- Streptococcus pyogenes Agent Information Sheet
- Streptococcus pyogenes and streptococcal disease
- Strains of Streptococcus pyogenes from Severe Invasive Infections Bind HEp2 and HaCaT Cells More Avidly than Strains from Uncomplicated Infections
- Streptococcus pyogenes
- Asymptomatic carriage of Streptococcus pyogenes among school children in Sana’a city, Yemen
Streptococcus pyogenes Agent Information Sheet
Research Occupational Health Program (ROHPResearch Occupational Health Program ROHP is part of the …)
Streptococcus pyogenes Group A (β-hemolytic) streptococci (GAS), is an aerobic, gram-positive extracellular bacterium. It is made up of non-motile, non-sporing cocci that are less than 2 µm in length and that form chains and large colonies greater than 0.5 mm in size. It has a β-hemolytic growth pattern on blood agar and there are over 60 different strains of the bacterium.
pyogenes is responsible for a wide array of infections, including streptococcal sore throat, strep throat, pharyngitis, scarlet fever, impetigo, erysipelas, puerperal fever, necrotizing fasciitis, toxic shock syndrome, septicemia, acute rheumatic fever, acute post-streptococcal glomerulonephritis, and gas gangrene.
There are at least 517,000 deaths globally each year due to severe S. pyogenes infections and rheumatic fever disease alone causes 233,000 deaths. 1,800 invasive S.
pyogenes disease-related deaths are reported in the USA yearly, necrotizing fasciitis kills about 30% of patients and streptococcal toxic shock syndrome has a mortality rate of 30-70%.
Different clinical manifestations of this bacterium are more common in different parts of the world.
- Special Populations at RiskOutside of the laboratory, crowding and poor hygiene increase the chance of an outbreak of GAS infections.
Risk Group 2
Biosafety Lab 2 Practices
Modes of Transmission
|Skin Exposure (Needlestick, bite, or scratch):||Yes, hand contact with nasal discharge and skin contact with impetigo lesions|
|Mucous Membrane Splash to Eye(s), Nose or Mouth:||Yes, direct contact with mucosal tissue|
|Inhalation:||Yes, exposure to infected aerosols|
|Ingestion:||Yes, through contaminated food sources but rare|
The pathogen can be found in its carrier state in the anus, vagina, skin and pharynx and contact with these surfaces can spread the infection
pyogenesis an exclusively human pathogen.
Symptoms vary depending on the type of infection and can affect a variety of organ systems. For streptococcal sore throat, symptoms are characterized by fever, enlarged tonsils, tonsillar exudate, sensitive cervical lymph nodes and malaise. Scarlet fever manifestations include fever and a pink-red rash.
Impetigo will result in infection of the superficial layers of skin. Acute rheumatic fever will result in joint inflammation, carditis, and nervous system complications. Post—streptococcal glomerulonephritis causes hematuria, fever, edema, and hypertension.
More serious complications may include severe skin infections and subsequent tissue destruction.
The incubation period is usually 1-3 days.
This bacteria is susceptible to 1% sodium hypochlorite, 4% formaldehyde, 2% glutaraldehyde, 70% ethanol, 70% propanol, 2% peracetic acid, 3-6% hydrogen peroxide and 0,16% iodine. Bacteria are susceptible to moist heat (121 ºC for at least 15 minutes) and dry heat (170 ºC for at least 1 hour).
Survival Outside Host
The bacterium can survive on a dry surface for 3 days to 6.5 months. In contaminated food: found to survive in ice cream (18 days), raw and pasteurized milk at 15-37 ºC (96 hrs.), room temperature butter (48 hrs.), and neutralized butter (12-17 days). GAS has been found to last several days in cold salads at room temperature.
Personal protective equipment includes but is not limited to laboratory coats or gowns, disposable gloves, and safety glasses.
Research should be conducted using Biosafety Level 2 practices, equipment, and facility design.
In Case of Exposure/Disease
- For injuries in the lab which are major medical emergencies (heart attacks, seizures, etc…):
- Medical Campus: call or have a coworker call the Control Center at 617-414–4144.
- Charles River Campus: call or have a coworker call campus security at 617-353-2121.You will be referred to or transported to the appropriate health care location by the emergency response team.
- For lab exposures (needle sticks, bite, cut, scratch, splash, etc…) involving animals or infectious agents, or for unexplained symptoms or illness call the ROHP 24/7 hour number (1-617-358-ROHP (7647); or, 8-ROHP (7647) if calling from an on-campus location) to be connected with the BU Research Occupational Health Program (ROHP) medical officer. ROHP will refer you to the appropriate health care location.
