Daptomycin Therapy Research Articles

Acute respiratory failure due to daptomycin induced eosinophilic pneumonia

Daptomycin is an antibiotic that is being used with increasing frequency for the treatment of methicillin resistant Staphylococcus aureus (MRSA) infections. We report a 65-year-old male patient with vertebral osteomyelitis due to MRSA who developed acute respiratory failure secondary to eosinophilic pneumonia after starting daptomycin therapy. Bronchoscopy showed a bronchoalveolar lavage (BAL) with 33% eosinophilia and the transbronchial biopsies revealed organizing pneumonia with many eosinophils. The patient responded rapidly to drug cessation and steroid therapy. Eosinophilic pneumonia is a rare but potentially serious complication of daptomycin therapy that, if recognized early, responds quickly to drug cessation and steroid therapy.

Daptomycin versus Standard Therapy for Bacteremia and Endocarditis Caused by Staphylococcus aureus

Daptomycin versus Standard Therapy for Bacteremia and Endocarditis Caused by Staphylococcus aureus

Daptomycin therapy for Gram-positive bacterial infections: a retrospective study of 30 cardiac surgery patients

Daptomycin is the first in a class of agents known as lipopeptides, used for the treatment of Gram-positive infections. The aim of this study was to evaluate the outcome in patients who were treated with daptomycin in a 12-month period.

Methicillin-resistant Staphylococcus aureus (MRSA) mitral valve acute bacterial endocarditis (ABE) in a patient with Job’s syndrome (hyperimmunoglobulin E syndrome) successfully treated with linezolid and high-dose daptomycin

Job's syndrome (hyperimmunoglobulin E syndrome) is a congenitally acquired primary immune deficiency. The primary host defense defect in Job's syndrome is impaired phagocytosis. Accordingly, patients with Job's syndrome have difficulties eradicating staphylococcal infections. A continuous, high-grade Staphylococcus aureus bacteremia with a cardiac valve vegetation is the hallmark of S. aureus acute bacterial endocarditis (ABE). ABE may be caused by methicillin-sensitive Staphylococcus aureus or methicillin-resistant Staphylococcus aureus (MRSA). We report a case of Job's syndrome MRSA mitral valve ABE. Presumably because of impaired phagocytic function, his MRSA ABE was complicated by extensive metastatic septic complications manifested as brain abscess, multiple epidural abscesses, and multifocal vertebral osteomyelitis. The patient did not respond to 5 days of appropriately dosed linezolid and daptomycin and remained bacteremic because abscess drainage was not an option in this case and the continuous, high-grade MRSA bacteremia continued despite appropriate therapy. High-dose daptomycin (12 mg/kg intravenously every 24 hours) was given, and his MRSA bacteremia was rapidly terminated. Because daptomycin does not cross the blood-brain barrier in therapeutic concentrations, linezolid was used to treat the brain abscess. The extensiveness of infection in this case is remarkable and is probably related to impaired phagocytic function from Job's syndrome. High-dose daptomycin therapy rapidly cleared the bacteremia and cured the endocarditis and epidural abscesses/vertebral osteomyelitis. The patient was treated with 8 weeks of high-dose daptomycin therapy with no adverse effects. If MRSA and methicillin-sensitive S. aureus bacteremias are unresponsive to usually effective antistaphylococcal agents, and surgical drainage of abscesses and removal of infected devices are not clinically possible, then a prolonged, high dose of daptomycin is a therapeutic alternative in such situations. To the best of our knowledge, this is the first case of MRSA mitral valve ABE complicated by extensive epidural abscesses and vertebral osteomyelitis in a patient with Job's syndrome.

