Diagnosis and treatment of invasive fungal infections in cancer patients

Fungal infections continue to cause major complications in cancer patients. With the increasing use of aggressive chemotherapy causing prolonged granulocytopenia, and the progress made in the prophylaxis and treatment of bacterial infections, the risk of invasive mycoses has increased, particulaly in patients with hematological malignancies. The prognosis of these infections is poor unless they are diagnosed and treated promptly. Early diagnosis, particularly in neutropenic cancer patients, is often difficult and antifungal therapy is frequently unsuccessful because it is not instituted until the infection is in an advanced, fatal phase. In order to reduce the mortality associated with invasive fungal infections, antifungal therapy, usually amphotericin B, has been empirically carried out in neutropenic patients with fever unresponsive to broadspectrum antibacterial therapy. However, the absence of a marker of the fungal infection, the frequent occurrence in these patients of non-infective fever, which does not require any antimicrobial therapy, and the possible toxicity of amphotericin B represent the major limits of empiric antifungal therapy. In view of the above, the study of improved and less toxic antifungal agents, and the evaluation of new clinical and laboratory methods for an early diagnosis, have been the major goals in research on the opportunistic invasive fungal infections in the last years.Presented as an invited lecture at the 4th International Symposium: Supportive Care in Cancer, St. Gallen, Switzerland, 24–27 February 1993     

Invasive mold infections in cancer patients: 5 years' experience withAspergillus,Mucor, Fusarium andAcremonium infections

Twenty systemic mold infections due to hyphic fungi (molds) arising within the last 5 years in a 60-bed cancer department are analyzed. The most frequent risk factors were plants in ward (75%), prior therapy with broad spectrum antibiotics (70%), catheter insertion (70%), acute leukemia (65%) and neutropenia (60%). Before death, a definitive diagnosis was made in 40%, and a presumptive diagnosis in 60% of patients; post mortem the presumptive antemortem diagnosis was confirmed in all cases (100% of patients). Aspergillosis was the most common invasive fungal disease (55%), followed by mucormycosis (15%), fusariosis (15%), and acremoniosis (10%). Of 20 patients, 8 (40%) were cured or improved after antifungal therapy with amphotericin B, ambisome and/or itraconazole; 8/20 (40%) died of fungal infection and 4/20 (20%) of underlying disease with fungal infection. Even though the diagnosis was made and antifungal therapy started before death in 15/20 (75%), invasive mold infection had a 60% overall mortality in patients with malignant disease.     

Amphotericin B or ketoconazole therapy of fungal infections in neutropenic cancer patients.

Fungal infections in neutropenic cancer patients have increased in frequency and constitute an important cause of morbidity and mortality. Empiric antifungal therapy is often administered to those patients who have failed to respond to antibacterial antibiotics. We conducted a prospective, randomized trial of amphotericin B and ketoconazole for 172 neutropenic cancer patients with presumed or proven fungal infections. Overall, amphotericin B and ketoconazole were equally effective. Amphotericin B may have been more effective than ketoconazole for the treatment of pneumonia. Also, five of eight Candida tropicalis infections treated with amphotericin B responded, whereas all eight infections treated with ketoconazole failed to respond (P = 0.03). Response rates for localized fungal infections were similar with both drugs. Ketoconazole should not be used as empiric antifungal therapy at institutions where there is a high frequency of infections caused by Aspergillus spp. or C. tropicalis because this agent lacks activity in vitro against these species.     

New perspectives in the diagnosis of systemic fungal infections

Profound and prolonged neutropenia following chemotherapy is a major risk factor for systemic fungal infections. Mortality associated with disseminated fungal infection is high, and treatment with conventional amphotericin B is complicated by renal toxicity. Candida and Aspergillus are among the major pathogens in these patients. Many patients remaining neutropenic over a prolonged period of time will receive empirical antifungal therapy. The clinical and laboratory diagnoses of these infections are neither sensitive nor specific and are generally limited in the early detection of invasive fungal infection. However, several new approaches to diagnosis are being developed, which should be translated into routine practice, based on a greater understanding of the pathogenesis of systemic fungal infection and virulence determinants of fungal pathogens. These include antigen detection and polymerase chain reaction. Patients with presumed fungal infection require more intense and accurate monitoring for signs of disseminated infection. Early diagnosis may guide appropriate treatment and prevent mortality. Continued development of commercial tests should help achieve the objective of definitive diagnostic tests for systemic fungal infections.     

