载药妥布霉素人工骨（磷酸钙骨水泥）修复骨缺损的动物试验

目的 评价自固化磷酸钙骨水泥CPC（calcium phosphate cement)载药妥布霉素及植入兔体内后的CPC生物降解特性。方法 把CPC棒和妥布霉素CPC药棒植入兔股骨,观察其界面组织学等变化。结果 通过3个月观察,发现CPC棒和CPC药棒有部分被吸收现象,并且药棒中有新骨形成。结论 载药后的磷酸钙骨水泥仍然具有生物降解特性和骨转导作用。     

抗菌药物对眼部铜绿假单胞杆菌防突变浓度的测定

目的探讨氟喹诺酮药物和庆大霉素、妥布霉素对眼部分离的铜绿假单胞杆菌的防突变浓度（MPC），并比较MPC与最低抑菌浓度（MIC）的关系。方法采用美国国家临床实验室标准化委员会（NCCLS）微量液基法。应用含钙Muller Hinton肉汤培养基，测定环丙沙星敏感的铜绿假单胞杆菌对环丙沙星、氧氟沙星、左氧氟沙星和加替沙星以及庆大霉素、妥布霉素的MIC值，细菌接种量10^4 CFU；采用混菌法，菌接种量10^10 CFU，应用MHA培养基，药物与细菌和MHA混悬液1：19，测定MPC值。结果环丙沙星的MIC50为0．12mg／L，左氧氟沙星为0．25mg／L，氧氟沙星为1mg／L，妥布霉素为0．50mg／L，庆大霉素为2mg／L。环丙沙星对铜绿假单胞杆菌的MPC50和MPC90分别为4mg／L和8mg／L，左氧氟沙星、加替沙星和氧氟沙星均为8mg／L和32mg／L，妥布霉素分别为16mg／L和64mg／L，庆大霉素为32mg／L和128mg／L。结论新型氟喹诺酮类药物和庆大霉素、妥布霉素对铜绿假单胞杆菌有良好的抗菌作用，环丙沙星在预防铜绿假单胞杆菌产生耐药突变方面有明显优势。     

The effect of five antibacterial agents on the physiological levels of serum nitric oxide in mice

In addition to their action on microorganisms, antibacterial agents have been reported to affect host defense mechanisms. Nitric oxide (NO) that is produced by a number of cell types in the innate immune response is bactericidal, but when produced in excessive amounts it could be detrimental to the host. In this study, five antibacterial agents (gentamicin, tobramycin, imipenem, tigecycline, isoniazid) were compared with respect to their ability to affect NO production in mice. Groups of mice were injected with the different antibacterial agents, and at different time intervals post-injection serum NO levels were determined using the Griess reagent. All the antibacterial agents tested showed a significant effect in reducing NO levels in mice. It could be hypothesized that the excessive production of NO in infectious diseases is in most instances suppressed by the antibacterial agent(s) used.     

酸性染料比色法测定妥布霉素滴眼液的含量

目的：建立酸性染料比色法测定妥布霉素滴眼液的含量。方法：根据妥布霉素与酸性染料甲基橙在pH为5.8的介质中反应可生成有色离子对化合物的性质,在妥布霉素水溶液中加入0.1%甲基橙溶液、磷酸盐缓冲液（pH 5.8）、氯仿,混合振摇1分钟后静置分层,于435 nm波长处测定氯仿层吸光度并计算妥布霉素含量。结果：妥布霉素质量浓度在20.08～80.32 mg.L-1的范围内与离子对化合物的吸光度呈良好的线性关系（r=0.999 9）,平均回收率为100.9%（RSD=0.68%）。结论：该法快速、简便,结果准确可靠,可用于妥布霉素滴眼液的质量控制。     

Novel inhaled combined antibiotic formulations in the treatment of Pseudomonas aeruginosa airways infections in cystic fibrosis

In cystic fibrosis, chronic airways infection caused by Pseudomonas aeruginosa can be treated with inhaled antibiotics such as inhaled tobramycin, aztreonam or colistin. However, biofilm formation induced by this bacterium can reduce the effectiveness of such therapies and can contribute to antibiotic resistance. Inhaled antibiotic combination might represent an optimal antibiofilm strategy in this setting. This review discusses the rationale for combining the antibiotics as well as some emerging or existing combinations. Most of the combinations except for fosfomycin/tobramycin are at an early stage of development. The latter combination was found to be effective in Phase II clinical studies and is planned to be tested in Phase III trials. The clinical data on long-term efficacy are currently missing, but the existing evidence as well as the unmet therapeutic need can prompt the further evaluation of such compounds.     

