2014—2017年解放军总医院海南分院真菌分布及耐药性分析

目的 了解2014—2017年解放军总医院海南分院真菌的分布和耐药特点,为促进抗真菌药的合理应用、有效减缓真菌耐药提供参考。方法 提取解放军总医院海南分院2014年1月—2017年12月临床真菌分离和药敏相关数据,分析真菌的分布特征及其对常用抗真菌药的耐药率和变化趋势。结果 共纳入1 048份阳性真菌样本,呼吸道标本占41.89%,60岁以上患者（61.45%）和重症医学科（25.48%）分布比例最高;共分离出1 329株真菌,白色念珠菌、念珠菌属、热带念珠菌分别占24.53%、15.80%、13.69%。各种念珠菌对两性霉素B和5-氟胞嘧啶的敏感率基本保持在90%以上;热带念珠菌对伊曲康唑耐药率最高,达10%～20%,对氟康唑和伏立康唑的耐药率亦高于两性霉素B和5-氟胞嘧啶;白色念珠菌对伊曲康唑和伏立康唑的耐药率呈逐年快速上升趋势。结论 白色念珠菌和热带念珠菌感染应慎用唑类抗真菌药;两性霉素B和5-氟胞嘧啶是念珠菌感染的有效选择。     

1例重型颅脑损伤术后感染患者的药学监护

摘 要 目的： 探讨临床药师参与临床抗感染治疗用药过程的模式。方法: 对1例重型颅脑损伤双侧去骨瓣减压术后肺部和颅内感染患者的抗细菌和抗真菌治疗提出合理化用药建议,并进行用药监护。结果: 临床药师先后建议采用氟康唑治疗方案和两性霉素B治疗方案分别治疗32 d和28 d,治疗期间分别针对分流管相关表皮葡萄球菌和施氏假单胞菌感染提出治疗建议,对伏立康唑和两性霉素B不良反应预警和监护,针对药敏结果变化及时调整抗感染治疗,治疗效果明显。结论:临床药师参与药物治疗过程可优化治疗方案,有利于医药团队协作。     

急腹症患者术后不同时间拔除导尿管效果比较分析

目的 探讨急腹症患者手术后不同时间拔除留置尿管后的护理疗效。方法 安徽省立医院急诊外科2012年9月至2014年12月收治腹部手术后留置导尿管的患者218例, 218例患者随机分为观察组和对照组。观察组112例, 手术后24 h内在膀胱充盈下拔除尿管;对照组106例, 按常规术后24 h后不定时拔除尿管。观察两组患者拔除尿管后首次下床时间、肛门排气时间、拔管后发生尿潴留、尿路感染、尿道出血等并发症发生情况。结果 观察组患者拔尿管后首次下床时间、肛门排气时间早于对照组(P<0.05), 尿路感染、尿道出血、尿潴留发生率明显低于对照组(P<0.05)。结论 腹部术后24 h内在膀胱充盈状态下拔除尿管, 能促使患者早期活动, 尽早恢复肠蠕动, 减少拔管后再次尿潴留、尿路感染、尿道出血等并发症的发生。     

