Outbreaks of Imipenem Resistant Acinetobacter Baumannii Producing OXA-23 ��-Lactamase in a Tertiary Care Hospital in Korea

Purpose

Since November 2006, imipenem-resistant Acinetobacter baumannii isolates have increased in Kyung Hee University Hospital in Seoul, Korea. The purpose of this study was to determine the genetic basis and molecular epidemiology of outbreak isolates.

Materials and Methods

Forty-nine non-repetitive isolates of the 734 IRAB strains were investigated in order to determine their characteristics. The modified Hodge and the ethylenediaminetetraacetic acid (EDTA)-disk synergy test were performed for the screening of carbapenemase and metallo-β-lactamase production. Multiplex polymerase chain reaction (PCR) assays were performed for the detection of genes encoding for OXA-23-like, OXA-24-like, OXA-58-like and OXA-51-like carbapenemase. Pulsed-field gel electrophoresis (PFGE) was performed for strain identification.

Results

All isolates showed 100% resistance to ciprofloxacin and gentamicin, 97.9% resistance to cefepime, piperacillin/tazobactam, aztreonam, ceftazidime and piperacillin, 93.9% resistance to tobramycin and 57.1% resistance to amikacin. All of the 49 isolates (100%) showed positive results in the modified Hodge test and negative results in the EDTA-disk synergy test. They all (100%) possessed the encoding gene for an intrinsic OXA-51-like carbapenemase and an acquired OXA-23-like carbapenemase in the multiplex PCR assay. PFGE patterns revealed that all isolates were clonally related from A1 to A14.

Conclusion

It is concluded that all of the 49 IRAB isolates acquired resistance to imipenem by producing OXA-23 carbapenemase and they might have originated from a common source.     

注射用亚胺培南西司他丁钠诱发老年患者癫痫发作

1例71岁女性患者因怀疑院内感染给予亚胺培南西司他丁钠0.5 g,1次/8 h静脉滴注。第3天,患者突然出现抽搐、角弓反张、牙关紧闭,伴意识欠清、喘憋,持续约2~3 min,未予处理自行缓解。约15 min后上述症状再现,1~2 min后自行恢复正常。约75 min及2 h后症状再发,持续时间为3~5 min,两次均给予地西泮及醒脑静。第4次发作后约50 min上述症状再次发作,给予苯巴比妥效果欠佳,换用丙戊酸钠400 mg静脉泵入。约1 h后患者安静入睡。次日停用亚胺培南西司他丁钠,改为拉氧头孢钠,患者未再出现抽搐。     

耐亚胺培南铜绿假单胞菌的耐药性及耐药基因分析

目的了解耐亚胺培南铜绿假单胞菌（IRPa）β-内酰胺类酶的表达情况,比较产酶菌和非产酶菌的耐药性,并探讨产AmpC酶基因对其耐药表型的影响。方法采用EDTA协同试验检测β-内酰胺类酶,PCR扩增β-内酰胺类酶耐药基因及其序列测定确定其基因型。结果 112株耐亚胺培南铜绿假单胞菌中检出产β-内酰胺类酶菌85株（75.9%）,产酶菌株的耐药性比非产酶菌株的耐药性明显严重,对替卡西林/克拉维酸、头孢吡肟、头孢他啶、阿米卡星、庆大霉素、妥布霉素、环丙沙星耐药率均大于35.3%;耐药基因TEM、SHV、OXAI、MP-1、AmpC、VIM-2阳性率分别为53.57%、10.17%、2.71%、4.46%、46.43%、16.96%,且有42.85%的菌株表现为多基因耐药。结论产β-内酰胺酶菌株对大多数抗生素的耐药性明显高于非产酶菌株,耐药基因以产TEM、AmpC为主,少部分产SHV、OXA、IMP-1、VIM-2,产β-内酰胺酶是铜绿假单胞菌对亚胺培南耐药的重要机制。     

Clonal spread of carbapenem-resistant OXA-72-positive Acinetobacter baumannii in a Croatian university hospital

Background

From July to October 2008, 34 Acinetobacter baumannii isolates were involved in an outbreak at the Clinical Hospital Center, Zagreb. The aim of this study was to characterize the mechanisms of carbapenem resistance in our A. baumannii isolates and determine their epidemiology.

