Some strains of group A streptococci (GAS) cause severe infection. Severe infections are usually invasive, meaning that the bacteria has entered parts of the body where bacteria are not usually found, such as the blood, lungs, deep muscle or fat tissue. Those at greatest risk include children with chickenpox; persons with suppressed immune systems; burn victims; elderly persons with cellulitis, diabetes, vascular disease, or cancer; and persons taking steroid treatments or chemotherapy. Intravenous drug users also are at high risk. GAS is an important cause of puerperal fever worldwide, causing serious infection and, if not promptly diagnosed and treated, death in newly delivered mothers. Severe GAS disease may also occur in healthy persons with no known risk factors.

All severe GAS infections may lead to shock, multisystem organ failure, and death. Early recognition and treatment are critical. Diagnostic tests include blood counts and urinalysis as well as cultures of blood or fluid from a wound site.

Severe Group A streptococcal infections often occur sporadically but can be spread by person-to-person contact.

Public Health policies internationally reflect differing views of how the close contacts of people affected by severe Group A streptococcal infections should be treated. Health Canada and the US CDC recommend close contacts see their doctor for full evaluation and may require antibiotics; current UK Health Protection Agency guidance is that, for a number of reasons, close contacts should not receive antibiotics unless they are symptomatic but that they should receive information and advice to seek immediate medical attention if they develop symptoms. However, guidance is clearer in the case of mother-baby pairs: both mother and baby should be treated if either develops an invasive GAS infection within the first 28 days following birth (though some evidence suggests that this guidance is not routinely followed in the UK).

A subset of children with acute, rapid-onset of tic disorders and obsessive compulsive disorder (OCD) are hypothesized to be due to an autoimmune response to group A beta-hemolytic streptococcal infection (PANDAS).

The symptoms of strep throat usually improve within three to five days, irrespective of treatment. Treatment with antibiotics reduces the risk of complications and transmission; children may return to school 24 hours after antibiotics are administered. The risk of complications in adults is low. In children, acute rheumatic fever is rare in most of the developed world. It is, however, the leading cause of acquired heart disease in India, sub-Saharan Africa and some parts of Australia.

Complications arising from streptococcal throat infections include:

- Acute rheumatic fever

- Scarlet fever

- Streptococcal toxic shock syndrome

- Glomerulonephritis

- PANDAS syndrome

- Peritonsillar abscess

- Cervical lymphadenitis

- Mastoiditis

The economic cost of the disease in the United States in children is approximately $350 million annually.

In the western world, GBS (in the absence of effective prevention measures) is the main cause of bacterial infections in newborns, such as septicemia, pneumonia, and meningitis, which can lead to death or long-term after effects.

GBS infections in newborns are separated into two clinical types, early-onset disease (GBS-EOD) and late-onset disease (GBS-LOD). GBS-EOD manifests from 0 to 7 living days in the newborn, most of the cases of EOD being apparent within 24 h from birth. GBS-LOD starts between 7 and 90 days after birth.

The most common clinical syndromes of GBS-EOD are septicemia without apparent location, pneumonia, and less frequently meningitis. Bacteremia without a focus occurs in 80-85%, pneumonia in 10-15%, and meningitis in 5-10% of cases. The initial clinical findings are respiratory signs in more than 80% of cases. Neonates with meningitis often have an initial clinical presentation identical to presentation in those without meningeal affectation. An exam of the cerebrospinal fluid is often necessary to rule out meningitis.

Colonization with GBS during labour is the primary risk factor for the development of GBS-EOD. GBS-EOD is acquired vertically (vertical transmission), through exposure of the fetus or the baby to GBS from the vagina of a colonized woman, either "in utero" (because of ascending infection) or during birth, after rupture of membranes. Infants can also be infected during passage through the birth canal, nevertheless, newborns who acquire GBS through this route can only become colonized, and these colonized infants usually do not develop GBS-EOD.

Roughly 50% of newborns of GBS colonized mothers are also GBS colonized and (without prevention measures) 1-2% of these newborns will develop GBS-EOD.

In the past, the incidence of GBS-EOD ranged from 0.7 to 3.7 per thousand live births in the US, and from 0.2 to 3.25 per thousand in Europe.

In 2008, after widespread use of antenatal screening and intrapartum antibiotic prophylaxis, the Centers for Disease Control and Prevention of United States reported an incidence of 0.28 cases of GBS-EOD per thousand live births in the US.