- Under any of these scenarios, always inform the physician of your work in the laboratory and the agent(s) that you work with.
- Provide the wallet-size agent ID card to the physician.
Public Health Issues
Person to person transmission is common. The bacterium can remain in the body in its carrier state without causing illness in the host for weeks or months and is transmissible in this state.
In patients with strep pharyngitis, patients are infective in acute phase of the illness, usually 7-10 days, and for one week afterwards. With antibiotics, infective period is decreased to 24 hours. Standard precautions should be used.
If cluster of cases is suspected, transmission based precautions are utilized.
Monitor for symptoms. Confirm infection by bacteriological and serological testing, latex bead agglutination, fluorescent antibody staining or ELISA.
First Aid/Post Exposure Prophylaxis
Post exposure prophylaxis with antibiotics should be considered.
Perform one of the following actions:
|Skin Exposure (Needlestick or scratch):||Immediately go to the sink and thoroughly wash the wound with soap and water for 15 minutes. Decontaminate any exposed skin surfaces with an antiseptic scrub solution.|
|Mucous Membrane Splash to Eye(s), Nose or Mouth:||Exposure should be irrigated vigorously.|
|Splash Affecting Garments:||Remove garments that may have become soiled or contaminated and place them in a double red plastic bag.|
Percutaneous inoculation of GAS carries a significant risk for developing invasive infections, with the extreme instances of necrotizing fasciitis and/or streptococcal toxic shock syndrome. Mucous membrane inoculation would be most concerning to the eyes. These injuries may appear benign early, but without proper management may evolve into serious infections even with a small inoculum.
If any signs or symptoms of infection, admission should be considered, with Infectious Disease consult. Complete total of 2 doses of IV antibiotic (ceftriaxone 1g IV q24H or daptomycin 4 mg/kg IV q24h) before transitioning to oral antibiotics to complete a total of 7-10 days of treatment.
After IV course, preferred oral antibiotics would be cephalexin 500mg PO q12h (if given ceftriaxone IV); clindamycin 450mg PO q8h or levofloxacin 750mg PO q24h (if intolerant of penicillins and/or cephalosporins).
Public Health Agency of Canada; http://www.phac-aspc.gc.ca/lab-bio/res/psds-ftss/strep-pyogenes-eng.php
CDC BMBL: http://www.cdc.gov/biosafety/publications/bmbl5/BMBL.pdf
Streptococcus pyogenes and streptococcal disease
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Streptococcus pyogenes and Streptococcal Disease (page 1)
(This chapter has 4 pages)
© Kenneth Todar, PhD
Streptococcus pyogenes(Group A streptococcus) is a Gram-positive, nonmotile, nonsporeforming coccus that occurs in chains or in pairs of cells. Individual cells are round-to-ovoid cocci, 0.6-1.0 micrometer in diameter (Figure 1).
Streptococci divide in one plane and thus occur in pairs or (especially in liquid media or clinical material) in chains of varying lengths. The metabolism of S. pyogenes is fermentative; the organism is a catalase-negative aerotolerant anaerobe (facultative anaerobe), and requires enriched medium containing blood in order to grow.
Group A streptococci typically have a capsule composed of hyaluronic acid and exhibit beta (clear) hemolysis on blood agar.
Figure 1. Streptococcus pyogenes. Left. Gram stain of Streptococcus pyogenes in a clinical specimen. Right. Colonies of Streptococcus pyogenes on blood agar exhibiting beta (clear) hemolysis.
Streptococcus pyogenes is one of the most frequent pathogens of humans. It is estimated that between 5-15% of normal individuals harbor the bacterium, usually in the respiratory tract, without signs of disease. As normal flora, S.
pyogenes can infect when defenses are compromised or when the organisms are able to penetrate the constitutive defenses.
When the bacteria are introduced or transmitted to vulnerable tissues, a variety of types of suppurative infections can occur.
In the last century, infections by S. pyogenes claimed many lives especially since the organism was the most important cause of puerperal fever (sepsis after childbirth).
Scarlet fever was formerly a severe complication of streptococcal infection, but now, because of antibiotic therapy, it is little more than streptococcal pharyngitis accompanied by rash.
Similarly, erysipelas (a form of cellulitis accompanied by fever and systemic toxicity) is less common today.
However, there has been a recent increase in variety, severity and sequelae of Streptococcus pyogenes infections, and a resurgence of severe invasive infections, prompting descriptions of “flesh eating bacteria” in the news media.
