Safe and effective beta-lactamase dosing for microbiome protection
The present invention relates to, inter alia, safe and effective doses of a beta-lactamase for, e.g. microbiome protection.
1. A method of protecting a human patient's gastrointestinal microbiome, comprising administering an effective amount of a pharmaceutical composition comprising a beta-lactamase to a patient in need thereof, wherein:
the patient is undergoing treatment or has recently undergone treatment with a beta-lactam antibiotic, wherein the beta-lactam antibiotic is a penicillin or a cephalosporin;
the patient is undergoing treatment with a proton pump inhibitor, wherein the proton pump inhibitor is esomeprazole, omeprazole, lansoprazole, rabeprazole, pantoprazole, or dexlansoprazole; and
the beta-lactamase comprises an amino acid sequence having at least 98% identity with SEQ ID NO: 1.
2. The method of claim 1 , wherein the beta-lactam antibiotic and beta-lactamase are administered simultaneously.
3. The method of claim 1 , wherein the beta-lactam antibiotic and beta-lactamase are administered sequentially.
4. The method of claim 1 , wherein the beta-lactamase is administered orally.
5. The method of claim 1 , wherein the beta-lactam antibiotic is administered parenterally, optionally selected from intravenously and/or by infusion.
6. The method of claim 1 , wherein the protection of the patient's microbiome comprises treatment or prevention of a microbiome-mediated disorder selected from an antibiotic-induced adverse effect, C. difficile infection, and a C. difficile -associated disease.
7. The method of claim 6 , wherein the antibiotic-induced adverse effect and/or CDI or C. difficile -associated disease is one or more of: antibiotic-associated diarrhea, C. difficile diarrhea (CDD), C. difficile intestinal inflammatory disease, colitis, pseudomembranous colitis, fever, abdominal pain, dehydration and disturbances in electrolytes, megacolon, peritonitis, and perforation and/or rupture of the colon.
8. The method of claim 1 , wherein the protection of the patient's microbiome comprises maintenance of a normal intestinal microbiota selected from a healthy microbiota balance and a healthy ratio or distribution.