- Types of Group A Streptococcal Infections
- Cellulitis and Erysipelas
- Scarlet Fever
- Severe Strep Infections
- Strep Throat
- What are Streptococcal infections?
- α-haemolytic Streptococci
- β-haemolytic Streptococci
- The Different Types of Streptococci
- Group A Streptococcus
- Group B Streptococcus
- Group C and G Streptococci
- Pathogenicity of Virulent Species of Group C Streptococci in Human
- Antibiotic Susceptibilities of Group C and Group G Streptococci Isolated from Patients with Invasive Infections: Evidence of Vancomycin Tolerance among Group G Serotypes
Types of Group A Streptococcal Infections
Cellulitis and Erysipelas
Cellulitis is inflammation of the skin and deep underlying tissues. Erysipelas is an inflammatory disease of the upper layers of the skin. Group A strep (streptococcal) bacteria are the most common cause of cellulitis and erysipelas. To learn more or .
Impetigo is an infection of the top layers of the skin and is most common among children ages 2 to 6 years. It usually starts when bacteria get into a cut, scratch, or insect bite. To learn more .
Scarlet fever – or scarlatina – is a bacterial infection caused by group A Streptococcus or “group A strep.” This illness affects a small percentage of people who have strep throat or, less commonly, streptococcal skin infections. To learn more .
Severe Strep Infections
Some types of group A strep bacteria cause severe infections, such as
- Bacteremia (bloodstream infections) – To learn more visit .
- Toxic shock syndrome (multi-organ infection) – To learn more .
- Necrotizing fasciitis (flesh-eating disease) – To learn more .
Many things can cause that unpleasant, scratchy, and sometimes painful condition known as a sore throat. Viruses, bacteria, allergens, environmental irritants (such as cigarette smoke), chronic postnasal drip, and fungi can all cause a sore throat. While many sore throats will get better without treatment, some throat infections—including strep throat—may need antibiotic treatment. To learn more .
What are Streptococcal infections?
- There are many different types of Streptococci and infections vary in severity from mild throat infections to pneumonia.
- Streptococcal infections are primarily treated with antibiotics.
- Streptococci are divided into two key groups:
- alpha (α)-haemolytic Streptococci
- beta (β)-haemolytic Streptococci.
- This group is very common.
- Many strains live naturally in humans causing no symptoms.
- α-haemolytic Streptococci are split into two groups:
- Streptococcus pneumoniae
- Viridans Streptococci.
- S. pneumoniae is usually found on the surface of the skin and inside the throat.
- It causes infections in both adults and children.
- It is transmitted through coughs and sneezes.
- Minor infections can be treated relatively easily with antibiotics and include:
- sinusitis (inflammation of the sinuses)
- middle ear infections.
- More invasive infections pose a more serious threat to health and include:
- pneumonia (inflammation of the tissue in the lungs)
- meningitis (inflammation of the membranes covering the brain and spinal cord)
- bacteraemia (infection of the blood).
- People at the highest risk of invasive S. pneumoniae infections are:
- babies under six months old
- adults over 75 years old
- adults with a weak immune system.
A plate of Streptococcus pneumoniae.
Image credit: Nathan Reading on Flickr , via Wikimedia Commons
- This group of Streptococci are most often found in the mouth, gut and genital region.
- The most serious Viridans infections occur when the bacteria enters other regions of the body. For example, if Viridans gets into the bloodstream it can cause endocarditis (infection of the inner lining of the heart).
- Individuals with damaged heart valves or cardiac abnormalities and compromised immune systems are at particular risk.
- Symptoms include:
- weight loss
- respiratory problems
- problems with heart function in cases where endocarditis occurs.
Diagnosis and treatment of α-haemolytic infections
- Minor infections can be diagnosed by taking a sample of saliva or a swab of the affected tissue and testing for the presence of Streptococcal bacteria.
- For invasive infections additional tests may be required, such as a blood test for bacteraemia or cerebral spinal fluid test for meningitis.
- Minor infections may not require treatment or may be treated with antibiotics.
- Invasive infections usually result in a hospital stay.
- Severe invasive infections may require intensive treatment with intravenous antibiotics for 7-10 days. In some cases surgery may be required to remove or repair damaged tissue.
- β-haemolytic Streptococci are characterised as Group A Streptococci (GAS) and Group B Streptococci (GBS)
Group A (Streptococcus pyogenes)
- Streptococcus pyogenes is transmitted through coughs, sneezes or direct contact
- It can be either non-invasive (not spread into the bloodstream) or invasive (spread into the bloodstream and to other body sites)
- The most common of the non-invasive infections include:
- strep throat: sore throat specifically caused by streptococcal infection
- impetigo: contagious skin infection that causes sores and blisters
- scarlet fever: infectious disease causing a sore throat and characteristic red rash.
- Invasive infections are much rarer and occur when the bacteria infects other areas of the body such as the blood and organs. This can result in:
- pneumonia: inflammation of the tissue in the lungs
- bacteraemia: infection of the blood
- necrotising fasciitis: flesh-eating disease.
- Left untreated, potential complications of Group A infection include rheumatic fever, a disease that affects the joints, kidneys and heart.
Diagnosis and treatment of Group A infections
- For non-invasive infections a Rapid Strep Test (RST) can be carried out. This involves a doctor taking a throat or nose swab that is analysed for group A Streptococcus. An RST is one of the most common tests for this type of infection.
- For suspected invasive infections a blood test may be taken.
