Neonatal Host Defense against Staphylococcal Infections

Coombs, Melanie R. Power; Kronforst, Kenny; Levy, Ofer

doi:10.1155/2013/826303

Cited by 30 publications

(25 citation statements)

References 105 publications

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“…Toxins may contribute to MRSA persistence in the host, relapse of infections, tissue damage, and the production of proinflammatory cytokines [47, 51, 52]. The neonatal immune response to MRSA has not been elucidated so far [53]. Some data suggest that neonates are prone to developing hyperinflammation during staphylococcal infections [54, 55].…”

Section: Toxinsmentioning

confidence: 99%

New Threats from an Old Foe: Methicillin-Resistant Staphylococcus aureus Infections in Neonates

2018

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Methicillin-resistant Staphylococcus aureus (MRSA) is a ubiquitous human inhabitant and one of the important pathogens of neonatal infections. MRSA is associated with significant mortality and morbidity, especially in very immature preterm neonates. Moreover, MRSA may be implicated in adverse long-term neonatal outcomes, posing a substantial disease burden. Recent advances in molecular microbiology have shed light on the evolution of MRSA population structure and virulence factors, which may contribute to MRSA epidemic waves worldwide. Equipped with remarkable genetic flexibility, MRSA has successfully developed resistance to an extensive range of antibiotics including vancomycin, as well as antiseptics. In the face of these new challenges from MRSA, our armamentarium of anti-infective strategies is very limited and largely dependent on prevention measures. Active surveillance cultures followed by decolonization may be a promising approach to control MRSA infections, with its efficacy and safety in the specific population of neonates yet to be addressed by large multicenter studies.

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Section: Toxinsmentioning

confidence: 99%

New Threats from an Old Foe: Methicillin-Resistant Staphylococcus aureus Infections in Neonates

2018

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“…Coagulasenegative staphylococci such as S. epidermidis are the most common causes of bacteremia in preterm infants, especially those of low gestational age [12,13]. Staphylococcus epidermidis is a ubiquitous skin commensal responsible for approximately 50% of all cases of late-onset neonatal septicemia [14].…”

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confidence: 99%

Staphylococcus epidermidisBacteremia Induces Brain Injury in Neonatal Mice via Toll-like Receptor 2-Dependent and -Independent Pathways

Bi¹,

Qiao²,

Bergelson³

et al. 2015

J Infect Dis.

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Background. Staphylococcus epidermidis causes late-onset sepsis in preterm infants. Staphylococcus epidermidis activates host responses in part via Toll-like receptor 2 (TLR2). Epidemiologic studies link bacteremia and neonatal brain injury, but direct evidence is lacking.Methods. Wild-type and TLR2-deficient (TLR2−/−) mice were injected intravenously with S. epidermidis at postnatal day 1 prior to measuring plasma and brain cytokine and chemokine levels, bacterial clearance, brain caspase-3 activation, white/gray matter volume, and innate transcriptome.Results. Staphylococcus epidermidis bacteremia spontaneously resolved over 24 hours without detectable bacteria in the cerebrospinal fluid (CSF). TLR2−/− mice demonstrated delayed S. epidermidis clearance from blood, spleen, and liver. Staphylococcus epidermidis increased the white blood cell count in the CSF, increased interleukin 6, interleukin 12p40, CCL2, and CXCL1 concentrations in plasma; increased the CCL2 concentration in the brain; and caused rapid (within 6 hours) TLR2-dependent brain activation of caspase-3 and TLR2-independent white matter injury.Conclusions. Staphylococcus epidermidis bacteremia, in the absence of bacterial entry into the CSF, impairs neonatal brain development. Staphylococcus epidermidis bacteremia induced both TLR2-dependent and -independent brain injury, with the latter occurring in the absence of TLR2, a condition associated with an increased bacterial burden. Our study indicates that the consequences of transient bacteremia in early life may be more severe than commonly appreciated, and our findings may inform novel approaches to reduce bacteremia-associated brain injury.

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“…A study of human neonates showed impaired Th1 polarization in response to infection by Staphylococcus species [27], thought to result from programming by the maternal immune system in utero as a safeguard against catastrophic immune reactions, specifically by means of increased prevalence of Treg [28]. Maternal antibodies transferred through the placenta or in milk also interfere with effective vaccination, as these circulating antibodies can reduce the availability of antigen to the neonate’s own immune cells [17], and the neonatal Fc receptor increases the serum half-life of passively transferred antibodies [29].…”

Section: Neonatal Immunitymentioning

confidence: 99%

Neonatal Vaccination: Challenges and Intervention Strategies

Morris

Surendran²

2016

Neonatology

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Background: While vaccines have been tremendously successful in reducing the incidence of serious infectious diseases, newborns remain particularly vulnerable in the first few months of their life to life-threatening infections. A number of challenges exist to neonatal vaccination. However, recent advances in the understanding of neonatal immunology offer insights to overcome many of those challenges. Objective: This review will present an overview of the features of neonatal immunity which make vaccination difficult, survey the mechanisms of action of available vaccine adjuvants with respect to the unique features of neonatal immunity, and propose a possible mechanism contributing to the inability of neonates to generate protective immune responses to vaccines. Methods: We surveyed recent published findings on the challenges to neonatal vaccination and possible intervention strategies including the use of novel vaccine adjuvants to develop efficacious neonatal vaccines. Results: Challenges in the vaccination of neonates include interference from maternal antibody and excessive skewing towards Th2 immunity, which can be counteracted by the use of proper adjuvants. Conclusion: Synergistic stimulation of multiple Toll-like receptors by incorporating well-defined agonist-adjuvant combinations to vaccines is a promising strategy to ensure a protective vaccine response in neonates.

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Neonatal Host Defense against Staphylococcal Infections

Cited by 30 publications

References 105 publications

New Threats from an Old Foe: Methicillin-Resistant <b><i>Staphylococcus aureus</i></b> Infections in Neonates

New Threats from an Old Foe: Methicillin-Resistant <b><i>Staphylococcus aureus</i></b> Infections in Neonates

Staphylococcus epidermidisBacteremia Induces Brain Injury in Neonatal Mice via Toll-like Receptor 2-Dependent and -Independent Pathways

Neonatal Vaccination: Challenges and Intervention Strategies

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