Pharmacokinetic/pharmacodynamic analysis of weight- and height-scaled tobramycin dosage regimens for patients with cystic fibrosis

ConclusionsA tobramycin dose of 3  mg/cm/day rather than 10 mg/kg/day achieved similar PK/PD outcomes but dose and AUC0 –24 ranges were narrower and the incidence of high AUC0 –24 values was lower. Height-based doses should therefore be considered for patients with CF.
Source: Journal of Antimicrobial Chemotherapy - Category: Microbiology Source Type: research

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Authors: Saffioti C, Barco S, Cangemi G, Mesini A, Casciaro R, Cresta F, Castellani C, Bandettini R, Morelli P, Castagnola E PMID: 31583970 [PubMed - as supplied by publisher]
Source: Journal of Chemotherapy - Category: Cancer & Oncology Tags: J Chemother Source Type: research
Abstract Exacerbations of chronic Pseudomonas aeruginosa infections are a major treatment challenge in cystic fibrosis due to biofilm formation and hypermutation. We aimed to evaluate different dosage regimens of meropenem and tobramycin in monotherapies and combination against hypermutable carbapenem-resistant P. aeruginosa A hypermutable P. aeruginosa isolate (MICmeropenem and MICtobramycin 8 mg/L) was investigated in the dynamic CDC biofilm reactor over 120 h. Regimens were meropenem as standard (2 g 8-hourly, 30% epithelial lining fluid (ELF) penetration) and continuous infusion (CI, 6 g/day, 30% and 60% ELF p...
Source: Antimicrobial Agents and Chemotherapy - Category: Microbiology Authors: Tags: Antimicrob Agents Chemother Source Type: research
Abstract Antibiotic tolerance contributes to the inability of standard antimicrobial therapies to clear the chronic Pseudomonas aeruginosa lung infections that often afflict patients with cystic fibrosis (CF). Metabolic potentiation of bactericidal antibiotics with carbon sources has emerged as a promising strategy to re-sensitise tolerant bacteria to antibiotic killing. Fumarate (FUM), a C4-dicarboxylate, has been recently shown to re-sensitise tolerant P. aeruginosa to killing by tobramycin (TOB), an aminoglycoside antibiotic, when used in combination (TOB+FUM). Fumarate and other C4-dicarboxylates are taken up ...
Source: Antimicrobial Agents and Chemotherapy - Category: Microbiology Authors: Tags: Antimicrob Agents Chemother Source Type: research
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Source: Journal of Antimicrobial Chemotherapy - Category: Microbiology Source Type: research
ConclusionsThis study describes the structure of Tn6349, a novel composite transposon carrying several resistance determinants to anti-ribosomal drugs, includingcfr andpoxtA, from an oxazolidinone-resistant MRSA strain. Analysis of Tn6349 revealed a modular structure that could favour the mobilization of its resistance determinants.
Source: Journal of Antimicrobial Chemotherapy - Category: Microbiology Source Type: research
ConclusionsWe show that CF-associatedP. aeruginosa populations can quickly respond to antibiotic therapy and that responses are patient specific. Thus, resistance evolution can be a direct consequence of treatment, and drug efficacy can be lost much faster than usually assumed. The consideration of these patient-specific rapid resistance shifts can help to improve treatment of CF-associated infections, for example by deeper sampling of bacteria for diagnostics, repeated monitoring of pathogen susceptibility and switching between drugs.
Source: Journal of Antimicrobial Chemotherapy - Category: Microbiology Source Type: research
Abstract Inhaled aztreonam is increasingly used for chronic Pseudomonas aeruginosa suppression in patients with cystic fibrosis, but the potential for that organism to evolve aztreonam resistance remains incompletely explored. Here we performed genomic analysis of clonally related pre- and post-treatment clinical isolate pairs to identify genes that are under positive selection during aztreonam therapy in vivo We identified 16 frequently mutated genes associated with aztreonam resistance, the most prevalent being ftsI and ampC, 13 of which increased aztreonam resistance when introduced as single gene transposon mu...
Source: Antimicrobial Agents and Chemotherapy - Category: Microbiology Authors: Tags: Antimicrob Agents Chemother Source Type: research
Abstract Bacteria have acquired multiple mechanisms to evade the lethal effects of current therapeutics, hindering treatment of bacterial infections such as the pathogen P. aeruginosa, which is responsible for nosocomial and cystic fibrosis lung infections. One resistance mechanism involves membrane-embedded multidrug efflux pumps that can effectively extrude an array of substrates, including common antibiotics, dyes, and biocides. Among these is the small multidrug resistant (SMR) efflux protein, consisting of four transmembrane helices (TMs), that functions as an antiparallel dimer. TMs 1-3 comprise the substrat...
Source: Antimicrobial Agents and Chemotherapy - Category: Microbiology Authors: Tags: Antimicrob Agents Chemother Source Type: research
Conclusions This review describes how leukocyte-heparanase can be a double-edged sword in tumor progression; it can enhance tumor immune surveillance and tumor cell clearance, but also promote tumor survival and growth. We also discuss the potential of using heparanase in leukocyte therapies against tumors, and the effects of heparanase inhibitors on tumor progression and immunity. We are just beginning to understand the influence of heparanase on a pro/anti-tumor immune response, and there are still many questions to answer. How do the pro/anti-tumorigenic effects of heparanase differ across different cancer types? Does...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Mark E. Gray1,2*, James Meehan2,3, Paul Sullivan4, Jamie R. K. Marland4, Stephen N. Greenhalgh1, Rachael Gregson1, Richard Eddie Clutton1, Carol Ward2, Chris Cousens5, David J. Griffiths5, Alan Murray4 and David Argyle1 1The Royal (Dick) School of Veterinary Studies and Roslin Institute, University of Edinburgh, Edinburgh, United Kingdom 2Cancer Research UK Edinburgh Centre and Division of Pathology Laboratories, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom 3School of Engineering and Physical Sciences, Institute of Sensors, Signals and Systems, Heriot-Watt Univer...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
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