Secular Trends in Nosocomial Bloodstream Infections: Antibiotic-Resistant Bacteria Increase the Total Burden of Infection

Ammerlaan, Heidi S. M.; Harbarth, Stéphan Juergen; Buiting, A. G. M.; Crook, Derrick W.; Fitzpatrick, Fidelma; Hanberger, Håkan; Herwaldt, Loreen A.; Keulen, P. H. J. van; Kluytmans, Jan; Kola, Axel; Kuchenbecker, Ricardo; Lingaas, Egil; Meessen, N.E.L.; Morris-Downes, M.; Pottinger, Jean M.; Rohner, Peter; Santos, Rodrigo Pires dos; Seifert, Harald; Wisplinghoff, Hilmar; Ziesing, Stefan; Walker, A Sarah; Bonten, Marc J. M.

doi:10.1093/cid/cis1006

Cited by 149 publications

(110 citation statements)

References 16 publications

(16 reference statements)

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“…P. aeruginosa is the cause of a high percentage of nosocomial infections in critically ill patients. In the EPIC Ⅱ study Pseudomonas species caused 19.9% of infections in the ICU [1] while another multicenter study concerning bloodstream infections coming from 9 countries, showed that P. aeruginosa was the cause of bacteremia in 5.3% of cases [23] . Several mechanisms are implicated in the development of resistance in P. aeruginosa strains.…”

Section: P Aeruginosamentioning

confidence: 99%

Association between infections caused by multidrug-resistant gram-negative bacteria and mortality in critically ill patients

Paramythiotou

Routsi

2016

WJCCM

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The incidence of gram-negative multidrug-resistant (MDR) bacterial pathogens is increasing in hospitals and particularly in the intensive care unit (ICU) setting. The clinical consequences of infections caused by MDR pathogens remain controversial. The purpose of this review is to summarize the available data concerning the impact of these infections on mortality in ICU patients. Twenty-four studies, conducted exclusively in ICU patients, were identified through PubMed search over the years 2000-2015. Bloodstream infection was the only infection examined in eight studies, respiratory infections in four and variable infections in others. Comparative data on the appropriateness of empirical antibiotic treatment were provided by only seven studies. In ten studies the presence of antimicrobial resistance was not associated with increased mortality; on the contrary, in other studies a significant impact of antibiotic resistance on mortality was found, though, sometimes, mediated by inappropriate antimicrobial treatment. Therefore, a direct association between infections due to gram-negative MDR bacteria and mortality in ICU patients cannot be confirmed. Sample size, presence of multiple confounders and other methodological issues may influence the results. These data support the need for further studies to elucidate the real impact of infections caused by resistant bacteria in ICU patients.

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Section: P Aeruginosamentioning

confidence: 99%

Association between infections caused by multidrug-resistant gram-negative bacteria and mortality in critically ill patients

Paramythiotou

Routsi

2016

WJCCM

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“…stream infections, and they can have a mortality rate of 40 to 60% (3)(4)(5). Although bacteria are the predominant microorganisms, Candida species have emerged as one of the leading causes of hospital-acquired infections and are responsible for 80% of all nosocomial infections caused by fungi (6).…”

mentioning

confidence: 99%

β-(1,3)-Glucan Unmasking in Some Candida albicans Mutants Correlates with Increases in Cell Wall Surface Roughness and Decreases in Cell Wall Elasticity

et al. 2017

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Candida albicans is among the most common human fungal pathogens, causing a broad range of infections, including life-threatening systemic infections. The cell wall of C. albicans is the interface between the fungus and the innate immune system. The cell wall is composed of an outer layer enriched in mannosylated glycoproteins (mannan) and an inner layer enriched in ␤-(1,3)-glucan and chitin. Detection of C. albicans by Dectin-1, a C-type signaling lectin specific for ␤-(1,3)-glucan, is important for the innate immune system to recognize systemic fungal infections. Increased exposure of ␤-(1,3)-glucan to the immune system occurs when the mannan layer is altered or removed in a process called unmasking. Nanoscale changes to the cell wall during unmasking were explored in live cells with atomic force microscopy (AFM). Two mutants, the cho1Δ/Δ and kre5Δ/Δ mutants, were selected as representatives that exhibit modest and strong unmasking, respectively. Comparisons of the cho1Δ/Δ and kre5Δ/Δ mutants to the wild type reveal morphological changes in their cell walls that correlate with decreases in cell wall elasticity. In addition, AFM tips functionalized with Dectin-1 revealed that the forces of binding of Dectin-1 to all of the strains were similar, but the frequency of binding was highest for the kre5Δ/Δ mutant, decreased for the cho1Δ/Δ mutant, and rare for the wild type. These data show that nanoscale changes in surface topology are correlated with increased Dectin-1 adhesion and decreased cell wall elasticity. AFM, using tips functionalized with immunologically relevant molecules, can map epitopes of the cell wall and increase our understanding of pathogen recognition by the immune system.

