There are two medically important genera of gram-positive cocci: Staphylococcus and Streptococcus. Two of the most important human pathogens,Staphylococcus aureus and Streptococcus pyogenes, are described in this chapter. Staphylococci and streptococci are nonmotile and do not form spores.
Both staphylococci and streptococci are gram-positive cocci, but they are distinguished by two main criteria.
- Microscopically, staphylococci appear in grapelike clusters, whereas streptococci are in chains.
- Biochemically, staphylococci produce catalase (i.e., they degrade hydrogen peroxide), whereas streptococci do not.
Staphylococcus aureus causes abscesses, various pyogenic infections (e.g., endocarditis, septic arthritis, and osteomyelitis), food poisoning, scalded skin syndrome, and toxic shock syndrome. It is one of the most common causes of hospital-acquired pneumonia, septicemia, and surgical-wound infections. It is an important cause of skin infections, such as folliculitis, cellulitis, and impetigo. Staphylococcus epidermidis can cause endocarditis and prosthetic joint infections. Staphylococcus saprophyticus causes urinary tract infections. Kawasaki syndrome is a disease of unknown etiology that may be caused by certain strains of S. aureus.
Staphylococci are spherical gram-positive cocci arranged in irregular grapelike clusters (see Color Plate 1). All staphylococci produce catalase, whereas no streptococci do (catalase degrades H2O2 into O2 and H2O). Catalase is an important virulence factor because H2O2 is microbicidal and its degradation limits the ability of neutrophils to kill.
Color Plate 1
Staphylococcus aureus—Gram stain. Arrows point to two “grape-like” clusters of gram-positive cocci. Arrowhead points to neutrophil with pink segmented nuclei. Provider: Professor Shirley Lowe, University of California, San Francisco School of Medicine. With permission.
Three species of staphylococci are human pathogens: S. aureus, S. epidermidis, and S. saprophyticus (Table 15–1). Of the three, S. aureus is by far the most important. S. aureus is distinguished from the others primarily by coagulase production. Coagulase is an enzyme that causes plasma to clot by activating prothrombin to form thrombin. Thrombin then catalyzes the activation of fibrinogen to form the fibrin clot. S. epidermidis and S. saprophyticusare often referred to as coagulase-negative staphylococci (see Color Plate 15).
1All staphylococci are catalase-positive.
Color Plate 15
Coagulase test—Upper tube inoculated with Staphylococcus aureus; lower tube inoculated with Staphylococcus epidermidis. Arrow points to clotted plasma formed by coagulase produced by Staphylococcus aureus. Provider: Professor Shirley Lowe, University of California, San Francisco School of Medicine. With permission.
S. aureus produces a carotenoid pigment that imparts a golden color to its colonies. This pigment enhances the pathogenicity of the organism by inactivating the microbicidal effect of superoxides and other reactive oxygen species within neutrophils. S. epidermidis does not synthesize this pigment and produces white colonies. The virulence of S. epidermidis is significantly less than that of S. aureus. Two other characteristics further distinguish these species, namely, S. aureus usually ferments mannitol and hemolyzes red blood cells, whereas the others do not.
More than 90% of S. aureus strains contain plasmids that encode -lactamase, the enzyme that degrades many, but not all, penicillins. Some strains of S. aureus are resistant to the -lactamase-resistant penicillins, such as methicillin and nafcillin, by virtue of changes in the penicillin-binding protein in their cell membrane. These strains are commonly known as methicillin-resistant S. aureus (MRSA) or nafcillin-resistant S. aureus (NRSA). Rare strains called vancomycin-intermediate S. aureus (VISA), with reduced sensitivity to vancomycin, have emerged, as having strains fully resistant to vancomycin.
S. aureus has several important cell wall components and antigens.
- Protein A is the major protein in the cell wall. It is an important virulence factor because it binds to the Fc portion of IgG at the complement-binding site, thereby preventing the activation of complement. As a consequence, no C3b is produced, and the opsonization and phagocytosis of the organisms are greatly reduced. Protein A is used in certain tests in the clinical laboratory because it binds to IgG and forms a “coagglutinate” with antigen–antibody complexes. The coagulase-negative staphylococci do not produce protein A.
