scholarly journals Rapid Emergence of Resistance to Linezolid and Mutator Phenotypes in Staphylococcus aureus Isolates from an Adult Cystic Fibrosis Patient

2013 ◽  
Vol 57 (10) ◽  
pp. 5186-5188 ◽  
Author(s):  
Asmaa Tazi ◽  
Jeanne Chapron ◽  
Gerald Touak ◽  
Magalie Longo ◽  
Dominique Hubert ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Staphylococcus Aureus ◽  
Cystic Fibrosis Patient ◽  
Therapeutic Option ◽  
Clinical Isolates ◽  
23S Rrna ◽  
Mutator Phenotype ◽  
Content Type ◽  
Emergence Of Resistance ◽  
Rapid Emergence

ABSTRACTLinezolid has emerged as an important therapeutic option for the treatment ofStaphylococcus aureusin patients with cystic fibrosis. We report the rapid emergence, upon treatment with linezolid, of linezolid-resistantS. aureusclinical isolates through the accumulation of resistance-associated 23S rRNA mutations, together with acquisition of an altered mutator phenotype.

scholarly journals Activity of Telavancin against Staphylococcus aureus Isolates, Including Those with Decreased Susceptibility to Ceftaroline, from Cystic Fibrosis Patients

2018 ◽  
Vol 62 (9) ◽  
Author(s):  
Melanie Roch ◽  
Maria Celeste Varela ◽  
Agustina Taglialegna ◽  
Warren E. Rose ◽  
Adriana E. Rosato
Keyword(s):  
Cystic Fibrosis ◽  
Staphylococcus Aureus ◽  
Galleria Mellonella ◽  
Therapeutic Option ◽  
The United States ◽  
Infection Model ◽  
Content Type ◽  
Complicated Skin ◽  
Hospital Acquired

ABSTRACT Methicillin-resistant Staphylococcus aureus (MRSA) acquisition in cystic fibrosis (CF) patients confers a clinical outcome worse than that in non-CF patients with an increased rate of declined lung function. Telavancin, an approved lipoglycopeptide used to treat infections due to S. aureus, has a dual mode of action causing inhibition of peptidoglycan synthesis and membrane depolarization. MRSA infections in CF patients remain an important problem with no foreseeable decline in prevalence rates. Although telavancin is currently in clinical use for the treatment of complicated skin infections and hospital-acquired pneumonia, the activity against S. aureus infections in CF patients has not been investigated. In this work, we studied the activity of telavancin against CF patient-derived S. aureus strains collected from geographically diverse CF centers in the United States. We found that the telavancin MIC90 was 0.06 μg/ml, 8-fold lower than the ceftaroline or daptomycin MIC90 and 25-fold lower than the linezolid and vancomycin MIC90. We demonstrate that telavancin at serum free concentrations has rapid bactericidal activity, with a decrease of more than 3 log10 CFU/ml being achieved during the first 4 to 6 h of treatment, performing better in this assay than vancomycin and ceftaroline, including against S. aureus strains resistant to ceftaroline. Telavancin resistance was infrequent (0.3%), although we found that it can occur in vitro in both CF- and non-CF patient-derived S. aureus strains by progressive passages with subinhibitory concentrations. Genetic analysis of telavancin-resistant in vitro mutants showed gene polymorphisms in cell wall and virulence genes and increased survival in a Galleria mellonella infection model. Thus, we conclude that telavancin represents a promising therapeutic option for infections in CF patients with potent in vitro activity and a low resistance development potential.

scholarly journals Detection of Linezolid-Resistant Staphylococcus aureus with 23S rRNA and Novel L4 Riboprotein Mutations in a Cystic Fibrosis Patient in Spain

2013 ◽  
Vol 57 (5) ◽  
pp. 2428-2429 ◽  
Author(s):  
Federico Román ◽  
Carolina Roldán ◽  
Pilar Trincado ◽  
Carmen Ballesteros ◽  
Concepción Carazo ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Staphylococcus Aureus ◽  
Cystic Fibrosis Patient ◽  
23S Rrna

scholarly journals Emergence ofcfr-Mediated Linezolid Resistance in a Methicillin-Resistant Staphylococcus aureus Epidemic Clone Isolated from Patients with Cystic Fibrosis

