Treatment of invasive infections due to rare or emerging yeasts and moulds

Emerging fungal infections represent a serious problem in an immunocompromised host. Rapid developments in in vitro antifungal susceptibility testing and the availability of several new antifungal agents have provided excellent opportunities to treat infections that are caused by various Candida spp. and to some extend by Aspergillus spp. However, recently the epidemiology of fungal infections has significantly changed and several new pathogens have emerged. This article attempts to summarise the available data on the management of emerging infections with fungal infections that have recently gained importance. Updated recommendations on antifungal treatment are also discussed.     

Therapeutic strategies for invasive fungal infections in neonatal and pediatric patients

Invasive Candida and Aspergillus infections are the most commonly encountered fungal infections. They appear to be life threatening in the setting of profound immunosuppression, whereas cases that are resistant to antifungal therapy are occasionally encountered. Novel antifungal triazole and echinocandin agents appear to exhibit good activity as first-line or salvage therapy, whereas the use of amphotericin B formulations is particularly valuable in neonates. Significant differences in toxicity have been demonstrated among various antifungal agents with in vitro activity from available comparative data on fungal infections in children: however, no clear difference in treatment efficacy has been demonstrated. However, very little data are available about neonates. Host factors and responsible fungal species most frequently guide the choice of therapy.     

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.     

Clinically informative measures of the effect of drugs or other interventions

AIMS

Measures to compare two drugs are often affected by the background risk in the reference group; a ceiling effect results when the background risk is small. We review measures of the effect of drugs, including a special formulation of the relative risk difference, the attained effect or clinical result ratio, that addresses background risk and ceiling effect.

METHODS

Existing measures are the risk and odds ratios, the absolute and relative risk differences, and the number needed to treat. The attained effect is defined as the observed gain in success (the difference of proportion of success between the two interventions), divided by the maximum attainable gain, the maximum proportion of success one can expect. We illustrate the relationship between these measures with published results of two meta-analyses.

RESULTS

In studies of the effectiveness of cell salvage, the baseline risk ranged between 8 and 95%. This variability affected the risk difference and number needed to treat, while the attained effect, with a ceiling residual risk of 2%, showed that the gain in success was half the maximum attainable gain. In studies of the effectiveness of therapy in patients infected by the human immunodeficiency virus, where the baseline risk was less variable, and there was no ceiling effect, the maximum attained effect indicated that the gain could be much smaller.

CONCLUSION

The attained effect, interpreted as the proportion of effectiveness that remains to gain for future interventions, can usefully complete the number needed to treat as a clinically informative effect measure.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• Several comparative measures (ratios, differences, or the number needed to treat) are used to express the effect of a drug or another intervention.
• These measures can vary in the way they are affected by the background risk measured from the reference group.

WHAT THIS STUDY ADDS?

• This paper reviews the formulation, interpretation and limitations of measures of effect.
• We describe a little-known parameter, the attained effect or clinical result ratio, a positive reformulation of the relative risk difference, and suggest how available parameters can be best used to summarize results of studies of the effect of drugs.

     

Implications of Eligibility Criteria on the Generalizability of Alcohol and Drug Treatment Outcome Research: A Study of Real-World Treatment Seekers in Sweden and in Australia

Background: Clinical studies of alcohol and drug treatment outcomes frequently apply participant eligibility criteria (EC), which may exclude real-world treatment seekers, impairing the representativeness of studied samples. Some research exists on the impact of EC on alcohol treatment seekers. Little is known about drug treatment and country differences. Objectives: We tested and compared the degree to which commonly used EC exclude real-world treatment seekers with problem alcohol and drug use in Sweden and Australia, and compared the impact of EC on outcomes. Methods: Two large naturalistic and comparative service user samples were used. Respondents were recruited in Stockholm County (n = 1,865; data collection 2000–2002), and Victoria and Western Australia (n = 796; in 2012–2013). Follow-up interviews were conducted after 1 year. Cross-tabulations, Chi-square (χ²) tests and logistic regressions were used. Results: Percentages of the samples excluded by individual EC ranged from 5% (lack of education/literacy) to 70% (social instability) among Swedish alcohol cases and from 2% (low alcohol problem severity) to 69% (psychiatric medication) among Australian counterparts; and from 2% (age 60+ years) to 82% (social instability) among Swedish drug cases and from 1% (age 60+ years) to 67% (psychiatric medication) among Australian counterparts. Country differences and differences across substances appeared independent of country effect. Co-morbid psychiatric medication, noncompliance, poly drug use, and low education EC caused positive 1-year outcome bias; whereas female sex and old age introduced negative outcome bias. Conclusions/Importance: Commonly used EC exclude large proportions of treatment seekers. This may impair generalizability of clinical research, and the effects of many EC differ by country and drug type.     