- Most infections are treated with antibiotics:
- superficial skin infections can be treated with topical antibiotic ointments
- other infections can be treated with oral or intravenous antibiotics depending on the severity of the infection.
- Where the infection has caused a lot of skin damage, for example in cases of necrotising fasciitis, damaged tissue may be removed surgically.
Group B (Streptococcus agalactiae)
- Streptococcus agalactiae usually lives harmlessly inside the digestive system and female genitals.
- It can be transmitted sexually or from mother to baby during birth.
- Group B β-haemolytic Streptococcus tend to only affect new born babies as the bacteria can be passed onto the baby from the mother through the amniotic fluid (protective fluid that surrounds the foetus in the womb).
- Due to being continually exposed to it through our lifetimes most people quickly develop a natural immunity to Group B β-haemolytic Streptococcus.
- Symptoms of group B β-haemolytic streptococcal infection in a newborn baby include:
- being floppy and unresponsive
- poor feeding
- unusually high or low body temperature
- unusually fast or slow heart rate
- If left untreated, group B β-haemolytic streptococcal infections can also lead to much more serious conditions such as meningitis and pneumonia.
- Factors increasing risk of group B β-haemolytic streptococcal infection in new-born babies include:
- premature birth
- being part of a multiple birth
- having a mother with a history of group B streptococcal infection.
Diagnosis and treatment of Group B infections
- These infections are diagnosed by a blood, urine or cerebral spinal fluid sample to identify the bacteria.
- A culture of fluid from the vagina or rectum can also determine if a woman is infected.
- The infection is treated with antibiotics, often directly into the bloodstream (intravenously).
- Treatment of these infections may require a hospital stay.
Preventing Group B Streptococcal infection in newborns
- Healthcare professionals take measures during labour and after birth to prevent newborns becoming infected with Streptococcus.
- If a baby is known to be at risk of Streptococcus infection, antibiotic injections are given to the mother during labour or to the baby shortly after birth.
This page was last updated on 2015-06-19
The Different Types of Streptococci
Learn about the different types of strep bacteria, what kinds of illnesses they cause, and how to prevent infection.
A culture test is one way to detect streptococcus bacteria. Thinkstock
Although strep throat is a common form of infection from streptococcal bacteria, it is not the only kind. Streptococcal infections are any type of infection caused by the streptococcal, or “strep” group of bacteria.
There are a number of different streptococci, which create symptoms ranging from a mild throat infection to a life-threatening infection of the blood or organs. Anyone can be affected, from babies and small children to older adults.
Most strep infections can be treated with antibiotics.
Streptococci infections are divided into several groups: Group A streptococcus, Group B streptococcus, Group C streptococcus, and Group G streptococcus.
Group A Streptococcus
Group A strep, sometimes called GAS, tends to affect the throat and the skin. People may carry GAS in these areas yet not show any symptoms of illness. Most strep A infections cause relatively mild illness, but on rare occasions, these bacteria can lead to severe and even life-threatening disease.
Strep A infections spread through direct contact with mucus from the nose or throat of infected persons or through contact with infected wounds or sores. (1) Illnesses from strep A infection include:
Strep throat In general, strep throat is a mild illness, but it can be very painful. Symptoms include sore throat that comes on very quickly, pain when swallowing, fever, red and swollen tonsils (sometimes with white patches or streaks of pus), small red spots on the roof of the mouth, and swollen lymph nodes in the front of the neck. Strep throat may also be accompanied by headache, abdominal pain, nausea, or vomiting, especially in children. Illness typically manifests two to five days after exposure.
A doctor cannot tell if someone has strep throat just by looking, so a diagnostic test is needed. A rapid stress test involves swabbing the throat and running a lab test to see if GAS is the cause of the illness.
While most sore throats are caused by viruses, strep throat is caused by bacteria and therefore can only be treated with antibiotics.
While anyone can get strep throat, it’s more common among school-aged children 5 through 15. Parents and adults who are often in contact with children of these ages are more likely to get strep throat than adults who are not. (2)
Scarlet fever Also referred to as scarlatina, scarlet fever is a relatively mild illness characterized by a very red sore throat, a red rash that has a sandpaper feel, and a “strawberry,” or red and bumpy, tongue. Other symptoms can include fever, swollen glands in the neck, whitish coating on the tongue, and bright red skin in the underarm, elbow, or groin.
The illness typically begins with a fever and sore throat. The rash — caused by a toxin made by strep A bacteria — usually appears a day or two later, although it can begin before the illness or up to seven days later.
Scarlet fever is highly contagious. It can be spread from person to person when someone who is infected coughs or sneezes: the bacteria travels in small droplets in the air. You can get sick by breathing in those droplets or by touching something that the droplets have landed on and touching your nose or mouth. Drinking from the same glass or eating from the same plate as an infected person can also spread the illness. It is also possible to get scarlet fever sores on the skin caused by GAS.
Scarlet fever is treated with a course of antibiotics. Complications sometimes occur and can include abscesses around the tonsils, swollen lymph nodes in the neck, and sinus and ear infections. Other, more rare complications can affect the heart, including rheumatic fever, and kidney disease.
Like strep throat, scarlet fever is more common in children than adults, particularly those ages 5 through 15. Close contact with someone who has the infection is the biggest risk factor for getting the illness. There is no vaccine for scarlet fever, but people can protect themselves by practicing good hygiene, including using a tissue to cover your mouth when sneezing or coughing, washing hands frequently, using alcohol-based hand sanitizer if soap and water are unavailable, and coughing or sneezing into your upper sleeve or elbow rather than your hands if a tissue is not available. (3)
Impetigo This is an infection of the top layers of skin that typically starts when bacteria gets into a cut, scratch, or insect bite. It is usually caused by the bacteria Staphylococcus aureus but can also be caused by strep A. It is most common among children ages 2 to 6.
