首页 | 本学科首页   官方微博 | 高级检索  
相似文献
 共查询到20条相似文献,搜索用时 718 毫秒
1.
BACKGROUND: Ventilator-associated pneumonia (VAP) remains the leading cause of death in patients with intensive care unit (ICU) acquired infections associated with an attributable mortality around 30%. Increasing antimicrobial resistance in patients with VAP challenges intensivists to search for alternative therapeutic options. There is scarcity of data in the literature concerning the administration of aerosolized colistin in critically ill patients with VAP due to multidrug-resistant (MDR) Gram-negative pathogens. METHODS: To assess the safety and effectiveness of aerosolized colistin as an adjunctive to the intravenous antimicrobial therapy for the treatment of VAP due to MDR Gram-negative pathogens, we prospectively examined all patients, who received inhaled colistin. RESULTS: Sixty critically ill patients with a mean APACHE II score 16.7, received aerosolized colistin for the treatment of VAP due to MDR pathogens [Acinetobacter baumannii (37/60 cases), Pseudomonas aeruginosa (12/60 cases) and Klebsiella pneumoniae strains (11/60 cases)]. Half of the isolated pathogens were susceptible only to colistin. Mean (+/-SD) daily dosage of aerosolized colistin was 2.2 (+/-0.7) million international units (IU). All patients received 2946 inhalations of colistin and the mean duration of administration was 16.4 days. Fifty-seven patients received concomitant intravenous treatment with colistin or other antimicrobial agents. Bacteriological and clinical response of VAP was observed in 50/60 (83.3%) patients. No adverse effects related to inhaled colistin were recorded. All cause hospital mortality was 25% while mortality attributable to VAP was 16.7%. CONCLUSIONS: Aerosolized colistin may be considered as adjunctive to intravenous treatment in patients with VAP due to MDR Gram-negative bacteria susceptible to colistin in critically ill patients. Although colistin is safe and effective, the best route of administration remains unclear. In addition, controlled comparative studies are needed to establish its effectiveness and safety.  相似文献   

2.
Chronic airway infection and inflammation are key events in the clinical course of cystic fibrosis (CF). The most relevant, best investigated strain of bacteria in these circumstances is Pseudomonas aeruginosa. Since pulmonary infection with P. aeruginosa is localized in the lower conducting airways, treatment is accessible with the use of inhaled aerosolized antibiotics. Tobramycin inhalation solution was the first antibiotic to be developed and approved (in 1998) for use as an aerosolized antibiotic in patients with CF. The only other aerosolized antibiotic indicated for this use is aztreonam lysine solution for inhalation, which has been approved by both European and US authorities. In prospective, randomized, controlled trails, both agents exhibited a very acceptable safety profile, along with an increase in forced expiratory volume in 1 second and other clinically relevant endpoints. New developments focus on such components as reducing the treatment burden by using dry power inhalers, decreasing inhalation frequency to once daily, penetrating P. aeruginosa biofilms, and combining two antibiotics in one solution for inhalation. However, the ideal aerosolized antibiotic regimen for the treatment of chronic P. aeruginosa infection has yet not been selected.  相似文献   

3.
Pseudomonas aeruginosa pneumonia   总被引:3,自引:0,他引:3  
PURPOSE OF REVIEW: Recent articles of clinical interest on Pseudomonas aeruginosa respiratory tract infections including CAP, nosocomially-acquired pneumonia, particularly in the ventilated patient, and chronic infections in cystic fibrosis patients are reviewed. RECENT FINDINGS: The growing importance of P. aeruginosa as an etiologic agent of CAP, the occurrence of CAP in previously healthy adults and its high prevalence as an etiologic agent of late VAP are stressed in recent studies. The effect of antibiotics on the recovery of bacteria in respiratory samples of patients with VAP can be marked and as early as 12 h after administration of antimicrobials certain organisms are no longer cultivable; in contrast, P. aeruginosa can still be recovered even after 48 h of adequate therapy. Type III secretory proteins are recognized as important virulent factors in P. aeruginosa. This phenotype predicts a worse outcome in patients with VAP. Fluoroquinolones have a major role in the emergence of multiply resistant P. aeruginosa in patients with VAP. Pharmacokinetic/pharmacodynamic parameters of antimicrobials with antipseudomonal activity are gaining importance as a means of optimization of antibiotic therapy. In CF, the knowledge of the pharmacokinetics and bioavailability of inhaled tobramycin and its long term beneficial effect in lung function are important developments in this area. SUMMARY: P. aeruginosa continues to be a serious problem worldwide as a cause of respiratory tract infections in selected populations. Microbiologic diagnosis remains difficult and plagued with pitfalls. The application of modern PK/PD concepts should help to optimize antibiotic therapy of this increasingly difficult to treat infection, particularly at the respiratory tract level and with an increasing prevalence of resistance to all antipseudomonal agents. Inhaled antibiotics, particularly tobramycin, are increasingly used for the prevention and treatment of P. aeruginosa infection in CF patients.  相似文献   

