Comparison of the Efficacy and Tolerability of Amoxycillin/Clavulanic Acid 875mg b.i.d. with Cefuroxime 500mg b.i.d. in the Treatment of Chronic and Acute Exacerbation of Chronic Sinusitis in Adults

Abstract

The efficacy and safety of amoxycillin/clavulanic acid (AMX/CA) (875/125mg b.i.d. for 14 days) were compared with that of cefuroxime axetil (500mg b.i.d. for 14 days) in a multicenter, open, parallel-group, randomized clinical trial in 206 adults with chronic or acute exacerbation of chronic sinusitis. Clinical response was similar, with 95% of AMX/CA-, and 88% of cefuroxime-treated, clinically evaluable patients cured (95% confidence interval; -0.6% to +15%). In bacteriologically evaluable patients, cure rates, defined as eradication of the original pathogen with or without re-colonization with non-pathogenic flora, were also similar, with 65% of AMX/CA- and 68% of cefuroximetreated patients cured (95% confidence interval; ?18% to +15%). However, clinical relapse was significantly higher in the cefuroxime group: 7% (7/89) of clinically evaluable patients, compared with 0% (0/98) in the AMX/CA (p=0.0049) group. A similar incidence of possible or definite adverse events related to the study drug was reported for both treatments (AMX/CA 4.4%, cefuroxime 4.3%), the most frequent being diarrhea. Four adverse events were recorded as serious or life-threatening with only one considered related to the study drug (urticaria, cefuroxime). AMX/CA 875/125mg b.i.d. for 14 days is as effective and well tolerated as cefuroxime axetil 500mg b.i.d. for 14 days in the treatment of chronic, or acute exacerbation of chronic sinusitis, but is associated with a significantly lower clinical relapse rate.     

Microbiological and molecular diagnosis of deep localized cutaneous infection with Trichophyton mentagrophytes

We describe a healthy young woman with a localized deep dermal infection on the right side of the chest wall. It was caused by the dermatophyte Trichophyton mentagrophytes, and resolved after two pulses of oral itraconazole 200 mg twice daily for 1 week. As cultural and microscopic features did not enable a precise identification of the fungus, molecular investigation was undertaken. Patterns of HaeIII restriction digests of genomic DNA from the culture matched those from Arthroderma incurvata and A. benhamiae, which is the teleomorph of T. mentagrophytes var. mentagrophytes.     

Itraconazole treatment of allergic bronchopulmonary aspergillosis in patients with cystic fibrosis

BACKGROUND: Allergic bronchopulmonary aspergillosis (ABPA) in cystic fibrosis (CF) patients is a potentially fatal inflammatory disease due to the dual-type immune response provoked by the fungal antigens. Despite serious side effects long-term treatment with corticosteroids is often required. Itraconazole has been reported to be a useful steroid-sparing agent. METHODS: In a retrospective follow-up of 21 CF patients from a total of 250 treated once or twice within a five-year study period (1994-98), 9 patients were treated with systemic glucocorticosteroids in combination with itraconazole and 12 patients were treated with itraconazole (200-600 mg/day) as monotherapy. RESULTS: During treatment the percentage of Aspergillus fumigatus (AF)-positive sputum cultures significantly reduced (P < 0.05); precipitating antibodies to AF decreased significantly in all patients (P < 0.05); forced expiratory volume (FEV1) increased to pre-exacerbation level; total IgE levels decreased in 42% of patients on monotherapy and in 56% on combination therapy. Specific IgE (radioallergosorbant; RAST) level decreased in 6 of 21 patients. Eleven patients had transient increased levels of alanine transaminase (ALAT). One patient had isolated increase in alkaline phosphatase and another in aspartate transaminase (ASAT). CONCLUSIONS: High dose itraconazole as monotherapy or in combination with systemic glucocorticosteroids seems effective in CF patients with ABPA. No hepatotoxicity was observed during long-term therapy.     