- Teichoic acids are polymers of ribitol phosphate. They mediate adherence of the staphylococci to mucosal cells and play a role in the induction of septic shock.
- Polysaccharide capsule is also an important virulence factor. There are 12 serotypes, but types 5 and 8 cause 85% of infections. The capsule is poorly immunogenic, which has made producing an effective vaccine difficult.
- Surface receptors for specific staphylococcal bacteriophages permit the “phage typing” of strains for epidemiologic purposes. Teichoic acids make up part of these receptors.
- Most strains of S. aureus are coated with a small amount of polysaccharide capsule (microcapsule) that is antiphagocytic. There are 11 serotypes based on antigenicity of the capsular polysaccharide.
- The peptidoglycan of S. aureus has endotoxin-like properties; i.e., it can stimulate macrophages to produce cytokines and can activate the complement and coagulation cascades. This explains the ability of S. aureus to cause the clinical findings of septic shock yet not possess endotoxin.
Humans are the reservoir for staphylococci. The nose is the main site of colonization of S. aureus and approximately 30% of people are colonized at any one time. Chronic nasal carriage increases the risk of infection by S. aureus. The skin, especially of hospital personnel and patients, is also a common site of S. aureus colonization. Hand contact is an important mode of transmission and handwashing decreases transmission.
S. aureus is also found in the vagina of approximately 5% of women, which predisposes them to toxic shock syndrome. Additional sources of staphylococcal infection are shedding from human lesions and fomites such as towels and clothing contaminated by these lesions.
Disease caused by S. aureus is favored by a heavily contaminated environment (e.g., family members with boils) and a compromised immune system. Reduced humoral immunity, including low levels of antibody, complement, or neutrophils, especially predisposes to staphylococcal infections. Diabetes and intravenous drug use predispose to infections by S. aureus. Patients with chronic granulomatous disease (CGD), a disease characterized by a defect in the ability of neutrophils to kill bacteria, are especially prone to S. aureus infections (see Chapter 68).
S. epidermidis is found primarily on the human skin and can enter the blood stream at the site of intravenous catheters that penetrate through the skin.S. saprophyticus is found primarily on the mucosa of the genital tract in young women and from that site can ascend into the urinary bladder to cause urinary tract infections.
S. aureus causes disease both by producing toxins and by inducing pyogenic inflammation. The typical lesion of S. aureus infection is an abscess.Abscesses undergo central necrosis and usually drain to the outside (e.g., furuncles and boils), but organisms may disseminate via the bloodstream as well. Foreign bodies, such as sutures and intravenous catheters, are important predisposing factors to infection by S. aureus.
Several important toxins and enzymes are produced by S. aureus. The three clinically important exotoxins are enterotoxin, toxic shock syndrome toxin, and exfoliatin.
- Enterotoxin causes food poisoning characterized by prominent vomiting and watery, nonbloody diarrhea. It acts as a superantigen within the gastrointestinal tract to stimulate the release of large amounts of interleukin-1 (IL-1) and interleukin-2 (IL-2) from macrophages and helper T cells, respectively. The prominent vomiting appears to be caused by cytokines released from the lymphoid cells, which stimulate the enteric nervous system to activate the vomiting center in the brain. Enterotoxin is fairly heat-resistant and is therefore usually not inactivated by brief cooking. It is resistant to stomach acid and to enzymes in the stomach and jejunum. There are six immunologic types of enterotoxin, types A–F.
- Toxic shock syndrome toxin (TSST) causes toxic shock, especially in tampon-using menstruating women or in individuals with wound infections. Toxic shock also occurs in patients with nasal packing used to stop bleeding from the nose. TSST is produced locally by S. aureus in the vagina, nose, or other infected site. The toxin enters the bloodstream, causing a toxemia. Blood cultures typically do not grow S. aureus.
TSST is a superantigen and causes toxic shock by stimulating the release of large amounts of IL-1, IL-2, and tumor necrosis factor (TNF) (see the discussions of exotoxins in Chapter 7 and superantigens in Chapter 58). Approximately 5–25% of isolates of S. aureus carry the gene for TSST. Toxic shock occurs in people who do not have antibody against TSST.