Outcomes with daptomycin versus standard therapy for osteoarticular infections associated with Staphylococcus aureus bacteraemia

To evaluate the clinical characteristics, treatment and outcomes of patients with osteoarticular infections (OAIs) associated with Staphylococcus aureus bacteraemia (SAB). The clinical characteristics and outcomes for patients with OAI were described using a post hoc analysis of an open label, randomized trial comparing daptomycin with standard therapy (vancomycin or anti-staphylococcal penicillin with initial gentamicin) for the treatment of SAB. OAI occurred in 32 of 121 patients (21 daptomycin and 11 standard therapy) with complicated SAB (18 septic arthritis, 9 vertebral osteomyelitis and 7 others). Two patients had osteomyelitis in more than one site. Success rates seen in two groups were as follows: vertebral osteomyelitis [3/5 (60%) daptomycin versus 0/2 (0%) comparator], septic arthritis [7/11 (64%) versus 3/5 (60%)], sternal osteomyelitis [3/3 (100%) versus 1/2 (50%)] and long bone osteomyelitis [0/1 (0%) versus 1/1 (100%)]. Success rates in both treatment groups improved with surgical therapy. Creatine phosphokinase elevations to >500 IU/L occurred in one patient on daptomycin who discontinued therapy, whereas renal impairment developed in three patients on standard therapy, two of whom discontinued therapy. Two patients treated with daptomycin and one patient on vancomycin had increases in S. aureus MICs to daptomycin and vancomycin, respectively. Three patients treated with daptomycin died following completion of therapy, with mortality attributed to multiple co-morbid conditions and inadequate debridement of OAIs in these patients. No deaths were reported in the standard therapy group. Daptomycin may be considered an alternative to standard therapy in the treatment of patients with complicated SAB and OAI.

E. faecalis vancomycin-sensitive enterococcal bacteremia unresponsive to a vancomycin tolerant strain successfully treated with high-dose daptomycin

Enterococci are part of the normal flora of the gastrointestinal tract. Intra-abdominal and genitourinary enterococcal infections may be complicated by enterococcal bacteremia. Most strains of enterococci fecal flora in antibiotic-naive patients are E. faecalis. Because nearly all E. faecalis strains are sensitive to vancomycin, E. faecalis is synonymous with vancomycin-sensitive enterococci (VSE). E. faecium, which is nearly always vancomycin-resistant, is termed vancomycin-resistant enterococci (VRE). High-grade continuous enterococcal bacteremias may result in endocarditis. Persistent VSE and VRE bacteremias may be related to device-associated infections; intra-abdominal, pelvic, and/or renal abscesses; or enterococcal endocarditis. If these causes of persistent enterococcal bacteremia are eliminated, microbiologic and antimicrobial therapy-related causes for persistent bacteremia should be considered. We present a case of a male with a E. faecalis (VSE) bacteremia unresponsive to parenteral vancomycin therapy but sensitive to vancomycin in vitro (minimum inhibitory concentration [MIC] = 1 microg/mL). The patient was treated with high-dose daptomycin (12 mg/kg intravenously [IV] q 24 hours) empirically pending susceptibility testing. High-dose daptomycin therapy cleared the patient's E. faecalis bacteremia. Subsequently, it was determined that the strain of E. faecalis was "tolerant" of vancomycin (MIC = 1 microg/mL, MBC = >64 microg/mL). We believe this is the first case of enterococcal (VSE) bacteremia unresponsive to vancomycin tolerant strain of E. faecalis that responded to high-dose daptomycin (12 mg/kg IV q 24 hours) therapy.