Minimal inhibitory concentration (MIC) of caspofungin and itraconazole inhibiting growth of Candida strains calculated from the linear regression equation

PurposeThe aim of the study was to compare the susceptibility of Candida species to caspofungin and itraconazole.Material and methods118 strains of Candida species were used in the study: 8 pattern strains and 110 strains isolated from different ontocenoses. The susceptibility of fungi strains to drugs was determined by diffusion in agar gel. The minimal inhibitory concentration (MIC) was calculated from the linear regression equation with the use of the method by Kad?ubowski.ResultsThe MIC value for caspofungin for the pattern strains ranged from 0.321 mg/L to 0.552 mg/L and for itraconazole from 0.019 mg/L to 0.11 mg/L. All the analyzed strains isolated from patients exhibited susceptibility to caspofungin; 5 strains of Candida albicans (8.06%) proved to be resistant to itraconazole. The MIC values for caspofungin ranged from 0.114 mg/L to 1.26 mg/L and for itraconazole from 0.012 mg/L to 16.1 mg/L.Conclusions1. All the studied pattern strains are susceptible to the examined drugs; all those isolated from patients show susceptibility to caspofungin; some Candida albicans strains (8.06%) are resistant to itraconazole. 2. The mean MIC values calculated from the activity curves are 0.426 mg/L for caspofungin and 1.0245 mg/L for itraconazole. 3. The mean MIC values calculated for caspofungin are lower than for itraconazole in the case of Candida albicans, C. glabrata and C. tropicalis. Having compared the influence of the drugs on C. famata, C. lusitaniae, C. parapsilosis and C. ciferri we proved there are statistically significant differences (0.0046>p<0.044).     

中国志愿受试者多剂量口服伊曲康唑后血液和指甲药代动力学研究

目的：对９例中国健康志愿者多剂量口服西安扬森公司生产的伊曲康唑后的血液和指甲药代动力学进行研究。方法：用高效液相色谱法测定血清和指甲中药物浓度，以３ｐ８７实用药代动力学程序计算稳态后，一次给药的药代动力学参数。结果：血中药物消除半衰期（ｔ１／２）平均为４１．５６ｈ；血中药物最高浓度（Ｃｍａｘ）平均为１２３０．８３ｎｇ／ｍｌ；血中药物达最高浓度的时间（Ｔｍａｘ）平均为４．３８ｈ；血药浓度－时间曲线下面积（ＡＵＣ）平均为６６３９６．５２ｎｇ·ｈ／ｍｌ。停药后ｄ７和９个月，受试者指甲中伊曲康唑的平均浓度分别为（９５７±１００９）ｎｇ／ｇ和（２３１±４１８）ｎｇ／ｇ。     

Efficacy and safety of intravenous itraconazole followed by oral itraconazole solution in the treatment of invasive pulmonary mycosis

Background  Invasive pulmonary mycosis is the most common type of invasive fungal infection. It is often severe and difficult to treat, and is accompanied by high mortality. In this study, we aimed to evaluate the efficacy and safety of intravenous itraconazole followed by oral itraconazole solution in the treatment of invasive pulmonary mycosis and to determine the distribution of different fungi species.

Methods  This was a multi-center, open-label study which enrolled 71 patients who were diagnosed as invasive pulmonary mycosis between July 2007 and January 2009. All patients received intravenous itraconazole therapy followed by oral itraconazole solution with a total treatment duration of 6 weeks. Intravenous itraconazole was given at a dose of 200 mg bid (intravenous infusion every 12 hours) for the first two days, 200 mg qd for the subsequent 12 days. Sequential oral itraconazole solution was given at a dose of 200 mg bid for 4 weeks. Efficacy and safety were assessed according to clinical as well as microbiological criteria.

Results  Seventy one patients participated in this study. Of the 60 patients in the full analysis dataset, the clinical response rate was 61.7% and the mycological eradication rate was 66.7%. The overall response rate was 66.7%. Drug-related adverse events occurred in 18.0% of patients: hypokalemia, liver function impairment and mild gastrointestinal side effects were the most common. One patient suffered from severe adverse event, with limb and facial swelling.