2015 ◽  
Vol 60 (3) ◽  
pp. 1878-1882 ◽  
Author(s):  
Juan de Dios Caballero ◽  
María Dolores Pastor ◽  
Ana Vindel ◽  
Luis Máiz ◽  
Genoveva Yagüe ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Staphylococcus Aureus ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
23S Rrna ◽  
Epidemic Clone ◽  
Methicillin Resistant ◽  
Content Type ◽  
Linezolid Resistance

Resistance to linezolid (LZD) in methicillin-resistantStaphylococcus aureus(MRSA) isolates from patients with cystic fibrosis (CF) is due mainly to ribosomal mutations. We report on four CF patients with LZD-resistant MRSA bronchopulmonary infections by strains carrying thecfrgene. Strains from one patient also harbored the G2576U mutation (23S rRNA) and the G139R substitution (L3 protein). All strains belonged to the epidemic clone ST125 MRSA IVc. Our results support the monitoring of LZD resistance emergence in CF and non-CF MRSA isolates.

scholarly journals Pseudomonas aeruginosa PA14 Enhances the Efficacy of Norfloxacin against Staphylococcus aureus Newman Biofilms

2020 ◽  
Vol 202 (18) ◽  
Author(s):  
Giulia Orazi ◽  
Fabrice Jean-Pierre ◽  
George A. O’Toole
Keyword(s):  
Cystic Fibrosis ◽  
Staphylococcus Aureus ◽  
Pseudomonas Aeruginosa ◽  
Antimicrobial Agents ◽  
Respiratory Infections ◽  
Multiple Infection ◽  
Bacterial Biofilms ◽  
Interspecies Interactions ◽  
Chronic Infections ◽  
Content Type

ABSTRACT The thick mucus within the airways of individuals with cystic fibrosis (CF) promotes frequent respiratory infections that are often polymicrobial. Pseudomonas aeruginosa and Staphylococcus aureus are two of the most prevalent pathogens that cause CF pulmonary infections, and both are among the most common etiologic agents of chronic wound infections. Furthermore, the ability of P. aeruginosa and S. aureus to form biofilms promotes the establishment of chronic infections that are often difficult to eradicate using antimicrobial agents. In this study, we found that multiple LasR-regulated exoproducts of P. aeruginosa, including 2-heptyl-4-hydroxyquinoline N-oxide (HQNO), siderophores, phenazines, and rhamnolipids, likely contribute to the ability of P. aeruginosa PA14 to shift S. aureus Newman norfloxacin susceptibility profiles. Here, we observe that exposure to P. aeruginosa exoproducts leads to an increase in intracellular norfloxacin accumulation by S. aureus. We previously showed that P. aeruginosa supernatant dissipates the S. aureus membrane potential, and furthermore, depletion of the S. aureus proton motive force recapitulates the effect of the P. aeruginosa PA14 supernatant on shifting norfloxacin sensitivity profiles of biofilm-grown S. aureus Newman. From these results, we hypothesize that exposure to P. aeruginosa PA14 exoproducts leads to increased uptake of the drug and/or an impaired ability of S. aureus Newman to efflux norfloxacin. Surprisingly, the effect observed here of P. aeruginosa PA14 exoproducts on S. aureus Newman susceptibility to norfloxacin seemed to be specific to these strains and this antibiotic. Our results illustrate that microbially derived products can alter the ability of antimicrobial agents to kill bacterial biofilms. IMPORTANCE Pseudomonas aeruginosa and Staphylococcus aureus are frequently coisolated from multiple infection sites, including the lungs of individuals with cystic fibrosis (CF) and nonhealing diabetic foot ulcers. Coinfection with P. aeruginosa and S. aureus has been shown to produce worse outcomes compared to infection with either organism alone. Furthermore, the ability of these pathogens to form biofilms enables them to cause persistent infection and withstand antimicrobial therapy. In this study, we found that P. aeruginosa-secreted products dramatically increase the ability of the antibiotic norfloxacin to kill S. aureus biofilms. Understanding how interspecies interactions alter the antibiotic susceptibility of bacterial biofilms may inform treatment decisions and inspire the development of new therapeutic strategies.

scholarly journals In Vitro Activity of Rifamycin Derivatives against Nontuberculous Mycobacteria, Including Macrolide- and Amikacin-Resistant Clinical Isolates

