Pneumonia relevant to lung transplantation and pathogen distribution

Background Pneumonia is the most common cause of morbidity and mortality in lung transplant （LT） recipients. The aim of the present study was to evaluate the incidence, etiology, risk factors and prognosis of pneumonia in LT recipients. Methods The LT cohort consisted of 28 recipients receiving LT in Beijing Chao-Yang Hospital from August 2005 to April 2011. Data collected included demographic data, underlying disorders, time and type of transplant, follow-up information, date of last follow-up, and patient status. A retrospective analysis was made of observational data that were prospectively collected. Results Twenty-two patients of 28 LT recipients had 47 episodes of pneumonia throughout the study period. Thirty- eight episodes of pneumonia in 19 recipients occurred post-LT with a median follow-up of 257.5 days （1-2104 days）, the incidence of pneumonia was 192.4 episodes per 100 LT/year and its median time of onset was 100.5 days （0-946 days） post-transplantation. Bacteria, virus and fungi accounted for 62%, 16% and 15% of the microbial pathogens, respectively. The most frequent were Pseudomonas aeruginosa （20%）, cytomegalovirus （CMV） （15%）, and Aspergillus fumigatus （10%）. A total of 29% （11/38） of pneumonias occurred in the first month post-LT, and then the incidence decreased gradually. The incidence of CMV pneumonia was 25% （7/28） with a median time of 97 days （10-971 days）. More than one bacterial infection and CMV infection were independent risk factors for aspergillus infection. The incidence of pulmonary tuberculosis （TB） was 18% （5/28）, and the history of TB was a risk factor for TB relapse. There were 58% （7/12） of recipients who died of infection, and 71% （5/7） of these died in the first year after LT. Conclusions Pneumonia is still a major cause of morbidity and mortality in LT recipients. The most frequent microorganisms were Pseudornonas aeruginosa, CMV, and Aspergillus fumigates. The incidence of CMV pneumonia decreases with a delayed median time of onset. More than one incidence of bacterial infection and CMV infection are independent risk factors for aspergillus infection. LT recipients are at high risk for TB, and the history of TB is a risk factor for TB relapse.     

Diagnosis and treatment of fungal infection after liver transplantation

Background  Liver transplantation is the most effective treatment for end-stage liver diseases; however, infections after transplantation can seriously affect the patient’s health. The aim of this research was to investigate the diagnosis and treatment of fungal infection following liver transplantation.

Methods  Clinical data for 232 liver transplant patients at risk of fungal infection were examined for the presence of fungus in the blood, fluid, sputum, urine and stools of patients and by chest or abdominal CT scans. Patients diagnosed with a fungal infection were treated with Fluconazole or, if this was not effective, Voriconazole or Amphotericin B. Immunosuppressive therapy was also reviewed.

Results  Thirty-seven of 232 (15.9%) patients were diagnosed with a fungal infection, which occurred 4 to 34 days post-transplantation. Candida infections were diagnosed in 23 cases (62.2%) and Aspergillus infections in 12 cases (32.4%). Twenty-one cases were effectively treated with Fluconazole, 11 cases with Voriconazole, and two cases with Amphotericin B; however, three cases were not effectively treated with any of the antifungal agents. Overall, treatment was effective in 91.9% of patients.

Conclusions  Fungal infection has a significant influence on survival rate after liver transplantation. Imaging studies, and pathogenic and biopsy examinations can diagnose fungal infections, which can be effectively treated with antifungal agents such as Fluconazole, Voriconazole or Amphotericin B.