腹腔镜胆囊切除致胆道损伤的治疗研究

目的 总结腹腔镜胆囊切除致胆道损伤的治疗经验。方法 对1992年12月-2002年12月30例患者进行回顾分析。结果 所有患者最终均需手术治疗。手术方式根据损伤部位、类型、损伤后发现的时间决定。随访率(28／30)为93．33％，随访时间1—10年。优良率达86．67％。结论 作者认为术中发现即行对端吻合或修复 T管引流，术后数天发现或多次重建失败者，最宜行规范的胆肠吻合术，疗效满意。     

The reformulation of Amphotericin B for oral administration to treat systemic fungal infections and visceral leishmaniasis

Amphotericin B (AmB) is a parenterally administered broad-spectrum antifungal and leishmanicidal drug that has been on the market for over sixty years. Unfortunately, significant infusion-related side effects and renal toxicity often accompany treatment, limiting its clinical applications. Lipid-based formulations have somewhat ameliorated the associated toxicity, but the increased cost of formulations restricts widespread use. AmB is amphipathic and exhibits low solubility and permeability, resulting in negligible absorption when administered orally. Advances in drug delivery systems have overcome some of the solubility issues that prevent oral bioavailability and new formulations are currently in development. The existence of an effective, safe and inexpensive oral formulation of amphotericin B would have significant applications for the treatment of disseminated fungal infections and would dramatically expand access to treatment of visceral leishmaniasis by introducing a readily available highly tolerated oral formulation of a drug with known efficacy.     

Patterns of Abstinence or Continued Drug Use Among Methadone Maintenance Patients and Their Relation to Treatment Retention

The efficacy and effectiveness of methadone maintenance treatment (MMT) in the medical management of opioid addiction has been well-established, but treatment outcomes are compromised by the continued use of licit and illicit drugs during MMT. The present study examined the relationship between in-treatment illicit drug use and retention and dropout of 604 MMT patients in Washington, D.C. Sixty-eight percent of patients did not test positive for an unprescribed drug during the study period. Of patients who tested positive for an illicit drug during the baseline period, 55% tested positive for cocaine, 44% for opiates, 23% for THC, 20% for benzodiazepines, 7% for PCP, and 4% for amphetamines. Those testing positive were three times more likely to leave treatment than those who did not test positive. Testing positive for one drug doubled the rate of attrition; testing positive for multiple drugs quadrupled the risk of attrition. Non-prescribed opioid or benzodiazepine use was a predictor of MMT dropout, but prescribed opioid or benzodiazepine use was not. Continued illicit drug use poses significant risk for subsequent premature termination of MMT. Assertive clinical management of continued illicit drug use could provide mechanisms to enhance MMT retention and long-term recovery outcomes.     

侵袭性真菌病患者伏立康唑不良反应分析及临床处理经验

目的 通过分析台州市中心医院发生伏立康唑不良反应的病历信息以及临床处理成效,为安全有效使用伏立康唑提供参考。方法 回顾性分析台州市中心医院2015年12月-2020年12月280例侵袭性真菌病患者伏立康唑血药浓度监测结果,采用Naranjo's量化评分表判断伏立康唑相关药物不良反应,NCI-CTCAE标准评价不良反应严重程度,同时总结归纳发生不良反应后临床主要处理措施及转归。结果 共52例患者出现不良反应,未见危及生命不良反应,中位谷浓度3.80（1.80,5.93）μg·mL^-1。主要不良反应为肝毒性、中枢神经系统毒性和视觉障碍,谷浓度分别为（5.17±3.39）,（4.45±3.74）和（4.21±3.01）μg·mL^-1。发生不良反应者谷浓度高于未发生者（P<0.05）,同时两者之间的年龄、性别、基础疾病、感染部位差异无统计学意义;发生肝毒性者谷浓度高于未发生不良反应者（P<0.05）。不良反应的处理方式主要为根据患者NCI分级和谷浓度,分别选择终止伏立康唑治疗、对症治疗、减量50%等。最终,51例患者经处理后转归良好。结论 伏立康唑不良反应不受年龄、性别、基础疾病和感染部位影响,但谷浓度高者更易发生。为保证安全用药,可尝试将4 μg·mL^-1作为谷浓度上限;处理不良反应时需要考虑谷浓度和NCI分级选择合适的处理方式。     

