Albendazole residues in goat's milk: Interferences in microbial inhibitor tests used to detect antibiotics in milk

Albendazole (ABZ) residues in goat's milk and their effect on the response of microbial inhibitor tests used for screening antibiotics were evaluated. A total of 18 Murciano-Granadina goats were treated with ABZ and individually milked once a day over a 7-day period. ABZ quantification was performed by high performance liquid chromatography. The ABZ parent drug was not detected. The maximum concentration of its metabolites (ABZ sulfoxide, ABZ sulfone, and ABZ 2-aminosulfone) was reached on the 1^st day post treatment (260.0 ± 70.1 μg/kg, 112.8 ± 28.7 μg/kg, 152.0 ± 23.6 μg/kg, respectively), decreasing to lower than the maximum residue limit (MRL, 100 μg/kg) on the 3^rd day post treatment. Milk samples were also analyzed by microbial tests [Brilliant Black Reduction Test (BRT) MRL, Delvotest SP-NT MCS and Eclipse 100], and only one positive result was found for Delvotest SP-NT MCS and Eclipse 100. However, a high occurrence of positive outcomes was obtained for BRT MRL during 6 days post treatment, whereas ABZ residues were not detected from the 4^th day post administration, suggesting that factors other than the antiparasitic agent might affect the microbial test response.     

282例β-内酰胺类抗菌药的不良反应分析

目的：了解我院2009—2010年β-内酰胺类抗菌药不良反应发生情况,分析其影响因素,以促进临床合理用药。方法：收集我院2009—2010年上报告国家药品不良反应监测中心的282例β-内酰胺类抗茵药的药品不良反应（ADR）报告,分别从患者年龄、性别、给药途径、使用药物种类以及临床表现等方面进行统计分析。结果：ADR涉及β-内酰胺类抗菌药共33种,以头孢曲松居首位,其次为头孢呋辛和氨曲南;以静脉途径给药引发的ADR最多;282例ADR中,大于60岁患者构成比最高（28．72％）;临床表现以皮肤及其附件损害最常见。结论：β-内酰胺类抗菌药发生ADR与年龄、给药途径等多种因素相关,应规范β-内酰胺类抗茵药的临床应用,减少ADR的发生。     

β-内酰胺类抗生素使用情况及细菌耐药性分析

目的 分析某院β-内酰胺类抗生素的使用及病原菌耐药情况,为临床合理用药提供参考依据.方法 统计分析某院2008年1月至2009年12月β-内酰胺类抗生素的用药频度(DDDs)、总消耗金额、日治疗费用(DDC)和病原菌耐药率.结果 调查期内β-内酰胺类抗生素中头孢菌素类抗生素使用最为广泛;青霉素钠的日治疗费用最低,序号比最大;大多数抗生素在调查期内耐药率的差异不显著,但均产生不同程度的耐药率.结论 某院β-内酰胺类抗生素应用存在不合理现象,应加强抗生素的监管及用药前的药敏监测以减少抗生素不合理使用.     

2007-2009年南京地区23家医院抗感染药物利用分析

目的:分析2007-2009年南京地区抗感染药物应用状况及趋势,为临床合理应用抗感染药及其科学管理提供依据。方法:应用金额排序法和用药频度排序法,对南京地区23家医院2007-2009年临床使用的抗感染药物进行统计和分析。结果:2007-2009年抗感染药物用药总额增长迅速,到2010年为止,金额已过10亿元,年均增长率为22.38%,其中β内酰胺类药物占市场份额的一半以上。位于DDDs排序前列的为左氧氟沙星、罗红霉素和阿莫西林。结论:2007-2009年南京地区抗感染药物各品种使用基本规范,但仍应加强对于β内酰胺类、喹诺酮类药物及大环内酯类等药物的管理,以提高药物疗效,减少药物耐药性。     

Chlorinated pesticide residues in human breast milk collected from southern Jordan in 2012/2013

Chlorinated pesticide residues in human breast milk from five southern Jordan districts were analyzed in 2012/2013. The total number of samples from all districts was 100. The number of samples gathered from each district was collected according to their population densities. The present study shows that 59% of the samples which contained pesticides’ residues were p,p’-DDE, 30% contained β-HCH, 10% contained p,p′-DDT, 6% contained α-HCH, 2% contained heptachlor and 1% contained endrin. These human milk samples were free of aldrin, dieldrin, α-endosulfan, β-endosulfan, HCB, γ-HCH, o,p′-DDD, o,p′-DDT and o,p′-DDE. The levels of the six mentioned compounds detected in all mother’s milk samples were higher in Ghor El-Safi district compared with the other four districts. In this study, it is recommended to continue the pesticides residues monitoring in all parts of Jordan, particularly in Ghor El-Safi district and other regions in the cultivated Jordan Valley.     

