Bloodstream infection (BSI) is defined by positive blood cultures in a patient with systemic signs of infection and may be either secondary to a documented source or primary-that is, without identified origin. Community-acquired BSIs in immunocompetent adults usually involve drug-susceptible bacteria, while healthcare-associated BSIs are frequently due to multidrug-resistant (MDR) strains. Early adequate antimicrobial therapy is a key to improve patient outcomes, especially in those with criteria for sepsis or septic shock, and should be based on guidelines and direct examination of available samples. Local epidemiology, suspected source, immune status, previous antimicrobial exposure, and documented colonization with MDR bacteria must be considered for the choice of first-line antimicrobials in healthcare-associated and hospital-acquired BSIs. Early genotypic or phenotypic tests are now available for bacterial identification and early detection of resistance mechanisms and may help, though their clinical impact warrants further investigations. Initial antimicrobial dosing should take into account the pharmacokinetic alterations commonly observed in ICU patients, with a loading dose in case of sepsis or septic shock. Initial antimicrobial combination attempting to increase the antimicrobial spectrum should be discussed when MDR bacteria are suspected and/or in the most severely ill patients. Source identification and control should be performed as soon as the hemodynamic status is stabilized. De-escalation from a broad-spectrum to a narrow-spectrum antimicrobial may reduce antibiotic selection pressure without negative impact on mortality. The duration of therapy is usually 5-8 days though longer durations may be discussed depending on the underlying illness and the source of infection. This narrative review covers the epidemiology, diagnostic workflow and therapeutic aspects of BSI in ICU patients and proposed up-todate expert statements.
Empirical broad spectrum antimicrobial therapy prescribed in life-threatening situations should be de-escalated to mitigate the risk of resistance emergence. Definitions of de-escalation (DE) vary among studies, thereby biasing their results. The aim of this study was to provide a consensus definition of DE and to establish a ranking of β-lactam according to both their spectra and their ecological consequences. Twenty-eight experts from intensive care, infectious disease and clinical microbiology were consulted using the Delphi method (four successive questionnaires) from July to November 2013. More than 70% of similar answers to a question were necessary to reach a consensus. According to our consensus definition, DE purpose was to reduce both the spectrum of antimicrobial therapy and the selective pressure on microbiota. DE included switching from combination to monotherapy. A six-rank consensual classification of β-lactams allowing gradation of DE was established. The group was unable to differentiate ecological consequences of molecules included in group 4, i.e. piperacillin/tazobactam, ticarcillin/clavulanic acid, fourth-generation cephalosporin and antipseudomonal third-generation cephalosporin. Furthermore, no consensus was reached on the delay within which DE should be performed and on whether or not the shortening of antibiotic therapy duration should be included in DE definition. This study provides a consensual ranking of β-lactams according to their global ecological consequences that may be helpful in future studies on DE. However, this work also underlines the difficulties of reaching a consensus on the relative ecological impact of each individual drug and on the timing of DE.
The mercury resistance gene merA has often been found together with antibiotic resistance genes in human commensal Escherichia coli. To study this further, we analysed mercury resistance in collections of strains from various populations with different levels of mercury exposure and various levels of antibiotic resistance. The first population lived in France and had no known mercury exposure. The second lived in French Guyana and included a group of Wayampi Amerindians with a known high exposure to mercury. Carriage rates of mercury resistance were assessed by measuring the MIC and by detecting the merA gene. Mercury-resistant E. coli was found significantly more frequently in the populations that had the highest carriage rates of antibiotic-resistant E. coli and in parallel antibiotic resistance was higher in the population living in an environment with a high exposure to mercury, suggesting a possible co-selection. Exposure to mercury might be a specific driving force for the acquisition and maintenance of mobile antibiotic resistance gene carriage in the absence of antibiotic selective pressure. INTRODUCTIONMercury is a heavy metal that occurs naturally in the environment in various forms (Barkay et al., 2003). Methylmercury, one of the most potent neurotoxins known, has adverse effects on the health of animals and humans (Magos & Clarkson, 2006). The consumption of fresh, contaminated fish is the most common means by which humans are exposed to mercury (Barkay et al., 2003). Human activity releases mercury into the air, water and soil (Barkay et al., 2003). The prevalence of mercuryresistant bacteria has been shown to increase in mercurypolluted environments (Barkay & Olson, 1986;Rasmussen & Sorensen, 1998) mainly through selection for acquisition of resistance.The principal mechanism of bacterial resistance to mercury is the reduction of the reactive ionic form of mercury (Hg 2+ ) to the less-reactive, volatile, elemental form (Hg 0 ) (Barkay et al., 2003). This reaction is catalysed by the cytosolic flavoenzyme mercuric reductase (MerA) (Fox & Walsh, 1982). Briefly, the mer locus consists of genes encoding synthesis of MerA and a transport system which brings Hg 2+ into the cytoplasm for reduction by MerA. The genes for the entire system are arranged as an operon (the mer operon) under both positive and negative genetic regulatory control (Lee et al., 1993), and are often part of the Tn21-like transposons, which themselves can carry class 1 integrons, that cannot mobilize without the help of a transposon or an ISCR element, with one or more antibiotic resistance genes (Liebert et al., 1999). It is not clear whether the genetic linkage between antibiotic and mercury resistance is based on selection by an antibiotic pressure, by a mercury pressure, by a combined pressure or due to some other mechanism. Nonetheless, regardless of the presence of dental amalgam fillings that contain mercury, resistance to mercury is widely distributed among bacteria isolated from healthy adults and children, with the pre...
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.