromm BS, Reddy BR. Slow response to vancomycin or vancomycin plus rifampin in methicillin-resistant Staphylococcus aureus endocarditis. Ann Intern Med 1991;115:674-680. [CrossRef][Web of Science][Medline]
10. Small PM, Chambers HF. Vancomycin for Staphylococcus aureus endocarditis in intravenous drug users. Antimicrob Agents Chemother 1990;34:1227-1231. [Free Full Text]
11. Barry AL, Fuchs PC, Brown SD. In vitro activities of daptomycin against 2,789 clinical isolates from 11 North American medical centers. Antimicrob Agents Chemother 2001;45:1919-1922. [Free Full Text]
12. Carpenter CF, Chambers HF. Daptomycin: another novel agent for treating infections due to drug-resistant gram-positive pathogens. Clin Infect Dis 2004;38:994-1000. [CrossRef][Web of Science][Medline]
13. Critchley IA, Blosser-Middleton RS, Jones ME, Thornsberry C, Sahm DF, Karlowsky JA. Baseline study to determine in vitro activities of daptomycin against gram-positive pathogens isolated in the United States in 2000-2001. Antimicrob Agents Chemother 2003;47:1689-1693. [Free Full Text]
14. Snydman DR, Jacobus NV, McDermott LA, Lonks JR, Boyce JM. Comparative in vitro activities of daptomycin and vancomycin against resistant gram-positive pathogens. Antimicrob Agents Chemother 2000;44:3447-3450. [Free Full Text]
15. Arbeit RD, Maki D, Tally FP, Campanaro E, Eisenstein BI, Daptomycin 98-01 and 99-01 Investigators. The safety and efficacy of daptomycin for the treatment of complicated skin and skin-structure infections. Clin Infect Dis 2004;38:1673-1681. [CrossRef][Web of Science][Medline]
16. Li JS, Sexton DJ, Mick N, et al. Proposed modifications to the Duke criteria for the diagnosis of infective endocarditis. Clin Infect Dis 2000;30:633-638. [CrossRef][Web of Science][Medline]
17. Performance standards for antimicrobial testing: 15th informational supplement. CLSI/NCCLS document M100-S15. Wayne, Pa.: Clinical and Laboratory Standards Institute, 2005.
18. Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron 1976;16:31-41. [Web of Science][Medline]
19. Fowler VG Jr, Sakoulas G, McIntyre LM, et al. Persistent bacteremia due to methicillin-resistant Staphylococcus aureus infection is associated with agr dysfunction and low-level in vitro resistance to thrombin-induced platelet microbicidal protein. J Infect Dis 2004;190:1140-1149. [CrossRef][Web of Science][Medline]
20. Howden BP, Ward PB, Charles PG, et al. Treatment outcomes for serious infections caused by methicillin-resistant Staphylococcus aureus with reduced vancomycin susceptibility. Clin Infect Dis 2004;38:521-528. [CrossRef][Web of Science][Medline]
21. Staphylococcus aureus resistant to vancomycin -- United States, 2002. MMWR Morb Mortal Wkly Rep 2002;51:565-567. [Medline]
22. Vancomycin-resistant Staphylococcus aureus -- Pennsylvania, 2002. MMWR Morb Mortal Wkly Rep 2002;51:902-902. [Medline]
23. Charles PG, Ward PB, Johnson PD, Howden BP, Grayson ML. Clinical features associated with bacteremia due to heterogeneous vancomycin-intermediate Staphylococcus aureus. Clin Infect Dis 2004;38:448-451. [CrossRef][Web of Science][Medline]