2007—2010年广西医科大学第六附属医院住院患者抗菌药物应用分析

目的:调查2007—2010年我院住院患者抗菌药物应用情况,分析抗菌药物使用的特点及其变化趋势,为临床合理用药和科学管理抗菌药物提供参考。方法:通过院内信息系统查询统计2007—2010年我院住院患者抗菌药物使用量和销售金额,采用用药金额排序法和限定日剂量(DDD)法对抗菌药物合理应用的情况进行分析与评估。结果:4年来β-内酰胺类及β-内酰胺酶抑制剂、头孢菌素类及氟喹诺酮类抗菌药物年销售金额(万元)分别占所有抗菌药物年销售金额的72.20%(1 260.53/1 745.90)、68.75%(1 429.06/2 078.67)、78.61%(2 185.85/2 780.56)和84.80%(3 061.42/3 610.48),β-内酰胺类及β-内酰胺酶抑制剂的销售金额和氟喹诺酮类药用药频度(DDDs)一直居第1位,抗真菌药用量逐年增加,排序逐年靠前。结论:我院抗菌药物用药结构比较稳定,选择和用药基本合理,但仍存在问题,应减少细菌耐药率的发生,提高临床抗感染治疗的效果,保证用药更安全、有效和经济。     

Occurrence of aflatoxin M1 in raw milk collected from traditional dairies in Morocco

A survey of the presence of aflatoxin M1 (AFM1) was carried out on eight traditional dairies belonging to four sectors of Fez city situated in the northern center of Morocco. Raw milk samples were collected between October 2009 and September 2010, and analyzed by LC-fluorescence detection after immunoaffinity purification. AFM1 was detected in 13 out of 48 samples (27%) at concentrations ranged between 10 and 100 ng/l. Within these positive samples, four (∼8% of the total) were above the European legislation limit of 50 ng/l. This study revealed a variation of contamination from one sector to another with a higher incidence in milk samples collected in autumn compared to those collected in other seasons suggesting a link between feeding practices, such as the use of silage and AFM1 contamination. This is the first report on AFM1 contamination in raw milk directly collected from Moroccan traditional dairies. The levels of contamination found justify more detailed and continuous monitoring to assess the public health implication and reduce consumers’ exposure to AFM1.     

β内酰胺类/β内酰胺酶抑制剂复方抗菌药的药代动力学/药效学研究进展

β内酰胺类/β内酰胺酶抑制剂复方制剂是治疗产β内酰胺酶耐药菌感染的药物之一。β内酰胺类药物的T>MIC用于确定给药方法、给药剂量,预测药物临床治疗效果。其与β内酰胺酶抑制剂组成的复方抗菌药物,仍是时间依赖性抗菌药物;复方制剂的抗菌药需T>MIC超过给药间隔的40%～50%。需注意复方制剂两组分间的药代动力学应具备良好的同步性。     

宁波地区大肠埃希菌和肺炎克雷伯菌质粒AmpC酶基因检测

目的 了解近年宁波地区大肠埃希菌和肺炎克雷伯菌临床分离株中质粒AmpC酶基因流行状态.方法 用K-B法对临床分离的大肠埃希菌和肺炎克雷伯菌作耐药表型分析,通过聚合酶链反应(PCR)检测AmpC酶基因,然后用三维试验予以证实.结果 140株大肠埃希菌和肺炎克雷伯菌中,质粒AmpC醇基因阳性率2009、2010、2011年分别为4.4％(2/45)、8.6％(3/35)、13.3％(8/60);其中2009和2010年所检出的均为DHA基因型,2011年分别从2株大肠埃希菌和1株肺炎克雷伯菌中检出ACT-1基因.结论 宁波地区临床分离的大肠埃希菌和肺炎克雷伯菌中质粒AmpC酶基因的流行率有增长趋势.     

