Combination Therapy with TCM Preparation Kumu Injection and Azithromycin against Bacterial Infection and Inflammation: In Vitro and In Vivo

Meiyu Yu; Xuejing Gu; Yanzheng Qu; Fuyou Sun; Yanli Li; Feng Zhao; Hui Xu

doi:10.1155/2022/8533005

Combination Therapy with TCM Preparation Kumu Injection and Azithromycin against Bacterial Infection and Inflammation: In Vitro and In Vivo

Evid Based Complement Alternat Med. 2022 Mar 16:2022:8533005. doi: 10.1155/2022/8533005. eCollection 2022.

Authors

Meiyu Yu¹, Xuejing Gu², Yanzheng Qu¹, Fuyou Sun¹, Yanli Li^{2

3}, Feng Zhao², Hui Xu²

Affiliations

¹ Department of Pharmacy, Yantai Muping Hospital of Traditional Chinese Medicine, Yantai 264100, China.
² School of Pharmacy, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Yantai University, Yantai 264005, China.
³ Department of Pharmacy, Binzhou Hospital of Traditional Chinese Medicine, Binzhou 256600, China.

Abstract

Background: Azithromycin (AZM) is one of the most common broad-spectrum antibiotics. However, drug resistance is increasing and combination therapy has attracted great attention. AZM is usually combined with traditional Chinese medicine (TCM) preparations with heat-clearing and detoxifying effects, including Kumu injection (KM) made from Picrasma quassioides (D. Don) Benn.

Purpose: The present study aimed to investigate synergistic antimicrobial and anti-inflammatory activities of KM plus AZM with the aim of understanding the mechanism of clinical efficacy of combination regimens.

Methods: Seven common bacterial clinical isolates and LPS-induced RAW 264.7 cells were used for assay of in vitro potency. The minimum inhibitory concentration (MIC) was determined for each drug, followed by synergy testing through the checkerboard method and fractional inhibitory concentration index (FICI) for quantifying combined antibacterial effects. The rat model of Klebsiella pneumoniae-induced pneumonia was developed and subjected to various drug treatments, namely, AZM, KM, or AZM plus KM, intravenously administered at 75 mg/kg once a day for one week. The combination effects then were evaluated according to pharmacodynamics and pharmacokinetic assessments.

Results: KM-AZM combination synergistically inhibits in vitro growth of all the test standard strains except Pseudomonas aeruginosa and also the drug-resistant strains of Staphylococcus aureus, Streptococcus pneumoniae, Shigella dysenteriae, Klebsiella pneumoniae, and Escherichia coli. Despite an additive effect against NO, KM plus AZM at an equal dose could synergistically suppress overrelease of the inflammatory cytokines TNF-α and IL-6 by LPS-induced RAW 264.7 cells. The combination significantly inhibited the proliferation of K. pneumoniae in the rat lungs, mainly by inactivating MAPKs and NF-κB signaling pathways. KM-AZM combination caused a onefold increase in apparent distribution volume of AZM, along with a significant decrease of AZM level in the livers and heart for pharmacokinetics.

Conclusion: KM-AZM combination displayed synergistic antibacterial and anti-inflammatory effects beneficial to the therapeutic potential against bacterial infection.