- Exfoliatin causes “scalded skin” syndrome in young children. It is “epidermolytic” and acts as a protease that cleaves desmoglein in desmosomes, leading to the separation of the epidermis at the granular cell layer.
- Several toxins can kill leukocytes (leukocidins) and cause necrosis of tissues in vivo. Of these, one of the most important is alpha toxin, which causes marked necrosis of the skin and hemolysis. The cytotoxic effect of alpha toxin is attributed to the formation of holes in the cell membrane and the consequent loss of low-molecular-weight substances from the damaged cell.
A second important toxin, P-V leukocidin, is a pore-forming toxin that kills cells, especially white blood cells, by damaging cell membranes. The importance of P-V leukocidin as a virulence factor is indicated by the severe skin and soft tissue infection caused by methicillin-resistant S. aureusstrains that produce this leukocidin. A severe necrotizing pneumonia is also caused by strains of S. aureus that produce P-V leukocidin.
- The enzymes include coagulase, fibrinolysin, hyaluronidase, proteases, nucleases, and lipases. Coagulase, by clotting plasma, serves to wall off the infected site, thereby retarding the migration of neutrophils into the site. Staphylokinase is a fibrinolysin that can lyse thrombi.
STAPHYLOCOCCUS EPIDERMIDIS & STAPHYLOCOCCUS SAPROPHYTICUS
Unlike S. aureus, these two coagulase-negative staphylococci do not produce exotoxins. Thus, they do not cause food poisoning or toxic shock syndrome. They do, however, cause pyogenic infections. For example, S. epidermidis is a prominent cause of pyogenic infections on prosthetic implants such as heart valves and hip joints.
The important clinical manifestations caused by S. aureus can be divided into two groups: pyogenic and toxin-mediated (Table 15–2). S. aureus is a major cause of skin, soft tissue, bone, joint, lung, heart, and kidney infections. In the following list, the first seven are pyogenic in origin, whereas the last three are toxin-mediated.
IV = intravenous.
1For simplicity, many forms of disseminated diseases caused by S. aureus, e.g., osteomyelitis, arthritis, were not included in the table.
STAPHYLOCOCCUS AUREUS: PYOGENIC DISEASES
- Skin infections are very common. These include impetigo, furuncles, carbuncles, paronychia, cellulitis, folliculitis, hydradenitis suppurativa, conjunctivitis, eyelid infections (blepharitis), and postpartum breast infections (mastitis). Severe necrotizing skin and soft tissue infections are caused by methicillin-resistant S. aureus strains that produce P-V leukocidin. These infections are typically community-acquired rather than hospital-acquired.
These community-acquired, methicillin-resistant strains of S. aureus (CA-MRSA) cause severe infections, especially among the homeless and intravenous drug users. Athletes who engage in close personal contact such as wrestlers and football players are also at risk. Note that hospital-acquired MRSA (HA-MRSA) causes approximately 50% of all nosocomial S. aureus infections. Molecular analysis reveals that the CA-MRSA strains are different from the HA-MRSA strains.
- Septicemia (sepsis) can originate from any localized lesion, especially wound infection, or as a result of intravenous drug abuse. Sepsis caused byS. aureus has clinical features similar to those of sepsis caused by certain gram-negative bacteria such as Neisseria meningitidis (see Neisseria ).
- Endocarditis may occur on normal or prosthetic heart valves, especially right-sided endocarditis (tricuspid valve) in intravenous drug users. (Prosthetic valve endocarditis is often caused by S. epidermidis.)
- Osteomyelitis and arthritis may arise either by hematogenous spread from a distant infected focus or be introduced locally at a wound site. S. aureus is a very common cause of these diseases, especially in children.
- Postsurgical wound infections are an important cause of morbidity and mortality in hospitals. S. aureus is the most common cause.
