Declining Aminoglycoside (AG) Use and Associated Changes in Proportions and Rates of Gentamicin-Resistance (G-R) Among Gram-Negative Bacteria

Background: Few new drugs are under development for resistant gram-negative pathogens. We previously reported that mean AG antibiotic use declined significantly between 2002 and 2006 in 22 university hospitals (Arch Int Med 2008;168:2254-60). Declining AG use has previously been reported from single-centers to be accompanied by declining G-R for some organisms. AGs may be regaining activity against some gram-negative organisms, although this is not currently tracked by US surveillance programs.

Objective: To measure AG use in a consortium of academic medical centers and associated changes in G-R for selected organisms.

Methods: We measured individual and total AG use by Days of Therapy (DOT) per 1000 patient days (PD) for 2002-2008 in 26 US academic medical centers that participate in the University HealthSystem Consortium (UHC) Clinical Resource Manager (CRM). We obtained annual hospital-wide antibiograms and examined G-R by proportions (% G-R) and incidence rates (number G-R /1000 PD) for P. aeruginosa, A. baumannii, K. pneumoniae and E.coli. Mixed model repeated measures ANOVA assessed changes in use and resistance over time.

Results: Gentamicin represented 62% of total AG use for the study period; tobramycin was 29% and amikacin was 9%. Total mean AG use declined by 34% (range = 0 to 72%) during the study period (Figure) driven by decreasing gentamicin use (p<.001); amikacin and tobramycin did not significantly change. The mean proportion of G-R P. aeruginosa decreased 25%, from 28% in 2002 to 21% in 2008 (p=.005); G-R E. coli increased 100%, from 5% to 10% (p=.0001);  K. pneumoniae and A. baumannii  did not change. The rates of G-R P. aeruginosa declined 45% over the study period (Figure, p<.0001); E. coli increased 127% (p<0.0001), K. pneumonie and A. baumannii did not significantly change.

Conclusions: AG use continues to decline in this sample of academic medical centers, and is paralleled by a decline in G-R P. aeruginosa.  However, G-R among E. coli is increasing and has not changed for K. pneumoniae and A. baumannii.