4th Department of Internal Medicine, National and Kapodistrian University of Athens, Medical School, Greece.
4th Department of Internal Medicine, National and Kapodistrian University of Athens, Medical School, Greece.
Clin Microbiol Infect. 2016 Jun;22(6):499-506. doi: 10.1016/j.cmi.2016.01.021. Epub 2016 Feb 3.
The emergence of infections by multidrug-resistant (MDR) Gram-negative bacteria, which is accompanied by considerable mortality due to inappropriate therapy, led to the investigation of whether adjunctive treatment with one polyclonal IgM-enriched immunoglobulin preparation (IgGAM) would improve outcomes. One hundred patients in Greece with microbiologically confirmed severe infections by MDR Gram-negative bacteria acquired after admission to the Intensive Care Unit and treated with IgGAM were retrospectively analysed from a large prospective multicentre cohort. A similar number of patient comparators well-matched for stage of sepsis, source of infection, appropriateness of antimicrobials and co-morbidities coming from the same cohort were selected. All-cause 28-day mortality was the primary end point; mortality by extensively drug-resistant (XDR) pathogens and time to breakthrough bacteraemia were the secondary end points. Fifty-eight of the comparators and 39 of the IgGAM-treated cases died by day 28 (p 0.011). The OR for death under IgGAM treatment was 0.46 (95% CI 0.26-0.85). Stepwise regression analysis revealed that IgGAM was associated with favourable outcome whereas acute coagulopathy, cardiovascular failure, chronic obstructive pulmonary disease and chronic renal disease were associated with unfavourable outcome. Thirty-nine of 62 comparators (62.9%) were infected by XDR Gram-negative bacteria and died by day 28 compared with 25 of 65 cases treated with IgGAM (38.5%) (p 0.008). Median times to breakthrough bacteraemia were 4 days and 10 days, respectively (p <0.0001). Results favour the use of IgGAM as an adjunct to antimicrobial treatment for the management of septic shock caused by MDR Gram-negative bacteria. A prospective randomized trial is warranted.
多药耐药（MDR）革兰氏阴性菌感染的出现伴随着因治疗不当导致的高死亡率，这促使人们研究是否辅助使用一种多克隆 IgM 浓缩免疫球蛋白制剂（IgGAM）可以改善治疗效果。从一个大型前瞻性多中心队列中，回顾性分析了希腊 100 例在重症监护病房（ICU）获得性、经微生物学证实的 MDR 革兰氏阴性菌严重感染患者，这些患者接受了 IgGAM 治疗。从同一队列中选择了数量相同的患者对照，这些对照患者在脓毒症分期、感染源、抗菌药物的适当性和合并症方面具有可比性。全因 28 天死亡率是主要终点；广泛耐药（XDR）病原体死亡率和突破菌血症时间是次要终点。28 天内，58 名对照患者和 39 名 IgGAM 治疗病例死亡（p 0.011）。IgGAM 治疗下死亡的 OR 为 0.46（95%CI 0.26-0.85）。逐步回归分析显示，IgGAM 与良好的结果相关，而急性凝血功能障碍、心血管衰竭、慢性阻塞性肺疾病和慢性肾脏疾病与不良结果相关。62 名对照患者中有 39 名（62.9%）感染了 XDR 革兰氏阴性菌，在 28 天内死亡，而 65 例接受 IgGAM 治疗的患者中有 25 例（38.5%）死亡（p 0.008）。突破菌血症的中位时间分别为 4 天和 10 天（p<0.0001）。结果支持将 IgGAM 用作治疗 MDR 革兰氏阴性菌引起的败血症性休克的辅助治疗药物。需要进行前瞻性随机试验。