Daptomycin in the Treatment of Bacteremia

The aim of this study was to describe the clinical experience with daptomycin in the treatment of bacteremia. Patients with a diagnosis of catheter-related or non–catheter-related bacteremia and no other concurrent infection were identified from the Cubicin Outcomes Registry and Experience (CORE) 2004. Treatment success was determined by investigators using protocol criteria and defined as cure or improvement. Of 168 patients with bacteremia, 126 were clinically evaluable. Of those, 52 (41%) patients were aged ≥66 years, 54 (43%) received daptomycin in an intensive care unit, and 25 (20%) had chronic renal failure. The most common pathogens isolated were methicillin-resistant Staphylococcus aureus (33%), vancomycin-resistant enterococci (30%), and coagulase-negative staphylococci (30%). Of 126 patients, 86% received daptomycin after previous antibiotic therapy and most (69%) received concomitant antibiotics with daptomycin. Daptomycin therapy was started at a median dose of 4.0 mg/kg (range, 2.5 to 9.2 mg/kg). Daptomycin therapy had an overall clinical success rate of 89%. Clinical success was independent of baseline renal function, daptomycin dose, pathogen, first-line use, or concomitant antibiotic therapy. These results support the findings of a recent study in which daptomycin was demonstrated to be an effective option in the treatment of S aureus bacteremia. Data in the current study provide insight into the clinical experience using daptomycin to treat bacteremia caused by other gram-positive pathogens. Given the limitations of retrospective studies and lack of follow-up data, additional studies are needed to make definitive evaluations with these pathogens.

Daptomycin in the Treatment of Patients with Infective Endocarditis: Experience from a Registry

Daptomycin (Cubicin; Cubist Pharmaceuticals, Inc., Lexington, MA) is a first-in-its-class cyclic lipopeptide approved for the treatment of patients with complicated skin and skin-structure infections due to susceptible gram-positive pathogens and recently approved for Staphylococcus aureus bloodstream infections including right-sided infective endocarditis. The clinical experience of patients registered in the Cubicin Outcomes Registry and Experience (CORE) 2004 database with daptomycin-treated infective endocarditis is described. The registry data were collected retrospectively by trained investigators to document real-world clinical experience. Study limitations included uncontrolled diagnostic criteria, noncomparative data, and lack of follow-up assessments. A total of 49 patients had a diagnosis of endocarditis: 38 with left-sided or both left-sided and right-sided endocarditis, and 11 with right-sided endocarditis alone. Renal failure was the most common comorbid condition. In all, 27 (55%) of the 49 patients had an initial creatinine clearance of ≤30 mL/min, and 14 (29%) were supported by dialysis. Staphylococcus aureus (59%; 83%, methicillin resistant) and enterococci (29%; 43%, vancomycin resistant) were the most commonly identified pathogens. In most instances, patients received gram-positive therapy before receiving daptomycin (43 of 49 [88%]). The median starting dose of daptomycin was 6 mg/kg (range, 4 to 7 mg/kg); 27 (55%) of the patients received a dose of ≥6 mg/kg. Daptomycin therapy was successful for 31 (63%) of the patients: cure was seen in 18 (37%) and improvement in 13 (27%). Therapy failed in 4 (8%) of the patients, and 14 (29%) of the cases were nonevaluable. The median duration of therapy in successful cases was 27 days. No differences in clinical response were observed based on baseline renal function, primary pathogen, or site of endocarditis. The results from the CORE 2004 database suggest that daptomycin should be considered a possible treatment for patients with right-sided infective endocarditis involving S aureus. Further studies are needed to extend daptomycin’s experience in left-sided or enterococcal endocarditis.

Cubicin Outcomes Registry and Experience (CORE) Methodology

The Cubicin Outcomes Registry and Experience (CORE), was designed to retrospectively collect the real-world postmarking experience of patients who received daptomycin. A standardized case report form was used by trained investigators from 45 institutions across the United States. Data on 1,160 patients from November 2003 until December 2004 were collected on demographics, infections, treatments and outcomes at the end of daptomycin therapy. The data from CORE 2004 provide insight into the early clinical use of daptomycin.

