title: Improving outcomes of severe infections by multidrug-resistant pathogens with polyclonal IgM-enriched immunoglobulins.
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.
authors: 4th Department of Internal Medicine, National and Kapodistrian University of Athens, Medical School, Greece. Electronic address: egiamarel@med.uoa.gr.
authors: E J
authors: EJ
authors: Giamarellos-Bourboulis
authors: 4th Department of Internal Medicine, National and Kapodistrian University of Athens, Medical School, Greece.
authors: N
authors: N
authors: Tziolos
authors: 1st Department of Critical Care Medicine, National and Kapodistrian University of Athens, Medical School, Greece.
authors: C
authors: C
authors: Routsi
authors: Intensive Care Unit, "Korgialeneion-Benakeion" General Hospital of Athens, Greece.
authors: C
authors: C
authors: Katsenos
authors: 2nd Department of Critical Care Medicine, National and Kapodistrian University of Athens, Medical School, Greece.
authors: I
authors: I
authors: Tsangaris
authors: Department of Critical Care Medicine, University of Thrace, Medical School, Greece.
authors: I
authors: I
authors: Pneumatikos
authors: Intensive Care Unit, "Aghios Dimitrios" General Hospital of Thessaloniki, Greece.
authors: G
authors: G
authors: Vlachogiannis
authors: Department of Critical Care Medicine, University of Thrace, Medical School, Greece.
authors: V
authors: V
authors: Theodorou
authors: Intensive Care Unit, Tzaneion General Hospital of Piraeus, Greece.
authors: A
authors: A
authors: Prekates
authors: Intensive Care Unit, "G.Gennimatas" General Hospital of Thessaloniki, Greece.
authors: E
authors: E
authors: Antypa
authors: Department of Critical Care Medicine, University of Ioannina, Medical School, Greece.
authors: V
authors: V
authors: Koulouras
authors: Intensive Care Unit, "G.Papanikolaou" General Hospital of Thessaloniki, Greece.
authors: N
authors: N
authors: Kapravelos
authors: Department of Internal Medicine, University of Patras, Medical School, Greece.
authors: C
authors: C
authors: Gogos
authors: Intensive Care Unit, "G.Gennimatas" General Hospital of Thessaloniki, Greece.
authors: E
authors: E
authors: Antoniadou
authors: Intensive Care Unit, "Korgialeneion-Benakeion" General Hospital of Athens, Greece.
authors: K
authors: K
authors: Mandragos
authors: 2nd Department of Critical Care Medicine, National and Kapodistrian University of Athens, Medical School, Greece.
authors: A
authors: A
authors: Armaganidis
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D024901:Drug Resistance, Multiple, Bacterial; D005260:Female; D016905:Gram-Negative Bacterial Infections / Q000188:drug therapy* / Q000382:microbiology / Q000401:mortality; D006115:Greece; D006801:Humans; D007075:Immunoglobulin M / Q000008:administration & dosage*; D007155:Immunologic Factors / Q000008:administration & dosage*; D007362:Intensive Care Units; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012189:Retrospective Studies; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D007075:Immunoglobulin M; D007155:Immunologic Factors
keywords: Antimicrobial resistance; IgM immunoglobulin; bacteraemia; mortality; septic shock