皮肤癣菌感染动物模型的建立及抗真菌治疗的评价

目的 建立皮肤癣菌感染动物模型并评价抗真菌药物对该模型的体内疗效。方法 选择38只健康豚鼠,随机分为须癣毛癣菌感染组和犬小孢子菌感染组,用磨砂法建立皮肤癣菌感染的动物模型,每组各有1只为阴性对照。每组18只感染动物再随机分为伊曲康唑治疗组、特比萘芬治疗组、未治疗组3个组。在治疗后的第8、11、14天分别对动物模型进行皮肤病变评分和真菌学检查。结果 未进行治疗的感染动物均出现明显的皮损,且真菌学检查为阳性。须癣毛癣菌感染的伊曲康唑治疗组动物皮损评分和真菌学治愈率在第8、11、14天分别为9、1、0,66.7%、83.3%、83.3%;特比萘芬治疗组分别为8、5、1,83.3%、83.3%、83.3%;未治疗组分别为48、52、40,0%、0%、0%。犬小孢子菌感染的伊曲康唑治疗组动物皮损评分和真菌学治愈率在第8、11、14天分别为3、0、0,83.3%、83.3%、83.3%,特比萘芬治疗组分别为9、2、0,83.3%、83.3%、83.3%,未治疗组分别为46、47、39,0%、0%、0%。两组与未治疗组比较,差异均有统计学意义（P < 0.01）,但伊曲康唑治疗组与特比萘芬治疗组比较差异无统计学意义（P > 0.05）。结论 伊曲康唑治疗须癣毛癣菌和犬小孢子菌感染的动物模型有良好的疗效,特比萘芬有相似的结果。     

Experimental aspergillosis in guinea pigs: influence of itraconazole on fungaemia and invasive fungal growth

Summary. The guinea pig model of experimental aspergillosis was used to evaluate the efficacy of itraconazole 2.5 and 5 mg kg^-1 in preventing the invasive phase of the disease when animals were already loaded with Aspergillus conidia. Evaluations were made by recording the survival rates, culturing fragments of nine organs, examining seven organs by means of histochemistry and immunohistochemistry (mAb EB-Al to Aspergillus galactomannan) and by serological titration of galactomannan. The data indicate that itraconazole is highly effective in preventing true invasive aspergillosis. Serological evaluations of antigenaemia suggest that low titres may only reflect fungaemia, while titres of 1:8 and above are suggestive of invasive disease.
Zusammenfassung. Das Meerschweinchen-Modell der experimentellen Aspergillose wurde eingesetzt, um die Wirkung von 2,5 mg und 5 mg kg^-1 Itraconazol zur Prävention der invasiven Krankheitsphase zu bewerten, wenn die Versuchstiere bereits mit Aspergillus -Konidien beladen sind. Die Bewertung stützt sich auf die Überlebensrate, auf Pilzkulturen aus neun verschiedenen Organen, auf histochemische und immunhistochemische Untersuchungen von sieben Organen mittels MOB EB-Al-Antikörpern gegen Aspergillus -Galactomannan sowie auf die Serotitration dieses Antigens. Die Ergebnisse belegen die hohe Wirksamkeit des Itraconazols in der Prävention der echt invasiven Aspergillose. Antigen-Titrationen im Serum sprechen dafür, daß geringe Titer lediglich das Fungämie-Stadium widerspiegeln, während Antigentiter ≥ 1:8 eine invasive Aspergillose belegen.     

Kontroversen bei der Standardisierung der Empfindlichkeits-prüfung von Hefen gegen Azol-Antimyotika

Zusammenfassung. Die unterschiedlichen physikalisch-chemischen Eigenschaften der therapeutisch ein-gesetzten Azol-Antimykotika erfordern ein Testverfahren, welches diesen gerecht wird. Fluconazol kann innerhalb der Gruppe der Azol-Antimykotika aufgrund seiner Hydrophilie als unproblematische Testsubstanz angesehen werden. Die extreme Hydrophobizität des Itraconazols läßt eine Übertragung der Testbedingungen für Fluconazol auf die Itraconazoltestung nicht zu. Die aktuellen Empfehlungen des NCCLS werden dieser Problematik nicht gerecht. Deshalb ist es notwendig, einen einheitlichen Standard für die In-vitro-Testung der Gruppe der Azol-Antimykotika festzulegen.
Summary. Due to the different physical-chemical conditions of the therapeutical azoles it is necessary to choose an adequate testing procedure. In the group of azoles caused by its hydrophilia fluconazole susceptibility testing can be handled easily. However it is not possible to take the same test conditions for itraconazole as for fluconazole due to the extreme high hydrophobicity of itraconazole. The current recommendations of NCCLS should be considering these problems. Therefore it is necessary to standardize susceptibility testing for all azoles possible.     