Preparation of aminoglycoside-loaded chitosan nanoparticles using dextran sulphate as a counterion

The objective of this study was to apply the specific acid-catalysed hydrolysis of ethyl acetate to completing solvent extraction during an emulsion-based microencapsulation process. The dispersed phase consisting of poly-D,L-lactide-co-glycolide and ethyl acetate was emulsified in an acid catalyst containing aqueous phase. Catalytic hydrolysis of ethyl acetate led to its continual leaching from the dispersed phase of the emulsion, thereby triggering microsphere hardening with high efficiency. Ketoprofen was successfully encapsulated into microspheres via this technique, and liquid chromatography–mass spectrometry showed that its structural integrity was preserved during microencapsulation. Compared to typical solvent extraction approaches, the acid-catalysis technique helped minimize the consumption of a quench liquid. Also, the resultant microspheres displayed excellent dispersibility and decreased propensity for aggregation. Furthermore, the new method provided better drug encapsulation efficiency and lower levels of residual ethyl acetate in microspheres. In conclusion, the acid-catalysis approach had great potential for the preparation of versatile microspheres and nanoparticles.     

Inhaled antibiotics for the treatment of chronic bronchopulmonary Pseudomonas aeruginosa infection in cystic fibrosis: systematic review of randomised controlled trials

Introduction: Inhaled antibiotics are probably the safest and most effective therapy for Pseudomonas aeruginosa chronic lung infection in cystic fibrosis (CF) patients.

Areas covered: To summarise the available evidence, a systematic review of the three currently available inhaled antibiotics (aztreonam lysine (AZLI), colistin (COL) and tobramycin (TOB)) was performed. The three AZLI placebo-controlled studies showed that the improvements in FEV₁ and mean sputum P. aeruginosa density were statistically significant better than with placebo. The two COL placebo-controlled studies involved few patients but showed that COL was better than placebo in terms of maintenance of some pulmonary function parameters. The tobramycin inhalation solution (TIS) and tobramycin inhalation powder studies showed that the efficacy of both formulations was similar but significantly better than placebo. In the comparative studies, TIS showed more efficacy than COL solution, colistin inhalation powder showed non-inferiority to TIS and AZLI was superior to TIS.

Expert opinion: Placebo-controlled and comparative clinical trials have shown that clinical evidence of inhaled antibiotics is very different. The choice of treatment for each individual CF patient must be based on the features of the drug (clinical evidence on efficacy and safety), the inhalation system and the patient characteristics. Development of new inhaled antibiotics will allow new end points of efficacy and therapy regimens to be assessed.     

Effects of iron depletion on antimicrobial activities against planktonic and biofilm Pseudomonas aeruginosa

Objectives Iron plays an important role in the development of Pseudomonas aeruginosa biofilm. Here we evaluated effects of iron depletion on the antimicrobial activity of ceftazidime, tobramycin and ciprofloxacin against planktonic and biofilm Pseudomonas aeruginosa. Methods We tested the sensitivities of wild‐type PAO1, type‐IV pilus mutant PAO‐ΔpilHIJK and the quorum‐sensing mutant PAO‐JP2 P. aeruginosa planktonic cultures and biofilms to antibiotics under iron‐depleted conditions. Key findings In planktonic bacteria, the minimum concentration that inhibited visible growth (MIC) of ciprofloxacin was increased slightly in an iron‐depleted environment in all three strains, whereas the MIC of tobramycin was similar in iron‐depleted and control environments. The MIC of ceftazidime increased in the PAO‐JP2 strain when iron was depleted. Tobramycin achieved the best bactericidal effect in biofilms. Viable counts were reduced by one log under iron‐depleted conditions in all three strains when tobramycin reached 4 MIC and when ceftazidime and ciprofloxacin reached 8 MIC. Conclusions This study suggests that once the biofilm is formed, iron depletion may only slightly promote the bactericidal effect of antibiotics on PAO1, PAO‐ΔpilHIJK and PAO‐JP2. Although these changes were relatively small, iron as one of the environmental factors should not be ignored when evaluating bactericidal effect of antibiotics. The combination of an iron chelator and antibiotics may have therapeutic value under certain bacterial growth conditions.