@article{3101106,
    title = "Improving outcomes of severe infections by multidrug-resistant pathogens with polyclonal IgM-enriched immunoglobulins",
    author = "Giamarellos-Bourboulis, E.J. and Tziolos, N. and Routsi, C. and Katsenos, C. and Tsangaris, I. and Pneumatikos, I. and Vlachogiannis, G. and Theodorou, V. and Prekates, A. and Antypa, E. and Koulouras, V. and Kapravelos, N. and Gogos, C. and Antoniadou, E. and Mandragos, K. and Armaganidis, A. and Hellenic Sepsis Study Group",
    journal = "Clinical Microbiology and Infection",
    year = "2016",
    volume = "22",
    number = "6",
    pages = "499-506",
    publisher = "Elsevier B.V.",
    issn = "1198-743X",
    doi = "10.1016/j.cmi.2016.01.021",
    keywords = "immunoglobulin M;  immunoglobulin M;  immunologic factor, adult;  antibiotic resistance;  antibiotic therapy;  Article;  blood clotting disorder;  chronic kidney disease;  chronic obstructive lung disease;  comorbidity;  controlled study;  disease severity;  female;  Gram negative bacterium;  heart failure;  hospital admission;  human;  intensive care unit;  major clinical study;  male;  middle aged;  outcome assessment;  priority journal;  prospective study;  retrospective study;  septic shock;  aged;  clinical trial;  Gram-Negative Bacterial Infections;  Greece;  microbiology;  mortality;  multicenter study;  multidrug resistance;  survival analysis;  treatment outcome;  very elderly, Adult;  Aged;  Aged, 80 and over;  Drug Resistance, Multiple, Bacterial;  Female;  Gram-Negative Bacterial Infections;  Greece;  Humans;  Immunoglobulin M;  Immunologic Factors;  Intensive Care Units;  Male;  Middle Aged;  Prospective Studies;  Retrospective Studies;  Survival Analysis;  Treatment Outcome",
    abstract = "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. © 2016 The Authors"
}