Antimicrobial Susceptibility Testing in Cystic Fibrosis — An Unfortunate Failure
By Stan Deresinski, MD, FACP, FIDSA
Clinical Professor of Medicine, Stanford University
Dr. Deresinski reports no financial relationships relevant to this field of study.
SYNOPSIS: The results of antimicrobial susceptibility testing of respiratory isolates from patients with cystic fibrosis failed to predict outcomes of antibiotic therapy.
SOURCE: Somayaji R, Parkins MD, Shah A, et al; Antimicrobial Resistance in Cystic Fibrosis International Working Group. Antimicrobial susceptibility testing (AST) and associated clinical outcomes in individuals with cystic fibrosis: A systematic review. J Cyst Fibros 2019;18:236-243.
Somayaji and colleagues, on behalf of the Antimicrobial Resistance in Cystic Fibrosis International Working Group, examined the ability of antimicrobial susceptibility testing to predict the results of antibiotic therapy in patients with cystic fibrosis (CF), as well as whether this predictive value was affected by the testing method. They identified 20 studies that met their criteria, most of which dealt with Pseudomonas aeruginosa. Thirteen of the studies dealt with the treatment of pulmonary exacerbations and the rest with maintenance therapy.
Of the 16 studies addressing the overall issue of the predictive value of susceptibility testing regardless of the method used, 13 found no benefit. Four studies addressed the methodology question, and none found evidence of a positive effect. The methods evaluated included bactericidal combination (as many as four agents at once) antibiograms as well as the testing of organisms growing as biofilm.
This analysis indicates that in vitro antimicrobial susceptibility testing fails to provide guidance to the clinician regarding antibiotic therapy of pulmonary infections in patients with CF. A large retrospective study in children with CF that was published too recently to be included in this analysis involved 6,451 pulmonary exacerbations, for which 2,518 susceptibility tests were performed. Similarly, this study failed to detect the benefit of such testing.1 It should be recognized that the study by Somayaji and colleagues was largely confined to infections with P. aeruginosa, and the results may not apply to, e.g., Staphylococcus aureus infections.
Several reasons may account for these findings.2 These include the frequent polymicrobial nature of the infections, the presence of heteroresistance, the presence of persisters, the growth in biofilm, and the segregated growth within microenvironments. Additionally, the administration of antibiotics by inhalation further confounds the issue. The results reviewed here are consistent with the admonition by Waters and colleagues that the best guide for the clinician is the clinical response, not the in vitro susceptibility results. When the latter indicates resistance to the administered antibiotic but the patient is clinically improved, the susceptibility results should be ignored.
- Cogen JD, Whitlock KB, Gibson RL, et al. The use of antimicrobial susceptibility testing in pediatric cystic fibrosis pulmonary exacerbations. J Cyst Fibros 2019 May 28. doi: 10.1016/j.jcf.2019.05.012. [Epub ahead of print].
- Waters VJ, Kidd TJ, Canton R, et al; Antimicrobial Resistance International Working Group in Cystic Fibrosis. Reconciling antimicrobial susceptibility testing and clinical response in antimicrobial treatment of chronic cystic fibrosis lung infections. Clin Infect Dis 2019;69:1812-1816.
The results of antimicrobial susceptibility testing of respiratory isolates from patients with cystic fibrosis failed to predict outcomes of antibiotic therapy.
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