4.
PURPOSE OF REVIEW: The purpose of this review is to summarize modern data pertaining to the use of aerosolized antimicrobials for the treatment of and prophylaxis against pulmonary infections. RECENT FINDINGS: Few recent publications have examined the safety and efficacy of nebulized antibiotics. Two well conducted trials have been published that describe the utility of tobramycin solution for inhalation among cystic fibrosis patients. A couple of good reviews have also been published that have summarized the use of aerosolized antibiotics in other patient populations. SUMMARY: Data regarding this topic are scarce. At this time, data support the use of aerosolized tobramycin solution for inhalation in cystic fibrosis patients infected or colonized by Pseudomonas aeruginosa. Apart from this situation, widespread aerosolized administration of other agents in cystic fibrosis and non-cystic fibrosis patient populations should not be advocated.  相似文献   

5.
There are no approved pharmacologic agents to enhance mucus clearance in non-cystic fibrosis (CF) bronchiectasis. Evidence supports the use of hyperosmolar agents in CF, and studies with inhaled mannitol and hypertonic saline are ongoing in bronchiectasis. N-acetylcysteine may act more as an antioxidant than a mucolytic in other lung diseases. Dornase α is beneficial to patients with CF, but is not useful in patients with non-CF bronchiectasis. Mucokinetic agents such as β-agonists have the potential to improve mucociliary clearance in normals and many disease states, but have not been adequately studied in patients with bronchiectasis.  相似文献   

6.
The efficacy of inhaled sympathomimetic and anticholinergic agents on airway obstruction in cystic fibrosis (CF) has been proven in several studies. However, studies comparing combined therapy with monotherapy led to divergent results, probably due to different study designs, different dosages, and the small numbers of patients investigated. Therefore, we wanted to answer the question which inhalation has the best short term effect: a sympathomimetic or an anticholinergic agent, or the combination of both. We investigated 17 patients with CF on 4 successive days in the morning, using pulmonary function testing before and 30 min after inhalation. Each patient received aerosolized salbutamol (SB, maximum dose (max.) 2.5 mg), ipratropium bromide (IB, max. 0.5 mg), the combination of both, or placebo (normal saline) in a randomized, double-blind crossover design. The mean forced expiratory volume in the first second improved significantly (adjusted P-value < 0.017) after each treatment compared to placebo. Analysis of variance showed that SB and combination therapy with SB and IB were superior to IB alone, without significant difference between SB and combination therapy. Response of a patient to combined therapy was usually associated with response to SB. Long-term efficacy and side effects of treatment with bronchodilators still remain to be investigated after this short term study. We conclude that in CF patients bronchodilator therapy with sympathomimetic agents is usually sufficient. Only in cases with proven additional benefit from inhalation by anticholinergics should combination therapy be recommended.  相似文献   

7.
Antimicrobial therapy is an important aspect of disease management for patients with bronchiectasis. Delivery of an inhaled antibiotic is an appealing alternative to oral or intravenous administration because the antibiotic is delivered in high concentrations directly to the site of infection, eliminating the need for high systemic concentrations and reducing the risk of systemic toxicity. In recent controlled studies these potential benefits have been assessed in patients with bronchiectasis who became colonized by P. aeruginosa and the results support the use of nebulized antibiotics. In up to one-third of patients P. aeruginosa was eradicated from their sputum by inhaled antibiotic therapy and up to 62 % of patients showed improved medical condition. The further development of new aerosol devices supported by clinical testing will allow effective management of patients with bronchiectasis by an inhalation therapy that minimizes time constraints and drug loss which may improve health status and quality of life.  相似文献   

