伊曲康唑注射液治疗老年人侵袭性肺曲霉病

目的:研究伊曲康唑注射液治疗老年人侵袭性肺曲霉病的临床疗效及安全性。方法:对15例60 a以上应用伊曲康唑治疗的侵袭性肺曲霉病病人的资料进行分析。其中男性11例,女性4例,年龄(72±s 7)a;确诊病例3例,临床诊断很可能病例8例,临床诊断可能病例4例。伊曲康唑注射液d 1～2,每日400mg,分2次静脉滴注,以后200 mg·d-1静脉滴注。观察临床疗效、用药时间、预后及不良反应。结果:总有效率60％(9／15)。3例确诊病例中显效1例,进步1例,无效1例。临床诊断很可能病例中痊愈2例,显效2例,无效4例。临床诊断可能病例中痊愈3例,显效1例。曲霉菌完全清除9例,真菌交替3例,未清除3例。不良反应为头痛1例。结论:早期、足量、足疗程应用伊曲康唑注射液治疗老年人侵袭性肺曲菌病疗效好,安全。     

Echinocandins: A ray of hope in antifungal drug therapy

Invasive fungal infections are on the rise. Amphotericin B and azole antifungals have been the mainstay of antifungal therapy so far. The high incidence of infusion related toxicity and nephrotoxicity with amphotericin B and the emergence of fluconazole resistant strains of Candida glabrata egged on the search for alternatives. Echinocandins are a new class of antifungal drugs that act by inhibition of β (1, 3)-D- glucan synthase, a key enzyme necessary for integrity of the fungal cell wall.Caspofungin was the first drug in this class to be approved. It is indicated for esophageal candidiasis, candidemia, invasive candidiasis, empirical therapy in febrile neutropenia and invasive aspergillosis. Response rates are comparable to those of amphotericin B and fluconazole. Micafungin is presently approved for esophageal candidiasis, for prophylaxis of candida infections in patients undergoing hematopoietic stem cell transplant (HSCT) and in disseminated candidiasis and candidemia. The currently approved indications for anidulafungin are esophageal candidiasis, candidemia and invasive candidiasis.The incidence of infusion related adverse effects and nephrotoxicity is much lower than with amphotericin B. The main adverse effect is hepatotoxicity and derangement of serum transaminases. Liver function may need to be monitored. They are, however, safer in renal impairment. Even though a better pharmacoeconomical choice than amphotericin B, the higher cost of these drugs in comparison to azole antifungals is likely to limit their use to azole resistant cases of candidial infections and as salvage therapy in invasive aspergillosis rather than as first line drugs.     

Fluconazole treatment of systemic mycoses

Efficacies of fluconazole, a new triazole antifungal agent, were evaluated in 11 cases of systemic mycoses (1 case each of candiduria, pulmonary cryptococcosis, pulmonary aspergillosis, pulmonary penicilliosis and suspected fungal pulmonary infection, and 3 cases each of candidemia and Candida endophthalmitis). The clinical efficacies were excellent or good in 8 out of 9 cases and poor in 1. Side effects observed were mild with 1 incident each of gastrointestinal symptom and reversible leukopenia. This drug appears to be promising in treatment of systemic mycoses.     

Treatment of complicated urinary tract infections caused by fungi

The predisposing factors of funguria and the clinical efficacy of treatment with ketoconazole, a new oral imidazole antifungal drug were studied in 10 patients with complicated urinary tract infection due to fungi. Preceding antibiotic therapy, presence of indwelling catheter and malignant tumor were regarded as the important factors that predisposed to the fungal urinary tract infections. Patients received 200 mg of ketoconazole once a day for 5 to 14 days. Of the 9 patients in whom clinical efficacy of ketoconazole was evaluated, excellent response was obtained in 4 patients, moderate in 2 and poor in 3 patients. Of the 9 strains of fungi isolated before treatment, 6 strains or 67% were eradicated after treatment. Neither subjective nor objective side effects were observed in any of 10 patients receiving ketoconazole, and laboratory tests showed elevated BUN and serum creatinine in 1 patient. From the results obtained in this study, ketoconazole was regarded as useful in the treatment of complicated urinary tract infection due to fungi.     

