Anti-infection strategies against pleural empyema include the use of antibiotics and drainage treatments, but bacterial eradication rates remain low. A major challenge is the formation of biofilms in the pleural cavity. DNase has antibiofilm efficacy in vitro, and intrapleural therapy with DNase is recommended to treat pleural empyema, but the relevant mechanisms remain limited. Our aim was to investigate whether DNase I inhibit the early biofilm formation in Pseudomonas aeruginosa- or Staphylococcus aureus-induced empyema models. We used various assays, such as crystal violet staining, confocal laser scanning microscopy (CLSM) analysis, peptide nucleic acid-fluorescence in situ hybridization (PNA-FISH), and scanning electron microscopy (SEM) analysis. Our results suggested that DNase I significantly inhibited early biofilm formation in a dose-dependent manner, without affecting the growth of P. aeruginosa or S. aureus in vitro. CLSM analysis confirmed that DNase I decreased the biomass and thickness of both bacterial biofilms. The PNA-FISH and SEM analyses also revealed that DNase I inhibited early (24h) biofilm formation in two empyema models. Thus, the results indicated that DNase inhibited early (24h) biofilm formation in P. aeruginosa- or S. aureus-induced rabbit empyema models and showed its therapeutic potential against empyema biofilms.

ObjectivesCombination treatment with erlotinib plus bevacizumab has the potential to become a standard treatment regimen for patients with epidermal growth factor receptor mutation-positive (EGFRm+) advanced non-small cell lung cancer (NSCLC). This study aimed to investigate the efficacy and safety of erlotinib plus bevacizumab in patients with EGFRm+ advanced NSCLC.DesignSystematic review and meta-analysis.Data sourcesThe PubMed, Embase, Web of Science and Cochrane Library databases were searched, from inception to 15 January 2022.Eligibility criteriaWe included randomised controlled trials (RCTs), reported in English, assessing the efficacy of erlotinib plus bevacizumab versus erlotinib monotherapy in patients with EGFRm+ advanced NSCLC.Data extraction and synthesisThe main objective was to assess overall survival (OS), progression-free survival (PFS), objective response rate (ORR) and adverse events (AEs). Two independent reviewers extracted data and assessed the risk of bias. A random-effects model was used where there was evidence for homogeneous effects.ResultsFour RCTs (reported across six publications) were included in the meta-analysis, with a total of 775 patients included in the pooled analyses of PFS, OS and ORR (387 in the erlotinib plus bevacizumab intervention group and 388 in the erlotinib group). Compared with the erlotinib alone group, the erlotinib plus bevacizumab group achieved a significantly prolonged PFS (HR: 0.59; 95% CI 0.49 to 0.72; p<0.00001; I2=0%), but OS (HR: 0.95; 95% CI 0.78 to 1.15; p=0.59; I2=0%) and ORR (OR: 1.25; 95% CI 0.89 to 1.74; p=0.19; I2=0%) were not significantly prolonged. A total of 776 cases were used for a pooled analysis of AEs. Regarding AEs, combined treatment significantly increased the incidence of diarrhoea (51% vs 43%, 95% CI 1.03 to 1.38; p=0.006), haemorrhagic events (41% vs 20%, 95% CI 1.12 to 6.31; p=0.03), proteinuria (25% vs 3%, 95% CI 4.86 to 17.66; p<0.0001) and hypertension (40% vs 8%, 95% CI 3.66 to 7.88; p<0.0001).ConclusionsErlotinib plus bevacizumab for the treatment of patients with EGFRm+ advanced NSCLC was associated with significantly prolonged PFS compared with erlotinib alone, but the combination did not prolong OS.

IntroductionPseudomonas aeruginosa is a common clinical opportunistic pathogen. Antibiotic resistance of P. aeruginosa is frequent, and it affects the clinical curative effect and leads to recurrent infections, disease progression, and difficult treatment, especially in cystic fibrosis patients. The drug-resistance mechanism of P. aeruginosa is complex, and biofilms play an important role. Given the widespread antibiotic resistance of P. aeruginosa, the discovery of a drug that can prevent or eradicate biofilm formation is imperative. Daphnetin (DAP), a coumarin derivative, is a safe, non-toxic, natural compound with antibacterial and anti-biofilm properties. Herein, this study highlights the bacterial motility effects, antibacterial effect, pyocyanin production, and anti-biofilm potential of DAP against P. aeruginosa.MethodsIn this study, the minimal inhibitory concentration of DAP against P. aeruginosa was determined using the microdilution method. The antibiofilm activity of DAP against P. aeruginosa was determined using crystal violet staining, colony-forming unit enumeration, and scanning electron microscopy. The effect of DAP on P. aeruginosa motility was detected using the swimming, swarming, and twitching agar plates to measure the diameter of the concentric area.ResultsWe found that DAP at concentrations of 0.445–1.781 mg/mL and 0.89–1.781 mg/mL can effectively inhibit biofilm formation and eradicate the formed biofilm of P. aeruginosa, respectively. DAP reduced pyocyanin production and inhibited bacterial motility of P. aeruginosa.DiscussionIn conclusion, our results support the conclusion that DAP can effectively eradicate formed biofilm and inhibit biofilm formation, bacterial motility, and pyocyanin production of P. aeruginosa and may represent a natural anti-biofilm therapeutic agent.