24. Smith TL, Pearson ML, Wilcox KR, et al. Emergence of vancomycin resistance in Staphylococcus aureus. N Engl J Med 1999;340:493-501. [Free Full Text]
25. Korzeniowski O, Sande MA. Combination antimicrobial therapy for Staphylococcus aureus endocarditis in patients addicted to parenteral drugs and in nonaddicts: a prospective study. Ann Intern Med 1982;97:496-503. [Free Full Text]
26. Baddour LM, Wilson WR, Bayer AS, et al. Infective endocarditis: diagnosis, antimicrobial therapy, and management of complications: a statement for healthcare professionals from the Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease, Council on Clinical Cardiology, Stroke, and Cardiovascular Surgery and Anesthesia, American Heart Association -- executive summary. Circulation 2005;111:3167-3184. [Erratum, Circulation 2005;112:2373.] [Free Full Text]
27. Hayden MK, Rezai K, Hayes RA, Lolans K, Quinn JP, Weinstein RA. Development of daptomycin resistance in vivo in methicillin-resistant Staphylococcus aureus. J Clin Microbiol 2005;43:5285-5287. [Free Full Text]
28. Rex JH, Bennett JE, Sugar AM, et al. A randomized trial comparing fluconazole with amphotericin B for the treatment of candidemia in patients without neutropenia. N Engl J Med 1994;331:1325-1330. [Free Full Text]

In addition to the authors, the following persons participated in the S. aureus Endocarditis and Bacteremia Study: Patient Enrollment: Amarillo, Tex. — R. Akins; Atlanta — H. Albrecht; Denver — M. Barron, M. Bessesen; Fargo, N.D. — P. Carson; New York — D. Fierer; Danville, Pa. — M. Foltzer; St. Louis — D. Goodenberger; Winston-Salem, N.C. — K. High; Manhasset, N.Y. — B. Hirsch; Besançon CEDEX, France — B. Hoen; Buffalo, N.Y. — C. Hsiao; San Francisco — H. Lampiris; Philadelphia — M. Levison, B. Suh; Bethlehem, Pa. — T.P. Le; Leuven, Belgium — W. Peetermans; Chicago — D. Pitrak, J.P. Quinn, J. Segreti; Louisville, Ky. — J. Ramirez; Boston — P.A. Rice; Regensburg, Germany — B. Salzberger; Cumberland, Md. — J. Stone; Akron, Ohio — J. Tan; Rochester, Minn. — Z. Temesgen; Data and Safety Monitoring Committee: New York — K. Freeman; Charleston, S.C. — J. John, Jr.; Springfield, Mass. — D. Longworth; Cubist Pharmaceuticals Study Team: J. Alder, D. Anastasiou, R. Arbeit, J. Aziz, K. Blackerby, E. Campanaro, M. Campion, B. Eisenstein, J. Lufkin, S. Luperchio, C. Otradovec, C. Rundlett, U. Stoutenburgh, G. Thorne, P. Tipirneni.

Abstract PDF PDA Full Text PowerPoint Slide Set Supplementary Material Editorial by Grayson, M. L. Letters Add to Personal Archive Add to Citation Manager Notify a Friend E-mail When Cited E-mail When Letters Appear PubMed Citation

Related Letters:

Therapy for Methicillin-Resistant Staphylococcus aureus
Siegman-Igra Y., Torres-Tortosa M., Caballero-Granado F. J., Canueto J., Jetton L., Cosgrove S. E., Fowler V. G. Jr., Boucher H. W., Moran G. J., Talan D. A.
