Safety of aerosol tobramycin administration for 3 months to patients with cystic fibrosis

To determine the potential toxicity of prolonged aerosol tobramycin administration, 22 patients with cystic fibrosis were monitored while receiving inhaled tobramycin three times a day for 12 weeks. Prior to, four times during administration and approximately 6 weeks after discontinuation of treatment, we assessed pulmonary function, weight, height, body temperature, eighth cranial nerve function, serum creatinine, blood urea nitrogen, urinary creatinine clearance, plasma iothalamate clearance, urinary beta-2 microglobulin concentration, and Pseudomonas aeruginosa density in sputum. There was no detectable laboratory evidence of nephrotoxicity. Neither a decrease in auditory acuity (range 250-20,000 Hz) nor vestibular dysfunction was detected. Pulmonary function tests significantly improved during the first month in all subjects (P less than 0.05) but returned to enrollment values by the end of the 12th week of administration of tobramycin aerosol. Sputum P. aeruginosa density initially decreased from a mean of 10(7) cfu/gm to a mean of 10(4) cfu/gm after 2 weeks of aerosol tobramycin administration and remained significantly below the enrollment value throughout. Coincident with the reduced bacterial density, a reduction in cough frequency and sputum production, as well as a weight gain was observed. Seventy-three percent of the patients with sputum P. aeruginosa isolates susceptible to tobramycin on enrollment yielded resistant organisms during aerosol administration. However, 1 year later all sputum P. aeruginosa isolates obtained from patients were susceptible to tobramycin. We conclude that thrice daily aerosol tobramycin administration for 3 months is not associated with detectable eighth cranial nerve or renal toxicity. Transient emergence of tobramycin resistant P. aeruginosa may occur.     

选择性口咽去污染防治呼吸机相关性肺炎的临床观察

目的观察口咽去污染对降低机械通气患者呼吸机相关性肺炎（VAP）发病率的意义。方法选择某院2012年1-6月入住重症监护室(ICU)内72 h以上且机械通气时间超过48 h的患者60例,随机分为实验组和对照组各30例。所有入选病例均给予静脉滴注头孢噻肟4 d,实验组机械通气全程用妥布霉素局部滴入口咽部,对照组用生理盐水局部滴入,记录两组患者发生VAP的病例数、发病时间及机械通气时间、ICU住院时间、病死率。定期留取气管内痰液进行细菌培养。结果实验组VAP的发病率为30.00%,明显低于对照组的63.33%; VAP的发病时间为(9.37±6.62)d,迟于对照组的(5.17±4.72)d;总机械通气时间为(7.63±6.91)d,低于对照组的(12.26±9.36)d;住ICU时间为(13.56±7.22)d,低于对照组的(16.79±11.16)d;上述项两组比较,均P<0.05。两组病死率比较,差异无统计学意义(P＞0.05)。结论口咽去污染是防治VAP的有效方法,能有效降低VAP发生率,使VAP发病时间延迟,并减少机械通气时间及入住ICU时间。     

Tobramycin suppresses HUWE1 degradation to control MCL-1 stability during tumour development

HUWE1 is an E3 ubiquitin ligase that is involved in cancer cell proliferation by regulating MCL-1 stability. The HECT domain has been shown to be required for the ubiquitin ligase activity of HUWE1. To identify efficient drugs that impair the activity of HUWE1, and thus decrease MCL-1 accumulation, we screened 2000 candidate compounds that might suppress HUWE1 activity. To evaluate these 2000 candidates, the HECT domain of HUWE1, which is the catalytic domain responsible for MCL1 ubiquitination, was selected as a conjugation site, and putative binding candidates were filtrated. Tobramycin emerged as one of the compounds that show efficient binding ability with the HECT domain of HUWE1. The surface plasmon resonance (SPR) results validated the specific binding of Tobramycin with the HECT domain. Subsequent analyses demonstrated its potential to inhibit cancer cell proliferation by binding to the HECT domain of HUWE1 and impeding the HUWE1-mediated ubiquitination of MCL-1. Consequently, the accumulation of MCL-1 inhibited the proliferation of tumour cells, while the apoptosis rates were not significantly altered after Tobramycin treatment. In vitro experiments showed that Tobramycin could inhibit cell proliferation by regulating the G2/M transition in cancer cell models, including A549 and HeLaCaco2 cell lines. Our results indicated that Tobramycin could be a potential new probe to develop targeted therapies for the prevention or treatment of HUWE1-overexpressing cancers.     

A successful antibiotic treatment by a new administration route: a case report of a subcutaneous administration of ceftazidime and tobramycin

When intramuscular or intravenous administrations of parenteral drugs are not possible, the use of other routes (e.g., subcutaneous route) should be considered. We report a patient with Duchenne muscular dystrophy, who was hospitalized for acute pneumonia due to antibiotic‐resistant strains of bacteria. Our patient was successfully recovered with antimicrobial therapy by subcutaneous administration of ceftazidime and tobramycin, for which no safety and efficacy data are available in humans. To the best of our knowledge, this case is the first supporting the subcutaneous administration safety and potential efficacy of both ceftazidime and tobramycin in humans.     