A complete explanation for the decline and resurgence is not known. Today, the pathogen is of major concern because of the occasional cases of rapidly progressive disease and because of the small risk of serious sequelae in untreated infections. These diseases remain a major worldwide health concern, and effort is being directed toward clarifying the risk and mechanisms of these sequelae and identifying rheumatogenic and nephritogenic strains of streptococci.
Acute Streptococcus pyogenes infections may present as pharyngitis (strep throat), scarlet fever (rash), impetigo (infection of the superficial layers of the skin) or cellulitis (infection of the deep layers of the skin).
Invasive, toxigenic infections can result in necrotizing fasciitis, myositis and streptococcal toxic shock syndrome.
Patients may also develop immune-mediated post-streptococcal sequelae, such as acute rheumatic fever and acute glomerulonephritis, following acute infections caused by Streptococcus pyogenes.
Streptococcus pyogenes produces a wide array of virulence factors and a very large number of diseases.
Virulence factors of Group A streptococci include: (1) M protein, fibronectin-binding protein (Protein F) and lipoteichoic acid for adherence; (2) hyaluronic acid capsule as an immunological disguise and to inhibit phagocytosis; M-protein to inhibit phagocytosis (3) invasins such as streptokinase, streptodornase (DNase B), hyaluronidase, and streptolysins; (4) exotoxins, such as pyrogenic (erythrogenic) toxin which causes the rash of scarlet fever and systemic toxic shock syndrome.
Classification of Streptococci
Hemolysis on blood agar
The type of hemolytic reaction displayed on blood agar has long been used to classify the streptococci. Beta -hemolysis is associated with complete lysis of red cells surrounding the colony, whereas alpha-hemolysis is a partial or “green” hemolysis associated with reduction of red cell hemoglobin.
Nonhemolytic colonies have been termed gamma-hemolytic. Hemolysis is affected by the species and age of red cells, as well as by other properties of the base medium. Group A streptococci are nearly always beta-hemolytic; related Group B can manifest alpha, beta or gamma hemolysis. Most strains of S.
pneumoniae are alpha-hemolytic but can cause ß-hemolysis during anaerobic incubation. Most of the oral streptococci and enterococci are non hemolytic. The property of hemolysis is not very reliable for the absolute identification of streptococci, but it is widely used in rapid screens for identification of S.
pyogenes and S. pneumoniae.
The cell surface structure of Group A streptococci is among the most studied of any bacteria (Figure 2). The cell wall is composed of repeating units of N-acetylglucosamine and N-acetylmuramic acid, the standard peptidoglycan.
Historically, the definitive identification of streptococci has rested on the serologic reactivity of “cell wall” polysaccharide antigens as originally described by Rebecca Lancefield. Eighteen group-specific antigens (Lancefield groups) were established. The Group A polysaccharide is a polymer of N-acetylglucosamine and rhamnose.
Some group antigens are shared by more than one species. This polysaccharide is also called the C substance or group carbohydrate antigen.
Strains of Streptococcus pyogenes from Severe Invasive Infections Bind HEp2 and HaCaT Cells More Avidly than Strains from Uncomplicated Infections
Epidemiologically unrelated Streptococcus pyogenes strains isolated from blood, throat, and skin were assayed for adherence to HEp2 and HaCaT cells. Invasive isolates showed significantly higher avidity for these cell lines than isolates from skin and throat. In general, S. pyogenes showed greater binding to HaCaT cells than to HEp2 cells.
Streptococcus pyogenes (group A streptococcus [GAS]) is an etiological agent for diverse human diseases, including pharyngitis, pyoderma, and severe invasive diseases. In addition, the pathogen is associated with potentially life-threatening sequelae such as poststreptococcal glomerulonephritis and acute rheumatic fever.
In the Northern Territory (NT) of Australia the incidence of acute rheumatic fever is very high among the indigenous population (3), despite a low throat isolation rate of GAS. Furthermore, pyoderma from GAS infection is extremely common and poststreptococcal glomerulonephritis is endemic in many remote Aboriginal communities (4, 7).
While asymptomatic throat carriage is often the reported reservoir for strains associated with invasive disease (5), in populations where impetigo is endemic, such as in Aboriginal communities in the NT, the primary reservoir is the skin.
Irrespective of which tissue is the primary site of infection, the first event the pathogen needs to achieve is adherence to host cells. The S. pyogenes genome encodes numerous genes that could be regarded as encoding adhesins.
These genes are highly regulated, and individual strains do not have the genetic potential to encode all of these proteins. The adhesins include M protein (an antiphagocytic molecule), capsule, and fibronectin binding proteins. There are many different fibronectin binding proteins, such as SI (8, 12), PrtF2 (9, 10), p54 (2), and SII (11).