Comparison of fluconazole with oral polyenes in the prevention of fungal infections in neutropenic patients

The goal of this prospective randomized single-center study was the comparison of safety and efficacy of high-dose oral/intravenous fluconazole (400 mg daily) (group A) with oral nystatin plus miconazole inhalations (group B) in the prevention of fungal infections on a hemato-oncological isolation Ward. Of 157 patients admitted to the isolation ward during the study period only 90 (57%) were eligible for randomization; 22 (14%) had a fungal infection at admission. Of the 90 randomized patients, 89 were evaluable, 43 in group A and 46 in group B. The age, sex, diagnosis, planned therapy and risk factors for fungal infections at admission as well as the duration of neutropenia were in the same proportions in both groups. Oral thrush and mucocutaneous candidiasis were prevented in all patients of both groups, and 29 patients (32%: 17 in group A, 12 in group B) were discharged after successful prophylaxis (NS). Empiric amphotericin B was given according to predetermined criteria to 45 patients (51%: 23 group A, 22 group B; NS). Fluconazole significantly delayed the time before the start of intravenous amphotericin B. It was begun after a median of 10 days (0–45 days, range) of neutropenia below 0.5x10⁹ granulocytes/l in group A and 7.5 days (0–26, range) in group B (P<0.05). The duration of successful prophylaxis was significantly longer in group A (26 days median) than in group B (21 days, median) (P<0.05). Systemic fungal infection was documented in 3 patients (1 group A, 2 group B; NS). Colonisation with Candida persisted for more than 14 days or occurred de novo after admission in 1 patient in group A and in 7 patients in group B (NS). Oral nystatin had to be discontinued because of oral intolerance in 3 patients and fluconazol had to be stopped because of increased liver values in one patient. Compliance was worse (P<0.01) in group B; 82% of the planned dose was given in group B compared to 99% in group A. Both regimens successfully prevented oral fungal complications. Fluconazole was better tolerated and delayed the need for empiric amphotericin B. Neither approach cancelled the need for the empiric use of amphotericin B nor prevented fungal infections or colonization. Systemic fungal infections occur probably independently of oral or mucocutaneous candidiasis.     

Tuboovarian abscess caused by Candida glabrata in a febrile neutropenic patient

Deep-seated Candida infections are strongly associated with mortality and morbidity of patients, and need early diagnosis. The frequency of deep-seated fungal infection has recently been growing. We encountered a tuboovarian abscess caused by Candida glabrata after chemotherapy with an anticancer drug, methotrexate, in a febrile neutropenic patient. The susceptibilities to fluconazole and amphotericin B were 16 and 0.5µg/ml, respectively. Although combination therapy of fluconazole and amphotericin B was effective, left salpingectomy was laparoscopically performed because the left adnexal tumor continued to exist asymptomatically after 1 month.     