Clinical Experience with Daptomycin for the Treatment of Patients with Osteomyelitis

Data from a registry were analyzed to describe the clinical experience with daptomycin (Cubicin; Cubist Pharmaceuticals, Inc., Lexington, MA) for the treatment of patients with osteomyelitis. The Cubicin Outcomes Registry and Experience (CORE) 2004 database was used to identify patients treated for osteomyelitis. Posttherapy follow-up outcome assessments were collected for a subset of these patients. A total of 67 patients with osteomyelitis were clinically evaluable for outcome at the end of daptomycin therapy and had outcome assessed at a posttherapy visit. The median follow-up interval after the last dose of daptomycin was 76 days (range, 1 to 547 days). The median initial dose was 5.6 mg/kg (range, 3.2 to 7.5 mg/kg), and the median duration of therapy was 35 days (range, 3 to 546 days). Daptomycin was given concurrently with other antibiotics in 48% of cases. Methicillin-resistant Staphylococcus aureus was the most common pathogen (45%). Clinical outcomes at follow-up were cure, 42 (63%); improved, 13 (19%); failure, 7 (10%); and nonevaluable, 5 (7%). A total of 82% of patients with an orthopedic device (n = 17) were successfully treated, as were 88% of patients with concurrent bacteremia (n = 16). Failures were more likely if surgical debridement was not performed (24% vs. 5%; P = 0.045). The clinical success rate for patients treated with an initial daptomycin dose >4 mg/kg was significantly higher than for patients treated with an initial dose ≤4 mg/kg (88% vs. 65%; P = 0.013, χ 2 test). Daptomycin had a 94% success rate when used alone with no follow-up antibiotics. The results indicate that daptomycin is being used in clinical practice to treat patients with osteomyelitis caused by gram-positive pathogens including MRSA. Prospective, controlled clinical trials of daptomycin are warranted that include rigorous data collection and long-term follow-up analysis.

A Young Man with Pyomyositis and Bullous Disease

Diagnosis: linear IgA bullous dermatosis (LABD). Direct immunofluorescence staining of the skin biopsy specimen obtained from the left thigh, the predominant site of the outbreak of multiple small bullae (figures 1 and 2), revealed the presence of linear IgA deposits along the basement membrane (figure 3) consistent with the diagnosis of LABD related to vancomycin therapy. LABD is an autoimmune subepidermal vesiculobullous disease characterized by IgA deposition in a linear pattern along the basement membrane zone [1]. The disease is mediated by autoantibodies directed against several components of the basement membrane zone [2, 3]. Among antimicrobial drugs, vancomycin is the agent that is most frequently involved in cases of drug-induced LABD. Vancomycin-induced LABD is not dose dependent and has heterogenous presentation, ranging from benign erythema multiforme to toxic epidermal necrolysis [4–6]. The lesions appear 1–15 days after initiation of vancomycin therapy. Spontaneous and complete healing occurs after withdrawal of vancomycin therapy. However, new lesions could still appear up to 2 days after withdrawal of treatment with the drug. The use of steroids and dapsone do not seem to improve the outcome [4]. Rechallenge reproduces the disease with more-rapid and moresevere onset; however, successful rechallenge has been reported [7]. In our patient, vancomycin therapy was switched to daptomycin therapy, and the patient’s bullous rash resolved several days later.

Perspectives on Daptomycin Resistance, with Emphasis on Resistance in Staphylococcus aureus

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

Effectiveness and duration of daptomycin therapy in resolving clinical symptoms in the treatment of complicated skin and skin structure infections

ABSTRACTObjective: Compare the rapidity of the resolution of clinical signs and symptoms of complicated skin and skin structure infections (cSSSIs) caused by Gram-positive organisms between daptomycin and comparator agents.Patients and methods: A subset of South African patients with Gram-positive cSSSIs and no or one comorbid condition from two phase III clinical trials were included in the analysis. Patients were treated with daptomycin (n = 174) or comparator (penicillinase-resistant penicillins [n = 146] or vancomycin [n = 6]). The presence and severity of eight clinical signs and symptoms were evaluated at baseline, day 3 or 4 of treatment, end of therapy, and at test of cure (6–20 days after the last dose).Results: Of the 326 patients included in this analysis, the clinical success rates between daptomycin and comparator treatments was comparable. Overall, the severity of symptoms in the daptomycin-treated patients improved more quickly ( p = 0.04) than comparator treatment. At the day 3/4 evaluation, of the eight signs and symptoms, severity significantly decreased for induration ( p = 0.03) and erythema ( p = 0.05); a statistical trend was noted for necrotic tissue ( p = 0.10) and edema ( p = 0.10) in daptomycin-treated patients. Daptomycin treatment resulted in a shorter median duration of therapy than those receiving comparator treatment (7 vs. 8 days, p < 0.0001). Both treatments were well tolerated.Conclusion: Daptomycin produced a more rapid clinical improvement than comparators, as evidenced by significant reductions in the severity of induration and erythema, with a shorter duration of antibiotic therapy. However, this population was relatively young and healthy; therefore, these results may not be generalizable to all populations.