The adherence capacity of an individual strain could vary depending on the repertoire of genes for the adhesins that the strain possesses and their level of expression. This in turn may reflect the differences in the ability to colonize and persistently infect different tissue sites.
A corollary of this is that isolates from different tissue sites may exhibit differences in adherence capacity. To test this, we have determined the extent of binding of GAS isolates from skin, throat, and blood to HEp2 and HaCaT cell lines, representing human laryngeal epithelial cells and keratinocytes, respectively.
GAS isolates from the NT were collected between 1990 and 2002. The 72 strains analyzed in this study were isolated from blood (n = 26), skin (n = 22), and throat (n = 24) (Table 1). Blood isolates were from severe disease, and the remaining strains were from uncomplicated infections. The isolates were Vir typed as described previously (6).
Vir typing involves restriction fragment length polymorphism of the mga regulon, which includes the gene for highly variable M protein. To ensure inclusion of epidemiologically unrelated strains, one representative isolate from each Vir type was included.
Cultures were grown overnight at 37°C in an orbital shaker to stationary phase in Todd-Hewitt broth (Oxoid, Basingstoke, United Kingdom) supplemented with 1% yeast extract. To prepare the GAS inoculum for adherence assays, overnight cultures were centrifuged, and the pellets were washed in phosphate-buffered saline (PBS; Life Technologies Gibco BRL, New York, N.Y.
) and resuspended in serum-free and antibiotic-free RPMI 1640 medium (Life Technologies) to an optical density at 600 nm of 0.05. This represents approximately 1 × 107 to 1.5 × 107 bacteria per ml.
Human laryngeal epithelial (HEp2) cells were maintained in RPMI 1640 medium supplemented with 10% fetal calf serum (Life Technologies), 1% Fungizone (Life Technologies), 20 μg of vancomycin HCl (David Bull Laboratories, Sydney, Australia) per ml, and 100 μg of streptomycin sulfate (Sigma, St. Louis, Mo.) per ml.
Human adult skin keratinocytes (HaCaT cells) were maintained in Dulbecco's modified Eagle medium (Life Technologies) supplemented with 10% heat-inactivated fetal calf serum.
For adherence assays, ∼105 cells/ml were seeded onto 12-mm-diameter glass coverslips in the bottoms of 24-well tissue culture plates (Nunc, Roskilde, Denmark). After overnight growth at 37°C in 5% CO2 atmosphere, the cells were washed with PBS (pH 7.4) and inoculated with 500 μl of the GAS inoculum.
After 2 h of incubation at 37°C, the coverslips were washed five times by adding 1 ml of PBS to each well, and after gentle mixing, the wash solution was removed by aspiration. After removal of the nonadherent bacteria, the host cells and adherent bacteria were fixed with 95% methanol and air-dried.
After heat fixing, the coverslips were placed on slides and Gram stained for viewing under oil immersion. In each experiment, cells in several random fields were analyzed, and attachment was expressed as the average number of GAS chains per cell.
All assays were performed in duplicate, and the mean binding was determined for each strain. All statistical analyses were performed with Stata Statistics/Data Analysis program version 7.0 (Stata Corporation, College Station, Tex.). Data were analyzed with t tests.
GAS strains adhered to both cell types, and the degree of binding varied from strain to strain (Table 1). There was good correlation between independent experiments with 20 isolates repeated at two time intervals (data not shown), suggesting the avidity of binding is reproducible and strain specific.
Overall, GAS binding to HaCaT cells is greater than to HEp2 cells (P < 0.05). When the data in Table 1 were separated the tissue site of isolation, an average of 270 chains of GAS strains from blood bound to 50 HaCaT cells (Fig. 1). In contrast, skin and throat isolates bound on average only 169 and 178 chains per 50 HaCaT cells, respectively.
These differences are statistically significant (P = 0.0044 and 0.0063, respectively). Interestingly, for HEp2 cells the differences are less pronounced and not statistically significant.
However, when the data were reanalyzed invasive versus uncomplicated infections by combining data for the skin and throat isolates, significant differences between the two categories were found in both cell lines (P = 0.0011 for HaCaT; P = 0.0238 for HEp2).
Earlier work from this laboratory showed that many commonly circulating strains of S. pyogenes could cause invasive disease with skin as the primary site of infection (1).
These observations are consistent with the present findings of higher avidity of the NT GAS strains for HaCaT than HEp2 cell lines and blood isolates being able to bind in greater numbers than the isolates from uncomplicated infections. Possible explanations for the high adherence propensity of S.
pyogenes blood isolates include both genotypic and phenotypic differences between isolates from invasive and noninvasive disease sources. Further studies are required to define the nature of this binding avidity and to determine whether it is consistent within clonal populations.