Though maternal GBS colonization is the key determinant for GBS-EOD, other factors also increase the risk. These factors are:

- Onset of labour before 37 weeks of gestation (premature birth)

- Prolonged rupture of membranes (longer duration of membrane rupture) (≥18 h before delivery)

- Intrapartum (during childbirth) fever (>38 °C, >100.4 °F)

- Amniotic infections (chorioamnionitis)

- Young maternal age

Nevertheless, most babies who develop GBS-EOD are born to colonized mothers without any of these risk factors. Heavy GBS vaginal colonization is also associated with a higher risk for GBS-EOD. Women who had one of these risk factors but who are not GBS colonized at labour are at low risk for GBS-EOD compared to women who were colonized prenatally, but had none of the aforementioned risk factors.

Presence of low levels of anticapsular antibodies against GBS in the mother are also of great importance for the development of GBS-EOD.

Because of that, a previous sibling with GBS-EOD is also an important risk factor for the development of the infection in subsequent deliveries, probably reflecting the lack of protective antibodies in the mother.

Overall, the case fatality rates from GBS-EOD have declined, from 50% observed in studies from the 1970s to between 2 and 10% in recent years, mainly as a consequence of improvements in therapy and management. Fatal neonatal infections by GBS are more frequent among premature infants.

GBS-LOD affects infants from 7 days to 3 months of age and has a lower case fatality rate (1%-6%) than GBS-EOD. Clinical syndromes of GBS-EOD are bacteremia without a focus (65%), meningitis (25%), cellulitis, osteoarthritis, and pneumonia.

Prematurity has been reported to be the main risk factor. Each week of decreasing gestation increases the risk by a factor of 1.34 for developing GBS-LOD.

GBS-LOD is not acquired through vertical transmission during delivery; it can be acquired later from the mother from breast milk or from environmental and community sources.

GBS-LOD commonly shows nonspecific signs, and diagnosis should be made obtaining blood cultures in febrile newborns. Hearing loss and mental impairment can be a long-term consequence of GBS meningitis.

Strep throat is caused by group A beta-hemolytic streptococcus (GAS or S. pyogenes). Other bacteria such as non–group A beta-hemolytic streptococci and fusobacterium may also cause pharyngitis. It is spread by direct, close contact with an infected person; thus crowding, as may be found in the military and schools, increases the rate of transmission. Dried bacteria in dust are not infectious, although moist bacteria on toothbrushes or similar items can persist for up to fifteen days. Contaminated food can result in outbreaks, but this is rare. Of children with no signs or symptoms, 12% carry GAS in their pharynx, and, after treatment, approximately 15% of those remain positive, and are true "carriers".

Though GBS colonization is asymptomatic and, in general, does not cause problems, it can sometimes cause serious illness for the mother and the baby during gestation and after delivery. GBS infections in the mother can cause chorioamnionitis (intra-amniotic infection or severe infection of the placental tissues) infrequently, and postpartum infections (after birth). GBS urinary tract infections may induce labour and cause premature delivery (preterm birth) and miscarriage.

There are several risk factors that increase the likelihood of developing bacteremia from any type of bacteria. These include:

- HIV infection

- Diabetes Mellitus

- Chronic hemodialysis

- Solid organ transplant

- Stem cell transplant

- Treatment with glucocorticoids

- Liver failure

The most common cause is viral infection and includes adenovirus, rhinovirus, influenza, coronavirus, and respiratory syncytial virus. It can also be caused by Epstein-Barr virus, herpes simplex virus, cytomegalovirus, or HIV. The second most common cause is bacterial infection of which the predominant is Group A β-hemolytic streptococcus (GABHS), which causes strep throat. Less common bacterial causes include: "Staphylococcus aureus" (including methicillin resistant Staphylococcus aureus or MRSA ),"Streptococcus pneumoniae", "Mycoplasma pneumoniae", "Chlamydia pneumoniae", "Bordetella pertussis", "Fusobacterium" sp., "Corynebacterium diphtheriae", "Treponema pallidum", and "Neisseria gonorrhoeae".

Anaerobic bacteria have been implicated in tonsillitis and a possible role in the acute inflammatory process is supported by several clinical and scientific observations.

Under normal circumstances, as viruses and bacteria enter the body through the nose and mouth, they are filtered in the tonsils. Within the tonsils, white blood cells of the immune system destroy the viruses or bacteria by producing inflammatory cytokines like phospholipase A2, which also lead to fever. The infection may also be present in the throat and surrounding areas, causing inflammation of the pharynx.

