Amphotericin B with and without itraconazole for invasive aspergillosis: A three-year retrospective study.

BACKGROUND: Treatment of invasive aspergillosis is frequently unsuccessful, so innovations in therapy are needed. Clinical studies demonstrate that itraconazole may be an effective alternative to amphotericin B. Itraconazole also has been combined with amphotericin B in animal models of aspergillosis, but this regimen produced antagonistic effects. OBJECTIVES: To determine the role of itraconazole in the adjunctive treatment of invasive aspergillosis. METHODS: A review was conducted of all patients with definite or probable aspergillosis from January 1995 to December 1997 who were treated with conventional amphotericin B alone or in combination with itraconazole. RESULTS: Of 21 patients, 10 received amphotericin B and 11 received the combination. The two groups of patients were comparable clinically at baseline (including similar mean APACHE III scores). Both groups received similar doses and days of amphotericin B treatment. Of the patients who received combination therapy, nine (82%) were cured or improved, and of those who received only amphotericin B, five (50%) were cured or improved. CONCLUSIONS: This study demonstrates that itraconazole and amphotericin B given together are not clinically antagonistic and that the promise of combination therapy for aspergillosis should be evaluated further in a randomized clinical trial.     

两性霉素B、氟康唑和伊曲康唑治疗AIDS合并马尔尼菲青霉病疗效的Meta分析

目的采用Meta分析评价两性霉素B、氟康唑与伊曲康唑对AIDS合并马尔尼菲青霉病(penicilliosis marneffei,PSM)的治疗效果。方法检索Cochrane图书馆、美国国立医学图书馆Pub Med数据库、美国Ovid数据库、荷兰医学文摘数据库、万方数据库、中国知网CNKI全文数据库和中国生物医学文献数据库,按照Cochrane协作网推荐的纳入标准筛选文献并进行质量评价,采用Stata 12.0进行Meta分析。结果纳入文献6篇,AIDS合并PSM共893例,其中两性霉素B治疗467例,氟康唑治疗152例,伊曲康唑治疗274例。Meta分析结果显示:两性霉素B治疗好转率高于氟康唑[OR=7.138(95%CI 1.761~28.932),P0.05],病死率低于氟康唑[OR=0.507(95%CI 0.294~0.875),P0.05],差异均具有统计学意义;两性霉素B与伊曲康唑对比,治疗好转率[OR=0.777(95%CI 0.498~1.212),P0.05]和病死率[OR=1.427(95%CI 0.890~2.287),P0.05]差异均无统计学意。结论两性霉素B治疗AIDS合并PSM效果优于氟康唑,与伊曲康唑比较疗效无明显差异。今后应积累更多前瞻性资料进一步证实。     

Amphotericin B and lysine acetylsalicylate in the combined treatment of nasal polyposis associated with mycotic infection.

BACKGROUND: Fungal infection may be secondary to nasal polyposis or represent a real etiopathogenic factor in the infection itself. OBJECTIVE: The aim of this study was to evaluate the effectiveness of a combined treatment with lysine acetylsalicylate (LAS) and amphotericin B in preventing recurrence in patients with nasal polyposis with accompanying mycotic infection in comparison with a control group with nasal polyposis and fungal infection who did not receive antifungal therapy. PATIENTS AND METHODS: A total of 115 patients with nasal polyposis were randomly assigned to 4 different groups and treated as follows: (1) group A, 25 patients were first surgically treated and then treated with LAS; (2) group B, 25 patients received 40 mg of triamcinolone retard intramuscularly 3 times every 10 days (total dose 120 mg) and then they were treated with LAS; (3) group C, 16 patients were surgically treated and then treated with LAS and amphotericin B; (4) group D: 23 patients were treated with a medical polypectomy and steroids (as in the group B) and then with LAS and amphotericin B. RESULTS: We found no significant differences between groups C and D, groups C and A, or groups B and D. However, the recurrence of nasal polyps in the groups treated with amphotericin B plus LAS (C and D) was significantly lower (P = .018) than in the 2 groups treated only with LAS (A and B). CONCLUSION: Our results indicate that long term topical treatment with LAS and amphotericin B may be clinically effective in the treatment of patients with nasal polyposis associated with fungal infection.     