Extract | Full Text | PDF  
N Engl J Med 2006; 355:2153-2155, Nov 16, 2006. Correspondence

This article has been cited by other articles:

• Steenbergen, J. N., Mohr, J. F., Thorne, G. M. (2009). Effects of daptomycin in combination with other antimicrobial agents: a review of in vitro and animal model studies. J Antimicrob Chemother 64: 1130-1138 [Abstract] [Full Text]  
• Nguyen, H. M., Graber, C. J. (2009). Limitations of antibiotic options for invasive infections caused by methicillin-resistant Staphylococcus aureus: is combination therapy the answer?. J Antimicrob Chemother 0: dkp377v1-dkp377 [Abstract] [Full Text]  
• Miro, J. M., Garcia-de-la-Maria, C., Armero, Y., Soy, D., Moreno, A., del Rio, A., Almela, M., Sarasa, M., Mestres, C. A., Gatell, J. M., Jimenez de Anta, M. T., Marco, F., and the Hospital Clinic Experimental Endocarditis, (2009). Addition of Gentamicin or Rifampin Does Not Enhance the Effectiveness of Daptomycin in Treatment of Experimental Endocarditis Due to Methicillin-Resistant Staphylococcus aureus. Antimicrob. Agents Chemother. 53: 4172-4177 [Abstract] [Full Text]  
• Murillo, O., Garrigos, C., Pachon, M. E., Euba, G., Verdaguer, R., Cabellos, C., Cabo, J., Gudiol, F., Ariza, J. (2009). Efficacy of High Doses of Daptomycin versus Alternative Therapies against Experimental Foreign-Body Infection by Methicillin-Resistant Staphylococcus aureus. Antimicrob. Agents Chemother. 53: 4252-4257 [Abstract] [Full Text]  
• Endorsed by the European Society of Clinical Micro, , Authors/Task Force Members, , Habib, G., Hoen, B., Tornos, P., Thuny, F., Prendergast, B., Vilacosta, I., Moreillon, P., de Jesus Antunes, M., Thilen, U., Lekakis, J., Lengyel, M., Muller, L., Naber, C. K., Nihoyannopoulos, P., Moritz, A., Zamorano, J. L., ESC Committee for Practice Guidelines (CPG), , Vahanian, A., Auricchio, A., Bax, J., Ceconi, C., Dean, V., Filippatos, G., Funck-Brentano, C., Hobbs, R., Kearney, P., McDonagh, T., McGregor, K., Popescu, B. A., Reiner, Z., Sechtem, U., Sirnes, P. A., Tendera, M., Vardas, P., Widimsky, P., Document Reviewers, , Vahanian, A., Aguilar, R., Bongiorni, M. G., Borger, M., Butchart, E., Danchin, N., Delahaye, F., Erbel, R., Franzen, D., Gould, K., Hall, R., Hassager, C., Kjeldsen, K., McManus, R., Miro, J. M., Mokracek, A., Rosenhek, R., San Roman Calvar, J. A., Seferovic, P., Selton-Suty, C., Uva, M. S., Trinchero, R., van Camp, G. (2009). Guidelines on the prevention, diagnosis, and treatment of infective endocarditis (new version 2009): The Task Force on the Prevention, Diagnosis, and Treatment of Infective Endocarditis of the European Society of Cardiology (ESC). Eur Heart J 30: 2369-2413 [Full Text]  
• Nathwani, D. (2009). Developments in outpatient parenteral antimicrobial therapy (OPAT) for Gram-positive infections in Europe, and the potential impact of daptomycin. J Antimicrob Chemother 64: 447-453 [Abstract] [Full Text]  
• Sun, W., Chen, H., Liu, Y., Zhao, C., Nichols, W. W., Chen, M., Zhang, J., Ma, Y., Wang, H. (2009). Prevalence and Characterization of Heterogeneous Vancomycin-Intermediate Staphylococcus aureus Isolates from 14 Cities in China. Antimicrob. Agents Chemother. 53: 3642-3649 [Abstract] [Full Text]  