Sometimes, tonsillitis is caused by an infection of spirochaeta and treponema, in this case called Vincent's angina or Plaut-Vincent angina.

Some cases of pharyngitis are caused by fungal infection such as Candida albicans causing oral thrush.

The newborn`s exposure to the maternal vaginal bacterial flora which contains aerobic and anaerobic bacterial flora can lead to the development of anaerobic bacterial infection. These infections include cellulitis of the site of fetal monitoring (caused by "Bacterodes" spp.), bacteremia, aspiration pneumonia (caused by "Bacterodes" spp.), conjunctivitis (caused by clostridia,) omphalitis (caused by mixed flora), and infant botulism. Clostridial species may play a role in necrotizing enterocolitis. Management of these infection necessitates treating of the underlying condition(s) when present, and administration of proper antimicrobial therapy

Since the advent of penicillin in the 1940s, a major preoccupation in the treatment of streptococcal tonsillitis has been the prevention of rheumatic fever, and its major effects on the nervous system (Sydenham's chorea) and heart. Recent evidence would suggest that the rheumatogenic strains of group A beta hemolytic strep have become markedly less prevalent and are now only present in small pockets such as in Salt Lake City, USA. This brings into question the rationale for treating tonsillitis as a means of preventing rheumatic fever.

Complications may rarely include dehydration and kidney failure due to difficulty swallowing, blocked airways due to inflammation, and pharyngitis due to the spread of infection.

An abscess may develop lateral to the tonsil during an infection, typically several days after the onset of tonsillitis. This is termed a peritonsillar abscess (or quinsy).

Rarely, the infection may spread beyond the tonsil resulting in inflammation and infection of the internal jugular vein giving rise to a spreading septicaemia infection (Lemierre's syndrome).

In chronic/recurrent cases (generally defined as seven episodes of tonsillitis in the preceding year, five episodes in each of the preceding two years or three episodes in each of the preceding three years), or in acute cases where the palatine tonsils become so swollen that swallowing is impaired, a tonsillectomy can be performed to remove the tonsils. Patients whose tonsils have been removed are still protected from infection by the rest of their immune system.

In strep throat, very rarely diseases like rheumatic fever or glomerulonephritis can occur. These complications are extremely rare in developed nations but remain a significant problem in poorer nations. Tonsillitis associated with strep throat, if untreated, is hypothesized to lead to pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS).

Gram negative bacterial species are responsible for approximately 24% of all cases of healthcare-associated bacteremia and 45% of all cases of community-acquired bacteremia. In general, gram negative bacteria enter the bloodstream from infections in the respiratory tract, genitourinary tract, gastrointestinal tract, or hepatobiliary system. Gram-negative bacteremia occurs more frequently in elderly populations (65 years or older) and is associated with higher morbidity and mortality in this population.

"E.coli" is the most common cause of community-acquired bacteremia accounting for approximately 75% of cases. E.coli bacteremia is usually the result of a urinary tract infection. Other organisms that can cause community-acquired bacteremia include "pseudomonas aeruginosa", "klebsiella pneumoniae", and "proteus mirabilis". "Salmonella" infection, despite mainly only resulting in gastroenteritis in the developed world, is a common cause of bacteremia in Africa. It principally affects children who lack antibodies to Salmonella and HIV+ patients of all ages.

Among healthcare-associated cases of bacteremia, gram negative organisms are an important cause of bacteremia in the ICU. Catheters in the veins, arteries, or urinary tract can all create a way for gram negative bacteria to enter the bloodstream. Surgical procedures of the genitourinary tract, intestinal tract, or hepatobiliary tract can also lead to gram negative bacteremia. "Pseudomonas" and "enterobacter" species are the most important causes of gram negative bacteremia in the ICU.

Pharyngitis may also be caused by mechanical, chemical or thermal irritation, for example cold air or acid reflux. Some medications may produce pharyngitis such as pramipexole and antipsychotics.

