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Effect of Tanreqing injection on multidrug resistance organisms: A test-negative case-control study and network
Wen Wang1, Jiayue Xu1, Qinhuai Lai1
1Institute of Integrated Traditional Chinese and Western Medicine, Chinese Evidence-based Medicine Center and Cochrane China Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China; NMPA Key Laboratory for Real World Data Research and Evaluation in Hainan, Chengdu, 610041, China; Sichuan Center of Technology Innovation for Real World Data, Chengdu, China.
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 [ORadj] 0.51; 95 % confidence interval [CI]: 0.35-0.74) and CRKP (ORadj 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 (ORadj 1.12; 95 % CI: 0.90-1.38), MRSA (ORadj 1.13; 95 % CI: 0.50-2.54), CRPA (ORadj 0.79; 95 % CI: 0.52-1.20) and CRAB (ORadj 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.
Insights
Tanreqing (TRQ) injection may reduce the risk of carbapenem-resistant Klebsiella pneumoniae (CRKP) infections in intensive care units (ICUs). This study explored TRQ
Area of Science:
- Infectious Diseases
- Pharmacology
- Critical Care Medicine
Background:
- Multidrug-resistant organisms (MDROs) are a significant threat in intensive care units (ICUs).
- Tanreqing (TRQ) injection's effectiveness against MDROs in real-world clinical settings remains under-investigated.
- Existing in vitro data suggests TRQ's potential antimicrobial activity.
Purpose of the Study:
- To investigate the treatment patterns of Tanreqing (TRQ) injection in ICU patients.
- To evaluate the real-world effectiveness of TRQ in combating MDRO infections when used alongside antibiotics.
Main Methods:
- A real-world, test-negative case-control study was conducted using a large, multicenter ICU database.
- Patients infected with specific MDROs (e.g., MRSA, CRAB, VRE, CRPA, CRE, CRKP) or antibiotic-sensitive strains were analyzed.
- Marginal structural models were employed to control for time-varying confounders, and network pharmacology was used to explore mechanisms of action.
Main Results:
- Over half of the 2890 included patients received TRQ injection with antibiotics, with variable durations.
- TRQ injection was associated with a reduced likelihood of carbapenem-resistant Enterobacter sp. (CRE) and carbapenem-resistant Klebsiella pneumoniae (CRKP) infections.
- Network pharmacology indicated TRQ may combat CRKP by altering metabolic pathways and inhibiting beta-lactamase.
Conclusions:
- Tanreqing (TRQ) injection use in ICUs showed an association with a lower risk of CRKP infections.
- The findings suggest TRQ may modulate beta-lactam antibiotic resistance and metabolic pathways, contributing to its effectiveness.
- Further research is warranted to fully elucidate TRQ's role in managing MDRO infections.
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