Symptoms begin as itchy red or pimple-like sores surrounded by red skin, usually on the face, arms, or legs, that are filled with pus. Impetigo is contagious and can be spread by contact with sores or nasal discharge of an infected person. It can be treated with a round of antibiotics. (4)
Post-streptococcal glomerulonephritis Also referred to as PSGN, this is a kidney disease that can develop after a strep A infection. PSGN is not a GAS infection of the kidneys. It’s a result of the body’s immune system fighting off the strep A infection. PSGN usually occurs 10 days after strep throat or scarlet fever and about three weeks after a strep A skin infection.
Symptoms of PSGN include dark, reddish-brown urine, swelling in the face, hands and feet, decreased amount of urine or decreased need to urinate, and fatigue.
The condition is treated by managing symptoms, including limiting salt and water intake or prescribing medication to reduce swelling. Antibiotics can also help kill any strep A bacteria left in the body.
Most people with PSGN recover within a few weeks, but in rare instances long-term kidney damage, including kidney failure, can occur. (5)
Group B Streptococcus
Group B streptococcus, also known as group B strep or GBS, is a type of bacteria that can cause illness in people of all ages, though it can be particularly severe in newborns, most commonly causing sepsis, pneumonia, and meningitis. In adults, the most common health issues caused by GBS include urinary tract infections, skin infections, bloodstream infections, pneumonia, skin and soft-tissue infections, and bone and joint infections.
In babies, strep B infections occur as either early-onset or late-onset. Early-onset occurs in babies younger than 1 week old and the infection is most often passed from mother to baby during labor. Symptoms of strep B infection in newborn babies usually develop within the first few hours or days of giving birth and include being floppy or unresponsive, poor feeding, grunting when breathing, and unusually fast or slow breathing and heartbeat. (6)
Antibiotics given to the mother during labor can help prevent the spread of the infection to the baby.
Late-onset strep B infection in babies occurs at one week through 3 months old and is sometimes passed from mother to baby but it can also come from another source.
Early-onset used to be the most common type of strep B infection in newborns, but because of prevention efforts, both early-onset and late-onset occur at similar low rates, according to the CDC.
In adults, strep B infection occurs less frequently than in babies, but it can affect anyone. The sources of disease caused by GBS in adults is unknown, but the bacteria are present in the gastrointestinal tract and may be the source of infection.
If the infection leads to sepsis or pneumonia, it can be fatal. On average, 1 in 20 nonpregnant adults with an invasive strep B infection dies, the CDC reports. The chance of strep B infection increases with age. Younger adults who do not have any other medical conditions have a lower risk of death from GBS. (7)
Group C and G Streptococci
Group C and G streptococci are much less understood than strep A and B because the diseases caused by these bacteria are far less common.
Group C and G strep most commonly live in animals such as horses and cattle and can spread to humans through raw milk or contact with these animals. The bacteria can also live in people’s throats and on human skin, particularly in areas damaged by conditions like eczema or on mucous surfaces, such as the vagina or bowel.
Infections can be treated with antibiotics, but severe infections can be fatal, especially when they have entered the bloodstream. Cases are most common in adults older than 75. (8)
Streptococcus, (genus Streptococcus), group of spheroidal bacteria belonging to the family Streptococcaceae. The term streptococcus (“twisted berry”) refers to the bacteria’s characteristic grouping in chains that resemble a string of beads. Streptococci are microbiologically characterized as gram-positive and nonmotile.
Streptococcus contains a variety of species, some of which cause disease in humans and animals, while others are important in the manufacture of certain fermented products. Streptococcus pyogenes, often referred to as group A streptococcus bacteria, can cause rheumatic fever, impetigo, scarlet fever, puerperal fever, streptococcal toxic shock syndrome, strep throat, tonsillitis, and other upper respiratory infections. Necrotizing fasciitis, a rapidly spreading infection of the skin and underlying tissue caused by S. pyogenes, has been popularly referred to as the “flesh-eating disease.” Streptococcus agalactiae, or group B streptococcus bacteria, can cause infections of the bladder and uterus in pregnant women; in newborn infants infection with the bacterium may result in sepsis (blood poisoning), meningitis (inflammation of the membranes covering the brain and spinal cord), or pneumonia. Streptococcus pneumoniae, also called pneumococcus, is an important human pathogen that causes pneumonia, sinusitis, otitis media, and meningitis. Fecal (enterococcal) species occur in great numbers in the bowel and can cause urinary tract infections and endocarditis. S. mutans, belonging to the viridans species, inhabits the mouth and contributes to tooth decay. Among the lactic species, S. lactis and S. cremoris are used in commercial starters for the production of butter, cultured buttermilk, and certain cheeses.
Streptococci generally are classified by the type of carbohydrate contained in the cell wall, a system called the Lancefield classification.
Pathogenicity of Virulent Species of Group C Streptococci in Human
Group C streptococci (GCS) are livestock pathogens and they often cause zoonotic diseases in humans. They are Gram-positive, in mostly β-hemolytic and facultative anaerobes. Because of their close evolutionary kinship with group A streptococci (GAS), GCS share many common virulence factors with GAS and cause a similar range of diseases. Due to the exchange of genetic material with GAS, GCS belong to bacteria that are difficult to be distinguished from group A streptococci; GCS are often treated in microbiological diagnostics as contamination of the culture. This report focuses mainly on the pathogenicity of virulent species of GCS and their association with human diseases. The condition that is most frequently quoted is pharyngitis. In this paper, the virulence factors have also been mentioned and an interesting link has been made between GCS and the pathogenesis of rheumatic diseases among the native people of India and Aboriginal populations.
