Use of a<i>Staphylococcus aureus</i>Conjugate Vaccine in Patients Receiving Hemodialysis

Shinefield, Henry R.; Black, Steven; Fattom, Ali; Horwith, Gary; Rasgon, Scott; Ordóñez, J.A.; Yeoh, Hock H.; Law, David; Robbins, John B.; Schneerson, Rachel; Muenz, Larry R.; Fuller, Steven A.; Johnson, Joanie; Fireman, Bruce; Alcorn, Harry; Naso, Robert

doi:10.1056/nejmoa011297

Cited by 429 publications

(283 citation statements)

References 22 publications

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“…The majority of S. aureus strains produce microcapsules (10,239,368). Although 11 serotypes of S. aureus have been found, most clinical isolates produce polysaccharide capsule type 5 or 8 (312). The type 5 and 8 capsules are structurally very similar and differ only in the linkages between sugars and in O-acetylation (239).…”

Section: Molecular Mechanisms Of Resistancementioning

confidence: 99%

Reduced Vancomycin Susceptibility inStaphylococcus aureus, Including Vancomycin-Intermediate and Heterogeneous Vancomycin-Intermediate Strains: Resistance Mechanisms, Laboratory Detection, and Clinical Implications

et al. 2010

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SUMMARY The emergence of vancomycin-intermediate Staphylococcus aureus (VISA) and heterogeneous vancomycin-intermediate Staphylococcus aureus (hVISA) over the past decade has provided a challenge to diagnostic microbiologists to detect these strains, clinicians treating patients with infections due to these strains, and researchers attempting to understand the resistance mechanisms. Recent data show that these strains have been detected globally and in many cases are associated with glycopeptide treatment failure; however, more rigorous clinical studies are required to clearly define the contribution of hVISA to glycopeptide treatment outcomes. It is now becoming clear that sequential point mutations in key global regulatory genes contribute to the hVISA and VISA phenotypes, which are associated predominately with cell wall thickening and restricted vancomycin access to its site of activity in the division septum; however, the phenotypic features of these strains can vary because the mutations leading to resistance can vary. Interestingly, changes in the staphylococcal surface and expression of agr are likely to impact host-pathogen interactions in hVISA and VISA infections. Given the subtleties of vancomycin susceptibility testing against S. aureus, it is imperative that diagnostic laboratories use well-standardized methods and have a framework for detecting reduced vancomycin susceptibility in S. aureus.

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Section: Molecular Mechanisms Of Resistancementioning

confidence: 99%

Reduced Vancomycin Susceptibility inStaphylococcus aureus, Including Vancomycin-Intermediate and Heterogeneous Vancomycin-Intermediate Strains: Resistance Mechanisms, Laboratory Detection, and Clinical Implications

et al. 2010

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“…StaphVAX has not been shown to be efficacious in reducing the risk for Staphylococcus aureus bacteremia in hemodialysis patients, although it may confer some benefit during the first 40 wk after administration (50). Although administration of a booster dose of StaphVAX a mean of 958 d after the initial vaccination was shown to increase antibody levels, whether this same response would be observed if the vaccine were administered earlier is unclear (51).…”

Section: Vaccinationmentioning

confidence: 99%

Epidemiology of Acute Infections among Patients with Chronic Kidney Disease

Dalrymple¹,

Go²

2008

Clinical Journal of the American Society of Nephrology

197

183

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The objectives of this review were (1) to review recent literature on the rates, risk factors, and outcomes of infections in patients who had chronic kidney disease (CKD) and did or did not require renal replacement therapy; (2) to review literature on the efficacy and use of selected vaccines for patients with CKD; and (3) to outline a research framework for examining key issues regarding infections in patients with CKD. Infection-related hospitalizations contribute substantially to excess morbidity and mortality in patients with ESRD, and infection is the second leading cause of death in this population. Patients who have CKD and do not require renal replacement therapy seem to be at higher risk for infection compared with patients without CKD; however, data about patients who have CKD and do not require dialysis therapy are very limited. Numerous factors potentially predispose patients with CKD to infection: advanced age, presence of coexisting illnesses, vaccine hyporesponsiveness, immunosuppressive therapy, uremia, dialysis access, and the dialysis procedure. Targeted vaccination seems to have variable efficacy in the setting of CKD and is generally underused in this population. In conclusion, infection is a primary issue when caring for patients who receive maintenance dialysis. Very limited data exist about the rates, risk factors, and outcomes of infection in patients who have CKD and do not require dialysis. Future research is needed to delineate accurately the epidemiology of infections in these populations and to develop effective preventive strategies across the spectrum of CKD severity.