2018-2022年深圳市妇幼保健院分离真菌的分布及耐药情况分析

目的 调查分析南方医科大学附属深圳妇幼保健院分离真菌的分布特点和药物敏感性情况,为妇幼真菌感染疾病的临床诊治、耐药性监测和流行病学研究提供参考。方法 回顾分析南方医科大学附属深圳妇幼保健院2018年1月-2022年12月标本采集、真菌鉴定和抗真菌药敏试验的结果数据。结果 共分离真菌3 350株,前2位分别为白色念珠菌1 542株、光滑念珠菌223株。阳性标本以阴道分泌物/宫颈分泌物为主。妇科和产科分离到的真菌最多。白色念珠菌对伊曲康唑、伏立康唑的5年耐药率分别为9.58%、4.12%,对两性霉素B和5-氟胞嘧啶的5年敏感率分别为99.79%、98.01%,对氟康唑的历年敏感率有逐渐升高的态势。光滑念珠菌、近平滑念珠菌和热带念珠菌对两性霉素B及5-氟胞嘧啶的敏感率均为100.00%。克柔念珠菌对两性霉素B和伏立康唑100.00%敏感。结论 南方医科大学附属深圳妇幼保健院分离真菌以念珠菌属为主,其中白色念珠菌最多。阴道分泌物/宫颈分泌物是主要真菌阳性分离标本。白色念珠菌对两性霉素B的耐药率最低、敏感率最高,对伊曲康唑的耐药率最高、敏感率最低。光滑念珠菌、近平滑念珠菌、热带念珠菌和克柔念珠菌对两性霉素B和5-氟胞嘧啶均无耐药性。光滑念珠菌对伊曲康唑耐药率最高、敏感率最低。     

小剂量氟康唑治疗慢性阻塞性肺疾病继发肺部真菌感染的回顾性分析

目的 探究对慢性阻塞性肺疾病（COPD）继发肺部真菌感染患者应用小剂量氟康唑的临床疗效分析。方法 选取2016年2月-2018年2月信阳市中心医院收治的COPD继发肺部感染患者共58例作为研究对象，随机分为观察组（29例）和对照组（29例）。对照组患者应用广谱抗菌药物及解痉平喘、雾化吸入糖皮质激素等治疗；观察组在对照组基础上应用小剂量氟康唑胶囊，100 mg/次，1次/d。两组治疗时间为2周。观察比较两组患者治疗效果，真菌清除情况及不良反应发生率。结果 治疗后，观察组总有效率为93.10%，显著高于对照组的68.97%，差异具有统计学意义（P<0.05）。治疗后，观察组和对照组患者真菌清除率分别为96.55%和62.07%，观察组真菌清除率明显高于对照组，且差异具有统计学意义（P<0.05）。观察组中出现1例胃肠道反应，而对照组中出现1例肝功能损害，1例皮疹，两组患者的不良反应发生情况无显著差异。结论 小剂量氟康唑对COPD继发肺部真菌感染疗效显著，不良反应较少，建议临床推广应用。     

2015—2019年连云港市第二人民医院感染真菌患者菌株分布及耐药性分析

目的 分析2015—2019年连云港市第二人民医院真菌培养阳性标本的病原菌分布情况和耐药状况。方法 收集2015年1月—2019年12月在连云港市第二人民医院所有的真菌培养和药敏试验阳性的标本共663例,应用DL-96Ⅱ细菌测定系统的体外诊断试剂DL-96FOUNGUS对样本进行真菌鉴定,以5种常见抗真菌药物为例,采用MIC法开展对样本中已鉴定真菌的药物敏感性试验,并应用WHONET 5.6软件进行对于该试验结果的统计学分析。结果 2015—2019年连云港市第二人民医院共分离出真菌663株。按照菌种类型分类,可得到如下比例：白色假丝酵母菌占49.9%（331/663）、热带假丝酵母菌占15.2%（101/663）、都柏林假丝酵母菌占8.3%（55/663）、光滑假丝酵母菌14.9%（99/663）、其他假丝酵母菌占11.6%（77/663）。白色假丝酵母菌对伏立康唑、氟康唑、伊曲康唑3种抗菌药物仍具有耐药性;热带假丝酵母菌对氟胞嘧啶、两性霉素高度敏感,对伏立康唑、氟康唑、伊曲康唑表现为耐药;光滑假丝酵母菌对氟胞嘧啶和两性霉素B的敏感性最高。结论 白色假丝酵母菌、热带假丝酵母菌、光滑假丝酵母菌是真菌感染的主要常见致病菌,以热带假丝酵母菌为主的多种假丝酵母菌对于氟康唑、伊曲康唑等临床常用抗菌药物耐药性日渐增长。     