Methods

Antibiotic susceptibilities were determined by broth microdilution. PCR was used to detect the presence of carbapenemases. Genotyping of the isolates was performed by random amplification of polymorphic DNA (RAPD), pulsed-field gel electrophoresis (PFGE), and repetitive sequence-based PCR (rep-PCR).

Results

Thirty-three carbapenem-resistant isolates were positive for the acquired bla_OXA-72 and one unrelated isolate was positive for bla_OXA-58. The bla_OXA-72-positive isolates were shown to be clonally related by RAPD, rep-PCR, and PFGE.

Conclusions

On the basis of susceptibility testing, β-lactamase characterization, and genotyping of the isolates we can conclude that clonal spread of endemic isolates was responsible for the high frequency of OXA-72-positive multidrug-resistant A. baumannii in this setting. Most of the isolates originated from the intensive care unit indicating local dissemination within the hospital and pointing to the potential source of isolates.     

鲍曼不动杆菌OXA基因的检测及ISAba1对其表达的影响

[目的]了解鲍曼不动杆菌的OXA-碳青霉烯酶基因分布情况及插入序列1(ISAba1)对OXA -23基因表达的影响.[方法]收集临床分离的鲍曼不动杆菌无重复株110株.多重PCR扩增OXA - 23 - like、OXA - 24 - like、OXA - 51 - like、OXA - 58 - like基因,并测序...     

亚胺培南/西司他丁抢救恶性血液病化疗后并发G~-菌感染性休克临床分析

目的通过亚胺培南/西司他丁（泰能）抢救20例恶性血液病化疗后并发G-菌感染性休克的研究,总结临床经验,提高诊治水平。方法回顾性分析我院2002～2009年泰能抢救恶性血液病化疗后并发G-菌感染性休克20例的临床表现和诊疗过程。结果泰能抢救G-菌感染性休克疗效满意,主要不良反应是恶心呕吐。结论 G-菌是引起恶性血液病患者化疗后并发感染性休克重要原因之一,经验性使用泰能是适宜的。     

耐亚胺培南革兰阴性杆菌的临床分布及耐药性

目的：了解2007年1月～2009年12月我院老年患者亚胺培南耐药革兰阴性杆菌菌株的分离情况、临床分布及耐药性趋势.方法：收集该院2007年～2009年临床各类标本中分离到的245株耐亚胺培南革兰阴性杆菌,采用德灵Microscan微生物鉴定及药敏分析系统,对菌株进行鉴定及药敏试验.结果：2007年～2009年共分离到245株亚胺培南耐药株,其中非发酵菌科235株,占96%,以铜绿假单胞菌最多,占81.1%;其次为鲍曼不动杆菌,占15.6%,且鲍曼不动杆菌的亚胺培南耐药株呈逐年上升趋势,从2007年的5.8%上升至2009年的22.8%,而肠杆菌科亚胺培南耐药株仅占4%.耐亚胺培南的菌株对B内酰胺类生素耐药率为53.0%～100%,对喹诺酮类抗生素耐药率为60.2%～83.2%,对氨基糖苷类抗生素的耐药率相对较低,为28.2%～51.5%,其中以阿米卡星最为敏感.结论：亚胺培南对肠杆菌科具有非常强的体外抗茵活性,对非发酵菌科的体外抗菌活性较差.耐亚胺培南菌株大多存在多重耐药性,甚至泛耐药,临床应根据药敏试验的结果选用敏感的抗菌药物治疗.     