- Pneumonia can occur in postoperative patients or following viral respiratory infection, especially influenza. Staphylococcal pneumonia often leads to empyema or lung abscess; in many hospitals it is the most common cause of nosocomial pneumonia in general and especially of ventilator-associated pneumonia in intensive care units. CA-MRSA causes a severe necrotizing pneumonia.
- Abscesses can occur in any organ when the organism circulates in the bloodstream (bacteremia). These abscesses are often called “metastatic abscesses” because they occur by the spread of bacteria from the original site.
STAPHYLOCOCCUS AUREUS: TOXIN-MEDIATED DISEASES
- Food poisoning (gastroenteritis) is caused by ingestion of enterotoxin, which is preformed in foods and hence has a short incubation period (1–8 hours). In staphylococcal food poisoning, vomiting is typically more prominent than diarrhea.
- Toxic shock syndrome is characterized by fever; hypotension; a diffuse, macular, sunburn-like rash that goes on to desquamate; and involvement of three or more of the following organs: liver, kidney, gastrointestinal tract, central nervous system, muscle, or blood.
- Scalded skin syndrome is characterized by fever, large bullae, and an erythematous macular rash. Large areas of skin slough, serous fluid exudes, and electrolyte imbalance can occur. Hair and nails can be lost. Recovery usually occurs within 7–10 days. This syndrome occurs most often in young children.
STAPHYLOCOCCUS AUREUS: KAWASAKI SYNDROME
Kawasaki syndrome (KS) is a disease of unknown etiology that is discussed here because several of its features resemble toxic shock syndrome caused by the superantigens of S. aureus (and S. pyogenes). KS is a vasculitis involving small and medium-size arteries, especially the coronary arteries.
Clinically, KS is characterized by a high fever of at least 5 days’ duration; bilateral nonpurulent conjunctivitis; lesions of the lips and oral mucosa (such as strawberry tongue, edema of the lips, and erythema of the oropharynx); a diffuse erythematous, maculopapular rash; erythema and edema of the hands and feet that often ends with desquamation; and cervical lymphadenopathy.
The most characteristic clinical finding of KS is cardiac involvement, especially myocarditis, arrhythmias, and regurgitation involving the mitral or aortic valves. The main cause of morbidity and mortality in KS is aneurysm of the coronary arteries.
KS is much more common in children of Asian ancestry, leading to speculation that certain major histocompatibility complex (MHC) alleles may predispose to the disease. It is a disease of children under 5 years of age, often occurring in mini-outbreaks. It occurs worldwide but is much more common in Japan.
There is no definitive diagnostic laboratory test for KS. Effective therapy consists of high-dose immune globulins (IVIG), which promptly reduces the fever and other symptoms and, most importantly, significantly reduces the occurrence of aneurysms.
STAPHYLOCOCCUS EPIDERMIDIS & STAPHYLOCOCCUS SAPROPHYTICUS
There are two coagulase-negative staphylococci of medical importance: S. epidermidis and S. saprophyticus. S. epidermidis infections are almost always hospital-acquired, whereas S. saprophyticus infections are almost always community-acquired.
S. epidermidis is part of the normal human flora on the skin and mucous membranes but can enter the bloodstream (bacteremia) and cause metastatic infections, especially at the site of implants. It commonly infects intravenous catheters and prosthetic implants, e.g., prosthetic heart valves (endocarditis), vascular grafts, and prosthetic joints (arthritis or osteomyelitis) (Table 15–2). S. epidermidis is also a major cause of sepsis in neonates and of peritonitis in patients with renal failure who are undergoing peritoneal dialysis through an indwelling catheter. It is the most common bacterium to cause cerebrospinal fluid shunt infections.
Strains of S. epidermidis that produce a glycocalyx are more likely to adhere to prosthetic implant materials and therefore are more likely to infect these implants than strains that do not produce a glycocalyx. Hospital personnel are a major reservoir for antibiotic-resistant strains of S. epidermidis.
S. saprophyticus causes urinary tract infections, particularly in sexually active young women. Most women with this infection have had sexual intercourse within the previous 24 hours. This organism is second to Escherichia coli as a cause of community-acquired urinary tract infections in young women.
