SIS年会：多重耐药及抗生素合理性与感染不动杆菌的危重患者的死亡率无关

达拉斯(EGMN)——美国外科感染学会(SIS)年会上公布的一项回顾性分析显示，多重耐药及抗生素合理性与感染不动杆菌的危重患者的死亡率无关。

这项分析由俄亥俄州立大学哥伦布分校的Claire Murphy博士及其同事进行，分析的对象是2006年1月~2009年12月间收治的156例外科和内科ICU患者。这些患者至少有1次不动杆菌培养阳性并具有相关临床症状。院内死亡率为35%。死亡患者的APACHE II(急性生理学和长期健康评估II)评分显著高于存活患者(22.3 vs. 19.5；P=0.02)，并且多为外科患者(50% vs. 33.3%；P=0.04)及处于免疫抑制状态(33.3% vs. 16.7%；P=0.02)。

存活患者的年龄明显较小(53岁vs. 59岁；P=0.006)，并且既往定植或感染耐甲氧西林金黄色葡萄球菌的比例较高(4% vs. 2%；P=0.04)。在所有患者中，不动杆菌感染最常见于肺部。存活患者的肺部感染发生率较高(82.5% vs. 67%；P=0.02)，而非存活患者的不动杆菌菌血症(包括继发性和导管相关菌血症)发生率较高(43% vs. 8%；P＜0.001)。

存活患者和非存活患者的多重耐药率相似，分别为64%和70.4%，但非存活患者对头孢吡肟(Maxipime)、亚胺培南(Primaxin IV/Primaxin IM)和替加环素(Tygacil)的耐药性略呈增加趋势。非存活患者和存活患者的合理经验抗生素治疗率无明显差异，分别为18.5%和28.4%，但存活患者中有较大比例使用广谱碳青霉烯类作为经验治疗(33% vs. 17%；P=0.02)。非存活患者的ICU驻留时间、住院时间和机械通气时间也与存活患者相似。

校正潜在混杂因素的多因素分析显示，死亡的独立预测因素为脓毒症[比值比(OR)=14.1；P＜0.001]、免疫抑制(OR=2.76；P=0.04)和疾病严重程度较高(通过APACHE II评分评价)(OR=1.1；P=0.002)。使用碳青霉烯类抗生素亚胺培南作为导向治疗具有保护作用(OR=0.29；P=0.012)。

特邀评论专家——迈阿密大学健康系统的外科教授Nicholas Namias博士询问，碳青霉烯类的使用是否是以分离株易感模式为导向，以及如果使用粘菌素等抗生素是否可取得更好的效果。Murphy博士回答，碳青霉烯类的选择确实是以易感模式为导向。此外，Murphy博士指出，临床医生倾向于使用碳青霉烯类，因为碳青霉烯类的效果可能优于粘菌素，特别是对于复杂病例，如肥胖患者或接受肾脏替代治疗的患者。

Namias博士还询问，经验治疗是如何选择的，以及如果该分析仅纳入碳青霉烯类耐药患者的话，会得出什么结果。Murphy博士回应称，其所在医院每年都对ICU的抗菌谱进行分析，以此确定标准经验治疗。Murphy博士表示，对于具有不动杆菌感染风险的ICU患者，应考虑使用碳青霉烯类进行经验治疗。该研究中半数以上的患者对碳青霉烯类耐药。Murphy博士认为，对于碳青霉烯类耐药患者，使用碳青霉烯类进行治疗仍可取得较好效果，因为体外数据显示碳青霉烯类与粘菌素、替加环素和阿米卡星等其他抗生素之间有协同作用。

研究者声明无相关经济利益冲突。

DALLAS (EGMN) – In a surprising twist, multidrug resistance and antibiotic appropriateness were not correlated with mortality in a retrospective analysis of critically ill patients infected with Acinetobacter bacillus.

