Late Breaking Original Research
Tuesday, November 14, 2023
08:30 AM–10:00 AM
Abstract
Introduction:
Acinetobacter baumannii poses a threat to public health due to limited treatments and high mortality. Eravacycline (ERV), tigecycline (TGC), and minocycline (MIN) are potential treatment options due to their stability against multiple resistance mechanisms. Combination therapy is standard treatment for moderate to severe carbapenem-resistant
A. baumannii (CRAB) infections. However, there has been limited data regarding the role of tetracyclines (TETs) in combination with other agents against
A. baumannii.
Research Question or Hypothesis: We sought to evaluate the in vitro activity of tetracycline-derivatives alone and in combination against A. baumannii strains.
Study Design: Susceptibility testing and time-kill assay (TKA)
Methods: Ninety-three A. baumannii strains were obtained from HonorHealth Network, Abrazo Community Health Network (Phoenix, AZ), and the FDA-CDC Antimicrobial Resistance Isolate Bank (Atlanta, GA). ERV, MIN, TGC, meropenem (MEM), sulbactam (SUL), and colistin (COL) were purchased. MIC was performed using broth microdilution according to CLSI. TKA was performed against 4 strains in duplicate. Antimicrobials were tested at 1xMIC alone and in combination. Synergy was defined as = 2-log10 decrease at 24h in combination compared to alone, and antagonism was defined as = 2-log10 increase.
Results: MIC50/90 (µg/mL) for ERV, TGC, MIN, MEM, SUL, and COL were 1/2, 2/8, 8/16, 64/256, 16/64, and 1/2, respectively. The strains for TKA were H-3945 (pan-susceptible), AR-309 (TGC-S, CFDC-R CRAB), and AR-306/307 (pan-resistant). Bactericidal activity was not observed with monotherapy at 24h. TGC+MER and TGC+SUL demonstrated synergistic activity at 24H with all strains, including AR-307 (-4.88±0.02 log10 CFU/mL). Synergy was observed with ERV+MER against all CRAB strains. ERV+COL was the most active combination against AR-309 compared to other combinations (-6.49±0.05 log10 CFU/mL).
Conclusion: Our study demonstrated both ERV- and TGC-based combinations as the most active, particularly with MER against pan-R CRAB infections. In vitro pharmacokinetic/pharmacodynamic and in vivo studies are warranted to confirm these findings.
Presenting Author
Spencer Harris PharmDMidwestern University - Glendale Campus
Authors
Vanthida Huang Pharm.D., BSPHM, FCCP
Midwestern University, College of Pharmacy-Glendale
Tho H. Pham PharmD, BCIDP
Midwestern University College of Pharmacy-Glendale Campus