Therapie von Infektionen durch Schwärzepilze

Zusammenfassung. Da Schwärzepilze zu den seltenen Erregern von Mykosen zählen, begründen sich Therapieempfehlungen vorwiegend auf Einzelfallbeobachtungen. Bei Eumyzetomen und herdförmigen Phaeohyphomykosen des Zentralnervensystems (z. B. durch Cladophialophora bantiana, Exophiala dermatitidis ) und in bestimmten Fällen einer Chromoblastomykose ist die Resektion in toto Therapie der Wahl, ggf. mit antimykotischer Begleitmedikation. Zur antimykotischen Therapie ex juvantibus bei Phaeohyphomykosen ist z. Z. ein Therapicerfolg mit einer Kombinationsbehandiung aus Itraconzol und 5-Fluorcytosin am ehesten zu erwatten. Eine ausreichende Therapiedauer ist für den Erfolg maßgebend.
Summary. Since dematiaceous fungi belong to the group of rare infectious agents causing mycoses, therapeutic recommendations are mainly deduced from observations of single cases. In cases of eumycetoma or focal phaeohyphomycoses of the central nervous system (e.g. caused by Cladophialophora bantiana or Exophiala dermatitidis ) and in certain cases of chromoblastomycoses, the resection in loto is the therapy of choice, which may be accompanied by antimycotic medication. As antimycotic therapy ex juvantibus in case of phaeohyphomycoses, a simultaneous application of itraconazole and 5-fluorocytosine is presently most promising. The success depends on an adequate duration of therapy.     

In vitro activity of terbinafine and itraconazole against Aspergillus species isolated from otomycosis

The minimum inhibitory concentrations (MIC, microg ml-1) of itraconazole and terbinafine against overall 34 Aspergillus isolates from the external ear canals with otomycosis have been determined with M38-P microdilution method suggested by National Committee for Clinical Laboratory Standards (NCCLS). MIC intervals in 48 h determined by taking MIC-2 value of itraconazole (the lowest drug concentration causing 50% inhibition of visible fungal growth) and MIC-0 value of terbinafine (the lowest drug concentration causing 100% inhibition of visible fungal growth) as a basis have been found as follows: 0.125-1 and 0.06-0.5 microg ml-1 for A. niger (22 strains), 0.06-0.25 and 0.06-0.125 microg ml-1 for A. flavus (10 strains), 0.125 and 0.125-0.5 microg ml-1 for A. terreus (two strains). It has been observed that both of the antifungal agents showed an in vitro activity against all Aspergillus species tested.     

The epidemiology of pseudallescheriasis complicating transplantation: nosocomial and community-acquired infection

The epidemiology of two cases of pseudallescheriasis in organ transplant patients are described and the disease in that population is reviewed. Disseminated hospital-acquired infection occurred in a liver transplant recipient and was fatal despite therapy with miconazole. A heart transplant recipient developed localized disease following soil contamination of soft tissue trauma which was cured with surgical resection and miconazole therapy. Itraconazole showed in vitro activity against Pseudallescheria boydii and should be evaluated in pseudallescheriasis. P. boydii infections are important complications of transplantation and should be considered in the differential diagnosis of community-acquired as well as nosocomial fungal infections in this population.     

Itraconazole treatment of pulmonary aspergillosis in leukaemia patients during a nosocomial epidemic associated with indoor building renovation

During indoor building renovation a nosocomial epidemic of pulmonary aspergillosis occurred in a haematological ward, involving 10 patients with acute leukaemia undergoing intensive chemotherapy. Antifungal treatment included the combination of amphotericin B and 5-fluorocytosine during periods of granulocytopenia, followed by itraconazole after bone-marrow recovery. In five patients, lung aspergillomas disappeared completely, while significant improvement was observed in a further two patients. Itraconazole appeared to contribute significantly to the result, but the drug did not work during granulocytopenic episodes. Air analyses showed increased counts of fungal spores in ward locations with heavy traffic of patients and staff, suggesting the need to identify and avoid risk areas when placing patients undergoing intensive chemotherapy.     

Treatment of human cutaneous sporotrichosis with itraconazole

Eighteen adult white male patients with cutaneous sporotrichosis were treated with itraconazole following different daily dose schemes. Cure was obtained in all cases after periods of 15-75 days (median 44 days) with total doses between 3.1 and 14.8 g (median 8.4 g). No serious side effects were observed and no relapses occurred in the follow-up period of between 1 and 26 months (median 14.7). These results show that itraconazole represents a safe and effective drug for the treatment of sporotrichosis. Comparison with other studies leads us to consider a daily dose of 200 mg as the most appropriate. A concomitant warming of the affected limbs should be recommended.