Original Research
Sunday, October 13, 2024
12:45 PM–02:15 PM
Abstract
Introduction:
Despite the increased prevalence and severity of multidrug-resistant (MDR) Acinetobacter baumannii, data on optimal treatment remains limited. Although dual combinations with eravacycline (ERV)- or tigecycline (TGC)-based demonstrate synergy and rapid initial kill, bacterial regrowth occurs soon after. Thus, there is a need for novel tetracycline-based combinations to achieve bacterial kill and suppress the development of resistance.
Research Question or Hypothesis:
Evaluate the in vitro activities of tetracycline-based triple therapies against MDR-AB
Study Design:
Time-kill assay (TKA)
Methods:
Two A. baumannii strains, H-3945 (pan-susceptible) and CDC-306 (MDR) were evaluated. Broth microdilution was performed according to CLSI using commercially purchased ERV, meropenem (MER), sulbactam (SUL), rifampin (RIF), and TGC. TKA was performed in duplicate at 0.25xMIC and free steady-state (fCss) concentrations based on population pharmacokinetic data. Synergy was defined as =2 log10 CFU/mL reduction at 24h in combination compared to the most active monotherapy, and additive effects as >1 and <2 log10-CFU/mL reduction. Other activities were considered indifferent.
Results:
H-3945/CDC-306 MICs (mg/L) were as follows: ERV (0.0625/4), MER (0.25/256), SUL (4/64), RIF (4/8), and TGC (0.25/8). At 0.25xMIC, synergy was seen with TGC+SUL+RIF (-3.72±0.2 log10 CFU/mL) and TGC+MER+RIF (-5.08±0.00 log10 CFU/mL) against H-3945. For CDC-306, TGC+MER+RIF achieved additive effect (-1.63±0.75 log10 CFU/mL), and synergy was observed with TGC+MER+SUL (-3.48±0.42 log10-CFU/mL), ERV+MER+SUL (-3.37±0.06 log10 CFU/mL) and ERV+MER+RIF (-2.99±0.11 log10 CFU/mL). Triple therapies at fCss failed to achieve synergy or additive effects for both strains.
Conclusion:
ERV- and TGC-based triple therapy demonstrated synergy against A. baumannii. Further investigation is warranted to evaluate dual vs triple therapy.
Presenting Author
Spencer Harris PharmDMidwestern University - Glendale Campus
Authors
Vanthida Huang Pharm.D., BSPHM, FCCP
Midwestern University, College of Pharmacy-Glendale
Tho Pham PharmD, BCIDP
University of Arizona R Ken Coit College of Pharmacy