     

Analysis on the imaging features of AIDS with pulmonary fungal infection

Background Pulmonary fungal infection is one type of the common opportunistic infections in AIDS patients. The disease is hard to diagnose because of its complicated imaging features. The objective of this study was to investigate the imaging performance characteristics of pulmonary fungal infection in AIDS patients.Methods Fifty-one patients with AIDS complicated with pulmonary fungal infection and 56 patients of non-AIDS with pulmonary fungal infection were examined by CT scans and high-resolution CT scans. The contrast enhanced scans were performed in patients with the mass or suspected enlarged mediastinal lymph nodes. Results were compared between the two groups.Results The most common fungal infection in the two groups of patients was Candida albicans. The infection rates were 54.8% （28 cases） in the group （AIDS patients with pulmonary fungal infection） and 58.3% （32 cases） in another group （non-AIDS patients with pulmonary fungal infection）. In the two groups, the difference in diffuse distribution and the difference in incidence of affected upper and lower lobes in the bilateral lung fields were statistically significant. The differences in patchy or large consolidation shadow, cavitas, enlarged lymph nodes in mediastinum and pleural effusion were also significant when comparing the two groups.Conclusions The lesion in most of AIDS patients with pulmonary fungal infection tends to exhibit diffuse distribution,patchy or large consolidation shadow covering a more extensive region. The differences between AIDS with pulmonary fungal infection and non-AIDS with pulmonary fungal infection are statistically significant in lesion location and complicated imaging features. The most common fungal infection in AIDS patients is Candida albicans.     

Fungal infection in organ transplant patients

Purpose To review the characteristics and evolution of the fungal spectrum, and the risk factors causing fungal infection, and to make progress in diagnosing fungal infection after organ transplantation.Data sources An English-language literature search (MEDLINE 1990 -2000) and bibliographic review of textbooks and review articles.Study selection Twenty-three articles were selected from the literature that specifically addressed the stated purpose.Results Fungal infections in organ transplant patients were generally divided into two types:①disseminated primary or reactivation infection with one of the geographically restricted systemic mycoses; ②opportunistic infection by fungal species that rarely cause invasive infection in normal hosts. The risk factors of fungal infection after a transplant can be evaluated and predicted according to the organ recipient‘s conditions before, during and after the transplant. Progress in eady diagnostic methods during the past 10 years has mainly revolved around two aspects, culture and non-culture.Conclusions It is important to undertake a systemic evaluation on the condition of the organ recipient before,during and after a transplant;should any risk factor for tungal infection be suspected,diagnosis should be made as early as possible by employing mycological techniques including culture and non-culture methods.     

Coagulase-negative staphylococcus and enterococcus as predominant pathogens in liver transplant recipients with Gram-positive coccal bacteremia

Background Gram-positive bacteria such as Staphylococcus aureus have been a common cause of infection among liver transplant （LT） recipients in recent decades. The understanding of local epidemiology and its evolving trends with regard to pathogenic spectra and antibiotic susceptibility is beneficial to prophylactic and empiric treatment for LT recipients. This study aimed to investigate etiology, timing, antibiotic susceptibility and risk factors for multidrug resistant （MDR） Gram-positive coccal bacteremia after LT.Methods A cohort analysis of prospectively recorded data was performed to investigate etiologies, timing, antibiotic susceptibility and risk factors for MDR Gram-positive coccal bacteremia in 475 LT recipients.Results In 475 LT recipients in the first six months after LT, there were a total of 98 episodes of bacteremia caused by Gram-positive cocci in 82 （17%） patients. Seventy-five （77%） bacteremic episodes occurred in the first post-LT month.The most frequent Gram-positive cocci were methicillin-resistant coagulase-negative staphylococcus （CoNS, 46 isolates）,methicillin-resistant Staphylococcus aureus （MRSA, 13） and enterococcus （34, E. faecium 30, E. faecalis 4）. In all Gram-positive bacteremic isolates, 59 of 98 （60%） were MDR. Gram-positive coccal bacteremia and MDR Gram-positive coccal bacteremia predominantly occurred in patients with acute severe exacerbation of chronic hepatitis B and with fulminant/subfulminant hepatitis. Four independent risk factors for development of bacteremia caused by MDR Gram-positive coccus were： LT candidates with encephalopathy grades Ⅱ-Ⅳ （P=0.013, OR： 16.253, 95% CI：1.822-144.995）, pre-LT use of empirical antibiotics （P=0.018, OR： 1.029, 95% CI： 1.002-1.057）, post-LT urinary tract infections （P 〈0.001, OR： 20.340, 95% CI： 4.135-100.048） and abdominal infection （P=0.004, OR： 2.820, 95% CI：1.122-10.114）. The main infectious manifestations were coinfections due to gram-positive cocci and gram-negative bacilli.Conclusions Methicillin-resistant CoNS and enterococci are predominant pathogens among LT recipients with Gram-positive coccal bacteremia. Occurrences of Gram-positive coccal bacteremia may be associated with the severity of illness in the perioperative stage.     