不同时机两性霉素B脂质体治疗慢性阻塞性肺疾病合并侵袭性肺部真菌感染的疗效及安全性探讨

目的 探讨不同时机两性霉素B脂质体治疗慢性阻塞性肺疾病（COPD）合并侵袭性肺部真菌感染（IPFI）的疗效及安全性.方法 本文回顾性分析我科2010年8月至2012年2月,COPD合并IPFI的28例患者应用两性霉素B脂质体的临床资料,其诊断标准参见中华医学会呼吸分会制定的《慢性阻塞性肺病诊治规范2007修订版》和《侵袭性肺部真菌感染的诊断标准与治疗原则（草案）》,观察并探讨了不同时机两性霉素B脂质体治疗COPD合并IPFI有效性及治疗时机选择等,治疗期间监测肺影像学、肝肾功能电解质、体温等变化,以观察两性霉素B脂质体不良反应.结果 临床诊断、拟诊各22、6例;抢先/经验治疗组有效率为76.47％,高于挽救/目标治疗组的45.45％,差异有统计学意义（P＜0.05）;疗程比较方面：挽救治疗组疗程为（22.32 ±5.45）d,长于抢先治疗组的（13.40±4.34）d,差异有统计学意义（P＜0.05）;不良反应发生率比较：挽救治疗组不良反应率（57.14％）高于抢先治疗组不良反应率（39.29％）,且差异具有统计学意义（P＜0.05）.结论 两性霉素B脂质体是治疗COPD合并IPFI安全有效的药物,抢先治疗能提高疗效,且能减少不良反应发生率,临床工作中值得进一步研究证实.     

Itraconazole oral solution for primary prophylaxis of fungal infections in patients with hematological malignancy and profound neutropenia: a randomized, double-blind, double-placebo, multicenter trial comparing itraconazole and amphotericin B

Systemic and superficial fungal infections are a major problem among immunocompromised patients with hematological malignancy. A double-blind, double-placebo, randomized, multicenter trial was performed to compare the efficacy and safety of itraconazole oral solution (2.5 mg/kg of body weight twice a day) with amphotericin B capsules (500 mg orally four times a day) for prophylaxis of systemic and superficial fungal infection. Prophylactic treatment was initiated on the first day of chemotherapy and was continued until the end of the neutropenic period (>0.5 x 10(9) neutrophils/liter) or up to a maximum of 3 days following the end of neutropenia, unless a systemic fungal infection was documented or suspected. The maximum treatment duration was 56 days. In the intent-to-treat population, invasive aspergillosis was noted in 5 (1.8%) of the 281 patients assigned to itraconazole oral solution and in 9 (3.3%) of the 276 patients assigned to oral amphotericin B; of these, 1 and 4 patients died, respectively. Proven systemic fungal infection (including invasive aspergillosis) occurred in 8 patients (2.8%) who received itraconazole, compared with 13 (4.7%) who received oral amphotericin B. Itraconazole significantly reduced the incidence of superficial fungal infections as compared to oral amphotericin B (2 [1%] versus 13 [5%]; P = 0.004). Although the incidences of suspected fungal infection (including fever of unknown origin) were not different between the groups, fewer patients were administered intravenous systemic antifungals (mainly intravenous amphotericin B) in the group receiving itraconazole than in the group receiving oral amphotericin B (114 [41%] versus 132 [48%]; P = 0.066). Adequate plasma itraconazole levels were achieved in about 80% of the patients from 1 week after the start of treatment. In both groups, the trial medication was safe and well tolerated. Prophylactic administration of itraconazole oral solution significantly reduces superficial fungal infection in patients with hematological malignancies and neutropenia. The incidence of proven systemic fungal infections, the number of deaths due to deep fungal infections, and the use of systemic antifungals tended to be lower in the itraconazole-treated group than in the amphotericin B-treated group, without statistical significance. Itraconazole oral solution is a broad-spectrum systemic antifungal agent with prophylactic activity in neutropenic patients, especially for those at high risk of prolonged neutropenia.     