Laboratory and clinical study of intravenous miconazole

Laboratory and clinical study was carried out on miconazole (MCZ), a new synthetic imidazole. The antifungal activity of MCZ was studied and expressed as MICs for clinical isolates. The drug proved to have the highest activity against Cryptococcus neoformans, with MICs of no more than 0.16 micrograms/ml for all isolates of this species. MICs of Torulopsis glabrata were 0.08-5 micrograms/ml for all isolates and those of Candida albicans and Candida tropicalis were 5-20 micrograms/ml for more than 90% of the isolates. Most of other strains were less than 10 micrograms/ml. When 3 healthy adult men were administered each with 200 mg of MCZ by intravenous drip infusion for 1.25 hours, the mean serum MCZ concentration was 1.39 micrograms/ml at the end of the infusion, then decreased rapidly to 0.49 microgram/ml in following 30 minutes, and then decreased gradually to 0.17 microgram/ml 6 hours later. The mean cumulative urinary excretion rate of the drug was as low as 3.0% at this stage. A total of 25 patients with ages of 30-78 years, comprising 17 men and 8 women, were treated with 200-1,800 mg of MCZ daily for 3-93 days. The clinical effectiveness was ascertained in 19 cases among the patients; 9 cases with candidiasis, 3 with cryptococcosis and 7 with aspergillosis. Clinical responses were excellent in 2, good in 9 and poor in 8 cases, and its efficacy rates was 58%. The efficacy rate of the combination therapy with other antifungal agents was 60% in comparison with 57% of MCZ alone. Adverse reactions to the drug such as nausea, vomiting and anorexia were observed in 3 cases (12%). Abnormal changes in laboratory parameters were also observed: 3 patients with elevations of GOT and GPT, and another with eosinophilia.     

The echinocandins: comparison of their pharmacokinetics, pharmacodynamics and clinical applications

Caspofungin, micafungin and anidulafungin are three drugs of the echinocandin class of antifungals available for intravenous treatment of invasive candidiasis and aspergillosis. They exhibit high in vitro and in vivo activities against Candida spp. and Aspergillus spp. In various clinical studies investigating candidemia and invasive candidiasis, Candida esophagitis, and fever in neutropenia, the clinical efficacy of the echinocandin tested was similar to that of established antifungals. Antifungal activity against strains no longer susceptible to conventional antifungal agents, such as fluconazole and amphotericin B suggests that echinocandins can be used as salvage therapy in life-threatening fungal infections. There is no cross-resistance to other antifungals. Excellent safety and tolerability of treatment with caspofungin has been documented over a total of 4.3 million patient days. Echinocandins are poor substrates of the cytochrome P450 enzyme family and can be safely co-administered with most drugs without the need for dosage adaptation. No dose reduction is required in renal impairment. A reduction in the daily maintenance dose has been recommended for caspofungin, but not for micafungin and anidulafungin in patients presenting with mild to moderate hepatic failure.     

Therapeutic efficacy of ceftibuten in chronic respiratory tract infections

We evaluated the therapeutic efficacy of ceftibuten (CETB, 7432-S), a new cephem antibiotic for oral use, in chronic respiratory tract infections. A daily dose of 400 mg (b.i.d.: 15 cases) or 600 mg (t.i.d.: 5 cases) of CETB was given orally for 3-14 days (mean: 10.6 days) to 20 patients: 9 with infected bronchiectasis, 3 with infection supervened on pulmonary emphysema, 3 with acute pneumonia (supervened on bronchiectasis in 2 of 3 cases), 2 with infected bronchial asthma, 1 each with infection supervened on old pulmonary tuberculosis, chronic bronchitis and pulmonary fibrosis. The clinical effects were excellent in 3, good in 11, fair in 3 and poor in 3. Eighteen strains were identified as causative organisms. Eight of 15 strains for which bacteriological responses were evaluable were eradicated by the use of CETB. Eosinophilia in 2 patients and an elevation of S-GPT value was observed in 1 patient. These adverse reactions disappeared after the completion of the therapy. From the above results, we conclude that CETB is one of the most useful antibiotics for oral use as a first choice in chronic respiratory tract infections.     