Group C streptococci, according to Lancefield’s work of 1933, belong to Gram-positive bacteria, catalase-negative and facultative anaerobes . The division of streptococci into groups was made by Lancefield; the research concerned 106 strains of Streptococcus haemolyticus isolated from many sources (humans, animals, and dairy products) and was based on the carbohydrate C expressed in the wall of bacteria . Using sera, agglutination reactions, and reactions of precipitation Lancefield classified the strains into respective groups . Based on the results of the anti-C precipitin test, it was stated that the strains of group C came from various sources other than human and numbered 49 strains. Those strains of group C can hardly, or impossibly, be distinguished from human hemolytic streptococci .
GCS identification can be difficult due to their close kinship with group A streptococci—they have a common evolutionary origin, and they are well-known for their exchange of genetic material, share many of their virulence genes, and cause similar diseases . The study of the epidemiology of human GCS infections has recently been made possible mainly owing to the development of modern methods of molecular diagnosis. GCS are mainly livestock commensals or pathogens, although they can also be the part of the human flora of the nose, throat, intestines, or skin . The main origin of virulent species of GCS that cause human diseases is animals, unpasteurized milk, and unpasteurized dairy products . Infections caused by streptococci can be invasive or noninvasive, and they cannot be distinguished merely on the basis of their clinical presentation .
Astete reports that Streptococcus equi is regarded as the immediate antecedent of group C streptococci and is also the cause of almost 2% of all infections caused by GCS . Table 1 depicts the species currently belonging to GCS (Table 1). According to Facklam GCS contains four species: S. dysgalactiae subs. dysgalactiae, S. dysgalactiae subs. equisimilis, S. equi subs. equi, S. equi subs. zooepidemicus, and S. constellatus subs. pharyngis . The streptococcus of group C, which most often causes infection in humans, is Streptococcus dysgalactiae subs. equisimilis (SDSE) ; it may cause skin infections (cellulitis) and recurrent blood infections . According to Clarke the GCS species, not mentioned before, most often isolated from the human throat is S. milleri , also known as S. anginosus group .
Table 1 Phenotypic characteristics of group C streptococci.
In contemporary laboratories the identification according to the carbohydrate group GCS strains may be conducted by means of latex agglutination . Aside from the classification according to the carbohydrate group, there are many other identification methods, which will allow us to discriminate species within GCS and to discriminate GCS from other streptococci. Some selected phenotypic features of the GCS species are shown in Table 1 (Table 1).
Phenotypes of group C streptococci and group G streptococci (GGS) form a large colony, which makes them different from the phenotypes belonging to the S. anginosus group, which form a small colony, irrespective of the carbohydrate group . The aforementioned S. anginosus group (called S. milleri by some authors) contains three species: S. anginosus, S. constellatus, and S. intermedius . The species that belong to the S. anginosus group contain in their cellular wall the carbohydrate groups A, C, F, and G or they contain none . GCS and S. anginosus group can be identified on the basis of β-hemolytic activity . All the species of the S. anginosus group and almost all the phenotypes of GCS cause beta-hemolysis except S. dysgalactiae subs. dysgalactiae . In order to discriminate GCS or GGS from GAS the PYR test is applied (the L-pyroglutamyl amino-peptidase test) . The PYR test shows a positive result only in the case of GAS; both in the case of GCS and in the S. anginosus group no positive reaction had been found .
In Angeletti’s work we find two reliable optochin sensitivity and bile solubility tests, the tests mentioned also in Facklam’s observation . Facklam shows that virulent streptococci, including those from group C, manifest a negative reaction in optochin sensitivity and bile solubility tests . Aside from the aforementioned methods, Clarke et al. report that GCS can also be differentiated from other species through their capacity for sorbitol and trehalose fermentation (, Table 1). Among the phenotypes belonging to GCS, only S. equi subs. zooepidemicus can ferment sorbitol, whereas S. dysgalactiae subs. dysgalactiae manifests variable reactions . Almost all the phenotypes of GCS, except S. equi subs. equi and S. equi subs. zooepidemicus, which manifests a variable response, ferment trehalose . It is interesting to note that none out of the 49 strains attributed in 1933 by Lancefield to group C fermented trehalose .
One can include within the molecular techniques of streptococci identification the emm typing, MALDI-TOF MS method (Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry), and the sequencing of selected genes. The examination of the presence of emm and emm-like genes, called emm typing, allows us to determine the M protein serotypes . In Dinkla’s research the emm types were identified by means of PCR analysis, with the use of starters recommended by the Center of Disease Control . In the case of GAS the emm gene sequence technique is combined with T typing, a fact that is not possible in GCS or GGS, for GCS/GGS contain no T proteins .
MALDI-TOF MS identification is based on the protein composition of cell bacteria, especially ribosomal proteins. In Angeletti’s tests 158 strains have been isolated, all of them belonging to the viridans group streptococci (VGS), and examined in the MALDI-TOF MS; then genes tuf, sodA, and rpoB were amplified and sequenced . It has been stated that in Angeletti MALDI-TOF MS sensitivity obtained 100% in comparison with the phenotypical tests . To identify S. dysgalactiae subs. equisimilis strains Ciszewski presents the RISA method (analysis of ribosomal intergenic region) . In the RISA method, in the course of PCR reaction, one uses S. dysgalactiae species-specific primers and SDSE subspecies-specific primers .