Prevention and management of oral infections in cancer patients

 The successful prevention and management of oral infections and infections from the oral cavity in cancer patients are based on identification of risk patients, selection of patients for prophylactic measures, diagnosis of infection and implementation of directed or empiric antimicrobial therapy. Identification of patients at risk for infection is based on each patient's type of oral microbial colonization and the presence of latent viral infections. Systemic and local resistance to infection will be decisive, and in many patients the risk can be estimated from the expected myelosuppressive effect of anticancer treatment. Diagnosis of infection is often based on clinical findings together with the results of microbiological investigations. Biopsies could be useful, but can seldom be obtained. Blood samples are mandatory for isolation of microorganisms involved in systemic infections in myelosuppressed patients. Prevention of infection requires both local and systemic measures. Elimination of the risk of a breach in the first line of defence is urgent, and the maintenance of mucosal integrity is important. Monitoring microbial colonization is common, as is the institution of antiviral prophylaxis in patients with increased anti-HSV IgG (ELISA >10 000). Antifungal prophylaxis, to avoid colonization and superinfection, should be instituted in patients with low neutrophil counts. Gastrointestinal prophylaxis with quinolones is also commonly used in these patient groups. Treatment of oral infections in cancer patients should include systemic antimicrobial agents in most cases. Special attention should be directed to oral infections in neutropenic (<0.5×l0⁹/l) patients in whom oral microorganisms are the leading cause of bacteraemia. Invasive fungal infections of the oral cavity can be associated with systemic fungal infection and are indications for the use of liposomal amphotericin B. Published online: 21 May 1999     

Strategies for managing systemic fungal infection and the place of itraconazole

Systemic fungal infections are an increasing cause of mortality and morbidity in patients with haematological malignancies and certain other conditions associated with profound immunosuppression. The majority of such infections are caused by Aspergillus and Candida species. In recent years, the number of available drugs effective in the therapy of these difficult infections has expanded. Large clinical trials have been performed in different settings such as prophylaxis, empirical and first-line therapy. For prophylaxis, the azoles fluconazole and itraconazole have been most widely studied. These azoles are available in both oral and intravenous formulations. Itraconazole has a wide spectrum of activity including Aspergillus, Candida albicans and non-albicans species. Two large studies comparing the use of itraconazole with fluconazole for primary prophylaxis in high-risk patients who were recipients of allogeneic stem cell transplants have recently been reported. These have confirmed that itraconazole is effective in this setting in reducing the rate of systemic fungal infections. However, there are concerns with regard to increased toxicity and the potential for drug interactions with itraconazole compared with fluconazole. In the empirical setting, large randomized studies support the use of caspofungin and liposomal amphotericin B. Voriconazole and lipid-associated amphotericin B have been shown to be effective in first-line therapy and caspofungin for salvage. New approaches to management include efforts at improving diagnosis, combination antifungal therapy and treatment strategies for emerging moulds.     

纤维支气管镜检查在肺部真菌感染诊断中的应用

目的 探讨纤维支气管镜检查在肺部真菌感染诊断中的作用。方法 对12例具有真菌感染高危因素的患者进行纤维支气管镜检查，在病变部位进行支气管肺灌洗或肺活检，分别进行真菌培养和组织病理检查。结果 12例患者中有7例诊断为念珠菌肺炎（4例为光滑念珠菌，2例为热带念珠菌，1例为白念珠菌），3例诊断为曲霉肺炎，1例诊断为肺毛霉感染，1例诊断为奴卡菌肺炎。其中6例患者同时合并细菌感染，所有患者根据体外药物敏感试验进行抗真菌和细菌治疗。有5例患者应用了两性霉素B和脂质体两性霉素B，3例应用了伊曲康唑，2例患者联合应用了卡泊芬净。12例患者中治愈5例．死亡5例。放弃治疗2例。结论 纤维支气管镜检查对肺部真菌感染的诊断有一定的价值。     

国产两性霉素B治疗侵袭性真菌感染

目的观察国产静脉用两性霉素B对血液系统恶性肿瘤患者侵袭性真菌感染(IFI)的临床疗效及安全性。方法40例恶性血液病患者使用华北制药厂生产的两性霉素B,剂量为5￣50mg/d,用药天数8￣66d,中数22d。结果两性霉素B临床总有效率为75%,真菌清除率63.6%,不良反应发生率中寒战、发热57.5%,低血钾40%,消化道反应20%,肾功能损害15%。结论两性霉素B抗菌谱较广,且疗效好,为治疗IFI的高效药物,但因其不良反应较大,限制其使用。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。     