临床药师参与心血管内科临床治疗实践的回顾性研究及思路探讨

目的 研究和探讨临床药师在心血管内科开展药学服务的类别和内容,为药师参与临床治疗提供思路。方法 通过统计临床用药干预建议的类别及接受率,结合病例分析临床药师参与临床工作的内容与方法。结果 临床干预建议中,非专科用药干预建议略多于专科用药,分别占53.5%和46.5%;其中非专科用药接受率比专科用药略高,为90.8%。结论 临床药师应掌握专科主要病种的治疗药物,熟悉常见合并症非专科治疗用药的使用方法,具备良好的沟通技能,以便为临床提供多种形式的药学服务,促进药物应用更加安全、有效。     

门急诊抗菌药物处方调查分析

抗菌药物临床应用专项整治活动自2011年7月开展以来,该院对门急诊抗菌药物处方采取逐张点评的方式,实施专项点评、整治。现对2011年第四季度和2012年第四季度门急诊抗菌药物的应用情况进行对比分析,从统计的数据变化来看,专项整治活动取得了明显的进展,抗菌药物的不合理使用情况有了很大的改善。     

儿童坏死性肺炎临床特点及诊治方法分析

目的:分析总结儿童坏死性肺炎(NP)的临床特征及诊治方法,以提高儿科临床对NP的诊疗水平。方法:回顾性分析2012年6月至2015 年6月在自贡市第一人民医院接受治疗的47例NP患儿的临床资料,总结儿童NP的临床表现、影像学特征、病原学特点、治疗方法及预后。结果:47例患儿均表现出持续发热、咳嗽,部分伴有肺部湿啰音。病原学检查结果显示,11例细菌培养阳性(分别为肺炎链球菌5例、金黄色葡萄球菌2例、鲍曼不动杆菌2例、草绿色链球菌2例,其中7例合并肺炎支原体IgM抗体阳性),35例细菌培养结果阴性(其中14例单纯肺炎支原体IgM抗体阳性,9例单纯肺炎衣原体IgM阳性,6例肺炎支原体IgM抗体阳性合并肺炎衣原体IgM抗体阳性,6例病原学检查结果均阴性),1例白假丝酵母菌培养阳性。胸部CT检查结果显示,所有患儿均可见多发性小空洞,16例合并胸腔积液。所有患儿均给予茁鄄内酰胺类抗生素静脉滴注,并酌情给予头孢吡肟、美罗培南、利奈唑胺、万古霉素、阿奇霉素和(或)红霉素治疗,胸腔穿刺治疗16例,随访3~6个月,所有患儿均预后良好。结论:儿童NP可能与肺炎支原体(MP)或衣原体(CP)感染有关,但不能除外细菌感染,该病热程及病程较长,影像学表现明显,积极采取抗生素治疗可取得良好预后。     

维C银翘片过量致重度肝损害1例的救治

1名26岁女性,一次性服用维C银翘片150片(含对乙酰氨基酚15.75g)。6h后出现头晕、恶心、呕吐,14h后症状加重且出现乏力,皮肤、黏膜轻度黄染,肝区叩痛。实验室检查显示:ALT6127U/L,AST4014U/L,TBil40μmol/L,DBil21μmol/L,APTT27.9s,PT29.4s。诊断为对乙酰氨基酚所致急性重度肝损害。给予对症治疗3周,患者肝功能恢复正常。     