• LaPlante, K. L., Woodmansee, S. (2009). Activities of Daptomycin and Vancomycin Alone and in Combination with Rifampin and Gentamicin against Biofilm-Forming Methicillin-Resistant Staphylococcus aureus Isolates in an Experimental Model of Endocarditis. Antimicrob. Agents Chemother. 53: 3880-3886 [Abstract] [Full Text]  
• Livermore, D. M. (2009). Has the era of untreatable infections arrived?. J Antimicrob Chemother 64: i29-i36 [Abstract] [Full Text]  
• Vandecasteele, S. J., Boelaert, J. R., De Vriese, A. S. (2009). Staphylococcus aureus Infections in Hemodialysis: What a Nephrologist Should Know. CJASN 4: 1388-1400 [Abstract] [Full Text]  
• Chakraborty, A., Roy, S., Loeffler, J., Chaves, R. L. (2009). Comparison of the pharmacokinetics, safety and tolerability of daptomycin in healthy adult volunteers following intravenous administration by 30 min infusion or 2 min injection. J Antimicrob Chemother 64: 151-158 [Abstract] [Full Text]  
• Mave, V., Garcia-Diaz, J., Islam, T., Hasbun, R. (2009). Vancomycin-resistant enterococcal bacteraemia: is daptomycin as effective as linezolid?. J Antimicrob Chemother 64: 175-180 [Abstract] [Full Text]  
• Leonard, S. N., Vidaillac, C., Rybak, M. J. (2009). Activity of Telavancin against Staphylococcus aureus Strains with Various Vancomycin Susceptibilities in an In Vitro Pharmacokinetic/Pharmacodynamic Model with Simulated Endocardial Vegetations. Antimicrob. Agents Chemother. 53: 2928-2933 [Abstract] [Full Text]  
• Moise, P. A, Hershberger, E., Amodio-Groton, M. I, Lamp, K. C (2009). Safety and Clinical Outcomes when Utilizing High-Dose (>=8 mg/kg) Daptomycin Therapy. The Annals of Pharmacotherapy 43: 1211-1219 [Abstract] [Full Text]  
• Legendre, D. (2009). Is vancomycin obsolete?. Am J Health Syst Pharm 66: 977-978 [Full Text]  
• Odero, R. O., Cleveland, K. O., Gelfand, M. S. (2009). Rhabdomyolysis and acute renal failure associated with the co-administration of daptomycin and an HMG-CoA reductase inhibitor. J Antimicrob Chemother 63: 1299-1300 [Full Text]  
• Moise, P. A., Smyth, D. S., Robinson, D. A., El-Fawal, N., McCalla, C., Sakoulas, G. (2009). Genotypic and phenotypic relationships among methicillin-resistant Staphylococcus aureus from three multicentre bacteraemia studies. J Antimicrob Chemother 63: 873-876 [Abstract] [Full Text]  
• Gould, F. K., Brindle, R., Chadwick, P. R., Fraise, A. P., Hill, S., Nathwani, D., Ridgway, G. L., Spry, M. J., Warren, R. E., on behalf of the MRSA Working Party of the British, (2009). Guidelines (2008) for the prophylaxis and treatment of methicillin-resistant Staphylococcus aureus (MRSA) infections in the United Kingdom. J Antimicrob Chemother 63: 849-861 [Abstract] [Full Text]  
• Hughes, D. W., Frei, C. R., Maxwell, P. R., Green, K., Patterson, J. E., Crawford, G. E., Lewis, J. S. II (2009). Continuous versus Intermittent Infusion of Oxacillin for Treatment of Infective Endocarditis Caused by Methicillin-Susceptible Staphylococcus aureus. Antimicrob. Agents Chemother. 53: 2014-2019 [Abstract] [Full Text]  
• Rehm, S., Campion, M., Katz, D. E., Russo, R., Boucher, H. W. (2009). Community-based outpatient parenteral antimicrobial therapy (CoPAT) for Staphylococcus aureus bacteraemia with or without infective endocarditis: analysis of the randomized trial comparing daptomycin with standard therapy. J Antimicrob Chemother 63: 1034-1042 [Abstract] [Full Text]  
