伏立康唑角膜基质内注射联合纳他霉素滴眼治疗真菌性角膜炎的疗效评估

目的:探讨伏立康唑角膜基质内注射联合纳他霉素滴眼治疗真菌性角膜炎(FK)的临床疗效.方法:选择2014年3月~2016年9月我院眼科收治的FK患者84例(84眼),按随机数字表法分为对照组与观察组,各42例(42眼).对照组采用纳他霉素及伏立康唑滴局部滴眼,观察组在对照组基础上加用伏立康唑角膜基质内注射,比较两组的疗效.结果:观察组的治疗总有效率为92.86%,显著高于对照组的76.19%;观察组眼部异物感、前房积脓、角膜溃疡、畏光流泪消退时间均较对照组明显缩短;治疗后第3d、7d、14d及28d,观察组的角膜病变严重程度评分、角膜溃疡面积均显著低于对照组,视力显著高于对照组;观察组的不良反应率为7.14%,与对照组的2.38%比较差异无统计学意义;观察组3个月复发率为3.45%,显著低于对照组的26.32%.结论:伏立康唑角膜基质内注射联合纳他霉素滴眼治疗FK疗效确切、安全可靠,能促进临床症状体征消退,改善患者的视力状态并降低复发率,值得推广应用.     

Pharmacokinetic interactions of efavirenz and voriconazole in healthy volunteers

AIMS

Co-administration of standard-dose voriconazole and efavirenz results in a substantial decrease in voriconazole levels, while concurrently increasing efavirenz levels. Hence, concomitant use of standard doses of these drugs was initially contraindicated. This study assessed different dose combinations of efavirenz and voriconazole, with the goal of attaining a dose combination that provides systemic exposures similar to standard-dose monotherapy with each drug.

METHODS

This was an open-label, four-treatment, multiple-dose, fixed-sequence study in 16 healthy males. Steady-state pharmacokinetics were assessed following two test treatments (voriconazole 300 mg q12 h + efavirenz 300 mg q24 h and voriconazole 400 mg q12 h + efavirenz 300 mg q24 h) and compared with standard-dose monotherapy (voriconazole 200 mg q12 h or efavirenz 600 mg q24 h).

RESULTS

Dose adjustment to voriconazole 300 mg q12 h with efavirenz 300 mg q24 h decreased voriconazole area under the concentration–time curve (AUC_τ) and maximum concentration (C_max), with changes of −55% [90% confidence interval (CI) −62, −45] and −36% (90% CI −49, −21), respectively, when compared with monotherapy. Voriconazole 400 mg q12 h plus efavirenz 300 mg q24 h decreased voriconazole AUC_τ (−7%; 90% CI −23, 13) and increased C_max (23%; 90% CI −1, 53), while increasing efavirenz AUC_τ (17%; 90% CI 6, 29) and not changing C_max when compared with the respective monotherapy regimens. No serious adverse events were observed with voriconazole plus efavirenz.

CONCLUSIONS

When co-administered, voriconazole dose should be increased to 400 mg q12 h and efavirenz dose decreased to 300 mg q24 h in order to provide systemic exposures similar to standard-dose monotherapy.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• Efavirenz 400 mg q24 h reduces exposure to voriconazole 200 mg q12 h when the two drugs are co-administered.
• Furthermore, voriconazole increases the systemic exposure of efavirenz.
• Co-administration was therefore initially contraindicated.

WHAT THIS STUDY ADDS

• The doses of efavirenz and voriconazole can be adjusted to provide adequate exposure to both drugs when the two are co-administered, without compromising safety.
• Appropriate adjustment of doses for both drugs may thus represent an alternative to a mere contraindication.

