阿奇霉素对支气管哮喘患者肺功能及细胞因子的影响

 目的 评价阿奇霉素治疗支气管哮喘的临床疗效,对肺功能和细胞因子的影响及其治疗安全性。方法 本实验40例哮喘患者,随机分入阿奇霉素联合吸入性糖皮质激素加长效β2-肾上腺素受体激动剂组,或吸入性糖皮质激素加长效β₂-肾上腺素受体激动剂组,评估治疗前后各组患者哮喘控制测试评分、肺功能、诱导痰标本内细胞因子IL-4、IL-5和IFN-γ的浓度变化,及阿奇霉素的不良反应。结果 治疗12周后,两组患者的哮喘控制测试评分、肺功能指标较治疗前均明显改善,诱导痰细胞因子的浓度亦明显下降,差异有统计学意义;阿奇霉素组诱导痰标本内细胞因子浓度较对照组下降明显,差异有统计学意义;两组均未出现严重的不良事件。结论 阿奇霉素联合吸入性糖皮质激素加长效β₂-肾上腺素受体激动剂治疗哮喘安全有效,可有效降低哮喘患者气道内 Th2 细胞因子含量。     

红霉素、阿奇霉素序贯疗法治疗小儿支原体肺炎30例

目的观察红霉素、阿奇霉素序贯疗法对小儿支原体肺炎的疗效和不良反应。方法把确诊为支原体肺炎患儿随机分为阿奇霉素组、红霉素组及联合治疗组（红霉素、阿奇霉素序贯治疗）共3组,每组30例,对其临床疗效,治疗费用及药物不良反应进行评价。结果3组有效率比较,差异均无显著性（P〉0．05）。住院天数、治疗费用以联合治疗组最低,且联合治疗组、阿奇霉素组与红霉素组比较,差异均有显著性（P〈0．01）。药物不良反应发生率以联合治疗组、阿奇霉素组为低。联合治疗组、阿奇霉素组与红霉素组不良反应率比较,差异均有显著性（P〈0．05）。结论联合治疗组治疗支原体肺炎优于其他两组,同时可减少经济费用,且副作用少。     

小儿静脉滴注阿奇霉素时胃肠道副反应的防治

目的 比较磷酸铝凝胶(aluminum phosphate)和蒙脱石散剂(dioctahedral smectite)对小儿阿奇霉素静滴时胃肠道副反应的防治效果.方法 315例支原体肺炎患儿,随机分为硫酸铝凝胶组、蒙脱石散剂组和对照组,各105例.观察三组在阿奇霉素静滴时胃肠道副反应(包括腹痛、腹泻、恶心、呕吐)的发生情况.结果 硫酸铝凝胶组和蒙脱石散剂组阿奇霉素静滴后胃肠道副反应发生率明显低于对照组(P＜0.01),硫酸铝凝胶组的发生率较蒙脱石散剂组更低(P＜0.05).三组的治疗效果无统计学差异(P＞0.05).结论 硫酸铝凝胶、蒙脱石散剂可明显减少阿奇霉素的胃肠道副反应,尤以硫酸铝凝胶的效果显著.     

The pharmacodynamic properties of azithromycin in a kinetics-of-kill model and implications for bacterial conjunctivitis treatment

Introduction

Antibiotics have traditionally been classified as bactericidal or bacteriostatic. Azithromycin belongs to the parent class of macrolides that are characteristically bacteriostatic. Some evidence suggests that this mol-ecule demonstrates bactericidal kill and has concentration-dependent effects. This study tests the hypothesis that azithromycin demonstrates a bactericidal, concentration-dependent antibiotic effect at concentrations corresponding to and exceeding published tear and conjunctival levels.

Methods

The antibacterial activity of different concentrations of azithromycin 1% in DuraSite® (AzaSite®; Inspire Pharmaceuticals Inc, Durham, NC, USA) was evaluated using a kinetics-of-kill model. Recent conjunctivitis isolates of Staphylococcus aureus, Streptococcus pneumoniae or Haemophilus influenzae were exposed to four concentrations of azithromycin (100, 250, 500 and 750 μg/ml). Starting concentrations were similar to the maximum concentrations (Cmax) that have been demonstrated in conjunctiva (83 μg/g) and tears (288 μg/ml) following topical ocular administration. The percentage of surviving bacteria at 30 and 60 minutes following exposure to each concentration were determined.

Results

Azithromycin failed to demonstrate bactericidal activity (i.e. a 3-log reduction in surviving bacteria) against S. aureus, S. pneumoniae or H. influenzae. Furthermore, the rate and extent of antibacterial activity with azithromycin did not change with higher concentrations, even at the highest tested concentration of 750 μg/ml.

