抗生素相关性腹泻

随着抗生素的广泛应用，抗生素相关性腹泻（AAD）日益受到关注，10％－20％的AAD是由难辨梭菌感染引起的，难辨梭菌在健康儿童中的带菌率约为25％－65％，但与儿童腹泻的关系尚有争议，发生AAD的高危因素有使用广谱抗生素，抗生素治疗大于3天，两项以上医学干预措施或伴随疾病，合理使用抗生素，严格控制广谱抗生素的使用是预防AAD的关键，对于轻型AAD，停用抗生素是最有效而简单的治疗措施。     

儿科抗生素相关性腹泻

近年来,儿科临床抗生素使用十分广泛,滥用抗生素现象也非常严重。据了解,国内部分基层医院甚至个别三甲级医院门诊处方抗生素使用率达90%以上,其住院患者抗生素的使用率近100%。国外有报道称抗生素相关性腹泻 （antibiotic associated diarrhea,AAD）的发生率达5%～39%［1］,门诊儿童患者AAD的发生率达6.2%［2］。儿科肺炎使用抗生素后腹泻的发生率为50%［3］。 　　AAD在儿科临床相当常见,甚至有可能给患者带来灾难性后果,因此有必要引起临床医师（尤其是基层医疗单位儿科医师）对AAD的足够重视。     

布拉氏酵母菌散剂预防肺炎儿童抗生素相关性腹泻的疗效观察

目的 评价布拉氏酵母菌散剂治疗对肺炎儿童抗生素相关性腹泻(antibiotic-associated diarrhea,AAD)的预防作用.方法 采用双盲随机对照的方法将245例患有肺炎的住院儿童完全随机分成2组.预防组104例在抗生素治疗基础上加用布拉氏酵母菌散剂治疗;对照组141例,使用安慰剂及抗生素;出现腹泻后对照组加用布拉氏酵母菌散剂治疗,2组患儿均加用蒙脱石散口服和补液治疗.每日观察患儿排便次数及性状,统计2组患儿腹泻发生率、疗效、腹泻持续时间及肺炎总疗程.结果 预防组共16例(15.38％),对照组共41例(29.08％)患儿发生AAD.2组患儿AAD发生率差异有统计学意义(P＜0.05);与对照组相比,预防组发生AAD的风险下降了55.7％(RR =0.443,95％ CI0.233～0.845,P=0.012).预防组发生AAD的患儿腹泻持续时间及肺炎总疗程均较对照组短,差异有统计学意义(P分别为0.001、0.030).治疗期间未见药物不良反应.结论 早期使用布拉氏酵母菌散剂可有效降低肺炎住院患儿发生AAD的风险,改善疗效,缩短住院时间,未发现不良反应.     

益生菌在儿童抗生素相关性腹泻病的应用

儿童抗生素相关性腹泻(AAD)是指抗生素扰乱和破坏肠道菌群稳态,是儿科临床上最为常见的副反应。艰难梭菌相关性腹泻(CDAD)是AAD中的严重结肠炎类型。抗生素造成肠道菌群的结构改变,多样性减少,菌群组成结构重新分布;宿主肠黏膜免疫应答模式变化,开放病原菌侵入结合位点,诱导耐抗生素机会菌株的定植,感染易感性增高;菌群构成改变,干扰糖和胆汁酸代谢等原因引起腹泻。益生菌早期干预可以有效减低AAD和CDAD的发生率,临床上在使用抗生素同时应用益生菌是合理有效的。     

布拉酵母菌治疗婴幼儿抗生素相关性腹泻临床观察

<正>抗生素相关性腹泻(antibiotic associated diarrhea,AAD)是指应用抗生素后继发腹泻,为较常见的药物副反应。典型AAD发生率为5%～35%[1]。最近文献的一项荟萃分析显示,布拉酵母菌可成为临床医生控制健康婴儿和儿童罹患急性腹泻的有效药物手段,可缩短腹泻病程[2]。沈阳医     