A clinical evaluation of fluconazole in the treatment of deep mycosis

Fluconazole is a novel triazole antifungal agent developed by Pfizer Inc. and available in both oral and intravenous forms. It is characterized by a long serum half-life of 25 to 30 hours and good absorbability into tissues. In the present study, fluconazole was given to 12 patients with deep mycosis orally, intravenously or by local infusion. The patients included 4 cases of candidemia, 1 case each of candidemia and candiduria, candiduria, esophageal candidiasis, Candida hepatic abscess, pulmonary cryptococcosis and septicemia due to unspecified yeasts and 2 cases of pulmonary aspergillosis. Clinical efficacies of fluconazole against these infections were excellent in 2 cases, good in 8 and fair in 2. None of the patients reported any side effects. From the results of the study, fluconazole appears to be a useful and safe drug for the treatment of deep seated mycosis.     

Fungal infections in patients with neutropenia: challenges in prophylaxis and treatment

Fungal infections are a leading cause of mortality in patients with neutropenia. Candidiasis and aspergillosis account for most invasive fungal infections. General prophylactic measures include strict hygiene and environmental measures. Haemopoietic growth factors shorten the duration of neutropenia and thus may reduce the incidence of fungal infections. Fluconazole is appropriate for antifungal prophylaxis and should be offered to patients with prolonged neutropenia, such as high-risk patients with leukaemia undergoing remission induction or consolidation therapy and high-risk stem cell transplant recipients. Empirical antifungal therapy is mandatory in patients with persistent febrile neutropenia who fail to respond to broad-spectrum antibacterials. Intravenous amphotericin B at a daily dose of 0.6 to 1 mg/kg is preferred whenever aspergillosis cannot be ruled out. Lipid formulations of amphotericin B have demonstrated similar efficacy and are much better tolerated. Fluconazole is the best choice for acute candidiasis in stable patients; amphotericin B should be used in patients with unstable disease. Use of fluconazole is restricted by the existence of resistant strains (Candida krusei and, to a lesser extent, C. glabrata). Amphotericin B still remains the gold standard for invasive aspergillosis. Lipid formulations of amphotericin B are effective in aspergillosis and because they are less nephrotoxic are indicated in patients with poor renal function. Itraconazole is an alternative in patients who have good intestinal function and are able to eat. Mucormycosis, trichosporonosis, fusariosis and cryptococcosis are less common but require specific management. New antifungal agents, especially new azoles, are under development. Their broad in vitro spectrum and preliminary clinical results are promising.     

Clinical efficacy of fluconazole in urinary tract fungal infections

Fluconazole, a new antifungal agent was administered to 7 patients with complicated urinary tract fungal infections. Patients were 6 males and 1 female with ages of 29 to 83 years, with underlying conditions of bladder tumor (3 patients), neurogenic bladder (3 patients) and hydronephrosis (1 patient). Urinary fungi identified were Candida albicans in 5 patients and Candida tropicalis in 2 patients over 10(4) CFU/ml. These fungi were isolated at least twice in intervals of 5 to 7 days before treatment. Fluconazole was given either orally (4 patients) or intravenously (3 patients) in a dose of 50 mg per day. Clinical efficacies were excellent in 3 patients, moderate in 3 patients and poor in 1 patient, showing an efficacy rate of 85.7%. Mycologically, 6 Candida out of the 7 were eliminated. No side effects nor abnormal laboratory data were observed. In conclusion, fluconazole is effective and safe in the treatment of urinary tract fungal infections.     