A comparative review of conventional and lipid formulations of amphotericin B

Over the past 15 years, factors suh as corticosteroid treatment, cytotoxic chemotherapy, excessive use of broad spectrum antibiotics and HIV have led to an increased risk of serious fungal infections in both adults and pediatric patients. This increase in invasive fungal infections poses increasing difficulty in their treatment. Three new lipid formulations of amphotericin B are now available in the U.S.: amphotericin B lipid complex (Abelcet), amphotericin B colloidal dispersion (Amphotec), and liposomal amphotericin B (AmBisome). These newer formulations are substantially more expensive, but allow patients to receive higher doses for longer periods of time with decreased renal toxicity than conventional amphotericin B. The properties of these new agents are summarized in this review. Discussion of current national guidelines as well as those used at our institution are presented to provide guidance for the development of institution specific guidelines for the most cost-effective drug for most patients, some may benefit more from one of the newer lipid formulations.     

How to select an antifungal agent in critically ill patients

Fungal infections are common in critically ill patients and are associated with increased morbidity and mortality. Candida spp are the most commonly isolated fungal pathogens. The last 2 decades have seen an increased incidence of fungal infections in critical illness and the emergence of new pathogenic fungal species and also the development of more effective (better bioavailability) and safer (less toxicity, fewer drug interactions) drugs. The distinction between colonization and infection can be difficult, and problems diagnosing infection may delay initiation of antifungal treatment. A number of factors have been identified that can help to distinguish patients at high risk for fungal infection. The antifungal agents that are most frequently used in the intensive care unit are the first- and second-generation azoles and the echinocandins; amphotericin B derivatives (mainly the liposomal agents) are less widely used because of adverse effects. The choice of antifungal agent in critically ill patients will depend on the aim of therapy (prophylaxis, pre-emptive, empiric, definitive), as well as on local epidemiology and specific properties of the drug (antifungal spectrum, efficacy, toxicity, pharmacokinetic/pharmacodynamic properties, cost). In this article we will review all these aspects and propose an algorithm to guide selection of antifungal agents in critically ill patients.     

Systemic Antifungal Prophylaxis After Hematopoietic Stem Cell Transplantation: A Meta-Analysis

Background

Hematopoietic stem transplant recipients are subject to increased risk for invasive fungal infections.

Objective

This meta-analysis was undertaken to explore the comparative effectiveness of systemic antifungal prophylaxis in hematopoietic stem cell transplant recipients.

Methods

We searched PubMed and The Cochrane Register of Randomized Controlled Trials up to March 2013 for randomized studies on systemic antifungal prophylaxis after hematopoietic stem cell transplantation. We performed a meta-analysis on the relative effectiveness of systemic antifungal prophylaxis on proven or probable invasive fungal infections using direct and indirect effects. Relative effectiveness was reported as odds ratio (OR) for invasive fungal infections, causative agent, empirical antifungal therapy, and withdrawals due to drug adverse events.

Results

Twenty evaluable studies provided data on 4823 patients. The risk for invasive fungal infections while on prophylaxis was 5.1% (95% CI, 3.6−6.8%). In patients receiving fluconazole, risks of proven or probable invasive fungal infections (OR = 0.24; 95% CI, 0.11−0.50; number needed to treat [NNT] = 8), systemic candidiasis (OR = 0.11; 95% CI, 0.05−0.24; NNT = 7), and overall need for empiric antifungal treatment (OR = 0.60; 95% CI, 0.44−0.82; NNT = 8) were reduced compared with patients receiving placebo. Itraconazole was more effective than fluconazole for the prevention of aspergillosis (OR = 0.40; 95% CI, 0.19−0.83; NNT = 23) at the expense of more frequent withdrawals (OR = 3.01; 95% CI, 1.77−5.13; number needed to harm = 6). Micafungin was marginally more effective than fluconazole for the prevention of all mold infections (OR = 0.35; 95% CI, 0.10−1.18; NNT = 79) and invasive aspergillosis (OR = 0.19; 95% CI, 0.03−1.11; NNT = 78) and reducing the need for empiric antifungal treatment (OR = 0.40; 95% CI, 0.13−1.21; NNT = 8). There was a relative lack of comparisons between different antifungal prophylactic strategies, including the newer azoles, voriconazole and posaconazole, in this population. Direct effects derived from single studies showed marginally significant effects for voriconazole compared with fluconazole regarding invasive aspergillosis (OR = 0.50; 95% CI, 0.20−1.20; NNT = 35) and the need for empiric treatment (OR = 0.72; 95% CI, 0.50−1.06; NNT = 15). Voriconazole compared with itraconazole (OR = 0.59; 95% CI, 0.40−0.88; NNT = 8) and posaconazole compared with amphotericin B (OR = 0.28; 95% CI, 0.06−1.24, marginal significance; NNT = 3) were better regarding empirical antifungal treatment.