微生态制剂预防儿童抗生素相关性腹泻的Meta分析

目的抗生素在儿童的应用很普遍,最常见的副反应是胃肠道反应,而腹泻是胃肠道反应的直接表现。儿童是否可以常规应用微生态制剂预防抗生素相关性腹泻(AAD)仍存争议。用循证医学评估微生态制剂预防儿童AAD的临床疗效。方法检索Medline(Pub Med作为检索工具)、Ovid、Web of Science、Embase和Cochrane Library、中国生物医学文献数据库,国期刊全文数据库和维普中文科技期刊数据库等,并辅于手工检索,检索时间均从建库至2009-06-31,对同质资料进行Meta分析。结果最终有8篇完全随机对照试验(RCT)符合纳入标准,经Q检验被纳入RCT无统计学意义,应用固定效应模型进行统计分析,微生态制剂组与对照组相比,差异有统计学意义,相对危险度(RR)=0.36,95%CI:0.27～0.48,需要治疗数(NNT)=6.37,95%CI:5.06～8.03。结论微生态制剂在一定程度上能够减少儿童AAD的发生率,且尚无相关副反应的报道,这为儿童抗生素的使用中是否应用微生态制剂提供一定的参考。由于亚组分析单一微生态制剂的RCT尚少,要进一步系统评估具体某一种微生态制剂的预防作用则仍需将来有更多的RCT被纳入。     

重症细菌性肺炎患儿继发抗生素相关性腹泻临床分析

目的探讨重症细菌性肺炎患儿抗生素相关性腹泻(AAD)的发病及用药情况。方法回顾性分析2013年1月—2013年6月重症细菌性肺炎患儿抗生素应用情况。结果 187例患儿中,发生AAD 132例(70.59%);引发AAD的常见抗菌药物依次为三代头孢类、青霉素类、碳青霉烯类等。AAD组患儿年龄≤3岁、抗生素治疗7 d以及应用抗生素≥2种的比例均高于非AAD组,差异有统计学意义(χ2=89.81~119.45,P均0.001)。AAD患儿经停用或换用抗生素后腹泻好转。结论重症细菌性肺炎患儿AAD的发生率较高,与患儿年龄、抗菌药物使用时间、抗菌药物联用有关。     

儿童抗生素相关性艰难梭菌腹泻的病例对照研究

摘要 目的：探讨儿童抗生素相关性腹泻（AAD）中艰难梭菌感染（CDI）的发生情况及临床特点,为抗生素相关CDI的诊治提供依据。方法：纳入2016年6月1日至2017年10月1日在复旦大学附属儿科医院行CD毒素A/B检测和CD厌氧培养且符合AAD诊断标准的住院患儿,排除＜1月龄、粪便常规细菌培养和病毒检测等临床信息不完整的病例,重复病例仅纳入首次诊断AAD时的临床信息。毒素A/B检测阳性或结肠镜检查提示假膜性肠炎者CDI组;余为非CDI组。单人从病志中采集一般资料,基础疾病,出现AAD相关腹泻症状前2个月内的抗生素使用情况,1个月内的治疗和药物使用情况,实验室指标等。结果：符合本文纳入标准的AAD患儿150例,年龄40 d至15岁2月,中位年龄1.4岁,男103例(68.7%)。CDI组24例（16.0%）,非CDI组126例。①CDI组急性腹泻22例（中位腹泻天数8 d）,因克罗恩病导致的慢性腹泻急性加重1例;因结肠息肉导致的迁延性腹泻急性加重1例,发热11例（45.8%）,呕吐8例（33.3%）,腹痛2例（8.3%）,腹胀1例（4.2%）;1例（1/5,20%）结肠镜显示为伪膜性肠炎。②CDI组和非CDI组发病年龄,性别,基础疾病,腹泻前2个月内抗生素应用情况,腹泻前1个月内手术或糖皮质激素、免疫抑制剂和抑酸药应用情况,实验室指标差异无统计学意义(P＞0.05)。多因素logistic分析显示CDI和非CDI临床表现和常规实验室检测指标差异无统计学意义(P＞0.05)。③AAD的主要治疗措施为停用广谱抗生素,益生菌辅助治疗,CDI患儿症状无好转时加用甲硝唑（应用5~7 d后未见明显好转改口服万古霉素）。CDI组腹泻均好转或痊愈,非CDI组117例（94.4%）腹泻症状好转,9例死于腹泻外的其他原因。结论：儿童AAD中 CDI发生率为16.0%,发热、呕吐为最常见的临床表现,经治疗后预后良好,仅凭临床表现和实验室检测指标不能区分儿童ADD中CDI和非CDI。     