Condition predisposing to anaerobic infections include: exposure of a sterile body location to a high inoculum of indigenous bacteria of mucous membrane flora origin, inadequate blood supply and tissue necrosis which lower the oxidation and reduction potential which support the growth of anaerobes. Conditions which can lower the blood supply and can predispose to anaerobic infection are: trauma, foreign body, malignancy, surgery, edema, shock, colitis and vascular disease. Other predisposing conditions include splenectomy, neutropenia, immunosuppression, hypogammaglobinemia, leukemia, collagen vascular disease and cytotoxic drugs and diabetes mellitus. A preexisting infection caused by aerobic or facultative organisms can alter the local tissue conditions and make them more favorable for the growth of anaerobes. Impairment in defense mechanisms due to anaerobic conditions can also favor anaerobic infection. These include production of leukotoxins (by "Fusobacterium" spp.), phagocytosis intracellular killing impairments (often caused by encapsulated anaerobes and by succinic acid ( produced by "Bacteroides" spp.), chemotaxis inhibition (by "Fusobacterium, Prevotella" and "Porphyromonas" spp.), and proteases degradation of serum proteins (by Bacteroides spp.) and production of leukotoxins (by "Fusobacterium" spp.).

The hallmarks of anaerobic infection include suppuration, establishment of an abscess, thrombophlebitis and gangrenous destruction of tissue with gas generation. Anaerobic bacteria are very commonly recovered in chronic infections, and are often found following the failure of therapy with antimicrobials that are ineffective against them, such as trimethoprim–sulfamethoxazole (co-trimoxazole), aminoglycosides, and the earlier quinolones.

Some infections are more likely to be caused by anaerobic bacteria, and they should be suspected in most instances. These infections include brain abscess, oral or dental infections, human or animal bites, aspiration pneumonia and lung abscesses, amnionitis, endometritis, septic abortions, tubo-ovarian abscess, peritonitis and abdominal abscesses following viscus perforation, abscesses in and around the oral and rectal areas, pus-forming necrotizing infections of soft tissue or muscle and postsurgical infections that emerge following procedures on the oral or gastrointestinal tract or female pelvic area. Some solid malignant tumors, ( colonic, uterine and bronchogenic, and head and neck necrotic tumors, are more likely to become secondarily infected with anaerobes. The lack of oxygen within the tumor that are proximal to the endogenous adjacent mucosal flora can predispose such infections.

A drug-resistant strain of scarlet fever, resistant to macrolide antibiotics such as erythromycin, but retaining drug-sensitivity to beta-lactam antibiotics such as penicillin, emerged in Hong Kong in 2011, accounting for at least two deaths in that city—the first such in over a decade. About 60% of circulating strains of the group A "Streptococcus" which cause scarlet fever in Hong Kong are resistant to macrolide antibiotics, says Professor Kwok-yung Yuen, head of Hong Kong University's microbiology department. Previously, observed resistance rates had been 10–30%; the increase is likely the result of overuse of macrolide antibiotics in recent years.

Some patients may develop pneumonia, lymphadenopathy, or septic arthritis.

While the number of penicillin-resistant bacteria is increasing, penicillin can still be used to treat a wide range of infections caused by certain susceptible bacteria, including Streptococci, Staphylococci, Clostridium, and Listeria genera. The following list illustrates minimum inhibitory concentration susceptibility data for a few medically significant bacteria:

- "Listeria monocytogenes": from less than or equal to 0.06 μg/ml to 0.25 μg/ml

- "Neisseria meningitidis": from less than or equal to 0.03 μg/ml to 0.5 μg/ml

- "Staphylococcus aureus": from less than or equal to 0.015 μg/ml to more than 32 μg/ml

This disease is most common among the elderly, infants, and children. People with immune deficiency, diabetes, alcoholism, skin ulceration, fungal infections, and impaired lymphatic drainage (e.g., after mastectomy, pelvic surgery, bypass grafting) are also at increased risk.

Epiglottitis is typically due to a bacterial infection of the epiglottis. While it historically was most often caused by Haemophilus influenzae type B with immunization this is no longer the case. Bacteria that are now typically involved are "Streptococcus pneumoniae", "Streptococcus pyogenes", or "Staphylococcus aureus".

Other possible causes include burns and trauma to the area. Epiglottitis has been linked to crack cocaine usage. Graft versus host disease and lymphoproliferative disorder can also be a cause.

Most cases of erysipelas are due to "Streptococcus pyogenes" (also known as beta-hemolytic group A streptococci), although non-group A streptococci can also be the causative agent. Beta-hemolytic, non-group A streptococci include "Streptococcus agalactiae", also known as group B strep or GBS. Historically, the face was most affected; today, the legs are affected most often. The rash is due to an exotoxin, not the "Streptococcus" bacteria, and is found in areas where no symptoms are present; e.g., the infection may be in the nasopharynx, but the rash is found usually on the upper dermis and superficial lymphatics.

