Article

How Staphylococcus aureus Adapts to Its Host

Columbia University College of Physicians and Surgeons, New York, USA.
New England Journal of Medicine (Impact Factor: 55.87). 05/2011; 364(21):1987-90. DOI: 10.1056/NEJMp1100251
Source: PubMed
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    • "Interestingly, anemia was also more common in the group of women with mastitis, since women suffering from anemia might be more vulnerable to infections. In addition, iron supplements enhance growth and virulence of Staphylococcus aureus and other mastitis-associated species [34]; as a consequence, women receiving them may also be more prone to mastitis. No clinical trials have evaluated the impact of iron supplementation on mastitis but the study of iron acquisition pathways seems to be a good target to define the underlying mechanisms of mastitis severity [35]. "
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    ABSTRACT: Background The purpose of this study was to identify potential predisposing factors associated with human infectious mastitis. Methods We conducted a case–control study among breastfeeding women, with 368 cases (women with mastitis) and 148 controls. Data were collected by a questionnaire designed to obtain retrospective information about several factors related to medical history of mother and infant, different aspects of pregnancy, delivery and postpartum, and breastfeeding practices that could be involved in mastitis. Bivariate analyses and multivariate logistic regression model were used to examine the relationship between mastitis and these factors. Results The variables significantly- and independently-associated with mastitis were cracked nipples (P < 0.0001), oral antibiotics during breastfeeding (P < 0.0001), breast pumps (P < 0.0001), topical antifungal medication during breastfeeding (P = 0.0009), mastitis in previous lactations (P = 0.0014), breast milk coming in later than 24 h postpartum (P = 0.0016), history of mastitis in the family (P = 0.0028), mother-infant separation longer than 24 h (P = 0.0027), cream on nipples (P = 0.0228) and throat infection (P = 0.0224). Conclusions Valuable factors related to an increased risk of infectious mastitis have been identified. This knowledge will allow practitioners to provide appropriate management advice about modifiable risk factors, such as the use of pumps or inappropriate medication. They also could identify before delivery those women at an increased risk of developing mastitis, such as those having a familial history of mastitis, and thus develop strategies to prevent this condition.
    Full-text · Article · Jun 2014 · BMC Pregnancy and Childbirth
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    • "Secondly, it is often quoted that human defects in the ability to make antibodies are not associated with an increased risk of acquiring S. aureus infections [1] [77] [78], yet such defects are associated with higher risk of infections by other Gram positive bacteria such as Streptococcus pneumoniae and Str. pyogenes (group A streptococci). "
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    ABSTRACT: Staphylococcus aureus is a leading cause of both healthcare- and community-associated infections globally. S. aureus exhibits diverse clinical presentations, ranging from benign carriage and superficial skin and soft tissue infections to deep wound and organ/space infections, biofilm-related prosthesis infections, life-threatening bacteremia and sepsis. This broad clinical spectrum, together with the high incidence of these disease manifestations and magnitude of the diverse populations at risk, presents a high unmet medical need and a substantial burden to the healthcare system. With the increasing propensity of S. aureus to develop resistance to essentially all classes of antibiotics, alternative strategies, such as prophylactic vaccination to prevent S. aureus infections, are actively being pursued in healthcare settings. Within the last decade, the S. aureus vaccine field has witnessed two major vaccine failures in phase 3 clinical trials designed to prevent S. aureus infections in either patients undergoing cardiothoracic surgery or patients with end-stage renal disease undergoing hemodialysis. This review summarizes the potential underlying reasons why these two approaches may have failed, and proposes avenues that may provide successful vaccine approaches to prevent S. aureus disease in the future.
    Full-text · Article · Apr 2013 · Vaccine
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    • "We hypothesize that the principle HDPs to which these bacteremic organisms were exposed were platelet derived, resulting in an adaptive enhancement of resistance to tPMP killing. If so, these findings would also suggest that platelet-mediated defenses are critically important in protection against staphylococcal bacteremia [17, 18] . Alternatively, one could speculate that a certain proportion of this bacteremic patient population was initially colonized and infected by a cohort of isolates intrinsically more resistant to tPMP-mediated killing. "
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    ABSTRACT: Background: We hypothesized that, for methicillin-resistant Staphylococcus aureus (MRSA), in vitro daptomycin susceptibility could be influenced by exposures to endogenous host defense peptides (HDPs) prior to clinical exposure to daptomycin. Methods: Two endovascular HDPs were used: thrombin-induced platelet microbicidal protein (tPMP) and human neutrophil defensin-1 (hNP-1) from neutrophils. Forty-seven unique MRSA isolates obtained from bacteremic patients in multicenter prospective clinical trials were studied. Clinical characteristics, microbiologic parameters, prior vancomycin therapy, and susceptibilities to tPMP, hNP-1, and daptomycin were compared using univariate and multivariate analyses. Results: All strains were daptomycin susceptible. Daptomycin minimum inhibitory concentrations (MICs) were inversely related to in vitro tPMP (but not hNP-1) killing. Strains with a daptomycin MIC of 1 mg/L exhibited significantly less killing by tPMP, compared with strains with an MIC of ≤ 0.5 mg/L. Prior vancomycin therapy did not influence this relationship. Regression tree modeling confirmed that reduced tPMP-induced killing in vitro was the strongest predictor of higher daptomycin MICs within the daptomycin-susceptible range. Conclusions: Among daptomycin-susceptible MRSA isolates from patients who had never received daptomycin, higher daptomycin MICs tracked with increased resistance to killing by platelet-derived but not neutrophil-derived HDPs. These findings support the notion that endogenous exposure of MRSA to specific HDPs may play a role in selecting strains with an intrinsically higher daptomycin MIC phenotype.
    Preview · Article · Aug 2012 · The Journal of Infectious Diseases
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