2021 ◽  
Vol 65 (5) ◽  
Author(s):  
Dae Hun Kim ◽  
Su-Young Kim ◽  
Hee Jae Huh ◽  
Nam Yong Lee ◽  
Won-Jung Koh ◽  
...  
Keyword(s):  
Mycobacterium Avium ◽  
Nontuberculous Mycobacteria ◽  
Therapeutic Option ◽  
Vitro Activity ◽  
Clinical Isolates ◽  
Drug Resistant ◽  
In Vitro Activity ◽  
Content Type ◽  
Resistant Disease

ABSTRACT We evaluated the in vitro activity of rifamycin derivatives, including rifampin, rifapentine, rifaximin, and rifabutin, against clinical nontuberculous mycobacteria (NTM) isolates. Of the rifamycin derivatives, rifabutin showed the lowest MICs against all NTM species, including Mycobacterium avium complex, M. abscessus, and M. kansasii. Rifabutin also had effective in vitro activity against macrolide- and aminoglycoside-resistant NTM isolates. Rifabutin could be worth considering as a therapeutic option for NTM disease, particularly drug-resistant disease.

scholarly journals Complete Genome Sequence of Pseudomonas aeruginosa Strain AA2 (LMG 27630), an Early Isolate Recovered from the Airway of a German Cystic Fibrosis Patient

2020 ◽  
Vol 9 (26) ◽  
Author(s):  
Andrea Sass ◽  
Tom Coenye
Keyword(s):  
Cystic Fibrosis ◽  
Pseudomonas Aeruginosa ◽  
Respiratory Tract ◽  
Cystic Fibrosis Patient ◽  
Genome Sequence ◽  
Complete Genome Sequence ◽  
Opportunistic Pathogen ◽  
Content Type ◽  
Airway Infections ◽  
Early Isolate

ABSTRACT Pseudomonas aeruginosa is an opportunistic pathogen that is able to cause various infections, including airway infections in cystic fibrosis patients. Here, we present the complete closed and annotated genome sequence of P. aeruginosa AA2, an isolate obtained early during infection of the respiratory tract of a German cystic fibrosis patient.

scholarly journals Efficacy of Fosfomycin Compared to Vancomycin in Treatment of Implant-Associated Chronic Methicillin-Resistant Staphylococcus aureus Osteomyelitis in Rats

2014 ◽  
Vol 58 (9) ◽  
pp. 5111-5116 ◽  
Author(s):  
Wolfgang Poeppl ◽  
Tilman Lingscheid ◽  
Dominik Bernitzky ◽  
Uwe Y. Schwarze ◽  
Oliver Donath ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Drug Control ◽  
Once Daily ◽  
Methicillin Resistant ◽  
Content Type ◽  
Titanium Wire ◽  
Experimental Rat Model ◽  
Vancomycin Group ◽  
Emergence Of Resistance

ABSTRACTFosfomycin monotherapy was compared to therapy with vancomycin for the treatment of implant-associated methicillin-resistantStaphylococcus aureus(MRSA) osteomyelitis in an experimental rat model. The proximal tibiae were inoculated with 15 μl of a suspension containing 1 × 108to 5 × 108CFU/ml of a clinical isolate of MRSA with simultaneous insertion of a titanium wire. Four weeks later, treatment was started for 28 days with either 50 mg/kg of body weight vancomycin intraperitoneally twice daily (n= 11) or 75 mg/kg fosfomycin intraperitoneally once daily (n= 10). Eleven animals were left untreated. After treatment, quantitative cultures from bone were found to be positive for MRSA in all animals in the untreated group (median, 3.29 × 106CFU/g of bone) and the vancomycin group (median, 3.03 × 105CFU/g of bone). In the fosfomycin group, MRSA was detectable in 2 out of 10 (20%) animals (3.42 × 102and 1.51 × 103CFU/g of bone). Vancomycin was superior to the no-drug control (P= 0.002), and fosfomycin was superior to the no-drug control and vancomycin (P< 0.001). The cultures from the wires were positive in all untreated animals (median, 2.5 × 103CFU/implant), in 10 animals in the vancomycin group (median, 1.15 × 103CFU/implant), and negative in all animals in the fosfomycin group. Based on the bacterial counts from the implants, vancomycin was not superior to the no-drug control (P= 0.324), and fosfomycin was superior to the no-drug control and vancomycin (P< 0.001). No emergence of resistance was observed. In conclusion, it was demonstrated that fosfomycin monotherapy is highly effective for the treatment of experimental implant-associated MRSA osteomyelitis.

scholarly journals Pseudomonas aeruginosa Alginate Benefits Staphylococcus aureus?

