UCLA

ABSTRACT OF THE DISSERTATION

Approaches for Improving Antimicrobial Stewardship Programs

by

Olivia Ellis

Doctor of Philosophy in Environmental Health Sciences

University of California, Los Angeles, 2020

Professor Hilary Godwin, Co-Chair

Professor Richard Ambrose, Co-Chair

ABSTRACT OF THE DISSERTATION

Approaches for Improving Antimicrobial Stewardship Programs

by

Olivia Ellis

Doctor of Philosophy in Environmental Health Sciences

University of California, Los Angeles, 2020

Professor Hilary Godwin, Co-Chair

Professor Richard Ambrose, Co-Chair

The overarching objective of the work described in this thesis is to explore approaches for improving Antimicrobial Stewardship Programs (ASPs) in clinical settings. Three discrete topics were explored: (1) using an Adenosine Triphosphate (ATP) assay to evaluate differences in bioburden and cleaning efficiency between surface types in operating rooms; (2) validating the use of a PCR-based assay to be used to tailor treatment recommendations for patients with Neisseria gonorrhoeae; and (3) investigation of antimicrobial susceptibility trends of Stenotrophomonas maltophilia in a health system over time to provide insights into whether treatment guidelines for S. maltophilia need to be changed.

First, a commercial ATP detection assay was used to detect differences between the cleanliness of individual high touch surface types in operating rooms. This ATP testing assay revealed that irregularly shaped, uncovered surfaces (keyboards, overhead lights, and door handles) tend to harbor a larger bioburden than regularly shaped, covered surfaces (tables and mattresses). Additionally, surfaces were more likely to fail by ATP assay than by traditional Replicate Organism and Detection Plating (RODAC) methods. However, the majority of rooms (92%, 22/24) had least one surface that exceeded the 250 RLU threshold after turnaround cleaning via the ATP assay. Additionally, 42% (10/24) of the rooms had at least on surface that didn’t pass as clean after turnaround cleaning via the RODAC surface sample test. This study suggests that further experimentation to determine whether single use covers for irregularly shaped surfaces in operating rooms could reduce bioburden.

In the second study reported in this thesis, a Real Time-Polymerase Chain Reaction (RT-PCR) assay for detecting ciprofloxacin-susceptible Neisseria gonorrhoeae was validated at three locations: Los Angeles (UCLA), San Francisco Public Health Lab (SFPHL), and Philadelphia Public Health Lab (PPHL). In this study, clinical specimens that had tested positive for Neisseria gonorrhoeae by Nucleic Acid Amplification Testing (NAAT) were further tested for susceptibility to ciprofloxacin using the validated RT-PCR assay that can detect a mutation in the gyrase A (gyrA) gene, which confers resistance to ciprofloxacin. At UCLA, 57% (n=319/557) of the specimens that could be genotyped were gyrA Wild Type (WT). At SFPHL, 72% (n=134/185) of the genotyped specimens were WT and at PPHL, 64% (27/42) were WT. The goal of this study was to validate an Antimicrobial Susceptibility Test (AST) that would allow clinicians to more rapidly tailor treatment for patients with ciprofloxacin susceptible gonorrhea. We also assessed the utility of this assay for different samples types at different laboratories. For instance, the proportion of indeterminate N. gonorrhoeae varied significantly by testing laboratory and anatomical source (p < 0.00001, χ2 = 28.7). Therefore, post hoc pairwise Fisher’s exact statistical testing was performed. There was a statistically significant number of indeterminate rectal and pharyngeal specimens between UCLA and SFPHL for (p < 0.05, P= 0.0016) as well as indeterminate urine and pharyngeal (p < 0.05, P = 0.02). The number of indeterminate pharyngeal and urine and indeterminate rectal and urine specimens also varied significantly between SFPHL and PPHL, respectively (p < 0.05, P = 0.0013 and p < 0.05, P = 0.0221).

The third study reported in this thesis explores antibiotic treatment options for Stenotrophomonas maltophilia, which is an intrinsically multi-drug-resistant organism that poses an increasing threat to the health of immunocompromised patients in hospital settings. Antimicrobial susceptibility trends of Stenotrophomonas maltophilia isolates from a single health system were analyzed to elucidate possible trends in antimicrobial resistance over time. While resistance to trimethoprim-sulfamethoxazole (Bactrim) has been reported globally, 98% of all specimens tested at the health system between 2009-2018 were susceptible to Bactrim. 99% of all isolates tested were also susceptible to minocycline monotherapy. These antibiotics also show the most susceptibility when analyzed in combination (one or the other antibiotics were susceptible 100% of the time). The results of this study suggest that using larger data sets — both through combining data from multiple sites within the same network and by combining data from multiple years — may provide more robust treatment guidelines for clinicians who wish to choose the best empiric treatment for those with S. maltophilia.

Taken together, these studies provide support for improving the framework of ASPs through advanced environmental monitoring, reduction in AST turn-around time, and enhanced tracking of Antimicrobial Resistance (AMR) patterns. These studies provide important insights into how to improve the management and use of antimicrobials in clinical settings.