Evaluation of daptomycin treatment of Staphylococcus aureus bacterial endocarditis: an in vitro and in vivo simulation using historical and current dosing strategies

A failure to daptomycin therapy and subsequent emergence of a daptomycin non-susceptible isolate occurred during the 1990 clinical investigation of daptomycin for the treatment of Staphylococcus aureus bacteraemia and endocarditis. We attempted to determine if this occurrence was reproducible in vitro and if it could be prevented by various daptomycin dosing strategies. The daptomycin susceptible parent strain (SA-675) and the subsequent non-susceptible derivative (SA-684) were evaluated. In the rabbit endocarditis model, daptomycin 3 mg/kg every 8 h for 4 days was administered to simulate the study patient's pharmacokinetic exposure. Daptomycin doses of 1.5 and 3 mg/kg every 12 h and 6 and 10 mg/kg every 24 and 48 h were simulated in the in vitro model with simulated endocardial vegetations (SEVs). Daptomycin significantly reduced bacterial counts of SA-675 in rabbits, but one in 10(5)-10(6) organisms from vegetations of one animal had an 8-fold increase in MIC. Daptomycin 1.5 mg/kg every 12 h in the in vitro model demonstrated no activity against either strain; reduced susceptibility emerged in SA-675 (4-fold increase in MIC). Bactericidal activity was noted with 6 and 10 mg/kg dosing against SA-675 with no resistance detected. The activity of the 6 mg/kg regimen was reduced against SA-684 but significantly improved activity was noted with 10 mg/kg daily. The emergence of resistance was successfully recreated at suboptimal dosing regimens while the current recommended regimen of 6 mg/kg/day prevented the emergence of non-susceptible mutants. Daptomycin 10 mg/kg/day demonstrated even more enhanced killing. Further investigation with daptomycin 10 mg/kg is warranted.

Outcomes analysis of daptomycin use in a community hospital

This study was conducted to assess clinical and cost outcomes associated with the use of daptomycin. This objective was addressed through a consecutive patient chart review of the first 50 inpatients treated with daptomycin. Type of infection, identity of isolated pathogens, prior therapy, duration of therapy, length of hospitalization, cost of antibiotics, adverse events, and outcomes were evaluated. The analysis showed that mean patient age was 64 y, and mean length of hospitalization was 9.2 d. A total of 62% of patients had confirmed methicillin-resistant Staphylococcus aureus infection. The mean duration of daptomycin therapy was 7.5 d; however, in patients given treatment for complicated skin and skin structure infections, the mean duration of therapy was 6.1 d (n=15) and 7.1 d (n=16) for first- and second-line daptomycin therapy, respectively. The average course of daptomycin cost $727 (n=38) and $390 (n=11), respectively, in the subset of patients with renal insufficiency. In patients who did not respond to prior antibiotic treatment for a Gram-positive bacterial infection (n=26), the mean duration of prior therapy with antibiotics was 6.0 d and the cost was $287. For patients who were transitioned to outpatient daptomycin therapy (n=14), hospital charges were reduced by an estimated $102,340. In 48 patients (96%), infection was resolved with daptomycin therapy. Daptomycin was effective in resolving Grampositive infection in this aged patient population. Earlier identification of antibiotic failure, first-line use of daptomycin in patients with complicated skin and skin structure infections, and outpatient daptomycin therapy provided cost savings and improved clinical outcomes at this facility.

