The genus streptococcus is comprised of many species of Gram positive cocci arranged in chains. They are distinguished from the other major genus of Gram-positive cocci – Staphylococcus by their cellular arrangement and their inability to produce the enzyme catalase.
The starting point is hemolytic reactions on sheep’s blood agar:
These organisms are further divided into serologic subgroups called Lancefield groups designated by capital letters A, B, C etc. The two most important types of beta-hemolytic streptococci, by far, are Group A beta-hemolytic streptococcus (GAS) or Streptococcus pyogenes and Group B beta-hemolytic streptococcus (GBS) or Streptococcus agalactiae. Infections similar to those caused by GAS are occasionally caused by Group C and G beta-hemolytic streptococci.
Most of these species are referred to as a group – viridans streptococci. They are also sometimes referred to as “green strep” owing to the color of blood agar surrounding the colonies. Many different species comprise the viridans streptococci. Notable examples include Streptococcus mitis, S. mitior, and S. sanguis. However clinical microbiology laboratories generally do not have the ability (or the interest) to differentiate one species from the other. They are almost all normal inhabitants of the oropharynx.
The most important non-hemolytic streptococci are now not in the genus Streptococcus at all. They have been separated into the genus Enterococcus and have gained importance as pathogens in recent years. The former Streptococcus faecalis and Streptococcus faecium are now Enterococcus faecalis and Enterococcus faecium the two most important species of the genus and are also referred to as “Group D enterococci” a fact I mention only because older literature uses various names for these normal inhabitants of the human bowel.
Group A beta-hemolytic Streptococcus (GAS or Streptococcus pyogenes)
This organism is one of the most important human pathogens and is responsible for a wide variety of clinical manifestations. The only reservoir is human beings and it may be found in a proportion of the oropharynges of healthy individuals referred to as carriers. The main source of dissemination is symptomatically infected pharyngitis patients.
Several cell structures deserve mentioning as they help to explain pathogenesis:
Group specific carbohydrate is an integral part of the cell wall and is the moiety that is detected in Lancefield serotyping of beta-hemolytic Streptococci.
M Protein is exposed on the surface of the cell and is antigenic i.e. it stimulates a specific immunologic response that is protective. However, there are approximately 80 distinct M types and because immunity is type specific, repeat infections with different serotypes occur. It is anti-phagocytic for the organism and, hence, is an important virulence factor. Strains without M protein are not pathogenic.
Systemic Pyrogenic Exotoxins (SPEs) are produced by some strains and are responsible for the rash of scarlet fever. They have gained in importance recently as they appear to be involved in the pathogenesis of Streptococcal Toxic shock – like syndrome or “Toxic Strep Syndrome” and Severe Invasive GAS disease (necrotizing fasciitis or “flesh eating disease”).
Pharyngitis and Scarlet Fever
GAS is the only bacterium that causes significant pharyngitis in immunocompetent individuals. It is a relatively infrequent cause accounting for approximately 10% of sore throats assessed in a physicians office, the majority of cases being viral in origin. Diagnostic microbiology laboratories restrict the processing of throat cultures to determining if GAS is present or not. This is generally a fairly mild self limiting illness, though local complications can occur e.g. peritonsillar abscess or “quinsy”. However, it is the association of GAS pharyngitis with Rheumatic Fever that has made this illness far more important than it otherwise would be as discussed below. This is mainly a disease of 5-15 year olds but sporadically occurs at other ages.
Scarlet fever is said to occur when GAS infection is accompanied by a, very characteristic, diffuse exanthem and enanthem. The rash is a generalized, fine raised red rash, prominent on the face and trunk and, late in its course, is said to feel like sandpaper. Accentuation in the skin creases especially in the axillae, anticubital fossae and groin produce linear “Pastia’s lines” in some. Systemic pyrogenic exotoxins are responsible and disease is generally no more severe than GAS pharyngitis unaccompanied by Scarlet Fever rash. However, in earlier times Scarlet Fever was a feared complication associated with severe systemic features perhaps not unlike “Toxic Strep Syndrome” (see below) that was the cause of the untimely demise of Jim Henson of Muppet fame.
Cellulitis and Erysipelas and Impetigo
Infection of skin that does not localize and produce pus but spreads “horizontally” within the skin itself is referred to as cellulitis. Commonly affecting the lower legs, especially in persons with chronically edematous extremities, it can occur on any part of the skin and is often associated with severe systemic toxicity. Redness, swelling, pain and tenderness are the main findings and lymphatic spread of organisms may result in lymphangitic streaking, a phenomenon commonly referred to by the layman as “blood poisoning”.