• Chambers, H. F., Basuino, L., Diep, B. A., Steenbergen, J., Zhang, S., Tattevin, P., Alder, J. (2009). Relationship between Susceptibility to Daptomycin In Vitro and Activity In Vivo in a Rabbit Model of Aortic Valve Endocarditis. Antimicrob. Agents Chemother. 53: 1463-1467 [Abstract] [Full Text]  
• Kluytmans, J., Struelens, M. (2009). Meticillin resistant Staphylococcus aureus in the hospital. BMJ 338: b364-b364 [Full Text]  
• Leonard, S. N., Rybak, M. J. (2009). Evaluation of vancomycin and daptomycin against methicillin-resistant Staphylococcus aureus and heterogeneously vancomycin-intermediate S. aureus in an in vitro pharmacokinetic/pharmacodynamic model with simulated endocardial vegetations. J Antimicrob Chemother 63: 155-160 [Abstract] [Full Text]  
• Rehm, S. J., Boucher, H., Levine, D., Campion, M., Eisenstein, B. I., Vigliani, G. A., Corey, G.R., Abrutyn, E. (2008). Daptomycin versus vancomycin plus gentamicin for treatment of bacteraemia and endocarditis due to Staphylococcus aureus: subset analysis of patients infected with methicillin-resistant isolates. J Antimicrob Chemother 62: 1413-1421 [Abstract] [Full Text]  
• Hope, R., Livermore, D. M., Brick, G., Lillie, M., Reynolds, R., on behalf of the BSAC Working Parties on Resistanc, (2008). Non-susceptibility trends among staphylococci from bacteraemias in the UK and Ireland, 2001-06. J Antimicrob Chemother 62: ii65-ii74 [Abstract] [Full Text]  
• Hawkey, P. M. (2008). Pre-clinical experience with daptomycin. J Antimicrob Chemother 62: iii7-iii14 [Abstract] [Full Text]  
• Seaton, R. A. (2008). Daptomycin: rationale and role in the management of skin and soft tissue infections. J Antimicrob Chemother 62: iii15-iii23 [Abstract] [Full Text]  
• Levine, D. P. (2008). Clinical experience with daptomycin: bacteraemia and endocarditis. J Antimicrob Chemother 62: iii35-iii39 [Abstract] [Full Text]  
• Warren, R. E. (2008). Daptomycin in endocarditis and bacteraemia: a British perspective. J Antimicrob Chemother 62: iii25-iii33 [Abstract] [Full Text]  
• Livermore, D. M. (2008). Future directions with daptomycin. J Antimicrob Chemother 62: iii41-iii49 [Abstract] [Full Text]  
• Wargo, K. A., Eiland, E. H. III, Eiland, L. S. (2008). Management and Treatment Considerations for Infections Caused by Methicillin-Resistant Staphylococcus aureus. Journal of Pharmacy Practice 21: 324-336 [Abstract]  
• Doekel, S., Coeffet-Le Gal, M.-F., Gu, J.-Q., Chu, M., Baltz, R. H., Brian, P. (2008). Non-ribosomal peptide synthetase module fusions to produce derivatives of daptomycin in Streptomyces roseosporus. Microbiology 154: 2872-2880 [Abstract] [Full Text]  
• Rose, W. E., Leonard, S. N., Rybak, M. J. (2008). Evaluation of Daptomycin Pharmacodynamics and Resistance at Various Dosage Regimens against Staphylococcus aureus Isolates with Reduced Susceptibilities to Daptomycin in an In Vitro Pharmacodynamic Model with Simulated Endocardial Vegetations. Antimicrob. Agents Chemother. 52: 3061-3067 [Abstract] [Full Text]  
• Lodise, T. P., Graves, J., Evans, A., Graffunder, E., Helmecke, M., Lomaestro, B. M., Stellrecht, K. (2008). Relationship between Vancomycin MIC and Failure among Patients with Methicillin-Resistant Staphylococcus aureus Bacteremia Treated with Vancomycin. Antimicrob. Agents Chemother. 52: 3315-3320 [Abstract] [Full Text]  