8.
BACKGROUND: There is no information on serial pharmacokinetic assessment in the lungs after administration of aerosolized pentamidine. OBJECTIVE: The present study was performed to evaluate the elimination of aerosolized pentamidine from bronchial airways following inhalation. METHODS: We used 4 sheep with tracheotomies in the present study. Pentamidine (300 mg) was administered by inhalation to each animal. Serial bronchial washing to obtain epithelial lining fluid (ELF) was performed 1, 7, 10, 14, 21 and 28 days after administration of aerosolized pentamidine in each animal. The pentamidine concentration in the supernatant of ELF was measured by high-performance liquid chromatography. RESULTS: The maximal pentamidine level on the first day (12 h after inhalation) was 616.5 +/- 238.2 ng/ml (mean +/- SE) in ELF. The pentamidine levels rapidly decreased within 2 weeks (8.9 +/- 1.2 ng/ml at 14 days), followed by slow elimination (8.9 +/- 0.8 ng/ml at 28 days). Thus, inhaled pentamidine showed a rapid clearance from the bronchial wall within the first 2 weeks. CONCLUSIONS: These findings may be useful in designing and interpreting future studies of aerosolized pentamidine in patients who are receiving inhaled pentamidine, especially for those with failure of prophylaxis for Pneumocystis carinii pneumonia.  相似文献   

9.
Inhaled antimicrobial therapy   总被引:3,自引:0,他引:3  
Although antimicrobial therapy has been administered through the inhaled route for decades, it has always been controversial. There are relatively few accepted indications for this mode of administration. Well-controlled studies of aerosolized antibiotics in cystic fibrosis demonstrate that tobramycin on a cyclical basis may reduce sputum volume, bacterial counts, and improve pulmonary function. Preliminary data indicate that inhaled antibiotic therapy of ventilator-associated tracheobronchitis may reduce sputum volume, but the clinical significance of this finding remains to be determined. Inhaled pentamidine is used for prophylaxis of Pneumocystis carinii in patients with human immunodeficiency virus infection who are intolerant of oral prophylactic agents. Ribavirin has been used for 30 years to treat respiratory syncytial virus. The role, if any, of inhaled antifungal therapy with amphotericin B remains undetermined.  相似文献   

10.
目的采用荟萃分析方法对国内外已发表的文献进行综合分析,评价雾化吸入阿米卡星对呼吸机相关性肺炎治疗的有效性及安全性。方法全面检索PubMed、Embase、Cochrane Central Register of Controlled Trials、Web of Science数据库、中国知网、维普及万方数据库,获取数据检索时间限定为从建库至2018年11月,对比雾化吸入阿米卡星联合静脉抗生素治疗与单用静脉抗生素治疗的随机对照研究(RCTs),依照系统评价和荟萃分析优先报告的条目进行文献筛选、数据提取以及质量评价,采用Revman 5.3软件进行荟萃分析。结果共有8篇RCTs纳入研究。荟萃分析结果显示:与单用静脉抗生素治疗相比,雾化吸入阿米卡星联合静脉抗生素治疗显著提高临床治愈率(OR=2.59,95%CI:1.87~3.59,P<0.00001),增加细菌清除率(OR=2.87,95%CI:1.93~4.27,P<0.00001),雾化联合治疗组撤机率(OR=1.88,95%CI:1.16~3.04,P=0.01)。但雾化吸入阿米卡星联合静脉抗生素和单纯抗生素治疗2组的病死率差异无统计学意义(OR=1.39,95%CI:0.86~2.24,P=0.18),支气管痉挛发生率(OR=2.30,95%CI:1.00~5.30,P=0.05)、肾功能损伤率(OR=0.61,95%CI:0.34~1.11,P=0.10)差异无统计学意义。结论呼吸机相关性肺炎患者予以雾化吸入阿米卡星联合静脉抗生素较单用静脉抗生素能改善患者临床治愈率、细菌清除率及呼吸机撤机率,但不会降低患者病死率及增加支气管痉挛发生率和肾功能损伤率。  相似文献   