Smears from staphylococcal lesions reveal gram-positive cocci in grapelike clusters. Cultures of S. aureus typically yield golden-yellow colonies that are usually beta-hemolytic. S. aureus is coagulase-positive. Mannitol-salt agar is a commonly used screening device for S. aureus. Cultures of coagulase-negative staphylococci typically yield white colonies that are nonhemolytic. The two coagulase-negative staphylococci are distinguished by their reaction to the antibiotic novobiocin: S. epidermidis is sensitive, whereas S. saprophyticus is resistant. There are no generally useful serologic or skin tests. In toxic shock syndrome, isolation of S. aureus is not required to make a diagnosis as long as the clinical criteria are met.
For epidemiological purposes, S. aureus can be subdivided into subgroups based on the susceptibility of the clinical isolate to lysis by a variety of bacteriophages. A person carrying S. aureus of the same phage group as that which caused the outbreak may be the source of the infections.
In the United States, 90% or more of S. aureus strains are resistant to penicillin G. Most of these strains produce -lactamase. Such organisms can be treated with -lactamase-resistant penicillins, e.g., nafcillin or cloxacillin, some cephalosporins, or vancomycin. Treatment with a combination of a -lactamase-sensitive penicillin, e.g., amoxicillin, and a -lactamase inhibitor, e.g., clavulanic acid, is also useful.
Approximately 20% of S. aureus strains are methicillin-resistant or nafcillin-resistant by virtue of altered penicillin-binding proteins. These resistant strains of S. aureus are often abbreviated MRSA or NRSA, respectively. Such organisms can produce sizable outbreaks of disease, especially in hospitals. The drug of choice for these staphylococci is vancomycin, to which gentamicin is sometimes added. Trimethoprim-sulfamethoxazole or clindamycin can be used to treat non-life-threatening infections caused by these organisms. Note that these MRSA strains are resistant to all beta-lactam drugs, including both penicillins and cephalosporins.
Strains of S. aureus with intermediate resistance (so-called VISA strains) and with complete resistance to vancomycin have been isolated from patients. These strains are typically methicillin/nafcillin-resistant as well, which makes them very difficult to treat. A combination of two streptogramins, quinupristin-dalfopristin (Synercid), has been shown to be effective, but Synercid is available only as an investigational drug at this time. Streptogramins inhibit bacterial protein synthesis in a manner similar to macrolides but are bactericidal for S. aureus.
The treatment of toxic shock syndrome involves correction of the shock using fluids, pressor drugs, and inotropic drugs; administration of a -lactamase-resistant penicillin such as nafcillin; and removal of the tampon or debridement of the infected site as needed. Pooled serum globulins, which contain antibodies against TSST, may be useful.
Mupirocin is very effective as a topical antibiotic in skin infections caused by S. aureus. It has also been used to reduce nasal carriage of the organism in hospital personnel and in patients with recurrent staphylococcal infections.
Some strains of staphylococci exhibit tolerance; i.e., they can be inhibited by antibiotics but are not killed. (That is, the ratio of minimum bactericidal concentration [MBC] to minimum inhibitory concentration [MIC] is very high.) Tolerance may result from failure of the drugs to inactivate inhibitors of autolytic enzymes that degrade the organism. Tolerant organisms should be treated with drug combinations (see Chapter 10).
Drainage (spontaneous or surgical) is the cornerstone of abscess treatment. Previous infection provides only partial immunity to reinfection.
S. epidermidis is highly antibiotic resistant. Most strains produce -lactamase and many are methicillin/nafcillin-resistant due to altered penicillin-binding proteins. The drug of choice is vancomycin, to which either rifampin or an aminoglycoside can be added. Removal of the catheter or other device is often necessary. S. saprophyticus urinary tract infections can be treated with a quinolone, such as norfloxacin, or with trimethoprim-sulfamethoxazole.
There is no vaccine against staphylococci. Cleanliness, frequent hand washing, and aseptic management of lesions help to control spread of S. aureus.Persistent colonization of the nose by S. aureus can be reduced by intranasal mupirocin or by oral antibiotics, such as ciprofloxacin or trimethoprim-sulfamethoxazole, but is difficult to eliminate completely. Shedders may have to be removed from high-risk areas, e.g., operating rooms and newborn nurseries. Cefazolin is often used perioperatively to prevent staphylococcal surgical-wound infections.