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“…S. aureus has a particular propensity for developing multidrug resistance (e.g., methicillin-resistant S. aureus [MRSA] and vancomycin-intermediate S. aureus [VISA]), and serious infections with such strains result in enhanced attributable mortality (3).…”

mentioning

confidence: 99%

Frequency and Distribution of Single-Nucleotide Polymorphisms within mprF in Methicillin-Resistant Staphylococcus aureus Clinical Isolates and Their Role in Cross-Resistance to Daptomycin and Host Defense Antimicrobial Peptides

Bayer

Mishra

Chen

et al. 2015

Antimicrob Agents Chemother

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Staphylococcus aureus is the second leading cause of bacteremia worldwide and the most important pathogen in endovascular infections (1, 2). S. aureus has a particular propensity for developing multidrug resistance (e.g., methicillin-resistant S. aureus [MRSA] and vancomycin-intermediate S. aureus [VISA]), and serious infections with such strains result in enhanced attributable mortality (3).Since its FDA approval in 2003, daptomycin (DAP) has been utilized in many clinical settings, especially for recalcitrant MRSA infections, such as endocarditis (4-6). However, there have been a number of recently reported cases of clinical S. aureus strains that have evolved in vitro DAP resistance in the context of failing DAP treatment regimens, especially in endovascular syndromes. (Note that although the official term is daptomycin nonsusceptibility, we use the term daptomycin resistance in this paper for ease of presentation [7][8][9][10][11][12].) One of the major features of DAP-resistant (DAP r ) S. aureus strains is the acquisition of gain-in-function mutations in a relatively restricted cadre of genes, especially in the mprF locus (13-18). The MprF protein is responsible for the synthesis and translocation (flipping) of the unique positively charged phospholipid (PL) lysyl-phosphotidylglycerol (L-PG) from the inner-to-outer cell membrane (CM) leaflet (18)(19)(20). Increases in L-PG synthesis and flipping usually result in augmented positive surface charge; many investigators have speculated that this event leads to a charge-repulsive milieu for cationic molecules, such as host defense peptides (HDPs) and calcium-complexed DAP (13,(19)(20)(21)(22)(23). Over the past several years, a number of laboratories, including ours, have linked the presence of singlenucleotide polymorphisms (SNPs) within the mprF locus to the DAP r phenotype (13,14, 21,(24)(25)(26). These SNPs have occurred throughout the mprF open reading frame (ORF), although there are clearly hot spots within this locus for those SNPs linked to DAP resistance (13,14,19, 23). Investigations of mprF SNPs associated with DAP resistance in S. aureus have principally emerged from studies that used only a few or individual isogenic DAP-susceptible (DAP s ) and DAP r strain pairs. To address this limitation, in the current study, we assessed (i) the frequencies and distribution of putative mprF gain-in-function SNPs using 22 DAP s /DAP r isogenic clinical MRSA strain pairs, (ii) the relation-

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Secular Trends in Nosocomial Bloodstream Infections: Antibiotic-Resistant Bacteria Increase the Total Burden of Infection

Cited by 149 publications

References 16 publications

Association between infections caused by multidrug-resistant gram-negative bacteria and mortality in critically ill patients

Association between infections caused by multidrug-resistant gram-negative bacteria and mortality in critically ill patients

β-(1,3)-Glucan Unmasking in Some Candida albicans Mutants Correlates with Increases in Cell Wall Surface Roughness and Decreases in Cell Wall Elasticity

Frequency and Distribution of Single-Nucleotide Polymorphisms within mprF in Methicillin-Resistant Staphylococcus aureus Clinical Isolates and Their Role in Cross-Resistance to Daptomycin and Host Defense Antimicrobial Peptides

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