11.
Inhaled antibiotics offer an attractive alternative to systemic administration in cystic fibrosis (CF) for several reasons. Antibiotics can be administered directly to the site of infection with little systemic absorption, thereby minimizing toxicity. Aerosolization will permit chronic administration of antipseudomonal antibiotics while avoiding the risks and inconvenience of intravenous access. Modern aerosolized drug delivery systems enable endobronchial delivery of very high antibiotic concentrations, resulting in clinical improvement even in patients with bacterial organisms that traditionally would have been considered resistant. This article summarizes basic concepts of aerosol drug administration and reviews available data on the administration of a variety of drug classes for both suppressive therapy and acute exacerbations of cystic fibrosis, including toxicity and safety data. The aminoglycosides have been by far the most extensively studied class of antibiotics, culminating in U.S. Food and Drug Administration (FDA) approval of a specifically formulated tobramycin solution for inhalation. The available data on the development of antibiotic resistance and emergence of other organisms with long-term use of this agent are reviewed. Finally, a brief guideline for initiating and monitoring patients on antibiotic aerosols is provided for the clinician caring for CF patients.  相似文献   

12.
Bronchiectasis is a chronic disorder characterized by impaired mucociliary clearance and a relentless cycle of infection, inflammation and bronchial wall injury, which has a debilitating impact on the patient's quality of life and results in increased morbidity and mortality. It is a disease for which there are no currently registered therapeutic products, limited epidemiological data and no validated endpoints that have been accepted by the majority of regulatory authorities. This article reviews the evidence base for the efficacy of inhaled dry powder mannitol in patients with non-cystic fibrosis (CF) bronchiectasis. The few published papers on this topic concluded that mannitol, when inhaled as a dry powder, is a promising treatment for bronchiectasis. It is designed to hydrate the lungs and restore normal mucociliary clearance mechanisms in the lungs. Based on the available evidence, mannitol inhalation is well tolerated and improves the quality of life of patients with non-CF bronchiectasis. There is a need for well designed and adequately powered multicentre trials to establish the potential usefulness of mannitol as a treatment for non-CF bronchiectasis.  相似文献   

13.
铜绿假单胞菌致下呼吸道感染的药敏分析   总被引:1,自引:0,他引:1  
成炜  蒋捍东  马红 《山东医药》2006,46(34):10-11
目的探讨下呼吸道铜绿假单胞菌(PA)感染的药敏情况,供临床用药参考。方法对82例3次痰培养为PA的慢性阻塞性肺疾病(COPD)、支气管扩张症及呼吸机相关性肺炎(VAP)患者进行药敏分析。结果VAP耐药率最高,COPD、支气管扩张症相似;敏感性较高的药物依次为头孢哌酮-舒巴坦、哌拉西林-他唑巴坦、阿米卡星、美洛培南及亚胺培南。结论下呼吸道感染PA耐药率高,且VAP高于COPD及支气管扩张症。  相似文献   

14.
BACKGROUND: In cystic fibrosis (CF) patients, the absence or dysfunction of the chloride channel CF transmembrane conductance regulator (CFTR) results in reduced chloride ion transport in respiratory epithelial cells. Moli1901 stimulates an alternative chloride channel and may thus compensate for the CFTR deficiency in the airway epithelium of CF patients. METHODS: A phase II, placebo-controlled, double-blinded, single-center, multiple (5 consecutive days), rising-dose (daily dose, 0.5, 1.5, or 2.5 mg of Moli1901) study was conducted to investigate the safety and tolerability of multiple doses of aerosolized inhaled Moli1901 in 24 patients with CF and stable lung disease. RESULTS: Moli1901 was well tolerated in all but one CF patient, in whom a transient significant decrease in FEV(1) developed following inhalation, which resolved spontaneously, and in a second patient in whom transient throat numbness developed during drug inhalation. A significant improvement of FEV(1) was observed in the group receiving treatment with 2.5 mg/d Moli1901 compared to the group receiving placebo (p = 0.01 [Wilcoxon test]). Moli1901 was not detected in the plasma of the highest dose group. CONCLUSIONS: The inhalation of Moli1901 up to a total cumulative dose of 12.5 mg appears to be safe in adult patients with CF. In addition, Moli1901 had a sustained beneficial effect on pulmonary function, which supports further studies of its efficacy in CF patients.  相似文献   