• Lalani, T., Federspiel, J. J., Boucher, H. W., Rude, T. H., Bae, I.-G., Rybak, M. J., Tonthat, G. T., Corey, G. R., Stryjewski, M. E., Sakoulas, G., Chu, V. H., Alder, J., Steenbergen, J. N., Luperchio, S. A., Campion, M., Woods, C. W., Fowler, V. G. (2008). Associations between the Genotypes of Staphylococcus aureus Bloodstream Isolates and Clinical Characteristics and Outcomes of Bacteremic Patients. J. Clin. Microbiol. 46: 2890-2896 [Abstract] [Full Text]  
• McCalla, C., Smyth, D. S., Robinson, D. A., Steenbergen, J., Luperchio, S. A., Moise, P. A., Fowler, V. G. Jr., Sakoulas, G. (2008). Microbiological and Genotypic Analysis of Methicillin-Resistant Staphylococcus aureus Bacteremia. Antimicrob. Agents Chemother. 52: 3441-3443 [Abstract] [Full Text]  
• Schairer, J., Sankri-Tarbichi, A. G., Fairfax, M. R., Salimnia, H., Guzman, J. A. (2008). Methicillin-Resistant Staphylococcus aureus Infection With Intermediate Sensitivity to Vancomycin: A Case Report and Literature Review. J Intensive Care Med 23: 338-341 [Abstract]  
• Gqada, Z., Marais, B., Wasserman, E., Bamford, C., Orth, H., Sakoulas, G., Rose, W., Rybak, M. J., Pillai, S., Alder, J., Moellering, R. C. Jr., Eliopoulos, G. M. (2008). Clinical Rationale for Treatment of Endocarditis Caused by Methicillin-Susceptible Staphylococcus aureus Developing Nonsusceptibility to Daptomycin. J. Clin. Microbiol. 46: 2471-2472 [Full Text]  
• Marco, F., Garcia de la Maria, C., Armero, Y., Amat, E., Soy, D., Moreno, A., del Rio, A., Almela, M., Mestres, C. A., Gatell, J. M., Jimenez de Anta, M. T., Miro, J. M., for the Hospital Clinic Experimental Endocarditis, (2008). Daptomycin Is Effective in Treatment of Experimental Endocarditis Due to Methicillin-Resistant and Glycopeptide-Intermediate Staphylococcus aureus. Antimicrob. Agents Chemother. 52: 2538-2543 [Abstract] [Full Text]  
• Riedel, D. J., Weekes, E., Forrest, G. N. (2008). Addition of Rifampin to Standard Therapy for Treatment of Native Valve Infective Endocarditis Caused by Staphylococcus aureus. Antimicrob. Agents Chemother. 52: 2463-2467 [Abstract] [Full Text]  
• Hidron, A. I., Schuetz, A. N., Nolte, F. S., Gould, C. V., Osborn, M. K. (2008). Daptomycin resistance in Enterococcus faecalis prosthetic valve endocarditis. J Antimicrob Chemother 61: 1394-1396 [Full Text]  
• Waikar, S. S., Liu, K. D., Chertow, G. M. (2008). Diagnosis, Epidemiology and Outcomes of Acute Kidney Injury. CJASN 3: 844-861 [Abstract] [Full Text]  
• Abraham, G., Finkelberg, D., Spooner, L. M (2008). Daptomycin-Induced Acute Renal and Hepatic Toxicity Without Rhabdomyolysis. The Annals of Pharmacotherapy 42: 719-721 [Abstract] [Full Text]  
• REHM, S. J. (2008). Staphylococcus aureus: The new adventures of a legendary pathogen. Cleveland Clinic Journal of Medicine 75: 177-192 [Abstract] [Full Text]  
• Rose, W. E., Leonard, S. N., Sakoulas, G., Kaatz, G. W., Zervos, M. J., Sheth, A., Carpenter, C. F., Rybak, M. J. (2008). Daptomycin Activity against Staphylococcus aureus following Vancomycin Exposure in an In Vitro Pharmacodynamic Model with Simulated Endocardial Vegetations. Antimicrob. Agents Chemother. 52: 831-836 [Abstract] [Full Text]  