Comparison of binding of GAS to HaCaT and HEp2 cell lines. Statistically significant results are indicated by asterisks. Error bars represent standard errors.
Vir type, binding, and source of isolation of GAS isolates used in this study
We are indebted to D. Gordon and E. Giannakis for advice and for providing HaCaT cells.
Funds from Cooperative Research Centre for Aboriginal and Tropical Health supported this work.
- Received 20 March 2003.
- Returned for modification 1 May 2003.
- Accepted 6 May 2003.
PATHOGEN SAFETY DATA SHEET – INFECTIOUS SUBSTANCES
SECTION I – INFECTIOUS AGENT
NAME: Streptococcus pyogenes
SYNONYM OR CROSS REFERENCE: Group A (β-hemolytic) streptocci (GAS), streptococcal sore throat, strep throat, pharyngitis, scarlet fever, impetigo, erysipelas, puerperal fever, necrotizing fasciitis, toxic shock syndrome, septicaemia, acute rheumatic fever, acute post-streptococcal glomerulonephritis, gas gangrene
CHARACTERISTICS: Streptococcus pyogenes is an aerobic, gram-positive extracellular bacterium (1, 2). It is made up of non-motile, non-sporing cocci that are less then 2 µm in length and that form chains and large colonies greater then 0.5 mm in size (3, 4). It has a β-hemolytic growth pattern on blood agar and there are over 60 different strains of the bacterium (5, 6)
SECTION II – HAZARD IDENTIFICATION
PATHOGENICITY/TOXICITY: This bacterium is responsible for a wide array of infections (7, 8). It can cause streptococcal sore throat which is characterized by fever, enlarged tonsils, tonsillar exudate, sensitive cervical lymph nodes and malaise (6, 9). If untreated, strep throat can last 7-10 days (9).
Scarlet fever (pink-red rash and fever) as well as impetigo (infection of the superficial layers of skin) and pneumonia are also caused by this bacterium (3, 6, 7, 10). Septicaemia, otitis media, mastitis, sepsis, cellulitis, erysipelas, myositis, osteomyelitis, septic arthritis, meningitis, endocarditis, pericarditis, and neonatal infections are all less common infections due to S.
pyogenes (3, 6, 7).
Streptococcal toxic shock syndrome, acute rheumatic fever (joint inflammation, carditis and CNS complications), post-streptococcal glomerulonephritis (inflammation, hematuriia, fever, edema, hypertension, urinary sediment abnormalties and severe kidney pain) and necrotizing fasciitis (rapid and progressive infection of subcutaneous tissue, massive systematic inflammation, hemorrhagic bullae, crepitus and tissue destruction) are some of the more serious complications involving S. pyogenes infections (1, 6-8). There are at least 517,000 deaths globally each year due to severe S. pyogenes infections and rheumatic fever disease alone causes 233,000 deaths (8). 1,800 invasive S. pyogenes disease-related deaths are reported in the USA yearly, necrotizing fasciitis kills about 30% of patients and streptococcal toxic shock syndrome has a mortality rate of 30-70% (3, 11, 12).
EPIDEMIOLOGY: Different clinical manifestations of this bacterium are more common in different parts of the world. Streptococccal pharyngitits is predominant in temperate areas and peaks in late winter and early spring (5, 9). There are 616 million cases of pharyngitis caused by S.
pyogenes world-wide each year (5, 8). 15-20% of school-aged children has S. pyogenes in its carrier form in their throats and are more at risk of having the disease (5, 9). Impetigo is more common with children in warm humid climates and there are 111 million reported cases world-wide each year (5). There are 115.
6 million cases of rheumatic heart disease yearly and at least 18.1 million cases of invasive infections, predominantly in older populations (3, 8). Post-streptococcal glomerulonephritis is seasonal and is more common in children, young adults and males (1).
Crowding and poor hygiene increase the chance of an outbreak of GAS infections (1).
HOST RANGE: S. pyogenes is an exclusively human pathogen (5, 7).
INFECTIOUS DOSE: Unknown.
MODE OF TRANSMISSION: Transmission via respiratory droplets, hand contact with nasal discharge and skin contact with impetigo lesions are the most important modes of transmission (5, 9, 13).
The pathogen can be found in its carrier state in the anus, vagina, skin and pharynx and contact with these surfaces can spread the infection (5, 14, 15) The bacterium can be spread to cattle and then back to humans through raw milk as well as through contaminated food sources (salads, milk, eggs); however, cattle do not contract the disease (16-18). Necrotizing fasciitis is usually because of contamination of skin lesions or wounds with the infectious agent (12).