Efficacy of fluconazole and itraconazole in the treatment of oral candidiasis in HIV patients

A total of 46 strains of Candida were collected from HIV infected patients, of which 25 strains were isolated from patients with oral candidiasis, and 21 strains were from mouthwash samples of asymptomatic carriers. The most common species isolated was Candida albicans (73.9%), followed by Candida tropicalis (21.7%). In vitro susceptibility of the strains to fluconazole and itraconazole was tested using minimum inhibitory concentration (MIC) studies by agar dilution technique. Out of the 18 strains of C. albicans isolated from mouthwash samples, four were resistant to fluconazole whereas only two were resistant to itraconazole. Out of 16 strains of C. albicans isolated from oral lesions, one was resistant to fluconazole where as all were sensitive to itraconazole. Among the other species of Candida tested, C. tropicalis gave higher MIC values to both drugs than other species such as Candida guillermondii and Candida krusei. In vitro MIC values correlated well with in vivo responses in patients. Hence, itraconazole may be used as an alternative in the treatment of candidiasis, which does not respond to fluconazole therapy.     

两性霉素B治疗恶性血液肿瘤合并真菌感染40例临床分析

目的：观察静脉用两性霉素B对血液系统恶性肿瘤病人真菌感染的临床疗效及安全性。方法：40例恶性血液病患者（男27例,女13例,中数年龄35．5岁）,出现真菌感染者使用两性霉素B,剂量为5－50mg/d,用药天数为5－85d,中数21d.结果：两性霉素B临床总有效率为52．5％,真菌清除率为56．2％,不良反应发生率中寒战,发热2．5％,低血钾12．5％,肝肾功能损害各为15．0％。结论：两性霉素B因其抗菌谱较广,且疗效好,在治疗深部真菌感染中为高效药物,但因其不良反应较大,限制其使用。我们的研究表明：只要合理用药,定期监测肝肾功能,该药仍是一相对较为安全有效的药物。     

Successful treatment of candidal osteomyelitis with fluconazole following failure with liposomal amphotericin B

A case of multiple relapses of Candida albicans infection of deep tissues is described. Treatment was complicated by renal impairment, but therapy with a liposomal amphotericin product failed to eradicate the third recurrence which subsequently resolved after protracted exposure to oral fluconazole.     

Rosco纸片扩散法检测酵母样真菌对氟康唑、两性霉素B、伊曲康唑药敏试验的评价

目的 Rosco纸片扩散法在酵母样真菌药敏试验中的临床应用评价. 方法 应用 Rosco 纸片扩散法和美国临床实验室标准化委员会(NCCLS)M27-A宏量肉汤稀释法测定临床分离的110株老年病例中不同酵母样真菌菌株对氟康唑、两性霉素B、伊曲康唑的药敏状况,并以3株酵母菌株作质量控制. 结果 2种方法完全符合率是92.7%,未出现一种方法测得的敏感或耐药菌株,在用另一种方法检测中为耐药或敏感的严重错误. 结论 Rosco纸片扩散法可以替代NCCLS M-27A宏量肉汤稀释法在临床推广使用.     

拉米夫定联合小剂量乙型肝炎免疫球蛋白预防肝移植术后乙型肝炎复发

目的比较单用拉米夫定和拉米夫定联合个体化小剂量肌肉注射乙型肝炎免疫球蛋白两种方案,预防乙型肝炎相关良性终末期肝病患者肝移植术后乙型肝炎复发的疗效。方法111例因乙型肝炎相关良性终末期肝病患者在肝移植术前根据乙型肝炎免疫球蛋白的可获得性非随机分为单用组和联用组,单用组32例患者在移植术后接受拉米夫定100mg/d单药治疗,联用组79例患者在移植术后接受拉米夫定100mg/d和个体化小剂量肌肉注射乙型肝炎免疫球蛋白(维持血清抗- HBs滴度>100U/L)联合治疗。研究总体中位随访时间为32(1～88)个月,监测患者HBsAg、HBV DNA、抗-HBs和YMDD变异情况,随访患者生存率及乙型肝炎复发率。结果单用组共有5例患者乙型肝炎复发,其中3例发生HBV YMDD变异;肝移植术后1、2、3年累积乙型肝炎复发率分别为7.1%、14.3%、17.9%,患者生存率分别为87.5%、84.4%、74.6%。联合组共有2例患者乙型肝炎复发,且均发生YMDD变异;肝移植术后1、2、3年累积乙型肝炎复发率分别为0、1.8%、5.7%,患者生存率分别为83.5%、80.9%、77.6%。两组患者乙型肝炎复发率之间差异有统计学意义(P<0.05),单用组肝移植术前HBV DNA活跃复制与肝移植术后乙型肝炎复发相关(P<0.05),而联用组两者之间无相关性(P>0.05)。结论个体化小剂量肌肉注射乙型肝炎免疫球蛋白联合拉米夫定与单用拉米夫定相比,能更有效地降低良性终末期乙型肝炎患者肝移植术后乙型肝炎复发的风险。     