• Montero, C. I., Stock, F., Murray, P. R. (2008). Mechanisms of Resistance to Daptomycin in Enterococcus faecium. Antimicrob. Agents Chemother. 52: 1167-1170 [Abstract] [Full Text]  
• Chi, C.-Y., Lauderdale, T.-L., Wang, S.-M., Wu, J.-M., Yang, Y.-J., Liu, C.-C. (2008). Health Care-Associated Endocarditis Caused by Staphylococcus aureus with Reduced Susceptibility to Vancomycin. J. Clin. Microbiol. 46: 810-813 [Abstract] [Full Text]  
• Forrest, G. N, Donovan, B. J, Lamp, K. C, Friedrich, L. V (2008). Clinical Experience with Daptomycin for the Treatment of Patients with Documented Gram-Positive Septic Arthritis. The Annals of Pharmacotherapy 42: 213-217 [Abstract] [Full Text]  
• Ponticelli, C. (2008). New recommendations in the treatment of Gram-positive bacteraemia in dialysis patients. Nephrol Dial Transplant 23: 27-32 [Full Text]  
• Jones, T., Yeaman, M. R., Sakoulas, G., Yang, S.-J., Proctor, R. A., Sahl, H.-G., Schrenzel, J., Xiong, Y. Q., Bayer, A. S. (2008). Failures in Clinical Treatment of Staphylococcus aureus Infection with Daptomycin Are Associated with Alterations in Surface Charge, Membrane Phospholipid Asymmetry, and Drug Binding. Antimicrob. Agents Chemother. 52: 269-278 [Abstract] [Full Text]  
• Sakoulas, G., Rose, W., Rybak, M. J., Pillai, S., Alder, J., Moellering, R. C. Jr., Eliopoulos, G. M. (2008). Evaluation of Endocarditis Caused by Methicillin-Susceptible Staphylococcus aureus Developing Nonsusceptibility to Daptomycin. J. Clin. Microbiol. 46: 220-224 [Abstract] [Full Text]  
• Lalani, T., Boucher, H. W., Cosgrove, S. E., Fowler, V. G., Kanafani, Z. A., Vigliani, G. A., Campion, M., Abrutyn, E., Levine, D. P., Price, C. S., Rehm, S. J., Corey, G. R., Karchmer, A. W., for the S. aureus Endocarditis and Bacteraemia Stu, (2008). Outcomes with daptomycin versus standard therapy for osteoarticular infections associated with Staphylococcus aureus bacteraemia. J Antimicrob Chemother 61: 177-182 [Abstract] [Full Text]  
• Rupp, M. E., Holley, H. P. Jr., Lutz, J., Dicpinigaitis, P. V., Woods, C. W., Levine, D. P., Veney, N., Fowler, V. G. Jr. (2007). Phase II, Randomized, Multicenter, Double-Blind, Placebo-Controlled Trial of a Polyclonal Anti-Staphylococcus aureus Capsular Polysaccharide Immune Globulin in Treatment of Staphylococcus aureus Bacteremia. Antimicrob. Agents Chemother. 51: 4249-4254 [Abstract] [Full Text]  
• Mascio, C. T. M., Alder, J. D., Silverman, J. A. (2007). Bactericidal Action of Daptomycin against Stationary-Phase and Nondividing Staphylococcus aureus Cells. Antimicrob. Agents Chemother. 51: 4255-4260 [Abstract] [Full Text]  
• Yung, D., Kottachchi, D., Neupane, B., Haider, S., Loeb, M. (2007). Antimicrobials for right-sided endocarditis in intravenous drug users: a systematic review. J Antimicrob Chemother 60: 921-928 [Abstract] [Full Text]  
• Hill, E. E., Vanderschueren, S., Verhaegen, J., Herijgers, P., Claus, P., Herregods, M.-C., Peetermans, W. E. (2007). Risk Factors for Infective Endocarditis and Outcome of Patients With Staphylococcus aureus Bacteremia. Mayo Clin Proc. 82: 1165-1169 [Abstract] [Full Text]  
• Osborne, M. (2007). Update in Critical Care. ANN INTERN MED 147: 412-416 [Full Text]  