An alternative for the aforementioned molecular identification can be the sequencing of the 16S rRNA, in combination with gyrB gene sequencing generally regarded as a golden standard . Zhou’s test confirms that by having examined 181 isolates the similarities with the sequences in GenBank reached over 99% and 96% . According to Zhou et al., however, the sequencing of the gyrB gene can be more practical and more precise in identifying VGS strains than other methods .
The basis of species identification appears to be the phenotypical tests used by many researchers; they confirm the fact that they belong to a given species and that the findings of MALDI-TOF MS are correct. Molecular techniques allow us also to detect or confirm the presence of some features which cannot be examined by means of the phenotypical methods of biochemical tests. These two groups of methods are inseparably linked, and in order to precisely examine the group C streptococci one should combine the phenotypical methods with molecular techniques.
New methods of identification based on protein typing or genome typing are barely available in Polish laboratories; therefore latex tests prevail. Probably, such a situation is also typical of other East and Central European countries, or in the developing countries. Therefore literature contains mainly the findings from the highly developed countries.
3. Virulence Factors
The virulence factor in some species of GCS most frequently mentioned is the M protein, the protein that also belongs to group A streptococci . This antiphagocytic, fibrillar, and surface-exposed M protein is encoded by the emm gene . Bisno’s tests have shown that M protein can mainly be found in S. dysgalactiae subs. equisimilis isolates isolated from patients suffering from acute pharyngitis . There are over 80 well-known M protein serotypes of group A streptococci . In comparative research between M proteins of GAS and M proteins of GCS isolates SDSE was examined from people and it was found that the structures of M proteins of GAS were highly homological to M proteins of GCS in the C repeat region but the N terminus was unique .
It seems that M protein plays an important role in rheumatic fever (RF) . McDonald and Bramhachari have noticed that GCS isolates more often than GAS colonize the throats of Aboriginal population suffering from RF incidence and rheumatic heart disease (RHD) . Dinkla’s work seems to confirm that M and M-like proteins of group C streptococci take part in the pathogenesis of rheumatic fever in some geographic regions . All of the 70 isolates S. dysgalactiae subs. equisimilis belonged to GCS/GGS; 27 of them had the ability to bind collagen IV and these were subjected to further analysis . Out of 27 SDSE strains containing the emm gene, coding M proteins, 4 had the fog gene coding M-like fibrinogen binding protein of GGS (FOG) . These findings are confirmed in Haidan’s and Rantala’s reports where GCS/GGS isolates were found, and the isolates that have the fibronectin-binding protein property can aggregate human platelets and can toxically affect the endothelial cells . Dinkla’s research shows that 27 SDSE strains owe their ability to bind collagen IV to the hyaluronic acid capsule . Furthermore McDonald and Nataneli describe the capacities of GCS for cross reaction with cardiac epitopes and their superantigenic features .
Aside from M protein, some species of GCS (Table 2) can produce a surface-exposed protein (Szp), streptokinase, streptolysin O or streptolysin S , and hemolysins . Surface-exposed protein is produced by S. equi subs. zooepidemicus . Chandnani indicates the SDSE strain to produce streptokinase and streptolysin O and shows theories about the pathogenesis of rheumatic fever . There is a direct cytotoxic influence of streptolysin O on the cardiac cells and other organs or there are antigenic determinants between the components of an organism and some specific tissues, such as the brain or heart, that is a result of immunologic cross reactivity . Following a comparative analysis of the GAS genome with the SDSE genome, Silva and Watanabe confirm that they contain related virulence factors .
| : rheumatic fever.
: rheumatic heart disease.
Table 2 Virulence factors and morbidity against human of group C streptococci.
Besides the aforementioned virulence factors SDSE isolates have C5a peptidase, glyceraldehyde 3-phosphate dehydrogenase, and hyaluronidase . There are also several important GAS virulence factors, which are not found in the SDSE genome, for example, cysteine protease, and a superantigen homolog . SDSE enzymes, matrix metalloproteinases, and plasminogen binding GAPDH enzyme contribute to dissemination in the body and proliferation. An analysis of the genome of SDSE 167 strain has shown that it excretes lyases decomposing carbohydrates of the host, while at the same time this genome metabolizes carbohydrates in the Entner-Doudoroff pathway; this region contains the enzyme metabolizing polysaccharides, which may contribute to a higher virulence of SDSE 167 strain . Watanabe et al. claim that SDSE 167 strain is the most virulent human strain .
Among the diseases caused by the species of GCS the dominating ones are pharyngitis, meningitis, and endocarditis (Table 2). According to Danish data (1999–2002), GCS infections take the last place among streptococcal infections, but they constitute as many as 6% of all streptococcal infections . This has also been confirmed by the Norwegian observations of 1999–2013, where out of 512 invasive infections GCS was the cause of 24 cases (4,7%) . In both reports, the risk of infection increases with the patient’s age . Among other factors that predispose one to infections are diabetes, tumors, cardiac conditions, and alcohol abuse , whereas Rantala adds immunosuppressive therapy, multiple morbidities, and skin lesions as potential predisposing factors .