Streptococci of medical importance are listed in Table 15–3. All but one of these streptococci are discussed in this section; Streptococcus pneumoniae is discussed separately at the end of this chapter because it is so important.
1All streptococci are catalase-negative.
2S. bovis is a nonenterococcal group D organism.
3Both E. faecalis and S. bovis grow on bile-esculin agar, whereas other streptococci do not. They hydrolyze the esculin, and this results in a characteristic black discoloration of the agar.
4NA, not applicable.
5Viridans group streptococci include several species, such as S. anguis, S. mutans, S. mitis, S. gordoni, S. salivarius, S. anginosus, S. milleri, and S. intermedius.
Streptococci cause a wide variety of infections. S. pyogenes (group A streptococcus) is the leading bacterial cause of pharyngitis and cellulitis. It is an important cause of impetigo, necrotizing fasciitis, and streptococcal toxic shock syndrome. It is also the inciting factor of two important immunologic diseases, namely, rheumatic fever and acute glomerulonephritis. Streptococcus agalactiae (group B streptococcus) is the leading cause of neonatal sepsis and meningitis. Enterococcus faecalis is an important cause of hospital-acquired urinary tract infections and endocarditis. Viridans group streptococci are the most common cause of endocarditis. Streptococcus bovis also causes endocarditis.
Streptococci are spherical gram-positive cocci arranged in chains or pairs (see Color Plate 2). All streptococci are catalase-negative, whereas staphylococci are catalase-positive (Table 15–3).
Color Plate 2
Streptococcus pyogenes—Gram stain. Arrow points to a long chain of gram-positive cocci. Provider: Professor Shirley Lowe, University of California, San Francisco School of Medicine. With permission.
One of the most important characteristics for identification of streptococci is the type of hemolysis (see Color Plate 16).
Color Plate 16
Alpha hemolysis and beta hemolysis on blood agar—Short arrow points to an alpha-hemolytic colony, probably a viridans group streptococcus. Long arrow points to a beta-hemolytic colony, probably Streptococcus pyogenes. The specimen was a throat swab taken from a person with a sore throat. Provider: Professor Shirley Lowe, University of California, San Francisco School of Medicine. With permission.
- Alpha-hemolytic streptococci form a green zone around their colonies as a result of incomplete lysis of red blood cells in the agar.
- Beta-hemolytic streptococci form a clear zone around their colonies because complete lysis of the red cells occurs. Beta-hemolysis is due to the production of enzymes (hemolysins) called streptolysin O and streptolysin S (see the Pathogenesis section below).
- Some streptococci are nonhemolytic (gamma-hemolysis).
There are two important antigens of beta-hemolytic streptococci:
- C carbohydrate determines the group of beta-hemolytic streptococci. It is located in the cell wall, and its specificity is determined by an amino sugar.
- M protein is the most important virulence factor and determines the type of group A beta-hemolytic streptococci. It protrudes from the outer surface of the cell and interferes with ingestion by phagocytes; i.e., it is antiphagocytic. Antibody to M protein provides type-specific immunity. There are approximately 80 serotypes based on the M protein, which explains why multiple infections with S. pyogenes can occur. Strains of S. pyogenes that produce certain M protein types are rheumatogenic, i.e., cause primarily rheumatic fever, whereas strains of S. pyogenes that produce other M protein types are nephritogenic, i.e., cause primarily acute glomerulonephritis. Although M protein is the main antiphagocytic component of S. pyogenes, the organism also has a polysaccharide capsule that plays a role in retarding phagocytosis.
Classification of Streptococci
These are arranged into groups A–U (known as Lancefield groups) on the basis of antigenic differences in C carbohydrate. In the clinical laboratory, the group is determined by precipitin tests with specific antisera or by immunofluorescence.
