Effect of Tanreqing injection on multidrug resistance organisms: A test-negative case-control study and network pharmacology analysis

Abstract

Background: Multidrug resistance organisms (MDROs) pose a major threat in intensive care units (ICUs). Although in vitro studies suggested that Tanreqing (TRQ) was effective against MDROs, evidence about TRQ injection usage and its real-world effectiveness is lacking.

Purpose: This study aimed to investigate treatment pattern and real-world effectiveness of TRQ against MDRO infections among ICU patients being treated with antibiotics.

Study design: A real-world data study (i.e., test-negative case control) was conducted, using a large validated multicenter ICU database. Eligible cases were patients infected with any of the six monitored MDROs, including methicillin resistant Staphylococcus aureus (MRSA), carbapenem-resistant Acinetobacter baumannii (CRAB), vancomycin-resistant Enterococcus sp. (VRE), carbapenems-resistant Pseudomonas aeruginosa (CRPA), carbapenem-resistant Enterobacter sp. (CRE), or carbapenem-resistant Klebsiella pneumoniae (CRKP). The controls were individuals infected with antibiotic-sensitive strains.

Methods: We used marginal structural models to adjust for time-varying confounding. We also performed network pharmacology analysis to explore the mechanisms by which TRQ exerted effects against MRDOs.

Results: A total of 2890 patients were included. There were significant variations in timing and duration of use of TRQ injection. Over half (54.4 %) of patients received antibiotics plus TRQ injection, and the duration ranged from 1 to 83 days. The addition of TRQ injection was associated with lower probability of that patients become infected with CRE (adjusted odds ratio [OR_adj] 0.51; 95 % confidence interval [CI]: 0.35-0.74) and CRKP (OR_adj 0.55; 95 % CI: 0.36-0.83). Network pharmacology analysis suggested that TRQ exerts the effect against CRKP by modulating the metabolic pathways of K. pneumoniae and inhibit β-lactamase enzyme. No statistically significant differences were observed between TRQ infection with MDROs (OR_adj 1.12; 95 % CI: 0.90-1.38), MRSA (OR_adj 1.13; 95 % CI: 0.50-2.54), CRPA (OR_adj 0.79; 95 % CI: 0.52-1.20) and CRAB (OR_adj 1.36; 95 % CI: 0.67-2.76).

Conclusion: TRQ injection was associated with lower CRKP infection risk in ICU patients, potentially via modulation of β-lactam antibiotic resistance and metabolic pathways.

Keywords: Carbapenem-resistant Klebsiella pneumonia; Intensive care unit; Multicenter registry database; Multidrug resistance organisms; Tanreqing.