{"id":30795,"date":"2026-07-14T04:07:00","date_gmt":"2026-07-13T20:07:00","guid":{"rendered":"https:\/\/csccm.org.cn\/?p=30795"},"modified":"2026-07-14T05:43:08","modified_gmt":"2026-07-13T21:43:08","slug":"jama-netw-open%e5%8f%91%e8%a1%a8%e8%ae%ba%e6%96%87%ef%bc%9a%e8%be%be%e5%b7%b4%e4%b8%87%e6%98%9f%e6%b2%bb%e7%96%97%e5%a4%8d%e6%9d%82%e6%80%a7%e9%87%91%e9%bb%84%e8%89%b2%e8%91%a1%e8%90%84%e7%90%83","status":"publish","type":"post","link":"https:\/\/csccm.org.cn\/?p=30795","title":{"rendered":"[JAMA Netw Open\u53d1\u8868\u8bba\u6587]\uff1a\u8fbe\u5df4\u4e07\u661f\u6cbb\u7597\u590d\u6742\u6027\u91d1\u9ec4\u8272\u8461\u8404\u7403\u83cc\u83cc\u8840\u75c7\u7684\u836f\u4ee3\u52a8\u529b\u5b66"},"content":{"rendered":"\n

Original Investigation <\/p>\n\n\n\n

Infectious Diseases<\/p>\n\n\n\n

Pharmacokinetics of Dalbavancin in Complicated\u00a0Staphylococcus aureus<\/em>\u00a0Bacteremia: A Secondary Analysis of the DOTS Randomized Clinical Trial<\/h1>\n\n\n\n

Thomas P.\u00a0Lodise,\u00a0Nicholas A.\u00a0Turner,\u00a0Toshimitsu\u00a0Hamasaki, et al<\/h3>\n\n\n\n

JAMA Netw Open 2026;9;(4):e2611652.\u00a0doi:10.1001\/jamanetworkopen.2026.11652<\/h3>\n\n\n\n

Key Points<\/p>\n\n\n\n

Question<\/strong>  What are the pharmacokinetics of a 2-dose dalbavancin regimen used for consolidation therapy in complicated Staphylococcus aureus<\/em> bacteremia, and is dalbavancin exposure associated with clinical success?<\/p>\n\n\n\n

Findings<\/strong>  In this prespecified secondary analysis that included 97 adults with complicated S. aureus<\/em> bacteremia from a randomized clinical trial, kidney function, weight, albumin level, and age influenced dalbavancin pharmacokinetics. Total day 22 concentrations greater than 32 \u03bcg\/mL were associated with increased rates of day 70 clinical success, without corresponding increases in serious adverse events.<\/p>\n\n\n\n

Meaning<\/strong>  Although 2 doses of dalbavancin were noninferior to standard therapy in complicated S. aureus<\/em> bacteremia in the parent trial, these findings suggest that future studies should assess whether patients with day 22 concentrations of 32 \u03bcg\/mL or less may benefit from an additional dose.<\/a><\/p>\n\n\n\n

Abstract<\/p>\n\n\n\n

Importance<\/strong>  Dalbavancin is an alternative to prolonged intravenous therapy for complicated Staphylococcus aureus<\/em> bacteremia, yet its pharmacokinetics (PK) in patients with this condition are uncertain.<\/p>\n\n\n\n

Objective<\/strong>  To characterize dalbavancin PK and evaluate associations of total and unbound exposures of dalbavancin with clinical success in patients with complicated S aureus<\/em> bacteremia.<\/p>\n\n\n\n

Design, Setting, and Participants<\/strong>  This study was an exploratory prespecified secondary analysis of PK and exposure response within Dalbavancin as an Option for Treatment of S aureus<\/em> Bacteremia (DOTS), a multicenter, randomized, open-label, assessor-blinded clinical trial conducted from April 2021 to December 2023. Data analysis was conducted from January 2024 to December 2025. Adults with complicated S aureus<\/em> bacteremia who achieved bloodstream clearance were randomized to dalbavancin or standard therapy; PK analyses included dalbavancin recipients with at least 1 postdose concentration measurement.<\/p>\n\n\n\n

