Background: When grown in human serum, laboratory isolates of Pseudomonas aeruginosa exhibit tolerance to antibiotics at inhibitory concentrations. This phenomenon, known as serum-associated antibiotic tolerance (SAT), could lead to clinical treatment failure of pseudomonal infections. Our purpose in this study was to determine the prevalence and clinical impact of SAT in Pseudomonas isolates in hospitalized children.
Methods: The SAT phenotype was assessed in patients aged <18 years admitted with respiratory or blood cultures positive for P. aeruginosa. The SAT phenotype was a priori defined as a ≥2-log increase in colony-forming units when grown in human serum compared with Luria-Bertani medium in the presence of minocycline or tobramycin.
Results: SAT was detected in 29 (64%) patients. Fourteen patients each (34%) had cystic fibrosis (CF) and tracheostomies. Patient demographics and comorbidities did not differ by SAT status. Among CF patients, SAT was associated with longer duration of intravenous antibiotics (10 days vs 5 days; P < .01).
Conclusions: This study establishes that SAT exists in P. aeruginosa from human serum and may be a novel factor that contributes to differences in clinical outcomes. Future research should investigate the mechanisms that contribute to SAT in order to identify novel targets for adjunctive antimicrobial therapies.
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http://dx.doi.org/10.1093/jpids/piz094 | DOI Listing |
Antibiotics (Basel)
July 2023
Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, NY 14642, USA.
is a nosocomial pathogen of serious healthcare concern that is becoming increasingly difficult to treat due to antibiotic treatment failure. Recent studies have revealed that clinically defined antibiotic-susceptible strains upregulate the expression of a repertoire of putative drug efflux pumps during their growth under biologically relevant conditions, e.g.
View Article and Find Full Text PDFFront Vet Sci
February 2022
National Risk Assessment Laboratory for Antimicrobial Resistance of Animal Original Bacteria, College of Veterinary Medicine, South China Agricultural University, Guangzhou, China.
Danofloxacin is a synthetic fluoroquinolone with broad-spectrum activity developed for use in veterinary medicine. The aim of this study was to evaluate the pharmacokinetic/pharmacodynamic (PK/PD) targets, PK/PD cutoff values and the optimum doses of danofloxacin against and in piglets. Single dose serum pharmacokinetics was determined in piglets after intravenous and intramuscular administration of 2.
View Article and Find Full Text PDFPathogens
November 2021
Department of Microbial Pathogenesis and Immunology, Texas A&M Health Science Center, Bryan, TX 77807, USA.
Our understanding of how the host immune system thwarts bacterial evasive mechanisms remains incomplete. Here, we show that host protease neutrophil elastase acts on and to destroy factors that prevent serum-associated, complement-directed killing. The protease activity also enhances bacterial susceptibility to antibiotics in sera.
View Article and Find Full Text PDFChemMedChem
September 2020
Department of Medicinal Chemistry and Molecular Pharmacology College of Pharmacy, Purdue University, 575 Stadium Mall Dr., West Lafayette, IN, 47907.
Acinetobacter baumannii is a nosocomial pathogen of urgent concern for public health due to rising rates of multidrug and pandrug resistance. In the context of environmental cues such as growth in human serum, A. baumannii is known to display adaptive efflux, in which a multitude of efflux-associated genes are upregulated, resulting in efflux-mediated drug tolerance in strains that are otherwise susceptible to antibiotic therapy.
View Article and Find Full Text PDFBMC Vet Res
March 2020
National Risk Assessment Laboratory for Antimicrobial Resistance of Animal Original Bacteria, College of Veterinary Medicine, South China Agricultural University, Guangzhou, China.
Background: Gamithromycin is a macrolide approved for the treatment of bovine and swine respiratory diseases. Our study aims to establish the clinical breakpoint and optimum dose regimen for gamithromycin against Haemophilus parasuis in piglets.
Results: Gamithromycin was well absorbed and fully bioavailable (87.
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