Human Cathelicidin LL-37 Resistance and Increased Daptomycin MIC in Methicillin-Resistant Staphylococcus aureus Strain USA600 (ST45) Are Associated with Increased Mortality in a Hospital Setting

Sakoulas, George; Guram, Kripa; Reyes, Katherine; Nizet, Victor; Zervos, Marcus J.

doi:10.1128/jcm.00189-14

Cited by 17 publications

(13 citation statements)

References 21 publications

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“…In order to minimize the potential for confounding phylogenetic differences, we focused on ST45/USA600 MRSA, a lineage found in Detroit, Michigan that is associated with increased all-cause mortality [16]. Forty-four well-characterized sequential ST45/USA600 isolates with documented clinical outcomes [17] were identified and selected for this study. Of these 44 isolates, 21 were isolated from patients who survived the infection, and 23 were isolated from decedents.…”

Section: Methodsmentioning

confidence: 99%

Reduced Production of Bacterial Membrane Vesicles Predicts Mortality in ST45/USA600 Methicillin-Resistant Staphylococcus aureus Bacteremia

et al. 2019

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Immune biomarkers can stratify mortality risk in staphylococcal bacteremia. Microbial biomarkers may provide more consistent signals during early infection. We demonstrate that in ST45/USA600 bacteremia, bacterial membrane vesicle production in vitro predicts clinical mortality (773 vs. 116 RFU, survivors vs. decedents, p < 0.0001). Using a threshold of 301 relative fluorescence units (RFU), the sensitivity and specificity of the membrane vesicles to predict mortality are 78% and 90%, respectively. This platform is facile, scalable and can be integrated into clinical microbiology lab workflows.

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Section: Methodsmentioning

confidence: 99%

Reduced Production of Bacterial Membrane Vesicles Predicts Mortality in ST45/USA600 Methicillin-Resistant Staphylococcus aureus Bacteremia

et al. 2019

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“…In stark contrast to vancomycin, which enjoyed decades of resistance-free use, alternative therapies like daptomycin, linezolid, telavancin, third generation cephalosporins (for example, ceftaroline) and the glycylcycline tigecycline antibiotic classes have led to resistance soon after their clinical introduction. 110 Resistance via impediment of glycopeptide access A significant body of work has been devoted to the identification of mutations delineating the genetic differences between VSSA and VISA. 79,83,111,112 Although considerable genetic and transcriptional variability between different lineages results in a myriad of phenotypic outcomes, cell wall aberrations are a feature observed consistently in response to the physiological stress imposed by antibiotic treatment.…”

Section: Vancomycin Resistance and Heteroresistancementioning

confidence: 99%

Glycopeptide antibiotics: Back to the future

et al. 2014

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Glycopeptide antibiotics have been a key weapon in the fight against bacterial infections for over half a century, with the progenitors, vancomycin (1) and teicoplanin (2), still used extensively. The increased occurrence of resistance and the effectiveness of these 'last resort' treatments for Gram-positive infections has led to the discovery and clinical development of second generation, semisynthetic lipoglycopeptide derivatives such as telavancin (3), dalbavancin (4) and oritavancin (5), which all possess broader spectra of activity and improved pharmacokinetic properties. Two of these new antibiotics, telavancin (3) and dalbavancin (4), were approved in the past 5 years and the third, oritavancin (5), is awaiting regulatory approval. In this review, the discovery, development and associated resistance of vancomycin (1) and teicoplanin (2), and semi-synthetic glycopeptides, telavancin (3), dalbavancin (4) and oritavancin (5), are detailed. The clinical implications of glycopeptide resistance, especially vancomycin (1), as well as the future prospects for current glycopeptide drugs and the development of new glycopeptides are discussed.

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“…Comparison of MSSA with MRSA strains revealed that MRSA strains were less susceptible to AMPs (15). Indeed, numerous studies have shown a correlation between methicillin and human cathelicidin LL-37 resistance (76,88,108). Moreover, staphylococcal metalloproteinase aureolysin can cleave LL-37, and iron-regulated surface protein A (isdA) can impart resistance to human β-defensin 2 (13,95).…”

Section: Staphylococcus Pseudintermediusmentioning

confidence: 99%

Staphylococcus pseudintermedius, both commensal and pathogen

Chrobak-Chmiel¹,

Golke²,

Dembele³

et al. 2018

Medycyna Weterynaryjna

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Staphylococcus pseudintermedius is considered to be a both commensal and opportunistic canine pathogen. The anal, perineal and nasal locations appear to be the main S. pseudintermedius colonization sites, from which bacteria are transmitted to other body sites, causing secondary infections. When the immune system is compromised because of an underlying condition, the skin becomes susceptible to infection. Thus, the host’s condition seems to play a crucial role in the pathogenesis of S. pseudintermedius infections. There are some predisposing factors, one of which is atopic dermatitis. The pathogenic effects of S. pseudintermedius are mediated by several virulence factors, for instance superantigens, which play an important role by causing dermatitis. The immune system has evolved many different mechanisms to recognize and deal with pathogens, but bacteria have also developed various strategies to evade them. In this review, we focus on early stages of the innate immune response with particular emphasis on the mechanisms of recognition of staphylococci and the action of antimicrobial peptides. .

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Human Cathelicidin LL-37 Resistance and Increased Daptomycin MIC in Methicillin-Resistant Staphylococcus aureus Strain USA600 (ST45) Are Associated with Increased Mortality in a Hospital Setting

Cited by 17 publications

References 21 publications

Reduced Production of Bacterial Membrane Vesicles Predicts Mortality in ST45/USA600 Methicillin-Resistant Staphylococcus aureus Bacteremia

Reduced Production of Bacterial Membrane Vesicles Predicts Mortality in ST45/USA600 Methicillin-Resistant Staphylococcus aureus Bacteremia

Glycopeptide antibiotics: Back to the future

Staphylococcus pseudintermedius, both commensal and pathogen

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