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Multiple-Dose Dalbavancin Regimens as the Predominant Treatment of Deep-Seated or Endovascular Infections: A Scoping Review.

ABSTRACT: Off-label use of dalbavancin for deep-seated and endovascular infections has been increasing. We performed a scoping review to evaluate the evidence for use of multiple-dose dalbavancin regimens as the predominant therapy for these indications. Predominant therapy was defined as use of dalbavancin without other concurrent antibiotics for more than half of the total treatment duration. Fifteen publications were identified; 2 were small, open-label randomized controlled trials and the remainder were retrospective observational studies or case reports. A total of 144 cases from these publications met eligibility criteria for inclusion in this review. Types of infections included osteoarticular infections, catheter-related or complicated bloodstream infections, and infective endocarditis. Overall, the evidence for use of multiple-dose regimens of dalbavancin for deep-seated and endovascular infections is limited by a paucity of data from controlled trials, heterogeneity of dosing regimens, and a lack of standardized clinical outcomes.

SUBMITTER: Cooper MM

PROVIDER: S-EPMC8562469 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature

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Multiple-Dose Dalbavancin Regimens as the Predominant Treatment of Deep-Seated or Endovascular Infections: A Scoping Review.

Cooper Margaret M MM Preslaski Candice R CR Shihadeh Katherine C KC Hawkins Kellie L KL Jenkins Timothy C TC

Open forum infectious diseases 20211027 11

Off-label use of dalbavancin for deep-seated and endovascular infections has been increasing. We performed a scoping review to evaluate the evidence for use of multiple-dose dalbavancin regimens as the predominant therapy for these indications. Predominant therapy was defined as use of dalbavancin without other concurrent antibiotics for more than half of the total treatment duration. Fifteen publications were identified; 2 were small, open-label randomized controlled trials and the remainder we ...[more]

PMID: 34738025

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Project description:Cutibacterium acnes, formerly known as Propionibacterium acnes, is a commensal of the human pilosebaceous unit but also causes deep-seated infection, especially in the context of orthopedic and neurosurgical foreign materials. Interestingly, little is known about the role of specific pathogenicity factors for infection establishment. Here, 86 infection-associated and 103 commensalism-associated isolates of C. acnes were collected from three independent microbiology laboratories. We sequenced the whole genomes of the isolates for genotyping and a genome-wide association study (GWAS). We found that C. acnes subsp. acnes IA1 was the most significant phylotype among the infection isolates (48.3% of all infection isolates; odds ratio [OR] = 1.98 for infection). Among the commensal isolates, C. acnes subsp. acnes IB was the most significant phylotype (40.8% of all commensal isolates; OR = 0.5 for infection). Interestingly, C. acnes subsp. elongatum (III) was rare overall and did not occur at all in infection. The open reading frame-based GWAS (ORF-GWAS) did not show any loci with a strong signal for infection association (no P values of ≤0.05 after adjustment for multiple testing; no logarithmic OR [logOR] of ≥|2|). We concluded that all subspecies and phylotypes of C. acnes, possibly with the exception of C. acnes subsp. elongatum, are able to cause deep-seated infection given favorable conditions, most importantly related to inserted foreign material. Genetic content appears to have a small effect on the likelihood of infection establishment, and functional studies are needed to understand the individual factors contributing to deep-seated infections caused by C. acnes. IMPORTANCE Opportunistic infections emerging from human skin microbiota are of ever-increasing importance. Cutibacterium acnes, being abundant on the human skin, may cause deep-seated infections (e.g., device-associated infections). Differentiation between invasive (i.e., clinically significant) C. acnes isolates and sole contaminants is often difficult. Identification of genetic markers associated with invasiveness not only would strengthen our knowledge related to pathogenesis but also could open ways to selectively categorize invasive and contaminating isolates in the clinical microbiology lab. We show that in contrast to other opportunistic pathogens (e.g., Staphylococcus epidermidis), invasiveness is apparently a broadly distributed ability across almost all C. acnes subspecies and phylotypes. Thus, our work strongly supports an approach in which clinical significance is judged from clinical context rather than by detecting specific genetic traits.

Project description:BackgroundElectrochemotherapy treats tumors by combining specific chemotherapeutic drugs with an intracellular target and electric pulses, which increases drug uptake into the tumor cells. Electrochemotherapy has been successfully used for treatment of easily accessible superficial tumor nodules. In this paper, we present the first case of deep-seated tumor electrochemotherapy based on numerical treatment planning.MethodsThe aim of our study was to treat a melanoma metastasis in the thigh of a patient. Treatment planning for electrode positioning and electrical pulse parameters was performed for two different electrode configurations: one with four and another with five long needle electrodes. During the procedure, the four electrode treatment plan was adopted and the patient was treated accordingly by electrochemotherapy with bleomycin. The response to treatment was clinically and radiographically evaluated. Due to a partial response of the treated tumor, the metastasis was surgically removed after 2 months and pathological analysis was performed.ResultsA partial response of the tumor to electrochemotherapy was obtained. Histologically, the metastasis showed partial necrosis due to electrochemotherapy, estimated to represent 40-50% of the tumor. Based on the data obtained, we re-evaluated the electrical treatment parameters in order to correlate the treatment plan with the clinical response. Electrode positions in the numerical model were updated according to the actual positions during treatment. We compared the maximum value of the measured electric current with the current predicted by the model and good agreement was obtained. Finally, tumor coverage with an electric field above the reversible threshold was recalculated and determined to be approximately 94%. Therefore, according to the calculations, a small volume of tumor cells remained viable after electrochemotherapy, and these were sufficient for tumor regrowth.ConclusionsIn this, the first reported clinical case, deep-seated melanoma metastasis in the thigh of the patient was treated by electrochemotherapy, according to a treatment plan obtained by numerical modeling and optimization. Although only a partial response was obtained, the presented work demonstrates that treatment of deep-seated tumor nodules by electrochemotherapy is feasible and sets the ground for numerical treatment planning-based electrochemotherapy.Trial registrationEudraCT:2008-008290-54.

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Multiple-Dose Dalbavancin Regimens as the Predominant Treatment of Deep-Seated or Endovascular Infections: A Scoping Review.

Publications

Multiple-Dose Dalbavancin Regimens as the Predominant Treatment of Deep-Seated or Endovascular Infections: A Scoping Review.

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