An infection of mainly the epidermis with significant lymphatic involvement, erysipelas is distinguished from cellulitis by its sharply demarcated, slightly raised borders. Classically, it occurs on the face in a “butterfly” distribution. The distinction between the two may be difficult and is clinically moot as investigation and therapy are the same.
Impetigo is a benign but unsightly condition commonly affecting the face of children that manifests as honey-colored crusts of exudate on an erythematous base. It generally responds to topical antibiotic therapy.
Severe Invasive Group A Streptococcal Disease and “Toxic Strep Syndrome”
Since about 1987 there has been an increase of severe GAS infections that are often rapidly progressive and have a high rate of mortality. The British tabloid press coined the term “flesh eating disease” and this designation is now common in the lay press. Early reports linked this resurgence in disease to specific M types (esp. M1) with the ability to produce Systemic Pyrogenic Exotoxin A (SPE-A). Strains with these characteristics had not been seen for many years. There were fears that a clone of GAS with increased virulence had re-emerged, was spreading and this was responsible for the change in epidemiology. However, as with most infectious diseases, the circumstance seems considerably more complicated and organisms of many M types producing all three types of SPEs have now been implicated. Fortunately, cases have remained rare (incidence of approx. 1 / 100,000 / year) and sporadic though transmission of bacteria with secondary cases has been described. Clinically, patients present with pain and systemic complaints disproportionate to their soft tissue infection. They progress rapidly to shock and death without interventions in the form of aggressive surgical debridement and antibiotics.
Post Streptococcal “Non Suppurative” Diseases
Though now very rare in industrialized countries, Rheumatic Fever is still a feared complication of GAS pharyngitis. Approximately two weeks after infection patients develop an acute inflammatory state with heart, joints, subcutaneous tissues and CNS bearing the brunt of the assault. The effects of carditis with deformity of heart valves makes up the major long term morbidity associated with the condition. Diagnosis is made clinically using the revised (1992) Jones Criteria which state that Rheumatic Fever is highly likely if supported by evidence of a preceding GAS infection and the presence of two major OR one major and two minor manifestations.
Supporting Evidence of GAS Infection
- Positive throat culture
- Positive antigen detection test (“Rapid Strep test”)
- Elevated or rising anti-streptococcal antibody titers
- Erythema Marginatum
- Subcutaneous Nodules
- Elevated acute phase reactants e.g. ESR
- Prolonged P – R interval on ECG
Post Streptococcal Acute Glomerulonephritis (AGN) Characterized by edema, hypertension, hematuria and proteinuria approximately 2 weeks after a GAS infection, Post Streptococcal AGN is a fairly common complication of both pharyngitis and skin infections especially in children. Thought to immunologically mediated, it is usually self limited and fairly benign but may result in permanent renal damage requiring dialysis or transplantation.
Group B beta-hemolytic Streptococcus (GBS or Streptococcus agalactiae)
GBS is a very important cause of neonatal sepsis that can have devastating consequences. Though also involved in many kinds of infections in adults particularly in debilitated individuals, it is disease in newborns that is most important.
Babies most at risk include those that are premature or are born to mothers with prolonged rupture of membranes. The organism is part of the normal flora of humans and is found in the gastrointestinal tract and/or vagina of 10-30% of people. Strategies to identify pregnant women who are colonized with GBS and then treat them with intra-partum (during labor) antibiotics if risk factors are present has reduced the incidence of serious GBS disease and is an area of active research and controversy.
These “green streptococci” are a heterogeneous group of species including, but not limited to, S. sanguis, S. oralis, S. mutans, S. mitis and S. sobrinus that inhabit the oropharynx, some of which are implicated in the genesis of dental caries but are rarely involved in other disease production with one notable exception. Subacute Bacterial Endocarditis (SBE) is an infection of heart valves that is commonly caused by this group of organisms. This is the reason that people with abnormal heart valves are advised to receive prophylactic antibiotics prior to dental manipulation.
The genus Enterococcus includes organisms that are normal inhabitants of the human gut that were formerly included within the genus Streptococcus. They are non-hemolytic and easily cultured in the lab. Until recent times they were viewed as relatively inconsequential, low virulence organisms that are involved mostly in mixed organism infections related to gut disruption.
Times have drastically changed. Enterococcus faecalis and E. faecium are now major nosocomial (hospital acquired) pathogens and some of the most antibiotic resistant bacteria that we deal with. Vancomycin resistant Enterococci (VRE) are an extremely serious threat and one of the first widespread examples of “re-entering the pre-antibiotic era” in which we have little or no effective antibiotic therapy available for serious infections. This is an excellent example of the need for extremely prudent antibiotic prescribing practices.