泌尿系感染者病原菌及耐药性分析

目的：了解近年来泌尿系细菌感染致病菌及耐药性，为合理应用抗生素，提供临床根据。方法：对泌尿系感染患者298株病原菌进行药物敏感试验。结果：大肠埃希菌仍是引发泌尿系感染的主要病原菌，占53％，其次是葡萄球菌属，占19．40％，肠杆菌属占10．06％，肠球菌属占4．70％等，各类菌属耐药情况。结论：临床医师必须关注本地病原菌分布及耐药情况，合理应用抗生素，减少耐药性播散。     

耐药与敏感肺结核病人疾病经济负担对照研究

目的研究耐药与敏感肺结核病人的疾病经济负担.方法调查了15个"WHO结核病耐药监测"县(市)耐药与敏感病人207例,利用经济学评价方法,探讨其疾病经济负担.结果例均家庭疾病经济负担:初治耐药组为3061.5元、敏感组为2103.7元;复治耐药组为8414.0元、敏感组为6798.1元.例均社会疾病经济总负担,耐药患者为14655.30元,敏感患者为5740.68元.耐药是敏感的2.6倍.结论耐药肺结核病患者无论是家庭疾病经济负担,还是社会疾病经济负担都要比药物敏感肺结核患者要高.     

医院内G-杆菌产酶检测及耐药性分析

目的了解医院常见G-杆菌的产酶及耐药情况为临床控制感染提供依据。方法收集2002-01～12住院病人分离的对三代头孢菌素至少有一种耐药的易产酶G-杆菌,采用传统K-B法进行药物监测,并使用改良的三维试验法检测细菌产酶情况。结果所监测大肠埃希菌与肺炎克雷伯杆菌超广谱β-内酰胺酶(ESBLs)的检出率为94.0%、100%,大肠埃希菌AmpC的检出率为3.0%;易产诱导酶阴沟肠杆菌、产气肠杆菌、弗劳地枸橼酸杆菌、粘质沙雷菌、奇异变形杆菌ESBLs检出率分别为47.0%、86.0%、80.0%、100%、40.0%。其中阴沟肠杆菌、产气肠杆菌、弗劳地枸橼酸杆菌AmpC酶的检出率为29.0%、14.0%、13.0%;鲍曼不动杆菌AmpC的检出率为33.0%;另外有7.0%的弗劳地枸橼酸杆菌、3.0%的大肠埃希菌产SSBL。亚胺培南是治疗严重易产酶细菌感染的首选药物。结论G-杆菌存在严重耐药,要正确区分细菌产酶机制,为临床控制感染提供正确的依据。     

临床标本中非发酵菌的分布及耐药性分析

目的了解临床标本中非发酵菌的分布及耐药状况,为合理使用抗菌药物提供依据。方法各种标本经分离培养,用ATB Expression细菌鉴定仪鉴定,用ATB PSE药敏试条进行药敏试验,并作统计分析。结果7 395份标本分离出非发酵1 106株,分离率为14.9%,以铜绿假单胞菌的分离率最高(45.7%),各种临床标本中以痰液标本的检出率最高;除嗜麦芽寡养单胞菌和脑膜脓毒金黄杆菌外,对亚胺培南的耐药率最低,其次为头孢哌酮/舒巴坦。结论非发酵菌在各种临床标本中分布不同,种类较多,各种细菌之间耐药性差异较大,临床应及时采集标本,作病原学检测及药敏试验,并根据药敏试验结果选择抗菌药物,以减少细菌耐药产生,控制医院感染。     

大肠埃希菌耐药性与头孢菌素类用量变化的相关性分析

目的通过调查医院1994～2002年大肠埃希菌对头孢类抗生素耐药性与该类药物年用量,探讨用药量和耐药性之间的相关性. 方法采用回顾性调查方法,对1994～2002年5种头孢菌素类的年用量与大肠埃希菌对这些药物的敏感性进行分析,计算各药DDDs,并用直线回归对耐药率与DDDs进行相关性分析. 结果9年来大肠埃希菌对5种头孢类抗生素的耐药率全部呈增长态势,其中使用频率较高的头孢唑林(CFZ)和头孢呋辛(CXM)的增长分别为25.9%和23.6%,使大肠埃希菌对这两药的耐药率接近40%;5种头孢类抗生素年用量变化不一,2002年与1994年相比CXM年用量增长了11倍,头孢他啶的年用量增长了3倍,头孢噻肟、头孢哌酮年用量呈波动性下降;耐药率和DDDs相关性分析显示,CXM用量与耐药率的变化呈显著正相关(r=0.768,P<0.05). 结论1994～2002年间大肠埃希菌对头孢类抗生素的耐药率逐年增长,头孢呋辛耐药率的增长与其年用量增加呈显著正相关.     

肠球菌属产酶耐药基因研究

目的为了解肠球菌属产酶耐药基因存在状况. 方法 20株肠球菌属进行了β-内酰胺酶TEM基因、氨基糖苷类修饰酶aac(6′)/aph(2″)和aph(3′)-Ⅲ基因和红霉素甲基化酶ermB基因检测. 结果 20株肠球菌属中有9株表型为青霉素/阿莫西林耐药并均检出TEM基因;12株对高浓度庆大霉素耐药并均检出aac(6′)/aph(2＂)和(或)aph(3′)-Ⅲ基因;19株耐红霉素肠球菌中,12株检出ermB基因;肠球菌中产β-内酰胺酶、氨基糖苷类修饰酶、红霉素甲基化酶的基因检出率均>50%. 结论肠球菌属耐药率已较高,且多数耐药菌已同时获得3～4个耐药基因.     