细菌性重症肺炎患儿抗生素相关性腹泻发病率及高危因素分析

目的探讨细菌性重症肺炎患儿抗生素相关性腹泻(AAD)的发生率及高危因素。方法收集2011年1月—2014年1月1 086例入院时未经抗生素治疗且无腹泻的细菌性重症肺炎患儿的临床资料,回顾性分析患儿AAD发生率及导致AAD发生的高危因素。结果 1 086例细菌性重症肺炎患儿AAD发生率为36.74%。多因素logistic回归分析结果显示,年龄≤2岁(OR=4.53,95%CI:2.38~8.85),有机械通气(OR=1.69,95%CI:1.23~3.99),抗生素联用(OR=4.75,95%CI:2.39~8.99),使用阿莫西林/克拉维酸(OR=3.24,95%CI:1.09~5.67)、哌拉西林/他唑巴坦(OR=3.68,95%CI:1.30~4.32)、头孢哌酮/舒巴坦(OR=3.98,95%CI:1.08~3.84)均为AAD发生的独立危险因素。结论细菌性重症肺炎患儿年龄≤2岁、有机械通气、联用抗生素、使用β-内酰胺类/β-内酰胺酶抑制剂均是AAD的高危因素。     

布拉氏酵母菌在儿童抗生素相关性腹泻中的应用

目的 观察布拉氏酵母菌(亿活)在抗生素相关性腹泻(AAD)中是否有预防及治疗作用,并比较其与枯草杆菌二联活菌(妈咪爱)的疗效.方法 选择167例呼吸道疾病的患儿使用广谱抗生素治疗,并出现AAD,将其随机分为亿活预防组、亿活治疗组、妈咪爱组及对照组,分别观察各组出现腹泻时抗生素的应用时间,以及出现腹泻后各组腹泻好转时间、治愈时间、腹泻程度等,比较各组疗效.结果 亿活预防组5例未出现AAD,亿活预防组出现AAD时抗生素应用时间为(9.09±5.49)d,亿活治疗组出现腹泻时抗生素的应用时间(5.60±3.00)d,二者比较差异有统计学意义(P＜0.01),且腹泻好转时间及治愈时间各组间比较差异均有统计学意义(Pa＜0.05).各组腹泻程度的比较差异无统计学意义.结论 亿活可预防AAD,且在AAD的治疗中发挥良好的作用.     

Effect of amino acid containing dialysis solutions on plasma amino acid profiles in children with chronic renal failure

Our previous studies demonstrated that, over single peritoneal dialysis cycles, amino acid-based dialysis solutions (AAD) were effective in dialyzing children with chronic renal failure (CRF) and offered metabolic advantages over traditional glucose dialysis solutions. The AAD, however, resulted in undesirable elevations of certain plasma amino acids, notably methionine. To further investigate the relationship between dialysate and plasma amino acid levels, we assessed the plasma amino acid response to a new AAD with relatively low methionine content (Vamin-based) over separate 5-h cycles with 1.3 and 2.3% AAD in eight patients with CRF (age 1-9 years) on continuous ambulatory peritoneal dialysis (CAPD). There was a net absorption of 70-73% of the amino acids, the net absorption of individual amino acids corresponding with the AAD composition. Plasma amino acid levels rose with AAD, peaking by 1 h postinfusion. Although most amino acids fell to preinfusion levels at the end of the cycle (including methionine), isoleucine with the 1.3% AAD and isoleucine, leucine, phenylalanine, and tyrosine with the 2.3% AAD remained significantly elevated. Having demonstrated in children that amino acids are absorbed from the peritoneal cavity in proportion to the AAD profile, modification of the current AAD is suggested.     

Probiotics in the prevention of antibiotic-associated diarrhea in children: a meta-analysis of randomized controlled trials

OBJECTIVE: To systematically evaluate the effectiveness of probiotics in preventing antibiotic-associated diarrhea (AAD) in children. STUDY DESIGN: The following electronic databases up to December 2005, in any language, were searched for studies relevant to AAD and probiotics: MEDLINE, EMBASE, and The Cochrane Library. Only randomized controlled trials (RCT) were considered for study inclusion. RESULTS: Six placebo-controlled, RCTs (766 children) were included. Treatment with probiotics compared with placebo reduced the risk of AAD from 28.5% to 11.9% (relative risk, RR, 0.44, 95% CI 0.25 to 0.77, random effect model). Preplanned subgroup analysis showed that reduction of the risk of AAD was associated with the use of Lactobacillus GG (2 RCTs, 307 participants, RR 0.3, 95% CI 0.15 to 0.6), S. boulardii (1 RCT, 246 participants, RR 0.2, 95% CI 0.07-0.6), or B. lactis & Str. thermophilus (1 RCT, 157 participants, RR 0.5, 95% CI 0.3 to 0.95). CONCLUSIONS: Probiotics reduce the risk of AAD in children. For every 7 patients that would develop diarrhea while being treated with antibiotics, one fewer will develop AAD if also receiving probiotics.     