Organizing Pneumonia and Pulmonary Eosinophilic Infiltration Associated with Daptomycin

To report a case of organizing pneumonia with pulmonary eosinophilic infiltrates in a patient receiving daptomycin. An 84-year-old man developed bilateral, irregularly shaped nodules and infiltrates in the mid and peripheral lung and multiple mediastinal lymph nodes following treatment with intravenous daptomycin for infection of his left knee prosthesis. His other symptoms included decreased appetite, weight loss (6.8 kg over 4-6 wk), malaise, and generalized weakness after 4 weeks of daptomycin therapy. Transthoracic needle biopsy revealed organizing pneumonia with scattered eosinophils. His symptoms and results of computed tomography (CT) scan improved in the month following discontinuation of daptomycin. The Naranjo probability scale indicated a probable reaction to daptomycin. Pulmonary reactions have been reported with numerous drugs and have a wide range of clinical and radiographic presentations. Clinical trials have shown that daptomycin is well tolerated and has an adverse effect profile similar to that of vancomycin and the semisynthetic penicillins. This case report suggests that chronic use of daptomycin caused organizing pneumonia with eosinophilic infiltrates in a patient treated for an infected knee prosthesis. A definite mechanism for this reaction is not known. We speculate that the chronic administration of daptomycin allowed drug accumulation in surfactant in the alveolar spaces. This may result in higher concentrations of drug near the alveolar epithelial surface, which could injure the epithelium, resulting in organizing pneumonia. Development of new pulmonary infiltrates in patients treated with chronic daptomycin therapy should alert healthcare workers to this potential association.

Eosinophilic pneumonia induced by daptomycin

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

Daptomycin versus Standard Therapy for Bacteremia and Endocarditis Caused by Staphylococcus aureus

Daptomycin versus Standard Therapy for Bacteremia and Endocarditis Caused by Staphylococcus aureus

Retrospective Evaluation of Daptomycin, a Lipopeptide Antibiotic, in Bone Marrow Transplant and Hematology/Oncology Patients.

Background: Daptomycin is a lipopeptide antibiotic with potent activity against many Gram-positive organisms. Efficacy in immunocompromised patients is unknown because these patients have been excluded from daptomycin premarketing studies.Methods: Patients with documented infections treated at the University of Michigan Health System in either the bone marrow transplant or hematology/oncology service were identified in the Cubicin® Outcomes Registry and Experience (COREsm 2004 and 2005). Demographic, disease state, clinical, and microbiologic data were collected. Clinical outcomes were assessed using the following definitions: Cure - clinical signs and symptoms are resolved and/or no additional antibiotic therapy is necessary or infection cleared with a negative culture reported at the end of daptomycin therapy; Improved - partial resolution of clinical signs and symptoms and/or additional antibiotic therapy is necessary at the end of daptomycin therapy; Failure - inadequate response to therapy or resistant, worsening or new/recurrent signs and symptoms, or the need for a change in antibiotic therapy or a positive culture reported at the end of daptomycin therapy; Nonevaluable - unable to determine response at the end of daptomycin therapy. Success was defined as cure or improved.Results: Fourteen patients are included in this analysis. Nine (64%) patients were female; 6 (43%) were ≥ 51 years of age. Two patients had an initial CrCl <30 mL/min, 1 was on hemodialysis. Eight (57%) patients had undergone allogeneic peripheral blood stem cell transplantation primarily for acute myeloid leukemia. The remaining 6 patients had papillary adenocarcinoma, endometrial carcinoma, dermatofibrosarcoma protuberans, acute lymphoblastic lymphoma, non-Hodgkin lymphoma, and Hodgkin lymphoma. The most common infection (n=11, 79%) was bacteremia; 7 (50%) patients had catheter-related bacteremia; 1 each (7%) had discitis, necrotizing fasciitis and urinary tract infection. Nine (64%) patients had vancomycin-resistant Enterococcus faecium (VRE) as a pathogen; 8 were bacteremic (3 with concurrent coagulase-negative staphylococci; CoNS). Methicillin-resistant Staphylococcus aureus (MRSA) was isolated in 3 (21%) patients; 2 were bacteremic (1 with concurrent CoNS). One additional patient had CoNS bacteremia. The patient with necrotizing fasciitis was culture negative. The initial daptomycin dose was 4 mg/kg in 8 (57%) patients and 6 mg/kg in 6 (43%) patients. All patients receiving 6 mg/kg were bacteremic. The dosing frequency was adjusted for renal function in all patients. The median duration of therapy was 14.5 days (range, 2 – 62). Nine (64%) patients received an antibiotic prior to daptomycin and 43% of patients received an antibiotic concomitantly. Seven catheters were removed; 5 from patients with catheter-related bacteremia. The median time to clinical response was 2 days (n=10, range 1 – 13). All patients with an outcome reported (n=11) were successfully treated, 3 (21%) patients were nonevaluable. Of the 11 bacteremic patients, 5 received 4 mg/kg and 6 received 6 mg/kg; 2 were nonevaluable (both 6 mg/kg) and 9 of 11 (82%) were successes.Conclusion: These data demonstrate that daptomycin therapy is associated with clinical success in hem/onc patients including those who have undergone allogeneic peripheral blood stem cell transplantation where bacteremia and VRE are prevalent.