比较万古霉素持续输注与间断输注引起肾毒性的荟萃分析

目的 比较万古霉素两种给药方式（持续输注与间断输注）引起的肾毒性。方法 计算机检索Embase、PubMed、The Cochrane Register of Controlled Trials和CBM、CNKI、万方数据库。采用Cochrane协作网提供的Revman5.2软件进行Meta分析。结果 共纳入2篇随机对照试验（RCT）和8篇观察性研究,共纳入患者1 764例,其中持续输注1 037例,间断输注727例。持续输注与间断输注引起的肾毒性发生率无显著性差异（P>0.05）。结论 万古霉素持续输注较间断输注不能有效降低肾毒性的发生率。     

隐球菌性脑膜炎24例临床特点分析

目的 分析隐球菌性脑膜炎患者的临床特点,为临床诊治提供参考依据。方法 回顾性分析安徽医科大学第一附属医院2008年1月至2018年12月收治的24例隐球菌性脑膜炎患者的临床资料。分析患者的基础疾病、临床症状、脑脊液（CSF）检查、头颅影像学资料及治疗与转归。结果 24例患者均出现头痛（100%）,19例（79.17%）出现发热;11例（45.83%）颅内压增高（≥300 mmH₂O）;16例（66.67%） CSF首次检查示隐球菌墨汁染色阳性,7例（29.17%）真菌培养阳性,19例（79.17%）送检隐球菌荚膜抗原检测均为阳性（100%）;21例（87.50%）患者接受两性霉素B （或其脂质体）联合氟胞嘧啶治疗,另外3例（12.50%）重症患者予以两性霉素B （或其脂质体）、氟胞嘧啶、氟康唑三联治疗。最终治愈11例（45.83%）,好转2例（8.33%）,死亡11（45.83%）例。所有死亡患者均考虑为高颅压致死。结论 高颅压是隐球菌性脑膜炎患者死亡的首要原因;CSF隐球菌荚膜抗原检测是诊断较敏感指标,效果优于CSF墨汁染色及真菌培养。     

2015-2019年甘肃医学院附属医院慢性阻塞性肺疾病急性加重期患者继发肺部真菌感染率趋势及耐药性分析

目的 了解2015-2019年甘肃医学院附属医院慢性阻塞性肺疾病急性加重期（AECOPD）患者继发肺部真菌感染率变化趋势、分布及耐药性特点。方法 提取2015-2019年甘肃医学院附属医院AECOPD患者临床真菌分离及药敏相关数据。结果 2015-2019年AECOPD患者继发肺部真菌感染率为13.37%,且呈上升趋势,真菌感染率从2015年的10.88%上升至2019年的15.71%;共分离出6种真菌,以白色念珠菌（52.41%）、光滑念珠菌（25.13%）、热带念珠菌（12.30%）、曲霉菌（8.02%）为主;主要以真菌与细菌的混合感染存在（64.61%）,其中以真菌与革兰阴性菌混合感染为主（70.43%）。氟康唑对各种念珠菌耐药率接近30%,对曲霉菌耐药率大于90%,伏立康唑和两性霉素B对各种念珠菌和曲霉菌的耐药率较小。结论 真菌感染在AECOPD患者中呈明显增长趋势,白色念珠菌、光滑念珠菌、热带念珠菌和曲霉菌常见,且主要为与细菌混合感染存在,氟康唑对真菌耐药率较高,伏立康唑成为治疗真菌感染的首选。     