根据β-内酰胺酶选择抗生素对降低细菌性重症肺炎患儿抗生素相关性腹泻发生率的作用

目的 探讨根据细菌β-内酰胺酶(BLs)选用β-内酰胺/β-内酰胺酶抑制剂(BL/BLI)对细菌性重症肺炎抗生素相关性腹泻(AAD)发生率的影响。方法 回顾性分析细菌性重症肺炎患儿临床资料,将未行BLs检测、经验性选用阿莫西林/克拉维酸的248例患儿及根据BLs选用阿莫西林或阿莫西林/克拉维酸的323例患儿作为阿莫西林组;将未检测BLs直接选用哌拉西林/他唑巴坦的208例患儿与根据BLs选用哌拉西林或哌拉西林/他唑巴坦的291例患儿作为哌拉西林组;将未检测BLs而直接选用头孢哌酮/舒巴坦的191例患儿及根据BLs选用头孢哌酮或头孢哌酮/舒巴坦的341例患儿作为头孢哌酮组,监测各组患儿的AAD发生率,分析是否根据BLs选用BL/BLI的重症肺炎患儿AAD发生率和临床症状差异。结果 各组未检测BLs直接选用BL/BLI患儿的AAD发生率均高于根据BLs选用BL(BLs阴性)或BL/BLI(BLs阳性)患儿的AAD发生率,P0.01。根据BLs选用BL/BLI患儿的AAD病程、抗生素使用时间和住院日均短于未检测BLs患儿者(P0.01)。结论 根据BLs选用BL/BLI对降低细菌性重症肺炎患儿AAD发生率和减轻症状有重要作用。     

Prevention of antibiotic-associated diarrhea in children by Clostridium butyricum MIYAIRI

BACKGROUND: Clostridium butyricum MIYAIRI (CBM) is a probiotic bacteria used for anti-diarrheal medicine in Japan. The preventive effect of CBM was investigated for antibiotic-associated diarrhea (AAD) in children. METHODS: One hundred and ten children who suffered from upper respiratory tract infection or gastroenteritis were divided into three groups. Twenty-seven of the patients received only antibiotics, 38 received CBM from the mid point of the antibiotic treatment and 45 concomitantly received CBM from the beginning of the antibiotic treatment. To examine the effects of CBM on AAD, the changes in intestinal flora were investigated. RESULTS: Diarrhea was observed in 59% of the subjects who received only antibiotics, and total fecal anaerobes, especially Bifidobacterium, were remarkably decreased. In contrast, diarrhea in the subjects who received CBM from either the middle or the beginning of the antibiotic therapy was decreased to 5% and 9%, respectively. Concomitant administration of CBM increased anaerobes and prevented the decrease of Bifidobacterium in the subjects who received antibiotics. CONCLUSIONS: Clostridium butyricum MIYAIRI is effective for both the treatment and the prophylaxis of AAD in children, as it normalizes the intestinal flora disturbed by antibiotics.     

Management of pediatric congenital atlantoaxial dislocation: a report of 23 cases from northern India

From July 1996 to August 2001, we operated on 23 children (age 4-12 years) with congenital atlantoaxial dislocation (AAD). Sixteen had reducible AAD and 6 had the fixed type, while a single patient had basilar invagination. Preoperatively, these children were divided into four functional grades depending on the level of neurological deficits and dependence on others for activities of daily living (Di Lorenzo grades I-IV). There were only 2 patients with no deficits (grade I), while 15 of the 23 children presented with severe neurological deficits and were completely dependent for all activities of daily living (grade IV). Stigmata suggestive of congenital AAD were documented in 6 children and radiological osseous anomalies in 18 children. Transoral decompression and posterior stabilization was performed in 7 children, while 16 patients underwent the posterior stabilization procedure only. All patients were immobilized with a hard cervical collar postoperatively. Six children developed one or other treatable complications, of whom reoperation was indicated in 3, but could only be undertaken in 2 children. Retightening of the wire was done in 1 and further decompression of the odontoid process was carried out in the other. There was no postoperative deterioration in patients with no preoperative deficits (grade I). Ten out of the 15 children who were completely dependent for all activities in the preoperative period (grade IV) improved, and 6 children achieved normalcy or near normalcy (grade I or II). Three children deteriorated in the postoperative period, of whom 2 subsequently improved at follow-up. There were 2 deaths in the series; both these patients belonged to the severely compromised group (grade IV) and in addition had respiratory compromise. Bony fusion at the posterior stabilization site could be seen in 14 out of 16 patients screened. The various problems faced by the authors in managing these very fragile and severely compromised children with cervicomedullary compression due to congenital atlantoaxial dislocation in a setting with limited resources are discussed.     