Group A streptococci (S. pyogenes) are one of the most important human pathogens. They are the most frequent bacterial cause of pharyngitis and a very common cause of skin infections. They adhere to pharyngeal epithelium via pili covered with lipoteichoic acid and M protein. Many strains have a hyaluronic acid capsule that is antiphagocytic. The growth of S. pyogenes is inhibited by the antibiotic bacitracin, an important diagnostic criterion (see Color Plate 17).
Color Plate 17
Bacitracin test—Arrow points to zone of inhibition of growth of group A streptococci (Streptococcus pyogenes) caused by bacitracin that has diffused from the disk labeled A. Upper half of blood agar plate shows beta hemolysis caused by group A streptococci, except in the region around the bacitracin disk. Lower half of blood agar plate shows beta hemolysis caused by group B streptococci (Streptococcus agalactiae) and there is no zone of inhibition around the bacitracin disk. Provider: Professor Shirley Lowe, University of California, San Francisco School of Medicine. With permission.
Group B streptococci (S. agalactiae) colonize the genital tract of some women and can cause neonatal meningitis and sepsis. They are usually bacitracin-resistant. They hydrolyze (breakdown) hippurate, an important diagnostic criterion.
Group D streptococci include enterococci (e.g., Enterococcus faecalis and Enterococcus faecium) and nonenterococci (e.g., S. bovis). Enterococci are members of the normal flora of the colon and are noted for their ability to cause urinary, biliary, and cardiovascular infections. They are very hardy organisms; they can grow in hypertonic (6.5%) saline or in bile and are not killed by penicillin G. As a result, a synergistic combination of penicillin and an aminoglycoside (such as gentamicin) is required to kill enterococci. Vancomycin can also be used, but vancomycin-resistant enterococci (VRE) have emerged and become an important and much feared cause of life-threatening nosocomial infections. More strains of E. faecium are vancomycin-resistant than are strains of E. faecalis.
Nonenterococcal group D streptococci, such as S. bovis, can cause similar infections but are much less hardy organisms; for example, they are inhibited by 6.5% NaCl and killed by penicillin G. Note that the hemolytic reaction of group D streptococci is variable: most are alpha-hemolytic, but some are beta-hemolytic and others are nonhemolytic.
Groups C, E, F, G, H, and K–U streptococci infrequently cause human disease.
Some produce no hemolysis; others produce alpha-hemolysis. The principal alpha-hemolytic organisms are S. pneumoniae and the viridans group of streptococci. The viridans streptococci (e.g., Streptococcus mitis, Streptococcus sanguis, and Streptococcus mutans) are not bile-soluble and not inhibited by optochin—in contrast to S. pneumoniae, which is bile-soluble and inhibited by optochin. Viridans streptococci are part of the normal flora of the human pharynx and intermittently reach the bloodstream to cause infective endocarditis. S. mutans synthesizes polysaccharides (dextrans) that are found in dental plaque and lead to dental caries. Streptococcus intermedius and Streptococcus anginosus (also known as the Streptococcus anginosus-milleri group) are usually alpha-hemolytic or nonhemolytic, but some isolates are beta-hemolytic. They are found primarily in the mouth and colon.
These grow under anaerobic or microaerophilic conditions and produce variable hemolysis. Peptostreptococci are members of the normal flora of the gut, mouth, and the female genital tract and participate in mixed anaerobic infections. The term “mixed anaerobic infections” refers to the fact that these infections are caused by multiple bacteria, some of which are anaerobes and others are facultatives. For example, peptostreptococci and viridans streptococci, both members of the oral flora, are often found in brain abscesses following dental surgery. Peptostreptococcus magnus andPeptostreptococcus anaerobius are the species frequently isolated from clinical specimens.
Most streptococci are part of the normal flora of the human throat, skin, and intestines but produce disease when they gain access to tissues or blood. Viridans streptococci and S. pneumoniae are found chiefly in the oropharynx;S. pyogenes is found on the skin and in the oropharynx in small numbers; S. agalactiae occurs in the vagina and colon; and both the enterococci and anaerobic streptococci are located in the colon.