OprD mutations and inactivation, expression of efflux pumps and AmpC, and metallo-β-lactamases in carbapenem-resistant Pseudomonas aeruginosa isolates from South Korea

During a polymerase chain reaction (PCR)-based surveillance study of β-lactam resistance, 19 OXA-48-positive enterobacterial isolates were detected at nine Belgian hospitals from January 2010 to April 2011. Most cases were presumed to have been locally acquired and were detected in patients who had not travelled abroad. Clonally related outbreaks occurred in two different cities. The majority of isolates co-produced several β-lactamases as well as non-β-lactam resistance genes. This report highlights the rapid emergence and spread of OXA-48-producing Enterobacteriaceae in Belgium.     

A General LC-MS/MS Method for Monitoring Potential β-Lactam Contamination in Drugs and Drug-Manufacturing Surfaces

Penicillins and some non-penicillin β-lactams may cause potentially life-threatening allergic reactions. Thus, possible cross contamination of β-lactams in food or drugs can put people at risk. Therefore, when there is a reasonable possibility that a non-penicillin product could be contaminated by penicillin, the drug products are tested for penicillin contamination. Here, a sensitive and rapid method for simultaneous determination of multiple β-lactam antibiotics using high performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) was developed and validated. Mass spectral acquisition was performed on a Q-Exactive HF mass spectrometer in positive ion mode with parallel reaction monitoring (PRM). The method was validated for seven β-lactam antibiotics including one or two from each class and a synthetic intermediate. The quantification precision and accuracy at 200 ppb were in the range of ± 1.84 to ± 4.56 and ??5.20 to 3.44%, respectively. The limit of detection (LOD) was 0.2 ppb, and the limit of quantitation (LOQ) was 2 ppb with a linear dynamic range (LDR) of 2–2000 ppb for all eight β-lactams. From various drug products, the recoveries of eight β-lactams at 200 and 2 ppb ranged from 93.8?±?3.2 to 112.1?±?4.2% and 89.7?±?4.6 to 110.6?±?1.9%, respectively. The application of the method for detecting cross contamination of trace β-lactams (0.2 ppb) and for monitoring facility surface cleaning was also investigated. This sensitive and fast method was fit-for-purpose for detecting and quantifying trace amount of β-lactam contamination, monitoring cross contamination in manufacturing processes, and determining potency for regulatory purposes and for quality control.     

新建医院金黄色葡萄球菌感染分布与耐药性分析

目的:探讨金黄色葡萄球菌感染分布及耐药特征,指导临床合理用药。方法:应用西门子公司MicroScan-40SI全自动细菌鉴定/药敏分析系统、K-B法药敏试验(美国BD)、β-内酰胺酶测试(OXOID),并以"WHONET5.3"软件对数据进行分析处理。结果:三年共检出病原菌2901株,金黄色葡萄球菌277株占(9.5%),其中产β-内酰胺酶86株,占31.0%,MRSA占SA感染标本总数的32.6%,MRSA耐药率介于2.4%-91.0%。本室三年来未检出耐万古霉素、替考拉宁、奎奴普丁/达福普汀、利奈唑胺菌株;耐药率低的抗生素有利福平、哌拉西林/他唑巴坦、阿莫西林/克拉维酸、复方磺胺甲口恶唑、头孢唑啉;耐药率高的有青霉素、氨苄西林、苯唑西林、红霉素等。结论:本组对新建民营医院三年金黄色葡萄球菌感染菌株的分布与耐药性进行统计分析,产β-内酰胺酶菌株比例较其他报告53.3%为低,头孢唑啉药物敏感性较稳定,但对其它β一内酰胺类抗菌药物耐药性高,并对β一内酰胺酶抑制剂耐药性出现逐年上升趋势,应引起关注。     

Association between augmented renal clearance,antibiotic exposure and clinical outcome in critically ill septic patients receiving high doses of β-lactams administered by continuous infusion: a prospective observational study