骨科感染创面铜绿假单胞菌耐亚胺培南临床分析

目的：探讨骨科感染创面铜绿假单胞菌对亚胺培南耐药的原因和可能机制。方法：检测37株骨科感染创面铜绿假单胞菌外膜蛋白OprD2及金属β-内酰胺酶的表达情况,分析铜绿假单胞菌感染患者临床情况。结果：37株实验菌株中,15株对亚胺培南敏感,22株对亚胺培南耐药,其中有17例与ICU或呼吸内科住院有关,耐药株患者中APACHEⅡ评分达12以上占45．5％,平均住院时间（26．9±7．5）d,2周内有亚胺培南或美罗培南使用史者45．5％（10／22）;敏感株患者中APACHEⅡ评分〉12者6．7％,平均住院时间（13．5±6．6）d,2周内有亚胺培南或美罗培南使用史者0％（0／15）。OprD2相对含量耐亚胺培南菌株组为（2．65±0．54）％,明显低于亚胺培南敏感菌株组的（5．38±0．81）％（P〈0．01）。37株实验菌株中产金属β-内酰胺酶5株（13．5％）,并均在耐亚胺培南菌株组中。结论：他科输入、病情危重免疫力低下、住院时间长、碳青霉烯类抗生素使用是骨科感染创面铜绿假单胞菌对亚胺培能耐药的主要原因,而OprD2的含量减少和产金属β-内酰胺酶是骨科感染创面铜绿假单胞菌对亚胺培能耐药的重要机制。     

HPLC测定人血清中亚胺培南的浓度

建立人血浆中亚胺培南浓度的高效液相色谱测定方法，探讨亚胺培南人体内药动学过程。以０．５ｍｏｌ／ＬＮ－２－羟乙基哌嗪－Ｎ－２－乙磺酸—５０％乙二醇（体积比１１）为稳定剂，以５－羟基－３－吲哚乙酸为内标，在μ－ＢｏｎｄａｐａｋＣ１８柱上，以０．３ｍｏｌ／Ｌ四乙基溴化铵乙醇液－２０ｍｍｏｌ／Ｌ磷酸氢二钾（体积比４９６）为流动相，检测波长２９８ｎｍ，对亚胺培南进行定量测定。结果血浆中亚胺培南在１～１００μｇ／ｍｌ浓度范围内具良好线性关系，血浆回收率为９８．６％±２．２５％（ｎ＝６）。血浆日内及日间ＲＳＤ分别为１．６９％～３．７６％和３．８２％～６．６７％。本方法简便、快捷、灵敏、准确；适用于临床血药浓度测定。     

Single-dose kinetics of imipenem/cilastatin during continuous arteriovenous haemofiltration in intensive care patients

The single i.v. dose kinetics of a fixed combination of imipenem/cilastatin were investigated in ten critically ill patients treated by continuous arteriovenous haemofiltration (CAVH). Eight patients suffered from acute renal failure and two had normal renal function. Both drugs were measured in plasma and ultrafiltrate by high-performance liquid chromatography. While the pharmacokinetics of both drugs are almost identical in patients with normal renal function, we found the following dissociation of pharmacokinetic parameters in our patients with renal failure: for imipenem the total clearance and elimination half-life was 104 +/- 12 ml/min and 2.2 +/- 0.1 h, respectively, and for cilastatin 29 +/- 10 ml/min and 13.8 +/- 4.5 h. The pharmacokinetics of imipenem and cilastatin differ from each other in renal failure because imipenem, unlike cilastatin, undergoes marked elimination by non-renal pathways. Our results did not differ from previously reported data in healthy volunteers and patients with impaired renal function. Elimination of imipenem by CAVH was low (7% of the dose). As a consequence of the unsatisfactory non-renal clearance of cilastatin, however, the fraction of the dose removed by CAVH was significantly greater (approximately 30%) than that of imipenem. This did not, however, correct the dissociation of the pharmacokinetic profiles of the two drugs. In conclusion, the dose of imipenem/cilastatin in critically ill patients with renal failure treated by CAVH should be modified according to renal function but elimination by CAVH does not need to be considered.