Aspergillus peritonitis in peritoneal dialysis: case report and a review of the literature

Aspergillus peritonitis is a rare complication of continuousambulatory peritoneal dialysis. The case is described of a 68-year-oldman in whom Aspergillus fumigatus was isolated from the peritonealdialysate after recurrent peritonitis with Gram-negative rodsin association with diverticulosis. Treatment consisting ofremoval of the catheter and intravenous administration of amphotericinB followed by oral itraconazole was successful. A review of the sparse literature (12 cases) displays uncertaintiesregarding diagnostic awareness, culture diagnosis, and therapeuticmanagement. Next to institution of appropriate antifungal therapy,early removal the peritoneal dialysis catheter is recommended,as delayed removal of the catheter appears to be associatedwith increased mortality and morbidity.     

口服伊曲康唑与外用酮康唑洗剂联合治疗糠秕孢子菌性毛囊炎

目的:观察口服伊曲康唑与外用酮康唑洗剂联合治疗糠秕孢子菌性毛囊炎的疗效。方法:选择临床症状典型,经真菌学检查确诊的糠秕孢子菌性毛囊炎病人52例,分为2组。治疗组27例中男性18例,女性9例,年龄(28±s11)a,与餐同服或餐后即服伊曲康唑200mg,qd,连续7d,同时外用2%酮康唑洗剂,qd,连续用药4wk。对照组25例中男性19例,女性6例,年龄(29±10)a,单纯口服伊曲康唑200mg,qd,疗程同上。观察用药后1,4wk,2组疗效。结果:对照组1,4wk有效率分别为52%和68%,治疗组分别为59%和96%,2组1wk疗效差异无显著意义,4wk疗效治疗组优于对照组。结论:口服伊曲康唑与外用酮康唑洗剂治疗糠秕孢子菌性毛囊炎疗效好。     

Use of a semi-physiological pharmacokinetic model to investigate the influence of itraconazole on tacrolimus absorption,distribution and metabolism in mice

1.?The aim of this study was to investigate the influence of itraconazole (ITCZ) on tacrolimus absorption, distribution and metabolism by developing a semi-physiological pharmacokinetic model of tacrolimus in mice.

2.?Mice were randomly divided into four groups, namely control group (CG, taking 3?mg kg^?1 tacrolimus only), low-dose group (LDG, taking tacrolimus with 12.5?mg kg^?1 ITCZ), medium-dose group (MDG, taking tacrolimus with 25?mg kg^?1 ITCZ) and high-dose group (HDG, taking tacrolimus with 50?mg kg^?1 ITCZ).

3.?Liver clearance (CL_li) decreased significantly (**p?<?0.01) in LDG (35.3%), MDG (45.2%) and HDG (58.7%) mice compared to CG mice. With respect to gut clearance (CL_gu), significant (**p?<?0.01) decrease was also revealed in LDG (35.9%), MDG (50.2%) and HDG (64.6%) mice. A significant (**p?<?0.01) higher tacrolimus brain-to-blood partition coefficient (K_t,br) was found in MDG (25.3%) and HDG (55.9%) mice than in CG mice. Moreover, a significant (*p?<?0.05) increase (16.3%) was found in the absorption rate constant (K_a) in HDG mice compared to CG mice. There was a significant (**p?<?0.01) association between ITCZ dose and the change in CL_gu (ΔCL_gu, r=??0.790), the change in CL_li (ΔCL_li, r=??0.787) and the change in K_t,br (ΔK_t,br, r?=?0.727), while the association between ITCZ dose and the change in K_a (ΔK_a) was not significant (p?>?0.05).

4.?These findings could be useful in predicting the efficacy and toxicity of tacrolimus, and drug–drug interaction of ITCZ and tarcolimus in human.     

临床药师参与2例肺曲霉菌感染合理用药病例报道

本文报道临床药师参与2例肺曲霉菌感染合理应用抗真菌治疗方案制定,取得良好疗效,避免了药物不良反应。临床药师深入临床一线,提供药学服务有助于提高疗效,减少不良反应。     

Epidemiology of invasive fungal infections in lung transplant recipients on long‐term azole antifungal prophylaxis

Lung transplant recipients (LTR) at our institution receive prolonged and mostly lifelong azole antifungal (AF) prophylaxis. The impact of this prophylactic strategy on the epidemiology and outcome of invasive fungal infections (IFI) is unknown. This was a single‐center, retrospective cohort study. We reviewed the medical records of all adult LTR from January 2002 to December 2011. Overall, 16.5% (15 of 91) of patients who underwent lung transplantation during this time period developed IFI. Nineteen IFI episodes were identified (eight proven, 11 probable), 89% (17 of 19) of which developed during AF prophylaxis. LTR with idiopathic pulmonary fibrosis were more likely to develop IFI (HR: 4.29; 95% CI: 1.15–15.91; p = 0.03). A higher hazard of mortality was observed among those who developed IFI, although this was not statistically significant (hazard ratio [HR]: 1.71; 95% confidence interval [CI] [0.58–4.05]; p = 0.27). Aspergillus fumigatus was the most common cause of IFI (45%), with pulmonary parenchyma being the most common site of infection. None of our patients developed disseminated invasive aspergillosis, cryptococcal or endemic fungal infections. IFI continue to occur in LTR, and the eradication of IFI appears to be challenging even with prolonged prophylaxis. Azole resistance is uncommon despite prolonged AF exposure.     

反向扩散法检测皮肤癣菌对伊曲康唑的敏感性

目的：探讨皮肤癣菌的药的敏感试验新方法。方法：建立反向扩散法，将抗真菌药物伊曲康唑稀释成不同浓度加入固体培养基中，用定量取材器从沙保罗琼脂上切取须癣毛癣菌和犬小孢子菌的菌落，种子药物培养基中，并采用抑制率行回归分析。结果：药的培养基药物浓度越高，受试菌株生长菌落越小。接种标本的大小与菌落直径的大小呈正相关。接种标本取靠近菌落中央或边缘部位，对菌落大小基本没有影响。结论：反向扩散法具有可靠、迅速和重复性较好等特点。     

Exploring the feasibility of the use of biopolymers as a carrier in the formulation of amorphous solid dispersions – Part I: Gelatin

Biopolymers have rarely been used so far as carriers in the formulation of amorphous solid dispersions (ASD) to overcome poor solubility of active pharmaceutical ingredients (APIs). In an attempt to enlarge our knowledge on this topic, gelatin, type 50PS was selected. A screening study was initiated in which twelve structurally different poorly soluble biopharmaceutical classification system (BCS) Class II drugs (carbamazepine, cinnarizine, diazepam, itraconazole, nifedipine, indomethacin, darunavir (ethanolate), ritonavir, fenofibrate, griseofulvin, ketoconazole and naproxen) were selected for evaluation. Solid dispersions of five different drug loadings of these twelve compounds were prepared by lyophilization and evaluated for their solid state properties by mDSC and XR(P)D, and in vitro dissolution performance. Even without any process optimization it was possible to form either fully amorphous or partially amorphous systems, depending on the API and API to carrier ratio. Hence in this respect, gelatin 50PS behaves as any other carrier. Dissolution of the API from the solid dispersions significantly exceeded that of their crystalline counterparts. This study shows the potential of gelatin as a carrier to formulate amorphous solid dispersions.