Date Approved

3-3-2026

Embargo Period

3-3-2026

Document Type

Thesis

Degree Name

M.S. Pharmaceutical Sciences

Department

Pharmaceutical Sciences

College

College of Science & Mathematics

Advisor

Valerie Carabetta, Ph.D.

Committee Member 1

Lark Perez, Ph.D.

Committee Member 2

Gregory Caputo, Ph.D.

Abstract

Acinetobacter baumannii is an opportunistic Gram-negative pathogen that poses a significant global health threat due to its remarkable ability to acquire multidrug (MDR) and extensively drug-resistant (XDR) phenotypes. Therapeutic failures are increasingly common as strains develop resistance to nearly all available antibiotics, including carbapenems, polymyxins, and tigecycline, leaving clinicians with limited treatment options. This study aimed to investigate combinatorial therapeutic approaches capable of revitalizing antibiotic efficacy against MDR/XDR A. baumannii clinical isolates. We evaluated the synergistic potential of durlobactam-sulbactam in combination with twelve commonly used antibiotics, including amikacin, rifampin, tobramycin, tigecycline, cefiderocol, and others. Initial screening using the disc diffusion assay identified strains M1 and M2 as highly resistant, showing no zones of inhibition with most monotherapies. However, when combined with durlobactam-sulbactam, several antibiotics demonstrated enhanced activity, evidenced by increased inhibition zones. These preliminary findings were validated through checkerboard synergy testing, which quantified the fractional inhibitory concentration index (FICI) to confirm synergistic interactions. Furthermore, we incorporated a practical infection control side project that introduced a bleach-spot assay as a rapid tool to distinguish mold from dirt in hospital settings, thereby reducing unnecessary room quarantines and preserving critical patient space. The findings from this research highlight the potential of strategic antibiotic combinations, particularly those involving novel β-lactamase inhibitors, to restore antimicrobial activity against otherwise untreatable strains. These insights are essential for guiding clinical decision-making and developing effective therapeutic regimens in the ongoing battle against antimicrobial resistance.

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