INCUBATION PERIOD: The incubation period is usually 1-3 days (9).
COMMUNICABILITY: If untreated, patients with streptococcal pharyngitis are infective during the acute phase of the illness, usually 7-10 days, and for one week afterwards; however, if antibiotics are used, the infective period is reduced to 24 hours (9). The bacterium can remain in the body in its carrier state without causing illness in the host for weeks or months and is transmissible in this state (5).
SECTION III – DISSEMINATION
RESERVOIR: Humans are primary reservoir for this bacterium (5, 7), although cattle can also act as a reservoir (16-18).
ZOONOSIS: Cows infected by humans are intermediate hosts and can pass the bacterium in their milk, which, if consumed unpasteurized, can infect other humans (16).
SECTION IV – STABILITY AND VIABILITY
DRUG SUSCEPTIBILITY: S. pyogenes infections are susceptible to a variety of drugs: β-lactams such as penicillin, as well as erythromycin, clindamycin, imipenem, rifampin, vanomycin, macrolides and lincomycin; however, certain strains of the bacterium have been found to resistant to macrolides, lincomycin, chloramphenicol, tetracyclines and cotrimoxazole (5, 7, 19, 20).
SUSCEPTIBILITY TO DISINFECTANTS: This bacteria is susceptible to 1% sodium hypochlorite, 4% formaldehyde, 2% glutaraldehyde, 70% ethanol, 70% propanol, 2% peracetic acid, 3-6% hydrogen peroxide and 0,16% iodine (2).
PHYSICAL INACTIVATION: Bacteria are susceptible to moist heat (121 ºC for at least 15 minutes) and dry heat (170 ºC for at least 1 hour) (21).
SURVIVAL OUTSIDE HOST: The bacterium can survive on a dry surface for 3 days to 6.5 months (22). It has been found to survive in ice cream (18 days), raw and pasteurized milk at 15-37 ºC (96 hrs), room temperature butter (48 hrs), and neutralized butter (12-17 days) (17). GAS has been found to last several days in cold salads at room temperature (18). SECTION V – FIRST AID / MEDICAL
SURVEILLANCE: Monitor for symptoms. Confirm infection by bacteriological and serological testing, latex bead agglutination, fluorescent antibody staining or ELISA (6).
Note: All diagnostic methods are not necessarily available in all countries.
FIRST AID/TREATMENT: Appropriate antibiotic treatment is necessary for a S. pyogenes infection. Penicillin is used for respiratory tract infections (pharyngitis) and macrolides or lincosamides are used if there are allergies (5, 6). Clindamycin may be used in cases of necrotizing fasciitis and surgical debridement of the affected area is necessary (2, 5).
IMMUNIZATION: None (6).
PROPHYLAXIS: Administering penicillin to carriers has been shown to reduce the number of people infected during an outbreak of streptococcal sore throat (18).
SECTION VI – LABORATORY HAZARDS
LABORATORY-ACQUIRED INFECTIONS: 78 laboratory-acquired infections by streptococcal agents have been reported as of 1983 (2).
SOURCES/SPECIMENS: Respiratory specimens, skin lesions, blood, sputum and wound exudates contain the infectious agent (5, 13, 23).
PRIMARY HAZARDS: Inhalation of infectious aerosols and contamination of mucocutaneous lesions are the primary hazards associated with working with this pathogen (1, 2, 10)
SPECIAL HAZARDS: None
SECTION VII – EXPOSURE CONTROLS / PERSONAL PROTECTION
RISK GROUP CLASSIFICATION: Risk group 2 (24).
CONTAINMENT REQUIREMENTS: Containment Level 2 facilities, equipment, and operational practices for work involving infectious or potentially infectious material, animals, or cultures.
PROTECTIVE CLOTHING: Lab coat. Gloves when direct skin contact with infected materials or animals is unavoidable. Eye protection must be used where there is a known or potential risk of exposure to splashes (25).
OTHER PRECAUTIONS: All procedures that may produce aerosols, or involve high concentrations or large volumes should be conducted in a biological safety cabinet (BSC) (25). The use of needles, syringes and other sharp objects should be strictly limited. Additional precautions should be considered with work involving animals or large scale activities (25).
SECTION VIII – HANDLING AND STORAGE
SPILLS: Allow aerosols to settle and, wearing protective clothing, gently cover spill with paper towels and apply appropriate disinfectant, starting at the perimeter and working towards the centre. Allow sufficient contact time before clean up (25).
