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Kurita America Inc.July 21, 20232 min read

Smart Applications of Antibiotics Critical  for Limiting Resistance Development

Chronic and acute bacterial infections are expected in ethanol plants, yet uncontrollable outbreaks can be costly due to lost yields, fermenter downtime and cleaning and repair costs. Lactic acid-producing bacteria thrive in fermentation conditions and are the most common contaminant. Antibiotics are a vital part of microbial control, yet overuse of the few antibiotics available to combat these infections penicillin G, virginiamycin and erythromycin is becoming increasingly problematic as antibiotic resistance becomes a significant issue. Surveys of ethanol plants have found isolates resistant to all three antibiotics in multiple locations.

Ethanol plants provide an ideal environment for resistance development: high cell density, available nutrients and continual exposure to sublethal doses of antibiotics. Additionally, antibiotic combination products specifically antagonistic combinations, such as penicillin and virginiamycin -  are problematic as they cause accelerated resistance development. One way to limit antibiotic resistance is to use cycling or periodic alternating of antibiotics with different modes of action. During antibiotic cycling, cells that develop resistance to the first antibiotic are eliminated when a different antibiotic is dosed, thus maintaining antibiotic susceptibility. Research has shown that alternating antibiotics is more advantageous than using multiple antibiotics simultaneously in nonoptimal combination products.

To confirm that use of antibiotic combinations accelerates the rate of antibiotic resistance, Kurita America conducted research using commercially available strains of bacteria found in ethanol plants Lactobacillus fermentum, Lactococcus lactis and Pediococcus pentosaceus and isolates from four operating ethanol facilities. Bacteria were grown in the presence of increasing concentrations of either a single antibiotic, a penicillin-virginiamycin combination or alternating antibiotics with penicillin one day followed by virginiamycin the next day to mimic drug cycling. If resistance developed, the bacteria were able to grow in increasingly higher antibiotic concentrations. For both the strains of lactic acid-producing bacteria and isolates from operating ethanol plants, use of the penicillin-virginiamycin combination increased the risk of multidrug resistance. After 10 days, bacteria exposed to the combination antibiotics were able to grow in the presence of 30 parts per
million (ppm) antibiotic, 10 times the allowed maximum dose.

The accelerated rate of resistance corroborates results seen in other published studies. In contrast, drug cycling was the most effective method for limiting antibiotic resistance for both lab strains and isolates from the field. When combination products are used and resistance develops, the bacteria are resistant to both penicillin G and virginiamycin, leaving erythromycin as the only potential antibiotic treatment.

Interestingly, it was found that cross-resistance between virginiamycin and erythromycin is
common. Fifty-seven percent of virginiamycin-resistant bacteria were resistant to erythromycin, leaving ethanol plants without microbial treatment options.

This scientific study, as well as many other published studies, demonstrates that how antibiotics are applied can impact resistance development. Without responsible and informed use of antibiotics, fuel ethanol plants will face multidrug resistant bacterial outbreaks, increased cleaning costs and lost profits.

About Jennifer Starner, Ph.D.

Dr. Starner received her doctorate in biochemistry from the University of Notre Dame and has worked at Kurita America for nearly ten years. Dr. Starner is a published author and has presented at the Fuel Ethanol Workshop (FEW), Gibbs Biophysical Society, National Science Foundation US-Mexico Workshop in Biological Chemistry, and Gordon Research Conference on Proteins.