Salvage treatment of histoplasmosis with posaconazole

Six patients received salvage treatment with posaconazole oral suspension (800 mg/day in divided doses) for severe forms of histoplasmosis. One patient had pulmonary disease and 5 had disseminated disease. Previous antifungal therapy consisted of amphotericin B, itraconazole, fluconazole, or voriconazole. Posaconazole treatment duration for individual patients ranged from 6 weeks to 34 weeks. All patients had successful clinical outcomes with significant clinical improvements noted during the first month of therapy. Although the number of patients evaluated in this case series is small, the findings are encouraging and provide preliminary evidence that posaconazole may be a useful salvage treatment option for histoplasmosis involving a variety of infected tissues and organs.     

Three-step empiric treatment for severely neutropenic patients with fever: Ceftazidime — Vancomycin — Amphotericin B

Summary In a prospective study 50 febrile episodes in severely neutropenic patients (neutrophils <500/mm³) were empirically treated with ceftazidime monotherapy. If no response was seen after 48 h, vancomycin was added. After another 72 h period, patients with persisting fever additionally received amphotericin B. In 29 episodes (58%) patients became afebrile with ceftazidime monotherapy. Another seven patients (14%) responded to the addition of vancomycin and five patients (10%) needed amphotericin B to become afebrile. A success of the study drugs without modification was seen in 40 episodes (80%), success with modification in three episodes (6%) and failure in six episodes (12%). One patient died of myocardial infarction. No other death occurred during the two-week observation period after entering the study. Though there were two gram-negative isolates resistant to ceftazidime, these patients were successfully treated with modification. It is concluded that the response-adapted additive sequence of ceftazidime, vancomycin and amphotericin B is an effective approach towards febrile episodes in severely neutropenic patients.

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Stufenweise, empirische Behandlung von neutropenischen Patienten mit Fieber: Ceftazidim — Vancomycin — Amphotericin B

Zusammenfassung In einer prospektiven Studie wurden 50 Fieberepisoden bei neutropenischen Patienten (neutrophile Granulozyten <500/mm³) empirisch mit einer Ceftazidim-Monotherapie behandelt. Trat nach 48 Stunden kein Ansprechen ein, wurde die Behandlung mit Vancomycin erweitert. Nach weiteren 72 Stunden wurde bei Patienten, die nicht ansprachen, eine systemische Amphotericin B-Therapie eingeleitet. In 29 Fieberepisoden (58%) entfieberten die Patienten unter Ceftazidim-Monotherapie. Sieben Patienten entfieberten erst nach Zugabe von Vancomycin und fünf Patienten nach Amphotericin B-Gabe. Ein Behandlungserfolg mit den Studienantibiotika ohne weitere Modifikation wurde in 40 Episoden (80%) beobachtet. In drei Episoden zeigte eine Modifikation Erfolg. Therapieresistent waren sechs Episoden (12%). Ein Patient verstarb an einem Myokardinfarkt. Alle anderen Patienten überlebten die zweiwöchige Beobachtungszeit. In zwei Fällen wurden Ceftazidim-resistente gramnegative Keime isoliert. Diese Patienten sprachen auf eine Modifikation der Behandlung an. Die am klinischen Erfolg orientierte additive Sequenz Ceftazidim, Vancomycin und Amphotericin B ermöglicht eine effektive und sichere empirische Behandlung von neutropenischen Patienten mit Fieber.