Genomics of Aminoglycoside Resistance in Pseudomonas aeruginosa Bloodstream Infections at a United States Academic Hospital

Pseudomonas aeruginosa is a frequent cause of antibiotic-resistant infections. Although P. aeruginosa is intrinsically resistant to many antimicrobial agents, aminoglycosides are active against this organism in the absence of acquired resistance determinants and mutations. However, genes encoding aminoglycoside modifying enzymes (AMEs) are found in many strains that are resistant to these agents. We examined the prevalence of phenotypic resistance to the commonly used aminoglycosides gentamicin, tobramycin, and amikacin in a collection of 227 P. aeruginosa bloodstream isolates collected over two decades from a single U.S. academic medical institution. Resistance to these antibiotics was relatively stable over this time period. High-risk clones ST111 and ST298 were initially common but decreased in frequency over time. Whole genome sequencing identified relatively few AME genes in this collection compared to the published literature; only 14% of isolates contained an AME gene other than the ubiquitous aph(3’)-IIb . Of those present, only ant(2”)-Ia was associated with phenotypic resistance to gentamicin or to tobramycin. One extensively drug-resistant strain, PS1871, contained 5 AME genes, most of which were part of clusters of antibiotic resistance genes embedded within transposable elements. These findings suggest that AME genes play a relatively minor role in aminoglycoside resistance at our institution but that multidrug-resistant strains remain a problem.