Fungal infection after a tragedy: a report of three cases of candidosis in a fire accident

Patients who suffer severe burns are at increased risk for local and systemic infections. The incidence of fungal infections has increased in recent years, and these infections represent a major issue in burn intensive care units. Herein, we report three cases of fungal infection due to Candida species occurring in patients undergoing supportive therapy and antibiotic treatment during their hospitalization. Two of these patients were infected with Candida parapsilosis, and one was infected with Candida albicans. The risk factors for these patients’ Candida infections were multiple and prolonged courses of antimicrobial treatment, steroid treatment, tracheal intubation and smoke inhalation. Susceptibility testing of nine antifungal compounds was performed, and the minimum inhibitory concentration (MIC) values of all isolated strains were lower than the breakpoint MIC value for resistance of the relevant drug. All three patients were cured by treatment with antifungal agents. Candida infection may occur 1–3 weeks after thermal injury, and the prompt recognition and treatment of such infections with antifungal therapies may result in decreased morbidity and mortality associated with these infections in burn patients.

     

Breakthrough trichosporonosis in patients receiving echinocandins: case report and literature review

Trichosporon species now ranks as the second most common cause of disseminated yeast infections with a high mortality rate. Breakthrough trichosporonosis in patients receiving echinocandins therapy is being recognized recently. We present a case of breakthrough trichosporonosis with acute viral myocarditis while receiving caspofungin therapy. Trichosporon infection should be considered in patients, who have risk factors for invasive fungal infection and develop unexplained clinical manifestations of infection despite treatment with echinocandins.

     

Aspergillus pneumonia in renal transplant recipients

Background Filamentous fungal infections are associated with a high morbidity and mortality in solid organ transplants The present study aimed to investigate the aspergillus pneumonia in renal transplant recipients, and its diagnosis as well as treatment. Methods Approximately 2000 cases of renal transplants were retrospectively studied and we focused on cases hospitalized during August 1, 2005 and February 1, 2007, as the study period. The clinical database and electronic records were analyzed. Recently published literature was reviewed. Results There was more diabetes and hypertension in the infected group than in the non-infected group （86% vs 62% and 57% vs 39%, respectively）. Eighty-six percent of recipients from the infected group had delayed graft function. Seven cases with aspergillus pneumonia were identified based on either fungal culture or radiology. Of the 7 cases, 4 died in a few days after diagnosis. Liposomal amphotericin B was used as a first-line therapy. Conclusions Incidences of fungal infection are increasing among renal transplant recipients. Early diagnosis and treatment are critical steps in curing aspergillosis.     

Efficacy and safety of intravenous itraconazole followed by oral itraconazole solution in the treatment of invasive pulmonary mycosis

Background  Invasive pulmonary mycosis is the most common type of invasive fungal infection. It is often severe and difficult to treat, and is accompanied by high mortality. In this study, we aimed to evaluate the efficacy and safety of intravenous itraconazole followed by oral itraconazole solution in the treatment of invasive pulmonary mycosis and to determine the distribution of different fungi species.

Methods  This was a multi-center, open-label study which enrolled 71 patients who were diagnosed as invasive pulmonary mycosis between July 2007 and January 2009. All patients received intravenous itraconazole therapy followed by oral itraconazole solution with a total treatment duration of 6 weeks. Intravenous itraconazole was given at a dose of 200 mg bid (intravenous infusion every 12 hours) for the first two days, 200 mg qd for the subsequent 12 days. Sequential oral itraconazole solution was given at a dose of 200 mg bid for 4 weeks. Efficacy and safety were assessed according to clinical as well as microbiological criteria.

Results  Seventy one patients participated in this study. Of the 60 patients in the full analysis dataset, the clinical response rate was 61.7% and the mycological eradication rate was 66.7%. The overall response rate was 66.7%. Drug-related adverse events occurred in 18.0% of patients: hypokalemia, liver function impairment and mild gastrointestinal side effects were the most common. One patient suffered from severe adverse event, with limb and facial swelling.