Eradication of early P. aeruginosa infection in children <7 years of age with cystic fibrosis: The early study

Objective

Antibiotic eradication treatment is the standard-of-care for cystic fibrosis (CF) patients with early Pseudomonas aeruginosa (Pa)-infection; however, evidence from placebo-controlled trials is limited.

泪道探通联合妥布霉素地塞米松填充治疗泪道阻塞

目的：探讨泪道探通术联合妥布霉素地塞米松眼膏填充治疗对泪道阻塞患者眼表症状和生活质量的影响。

方法：选取2016-10/2018-01我院收治的泪道阻塞患者120例120眼，按照治疗方法分为对照组(n=60)和观察组(n=60)。对照组予以单纯泪道探通术治疗，观察组予以泪道探通术联合妥布霉素地塞米松眼膏填充治疗。比较两组患者临床疗效、治疗前后眼表疾病指数量表(OSDI)评分及血清超敏C反应蛋白(hs-CRP)、降钙素原(PCT)水平的变化。

结果：观察组临床疗效明显优于对照组(P<0.05)。治疗后1mo，观察组OSDI总分及眼部不适频率评分、眼部不适对日常生活的影响评分、不良环境眼部不适发生频率评分均较术前明显降低(P<0.05)。治疗后1mo，观察组血清hs-CRP、PCT水平均明显低于对照组(P<0.05)。

结论：泪道探通术联合妥布霉素地塞米松眼膏填充治疗泪道阻塞疗效显著，能够有效改善患者眼表症状和生活质量。     

妥布霉素滴眼液和左氧氟沙星滴眼液治疗细菌性结膜炎的疗效观察

目的观察妥布霉素滴眼液和左氧氟沙星滴眼液治疗细菌性结膜炎的临床效果和安全性。方法回顾性分析2018年10月至2019年6月于该院门诊就诊的89例细菌性结膜炎患者的临床资料,所有患者依据就诊先后顺序分为对照组(43例)和研究组(46例)。对照组采用左氧氟沙星滴眼液治疗,研究组采用妥布霉素滴眼液治疗。比较两组临床疗效、细菌清除情况、眼表状况和不良反应发生情况。结果治疗后,研究组总有效率及细菌清除率高于对照组,差异均有统计学意义(P<0.05)。治疗前,两组泪膜破裂时间(BUT)、基础泪液分泌试验(SIt)结果比较,差异无统计学意义(P>0.05);治疗后,两组BUT、SIt结果均较治疗前下降,且对照组下降更为明显(P<0.05)。两组不良反应以眼部出现烧灼感、眼部瘙痒为主,组间不良反应发生率比较,差异无统计学意义(P>0.05)。结论妥布霉素滴眼液治疗细菌性结膜炎的效果优于左氧氟沙星滴眼液,更有利于细菌的清除,对眼表状态的影响较小,安全性更高。     

Physicochemical compatibility of mixtures of dornase alfa and tobramycin containing nebulizer solutions

Patients suffering from cystic fibrosis (CF) often need to inhale multiple doses of different nebulizable drugs per day. Patients attempt to shorten the time consuming administration procedure by mixing drug solutions/suspensions for simultaneous inhalation. The objective of this experimental study was to determine whether mixtures of the nebulizer solution dornase alfa (Pulmozyme®) with tobramycin nebulizer solutions (TOBI® and GERNEBCIN® 80 mg) are physico‐chemically compatible. Drug combinations were prepared by mixing the content of one respule Pulmozyme® with either one respule TOBI® or one ampoule GERNEBCIN® 80 mg. Test solutions were stored at room temperature and exposed to light. Dornase alfa activity and tobramycin concentrations were determined by using a kinetic colorimetric DNase activity assay and a fluorescence immunoassay, respectively. Physical compatibility was determined by visual inspection and measurements of pH and osmolality. Tobramycin concentration was not affected by mixing the drug products. In spite of the high variability of the dornase alfa potency assay, it is obvious that activity is especially affected by sodium metabisulfite, used as excipient in GERNEBCIN®. Patients should be advised, not to mix Pulmozyme® with GERNEBCIN® because of the incompatibility reaction. Further analytical studies are needed in order to determine the integrity and activity of dornase alfa in mixtures of Pulmozyme® with TOBI®. Finally clinical studies are necessary in order to demonstrate equivalent efficacy and safety of simultaneous inhalation in comparison to consecutive inhalation of both drugs. Pediatr Pulmonol. 2009; 44:134–141. © 2008 Wiley‐Liss, Inc.