This study assessed whether augmented renal clearance (ARC) impacts negatively on antibiotic concentrations and clinical outcomes in patients treated by high-dose β-lactams administered continuously. Over a 9-month period, all critically ill patients without renal impairment treated by one of the monitored β-lactams for a documented infection were eligible. During the first 3 days of antibiotic therapy, every patient underwent 24-h CL_Cr measurements and therapeutic drug monitoring. The main outcome was the rate of β-lactam underdosing, defined as a free drug concentration <4?×?MIC of the known pathogen. Secondary outcomes were rates of subexposure for β-lactams and therapeutic failure. The performance of CL_Cr in predicting underdosing was assessed by a ROC curve, and multivariable logistic regression was performed to determine risk factors for subexposure and therapeutic failure. A total of 79 patients were included and 235 samples were analysed. The rate of underdosing_<4×MIC was 12%, with a significant association with CL_Cr (P?<0.0001). A threshold of CL_Cr?≥?170?mL/min had a sensitivity and specificity of 0.93 (95% CI 0.77–0.99) and 0.65 (95% CI 0.58–0.71) for predicting β-lactam underdosing_<4×MIC. Mean CL_Cr values ≥170?mL/min were significantly associated with subexposure_<4xMIC [OR?=?10.1 (2.4–41.6); P?=?0.001]. Patients with subexposure_<4×MIC presented higher rates of therapeutic failure [OR?=?6.3 (1.2–33.2); P?=?0.03]. Mean CL_Cr values ≥170?mL/min remain a risk factor for subexposure to β-lactams despite high doses of β-lactams administered continuously. β-Lactam subexposure was associated with higher rates of therapeutic failure in septic critically ill patients.     

流感嗜血杆菌对β内酰胺类和氟喹诺酮类药物的耐药机制

目的研究流感嗜血杆菌(Hi)对β内酰胺类和氟喹诺酮类的敏感性和耐药机制。方法用琼脂二倍稀释法,检测Hi对β内酰胺类和氟喹诺酮类敏感性;Nitrocefin显色反应对所有菌株进行β内酰胺酶检测,PCR扩增检测Hi的β内酰胺酶基因(TEM-1和ROB-1)以及氟喹诺酮的耐药决定区(QRDR),并对特异条带测序并分析。结果对183株受试Hi,氨苄西林的敏感率为73.2%(134/183);对氨苄西林/舒巴坦、头孢噻肟和头孢吡肟均敏感率达100%。检出环丙沙星和莫西沙星不敏感Hi分别为2株(2/183)和3株(3/184),其中1株对环丙沙星和莫西沙星均不敏感。有34株(18.6%)TEM-1基因阳性;34株菌都携TEM-1型β内酰胺酶基因,未发现ROB-1基因;所有氟喹诺酮不敏感菌株的GyrA和ParC均发现一或多个氨基酸改变,且GyrA主要发生在84位和88位。结论除对氨苄西林外,Hi对头孢菌素和氟喹诺酮类保持较高敏感性。Hi对氨苄西林的耐药主要是产生β内酰胺酶,且主要为TEM-1型。QRDR的氨基酸改变是Hi对氟喹诺酮不敏感的主要机制。     

748例β-内酰胺类抗菌药物不良反应分析

目的了解蚌埠地区β-内酰胺类抗菌药物致药品不良反应(ADR)的发生情况。方法对2010年1～12月蚌埠地区上报的748例β-内酰胺类抗菌药物ADR病例报告,按性别、年龄、给药途径、药品类别、ADR累及系统-器官及临床表现等进行统计、分析。结果 ADR涉及的β-内酰胺类抗菌药物共26种,ADR发生频次以阿莫西林居首位,其次为头孢氨苄和头孢拉啶;主要的ADR类型为皮肤及其附件损害,占47.48%;1例严重ADR。结论应规范β-内酰胺类抗菌药物的临床应用,以减少ADR的发生率。     

我院抗菌药物使用季节变化规律分析

目的 了解医院不同季节抗茵药物使用量的变化规律,以利药品库房合理采购、医生合理用药.方法 以2009年9月至2010年8月抗茵药物使用金额占药品总金额的比例为考察指标,采用独立样本t检验,分析不同季节抗茵药物使用量的差异性.结果 抗茵药物使用总比例秋(x=27.12%)大于夏(x=21.08%),P<0.01;β-内酰胺类抗生素使用比例冬(x=19.58%)大于夏(x=15.65%).P<0.01;氟喹诺酮类抗茵药物使用比例秋(x=2.50%)大于夏(x=1.79%),P>0.05;硝咪唑类抗茵药物使用比例秋(x=3.15%)大于夏(x=0.92%),p<0.05.结论 所有抗菌药物使用比例总体表现为秋季明显多于夏季,其中β-内酰胺类抗生素使用比例冬季显著高于夏季,硝咪唑类抗茵药物使用比例秋季显著高于夏季,氟喹诺酮类抗茵药物使用比例与季节没有显著的相关性.     