金水宝联合血管紧张素受体阻滞剂治疗糖尿病肾病的Meta分析

目的 用循证医学的方法评价金水宝联合血管紧张素受体阻滞剂(ARB)治疗糖尿病肾病(DN)的疗效.方法 检索国内外科技期刊数据库,纳入金水宝联合ARB治疗DN的随机对照试验,并进行Meta分析.结果 共纳入15项研究1 095例患者,联合用药组可显著降低糖尿病肾病患者的24 h尿蛋白定量[P<0.000 01;MD=-0.10(-0.14,-0.06)g/24 h],血肌酐[P=0.000 8;MD=-16.25(-25.76,-6.73)μmol/L],尿素氮[P=0.000 2;MD=-1.20(-1.83,-0.57)mmol/L],尿白蛋白排泄率[P=0.000 5;MD=-19.33(-30.30,-8.37)μg/L],N-乙酰-β-D-葡萄糖苷酶(NAG酶)[P<0.000 01;MD=-4.92(-6.03,-3.80)U/L],尿白蛋白/肌酐[P<0.000 01;MD=-21.56(-26.84,-16.29)mg/g].表明联合用药可显著降低患者总胆固醇[P=0.000 5;MD=-0.58(-0.91,-0.25)mmol/L],三酰甘油[P<0.000 01;MD=-0.40(-0.51,-0.28)mmol/L].结论 金水宝联合ARB较单用ARB可进一步改善DN患者的肾功能,并有降血脂的作用.     

Management of candiduria

Candiduria, due to Candida albicans, Candida glabrata and other organisms, has increased in frequency due the use of broad-spectrum antibacterials, immunosuppressive agents and other factors. The optimal management of candiduria is unknown due to an undlear definition of fungal urinary tract infection and the lack of well-designed clinical trials. Removal of urinary catheters, ruling out obstruction/stones and documenting presence of post-void residuals are useful in the management of candiduria. Amphotericin B bladder irrigants and oral fluconazole may be used in certain patients who are high risk or with persistence of candiduria after removal of the urinary catheter.     

Comparison of two concentrations of amphotericin B bladder irrigation in the treatment of funguria in patients with indwelling urinary catheters.

The efficacy of amphotericin B bladder irrigation at two concentrations was studied. Patients with funguria (> or =15,000 colony-forming units of yeast per milliliter of urine), an indwelling urinary catheter, and a physician order for amphotericin B continuous bladder irrigation were randomly assigned to receive 10 or 50 mg of amphotericin B per liter of sterile water as a continuous irrigation for 72 hours at the rate of 42 mL/hr. Before the bladder irrigation began, the indwelling catheter was changed to a three-way catheter. Repeat urine cultures were performed 24 hours after the irrigation was discontinued. A total of 28 patients were enrolled from November 1993 to May 1995. The rate of eradication of the infection was 100% in the 50-mg/L group and 67% in the 10-mg/ L group. Subject enrollment was stopped prematurely because all the treatment failures occurred in the 10-mg/L group. Dose was the only variable significantly associated with outcome. Bladder irrigation with amphotericin B was more effective when the drug concentration was 50 mg/L rather than 10 mg/L.     

Amphotericin B lipid complex: in visceral leishmaniasis

Amphotericin B lipid complex is a lipid formulation of amphotericin B, an antifungal drug with activity against Leishmania spp. Amphotericin B lipid complex appears to enhance uptake of amphotericin B by infected macrophages in patients with visceral leishmaniasis (VL). In randomised, open-label, dose-ranging studies, short-course treatment with once-daily amphotericin B lipid complex (5-15 mg/kg total cumulative dose over 5 days), administered by intravenous infusion, produced high rates of apparent (day 19) [93-100%] and definitive (6 months) [79-100%] cures in Indian patients with antimonial-resistant VL. Amphotericin B lipid complex appeared to be as effective as liposomal amphotericin B or the conventional deoxycholate formulation in a randomised, open-label study conducted in India in a mixed population of patients with previously untreated or antimonial-resistant VL. In patients with HIV infection and VL, amphotericin B lipid complex 3 mg/kg/day for 5 or 10 days appeared to be as effective as meglumine antimonate 20 mg/kg/day for 28 days in a small randomised pilot study in southern Europe. Amphotericin B lipid complex was generally well tolerated in patients with VL. Infusion-related reactions were the most common adverse events associated with amphotericin B lipid complex.     

