Staphylococcus aureus Vaccines

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Attempts to reduce Staphylococcus aureus disease through vaccination date back to at least 1902, but this pathogen may be unrivaled among others in the sheer scale and scope of unsuccessful vaccine attempts. These challenges have inevitably led many to wonder whether a vaccine against Staphylococcus aureus is an attainable goal. This chapter will discuss the clinical importance of this major bacterial pathogen, the urgent need for a safe and effective staphylococcal vaccine, the barriers (thus far insurmountable) that have defined the S. aureus vaccine landscape over the past ∼120 years, and some potential paths forward in this important endeavor.

HISTORICAL PERSPECTIVE

Staphylococcus aureus was one of the first infectious organisms to be identified and characterized, a fact that is unsurprising when considering its fitness as a pathogen and its myriad clinical manifestations. Many scholars credit Alexander Ogston for the first isolation of S. aureus from a surgical wound infection and note that the organism was able to produce an abscess when injected into guinea pigs and mice. Reports of the work of Louis Pasteur with staphylococci in 1880 confirmed that he also produced abscesses in animals injected with pus from human staphylococcal infections. Ogston coined the term Staphylococcus for the genus in 1882. In 1884, Rosenbach divided the genus into the species aureus and albus. These designations remained until 1939 when Cowan differentiated S. epidermidis as a separate species based upon coagulase testing (slide agglutination), and this was further defined with serological testing in 1954. The Baird-Parker identification scheme of staphylococci and micrococci was accepted in 1965 and remained the standard until 1975 when Kloos and Sheffler offered a simplified scheme for the identification of Staphylococcus . Our current system for identifying staphylococci was adopted in 1999.

CLINICAL MANIFESTATIONS

The diversity and variability of clinical syndromes caused by S. aureus is a hallmark of this highly virulent pathogen. In children, S. aureus is recognized as the leading cause of bloodstream infection, both community-associated and in hospitalized children; musculoskeletal infections such as osteomyelitis, septic arthritis, and myositis; surgical site infection; cutaneous abscesses and furunculosis; spinal epidural abscess; cervical adenitis, bacterial parotitis; endocarditis; bacterial pericarditis; septic thrombophlebitis; necrotizing pneumonia; and complicated pneumonia with empyema. Many of these infections occur in otherwise healthy children with no clearly identifiable risk factors for an invasive infection. Further, S. aureus is among the leading causes of other clinical syndromes not mentioned above and is clearly capable of infecting any human tissue despite the presence of an ostensibly intact host response.

Adult patients are similarly afflicted by a wide variety of S. aureus clinical phenotypes, though risk factors for invasive disease are more often (though not always) present. Superficial/noninvasive S. aureus infections are particularly common even in previously healthy persons, especially in people playing contact sports and injecting drugs. Infections of the skin range from impetigo to abscess formation, cellulitis, or lymphadenitis, adjacent to an infectious focus. S. aureus also may cause several important ocular infections, including conjunctivitis, preseptal cellulitis, and endophthalmitis.

S. aureus is an important cause of endocarditis, being the leading cause in many regions of the world. The infected heart valves may have been previously normal, especially when the mitral or aortic valves are involved, and the clinical manifestations may be particularly severe. Pericarditis may be an isolated syndrome or may accompany endocarditis. Rates of S. aureus endocarditis have risen significantly over the past two decades, driven in part by the opioid epidemic in the United States. ^,

S. aureus is a major cause of respiratory tract infections, including retropharyngeal abscess and pneumonia. The latter may be a severe, necrotizing process with high mortality that often occurs several days into an acute influenza infection. Central nervous system infections are infrequent and usually involve an assisted portal of entry for the organism, such as extension from an infected sinus, a dermal sinus, or a meningomyelocele. Central nervous system infectious syndromes also include subdural and epidural empyema (including spinal epidural abscess) and, occasionally, meningitis.

S. aureus is also the cause of a number of toxin-mediated illnesses with clinical manifestations that reflect the effects of one or more secreted toxins. Examples include toxic shock syndrome (TSS), staphylococcal scalded skin syndrome, and food-borne gastroenteritis. Many staphylococcal toxins are also capable of acting as superantigens and contribute to severe sepsis syndromes with high associated morbidity and mortality, including purpura fulminans and the Waterhouse–Friderichsen syndrome.

S. aureus frequently complicates surgical procedures in which the integument is breached and indwelling foreign bodies are left in place. The insertion of plastic, metal, or Gore-Tex devices provides an opportunity for S. aureus to adhere, causing persistent infection. Success in eradicating the organisms from the inserted device often poses major challenges, even when the isolate is susceptible to the antibiotic used. Thus, certain patients, such as those needing hemodialysis, those with indwelling venous catheterization, indwelling intravascular Gore-Tex patches, artificial prostheses, or cerebrospinal fluid flow diversionary devices, are at high risk for S. aureus infections. Patients with impaired neutrophilic host response (including the neonatal population in general) and defective T-cell activation of the phagocyte host response are also a high risk of acquiring S. aureus disease