Conclusion This study showed that in patients with invasive pulmonary mycosis, intravenous itraconazole followed by oral itraconazole solution therapy was safe and effective.

     

Pulmonary fungal infections after bone marrow transplantation: the value of high-resolution computed tomography in predicting their etiology

Background  The correct diagnosis of etiology of fungal infection after bone marrow transplantation is very important to the choice of antifungal drugs and a premise for improvement of therapeutic efficacy. This study aimed to compare high-resolution computed tomography (HRCT) findings of the pulmonary fungal infections to determine whether the etiology of various fungal infections could be diagnosed with HRCT.

Methods  Eighty-five cases were enrolled. According to the pathogens responsible for fungal infections, the patients were classified into three groups including invasive aspergillosis (n=52), candidiasis (n=19) and cryptococcosis (n=14) groups. All the patients underwent HRCT scans. Two independent radiologists retrospectively analyzed the HRCT scans regarding CT patterns and distribution of lung abnormality.

Results  Most fungal infections in the three groups occurred in the neutropenic phase. There was no significant difference in the constituent ratio of fungal infections at different phases after bone marrow transplantation among the three groups. Agreement between the two observers for all the CT characteristics of fungal infections was excellent (k >0.75). There was a significant difference in occurrence ratio of mass among the three groups (P=0.02). Occurrence ratio of mass (43.3%, 13/30) in the group with invasive aspergillosis was higher than in each of other two groups (20.0%, 2/10; 14.3%, 1/7). There was no significant difference in other CT characteristics of nodules or masses; including number, margin, halo sign, cavitation and air-crescent sign. There was no significant difference in number, margin, air bronchogram and distribution of air-space consolidation.

Conclusions  The HRCT appearance of various pulmonary fungal infections has a great deal of overlap and is nonspecific. Mass is more common in invasive aspergillosis, which is helpful to the diagnosis of invasive aspergillosis after bone marrow transplantation.

     

Management of mycoses in surgical patients -- review of the literature

Fungal infections have been recognized as major cause of morbidity and mortality in neutropenic and non-neutropenic surgical intensive care patients. The incidence of Candida has increased: it is now the fourth most often isolated pathogen in bloodstream infections. The incidence of Aspergillus infection in transplant patients is highest in heart and lung transplants: 19-26%. Most invasive fungal infections in surgical patients are caused by Candida spp. and Aspergillus spp., less by Cryptococcus spp. and may be classified as local or organ-related, as (chronic) disseminated, and as fungemia. There is no highly specific and sensitive routine test for the diagnosis of Candida and Aspergillus infections available; clinical signs of fungal infections are rather unspecific. The significance of colonization remains undetermined. In non-neutropenic surgical patients central venous access and broad-spectrum antibiotics are independent risk factors for the development of fungal infection. Immunsuppression, e.g., transplantation, burn injury, can render patients susceptible to fungal infection. This has lead to the introduction of antifungal prophylaxis in transplant and burned patients which has reduced the mortality for Candida spp. infection significantly. There is no prophylaxis available against Aspergillus spp. and Cryptococcus spp. Treatment of fungal infections consists of surgical and medical treatment for most organ-related infections. Recommendations for the management of fungal infections exist mostly for neutropenic patients, only few reports address the fungal infection of the surgical intensive care patient. Amphotericin B has been recommended as first line treatment for most severe fungal infections with fluconazole as follow-up treatment. In case of the development of toxic side effects of amphotericin B, mostly fluconazole or lipid formulations of amphotericin were favored. However, a shift in Candida strains towards non-albicans spp. and more resistant species was observed during recent years. This has lead to treatment failures in severe Candida and Aspergillus infections. The prognosis for invasive Aspergillus infections remains poor despite amphotericin B treatment. Newer azoles, e.g. voriconazole, demonstrated stable activity against most of these strains and may offer an option in the treatment of refractory fungal infections.     

Primary cytomegalovirus and opportunistic infections. Incidence in renal transplant recipients.