中西医结合治疗耐药性肺结核病的临床观察

目的探讨中西医结合治疗耐药性肺结核病的临床疗效。方法选择门诊复治耐药肺结核病患者80例,分成治疗组和对照组。两组患者在给予相同抗结核药物治疗的基础上,治疗组40例,加服中药养阴润肺汤,对照组40例只给予口服抗结核药物治疗,疗程均为1个月。健康对照组40人外周血做对照。结果治疗组痰涂片和痰结核分枝杆菌培养的阴转、病灶吸收好转、血沉恢复正常与对照组比较差异有统计学意义（P〈0.05）;外周血中T淋巴细胞亚群变化治疗前、后比较差异有统计学意义（P〈0.05）,对照组治疗前后差异无统计学意义（P〉0.05）。结论中西医联合用药可以更好地改善耐药肺结核病患者免疫状况,促进临床症状的改善。     

Analysis of hepatitis B virus drug-resistant mutant haplotypes by ultra-deep pyrosequencing

Direct sequencing and reverse hybridization are currently the main methods for detecting drug-resistance mutations of hepatitis B virus (HBV). However, these methods do not enable haplotype analysis so they cannot be used to determine whether the mutations are co-located on the same viral genome. This limits the accurate identification of viral mutants that are resistant to drugs with a high genetic barrier. In our current study, ultra-deep pyrosequencing (UDPS) was used to detect HBV drug-resistance mutations in 25 entecavir-treated and five treatment-naive patients. Of the 25 entecavir-treated patients, 18 had experienced virological breakthrough and two exhibited reduced susceptibility to entecavir. The results obtained by UDPS were compared with those of direct sequencing, and the haplotypes of the drug-resistant HBV mutants were analysed. The average number of reads per patient covering the region in which drug-resistance mutations are located was 1735 (range 451-4526). UDPS detected additional drug-resistance mutations not detected by direct sequencing in 19 patients (mutation frequency range 1.1-23.8%). Entecavir-resistance mutations were found to be co-located on the same viral genome in all 20 patients displaying virological breakthrough or reduced susceptibility to entecavir. In conclusion, UDPS was not only sensitive and accurate in identifying drug-resistance mutations of HBV but also enabled haplotype analysis of the mutants. This method may offer significant advantages in explaining and predicting the responses of patients with HBV to antiviral therapy.     

Conversion from immediate-release to extended-release lamotrigine improves seizure control

BackgroundImmediate release lamotrigine (LTG-IR) dosing can be limited by peak toxicity. It is thought that peak levels are responsible for some adverse effects such as dizziness, blurred vision, double vision and unsteadiness. At the same time, trough levels may be associated with reduced seizure threshold. The use of extended release lamotrigine (LTG-XR) to replace LTG-IR will be associated with less fluctuation in drug levels-lower peak levels may reduce adverse effects and higher trough levels may improve seizure control. This hypothesis was tested by analyzing seizure control and adverse effects before and after conversion from LTG-IR to LTG-XR in patients who underwent such conversion in 2009–2011.MethodsWe searched our patient database to identify patients converted from LTG-IR to LTG-XR for persistent seizures or adverse effects from August 2009 until December 31, 2011. We included only patients who took LTG-IR and LTG-XR for at least 6 months each. We excluded patients with nonepileptic seizures, progressive cause of epilepsy, or not keeping a seizure record. We collected the following parameters: age at conversion, LTG-IR dose and dosing schedule, duration on that dose, LTG-XR dose and dosing schedule, LTG serum level before and after conversion, duration of LTG-XR treatment, seizure frequency before and after conversion, and change in adverse experience profile. We also recorded baseline AEDs and any AED change during the course of the analysis.ResultsFifty five patients (26 female) satisfied the inclusion/exclusion criteria. Their mean age was 45 years (range 23 to 86). Ten were on LTG-IR monotherapy, 24 took LTG-IR plus one other AED, most commonly levetiracetam, and the remaining 21 took LTG-IR plus at least 2 other AEDs. The mean LTG-IR dose was 544 mg/day (range 150–1100 mg/day). The mean LTG-IR serum level was 11.6 (available in 53 patients-range 4.6–21 mcg/ml). Twenty six patients were converted to the same dose and one patient took a mixture of LTG-XR and LTG-IR at the same total daily dose, while 21 had their dose slightly increased and 7 had their dose slightly decreased due to adverse effects. The mean serum level after conversion was 11.8 (available in 49 patients-range 2.6–21.2 mcg/ml). As a result of the conversion, 26 patients (47%) experienced >50% reduction in seizure frequency. There was a 46% median reduction in seizure frequency overall. Seven patients reported improvement in adverse effects.ConclusionA conversion from LTG-IR to LTG-XR can help improve seizure control in some individuals with drug-resistant epilepsy, in addition to improving tolerability. While it is indicated in individuals experiencing peak adverse effects, it should also be considered in patients who have received incomplete seizure control from LTG-IR.     

急性髓系白血病Bcl—2基因表达及其临床意义

目的：探讨Ｂｃｌ－２基因在急性髓系白血病（ＡＭＬ）中的作用。方法：应用ＡＰＡＡＰ法检测６７例ＡＭＬ患者骨髓单个核细胞Ｂｃｌ－２基因表达，半固体培养法检测ＣＦＵ－Ｌ形成能力，并观察临床化疗效果．结果：发现ＡＭＬ患者Ｂｃｌ－２基因表达显著高于正常对照组（Ｐ〈０．００１），分化较成熟的Ｍ３型白血病表达率显著低于其它各亚型白血病（Ｐ〈０．０１），Ｂｃｌ－２蛋白表达表达与ＣＦＵ－Ｌ形成无相关性同，与患者外周