[Mechanism of sensitization and clinical efficacy of ceftazidime combined with Tanreqing Injection in treating drug-resistant Pseudomonas aeruginosa].

Acute respiratory infection(ARI) caused by drug-resistant Pseudomonas aeruginosa(PA) is increasingly prevalent, posing a serious challenge to public health. To address this clinical issue, combination strategies involving antibiotics and adjuvants have garnered considerable attention. Tanreqing Injection(TRQ), a commonly used traditional Chinese medicine compound preparation in the clinical treatment of ARI, has been preliminarily shown to enhance the antibacterial efficacy of ceftazidime(CAZ) against drug-resistant PA. To elucidate the underlying sensitization mechanism, this study first employed stimulated emission depletion(STED) microscopy to observe morphological alterations in drug-resistant PA following drug administration. Subsequently, transcriptomic analysis was performed to identify differentially expressed genes(DEGs) in PA before and after TRQ treatment. Ethidium bromide(EtBr) accumulation was conducted to assess efflux pump function. N-phenyl-1-naphthylamine(NPN) uptake was conducted to assess outer membrane permeability. Nitrocefin-based colorimetric assay was conducted to assess β-lactamase activity. crystal violet(CV) staining was conducted to assess the effect of CAZ+TRQ on biofilm formation. 2,3-di-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazole-5-anilinoyl(XTT) reduction assay was conducted to assess the effect of CAZ+TRQ on viable bacterial counts within biofilms. These results indicated that TRQ significantly inhibited the efflux pump function of PA(P<0.01), increased outer membrane permeability(P<0.05), reduced β-lactamase activity(P<0.01), and synergizing with CAZ to inhibit early biofilm formation and the viable bacterial counts within biofilms(P<0.01). A clinical study enrolled 20 patients with ARI caused by drug-resistant PA, who were randomly divided into control group(CAZ monotherapy) and experimental group(CAZ combined with TRQ). The sputum culture negative conversion, changes in resistance-related gene expression, inflammatory indicators, and symptom scores were compared between the two groups. The results demonstrated that the experimental group exhibited a higher sputum culture negativity rate, more pronounced downregulation of resistance-related gene expression, greater improvement in inflammatory indicators(P<0.05), and a more substantial reduction in the cough and sputum assessment questionnaire(CASA-Q) scores(P<0.05). In conclusion, this study systematically demonstrated that the combination of CAZ and TRQ can modulate the resistance mechanism of PA through multiple targets, enhance antibacterial efficacy and significantly improve clinical infectious symptoms and inflammatory responses, thereby providing both experimental and clinical evidence for integrated traditional Chinese and western medicine to combat bacterial resistance.