DISPOSAL: Decontaminate all wastes before disposal by incineration, chemical disinfection or steam sterilization (25).
STORAGE: The infectious agent should be stored in a sealed and identified container (25).
SECTION IX – REGULATORY AND OTHER INFORMATION
REGULATORY INFORMATION: The import, transport, and use of pathogens in Canada is regulated under many regulatory bodies, including the Public Health Agency of Canada, Health Canada, Canadian Food Inspection Agency, Environment Canada, and Transport Canada. Users are responsible for ensuring they are compliant with all relevant acts, regulations, guidelines, and standards.
UPDATED: July 2010
PREPARED BY: Pathogen Regulation Directorate, Public Health Agency of Canada.
Although the information, opinions and recommendations contained in this Pathogen Safety Data Sheet are compiled from sources believed to be reliable, we accept no responsibility for the accuracy, sufficiency, or reliability or for any loss or injury resulting from the use of the information. Newly discovered hazards are frequent and this information may not be completely up to date.
Public Health Agency of Canada, 2010
Penicillin remains the drug of choice for S pyogenes . It issafe, inexpensive, and of narrow spectrum, and there is no direct or indirectevidence of loss of efficacy. Prior to the 1990's, S pneumoniaewas also uniformly sensitive to penicillin but a recent abrupt shift in theusefulness of penicillin has occurred.
The group D enterococci are resistant topenicillins, including penicillinase-resistant penicillins such as methicillin,nafcillin, dicloxacillin, and oxacillin, and are becoming increasingly resistantto many other antibiotics.
Group B streptococci are often resistant totetracycline but remain sensitive to the clinically achievable blood levels ofpenicillin, even though they have penicillin minimal inhibitory concentrations(MIC) considerably higher than those of S pyogenes .
Althoughthe duration of penicillin therapy varies with the degree of invasiveness,streptococcal pharyngitis is generally adequately treated with 10 days ofantibiotic therapy, and pneumococcal pneumonia with 7-14 days.
If penicillinallergy occurs, an alternative drug for treating pharyngitis is erythromycin,although sporadic erythromycin and tetracycline resistance has been reported,leaving clindamycin or the newer macrolides as possible treatments. The mostimportant goal of therapy in acute streptococcal pharyngitis is still to preventrheumatic fever.
However, therapy also hastens clinical recovery, avoidssuppurative complications and renders the patient non-infectious for others. Inaddition to antibiotics, the patient with S pyogenes myositisor necrotizing fasciitis requires surgical debridement.
Lifelong prophylaxisagainst recurrences of rheumatic fever is achieved with long-acting penicillinor erythromycin. Sulfonamides will not eradicate the streptococcus and thus arenot acceptable therapy for streptococcal pharyngitis, but sulfadiazine iseffective for preventing recurrent attacks of rheumatic fever.
Additionalprophylactic coverage before some dental and surgical procedures is necessary inthe presence of rheumatic heart disease or prosthetic heart valves. Althoughstreptococcal pharyngitis is usually a benign, self-limited disease, therapy isimportant to prevent rheumatic fever. There is no convincing evidence thatantibiotic therapy prevents glomerulonephritis. Disconcertingly, some patientsin recent outbreaks of acute rheumatic fever do not give a history of precedingpharyngitis.
Methods of treating the asymptomatic pharyngeal carrier of Spyogenes remain controversial.
Recent evidence suggests that up to20% of children and young adults are carriers, the carrier state involves norisk to the carrier or to others, and it is frequently difficult to eradicatedespite the exquisite sensitivity of the organism to penicillin in vitro. Asimilar failure of antibiotic therapy to eradicate nasopharyngeal carriage or toprevent reinfection with S pneumoniae also occurs.
Although antibiotic resistance in S pneumoniae is common in manyparts of the world, in the United States such strains previously had ageographically limited focus. Recent widespread emergence of Spneumoniae resistant to penicillin and other antibiotics has becomea microbial threat in the United States as well.
Even cefotaxime and ceftriaxoneresistance has been documented.
Isolates must be carefully screened forsusceptibility by oxacillin disc testing, with definitive MIC determination bythe E test (A B Biodisk NA, Piscataway, NJ), a convenient and reliable methodfor detection of resistance to penicillin and extended spectrumcephalosporins.