15.
Ventilator-associated pneumonia (VAP) is responsible for approximately half of the infections acquired in the intensive care unit (ICU) and represents one of the principal reasons for prescribing antibiotics in this setting. Because unnecessary prolongation of antimicrobial therapy and insufficient dosing of antibiotics at the site of infection in patients with true bacterial infection may lead to the selection of multidrug-resistant microorganisms without improving clinical outcome, efforts to reduce the duration of therapy and optimize pulmonary penetration of antimicrobial agents are warranted. An 8-day regimen can probably be standard for patients with VAP. Possible exceptions to this recommendation include immunosuppressed patients, those whose initial antimicrobial treatment was not appropriate for the causative microorganism(s), and patients whose infection was caused by very difficult-to-treat microorganisms and had no improvement in clinical signs of infection. Nebulizing concentration-dependent antibiotics such as aminoglycosides during mechanical ventilation can markedly increase tissue penetration in foci of pneumonia as compared with intravenous administration. The superiority in terms of pulmonary penetration and antibacterial efficacy of this route of administration was demonstrated in a model of ventilated piglets with and without bronchopneumonia.  相似文献   

16.
Abstract The increasing problem of antimicrobial resistance has forced the medical community to evaluate alternative preventive and therapeutic strategies for nosocomial pneumonia, infection that is associated with considerable morbidity and mortality. Among them, local administration of polymyxins into the respiratory tract represents a promising strategy. This review highlights recent evidence regarding the effectiveness and safety of this intervention in the prevention and treatment of patients with multidrug-resistant Gram-negative bacterial infections. Polymyxins can be administered directly to the respiratory tract through jet or ultrasonic nebulizers, dry powder inhalers, or by endotracheal instillation. Data from limited studies on pharmacokinetic and pharmacodynamic properties of aerosolized polymyxins suggest that while high sputum concentrations are achievable systemic exposure is limited. The incidence of colonization of the upper respiratory tract with Gramnegative bacteria, especially Pseudomonas aeruginosa was considerably reduced in two trials that assessed the effect of prophylactic administration of aerosolized polymyxins on the colonization of the respiratory tract of critically ill patients. Clinical trials that examined the value of aerosolized polymyxins in the prevention of lung infections resulted in conflicting findings. Although the incidence of Gram-negative bacterial pneumonia was decreased in the majority of the studies, no improvement in mortality was found. Possible selection of polymyxin-resistant microorganisms has been the major limitation. Treatment of Gram-negative bacterial nosocomial pneumonia with aerosolized polymyxins may be a beneficial supplemental to the conventional therapy; however, its value remains to be proved. The available evidence supports that the local administration of polymyxins into the respiratory tract for the prevention and treatment of multidrug-resistant (MDR) Gram-negative bacterial infections deserves further investigation.  相似文献   

17.

Purpose

Although investigations are limited, adjunctive aerosolized antibiotics have been advised in the setting of gram-negative ventilator-associated pneumonia (VAP). This study aimed to compare the efficiency of inhaled colistin with inhaled fosfomycin/tobramycin in treating VAP due to extensively drug-resistant (XDR) Acinetobacter baumannii.

Methods

This single center open-label randomized controlled trial included 60 patients who developed XDR A. bumannii VAP. Eligible participants were randomly assigned to two groups (no. 30). Regardless of the assignment, all participants received meropenem (2 g as a 3-h extended infusion every 8 h) plus intravenous colistin (a loading dose of 9 million IU and then 4.5 million IU every 12 h). The control group was given inhaled colistin (1 million IU every 8 h), and the case group received inhaled tobramycin/fosfomycin (300 mg every 12 h/80 mg every 12 h) as adjunctive therapy. The primary outcome was treatment duration, and the secondary outcomes were Clinical Pulmonary Infection Score (CPIS) trend and mortality rate in the groups. The decision to stop treatment was made by the treating physician.

Results

The mean treatment duration was 13.73 ± 3.22 days in the colistin group and 10.85 ± 2.84 days in the tobramycin/fosfomycin group; the mean treatment duration in the latter group was lower significantly (P = 0.001). CPIS was decreased in the groups significantly (P < 0.001), but the mean changes of CPIS were significantly different between the groups, and in the inhaled tobramycin/fosfomycin group, a greater reduction (P = 0.005) was observed. Two (6.67%) patients in the control group and three (10%) patients in the case group died.

