多重抗藥性原型與Acinetobacter菌感染的不良反應有關


  July 3, 2008 —根據抗微生物阻抗性2008年研討會中,Walter Reed陸軍醫學中心(WRAMC)的研究結果,確認阻抗性原型或者基因與其對於臨床結果的影響,可以幫助策劃、調整因應健康照護體系中,Acinetobacter菌屬多重抗藥性(MDR)問題的策略。
  
  資深作者、凱斯西儲大學醫學院Louis Stokes克里夫蘭退伍軍人醫學中心醫學副教授R. A. Bonomo醫師向Medscape Infectious Diseases表示,我們的實驗室對於鮑曼氏不動桿菌(Acinetobacter baumannii,Ab)菌的MDR基因基礎感到興趣,主要是因為在1995至1996年於克里夫蘭爆發嚴重的MDR Ab。
  
  Bonomo醫師表示,我們對於這些早期分離出來的菌種對carbapenem和cephalosporin產生阻抗性感到好奇,希望將它們和WRAMC所分離出來的菌種進行比較;當時的做法是,我們首先聚焦在克里夫蘭分離出來的Ab對於cephalosporin的阻抗,之後是WRAMC分離的菌對於carbapenem的阻抗;我們的研究,導致後續的一些嘗試,以確認藥物阻抗性是否有更不佳的結果。這些是很難進行的研究。
  
  發表的回溯醫療紀錄回顧了Acinetobacter菌種感染和/或定著在WRAMC研究中75名病患的效果,以評估某些阻抗性原型、基因或者增加死亡率或發病率的菌株類型。
  
  這些病患的血液、呼吸道、皮膚、尿道、腦膜和/或軟組織中,有Acinetobacter菌感染和/或定著;以曼-惠特尼U檢定和卡方分析來確認選擇性阻抗性決定因素和臨床結果之間的關係。
  
  這些病患的分離株進行敏感性檢測、阻抗性基因聚合酶連鎖反應擴大,以及兩種分子分類方法;75種病患分離株之中,73種是A baumannii,一種是 A johnsonii,一種是Acinetobacter 基因組第三類。
  
  分析發現許多有趣的關聯:獲得一種carbapenem阻抗 A baumannii 分離株與機械呼吸裝置有關,分離發現含有blaOXA carbapenemase這種酶;Carbapenem阻抗性與爆發的期間有關,在那些住院期間比較久的病患中,比較可能會有carbapenem阻抗Acinetobacter 菌屬;最後,amikacin-阻抗之A baumannii 與院內感染有關。
  
  Bonomo醫師表示,從這些資料中,顯然A baumannii感染對於住院的軍人和一般民眾有相當大的影響;我們接著發現,如果病患有Carbapenem阻抗之 MDR Ab原型者,會有最不好的結果;我們的分析認為,阻抗性原型和不佳結果之間或許有關聯。
  
  Medscape Infectious Diseases邀請賓州大學醫院的醫學與流行病學副教授、醫院流行病學專家Ebbing Lautenbach醫師回顧此研究。
  
  Lautenbach醫師並未直接參與此研究,他同時也是賓州大學醫學院流行病學與生物統計中心的資深學者。
  
  Lautenbach醫師表示,本文章的主要強度是研究對象夠多,聚焦在辨識不良結果的風險,闡述阻抗性原型和阻抗性機轉與結果的角色;事實是,分離株表現的感染和定著,釐清對於結果的實際影響是複雜的,而表現出定著的有機體較不可能有較差的結果。
  
  根據Lautenbach醫師表示,carbapenem阻抗性和carbapenem阻抗性不佳結果機轉之間的關聯,對於幫助辨識治療標靶是重要的。
  
  他結論表示,這些介入治療包括適當化經驗性抗生素治療,以及藉由調整阻抗的重要因素,而努力控制後續的阻抗的急迫性;最近幾年,Acinetobacter菌的感染發生率增加,這些有機體一般感染重症病患的事實,點出需要更清楚辨識此一有機體的風險、以及其對結果影響的急迫性。
  
  Veterans Affairs Merit Review與國家健康研究中心贊助此研究。Bonomo醫師和 Lautenbach醫師宣稱沒有關資金上的往來。
  
  抗微生物阻抗性2008年研討會:摘要S4。2008年6月23–25日。

Multidrug-Resistant Phenotype Linked to Adverse Outcomes in Acinetobacter Infections

By Laurie Barclay, MD
Medscape Medical News

July 3, 2008 — Determining resistance phenotypes or genes and their effect on clinical outcomes may help in devising strategies to modify the effect of multidrug-resistant (MDR) Acinetobacter species on healthcare delivery systems, according to the results of a study from the Walter Reed Army Medical Center (WRAMC) reported at the 2008 Annual Conference on Antimicrobial Resistance in Bethesda, Maryland.

