Revisiting Bacterial Interference in the Age of Methicillin-resistant Staphylococcus aureus: Insights Into Staphylococcus aureus Carriage, Pathogenicity and Potential Control.

Bacteria compete with each other for local supremacy in biologic and environmental niches. In humans, who host an array of commensal bacteria, the presence of one species or strain can sometimes prevent colonization by another, a phenomenon known as "bacterial interference." We describe how, in the 1960s, infants (and later adults) were actively inoculated with a relatively benign strain of Staphylococcus aureus, 502A, to prevent colonization with an epidemic S. aureus strain, 80/81. This introduced bacterial interference as a clinical approach to disease prevention, but little was known about the mechanisms of interference at that time. Since then, much has been learned about how bacteria interact with each other and the host to establish carriage, compete for niches and shift from harmless commensal to invasive pathogen. We provide an overview of these findings and summarize recent studies in which the genome and function of 502A were compared with those of the current epidemic strain, USA300, providing insight into differences in their invasiveness and immunogenicity. Although staphylococcal vaccines have been developed, none has yet been approved for clinical use. Further studies of staphylococcal strains and the molecular characteristics that lead to exclusion of specific bacteria from some niches may provide an alternative path to disease prevention.

Ambulatory heart rate range predicts mode-specific mortality and hospitalisation in chronic heart failure.

OBJECTIVE: We aimed to define the prognostic value of the heart rate range during a 24 h period in patients with chronic heart failure (CHF). METHODS: Prospective observational cohort study of 791 patients with CHF associated with left ventricular systolic dysfunction. Mode-specific mortality and hospitalisation were linked with ambulatory heart rate range (AHRR; calculated as maximum minus minimum heart rate using 24 h Holter monitor data, including paced and non-sinus complexes) in univariate and multivariate analyses. Findings were then corroborated in a validation cohort of 408 patients with CHF with preserved or reduced left ventricular ejection fraction. RESULTS: After a mean 4.1 years of follow-up, increasing AHRR was associated with reduced risk of all-cause, sudden, non-cardiovascular and progressive heart failure death in univariate analyses. After accounting for characteristics that differed between groups above and below median AHRR using multivariate analysis, AHRR remained strongly associated with all-cause mortality (HR 0.991/bpm increase in AHRR (95% CI 0.999 to 0.982); p=0.046). AHRR was not associated with the risk of any non-elective hospitalisation, but was associated with heart-failure-related hospitalisation. AHRR was modestly associated with the SD of normal-to-normal beats (R(2)=0.2; p<0.001) and with peak exercise-test heart rate (R(2)=0.33; p<0.001). Analysis of the validation cohort revealed AHRR to be associated with all-cause and mode-specific death as described in the derivation cohort. CONCLUSIONS: AHRR is a novel and readily available prognosticator in patients with CHF, which may reflect autonomic tone and exercise capacity.

Staphylococcal infections: a historical perspective.

Staphylococcus aureus is an unusually successful and adaptive human pathogen that can cause epidemics of invasive disease despite its frequent carriage as a commensal. Over the past 100 years and more, S aureus has caused cycles of outbreaks in hospitals and the community and has developed resistance to every antibiotic used against it, yet the exact mechanisms leading to epidemics of virulent disease are not fully understood. Approaches such as bacterial interference have been effective in interrupting outbreaks, but to better prevent staphylococcal disease, we will need to be vigilant about environmental factors that facilitate its spread. Even more importantly, we need to understand more about the mechanisms that lead to its virulence and transmission. With such information, it may be possible to develop a vaccine that will prevent endemic and epidemic staphylococcal disease.