The most frequent clinical form of invasive virulent species of GCS infections are infections of bones, joints, and blood infections, and the noninvasive infections of the upper respiratory tracts . The mortality rate during the first 30 days of the disease, in the Danish research, equaled 21%, whereas in the Norwegian research it equaled 9%, and it increased with age and with respect to the kind of disease . Ekelund et al. reports that the highest rate concerned patients with GAS (23%) and GCS infections (21%) ; in Oppegaard et al. the mortality rate in GAS infections was 13% . Both Ekelund et al. and Oppegaard et al. list similar diseases: skin infections (erysipelas, cellulitis), necrotizing fasciitis, and toxic shock syndrome .
Rantala presents two cases of elderly patients with recurring bacteremia caused by the most frequent GCS isolates, SDSE, and a broad range of diseases caused by the following subspecies: pharyngitis, tonsillitis, skin infection, soft tissue infection, wound infections, erysipelas, cellulitis, necrotizing fasciitis, streptococcal toxic shock-like syndrome, pneumonia, septic arthritis, osteomyelitis, meningitis, endocarditis, and bacteremia .
The findings of the British Health Protection Agency and Watanabe are alarming. They have shown a 100% increase of bacteremia between 2006 and 2012 and an increase of SDSE infections in Asia, Europe, and the USA . Of particular interest are the reports about the relations between GCS with the pathogenesis of rheumatic fever in Australia and India and first documented zoonotic diseases .
As has already been mentioned, though RF pathogenesis is not clear only in the upper respiratory tract infection, GAS may directly lead to rheumatic fever. Haidan’s studies have shown that in Australia higher indicators of isolation of GCS have been found as well as the highest rate of RF-dependent morbidity in the world , a fact which, as researchers say, may be related to high RF and RHD morbidity among Aboriginal communities of Australia .
Nataneli et al. have described an American case of poststreptococcal syndrome uveitis (PSU), which is the first documented case of complications following pharyngitis and caused by GCS infection . The patient was a 24-year-old man with HLA-B27 positive genotype (this genotype predisposing an individual also to poststreptococcal reactive arthritis). Morsch, however, describes the case of a 72-year-old man, suffering from tophaceous gout, in whom olecranon bursitis developed as the result of a GCS infection . The author notes that until now circa 15 cases of septic arthritis (GCS) have been documented, but none have been related to bursitis .
In publications one can find some data concerning zoonotic diseases. The first report describes the case of a 13-year-old boy who lived on a horse farm; he became ill with meningitis caused by S. equi subs. equi . The second case is of a 13-year-old girl suffering from meningitis caused by S. equi subs. zooepidemicus . A day before her illness she took part in horse races . A description of GCS-dependent meningitis with cavernous sinus in an 18-year-old man is worth mentioning . Virulent species of GCS can also cause, among other things, impetigo, epiglottitis, and polyarthritis .
(1)Virulent species of group C streptococci, which cause infection in people, are most often animals’ pathogens and belong to bacteria that are difficult to be identified. Due to the common origin of GCS and GAS the method of identification is to combine phenotypical and molecular techniques.(2)The study of the epidemiology of human GCS infections is possible owing to the application of modern NGS (Next Generation Sequencing) methods in routine investigations.(3)Some species of GCS, chiefly SDSE, have many virulence factors found in GAS like M protein, streptokinase, and streptolysins, but there are some that are missing like cysteine protease. There are assumptions that virulent species of GCS can be related to the pathogenesis of rheumatic fever and rheumatic heart disease, especially among Aboriginal population of Australia.(4)The main origins of virulent species of GCS are unpasteurized dairy products, animals, and humans.(5)The most frequent diseases are pharyngitis and meningitis. The most frequent GCS isolates from human infection is SDSE.(6)The predisposing factors are, among other things, age and chronic diseases. The range of GCS-dependent diseases is broad, including infections related to the respiratory system, skin infections and soft tissue infections, necrotizing fasciitis, streptococcal toxic shock syndrome, septic arthritis, osteomyelitis, endocarditis, and bacteremia.
Conflicts of Interest
The authors declare that there are no conflicts of interest regarding the publication of this paper.
Antibiotic Susceptibilities of Group C and Group G Streptococci Isolated from Patients with Invasive Infections: Evidence of Vancomycin Tolerance among Group G Serotypes
A retrospective review of medical records for 32 patients with invasive group C streptococcus (GCS) or group G streptococcus (GGS) infections was performed. MICs and minimum bactericidal concentrations (MBCs) of penicillin, erythromycin, and vancomycin for all isolates were obtained. Tolerance of vancomycin, defined as an MBC 32 or more times higher than the MIC, was exhibited by 18 GGS isolates (54%). The identification of tolerance in clinical isolates of GGS and GCS may have clinical implications in treating these seriously ill patients.
There is increasing interest in the role of Lancefield group C streptococci (GCS) and group G streptococci (GGS) as emerging nosocomial and opportunistic pathogens (31,35). The spectrum of human infection caused by these organisms includes primary and secondary bacteremia in normal and immunocompromised hosts, as well as cellulitis, endocarditis, skin and wound infections, meningitis, arthritis, osteomyelitis, pneumonia, abscesses, puerperal infections, and pharyngitis (2, 4-11,13-16, 19, 20, 26, 31, 35).
Besides being classified by the Lancefield group carbohydrate, the β-hemolytic streptococci are subdivided on the basis of whether they form large colonies or small colonies on sheep blood agar plates (BAP) (6, 7, 10, 13, 15). The large-colony phenotypes of group A and group B are associated with the pathogenic speciesStreptococcus pyogenes and Streptococcus agalactiae. Similarly, GCS and GGS large-colony phenotypes are those usually associated with human infection. GCS and GGS are classified in the same subspecies, Streptococcus dysgalactiae subsp. equisimilis subsp. nov. (34), and are termed S. pyogenes-like because these species share a number of virulence factors with group A streptococci (S. pyogenes). Small- colony-forming species are placed in the Streptococcus anginosus group (formerly known as Streptococcus milleri) and are less common causes of abscess formation and bacteremia (12, 15, 32).