Caspofungin: pharmacology,safety and therapeutic potential in superficial and invasive fungal infections

Invasive fungal infections are important causes of morbidity and mortality in hospitalised patients. Current therapy with amphotericin B and antifungal triazoles has overlapping targets and is limited by toxicity and resistance. The echinocandin lipopeptide caspofungin is the first of a new class of antifungal compounds that inhibit the synthesis of 1,3-β-D-glucan. This homopolysaccharide is a major component of the cell wall of many pathogenic fungi and yet is absent in mammalian cells. It provides osmotic stability and is important for cell growth and cell division. In vitro, caspofungin has broad-spectrum antifungal activity against Candida and Aspergillus spp. without cross-resistance to existing agents. The compound exerts prolonged post-antifungal effects and fungicidal activity against Candida spp. and causes severe damage of Aspergillus fumigatus at the sites of hyphal growth. Animal models have demonstrated efficacy against disseminated candidiasis and disseminated and pulmonary aspergillosis, both in normal and in immunocompromised animals. Caspofungin possesses favourable pharmacokinetic properties and is not metabolised through the cytochrome P450 (CYP) enzyme system. It showed highly promising antifungal efficacy in Phase II and III clinical trials in immunocompromised patients with oesophageal candidiasis. Caspofungin was effective in patients with invasive aspergillosis intolerant or refractory to standard therapies. Based on its documented antifungal efficacy and an excellent safety profile, caspofungin has been approved recently by the US Food and Drug Administration for the treatment of invasive aspergillosis in patients who are refractory to or intolerant of other therapies (i.e., amphotericin B, lipid formulations of amphotericin B, and/or itraconazole). Phase III clinical trials in patients with candidaemia and in persistently febrile neutropenic patients requiring empirical antifungal therapy are ongoing. This paper reviews the preclinical and clinical pharmacology of caspofungin and its potential role for treatment of invasive and superficial fungal infections in patients.     

Voriconazole : a review of its use in the management of invasive fungal infections

Voriconazole (VFEND), a synthetic second-generation, broad-spectrum triazole derivative of fluconazole, inhibits the cytochrome P450 (CYP)-dependent enzyme 14-alpha-sterol demethylase, thereby disrupting the cell membrane and halting fungal growth. In the US, intravenous and/or oral voriconazole is recommended in adults for the treatment of invasive aspergillosis, candidaemia in non-neutropenic patients, disseminated infections caused by Candida spp., oesophageal candidiasis, and in patients with scedosporiosis and fusariosis who are refractory to or intolerant of other antifungal therapy. In Europe, intravenous and/or oral voriconazole is recommended in adults and paediatric patients of at least 2 years of age for the treatment of invasive aspergillosis, candidaemia in non-neutropenic patients, fluconazole-resistant serious invasive Candida spp. infections, scedosporiosis and fusariosis.In large randomised trials, voriconazole was an effective and generally well tolerated primary treatment for candidiasis and invasive aspergillosis in adults and adolescents. More limited data also support the use of voriconazole for the treatment of invasive fungal infections in children, in those with rare fungal infections, such as Fusarium spp. or Scedosporium spp., and in those refractory to or intolerant of other standard antifungal therapies. The availability of both parenteral and oral formulations and the almost complete absorption of the drug after oral administration provide for ease of use and potential cost savings, and ensure that therapeutic plasma concentrations are maintained when switching from intravenous to oral therapy. On the other hand, the numerous drug interactions associated with voriconazole may limit its usefulness in some patients. Further clinical experience will help to more fully determine the position of voriconazole in relation to other licensed antifungal agents. In the meantime, voriconazole is a valuable emerging option for the treatment of invasive aspergillosis and rare fungal infections, including Fusarium spp. and Scedosporium spp. infections, and provides an alternative option for the treatment of candidiasis, particularly where the causative organism is inherently resistant to other licensed antifungal agents.     

