ABSTRACT
Antimicrobial resistance (AMR) has become a topic of great concern in recent years, with much effort being committed to developing alternative treatments for resistant bacterial pathogens. Drug combinational therapies have been a major area of research for several years, with modern iterations using combining well-established antibiotics and other antimicrobials with the aim of discovering complementary mechanisms. Previously, we characterised four GRAS antimicrobials that can withstand thermal polymer extrusion processes for novel medical device-based and therapeutic applications. In the present study, four antimicrobial bioactive-silver nitrate, nisin, chitosan and zinc oxide-were assessed for their potential combined use as an alternative synergistic treatment for AMR bacteria via a broth microdilution assay based on a checkerboard format. The bioactives were tested in arrangements of two-, three- and four-drug combinations, and their interactions were determined and expressed in terms of a synergy score. Results have revealed interesting interactions based on treatments against recognised test bacterial strains that cause human and animal infections, namely E. coli, S. aureus and S. epidermidis. Silver nitrate was seen to greatly enhance the efficacy of its paired treatment. Combinations with nisin, which is a lantibiotic, exhibited the most interesting results, as nisin has no effect against Gram-negative bacteria when used alone; however, it demonstrated antimicrobial effects when combined with silver nitrate or chitosan. This study constitutes the first study to both report on practical three- and four-drug combinational assays and utilise these methods for the assessment of established and emerging antimicrobials. The novel methods and results presented in this study show the potential to explore previously unknown drug combination compatibility measures in an ease-of-use- and high-throughput-based format, which can greatly help future research that aims to identify appropriate alternative treatments for AMR, including the screening of potential new bioactives biorefined from various sources.
ABSTRACT
BACKGROUND: Epidermal growth factor receptor tyrosine kinase inhibitors significantly prolong the progression-free survival of patients with non-squamous non-small cell lung cancer (NSCLC). However, most patients develop tumor regrowth and their prognosis remains poor. A new treatment strategy for NSCLC harboring EGFR mutation is therefore necessary. METHODS: In phase I, eligible patients were administered oral erlotinib daily and intravenous pemetrexed, carboplatin, and bevacizumab every 3 weeks for four cycles with maintenance of pemetrexed and bevacizumab until progressive disease was observed. The dose of erlotinib was 100 mg for dose level 1 and 150 mg for dose level 2. The doses of pemetrexed, carboplatin, and bevacizumab were fixed at 500 mg/m2, area under the concentration-time curve of 6 mg/mL · min, and 15 mg/kg, respectively. The dose-limiting toxicities were grade 3/4 neutropenia with fever or infection, grade 4 leukopenia lasting for ≥7 days, grade 4 thrombocytopenia, grade 3/4 uncontrollable nonhematological toxicity, and delayed administration of the subsequent cycle by >2 weeks because of adverse events. RESULTS: Six patients were enrolled in phase I (dose level 1, n = 3; dose level 2, n = 3). During the induction phase, grade 3 neutropenia without fever was observed in one patient at dose level 1 and two patients at dose level 2. Grade 3 anemia was reported in one patient at dose level 1 and grade 3 thrombocytopenia was reported in two patients at dose level 1 and dose level 2, respectively. CONCLUSION: Four-drug combination therapy is a feasible and promising.
ABSTRACT
Objective To compare the outcomes between interstitial cystitis/painful bladder syndrome (IC/PBS) patients treated with four-drug combination (heparin,lidocaine,sodium bicarbonate,gentamicin) and sodium hyaluronate intravesical instillation.Methods There were 23 IC/PBS patients from Jan.1,2011 to Mar.1,2013.Ten patients (group A) received four-drug combination (heparin 40 000 U,'gentamicin 160 000 U,sodium bicarbonate 1％,lidocaine 0.4％) instillation treatment.Thirteen patients received instillation of sodium hyaluronate (40 mg/50 ml) therapy (group B).In group B,intravesical instillations were performed weekly in the first 6-8 weeks,and monthly until one year.Patients in group A received intravesical instillation twice a week in the first 6-8 weeks and twice a month for 10 months.All the patients were instructed to retain the instillation volume for at least one hour.Clinical symptoms (24 h frequency of urination,maximal micturition volume),O'Leary-Sant symptom and problem index were assessed at baseline and 1,6 and 12 months after treatment.The 2 therapies were compared within curative effects and side effects.Results Twenty-two of the 23 patients were followed up to 12 months.Patients in group A had no adverse events reported.One case of group B dropped out from treatment for recurrent urinary tract infection,and the other two cases felt painful in bladder area during instillation.There was no significant difference in initial scores between the 2 groups (P＞0.05).At 1,6,12 months after intravesical instillation,interstitial cystitis symptom index,interstitial cystitis problem index,24 h frequency of urination,the maximum bladder capacity were improved in both groups.All indicators in group A and B were improved significantly after treatment compared with pretreatment (P ＜ 0.05).≥ 25％ decrease of interstitial cystitis symptom index or ≥25％ decrease of 24 h frequency of urination were defined as remission.Remission rates of the 2 groups at each time point were:1 month after treatment (100％ versus 100％,P=1.000),6 months after treatment (80％ versus 83％,P=1.000),1 year after treatment (70％ versus 75％,P=1.000).There were no significant differences between the 2 groups in all time points for the outcomes (P ＞ 0.05).Conclusion The four-drug combination intravesical instillation could achieve a similar effect with hyaluronic acid therapy in patients with IC/PBS.