Conclusions

Even when on antifungal therapy, invasive fungal infection will develop in 1 of 20 patients undergoing hematopoietic stem cell transplantation. There is evidence for the comparable effectiveness of different antifungal drugs used for prophylaxis. Fluconazole is the most widely studied agent, but micafungin might prove to be more effective. There is a relative paucity of studies for the newer azoles, although both voriconazole and posaconazole give proof of their comparative or higher effectiveness to fluconazole in single randomized studies.     

Eradication of severe neonatal systemic candidiasis with amphotericin B lipid complex

OBJECTIVE: To report the successful use of amphotericin B lipid complex in treating severe systemic candidiasis in a very-low-birth-weight infant. CASE SUMMARY: A preterm female infant, born at 25 weeks' gestational age with a birth weight of 870 g, had received full supportive care in the neonatal intensive care unit (NICU), including mechanical ventilation, total parenteral nutrition, and placement of central venous catheters. At seven weeks of age, she developed severe disseminated candidiasis, which failed to respond to conventional amphotericin B and fluconazole therapy. Her progressive deterioration was reversed only after amphotericin B lipid complex (A-complex) was substituted for conventional amphotericin B. The improvement in her condition was impressive, and she made a full recovery without any adverse effect. DISCUSSION: With increased reliance on invasive technologies for life support, systemic candida infections have become increasingly common among premature infants in the NICU. Such infections are potentially fatal for the high-risk neonate. A literature review shows limited documentation of the use of lipid-based formulations of amphotericin B, especially A-complex, in preterm infants. However, the collective experience with these products appears to show that they are effective and cause fewer adverse effects than conventional amphotericin B. The infant reported here had shown progressive deterioration from disseminated candidiasis until conventional amphotericin B therapy was replaced with A-complex. Her recovery corresponded to the clearance of the candidemia. CONCLUSIONS: With favorable results and increasing experience with lipid-based formulations of amphotericin B, it is reasonable to consider these new formulations as therapy for candidemia in preterm infants who are at a high risk of nephrotoxicity or who have failed conventional therapy.     

Candida infections in non-neutropenic children after the neonatal period

There are a variety of diseases, from local mucous membrane infections to invasive systemic infections, that are caused by Candida species. As a causative agent, Candida albicans is the most common; however, the other Candida species can also cause the same clinical syndromes. Most invasive fungal infections in children occur in the hospital setting. Candidemia is a serious condition associated with high morbidity and mortality and increased healthcare costs in pediatric patients. Children at the highest risk are those with prolonged intensive care unit stays, reduced immune function, recent surgery, prior bacterial infection, prior use of antibiotics and/or corticosteroids and other immunosuppressive agents, as well as use of a central venous catheter, total parenteral nutrition, mechanical ventilation and dialysis. Positive blood culture is the gold standard of candidemia; it should not be accepted as contamination or colonization in children with an intravascular catheter. However, in oropharyngeal or vulvovaginal candidiasis, culture of lesions is rarely indicated unless the disease is recalcitrant or recurrent. Recovery of Candida from the sputum should usually be considered as colonization and should not be treated with antifungal therapy. Antigen and antibody detecting tests are evaluated in invasive Candida infections; however, there are no published results in children, and their roles in diagnosis are also unclear. For the therapy of invasive Candida infections in non-neutropenic patients, fluconazole or an echinocandin is usually recommended. Alternatively, amphotericin B deoxycholate or lipid formulations of amphotericin B can also be used. The recommended therapy of Candida meningitis is amphotericin B combined with flucytosine. The combination therapy for Candida infections is usually not indicated. Prophylaxis in non-neonatal, immunocompetent children is not recommended.     

