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Updated: May 12, 2026

Quadruple-Checkerboard: A Modification of the Three-Dimensional Checkerboard for Studying Drug Combinations
Published on: July 24, 2021
New antibacterial administration treatment strategies
1University of Virginia Health System, Charlottesville, Virginia 22908, USA.
Background:
Antibiotic resistance of bacteria is associated with greater mortality, prolonged hospitalization, and increased healthcare costs. Optimization of antibiotic administration is crucial to limiting the spread of antibiotic resistance.
Methods:
A review of the literature was performed to evaluate novel administration techniques and their utility in decreasing the rate of antibiotic resistance.
Results:
Evidence from controlled studies has revealed patterns of improved antibiotic utilization and resistance patterns following the implementation of antibiotic guidelines and physician educational programs, although guidelines can encroach on physician autonomy. The spread of resistant pathogens is limited successfully by the use of formulary restrictions, although most formulary restriction policies are based on cost rather than on intent to limit resistance. Whereas the relationship between antibiotic dosing and resistance is intriguing, clinical data linking patient outcomes with different modes of antibiotic administration are lacking. Limited evidence is available to support that shorter duration of antibiotics reduces selective pressure and the development of resistance. Whereas there are data to support the use of antibiotic rotation as a means to limit antibiotic resistance, it remains unclear as to the optimal duration of rotation periods, optimal number of antibiotics utilized in a rotation protocol, types of antibiotics used in the protocol, and the order in which they should be used. Selective digestive decontamination appears to be useful in select groups of high-risk patients (i.e., patients with higher risks of death). The role of non-antibiotic measures (e.g., cytokines) to combat infection and reduce resistance requires further study.
Conclusions:
Strategies aimed at optimization of antibiotic utilization are key in limiting the emergence of resistance. The use of antibiotic guidelines, formulary restrictions, improved dosing, shorter courses of antibiotics, antibiotic cycling, selective digestive decontamination, and non-antibiotic therapies are promising approaches, which may prove to control antibiotic resistance over time.
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