IVIG-mediated protection against necrotizing pneumonia caused by MRSA

被引：71

作者：

Diep, Binh An ^{[1
]}

Le, Vien T. M. ^{[1
]}

Badiou, Cedric ^{[2
,3
]}

Le, Hoan N. ^{[1
]}

Pinheiro, Marcos Gabriel ^{[1
,4
]}

Duong, Au H. ^{[1
]}

Wang, Xing ^{[1
]}

Dip, Etyene Castro ^{[1
]}

Aguiar-Alves, Fabio ^{[1
,4
]}

Basuino, Li ^{[1
]}

Marbach, Helene ^{[1
]}

Mai, Thuy T. ^{[1
]}

Sarda, Marie N. ^{[5
]}

Kajikawa, Osamu ^{[6
]}

Matute-Bello, Gustavo ^{[6
]}

Tkaczyk, Christine ^{[7
]}

Rasigade, Jean-Philippe ^{[2
,3
]}

Sellman, Bret R. ^{[7
]}

Chambers, Henry F. ^{[1
]}

Lina, Gerard ^{[2
,3
]}

机构：

[1] Univ Calif San Francisco, Dept Med, Div HIV Infect Dis & Global Med, San Francisco, CA 94110 USA

[2] Univ Lyon 1, CNRS, ENS Lyon, INSERM U1111,UMR5308, Lyon, France

[3] Hosp Civils Lyon, Ctr Natl Reference Staphylocoques, Bron, France

[4] Univ Fed Fluminense, Pathol Program, Niteroi, RJ, Brazil

[5] Hosp Civils Lyon, Ctr Hosp Lyon Sud, Immunol Lab, Lyon, France

[6] Univ Washington, Sch Med, Dept Med, Div Pulm & Crit Care Med, Seattle, WA 98109 USA

[7] MedImmune LLC, Dept Infect Dis, Gaithersburg, MD 20878 USA

来源：

SCIENCE TRANSLATIONAL MEDICINE | 2016年 / 8卷 / 357期

关键词：

RESISTANT STAPHYLOCOCCUS-AUREUS; PANTON-VALENTINE LEUKOCIDIN; IMMUNOGLOBULIN-G; IMMUNE GLOBULIN; INFECTIONS; GUIDELINES; EMERGENCE; PROTEINS; STRAINS; GENES;

D O I：

10.1126/scitranslmed.aag1153

中图分类号：

Q2 [细胞生物学];

学科分类号：

071013 [干细胞生物学];

摘要：

New therapeutic approaches are urgently needed to improve survival outcomes for patients with necrotizing pneumonia caused by Staphylococcus aureus. One such approach is adjunctive treatment with intravenous immunoglobulin (IVIG), but clinical practice guidelines offer conflicting recommendations. In a preclinical rabbit model, prophylaxis with IVIG conferred protection against necrotizing pneumonia caused by five different epidemic strains of community-associated methicillin-resistant S. aureus (MRSA) as well as a widespread strain of hospital-associated MRSA. Treatment with IVIG, either alone or in combination with vancomycin or linezolid, improved survival outcomes in this rabbit model. Two specific IVIG antibodies that neutralized the toxic effects of a-hemolysin (Hla) and Panton-Valentine leukocidin (PVL) conferred protection against necrotizing pneumonia in the rabbit model. This mechanism of action of IVIG was uncovered by analyzing loss-of-function mutant bacterial strains containing deletions in 17 genes encoding staphylococcal exotoxins, which revealed only Hla and PVL as having an impact on necrotizing pneumonia. These results demonstrate the potential clinical utility of IVIG in the treatment of severe pneumonia induced by S. aureus.

引用

页数：13

共 36 条

[1]

Intravenous immunoglobulin for treating sepsis, severe sepsis and septic shock [J].

Alejandria, Marissa M. ;

Lansang, Mary Ann D. ;

Dans, Leonila F. ;

Mantaring, Jacinto Blas, III .

COCHRANE DATABASE OF SYSTEMATIC REVIEWS, 2013, (09)

[2]

Allelic replacement in Staphylococcus aureus with inducible counter-selection [J].

Bae, T ;

Schneewind, O .

PLASMID, 2006, 55 (01) :58-63

[3]

Barton Michelle, 2006, Can J Infect Dis Med Microbiol, V17 Suppl C, p4C

[4]

HUMAN HYPERIMMUNE GLOBULIN PROTECTS AGAINST THE CYTO-TOXIC ACTION OF STAPHYLOCOCCAL ALPHA-TOXIN INVITRO AND INVIVO [J].

BHAKDI, S ;

MANNHARDT, U ;

MUHLY, M ;

HUGO, F ;

RONNEBERGER, H ;

HUNGERER, KD .

INFECTION AND IMMUNITY, 1989, 57 (10) :3214-3220

[5]

Role of the Accessory Gene Regulator agr in Community-Associated Methicillin-Resistant Staphylococcus aureus Pathogenesis [J].

Cheung, Gordon Y. C. ;

Wang, Rong ;

Khan, Burhan A. ;

Sturdevant, Daniel E. ;

Otto, Michael .

INFECTION AND IMMUNITY, 2011, 79 (05) :1927-1935

[6]

Differences in potency of intravenous polyspecific immunoglobulin G against streptococcal and staphylococcal superantigens:: Implications for therapy of toxic shock syndrome [J].

Darenberg, J ;

Söderquist, B ;

Normark, BH ;

Norrby-Teglund, A .

CLINICAL INFECTIOUS DISEASES, 2004, 38 (06) :836-842

[7]

Intravenous immunoglobulin inhibits staphylococcal toxin-induced human mononuclear phagocyte tumor necrosis factor alpha production [J].

Darville, T ;

Milligan, LB ;

Laffoon, KK .

INFECTION AND IMMUNITY, 1997, 65 (02) :366-372

[8]

Molecular Epidemiology of Methicillin-Resistant Staphylococcus aureus, Rural Southwestern Alaska [J].

David, Michael Z. ;

Rudolph, Karen M. ;

Hennessy, Thomas W. ;

Boyle-Vavra, Susan ;

Daum, Robert S. .

EMERGING INFECTIOUS DISEASES, 2008, 14 (11) :1693-1699

[9]

Roles of 34 virulence genes in the evolution of hospital- and community-associated strains of methicillin-resistant Staphylococcus aureus [J].

Diep, BA ;

Carleton, HA ;

Chang, RF ;

Sensabaugh, GF ;

Perdreau-Remington, F .

JOURNAL OF INFECTIOUS DISEASES, 2006, 193 (11) :1495-1503

[10]

Effects of Linezolid on Suppressing In Vivo Production of Staphylococcal Toxins and Improving Survival Outcomes in a Rabbit Model of Methicillin-Resistant Staphylococcus aureus Necrotizing Pneumonia [J].

Diep, Binh An ;

Afasizheva, Anna ;

Le, Hoan N. ;

Kajikawa, Osamu ;

Matute-Bello, Gustavo ;

Tkaczyk, Christine ;

Sellman, Bret ;

Badiou, Cedric ;

Lina, Gerard ;

Chambers, Henry F. .

JOURNAL OF INFECTIOUS DISEASES, 2013, 208 (01) :75-82

← 1 2 3 4 →