The majority of GCS and GGS strains demonstrate in vitro susceptibility to penicillins, vancomycin, erythromycin, and cephalosporins (3,30). Antimicrobial tolerance, defined as a minimum bactericidal concentration (MBC) 32 or more times higher than the MIC, among GCS and GGS has been reported for penicillin and other agents (24, 27,29). Only a few clinical isolates have been reported to exhibit tolerance of vancomycin (24, 29). We previously reported tolerance of vancomycin among pharyngeal isolates of non-group A β-hemolytic streptococci (mostly GCS and GGS) from children (36). We chose to investigate further these antibiotic susceptibility patterns among GCS and GGS isolated from patients with invasive infections (bacteremia and meningitis, etc.), for whom similar findings of tolerance may have clinical implications.
(The study was performed at the Alfred I. duPont Hospital for Children, Wilmington, Del. This work was presented in part at the 97th General Meeting of the American Society for Microbiology held in May 1997 in Miami Beach, Fla. .)
At Christiana Care Health Systems a retrospective chart review was performed with 32 patients from whom GCS and GGS were isolated from sterile sites between December 1991 and March 1996. Clinical data were collected on all patients. Bacterial isolates were recovered from frozen storage (−70°C) for further evaluation. Isolate identification was performed with the API 20S Strep Strip (bioMerieux Vitek, Hazelwood, Mo.). Serotyping for GCS and GGS was performed with the PathoDx agglutination kit (Remel, Lenexa, Kans.).
MICs of penicillin, erythromycin, and vancomycin were performed by using National Committee for Clinical Laboratory Standards (NCCLS) broth microdilution methods (22). Tests were performed in cation-adjusted Mueller-Hinton broth with lysed horse blood (Remel; lot 5517). Dilutions tested ranged from 16 to 0.016 μg/ml for all drugs. Plates were prepared on-site (100 μl per well), and antibiotic powders were supplied by the respective manufacturers. Microtiter plates were prepared to include a positive growth control well and a medium sterility well. Plates were stored at −70°C until use and thawed completely at room temperature before inoculation. Organisms were grown in Trypticase soy broth (Becton Dickinson, Cockeysville, Md.; lot 100K7DEJS) for 2 h and then maintained at a 0.5 McFarland standard. Microtiter plates were inoculated with 0.01 ml of the standardized, diluted organism suspension and then incubated at 35°C in 6% carbon dioxide for 20 h. The MIC was interpreted as the lowest concentration of drug at which no growth was visible in the microtiter well. The NCCLS breakpoints for streptococci were used to interpret MIC results (23).
Wells with no visible growth were subcultured on BAP to determine the MBC (50 μl from each well). The BAP were incubated for 24 h at 35°C in carbon dioxide. The MBC was interpreted as the lowest concentration of drug at which fewer than five colonies were observed on the BAP.
All MIC and MBC assays were performed in duplicate for reliability. Broth macrodilution methods according to NCCLS standard procedures were used to confirm MIC and MBC broth microdilution results (21,22).
Streptococcus pneumoniae ATCC 49619 was used for quality control for all antimicrobials and was tested with each batch of microtiter plates. The results obtained were consistently within acceptable ranges for all drugs.
Between December 1991 and March 1996, 32 sterile-site isolates, 27 GGS and five GCS, were identified and retrieved for study. The demographic and clinical characteristics of the 27 patients for whom data were available are shown in Table 1.
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Clinical data for patients from whom GCS and GGS streptococci were isolateda
The microbiological and antibiotic susceptibility data, including MIC and MBC broth microdilution results, are summarized in Table2. Of the 27 GGS isolates, 23 were identified to species level as S. dysgalactiae subsp.equisimilis (large-colony phenotype), three were S. anginosus, and one isolate became nonviable prior to completion of species identification. Among the five GCG isolates, one was S. dysgalactiae subsp. equisimilis (large-colony phenotype) and four were S. anginosus. All MIC and MBC results obtained by broth macrodilution methods were nearly identical to the broth microdilution results presented in Table 2.
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MICs and MBCs of penicillin, erythromycin, and vancomycin for sterile-site isolates
All isolates were susceptible to penicillin, and their MICs ranged from ≤0.016 to 0.06 μg/ml. The MBCs ranged between ≤0.016 and 0.5 μg/ml, with no evidence of tolerance. Three isolates, two GGS (large-colony phenotype) and one GCS (large-colony phenotype), were resistant to erythromycin (MICs > 16 μg/ml). The range of erythromycin MICs was ≤0.016 to >16 μg/ml. All isolates were susceptible to vancomycin (MICs between 0.12 and 0.5 μg/ml). Eighteen isolates of GGS exhibited tolerance of vancomycin (MBCs 32 or more times higher than the MICs ).
The purpose of this study was to characterize the antibiotic susceptibility patterns of GCS and GGS isolated from sterile clinical sites. The characteristics of patients with GCS and GGS infections (predominantly bacteremia) in our study are consistent with previous reports linking these infections with underlying malignancy or immune system compromise (2, 4, 5, 9, 19, 31, 35). Given the retrospective nature of this study, no conclusions on the relationship between patient outcome and the presence of a tolerant organism can be made, because the majority of patients were at high risk and were not uniformly treated with vancomycin alone.