The Fluconazole Era: Management of Hematogenously Disseminated Candidiasis in the Nonneutropenic Patient

Hematogenously disseminated candidiasis arising from nosocomial fungal infection is a life-threatening complication in critically ill, nonneutropenic patients. The overall nosocomial fungal infection rate in United States hospitals doubled from 1980–1990. Until recently, amphotericin B was the only agent available for the treatment of life-threatening candidal infections, but its use is plagued by toxicities including nephrotoxicity and infusion-related reactions such as rigors and hypotension. The availability of fluconazole, which is regarded as much less toxic than amphotericin B, prompted a surge in research to determine if it is as efficacious in the management of candidemia and hematogenously disseminated candidiasis. Complicating the interpretation of studies is the broad range of infection severity, from candidemia that may be transient and self-limiting to life-threatening hematogenously disseminated candidiasis. Clinical trials comparing fluconazole and amphotericin B demonstrate the efficacy of fluconazole for catheter-associated candidemia in critically ill patients when the likely pathogen is Candida albicans. Amphotericin B should remain the first-line agent for the management of candidemia and hematogenously disseminated candidiasis in all other patients.     

Best practice guidelines for the management of adverse events associated with amphotericin B lipid complex

Importance of the field: Amphotericin B lipid complex is a widely used lipid-based formulation of amphotericin B, which has a broad spectrum of activity against a variety of fungal pathogens. It has also been shown to be significantly less nephrotoxic than conventional amphotericin B. However, infusional drug reactions, similar to those seen when using conventional amphotericin B, have been reported in a significant number of patients, so it is important that these are prevented or managed effectively, particularly in light of the changing epidemiology of systemic fungal infections.

Areas covered in this review: This article reviews effective strategies that can be used to reduce the risk of drug delivery reactions associated with amphotericin B lipid complex. Preserving renal function and managing spikes in serum creatinine levels are also discussed.

What the reader will gain: The aim of this paper is to provide healthcare professionals with clear guidance on the management of adverse events associated with amphotericin B lipid complex. Recommendations are based upon the published evidence and clinical experience from a number of different centres.

Take home message: Amphotericin B lipid complex represents a valuable therapeutic option in the treatment of fungal infections but improved strategies for the management of infusion-related adverse events are required.     

Fluconazole versus amphotericin B for the prevention of fungal infection in neutropenic patients with hematologic malignancy.

Effective prophylaxis against fungal infection is important in neutropenic patients with hematologic malignancies, but the best method remains unclear. We investigated the effectiveness of fungal prophylaxis with amphotericin B or fluconazole. We reviewed the data on fungal isolates, plasma (1-->3)-beta-D glucan (beta-D glucan) levels, febrile periods (the number of days with an axillary temperature > 38 degrees C), and the duration of an axillary temperature > 38 degrees C when the neutrophil count was < 500/microliter. Of the 124 patients studied, 57 had acute myelogenous leukemia, 19 had acute lymphoblastic leukemia, 18 had non-Hodgkin's lymphoma, six had chronic myeloid leukemia, three had adult T-cell leukemia, and five had chronic lymphocytic leukemia. There were no significant differences in clinical characteristics between the 70 patients treated with amphotericin B and the 54 patients given fluconazole. There was a significant decrease of fungal isolates (chi 2-test, p < 0.001), the plasma beta-D glucan level (Wilcoxon test, p = 0.0001), and the febrile period (t-test, p < 0.05) in the patients given fluconazole compared with those given amphotericin B. In neutropenic patients with hematologic malignancies, prophylaxis with fluconazole significantly decreased fungal isolation and other indicators of fungal infection when compared with amphotericin B. Fluconazole may therefore be more effective for fungal prophylaxis in these patients.     