Trichosporon species infection in bone marrow transplanted patients

Trichosporon species are emerging as opportunistic agents that cause systemic diseases in immunocompromised patients. Patients undergoing bone marrow transplant are submitted to intense and prolonged periods of neutropenia and consequently to several risk factors to fungal infections as the use of broad spectrum antibiotics and invasive devices. Two cases of fungal infections caused by Trichosporon asahii var. asahii and T. inkin in patients with bone marrow transplant are described T. asahii var. asahii was responsible for fungemia and the identification of this microorganism was later performed. T. inkin caused vascular accesses infection and was recovered from an implanted Hickman-Broviac catheter. Both patients were under oral fluconazole prophylaxis. The patient with systemic infection died despite the therapy with amphotericin B and the patient with catheter-related infection recovered from the fungal infection after catheter removal. Difficulties in the identification of this microorganism lead to delays in treatment and post-mortem diagnosis.     

造血干细胞移植后真菌感染的防治

目的 回顾性分析我院造血干细胞移植患者感染并发症的发生及防治情况.方法 分析我院1990年9月至2000年3月收治的150例次各种类型造血干细胞移植病例感染并发症的发生及防治情况,根据移植类型、感染发生与否、预防用药、病原学及感染部位等分组并进行统计学分析.结果 150例次病例感染的发生率为89.3%(134/150),3例患者死于感染,感染病死率为2%(3/150),这3例均为真菌感染.80例预防或治疗中用过泰能或头孢他啶的病例,真菌感染发生率为32.5%(26/80),而未用过泰能或头孢他啶的病例真菌感染的发生率仅为15.7%(11/70),差异有统计学意义(X2=12.0471,P<0.05).12例真菌感染病例采用小剂量两性霉素B(10 mg/d)治疗,治愈率为100%.结论 预防性应用广谱强力的抗生素并不能减少感染发生率,反而可能增加真菌感染的机会;小剂量两性霉素B是治疗真菌感染新的、有效而安全的方法 .     

Disseminated infection by Fusarium solani in acute lymphocytic leukemia: A case report

BACKGROUNDIn recent years, the rate of immunosuppressed patients has increased rapidly. Invasive fungal infections usually occur in these patients, especially those who have had hematological malignances and received chemotherapy. Fusariosis is a rare pathogenic fungus, it can lead to severely invasive Fusarium infections. Along with the increased rate of immune compromised patients, the incidence of invasive Fusarium infections has also increased from the past few years. Early diagnosis and therapy are important to prevent further development to a more aggressive or disseminated infection.CASE SUMMARYWe report a case of a 19-year-old male acute B-lymphocytic leukemia patient with fungal infection in the skin, eyeball, and knee joint during the course of chemotherapy. We performed skin biopsy, microbial cultivation, and molecular biological identification, and the pathogenic fungus was finally confirmed to be Fusarium solani. The patient was treated with oral 200 mg voriconazole twice daily intravenous administration of 100 mg liposomal amphotericin B once daily, and surgical debridement. Granulocyte colony-stimulating factor was administered to expedite neutrophil recovery. The disseminated Fusarium solani infection eventually resolved, and there was no recurrence at the 3 mo follow-up.CONCLUSIONOur case illustrates the early detection and successful intervention of a systemic invasive Fusarium infection. These are important to prevent progression to a more aggressive infection. Disseminate Fusarium infection requires the systemic use of antifungal agents and immunotherapy. Localized infection likely benefits from surgical debridement and the use of topical antifungal agents.