Thirty-five renal allograft recipients were studied concerning the relationship between cytomegalovirus (CMV), herpes simplex virus (HSV), and opportunistic bacterial and fungal infections. The incidence of opportunistic infections was determined for patients whose tests prior to transplantation were seronegative in complement fixation and indirect hemagglutination assays of CMV antibody and for those patients whose tests were seropositive. Among the six seronegative patients with seronegative tests, four (66%) experienced active CMV infection within two months, and four died of Candida or Aspergillus infection within six months after transplantation. Among the 22 patients with seropositive tests, only one (4%) had a fungal infection and it was nonfatal (P less than .05). The increased morbidity and mortality due to fungal and bacterial infections in transplant recipients with seronegative CMV tests appears, therefore, to be related to primary CMV infection rather than to generalized immunodeficiency.     

热带地区某综合医院院内真菌感染情况调查

目的 探讨住院患者医院内真菌感染的分布特点及危险因素,为制定有效的防控措施提供依据。方法 采用回顾性分析方法,对解放军总医院海南医院2013年1月—2017年12月住院患者中医院内真菌感染病例406例进行回顾性分析。以同期住院患者医院内非真菌感染病例1 514例为对照组,对可能的影响因素用χ²检验先进行单因素分析,将单因素分析有统计学意义（P<0.05）的变量引入非条件Logistic回归分析中行多因素分析。结果 >60岁年龄段发生真菌感染的比例最高,占66.50%。>70~80岁患者中死亡例数所占的比例最高,占26.67%。真菌感染患者中以假丝酵母菌属感染为主,占88.04%。真菌感染部位以肺部感染居首位,占47.6%。侵袭性念珠菌感染白色念珠菌感染所占的比例最高,占47.07%。危险因素分析：单因素χ²检验显示,9个变量是影响真菌感染的危险因素（P<0.05）,将9个变量纳入非条件 Logistic回归分析中,按照OR值的大小,分别为抗菌药物使用种类、年龄、是否曾住ICU、侵入性操作、住院时间。结论 加强老年患者保护性隔离措施,加强病房环境消毒隔离,对于高龄、接受侵入操作治疗患者应加强病原学监测,严格掌握抗菌药物的使用指征,有助于控制医院内真菌感染。     

Risk factors for invasive fungal infections in liver transplant patients

Identification of the risk factors associated with invasive fungal infections in liver transplant patients can improve the survival rate of liver transplant recipients by identifying those patients at high risks and allowing for more effective prophylactic therapy and pre-emptive/ empirical treatment.     

Epidemiology of opportunistic invasive mycoses

Invasive aspergillosis and disseminated candidiasis are the two major manifestations of opportunistic invasive mycoses. Their incidence has risen considerably during the past decades, due to more intensive anticancer chemotherapy, organ transplantations, intensive care, and aggressive surgical interventions. Especially bone marrow transplant recipients are at risk for developing invasive aspergillosis. Whether the infection is acquired through contaminated water or through airborne spores is a matter of much debate. Candidemia and disseminated candidiasis commonly originate from the gastrointestinal tract. Abdominal surgery and mucosal damage due to anticancer chemotherapy are the majors factor through which gut colonization may lead to invasive disease. A shift in the epidemiology of disseminated candidiasis has been noted, with an increasing incidence of Candida glabrata, C. tropicalis and C. krusei strains.     

肺移植术后曲霉菌感染的分析

目的研究肺移植术后患者发生曲霉菌感染的发病率和发病过程,探讨早期预防、检测和治疗曲霉菌感染的经验。方法回顾性分析2003年1月—2007年5月进行的15例单肺或双肺移植患者的临床资料,总结肺移植术后患者发生曲霉菌感染的发病率和发病过程以及诊疗经验。结果15例肺移植患者中,有5例(33%)患者在肺移植术后发生曲霉菌感染,其中气道内曲霉菌寄生、孤立性曲霉菌性支气管炎和侵袭性曲霉菌性肺炎这三种类型的发生率分别为13%、6%和13%。多数患者在术后1年内确诊。结论肺移植患者术后早期较容易发生曲霉菌感染。肺移植患者术后进行早期诊断和早期治疗对防治肺曲霉菌感染有着积极的作用,但是术前和术后早期使用抗真菌药物进行预防的效果还不确切。     