Acinetobacter infections among critically ill patients are increasing and have been associated with mortality rates of 26%-68%. The mortality rates are thought to be driven by high rates of multidrug resistance and subsequent delays in appropriate antimicrobial therapy, Claire Murphy, Pharm.D., explained at the annual meeting of the Surgical Infection Society.

She presented data on 156 surgical and medical ICU patients with at least one positive Acinetobacter culture and associated clinical symptoms who were admitted to an ICU between January 2006 and December 2009. In-hospital mortality was 35%.

Patients who died had significantly higher APACHE II (Acute Physiology and Chronic Health Evaluation II) II scores than did survivors (22.3 vs. 19.5; P = .02), and were more likely to be surgical patients (50% vs. 33.3%; P = .04) and to be in an immunosuppressed state (33.3% vs. 16.7%; P = .02).

Survivors were significantly younger (53 years vs. 59 years; P = .006), and – inexplicably – more likely to have prior colonization or infection with methicillin-resistant Staphylococcus aureus (4% vs. 2%; P = .04), said Dr. Murphy of the department of surgery at the Ohio State University, Columbus.

Respiratory infections were the most common source of Acinetobacter for all patients. Survivors were more likely to have respiratory sources of infection (82.5% vs. 67%; P = .02), whereas nonsurvivors had a higher incidence of Acinetobacter bacteremia, including both secondary and catheter-related bacteremias (43% vs. 8%; P less than .001).

Multidrug resistance rates were similar among survivors and nonsurvivors at 64% and 70.4%, respectively, although there was a slight trend toward increased resistance among nonsurvivors for cefepime (Maxipime), impinem (Primaxin IV/Primaxin IM), and tigecycline (Tygacil), she said.

Rates of appropriate empirical antibiotic coverage were not significantly different, at 18.5% among nonsurvivors and 28.4% among survivors, although survivors were more likely to receive a broad-spectrum carbapenem as empirical therapy (33% vs. 17%; P = .02).

ICU stay, hospital length of stay, and duration of mechanical ventilation were also similar.

In a multivariate analysis that was adjusted for potential confounders, the independent predictors of mortality were bacteremia (odds ratio, 14.1; P less than .001), immunosuppression (OR, 2.76; P = .04), and higher severity of illness by APACHE II score (OR, 1.1; P = .002).

The use of the carbapenem antibiotic imipenem as directed therapy was protective (OR, 0.29; P = .012).

“A carbapenem should be considered for [empirical] therapy in ICU patients at risk for Acinetobacter infection,” Dr. Murphy said.

Invited discussant Dr. Nicholas Namias, chief of trauma and professor of surgery at the University of Miami Health System, observed that the 35% mortality rate was disturbingly high, but not unexpected. He asked whether the use of carbapenems was forced, in a sense, by the susceptibility pattern of the isolate, and whether patients might have done better if they had been given an antibiotic like colistin.

Dr. Murphy agreed that the choice of carbapenem was directed by susceptibility patterns, and remarked that clinicians tend to lean toward a carbapenem because they’re more comfortable administering and dosing a carbapenem (particularly in complex cases, such as obese patients or those on renal replacement therapy) than colistin.

Dr. Namias also asked how empirical therapy is selected, and how the results might look if only carbapenem-resistant patients were included in the analysis. Dr. Murphy replied that the hospital does not have a fixed rotation, but reviews its ICU-specific antibiograms on an annual basis to determine its standard empirical therapy.

The investigators plan to study outcomes in carbapenem-resistant patients, said Dr. Murphy, but she pointed out that more than half of the patients in the current study were carbapenem resistant. She suggested that a carbapenem may still be beneficial in this setting because there are in vitro data showing synergy between carbapenems and other antibiotics, including colistin, tigecycline, and amikacin. Extended infusions of impinem were not used during the study period, although the hospital recently began using 4-hour infusions of doripenem (Doribax).

The authors reported no relevant conflicts of interest.