Administration of tailored feedstock to increase nitro-containing amphenicol antibiotic susceptibility
Inventors
Akingbade, Katherine L. • Sund, Christian J.
Assignees
United States Department of the Army
Publication Number
US-11684597-B2
Publication Date
2023-06-27
Expiration Date
2039-01-28
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Abstract
A method for increasing susceptibility of microorganisms to antibiotics includes providing a microorganism; administering an antibiotic including a nitro-containing amphenicol compound to the microorganism; and administering any of an uronic, aldonic, ulosonic, and aldaric feedstock to the microorganism. The feedstock is adapted to promote cell metabolism, and inhibit antibiotic inactivation pathways in the microorganism causing increased sensitivity of the microorganism to the nitro-containing amphenicol.
Core Innovation
The invention provides a method for increasing the susceptibility of microorganisms to nitro-containing amphenicol antibiotics by administering to the microorganism both a nitro-containing amphenicol antibiotic and a feedstock comprising a sugar acid selected from the group consisting of uronic, aldonic, ulosonic, and aldaric acids or salts thereof. The feedstock is adapted to promote cell metabolism and inhibit antibiotic inactivation pathways in the microorganism, thereby increasing sensitivity to the nitro-containing amphenicol.
The problem being addressed is the significant increase in antibiotic resistance due to overuse of antibiotics, which results in longer hospital stays, increased drug costs, and destruction of natural gut flora causing side effects such as intestinal inflammation and fatal diarrhea. Amphenicol antibiotics, typically used as last resort treatments for multidrug resistant infections, have serious side effects including bone marrow suppression and aplastic anemia. There are no existing methods or additives to increase susceptibility of microorganisms to amphenicol antibiotic compounds without administering additional antibiotics. Therefore, a more convenient approach is needed to increase susceptibility to amphenicol antibiotics while reducing side effects.
The method involves administering specific sugar acid feedstocks that alter microbial metabolism by decreasing intracellular NADH and NADPH production, which reduces nitro-containing amphenicol inactivation. For example, administering oxidized feedstocks such as galacturonic acid promotes ATP and reduced ferredoxin production but limits NADH production, impairing inactivation pathways. This targeted metabolic manipulation increases microorganism susceptibility to the antibiotic without impacting normal flora or requiring additional antibiotics, thus mitigating side effects and reducing treatment costs.
Claims Coverage
The patent claims encompass two independent method claims and one independent composition claim, each including inventive features relating to the administration of nitro-containing amphenicol antibiotics in combination with specific sugar acid feedstocks to increase susceptibility of microorganisms.
Method of increasing microorganism susceptibility by administering nitro-containing amphenicol and sugar acid feedstock
The method comprises providing a microorganism susceptible to nitro-containing amphenicol; administering an antibiotic composition containing a nitro-containing amphenicol compound; and administering a feedstock comprising a sugar acid selected from uronic, aldonic, ulosonic, and aldaric acids or their salts, wherein the feedstock promotes cell metabolism and inhibits antibiotic inactivation pathways, thus increasing sensitivity to the nitro-containing amphenicol.
Method of administering nitro-containing amphenicol and sugar acid feedstock to increase susceptibility
This method involves administering to a microorganism an antibiotic with a nitro-containing amphenicol compound and administering a feedstock of sugar acid selected from uronic, aldonic, ulosonic, and aldaric acids or salts, adapted to promote cell metabolism and inhibit antibiotic inactivation pathways to increase sensitivity.
Antibiotic composition comprising nitro-containing amphenicol and sugar acid feedstock
An antibiotic composition comprising a nitro-containing amphenicol compound selected from chloramphenicol and azidamfenicol, and a feedstock comprising a sugar acid from uronic, aldonic, ulosonic, or aldaric acids or salts, wherein the feedstock promotes cell metabolism and inhibits antibiotic inactivation pathways in microorganisms, causing increased sensitivity to the nitro-containing amphenicol.
The claims collectively cover methods of administering nitro-containing amphenicol antibiotics in combination with tailored sugar acid feedstocks that promote metabolism while inhibiting antibiotic inactivation pathways, and compositions combining these antibiotics with such feedstocks to enhance microorganism susceptibility.
Stated Advantages
Increases sensitivity of microorganisms to nitro-containing amphenicol antibiotics without requiring additional antibiotics.
Decreases the concentration of nitro-containing amphenicol antibiotic required for treatment, potentially reducing side effects.
Targets specific microorganisms by using feedstocks metabolized selectively, sparing normal flora.
Reduces the likelihood of antibiotic resistance by inhibiting antibiotic breakdown pathways.
Decreases treatment costs by lowering antibiotic dosages and using naturally occurring feedstocks.
Documented Applications
Treatment of anaerobic infections including intra-abdominal infections, gynecologic infections, septicemia, endocarditis, bone and joint infections, central nervous system infections, respiratory tract infections, skin and skin-structure infections, and oral and dental infections.
Use in combination with other antibiotics for treatment of mixed aerobic and anaerobic infections.
Control and support of microbiomes to improve health and performance.
Decontamination of biohazardous environments by applying feedstock and antibiotics to contaminated surfaces.
Formulation of feedstock as additives to suppositories, topical creams, ointments, eye drops, injections, and liquid oral antibiotic emulsions.
Administration as supplement for oral antibiotics such as an 'antibiotic chaser' in shake or drink form.
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