     

Voriconazole Prophylaxis in Lung Transplant Recipients

Lung transplant recipients have one of the highest rates of invasive aspergillosis (IA) in solid organ transplantation. We used a single center, nonrandomized, retrospective, sequential study design to evaluate fungal infection rates in lung transplant recipients who were managed with either universal prophylaxis with voriconazole (n = 65) or targeted prophylaxis (n = 30) with itraconazole ± inhaled amphotericin in patients at high risk (pre- or posttransplant Aspergillus colonization [except Aspergillus niger ]). The rate of IA at 1 year was better in lung transplant recipients receiving voriconazole prophylaxis as compared to the cohort managed with targeted prophylaxis (1.5% vs. 23%; p = 0.001). Twenty-nine percent of cases in the targeted prophylaxis group were in patients colonized with A. niger who did not receive itraconazole. A threefold or higher increase in liver enzymes was noted in 37–60% of patients receiving voriconazole prophylaxis as compared to 15–41% of patients in the targeted prophylaxis cohort. Fourteen percent in the voriconazole group as compared to 8% in the targeted prophylaxis group had to discontinue antifungal medications due to side effects. Voriconazole prophylaxis can be used in preventing IA in lung transplant recipients. Regular monitoring of liver enzymes and serum concentrations of calcineurin inhibitors are required to avoid hepatotoxicity and nephrotoxicity.     

1例肺镰刀菌病患者的护理

目的：探讨肺镰刀菌病患者的临床护理方法，提高治愈率。方法对收治的1例肺镰刀菌病患者观察病情变化，制定合理的护理措施。结果患者临床死亡。结论对肺镰刀菌病患者采取积极有效的观察和护理，可减少并发症的发生，减轻患者痛苦。     

Disseminated Pseudallescheria boydii (Scedosporium apiospermum) infection in a renal transplant patient

Abstract: Transplant recipients receive a number of immunosuppressive medications that result in an increased risk of infection, including infections with microbes that are normally not pathogenic. We describe a patient with end-stage renal disease who underwent kidney transplantation. Six months postoperatively, he presented with a lesion on his ankle, multiple thigh nodules, and right testicular pain. Biopsy of the ankle lesion demonstrated Pseudallescheria boydii ( Scedosporium apiospermum ), a common environmental fungus. Following orchiectomy, multiple fungal elements were found that were initially described as Aspergillus species, but later identified as P. boydii . In addition, multiple brain abscesses were found on magnetic resonance imaging. Despite treatment with multiple antifungal medications, the patient died of cardiac dysrhythmia. Current diagnostic and therapeutic alternatives for P. boydii are reviewed.     

Resource use and cost of treatment with voriconazole or conventional amphotericin B for invasive aspergillosis

BACKGROUND: Voriconazole, a broad-spectrum triazole, has demonstrated significantly improved survival compared with conventional amphotericin B (CAB) as initial therapy for invasive aspergillosis (IA). OBJECTIVE: To compare health care resource use and cost at 12 weeks following first-line treatment with voriconazole compared with CAB for IA using resource use data collected during a clinical trial. METHODS: Days of hospitalization, intensive care, antifungal drug use, and outpatient care were collected during a large randomized, controlled trial of patients with IA receiving initial treatment with voriconazole or CAB. Unit costs based on published data sources were applied to healthcare use to estimate 12-week costs following initiation of therapy. Resource use and costs were compared for each treatment arm overall and by survival. The sensitivity of total costs to changes in healthcare use and unit costs was examined. RESULTS: Total hospital days and intensive care unit (ICU) days were similar for voriconazole and CAB (total: 27.8 vs. 27.7, P=0.97 and ICU: 5.6 vs. 8.1, P=0.11). Among survivors, voriconazole was associated with similar numbers of total hospital days (29.8 vs. 32.0 days, P=0.54) to CAB, but fewer ICU days (3.9 vs. 8.2, P=0.03). For non-survivors, those treated with voriconazole had a similar number of total hospital days (23.0 vs. 21.8, P=0.73) and ICU days (9.8 vs. 7.9, P=0.44). Patients treated with voriconazole had significantly more days alive and out of the hospital than with CAB at 12 weeks (40.3 vs. 28.4 days, P<0.001). Total costs were similar with voriconazole compared with CAB ($78,860 vs. $83,857, P=0.51). Differences in cost were not sensitive to changes in the input parameter values. CONCLUSIONS: Using voriconazole first-line for treatment of IA resulted in significantly fewer deaths and similar treatment costs. Hospital-free survival was significantly greater for patients initially treated with voriconazole.