Prevalence of plasmid-mediated AmpC β-lactamase-producing Escherichia coli and spread of the ST131 clone among extended-spectrum β-lactamase-producing E. coli in Japan

In 2010, a total of 1327 clinical Escherichia coli isolates from five hospitals in the Kyoto and Shiga regions of Japan were analysed by PCR. The prevalences of plasmid-mediated AmpC β-lactamase (pAmpC)-producers, extended-spectrum β-lactamase (ESBL)-producers and co-producers of pAmpC and ESBL were 1.7%, 9.7% and 0.3%, respectively. Less than one-half of the pAmpC-producers were reported to be resistant to third-generation cephalosporins, cephamycins and β-lactam/β-lactam inhibitors using the old 2009 Clinical and Laboratory Standards Institute (CLSI) breakpoints. CMY-2 was the most prevalent pAmpC type (95%), and CTX-M-14 (38%), CTX-M-15 (26%) and CTX-M-27 (19%) were the most prevalent ESBL types. The worldwide O25b-ST131-B2 clone accounted for 11% of pAmpC-producers and 41% of ESBL-producers. The O25b-ST131-B2 clone was characterised by a CTX-M-27- or CTX-M-15-type ESBL and ciprofloxacin-non-susceptibility with quadruple mutations in the quinolone resistance-determining regions (S83L and D87N in GyrA and S80I and E84V in ParC). A significant proportion of pAmpC-producers and the O25b-ST131-B2 clone were found in Japan by a recent regional surveillance programme.     

Incredible pharmaceutical residues in human milk in a cohort study from Şanlıurfa in Turkey

Maternal milk is essential for optimum growth and development of an infant. The aim was to examine the presence of pharmaceutical residuals in breastmilk. This cohort study enrolled 90 healthy mother-infant pairs at 5−14 days after delivery and a control examination was performed 4–8 weeks later. Milk samples were taken at both visits. RANDOX Infiniplex kit performed residual analysis. More than half of mothers (54.4 %) had anti-inflammatory drug residues in at least one milk sample: those were 52.2 % for tolfenamic acid and 2.2 % for meloxicam and 1.1 % for metamizole. The most frequent residue group included the beta-lactam antibiotic group, which was detected in 93.3 % of mothers’ milk. The second one was the quinolone group (81.1 %). One-third of mothers expressed nitroxynil and one-fifth polymyxin in at least one sample. Almost all mothers had some unexpected drug residues in their milk. Additional studies from other countries can display maternal environmental exposures.     

2009～2011年武汉地区β-内酰胺类复方制剂利用情况调查

目的：了解武汉地区β-内酰胺类复方制剂使用情况,为合理用药提供依据。方法：对武汉地区32家医院2009～2011年β-内酰胺类复方制剂使用数量、消耗金额、用药频度（DDDs）和日均费用（DDC）进行统计分析。结果：2009～2011年头孢菌素类复方制剂销售额呈增长趋势,年增幅平均在34%以上,而青霉素类复方制剂多呈下降趋势,但阿莫西林/克拉维酸3年中用药频度始终居于首位。结论：随着抗菌药耐药情况日益严重,β-内酰胺类复方制剂抗菌药使用的合理性和经济学指标有待深入评价。     

注射用丙帕他莫单药及与β-内酰胺类药、质子泵抑制剂的配伍稳定性考察

目的:考察注射用丙帕他莫与β-内酰胺类药、质子泵抑制剂(PPI)的配伍稳定性。方法:采用高效液相色谱(HPLC)法测定丙帕他莫48 h内的含量变化,考察其p H值变化,并观察与β-内酰胺类药及PPI配伍后各溶液的外观变化。结果:丙帕他莫的水溶液不稳定,药物含量在7 h内可降解至90%以下,p H值在3 h内从5.37降至3.52,48 h后p H值降至1.87。丙帕他莫与β-内酰胺类药配伍3 h时肉眼可观察到液体乳光,配伍12 h时可观察到白色沉淀;与PPI配伍立即发生颜色的变化并逐渐形成深色沉淀。结论:丙帕他莫的水溶液稳定性差,与β-内酰胺类药物及PPI存在配伍禁忌。丙帕他莫临床上应现配现用,尽量在配伍1 h内用完且不与其他药物进行配伍,输液前后应冲管。