Antifungal activity and clinical efficacy of micafungin sodium (Funguard)

Micafungin sodium (MCFG) is a new lipopeptide antifungal agent of the echinocandin class. MCFG inhibits 1,3-beta-glucan synthesis in C. albicans and A. fumigatus in a non-competitive manner and has antifungal activity against both Aspergillus and Candida species. In neutropenic mouse models of disseminated candidiasis and pulmonary aspergillosis, the efficacy of MCFG was superior to that of fluconazole and itroconazole, but comparable to that of amphotericin B. The efficacy and safety of MCFG were investigated in 70 patients with deep-seated mycosis caused by Candida and Aspergillus species. The overall clinical response rates were 57.1% in aspergillosis and 78.6% in candidiasis. The incidence of adverse events related to micafungin was 17.9 %, and there was no dose-related occurrence of any adverse events. The results from this study indicated that micafungin was effective against aspergillosis and candidiasis, with no tolerability problems.     

A comparative evaluation of properties and clinical efficacy of the echinocandins

With the increase in prevalence of fungal infections, newer antifungal agents are needed to effectively treat invasive disease, and at the same time minimize adverse effects from therapy. The echinocandins comprise a novel class of antifungals; their mechanism of action involves inhibiting 1,3-β-D-glucan synthase, which is essential in cell wall synthesis for certain fungi. All three echinocandins are US FDA-approved for the treatment of esophageal candidiasis. Caspofungin and anidulafungin are licensed for the treatment of candidemia, and other select forms of invasive candidiasis. Micafungin is at present the only echinocandin approved for prophylaxis of fungal infections in hematopoietic stem cell transplants; whereas caspofungin is approved for empiric therapy of febrile neutropenia. Although all three echinocandins are active against Aspergillus, only caspofungin is presently approved for salvage therapy in invasive aspergillosis. Combination therapy with echinocandins plus other licensed antifungal therapy shows promise in treating invasive aspergillosis. This article will explore the similarities and differences among the echinocandins.     

A comparative evaluation of properties and clinical efficacy of the echinocandins

With the increase in prevalence of fungal infections, newer antifungal agents are needed to effectively treat invasive disease, and at the same time minimize adverse effects from therapy. The echinocandins comprise a novel class of antifungals; their mechanism of action involves inhibiting 1,3-beta-D-glucan synthase, which is essential in cell wall synthesis for certain fungi. All three echinocandins are US FDA-approved for the treatment of esophageal candidiasis. Caspofungin and anidulafungin are licensed for the treatment of candidemia, and other select forms of invasive candidiasis. Micafungin is at present the only echinocandin approved for prophylaxis of fungal infections in hematopoietic stem cell transplants; whereas caspofungin is approved for empiric therapy of febrile neutropenia. Although all three echinocandins are active against Aspergillus, only caspofungin is presently approved for salvage therapy in invasive aspergillosis. Combination therapy with echinocandins plus other licensed antifungal therapy shows promise in treating invasive aspergillosis. This article will explore the similarities and differences among the echinocandins.     

Anidulafungin: an evidence-based review of its use in invasive fungal infections

INTRODUCTION: Anidulafungin is a new echinocandin antifungal agent with indications for use in esophageal candidiasis and candidemia. The mortality and morbidity associated with fungal infections in healthcare facilities necessitates the development of new treatment options for these diseases. AIMS: This review assesses the pharmacology and evidence for the use of anidulafungin in the treatment of serious fungal infections. EVIDENCE REVIEW: There is substantial evidence that anidulafungin is a potent antifungal agent with activity against a broad range of fungal species. Likewise, evidence supports that anidulafungin is a well-tolerated antifungal agent. Clinical studies provide sufficient evidence for regulatory approval for esophageal candidiasis and candidemia, and limited evidence suggests that anidulafungin may be superior to fluconazole for candidemia and invasive candidiasis. The introduction of anidulafungin into clinical practice adds a third option for therapy in the echinocandin class. Research into its efficacy in other fungal infections is ongoing, and further studies into the impact of anidulafungin on economic outcomes will be beneficial. PLACE IN THERAPY: Current evidence supports the use of anidulafungin in the management of candidemia, esophageal candidiasis, and invasive candidiasis, as demonstrated by the successful results in large multicenter clinical trials.     