Conclusion This study showed that in patients with invasive pulmonary mycosis, intravenous itraconazole followed by oral itraconazole solution therapy was safe and effective.

     

Efficacy and safety of itraconazole as empirical antifungal therapy in febrile neutropenic patients with hematologic malignancies: an open-lable, multicenter, observational trial in a Chinese cohort

Background  Invasive fungal infection (IFI) is a common and fatal complication in neutropenic patients with hematological malignancy. Empirical antifungal therapy is widely used in practice due to the difficulty of pathogens determination and illness of the hosts. The aim of this study was to evaluate the efficacy and safety of itraconazole as empirical antifungal therapy for persistent fever in neutropenic patients with hematologic malignancies.

Methods  Two hundred and seventy-four patients with hematologic malignancies who had suspected fungal infections were enrolled in 18 centers across China between April 2008 and April 2009. Empirical antifungal therapy with intravenous itraconazole 200 mg twice daily was given for the first two days, followed by 200 mg once daily for the next 12 days. Oral itraconazole solution was sequential for follow-up therapy if necessary. Five composite end points were evaluated for the response, which was more restrictive and adopted for the first time in such study in China.

Results  The intent-to-treat analysis included data from 274 patients (full analysis set, FAS), of whom 248 were included as the per-protocol population (PPS). As the composite end point of five indices was concerned, the overall response rate was 43.4%. Seperately, defervescence was achieved in 90% of patients in which 55.5% occured during neutropenia. The mean time to defervescence was 2.71 days. Absence of breakthrough IFI during drug administration or within the first 7 days after study completion was observed in 71.5% of patients. Fifty-five point five percent patients with IFI at baseline was successfully treated. Ninety point five percent patients survived for at least 7 days after completing the study. PPS analysis revealed that the duration of neutropenia ≥10 days was a statistically significant negative predictor for the response. The withdrawal rate due to drug-related toxicity or lack of efficacy was 11.0%. The incidence of adverse events was 22.6%, in which 11.6% was study drug related. The most frequent adverse events were mild to moderate liver toxicity.

Conclusion  Itraconazole shows desirable efficacy and safety as empirical antifungal therapy for febrile neutropenic patients with hematologic malignancies.

     

伊曲康唑口服液预防血液病粒细胞缺乏时真菌感染

目的：观察粒细胞缺乏时应用伊曲康唑口服液预防真菌感染的疗效。方法：回顾性分析本中心患粒细胞缺乏病人104例,分两组：①预防组,②未预防组,给予伊曲康唑口服液预防侵袭性真菌感染为预防组,未预防组50例,对比分析两组发生真菌感染的情况。结果：当粒细胞缺乏时,伊曲康唑口服液预防组54例有38例出现感染,感染率70．37％,其中确诊侵袭性真菌感染1例,临床诊断3例,拟诊4例;未预防组50例中46例出现感染,感染率92％,其中确诊侵袭性真菌感染3例,临床诊断7例,拟诊7例。预防组总真菌感染率14．8％,未预防组总真菌感染率34．0％,两组比较差异有统计学意义。结论：恶性血液病患者粒细胞缺乏期应用伊曲康唑口服液,可以有效预防侵袭性真菌感染,降低侵袭性真菌感染的发病率,具有临床应用价值。     

三种常见抗真菌药口服治疗甲真菌病疗效观察

目的了解伊曲康唑、特比萘芬和氟康唑口服治疗甲真菌病的疗效。方法63例患者根据治疗药物的不同分为三组,伊曲康唑组41例,特比萘芬组13例,氟康唑组9例。分别在疗程结束后3个月和6个月时,进行真菌学检查和临床症状观察。结果伊曲康唑、特比萘芬和氟康唑治疗结束3个月和6个月的临床有效率分别为87．80％和92．68％、84．62％和92．31％、88．89％和88．89％;治疗结束3个月和6个月真菌学治愈率一致,分别为100％、92．31％和100％％。结论伊曲康唑与特比萘芬和氟康唑治疗甲真菌病均能取得较好的疗效。美扶因价格相对便宜,抗菌谱更广,具有更高的效价比。