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Antimicrobial Synergy Testing by the Inkjet Printer-assisted Automated Checkerboard Array and the Manual Time-kill Method
Published on: April 18, 2019
In vitro activities of nontraditional antimicrobials against multiresistant Acinetobacter baumannii strains isolated
M D Appleman1, H Belzberg, D M Citron
1Departments of Pathology, Los Angeles County-University of Southern California Medical Center, Los Angeles, CA 90033, USA. mapplema@hsc.usc.edu
Abstract:
Fifteen multiresistant Acinetobacter baumannii isolates from patients in intensive care units and 14 nonoutbreak strains were tested to determine in vitro activities of nontraditional antimicrobials, including cefepime, meropenem, netilmicin, azithromycin, doxycycline, rifampin, sulbactam, and trovafloxacin. The latter five drugs were further tested against four of the strains for bactericidal or bacteriostatic activity by performing kill-curve studies at 0.5, 1, 2, and 4 times their MICs. In addition, novel combinations of drugs with sulbactam were examined for synergistic interactions by using a checkerboard configuration. MICs at which 90% of the isolates tested were inhibited for antimicrobials showing activity against the multiresistant A. baumannii strains were as follows (in parentheses): doxycycline (1 microg/ml), azithromycin (4 microg/ml), netilmicin (1 microg/ml), rifampin (8 microg/ml), polymyxin (0.8 U/ml), meropenem (4 microg/ml), trovafloxacin (4 microg/ml), and sulbactam (8 microg/ml). In the kill-curve studies, azithromycin and rifampin were rapidly bactericidal while sulbactam was more slowly bactericidal. Trovafloxacin and doxycycline were bacteriostatic. None of the antimicrobials tested were bactericidal against all strains tested. The synergy studies demonstrated that the combinations of sulbactam with azithromycin, rifampin, doxycycline, or trovafloxacin were generally additive or indifferent.
Insights
This study evaluated novel antimicrobials against multiresistant Acinetobacter baumannii. While several drugs showed activity, none were bactericidal against all strains, and sulbactam combinations offered limited synergy.
Area of Science:
- Medical Microbiology
- Infectious Diseases
- Antimicrobial Resistance
Background:
- Multiresistant Acinetobacter baumannii poses a significant threat in intensive care units.
- Limited treatment options exist for infections caused by these challenging pathogens.
Purpose of the Study:
- To determine the in vitro activity of nontraditional antimicrobials against multiresistant Acinetobacter baumannii.
- To assess the bactericidal or bacteriostatic potential and synergistic interactions of specific antimicrobial combinations.
Main Methods:
- Minimum Inhibitory Concentrations (MICs) were determined for various antimicrobials.
- Kill-curve studies were performed to evaluate bactericidal/bacteriostatic activity.
- Checkerboard assays were used to investigate synergistic interactions with sulbactam.
Main Results:
- Doxycycline, azithromycin, netilmicin, rifampin, meropenem, and trovafloxacin demonstrated in vitro activity against multiresistant A. baumannii.
- Azithromycin and rifampin exhibited rapid bactericidal effects; sulbactam was slowly bactericidal.
- Trovafloxacin and doxycycline displayed bacteriostatic activity; no single agent was bactericidal against all isolates.
- Combinations of sulbactam with azithromycin, rifampin, doxycycline, or trovafloxacin showed additive or indifferent synergistic effects.
Conclusions:
- Several antimicrobials show promise against multiresistant Acinetobacter baumannii, but effective bactericidal monotherapy remains a challenge.
- Novel combinations with sulbactam did not yield significant synergistic improvements in vitro.
- Further research is needed to identify effective therapeutic strategies for Acinetobacter baumannii infections.
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