Efficacy of daptomycin in complicated skin and skin-structure infections due to methicillin-sensitive and ‐resistant Staphylococcus aureus : results from the CORE Registry

ABSTRACTObjective: To characterize postmarketing clinical experience with daptomycin in treating complicated skin and skin-structure infections (cSSSIs) due to cultureconfirmed MRSA and MSSA in real-life prescribing situations.Research design and methods: The Cubicin Outcomes Registry and Experience 2004 (CORE 2004) is a multicenter observational registry involving 45 separate institutions, designed to characterize infection types, pathogens, and outcomes of patients who were treated with daptomycin. A subset analysis of the CORE 2004 data was conducted to characterize patients with cSSSI due to culture-confirmed MRSA and MSSA, but without bacteremia, endocarditis, osteomyelitis, or other significant infectious processes. Clinical information, including patient demographics, antibiotic treatments, and clinical outcome, was analyzed. Adverse event data were not collected in CORE 2004.Main outcome measure: Clinical success (cured or improved) or failure was assessed at the end of daptomycin treatment.Results: A total of 165 patients were identified, including 145 patients (87.9%) with MRSA and 20 patients (12.1%) with MSSA infections. Most patients received daptomycin at a dosage of 4–6 mg/kg intravenously and at a frequency of once every 24 h. Daptomycin dosing frequency was adjusted to once every 48 h or thrice weekly in all seven patients who had received hemodialysis. Prior antibiotic therapy had been administered to 121/163 (74.2%) patients and concomitant antibiotic therapy to 65/165 (39.4%) of patients. Clinical success was achieved with daptomycin in 89.1% of patients overall, including 89.7% and 85.0% of those with MRSA and MSSA, respectively. Among patients with a successful outcome, the total days of daptomycin therapy (median days: MRSA = 13.0, MSSA = 11.0) and the days to clinical response (median days: MRSA = 3.5, MSSA = 2.0) were not significantly different for MRSA and MSSA patients (p = 0.27 and p = 0.15 respectively, median test).Conclusions: Given the limitations of this registry which include its retrospective nature; limited numbers of MSSA patients; and lack of specific information on adverse events, type and duration of prior antibiotic therapy, timing and duration of concomitant antibiotic therapy, concomitant surgical interventions, and possible on-therapy dosing adjustments), daptomycin appeared effective in postmarketing clinical practice in the treatment of cSSSI caused by MRSA and MSSA.