Conclusion

Similar to the parent macrolide class, azithromycin demonstrates bacteriostatic activity against common conjunctival pathogens up to the maximum tested concentration of 750 μg/ml (i.e. 2.6-times and 9-times published Cmax tear and conjunctival concentration, respectively). Azithromycin’s bacteriostatic effects and prolonged elimination half-life will likely lead to a corresponding increase in the emergence of macrolide-resistant isolates.

     

Single-dose azithromycin for the treatment of children with acute otitis media

Azithromycin is an azalide with in vitro activity against otitis media pathogens, good middle ear penetration and a prolonged half-life. A total of four clinical trials have evaluated the clinical success rate, safety and compliance of single-dose azithromycin (30 mg/kg) in the treatment of children with otitis media. Among all the patients treated with single-dose azithromycin (30 mg/kg), and presented previously in four published clinical trials, end-of-treatment clinical success was 88% (544 out of 619) and maintained clinical success at the end-of-study was 82% (498 out of 610). Three of the four studies included a mandatory baseline tympanocentesis. The overall end-of-treatment and end-of-study clinical success rates among all culture-positive patients was 84% (222 out of 263) and 80% (210 out of 263), respectively. Per pathogen end-of-treatment clinical success rates observed were 91% (125 out of 137) among patients with Streptococcus pneumoniae, 77% (75 out of 97) among patients with Haemophilus influenzae, 100% (14 out of 14) among patients with Moraxella catarrhalis, 64% (seven out of 11) among patients with baseline Streptococcus pyogenes and 25% (one out of four) among patients with a S. pneumoniae and H. influenzae mixed infection. Clinical success was observed in 90% (106 out of 118) of patients with baseline macrolide-susceptible S. pneumoniae and in 67% (14 out of 21) among patients with baseline macrolide-resistant S. pneumoniae (p = 0.01). Adverse events were uncommon, mostly mild and transitory gastrointestinal complaints, and in the two larger comparative trials, were less frequent than the rates observed with the comparator agents. Compliance was excellent (99–100%). Single-dose azithromycin (30 mg/kg) represents an alternative for the treatment of pediatric patients with uncomplicated acute otitis media, particularly in those geographic regions where high-level S. pneumoniae macrolide resistance is uncommon, and for those patients that require directly observed therapy or when compliance may be a problem.     

Treatment of Tularemia in Pregnant Woman,France

A pregnant woman who had oropharyngeal tularemia underwent treatment with azithromycin and lymph node resection and recovered without obstetrical complication or infection in the child. Azithromycin represents a first-line treatment option for tularemia during pregnancy in regions where the infecting strains of Francisella tularensis have no natural resistance to macrolides.     

Electron microscopic evidence of persistent chlamydial infection following treatment

Chlamydia trachomatis infections of the female and male genital tracts are often asymptomatic and, thus, tend to become persistent. In the persistent state the typical Chlamydia life cycle is arrested and standard antibiotic regimens do not always eradicate this infection. We sought to relate treatment failures in men and women with persistent chlamydial genital tract infections to electron microscopic evidence of chlamydial persistence and with atypical morphological forms of the organism. Of 16 patients with chlamydial persistence following azithromycin treatment, morphological variants of this organism were observed by electron microscopy from one endocervical sample and one male urethral sample. We document the presence of intracellular inclusions containing only reticulate bodies, extracellular monomembrane and polymembrane phagosomes containing elementary bodies and reticulate bodies with abnormal outer membranes in the process of dividing extracellularly. These observations parallel previous in vitro studies of chlamydial persistence under adverse conditions. This capacity of C. trachomatis to undergo atypical morphological alterations in vivo may contribute to its persistence and relative resistance to antibiotics.     

The dilemma of monotherapy or combination therapy in community‐acquired pneumonia

Scope

To study the factors associated with mortality in hospitalized patients with community‐acquired pneumonia treated with monotherapy or combination therapy.

Methods

PubMed and Scopus were searched. Patients receiving macrolides, β‐lactams and fluoroquinolones, as monotherapy or in combination, were included. Meta‐analyses and meta‐regressions were performed.

Results

Fifty studies were included. Overall, monotherapy was not associated with higher mortality than combination (RR 1.14, 95% CI 0.99‐1.32, I² 84%). Monotherapy was associated with higher mortality than combination in North American and retrospective studies. β‐lactam monotherapy was associated with higher mortality than β‐lactam/macrolide combination in the primary (1.32, 1.12‐1.56, I² 85%) and most sensitivity analyses. There was no difference in mortality between fluoroquinolone monotherapy and β‐lactam/macrolide combination (0.98, 0.78‐1.23, I² 73%). In meta‐regressions, the moderators that could partially explain the observed statistical heterogeneity were the frequency of cancer patients (P = .03) and Pneumonia Severity Index score IV (P = .008).

Conclusion

Due to the considerable heterogeneity and inclusion of unadjusted data, it is difficult to recommend a specific antibiotic regimen over another. Specific antibiotic regimens, study design and the characteristics of the population under study seem to influence the reported outcomes.