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  • 1
    Online Resource
    Online Resource
    Wiley ; 2006
    In:  Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy Vol. 26, No. 3 ( 2006-03), p. 347-352
    In: Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy, Wiley, Vol. 26, No. 3 ( 2006-03), p. 347-352
    Abstract: Study Objective . To evaluate the outcomes in patients with bacteremia and/or infective endocarditis who were treated with daptomycin. Design . Retrospective chart review. Setting . A university‐affiliated medical center in Chicago, Illinois, and a regional hospital in Fountain Valley, California. Patients . Thirty‐one inpatients treated with daptomycin for bacteremia and/or infective endocarditis. Measurements and Main Results . Patients were given daptomycin 4–6 mg/kg intravenously every 24–48 hours based on the practitioner's discretion and depending on the patient's clinical condition and presence of comorbidities. Primary end points were resolution of signs and symptoms of infection and discharge from the hospital. Methicillin‐resistant Staphylococcus aureus ([MRSA] 11 patients) and vancomycin‐resistant entercocci ([VRE] 11 patients) were the most common pathogens, whereas 7 patients had methicillin‐sensitive S. aureus infection and 1 patient had coagulase‐negative Staphylococcus infection. One patient with endocarditis had a negative culture result. Overall, 24 (77%) of the 31 patients achieved clinical resolution and were discharged, including all patients infected with MRSA; 7 patients died, 6 of whom had VRE infection. Duration of treatment for infective endocarditis lasted longer (typically 22–43 days) than that for bacteremia only (≤ 14 days), and no patients discontinued daptomycin because of adverse events. Conclusion . In these patients, daptomycin was safe and well tolerated even for extended durations of treatment. Daptomycin may provide an effective option for treating drug‐resistant gram‐positive bloodstream infections and endocarditis.
    Type of Medium: Online Resource
    ISSN: 0277-0008 , 1875-9114
    Language: English
    Publisher: Wiley
    Publication Date: 2006
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  • 2
    In: Drug Development Research, Wiley, Vol. 52, No. 3 ( 2001-03), p. 485-491
    Abstract: Gonadotropin‐releasing hormone (GnRH) stimulates the synthesis and secretion of the gonadotropins that maintain the reproductive axis in mammals. Efforts have focused on the characterization of novel, nonpeptidic orally active antagonists of the GnRH receptor. An erythromycin A derivative, A‐198401 (11‐deoxy‐11‐[carboxy (3,4‐dichlorophenethyl) amino]‐3‐O‐[4‐(S)‐methyl‐oxazolidin‐2‐one] carbamoyl‐5‐O‐(3′‐N‐desmethyl‐3′‐N‐cyclopropylmethyl) desosaminyl‐6‐O‐methyl‐erythronolide A 11,12‐(cyclic carbamate), showed nanomolar affinity for the human (CHO‐21) and rat GnRH receptors in vitro (pK values 8.7 ± 0.2 and 9.2 ± 0.14, respectively). In a functional in vitro assay, A‐198401 inhibited leuprolide‐induced release of luteinizing hormone (LH) from cultured rat pituitary cells with a pA 2 value of 8.8. Intravenous (IV) dosing of A‐198401 in castrate male rats produced a significant dose‐dependent suppression of LH production with an ED 80 value of 5.26 mg/kg. Sustained testosterone (T) suppression was observed after IV dosing of A‐198401 in the intact rat, with a 10‐mg/kg‐dose producing 9–24 h suppression. Analysis of the IV and PO data indicate that A‐198401 has a bioavailability of 15%. A‐198401 is a novel nonpeptide GnRH antagonist that produces significant and sustained suppression of LH and T production in animal models when dosed either IV or PO and may provide the basis for a therapeutic GnRH antagonist for the clinical treatment of reproductive hormone‐dependent diseases. Drug Dev. Res. 52:485–491, 2001. © 2001 Wiley‐Liss, Inc.
    Type of Medium: Online Resource
    ISSN: 0272-4391 , 1098-2299
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2001
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    SSG: 15,3
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  • 3
    In: Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy, Wiley, Vol. 31, No. 6 ( 2011-06), p. 527-536
    Abstract: Study Objective. To evaluate the clinical response and safety of high‐dose daptomycin for treatment of complicated gram‐positive infections. Design. Multicenter, retrospective, observational, case series analysis. Setting. Five academic medical centers in four major United States cities. Patients. Two hundred fifty adults, not undergoing dialysis, who received high‐dose daptomycin (≥ 8 mg/kg/day) for at least 72 hours for complicated gram‐positive infections between January 1, 2005, and March 1, 2010. Measurements and Main Results. Clinical and microbiologic outcomes were assessed at the end of high‐dose daptomycin therapy. Safety evaluations were recorded for all patients, and when available, baseline, end‐of‐therapy and highest observed serum creatine phosphokinase (CPK) levels were recorded. Methicillin‐resistant Staphylococcus aureus (MRSA) and vancomycin‐resistant Enterococcusfaecium (VRE) were the primary organisms isolated. The median dose of daptomycin was 8.9 mg/kg/day (interquartile range [IQR] 8.0–10.0 mg/kg/day). The median duration of daptomycin during hospitalization for MRSA and VRE infection was 10 days (IQR 5–16 days) and 13 days (IQR 6–18 days), respectively. Among the 250 patients, high‐dose daptomycin was primarily used as salvage therapy after vancomycin treatment (184 patients [73.6%] ). Primary infections included complicated bacteremia (119 patients [47.6%]), endocarditis (59 [23.6%] ), skin or wound (70 [28.0%]), and bone or joint (67 [26.8%] ). Overall, clinical response and microbiologic success were assessed in 83.6% (209/250 patients) and 80.3% (175/218 patients), respectively. Isolates from 13 patients (5.2%) developed nonsusceptibility to daptomycin, with most of these patients having extended vancomycin exposure. Three patients (1.2%) developed an adverse event attributable to high‐dose daptomycin therapy, with the event considered either mild or moderate in severity. The median end‐of‐therapy CPK level was 39 U/L (IQR 26–67 U/L). No significant correlation was found between daptomycin dose and highest observed CPK level.
    Type of Medium: Online Resource
    ISSN: 0277-0008 , 1875-9114
    Language: English
    Publisher: Wiley
    Publication Date: 2011
    detail.hit.zdb_id: 2061167-5
    detail.hit.zdb_id: 603158-4
    SSG: 15,3
    Location Call Number Limitation Availability
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