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“…Passive immunization with CP5 or CP8 antibodies has shown protection in rodent models of mastitis, bacteremia, endocarditis, and skin abscesses. 25,[39][40][41] Despite their failure in clinical trials when used alone in hemodialysis patients, 42,43 CP5 and CP8 conjugate vaccines are thought to be important components in a multivalent staphylococcal vaccine. 1,25,38,44 Because diverse S. aureus clinical isolates (both methicillin-sensitive and -resistant) produce surface-associated CP5 or CP8, 14,15,37 we considered that mAbs to CP5 or CP8 with opsonic activity might be included in a mAb cocktail to prevent or reduce staphylococcal bacteremia.…”

Section: Discussionmentioning

confidence: 99%

Antibodies toStaphylococcus aureuscapsular polysaccharides 5 and 8 perform similarlyin vitrobut are functionally distinctin vivo

et al. 2016

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The capsular polysaccharide (CP) produced by Staphylococcus aureus is a virulence factor that allows the organism to evade uptake and killing by host neutrophils. Polyclonal antibodies to the serotype 5 (CP5) and type 8 (CP8) capsular polysaccharides are opsonic and protect mice against experimental bacteremia provoked by encapsulated staphylococci. Thus, passive immunotherapy using CP antibodies has been considered for the prevention or treatment of invasive antibioticresistant S. aureus infections. In this report, we generated monoclonal antibodies (mAbs) against S. aureus CP5 or CP8. Backbone specific mAbs reacted with native and O-deacetylated CPs, whereas Oacetyl specific mAbs reacted only with native CPs. Reference strains of S. aureus and a selection of clinical isolates reacted by colony immunoblot with the CP5 and CP8 mAbs in a serotype-specific manner. The mAbs mediated in vitro CP type-specific opsonophagocytic killing of S. aureus strains, and mice passively immunized with CP5 mAbs were protected against S. aureus bacteremia. Neither CP8-specific mAbs or polyclonal antibodies protected mice against bacteremia provoked by serotype 8 S. aureus clinical isolates, although these same antibodies did protect against a serotype 5 S. aureus strain genetically engineered to produce CP8. We detected soluble CP8 in culture supernatants of serotype 8 clinical isolates and in the plasma of infected animals. Serotype 5 S. aureus released significantly less soluble CP5 in vitro and in vivo. The release of soluble CP8 by S. aureus may contribute to the inability of CP8 vaccines or antibodies to protect against serotype 8 staphylococcal infections.

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Use of aStaphylococcus aureusConjugate Vaccine in Patients Receiving Hemodialysis

Abstract: In patients receiving hemodialysis, a conjugate vaccine can confer partial immunity against S. aureus bacteremia for approximately 40 weeks, after which protection wanes as antibody levels decrease.

Cited by 429 publications

References 22 publications

Reduced Vancomycin Susceptibility inStaphylococcus aureus, Including Vancomycin-Intermediate and Heterogeneous Vancomycin-Intermediate Strains: Resistance Mechanisms, Laboratory Detection, and Clinical Implications

Reduced Vancomycin Susceptibility inStaphylococcus aureus, Including Vancomycin-Intermediate and Heterogeneous Vancomycin-Intermediate Strains: Resistance Mechanisms, Laboratory Detection, and Clinical Implications

Epidemiology of Acute Infections among Patients with Chronic Kidney Disease

Antibodies toStaphylococcus aureuscapsular polysaccharides 5 and 8 perform similarlyin vitrobut are functionally distinctin vivo

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