Therapeutic efficacy of imipenem/cilastatin sodium on respiratory tract infections in lung cancer patients]

Imipenem/cilastatin sodium (IPM/CS) was used to treat respiratory tract infections (RTI) in 54 patients with lung cancer. Out of the 54 patients studied, 53 were evaluable for the utility of IPM/CS; 42 had pneumonia, 9 had obstructive pneumonia, 1 had a lung abscess and 1 had acute bronchitis. The efficacy rate was 71.7%. Seventeen causative organisms were isolated from 14 patients. They included Staphylococcus aureus 5 strains, Staphylococcus epidermidis 4 strains, Staphylococcus sp. 2 strains, Enterococcus faecalis 1 strain, Pseudomonas aeruginosa 2 strains, Pseudomonas fluorescens 2 strains, Acinetobacter sp. 1 strain, and the eradication rate was 81.8%. Clinical adverse effects (nausea and vomiting) were observed in 1 patient. Abnormalities in laboratory test results were observed in 3 patients. They disappeared or returned to normal values after completion of therapy or discontinuation of IPM/CS administration. IPM/CS appears to be a useful antibiotic for RTI in patients with lung cancer.     

Empiric antifungal therapy in patients with febrile neutropenia

Invasive fungal infections, most commonly candidiasis or aspergillosis, are a major cause of morbidity and mortality among patients with neutropenia. Difficulty in diagnosing invasive fungal infections in these patients complicates decisions regarding pharmacotherapy. Because of the difficult diagnosis and the significant morbidity and mortality of fungal infections in patients with neutropenia, systemic antifungal agents are used as empiric antifungal therapy in patients with febrile neutropenia who are not responding to antibacterial therapy. The pharmacotherapy of invasive fungal infections has evolved rapidly within the past several years as numerous antifungal agents--different formulations of amphotericin B, azoles, and echinocandins--have become available for use as empiric antifungal therapy in patients with febrile neutropenia. Various levels of evidence support the use of these agents for this indication. Their use is limited, however, by drug intolerance, drug interactions, adverse-event profiles, and limited activity with some mold species. Thus, considerations for selecting an antifungal drug for empiric use in patients with febrile neutropenia should include the epidemiology of fungal infections in the individual patient's institution and the specific clinical circumstances of the patient.     

Current and future antifungal therapy: new targets for antifungal therapy

Invasive fungal infections will continue to cause major complications in immunocompromized patients. At the moment, the expansion of antifungal drug research has occurred because there is a critical need for new antifungal agents to treat these life-threatening invasive fungal infections. The overview of the development of antifungal therapy which is provided here demonstrates the increased interest in this very special area of infectious diseases. Although we now have some newer and less toxic antifungal agents that are currently available for clinical use, their clinical efficacy in some invasive fungal infections, such as aspergillosis and fusariosis, is not very good. Intense efforts in antifungal drug discovery are urgently needed to develop more promising and effective antifungal agents for use in the clinical arena.     

系统性红斑狼疮并发真菌感染的临床回顾性分析

目的探讨系统性红斑狼疮(SLE)并发真菌感染的危险因素、临床特点及防治措施。方法回顾性分析56例SLE合并真菌感染的临床资料。结果SLE并发真菌感染主要发生在消化道、皮肤及呼吸道(83.3%),患者的免疫功能低下、疾病的活动以及激素、免疫抑制剂、抗生素的不合理应用是其发病的主要危险因素。结论早期诊断及合理的治疗有助于改善SLE合并真菌感染患者的预后。