It is inappropriate to universally treat of pregnant women who are carriers ofgroup B streptococci, or their colonized neonates, for several reasons: the highcarrier rate; cost; the associated high risk of penicillin hypersensitivity; thepotential increase in infections with penicillin-resistant organisms; thedifficulty in altering colonization of women (even when their sexual partnerswere also treated); and the low risk of neonatal disease. The controversycontinues despite recent recommendations for universal screening of preg nantwomen and selective intrapartum chemoprophylaxis for screen-positive motherswith preterm labor, premature or prolonged rupture of membranes, fever in labor,multiple births or previous infants with group B streptococcal disease.
Clearly, penicillin has reduced the severe morbidity and mortality associatedwith S pneumoniae . The emergence of resistance has now forcedre-evaluation of empiric therapy. Clinicians must report clusters of Spneumoniae infection and be aware of local patterns of resistance.Penicillin susceptible organisms show MICs ≤ 0.06 mg/ml, intermediatestrains 0.1-1.
0 mg/ml and high level resistant strains ≥ 2 mg/ml. Fornonmeningeal infection by intermediate strains, parenteral penicillin at highdose can probably be used since the mechanism of resistance involves alterationin penicillin binding proteins (PBP) and saturation.
For meningeal infectionwith intermediate strains or any infection by high level resistant strains onlyceftriaxone and cefotaxime retain sufficient activity. Resistance even to theseextended spectrum cephalosporins was first reported for the US in 1991.
At thiswriting only vancomycin remains uniformly effective but as discussed below, itsuse incurs potential for selection of vancomycin resistant enterococci (VRE) orrisk of transferring vancomycin resistance from enterococci to Spneumoniae .
Currently, no single agent is reliably bactericidal against enterococci.
Seriousinfections with group D enterococci often require a classic synergistic regimecombining penicillin or ampicillin with an aminoglycoside, designed to weakenthe cell wall with the β-lactam and facilitate entry of thebacteriocidal aminoglycoside.
Other β-lactam drugs with good activityagainst enterococci include piperacillin and imipenem. An alternate drug ofchoice is vancomycin, but vancomycin-resistant strains of enterococci have beenisolated. Nosocomial acquisition of these resistant organisms is of graveconcern.
This antibiotic resistance among the streptococci/enterococci is an increasingproblem. Studies show that in vitro exchange of resistant DNAcan occur in conjugation via plasmids and transposons, or in transduction withbacteriophages. The mechanisms involved in the in vivo geneticexchange are not clearly defined.
Evidence is accumulating that otherstreptococci may be the important donors of resistance markers. Transposontransfer is thought to be the most ly mechanism in Spneumoniae , although point mutations also occur. In the setting ofheavy β-lactam use, selective pressure is important in emergence ofresistant strains.
The first penicillin-resistant S pneumoniaewere reported in 1967 in Australia and in 1974 in North America. In New Guinea,where the first penicillin-resistant strains were reported in 1971, one-third ofS pneumoniae isolates from patients with severepneumococcal disease were resistant by 1978.
In Hungary in 1992, 69% ofS pneumoniae isolates were penicillin resistant. Thisresistance is not β-lactamase mediated but due to alteration in PBPwhich results in decreased binding of penicillin by the organism, rendering thedrug less effective and requiring higher concentrations for saturation.
Somestrains resistant to erythromycin or tetracycline also have been reported, aswell as some multiply resistant strains.
In South Africa, outbreaks of infectionwith strains of S pneumoniae resistant to β-lactamantibiotics (penicillins and cephalosporins) as well as to tetracycline,chloramphenicol, erythromycin, streptomycin, clindamycin, sulfonamides, andrifampin were reported in 1977.
Although antibiotic resistance among Spneumoniae was infrequent in the United States, a major shiftoccurred from 1988 to 1990, resulting in the present situation of 15-25% ofS pneumoniae intermediately or completely resistant topenicillin. Communities with “low prevalence” have 5-10%resistance.
Single or multiply resistant strains are transmitted person toperson, especially in settings of frequent salivary exchange, antibiotic use andhand-to-hand transmission (as in day care centers) or of crowding (correctionsfacilities, homeless shelters, nursing homes, military training groups).
Controlof the problem of emerging, antibiotic-resistant S pneumoniaeis multifactorial: 1) surveillance for clusters of invasive disease, resistanceand prevalent serotypes; 2) education of physicians and the public aboutantibiotic use (decrease unnecessary antibiotic use for obviously viralinfections and decrease antibiotic prophylaxis for otitis by use of intermittentor expectant dosing or of non β-lactam based prophylaxissulfa. Usetopical treatment for impetigo, and short course therapies and narrow spectrumantibiotics); 3) adherence to infection control strategies in day care centers;4) aggressive promotion of the current 23-valent S pneumoniaevaccine and support of efforts to design a new vaccine effective in those
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