Objectives: To determine the current spectrum of Gram-positive bloodstream infections (BSI) in patients with hematologic malignancies at our institution, and to determine the in vitro activity of various fluoroquinolones against clinical Gram-positive isolates collected from such patients.
Methods: Institutional microbiology records from 493 consecutive episodes of Gram-positive BSI were reviewed. The in vitro activity of six fluoroquinolones against 477 clinical isolates was determined using an NCCLS approved, broth-dilution method.
Results: The most common Gram-positive organisms isolated from the bloodstream of patients with hematological malignancies were coagulase-negative staphylococci (33%), Staphylococcus aureus (15%), viridans group streptococci (10%), and the enterococci (8%). Acute leukemias were the most common underlying malignancies, and 73% of patients were neutropenic when they developed their BSI. The newer generation quinolones--moxifloxacin and gatifloxacin--had the best overall in vitro activity against the Gram-positive isolates tested, and were at least 2 to 8-fold more potent than the early generation quinolones (ofloxacin and ciprofloxacin). Of the 477 isolates tested, 405 (85%) were from patients receiving quinolone (ciprofloxacin or levofloxacin) prophylaxis.
Conclusions: In patients with hematologic malignancies, Gram-positive BSI are caused by a large number of bacterial species and many occur despite antimicrobial prophylaxis. The newer generation quinolones--moxifloxacin and gatifloxacin--have better in vitro activity against these organisms than early generation agents (ciprofloxacin and ofloxacin).
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http://dx.doi.org/10.1016/j.ijid.2005.05.007 | DOI Listing |
Proc Natl Acad Sci U S A
January 2025
Bioelectricity Laboratory, Department of Physiology and Biophysics, School of Medicine, University of California, Irvine, CA 92697.
Loss-of-function sequence variants in , which encodes the voltage-gated potassium channel Kv1.1, cause Episodic Ataxia Type 1 (EA1) and epilepsy. Due to a paucity of drugs that directly rescue mutant Kv1.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
January 2025
Center for Complexity and Biosystems, Department of Environmental Science and Policy, University of Milan, 20133 Milan, Italy.
Collective migration of cancer cells is often interpreted using concepts derived from the physics of active matter, but the experimental evidence is mostly restricted to observations made in vitro. Here, we study collective invasion of metastatic cancer cells injected into the mouse deep dermis using intravital multiphoton microscopy combined with a skin window technique and three-dimensional quantitative image analysis. We observe a multicellular but low-cohesive migration mode characterized by rotational patterns which self-organize into antiparallel persistent tracks with orientational nematic order.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
January 2025
Laboratory of Precision Medicine and Biopharmaceuticals, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.
Recurrent missense mutations in the human epidermal growth factor receptor 2 (HER2) have been identified across various human cancers. Among these mutations, the active S310F mutation in the HER2 extracellular domain stands out as not only oncogenic but also confers resistance to pertuzumab, an antibody drug widely used in clinical cancer therapy, by impeding its binding. In this study, we have successfully employed computational-aided rational design to undertake directed evolution of pertuzumab, resulting in the creation of an evolved pertuzumab variant named Ptz-SA.
View Article and Find Full Text PDFPLoS Negl Trop Dis
January 2025
Department of Pediatrics, National School of Tropical Medicine, Baylor College of Medicine, Houston, Texas, United States of America.
Background: The antigen Na-GST-1, expressed by the hookworm Necator americanus, plays crucial biochemical roles in parasite survival. This study explores the development of mRNA vaccine candidates based on Na-GST-1, building on the success of recombinant Na-GST-1 (rNa-GST-1) protein, currently assessed as a subunit vaccine candidate, which has shown promise in preclinical and clinical studies.
Methodology/findings: By leveraging the flexible design of RNA vaccines and protein intracellular trafficking signal sequences, we developed three variants of Na-GST-1 as native (cytosolic), secretory, and plasma membrane-anchored (PM) antigens.
J Neurochem
January 2025
State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
Severe trauma frequently leads to nerve damage. Peripheral nerves possess a degree of regenerative ability, and actively promoting their recovery can help restore the sensory and functional capacities of tissues. The neuropeptide calcitonin gene-related peptide (CGRP) is believed to regulate the repair of injured peripheral nerves, with neuronal transient receptor potential vanilloid type 1 (TRPV1) potentially serving as a crucial upstream factor.
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