Conclusion

The use of inhaled tobramycin/fosfomycin in cases with XDR A. bumannii VAP was associated with a shorter treatment duration in this open-label trial.  相似文献   

18.
In chronic Pseudomonas aeruginosa pulmonary infection of patients with cystic fibrosis (CF), antibiotic therapy generally fails to eradicate the bacterial pathogen. The mucoid bacterial phenotype, high sputum production by the host, and low airway levels of antibiotics seem to be responsible for the observed decrease in antibiotic efficacy. We hypothesized that early antibiotic treatment by inhalation in CF patients may be able to prevent or at least delay airway infection. In a prospective placebo-controlled, double-blind, randomized multicenter study, 22 CF patients received either 80 mg b.i.d. of aerosolized tobramycin or placebo for a period of 12 months shortly after the onset of P. aeruginosa pulmonary colonization. Two patients in the tobramycin and six patients in the placebo group stopped inhalation before the 12 month treatment period. Using life table analysis, the time to conversion from a P. aeruginosa-positive to a P. aeruginosa-negative respiratory culture was significantly shorter in the tobramycin-treated group than in the placebo group (P < 0.05, log rank test). Lung function parameters and markers of inflammation did not change in either group during treatment. The results of this study suggest that early tobramycin inhalation may prevent and/or delay P. aeruginosa pulmonary infection in CF patients. Pediatr. Pulmonol. 1998; 25:88–92. © 1998 Wiley-Liss, Inc.  相似文献   

19.
The number of patients with cystic fibrosis (CF) whose sputum culture has yielded Stenotrophomonas maltophilia has increased in the last 5 years at St. Christopher's Hospital for Children. We conducted a case-control study to determine risk factors for recovery of S. maltophilia in respiratory secretions from patients with CF. We reviewed the outpatient and inpatient records of patients colonized with S. maltophilia between 1993 and 1997, and of age-matched (at time of initial recovery of S. maltophilia) control patients with CF who had never had a positive sputum culture for S. maltophilia. Variables included age at time of CF diagnosis, gender, severity of CF (based on Shwachman-Kulczycki (S-K) scores and spirometry), frequency of hospitalizations, use of oral, intravenous, or inhaled antibiotics, and use of oral or inhaled corticosteroids in the 2 years prior to the first isolation of S. maltophilia from respiratory secretions. Statistical methods included stepwise logistic regression to determine risk factors for acquisition of S. maltophilia. During the study period, 58 patients with CF had a positive sputum or deep throat culture for S. maltophilia. The distribution of S. maltophilia acquisition by year increased from 7 patients in 1993 (incidence, 2.8%) to 16 in 1997 (incidence, 6.2%). Patients positive for S. maltophilia were found to have significantly worse growth parameters, S-K score, and spirometric values than S. maltophilia-negative CF controls (P < 0.05). Stepwise logistic regression demonstrated that treatment with long-term antibiotics (P = 0.0016) and number of days of intravenous antibiotic therapy (P = 0.035) were significant risk factors for S. maltophilia colonization in our group of CF patients. We conclude that patients with CF whose respiratory secretions yield S. maltophilia have an overall worse clinical status at the time of initial S. maltophilia isolation than noncolonized patients, and that preceding treatment with antibiotics may have predisposed them to the acquisition of this bacterium in their respiratory secretions.  相似文献   

20.
目的 探讨头孢哌酮/舒巴坦联合雾化妥布霉素治疗支气管扩张伴绿脓杆菌感染的疗效观察.方法 对入选的80例患者,随机分为观察组和对照组,观察组给予头孢哌酮/舒巴坦静脉输注及妥布霉素雾化吸入治疗,对照组将妥布霉素改为静脉输注,两组的疗效进行比较.结果 两组患者有关病情恢复时间的相关指标、治疗前后肺功能指标及总有效率进行比较,差异有统计学意义(P〈0.05).结论 头孢哌酮/舒巴坦静脉输注联合妥布霉素雾化吸入治疗支气管扩张伴铜绿假单胞菌感染的疗效安全、可靠.  相似文献   

设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号