Erysipelas infections can enter the skin through minor trauma, insect bites, dog bites, eczema, athlete's foot, surgical incisions and ulcers and often originate from streptococci bacteria in the subject's own nasal passages. Infection sets in after a small scratch or abrasion spreads, resulting in toxaemia.

Erysipelas does not affect subcutaneous tissue. It does not release pus, only serum or serous fluid. Subcutaneous edema may lead the physician to misdiagnose it as cellulitis, but the style of the rash is much more well circumscribed and sharply marginated than the rash of cellulitis.

Common (≥ 1% of people) adverse drug reactions associated with use of the penicillins include diarrhoea, hypersensitivity, nausea, rash, neurotoxicity, urticaria, and superinfection (including candidiasis). Infrequent adverse effects (0.1–1% of people) include fever, vomiting, erythema, dermatitis, angioedema, seizures (especially in people with epilepsy), and pseudomembranous colitis. Penicillin can also induce serum sickness or a serum sickness-like reaction in some individuals. Serum sickness is a type III hypersensitivity reaction that occurs one to three weeks after exposure to drugs including penicillin. It is not a true drug allergy, because allergies are type I hypersensitivity reactions, but repeated exposure to the offending agent can result in an anaphylactic reaction. Anaphylaxis will occur in approximately 0.01% of patients.

Pain and inflammation at the injection site is also common for parenterally administered benzathine benzylpenicillin, benzylpenicillin, and, to a lesser extent, procaine benzylpenicillin.

Streptococcus species are the cause of opportunistic infections in poultry leading to acute and chronic conditions in affected birds. Disease varies according to the Streptococcal species but common presentations include septicaemia, peritonitis, salpingitis and endocarditis.

Common species affecting poultry include:

- "S. gallinaceus" in broiler chickens

- "S. gallolyticus" which is a pathogen of racing pigeons and turkey poults

- "S. dysgalactiae" in broiler chickens

- "S. mutans" in geese

- "S. pluranimalium" in broiler chickens

- "S. equi subsp. zooepidemicus" in chickens and turkeys

- "S. suis" in psittacine birds

Scarlet fever occurs equally in both males and females. Children are most commonly infected, typically between 5–15 years old. Although streptococcal infections can happen at any time of year, infection rates peak in the winter and spring months, typically in colder climates.

The morbidity and mortality of scarlet fever has declined since the 18th and 19th century when there were epidemics caused by this disease. Around 1900 the mortality rate in multiple places reached 25%. In The improvement in prognosis can be attributed to the use of penicillin in the treatment of this disease. The frequency of scarlet fever cases has also been declining over the past century however, there have been several reported outbreaks of the disease in various countries in the past decade. The reason for these recent increases remains unclear in the medical community.

The elderly and those with a weakened immune system are especially vulnerable to contracting cellulitis. Diabetics are more susceptible to cellulitis than the general population because of impairment of the immune system; they are especially prone to cellulitis in the feet, because the disease causes impairment of blood circulation in the legs, leading to diabetic foot or foot ulcers. Poor control of blood glucose levels allows bacteria to grow more rapidly in the affected tissue, and facilitates rapid progression if the infection enters the bloodstream. Neural degeneration in diabetes means these ulcers may not be painful, thus often become infected. Those who have suffered poliomyelitis are also prone because of circulatory problems, especially in the legs.

Immunosuppressive drugs, and other illnesses or infections that weaken the immune system, are also factors that make infection more likely. Chickenpox and shingles often result in blisters that break open, providing a gap in the skin through which bacteria can enter. Lymphedema, which causes swelling on the arms and/or legs, can also put an individual at risk.

Diseases that affect blood circulation in the legs and feet, such as chronic venous insufficiency and varicose veins, are also risk factors for cellulitis.

Cellulitis is also common among dense populations sharing hygiene facilities and common living quarters, such as military installations, college dormitories, nursing homes, oil platforms, and homeless shelters.

The disease is spread by an infected horse when nasal discharge or pus from the draining lymph nodes contaminate pastures, feed troughs, brushes, bedding, tack etc.

Equines of any age may contract the disease, although younger and elderly equines are more susceptible. Young equines may lack immunity to the disease because they have not had prior exposure. Geriatric equines may have a weaker immune system.