"Our lab became interested in the genetic basis of the MDR Acinetobacter baumannii (Ab) isolates that were being recovered from our troops because in 1995 to 1996 we had an MDR Ab outbreak in one of our local burn units in Cleveland," senior author R. A. Bonomo, MD, an associate professor of medicine at Louis Stokes Cleveland Veterans Affairs Medical Center, Case Western Reserve University School of Medicine, in Cleveland, Ohio, told Medscape Infectious Diseases.

"We were intrigued as to the basis for carbapenem and cephalosporin resistance in these early isolates and wished to compare them to the isolates from WRAMC," Dr. Bonomo said. "As it turns out, we focused first on cephalosporin resistance in Ab in Cleveland and then carbapenem resistance in the WRAMC isolates; our studies led further to trying to determine if there were more unfavorable outcomes related to drug resistance. These are very difficult studies to perform."

The present retrospective medical record review looked at the effect of Acinetobacter species infection and/or colonization on clinical outcomes of 75 patients at WRAMC to evaluate the association of certain resistance phenotypes, genes, or clonal types with increased morbidity or mortality.

These patients had Acinetobacter species infection and/or colonization of the blood, respiratory tract, skin, urinary tract, meninges, and/or soft tissues. The Mann-Whitney U test and chi-square analyses determined the relationship between selected resistance determinants and clinical outcomes.

Isolates from these patients had been previously evaluated with susceptibility testing, polymerase chain reaction amplification of resistance genes, and 2 molecular typing methods. Of the 75 patient isolates, 73 were A baumannii, 1 was A johnsonii, and 1 was Acinetobacter genome species 3.

The analysis revealed several interesting associations. Recovery of a carbapenem-resistant A baumannii isolate was linked to the need for mechanical ventilation, as was possession of an isolate containing a blaOXA carbapenemase. Carbapenem resistance was associated with the duration of this outbreak, in that patients with longer lengths of stay were more likely to have a carbapenem-resistant Acinetobacter sp. isolate. Finally, the presence of amikacin-resistant A baumannii was linked to hospital-acquired infections.

"From these data, it is clear that the potential impact of A baumannii infections on military and civilian personnel in receiving hospitals is significant," Dr. Bonomo said. "We next asked if patients who had a MDR Ab with a carbapenem resistance phenotype would have a less favorable outcome. Our analysis suggested there might be a link between resistance phenotypes and poor outcomes."

Medscape Infectious Diseases asked Ebbing Lautenbach, MD, MPH, MSCE, an associate professor of medicine and epidemiology and associate hospital epidemiologist at the Hospital of the University of Pennsylvania, Philadelphia, to review this study. Dr. Lautenbach, who was not directly involved in this study, is also a senior scholar at the Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania School of Medicine, Philadelphia.

"The main strengths of this article are the large number of subjects included in the study, the focus on identifying risk factors for poor outcome, and elucidating the role of a resistance phenotype and resistance mechanisms with outcome," Dr. Lautenbach said. "The fact that isolates representing infection and colonization were included together makes teasing out the real impact on outcomes more complicated, in that organisms representing colonization would be unlikely to have a role in conferring a worse outcome."

The association between carbapenem resistance and mechanisms of carbapenem resistance with poor outcomes is important in helping better identify targets for intervention, according to Dr. Lautenbach.

"Such interventions could include optimizing empiric antibiotic therapy as well as efforts to curb further emergence of resistance by modifying important risk factors for resistance," he concluded. "The incidence of Acinetobacter infections has increased markedly in recent years. The fact that these organisms typically infect critically ill patients highlights the urgency of more clearly defining the risk factors for this organism and the impact of this organism on outcomes."

The Veterans Affairs Merit Review and National Institutes of Health supported this study. Dr. Bonomo and Dr. Lautenbach have disclosed no relevant financial relationships.

2008 Annual Conference on Antimicrobial Resistance: Abstract S4. June 23–25, 2008.

    
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