肝移植术后受体ICU真菌感染的临床分析

目的：探讨导致原位肝移植术后重症监护病房（ICU）真菌感染的病原学特征和临床高危因素．方法：回顾我院2000-11／2006-01施行的102例次原位肝移植临床资料，对可能导致术后真菌感染的围手术期相关因素进行分析，筛选临床高危因素．结果：肝移植术后平均ICU留住时间为11．0d（7～23d），其间真菌感染的发病率为16％（16／102），平均发病时间为术后11．8d（6～18d）．主要致病菌为白色念珠菌，约占75％，发生部位以肺部（73％）和血液（19％）多见．多因素Logistic回归分析显示术前UNOS评分、术后中心静脉导管留置时间以及术后细菌、病毒等其他感染是诱发肝移植术后受体真菌感染的高危因素．结论：真菌感染是发生于肝移植术后ICU内重要并发症．白色念珠菌是最常见的致病菌．针对以上高危因素及早采取合理、有效的防治措施是减少ICU真菌感染的关键．     

27例肝衰竭患者合并侵袭性真菌感染的临床研究

目的:探讨肝衰竭合并侵袭性真菌感染的临床特点,分析感染发生的危险因素。方法:选择我院收治的肝衰竭合并侵袭性真菌感染患者27例作为研究组,以同时期54例无真菌感染的肝衰竭患者作为对照组。分析研究组患者的临床特点,并对感染相关的可疑因素行Logic回归分析。结果:研究组患者感染部位依次为:肺部(37.0%)、消化道(22.2%)、泌尿道(14.8%)、血液(14.8%)、腹腔(11.1%);感染菌种:白假丝酵母菌(51.9%)和曲霉菌(18.5%);感染相关多因素分析发现:侵入性操作(OR=18.7;P<0.001)、联用抗生素≥2种(OR=8.49;P<0.001)、糖皮质激素(OR=6.31;P<0.001)、白细胞减少(OR=2.01;P=0.015)、MELD评分(OR=1.21;P<0.001)是真菌感染的独立危险因素。结论:肝衰竭患者多合并肺部的假丝酵母菌感染,其中侵入性操作、联用抗生素≥2种、肾上腺皮质激素、白细胞下降、基础疾病重是真菌感染的危险因素。     

Pharmacology and metabolism of voriconazole and posaconazole in the treatment of invasive aspergillosis-review of the literature

Invasive fungal infections, predominantly aspergillosis and candidiasis, are among the most important causes of morbidity and mortality in immunocompromised patients. Primarily, patients with acute leukemia undergoing myelosuppressive chemotherapy and allogeneic stem cell transplant recipients are affected. Up to 60% of patients with invasive aspergillosis, the most common invasive mycosis among patients with hematologic malignancies, may still die of their infection, once it has become clinically overt. The spectrum of antifungal agents for clinical use now has expanded over the past ten years and includes the novel class of the echinocandins and two newer generation triazoles with an extended spectrum of activity against a wide range of fungal pathogens. This review will address pharmacological characteristics of the two broad-spectrum antifungal azoles, voriconazole and Posaconazole, which are important for their proper use in clinical practice.     

危重症儿童侵袭性真菌感染分析

目的探讨危重儿童侵入性真菌感染的发生特点，病原学种类及治疗。方法回顾性分析1996年1月-2005年2月间的27例危重儿童真菌感染的易感因素、病原学特点及治疗效果。结果惠儿病情危重，易感因素有：使用广谱抗生素（24／27），机械通气（16／27），深静脉置管（14／27），肠外营养（16／27），应用化疗药物（5／27）。应用皮质醇激素治疗（6／27）。致病菌为白色念珠菌21例，热带念珠菌3例，酵母菌3例，曲霉菌1例。25例经抗真菌治疗者4例死亡，2例未治疗者死亡。结论危重儿童侵入性真菌感染与多种易感因素有关。合理选用抗真菌药物是治愈的关键。