Enzymatic diagnosis and carrier detection of aspartylglucosaminuria using blood samples.

The activity of the glycoprotein degrading lysosomal hydrolase, 4-L-aspartylglycosylamine amido hydrolase (AAD Gase, EC.3.5.1.26), was measured in plasma, buffy coat leukocytes, and separated lymphocytes (Ficoll separation) from 16 patients with aspartylglucosaminuria (AGU), 29 obligate heterozygotes, and 30 control subjects. In lymphocytes the AGU patients had unmeasurable or minimal AAD Gase activity with a mean of 3.9 U. The obligate heterozygotes showed AAD Gase activities ranging from 5 to 69 U with a mean of 34.1 U. Enzyme activities in the control group ranged from 91 to 243 U with a mean of 127.9 U, and were clearly separated from the values of the heterozygotes. In leukocytes the AGU patients had unmeasurable enzyme activity and obligate heterozygotes had enzyme levels closely similar to those in the lymphocytes from the same individuals. The AAD Gase activity in the leukocytes of the control group displayed a much wider variation than in the lymphocytes, ranging from 22 to 132 U with a mean of 70.7 U. In plasma the AGU patients had undetectable AAD Gase activity. The mean enzyme level of obligate heterozygotes was 72.2 U and that of control individuals 107.2 U, but the overlap between the groups was extensive. The results indicate that homozygous deficiency of AAD Gase, i.e., aspartylglucosaminuria can be reliably diagnosed using plasma, leukocytes, or separated lymphocytes. For carrier detection only separated lymphocytes allow a satisfactory differentiation between heterozygous and normal individuals. A group of 31 siblings of verified AGU cases and 11 children of identified carriers, whose spouses had normal AAD Gase activity, were investigated using the lymphocyte assay. The observed and expected frequencies (on the basis of Mendelian probabilities) were closely similar, suggesting that the lymphocyte assay can be used reliably for carrier detection.     

Second malignant neoplasms following childhood Hodgkin's disease: treatment and splenectomy as risk factors

The risk of second malignant neoplasm (SMN) was evaluated in 979 children with Hodgkin's disease. This cohort was diagnosed between 1955 and 1979 at one of the institutions of the Late Effects Study Group. Solid tumors, non-lymphocytic leukemia, and non-Hodgkin's lymphoma (NHL) developed in 18, 17, and 3 patients, respectively. The estimated cumulative probability of developing any SMN was 2% at 5 years from diagnosis, 5% at 10 years, and 9% at 15 years. The incidence is ninefold greater than the risk of acquiring cancer in 19 year-olds, the median age at which the diagnosis of SMN was made in this study population. For leukemia and NHL the corresponding probabilities were 1%, 3%, and 4% for the group as a whole but were increased (2%, 6%, and 8%) in patients who had suffered one or more recurrences. In order to analyze the risk of leukemia and NHL associated with alkylating agent chemotherapy, each patient was assigned a score of one for each alkylating agent administered for a 6-month period. Scores of 2, 4, 6, and 8 were associated with probabilities of leukemia or NHL of 2%, 3%, 6%, and 10%, respectively. In a multivariate analysis for leukemia/lymphoma that included AAD score, stage, and splenectomy, the effect of AAD score and splenectomy did not change substantially compared to the univariate results. AAD score remained statistically significant (P = .0001), and splenectomy was of borderline significance (P = .09). Of the 18 solid tumor SMNs, 15 developed within the field of radiation, and one other developed in tissue irradiated 34 years earlier for hemangioma. This study of a large and unselected group of children with Hodgkin's disease who received a variety of therapies demonstrates that children are as likely as adults to develop acute leukemia after alkylating agents and solid tumors in the field of radiation therapy.     

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??Antibiotic-associated diarrhea??AAD????which results from disturbance or destroying of balance in the gut microbiota caused by antibiotic therapy??is frequent pediatric complications. Clostridium difficile-associated diarrhea??CDAD?? is considered a severe colitis type of AAD. Antibiotics administration can result in gut microbiota alterations??i.e?? disturbance and redistribution in composition and significant drops in taxonomic diversity. Changes in the microbiota composition may lead to changes of host intestinal mucosal immune response pattern??being open to pathogen invasion binding sites??increased susceptibility to infection?? and induction of antibiotic resistant strains of colonization. Microbiota alterations cause decreased bacterial carbohydrate and disturbances of bile acid metabolism. The early intervention of probiotics can effectively reduce the incidence of AAD and CDAD. Clinical application of antibiotics and the use of probiotics at the same time are reasonable and effective.