Intervention<\/strong>  Dalbavancin 1500 mg intravenously on days 1 and 8 (1125 mg for patients with severe kidney impairment not receiving dialysis).<\/p>\n\n\n\n

Main Outcomes and Measures<\/strong>  Individual exposure metrics, including day 22 concentration and area under the concentration-time curve (AUC) from days 0 to 22, were derived using nonlinear mixed-effects population PK modeling. Exposure metrics were then assessed for association with clinical success at day 70 (exposure-response analysis).<\/p>\n\n\n\n

Results<\/strong>\u00a0\u00a0A total of 97 patients (mean [SD] age, 54.5 [15.8] years; 69 male [71.1%]) contributing 640 PK samples were included. Clearance was estimated at 0.066 L\/h (95% CI, 0.062 to 0.069 L\/h), and the central volume of distribution was estimated at 5.67 L (95% CI, 5.37 to 5.99 L). Interindividual variability was 22.6% (95% CI, 18.9% to 25.6%) for clearance and 19.7% (95% CI, 13.8% to 25.0%) for the central volume of distribution. Clearance increased with creatinine clearance according to a power function (exponent, 0.21; 95% CI, 0.16 to 0.30). Distribution volumes increased with body weight following power relationships, including the central volume (exponent, 0.57; 95% CI, 0.37 to 0.86), second peripheral volume (0.82; 95% CI, 0.37 to 1.46), and third peripheral volume (0.56; 95% CI, 0.30 to 0.82). Albumin was inversely associated with the second peripheral volume (exponent, \u22120.81; 95% CI, \u22121.79 to \u22120.32) and unbound-fraction scaling factor (exponent, \u22120.78; 95% CI, \u22120.98 to \u22120.54), and age was positively associated with the third peripheral volume via a power relationship (exponent, 0.63; 95% CI, 0.44 to 0.83). Among 93 evaluable patients, 72 individuals (77.4%) achieved clinical success at day 70. Patients with a day 22 concentration greater than 32 \u03bcg\/mL (30 patients [32.3% of evaluable patients receiving dalbavancin]) had higher clinical success compared with 63 patients with a day 22 concentration of 32 \u03bcg\/mL or less (29 patients [96.7%] vs 43 patients [68.3%]; adjusted difference, 25.3 percentage points; 95% CI, 3.5-47.0 percentage points) and experienced similar rates of serious adverse events (8 patients [26.7%] vs 27 patients [42.9%]; unadjusted difference, \u221216.2 percentage points, 95% CI \u221236.2 to 3.8 percentage points).<\/p>\n\n\n\n

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Conclusions and Relevance<\/strong>  In this study, dalbavancin pharmacokinetics were predictably influenced by kidney function, body weight, albumin levels, and age, and higher total day 22 concentrations were associated with greater clinical success without increased serious adverse events. These findings are exploratory and support further evaluation of exposure-guided dosing strategies.<\/p>\n\n\n\n

Trial Registration<\/strong>  Clinical Trials.gov Identifier: NCT04775953<\/a><\/p>\n","protected":false},"excerpt":{"rendered":"

Original Investigation  Infectious Diseases Pharma […]<\/p>\n","protected":false},"author":3,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":[],"categories":[32,23],"tags":[],"_links":{"self":[{"href":"https:\/\/csccm.org.cn\/index.php?rest_route=\/wp\/v2\/posts\/30795"}],"collection":[{"href":"https:\/\/csccm.org.cn\/index.php?rest_route=\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/csccm.org.cn\/index.php?rest_route=\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/csccm.org.cn\/index.php?rest_route=\/wp\/v2\/users\/3"}],"replies":[{"embeddable":true,"href":"https:\/\/csccm.org.cn\/index.php?rest_route=%2Fwp%2Fv2%2Fcomments&post=30795"}],"version-history":[{"count":1,"href":"https:\/\/csccm.org.cn\/index.php?rest_route=\/wp\/v2\/posts\/30795\/revisions"}],"predecessor-version":[{"id":30796,"href":"https:\/\/csccm.org.cn\/index.php?rest_route=\/wp\/v2\/posts\/30795\/revisions\/30796"}],"wp:attachment":[{"href":"https:\/\/csccm.org.cn\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=30795"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/csccm.org.cn\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=30795"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/csccm.org.cn\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=30795"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}