伊曲康唑预防血液病患者侵袭性真菌感染疗效的Meta分析

目的:系统评价伊曲康唑预防血液病患者化疗或造血干细胞移植(HSCT)后侵袭性真菌感染的有效性。方法:计算机检索Cochrane图书馆、Medline、EMbase、PubMed、中国生物医学文献光盘数据库(CBM)、中国科技期刊全文数据库(CNKI)、维普电子期刊全文数据库、万方数据库等,并手工检索相关会议的论文集,采用RevMan5.1软件进行Meta分析。结果:纳入14项研究,共4020例患者。Meta分析结果显示,伊曲康唑组真菌感染发生率和曲霉检出率均低于氟康唑组[OR=0.72,95%C(I0.54,0.96),P=0.02;OR=0.60,95%CI(0.39,0.93),P=0.02],高于泊沙康唑组[OR=4.90,95%CI(1.58,15.15),P=0.006;OR=14.25,95%CI(2.69,75.34),P=0.002],而与两性霉素B、卡泊芬净、伏立康唑组比较差异均无统计学意义。伊曲康唑组的总死亡率、念珠菌检出率与各对照组比较差异亦无统计学意义。结论:伊曲康唑预防血液病患者化疗或HSCT后侵袭性真菌感染优于氟康唑,较泊沙康唑差,与两性霉素B、伏立康唑、卡泊芬净等相当。     

symbol: see text]Caspofungin and [symbol: see text]voriconazole for fungal infections

Systemic fungal infections are difficult to treat and often fatal. Established treatment options include conventional amphotericin B or one of its lipid-based or liposomal formulations, or a triazole antifungal such as fluconazole or itraconazole. [symbol: see text]Caspofungin (Cancidas--Merck Sharp & Dohme) and [symbol: see text]voriconazole (Vfend--Pfizer) are two new antifungals for severe infections caused by Candida spp. (invasive candidiasis) and Aspergillus spp. (invasive aspergillosis). Caspofungin is the first licensed echinocandin antifungal, while voriconazole is a triazole. Promotional claims for caspofungin include that it "provides an effective, yet less toxic, alternative to amphotericin B" while voriconazole is claimed to offer "significantly improved survival in invasive aspergillosis compared with amphotericin B". Here we consider the place of caspofungin and voriconazole in managing patients with severe fungal infections.     

Fungal infections of the CNS: treatment strategies for the immunocompromised patient

Infections with fungi cause significant morbidity in the immunocompromised host and invasion of the CNS may lead to devastating consequences. Vulnerable individuals include those with haematological malignancies, transplant recipients, and those infected with HIV. Potential pathogens include yeasts, Aspergillus spp., other moulds of an increasing variety, and a range of dimorphic fungi, often associated with particular geographical locations. Antifungal treatments include polyenes such as amphotericin B and its lipid formulations, azoles such as fluconazole and itraconazole, and the more recent voriconazole and posaconazole. The new antifungal class of echinocandins, such as caspofungin, micafungin and anidulafungin, typically lack CNS penetration. Amphotericin B and flucytosine are used to initiate treatment for CNS yeast infections caused by Candida and Cryptococcus neoformans. Voriconazole is preferred for aspergillus, although amphotericin B, particularly in lipid formulation, is also useful. Reliable treatment data are lacking for CNS infections with most of the non-aspergillus moulds; posaconazole holds promise for the zygomycetes and perhaps some of the rarer pigmented fungi, but amphotericin B preparations are still recommended. Oral fluconazole is effective for the CNS manifestations of coccidioides, while histoplasmosis and blastomycoses typically require amphotericin B therapy. Effective treatment requires a definitive diagnosis, which is often challenging in the population at risk of CNS fungal infections.     

两性霉素B合并氟康唑对体外培养新生隐球菌酚氧化酶的影响

目的：研究两性霉素B合并氟康唑对体外培养新生隐球菌酚氧化酶活性的影响。方法：Novozyme234酶消化法获取原生质体；冷冻玻璃珠粉碎原生质体；Polecheck法测定酚氧化酶活性。结果：两性霉素B合并氟康唑组的新生隐球菌酚氧化酶活性较空白对照组明显降低（P＜0．001），但在大于和接近最低抑菌浓度上限的组间无明显差异。结论：两性霉素B合并氟康唑可降低新生隐球菌酚氧化酶活性，在大于或接近最低抑菌浓度上限时与药物浓度无关。