Serum-Associated Antibiotic Tolerance in Pediatric Clinical Isolates of Pseudomonas aeruginosa

Author:

Morrison John M12,Chojnacki Michaelle3,Fadrowski Jeffrey J4,Bauza Colleen5,Dunman Paul M3,Dudas Robert A12ORCID,Goldenberg Neil A6,Berman David M7

Affiliation:

1. Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA

2. Department of Medicine, Division of Hospital Medicine, Johns Hopkins All Children’s Hospital, St. Petersburg, Florida, USA

3. Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, New York, USA

4. Department of Pediatrics, Division of Nephrology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA

5. Department of Health Informatics, Johns Hopkins All Children’s Hospital, St. Petersburg, Florida, USA

6. Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA, and All Children’s Research Institute, Johns Hopkins All Children’s Hospital, St. Petersburg, Florida, USA

7. Department of Medicine, Division of Infectious Diseases, Johns Hopkins All Children’s Hospital, St. Petersburg, Florida, USA

Abstract

Abstract 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.

Funder

Johns Hopkins All Children’s Foundation

National Institutes of Health

Publisher

Oxford University Press (OUP)

Subject

Infectious Diseases,General Medicine,Pediatrics, Perinatology, and Child Health

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