鱼腥草热敏凝胶滴眼液的特性及临床疗效

目的观察鱼腥草热敏凝胶滴眼液的特性和临床疗效。方法以鱼腥草为主药、热敏材料泊洛沙姆407为辅料配制热敏凝胶滴眼液,测定其相转变温度、吸附量、凝胶累积溶蚀量,并与鱼腥草滴眼液和病毒唑滴眼液进行临床对照研究。结果其液态转变为凝胶的相转变温度为34.5℃,于37℃变成凝胶后其吸附量比液态滴眼液大大增加,凝胶累积溶蚀量与溶出介质加入量呈线性关系,40m in累积溶蚀量达98.76%;其临床疗效比同浓度的鱼腥草滴眼液和病毒唑滴眼液均好。结论鱼腥草热敏凝胶滴眼液是眼科长效制剂,滴眼次数少,临床疗效高。     

Correlates of Having Never Been HIV Tested among Entrants to Substance Abuse Treatment Clinics: Empiric Findings from Real-World New England Settings

Routine testing is the cornerstone to identifying HIV, but not all substance abuse treatment patients have been tested. This study is a real-world evaluation of predictors of having never been HIV tested among patients initiating substance abuse treatment. Participants (N = 614) from six New England clinics were asked whether they had ever been HIV tested. Eighty-five patients (13.8%) reported having never been tested and were compared to those who had undergone testing. Clinic, male gender (adjusted odds ratio (AOR) = 1.91, 95% confidence interval (CI) = 1.07–3.41), and having fewer employment (AOR = 0.31; 95% CI = 0.11–0.88) and medical problems (AOR = 0.40, 95% CI = 0.17–0.99) were independently correlated with having never been HIV tested. Thus, there is still considerable room for improved testing strategies as a clinically significant minority of substance abuse patients have never undergone HIV testing when they initiate treatment.     

护理干预对手足口病患儿治疗依从性及临床疗效的影响

目的探讨护理干预对手足口病患儿治疗依从性及临床疗效的影响。方法将80N手足口病患儿随机分为对照组和观察组各40例,对照组实施常规护理,观察组采用护理干预,比较二者治疗依从性和临床疗效。结果观察组患儿饮食、运动、用药及行为依从性明显好于对照组,差异存在统计学意义（P〈0．05）;观察组患儿体温恢复正常时间、皮疹消退时间、溃疡愈合时间以及用药时间均显著短于对照组,差异存在统计学意义（P〈0．05）。结论护理干预可显著提高手足口病患儿治疗依从性和临床疗效,促进患儿康复,值得临床推广应用。     

细菌耐药率与抗菌药物用量相关性分析及临床治疗对策

目的:了解本院抗菌药物的使用状况及细菌耐药率的变化趋势,为临床合理使用抗菌药物提供依据。方法:利用用药频度(DDDs)分析方法对本院2007～2008年抗菌药物消耗量进行统计,并对同期病原菌培养分离结果和药敏试验中各类抗菌药物的耐药率进行比较分析,寻找抗菌药物临床治疗对策。结果:药品用量DDDs排序为β-内酰胺类最高,其次为大环内酯类;本院病原菌感染动态为大肠埃希菌引起的感染最高,其次为铜绿假单胞菌和金黄色葡萄球菌;青霉素类和大环内酯类的耐药率较高,细菌耐药率与抗菌药物用量具有相关性。结论:抗感染治疗应参照药敏结果,结合临床疗效合理选用抗菌药物,控制抗菌药物用量,防止或减缓细菌耐药性产生。     

新生儿化脓性脑膜炎临床诊治经验与病原菌分析

目的:分析探讨新生儿化脓性脑膜炎的病原菌和临床诊治经验。方法:选取我院2014年2月至2016年1月收治的新生儿化脓性脑膜炎患儿60例,回顾性分析所有入选患儿的临床资料,包括实验室检查结果、临床表现、临床转归情况、头颅影像学检查结果、病原菌分布等。结果: 60例新生儿化脓性脑膜炎患儿外周血中C鄄反应蛋白的异常率高于外周血中白细胞异常率(χ2=6.384,P<0.05),脑脊液中的白细胞计数异常率高于蛋白含量异常率(χ2=11.284,P<0.01)。在对60例患儿的细菌血培养和脑脊液培养结果中,28例患儿细菌培养呈阳性,共分离病原菌33株且均为条件致病菌,其中19例(67.9%) 患儿分离菌株对3种以上的抗菌药物耐药,为多重耐药菌。结论:新生儿化脓性脑膜炎病原菌的耐药率越来越高,由于早期诊断的困难,该病的治疗和预后均不理想,因此,需要早期对高危因素患儿进行密切的临床监测和反复的脑脊液检查。