2020 ◽  
Vol 202 (8) ◽  
Author(s):  
Michael J. Schurr
Keyword(s):  
Cystic Fibrosis ◽  
Staphylococcus Aureus ◽  
Pseudomonas Aeruginosa ◽  
Cell Membrane ◽  
Membrane Integrity ◽  
Partial Explanation ◽  
Content Type ◽  
First Report ◽  
Cell Membrane Integrity ◽  
Link Type

ABSTRACT In this issue of Journal of Bacteriology, Price et al. show that the Pseudomonas aeruginosa-produced exopolysaccharide alginate protects Staphylococcus aureus by dampening the expression of P. aeruginosa virulence products that usually inhibit S. aureus respiration and cell membrane integrity when the two organisms compete in other environments (C. E. Price, D. G. Brown, D. H. Limoli, V. V. Phelan, and G. A. O’Toole, J Bacteriol 202:e00559-19, 2020, https://doi.org/10.1128/jb.00559-19). This is the first report that exogenously added alginate affects P. aeruginosa competition and provides a partial explanation for S. aureus and P. aeruginosa coinfections in cystic fibrosis.

scholarly journals The Ancestral N-Terminal Domain of Big Defensins Drives Bacterially Triggered Assembly into Antimicrobial Nanonets

mBio ◽  
2019 ◽  
Vol 10 (5) ◽  
Author(s):  
Karine Loth ◽  
Agnès Vergnes ◽  
Cairé Barreto ◽  
Sébastien N. Voisin ◽  
Hervé Meudal ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Antimicrobial Activity ◽  
Bactericidal Activity ◽  
Multidrug Resistant ◽  
High Salt ◽  
Clinical Isolates ◽  
Host Defense Peptides ◽  
Hydrophobic Domain ◽  
Content Type ◽  
Terminal Domain

ABSTRACT Big defensins, ancestors of β-defensins, are composed of a β-defensin-like C-terminal domain and a globular hydrophobic ancestral N-terminal domain. This unique structure is found in a limited number of phylogenetically distant species, including mollusks, ancestral chelicerates, and early-branching cephalochordates, mostly living in marine environments. One puzzling evolutionary issue concerns the advantage for these species of having maintained a hydrophobic domain lost during evolution toward β-defensins. Using native ligation chemistry, we produced the oyster Crassostrea gigas BigDef1 (Cg-BigDef1) and its separate domains. Cg-BigDef1 showed salt-stable and broad-range bactericidal activity, including against multidrug-resistant human clinical isolates of Staphylococcus aureus. We found that the ancestral N-terminal domain confers salt-stable antimicrobial activity to the β-defensin-like domain, which is otherwise inactive. Moreover, upon contact with bacteria, the N-terminal domain drives Cg-BigDef1 assembly into nanonets that entrap and kill bacteria. We speculate that the hydrophobic N-terminal domain of big defensins has been retained in marine phyla to confer salt-stable interactions with bacterial membranes in environments where electrostatic interactions are impaired. Those remarkable properties open the way to future drug developments when physiological salt concentrations inhibit the antimicrobial activity of vertebrate β-defensins. IMPORTANCE β-Defensins are host defense peptides controlling infections in species ranging from humans to invertebrates. However, the antimicrobial activity of most human β-defensins is impaired at physiological salt concentrations. We explored the properties of big defensins, the β-defensin ancestors, which have been conserved in a number of marine organisms, mainly mollusks. By focusing on a big defensin from oyster (Cg-BigDef1), we showed that the N-terminal domain lost during evolution toward β-defensins confers bactericidal activity to Cg-BigDef1, even at high salt concentrations. Cg-BigDef1 killed multidrug-resistant human clinical isolates of Staphylococcus aureus. Moreover, the ancestral N-terminal domain drove the assembly of the big defensin into nanonets in which bacteria are entrapped and killed. This discovery may explain why the ancestral N-terminal domain has been maintained in diverse marine phyla and creates a new path of discovery to design β-defensin derivatives active at physiological and high salt concentrations.

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