1. Academic Validation
  2. In vitro and in vivo evaluation of cephalosporins for the treatment of Lyme disease

In vitro and in vivo evaluation of cephalosporins for the treatment of Lyme disease

  • Drug Des Devel Ther. 2018 Sep 11;12:2915-2921. doi: 10.2147/DDDT.S164966.
Venkata Raveendra Pothineni 1 Mansi B Parekh 1 Mustafeez Mujtaba Babar 1 Aditya Ambati 2 Peter Maguire 1 Mohammed Inayathullah 1 Kwang-Min Kim 1 Lobat Tayebi 3 Hari-Hara Sk Potula 1 Jayakumar Rajadas 1 4
Affiliations

Affiliations

  • 1 Biomaterials and Advanced Drug Delivery, Stanford Cardiovascular Pharmacology Division, Cardiovascular Institute, School of Medicine, Stanford University, Palo Alto, CA, USA, jayraja@stanford.edu.
  • 2 Center for Sleep Sciences and Medicine, Department of Psychiatry and Behavioral Sciences, School of Medicine, Stanford University, Palo Alto, CA, USA.
  • 3 Department of Developmental Sciences, Marquette University School of Dentistry, Milwaukee, WI, USA.
  • 4 Department of Bioengineering and Therapeutic Sciences, Schools of Pharmacy and Medicine, University of California San Francisco, San Francisco, CA, USA, jayraja@stanford.edu.
Abstract

Background: Lyme disease accounts for >90% of all vector-borne disease cases in the United States and affect ~300,000 persons annually in North America. Though traditional Tetracycline antibiotic therapy is generally prescribed for Lyme disease, still 10%-20% of patients treated with current Antibiotic therapy still show lingering symptoms.

Methods: In order to identify new drugs, we have evaluated four cephalosporins as a therapeutic alternative to commonly used Antibiotics for the treatment of Lyme disease by using microdilution techniques like minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC). We have determined the MIC and MBC of four drugs for three Borrelia burgdorferi s.s strains namely CA8, JLB31 and NP40. The binding studies were performed using in silico analysis.

Results: The MIC order of the four drugs tested is cefoxitin (1.25 µM/mL) > cefamandole (2.5 µM/mL), > cefuroxime (5 µM/mL) > cefapirin (10 µM/mL). Among the drugs that are tested in this study using in vivo C3H/HeN mouse model, cefoxitin effectively kills B. burgdorferi. The in silico analysis revealed that all four cephalosporins studied binds effectively to B. burgdorferi proteins, SecA subunit penicillin-binding protein (PBP) and Outer surface protein E (OspE).

Conclusion: Based on the data obtained, cefoxitin has shown high efficacy killing B. burgdorferi at concentration of 1.25 µM/mL. In addition to it, cefoxitin cleared B. burgdorferi Infection in C3H/HeN mice model at 20 mg/kg.

Keywords

Borrelia burgdorferi; Lyme disease; antimicrobials; penicillin-binding proteins.

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