Our in vitro findings support the use of penicillin G as the antimicrobial agent of choice for GCS and GGS infections. All MICs were less than 0.03 μg/ml, and tolerance was not identified. All isolates in our study were susceptible to vancomycin (MICs ranging between 0.12 and 0.5 μg/ml), but 18 of 32 (54%) GGS demonstrated tolerance. No GCS isolates exhibited tolerance. Since there are few reports in the literature of GCS isolates examined for vancomycin tolerance, the significance of this difference between GCS and GGS is unclear.
Noble et al., in one of the most widely cited reports of vancomycin tolerance among GGS, reported eight of nine clinical isolates that were tolerant of vancomycin (24). Rolston et al. examined the in vitro activity of nine antimicrobial agents against 35 GGS and 26 GCS isolates from various clinical sites (29). One GGS isolate exhibited tolerance of vancomycin. The two reports in the literature of tolerance to vancomycin have shown significant variability in the percentage of tolerant GGS (eight of nine in Noble’s study and one of 35 in Rolston’s study). The causes of variability are hypothetical, given the small amount of previous data available, but may include the year of collection, geography, source of the isolate, and previous antibiotic use.
The significance of in vitro vancomycin tolerance is uncertain, and our findings do not necessarily reflect clinical efficacy. Recent evidence presented by Novak et al. demonstrates a molecular mechanism for vancomycin tolerance in S. pneumoniae. A rabbit meningitis model utilized in their studies indicated the failure of vancomycin therapy to eradicate tolerant organisms from the cerebrospinal fluid (25). Concerns about potential antibiotic tolerance in GCS and GGS and reports of clinical failures in patients with severe infections have led many authors to recommend combination therapy for synergy (aminoglycoside plus a cell wall-active agent) in the initial treatment of these patients (1, 17, 18, 27, 28, 31, 33, 35).
Our in vitro findings suggest that among high-risk patients with invasive GCS and GGS infections who cannot be treated with penicillin, tolerance of other antimicrobial agents, including vancomycin, should be closely monitored.
- Received 8 February 1999.
- Returned for modification 2 May 1999.
- Accepted 10 July 1999.
- Copyright © 1999 American Society for Microbiology
An unidentified woman suffers from a sore throat. (iStock)
In late fall and early spring, you’re probably not too concerned about catching colds and dealing with sore throats. You’re busy enjoying the changing seasons, and you should be. If you do happen to get a sore throat that lasts several days, you should see a doctor immediately. Streptococcal bacteria, the culprits that cause strep throat, thrive during these seasons, and the infection is easy to catch.
An Extreme Case of Strep Throat
While children may have a higher risk of getting strep throat, adults can catch it too. One man from Michigan found out just how seriously the infection can be if left untreated.
At first, Kevin went to see a doctor for pain that he was feeling in his stomach. One day later, he returned to the hospital with no improvement from medication, and doctors began to dig. Upon performing an exploratory surgery, they found his stomach filled with infection and eventually pinned strep throat as the cause.
During this process, Kevin’s organs began failing. Doctors had to stimulate more blood flow to his organs to keep him alive. Unfortunately, they weren’t able to save his hands and feet, requiring amputations on all four of Kevin’s limbs.
Strep Throat Complications
Yes, this case of strep throat is certainly extreme, but the contagious infection can cause many problems if ignored. One harmful complication is an infection to the kidneys.
If a strep infection goes untreated, the bacteria will often wreak havoc on your kidneys, causing swelling, blood in urine, and joint pain. If the infection goes this far, you will need to be watched closely to ensure that the medicine is working effectively.
In other undiagnosed cases, the strep infection can spread to major areas such as the skin, heart, blood, and nervous system. Some people progress on to such illnesses as scarlet fever, meningitis, or even toxic shock. Again, these extreme cases are rare, especially if the infection is treated at the first onset of symptoms.
So What Exactly is Strep Throat?
Strep throat is an infection caused by a contagious strain of bacteria called Streptococcus pyogenes, or group A strep. Each year, millions of people develop a mild form of strep infection, and 10–15 thousand go on to worsened cases.
People with the strep bacteria can spread the infection easily when they sneeze or cough. If they have any bacteria on their hands, they will contaminate food, door knobs, and any other touchable surfaces.
To prevent spreading bacteria, you should wash your hands multiple times throughout the day and wipe down commonly touched surfaces often. Don’t share food with someone who has strep throat, and avoid touching your face, especially your nose and eyes. If a family member gets strep throat, give them full rest from responsibilities and take extra care when cleaning.
Signs of Infection
Much of the time, you can probably link your sore throat to a cold. However, if you experience symptoms related to strep throat, you’ll want to see your doctor right away. These symptoms include:
- Prolonged sore throat (several days)
- Pain when swallowing
- Inflamed tonsils (a reddened throat, perhaps with some white areas)
- Sore and swollen lymph nodes in the neck
- Fever lasting more than 48 hours
- Spreading rash
In the event that you do have strep throat, your doctor will give you antibiotics to fight off the bacteria. You should rest for several days and keep away from friends and family as much as possible. Do not go to work or return to school until your doctor has given permission, or you may infect others around you.
If you don’t see improvement within two days, call a doctor. Otherwise, you should return to your normal self and busy life within a matter of days.
Although you don’t see cases as extreme as Kevin’s every day, you can still learn from his story. Strep throat can be potentially dangerous, causing major complications if left untreated. Take it seriously at the first onset of symptoms, and you’ll be up and running again in no time.