• Julian, K., Kosowska-Shick, K., Whitener, C., Roos, M., Labischinski, H., Rubio, A., Parent, L., Ednie, L., Koeth, L., Bogdanovich, T., Appelbaum, P. C. (2007). Characterization of a Daptomycin-Nonsusceptible Vancomycin-Intermediate Staphylococcus aureus Strain in a Patient with Endocarditis. Antimicrob. Agents Chemother. 51: 3445-3448 [Abstract] [Full Text]  
• Mergenhagen, K. A, Pasko, M. T (2007). Daptomycin Use After Vancomycin-Induced Neutropenia in a Patient with Left-Sided Endocarditis. The Annals of Pharmacotherapy 41: 1531-1535 [Abstract] [Full Text]  
• Rose, W. E., Rybak, M. J., Kaatz, G. W. (2007). Evaluation of daptomycin treatment of Staphylococcus aureus bacterial endocarditis: an in vitro and in vivo simulation using historical and current dosing strategies. J Antimicrob Chemother 60: 334-340 [Abstract] [Full Text]  
• Daum, R. S. (2007). Skin and Soft-Tissue Infections Caused by Methicillin-Resistant Staphylococcus aureus. NEJM 357: 380-390 [Full Text]  
• Falagas, M. E., Giannopoulou, K. P., Ntziora, F., Vardakas, K. Z. (2007). Daptomycin for endocarditis and/or bacteraemia: a systematic review of the experimental and clinical evidence. J Antimicrob Chemother 60: 7-19 [Abstract] [Full Text]  
• Weis, F., Beiras-Fernandez, A., Kaczmarek, I., Sodian, R., Vicol, C., Reichart, B., Weis, M. (2007). Daptomycin for Eradication of a Systemic Infection With a Methicillin-Resistant-Staphylococcus Aureus in a Biventricular Assist Device Recipient. Ann. Thorac. Surg. 84: 269-270 [Abstract] [Full Text]  
• Miro, J. M., Garcia-de-la-Maria, C., Armero, Y., de-Lazzari, E., Soy, D., Moreno, A., del Rio, A., Almela, M., Mestres, C. A., Gatell, J. M., Jimenez-de-Anta, M.-T., Marco, F., and the Hospital Clinic Experimental Endocarditis, (2007). Efficacy of Telavancin in the Treatment of Experimental Endocarditis Due to Glycopeptide-Intermediate Staphylococcus aureus. Antimicrob. Agents Chemother. 51: 2373-2377 [Abstract] [Full Text]  
• Vouillamoz, J., Moreillon, P., Giddey, M., Entenza, J. M. (2006). Efficacy of daptomycin in the treatment of experimental endocarditis due to susceptible and multidrug-resistant enterococci. J Antimicrob Chemother 58: 1208-1214 [Abstract] [Full Text]  
• French, G. L. (2006). Bactericidal agents in the treatment of MRSA infections--the potential role of daptomycin. J Antimicrob Chemother 58: 1107-1117 [Abstract] [Full Text]  
• Siegman-Igra, Y., Torres-Tortosa, M., Caballero-Granado, F. J., Canueto, J., Jetton, L., Cosgrove, S. E., Fowler, V. G. Jr., Boucher, H. W., Moran, G. J., Talan, D. A. (2006). Therapy for Methicillin-Resistant Staphylococcus aureus. NEJM 355: 2153-2155 [Full Text]  
• Nguyen, K. T., Ritz, D., Gu, J.-Q., Alexander, D., Chu, M., Miao, V., Brian, P., Baltz, R. H. (2006). Combinatorial biosynthesis of novel antibiotics related to daptomycin. Proc. Natl. Acad. Sci. USA 103: 17462-17467 [Abstract] [Full Text]  
• (2006). New Staph Drug Holds Its Own in Serious Infections. JWatch General 2006: 2-2 [Full Text]  
• (2006). Daptomycin for S. aureus Bacteremia and Endocarditis?. Journal Watch Cardiology 2006: 2-2 [Full Text]  
• Fister, K. (2006). What's new in the other general journals. BMJ 333: 490-490 [Full Text]  
• Grayson, M. L. (2006). The Treatment Triangle for Staphylococcal Infections.. NEJM 355: 724-727 [Full Text]  
• (2006). Staphylococcal Infections -- From the Surface to the Depths. JWatch Infect. Diseases 2006: 1-1 [Full Text]