Group A streptococci (S. pyogenes) cause disease by three mechanisms: (1) pyogenic inflammation, which is induced locally at the site of the organisms in tissue; (2) exotoxin production, which can cause widespread systemic symptoms in areas of the body where there are no organisms; and (3)immunologic, which occurs when antibody against a component of the organism cross-reacts with normal tissue or forms immune complexes that damage normal tissue (see the section on poststreptococcal diseases later in the chapter). The immunologic reactions cause inflammation, e.g., the inflamed joints of rheumatic fever, but there are no organisms in the lesions (Table 15–4).
The M protein of S. pyogenes is its most important antiphagocytic factor, but its capsule, composed of hyaluronic acid, is also antiphagocytic. Antibodies are not formed against the capsule because hyaluronic acid is a normal component of the body and humans are tolerant to it.
Group A streptococci produce three important inflammation-related enzymes.
- Hyaluronidase degrades hyaluronic acid, which is the ground substance of subcutaneous tissue. Hyaluronidase is known as spreading factorbecause it facilitates the rapid spread of S. pyogenes in skin infections (cellulitis).
- Streptokinase (fibrinolysin) activates plasminogen to form plasmin, which dissolves fibrin in clots, thrombi, and emboli. It can be used to lyse thrombi in the coronary arteries of heart attack patients.
- DNase (streptodornase) degrades DNA in exudates or necrotic tissue. Antibody to DNase B develops during pyoderma; this can be used for diagnostic purposes. Streptokinase-streptodornase mixtures applied as a skin test give a positive reaction in most adults, indicating normal cell-mediated immunity.
In addition, group A streptococci produce five important toxins and hemolysins.
- Erythrogenic toxin causes the rash of scarlet fever. Its mechanism of action is similar to that of the toxic shock syndrome toxin (TSST) of S. aureus;i.e., it acts as a superantigen (see S. aureus, above, and Chapter 58). It is produced only by certain strains of S. pyogenes lysogenized by a bacteriophage carrying the gene for the toxin. The injection of a skin test dose of erythrogenic toxin (Dick test) gives a positive result in persons lacking antitoxin ( i.e., susceptible persons).
- Streptolysin O is a hemolysin that is inactivated by oxidation (oxygen-labile). It causes beta-hemolysis only when colonies grow under the surface of a blood agar plate. It is antigenic, and antibody to it (ASO) develops after group A streptococcal infections. The titer of ASO antibody can be important in the diagnosis of rheumatic fever.
- Streptolysin S is a hemolysin that is not inactivated by oxygen (oxygen-stable). It is not antigenic but is responsible for beta-hemolysis when colonies grow on the surface of a blood agar plate.
- Pyogenic exotoxin A is the toxin responsible for most cases of streptococcal toxic shock syndrome. It has the same mode of action as does staphylococcal TSST; i.e., it is a superantigen that causes the release of large amounts of cytokines from helper T cells and macrophages (see Toxin Production and Effect of Superantigens on T Cells).
- Exotoxin B is a protease that rapidly destroys tissue and is produced in large amounts by the strains of S. pyogenes, the so-called “flesh-eating” streptococci, that cause necrotizing fasciitis.
Pathogenesis by group B streptococci (S. agalactiae) is based on the ability of the organism to induce an inflammatory response. However, unlike S. pyogenes, no cytotoxic enzymes or exotoxins have been described and there is no evidence for any immunologically induced disease. Group B streptococci have a polysaccharide capsule that is antiphagocytic, and anticapsular antibody is protective.
S. pyogenes causes three types of diseases: (1) pyogenic diseases such as pharyngitis and cellulitis, (2) toxigenic diseases such as scarlet fever and toxic shock syndrome, and (3) immunologic diseases such as rheumatic fever and acute glomerulonephritis. (See the section on Poststreptococcal Diseases, below.)
S. pyogenes (group A beta-hemolytic streptococcus) is the most common bacterial cause of sore throat. Pharyngitis is characterized by inflammation, exudate, fever, leukocytosis, and tender cervical lymph nodes. If untreated, spontaneous recovery occurs in 10 days. However, it may extend to otitis, sinusitis, mastoiditis, and meningitis. If the infecting streptococci produce erythrogenic toxin and the host lacks antitoxin, scarlet fever may result. Rheumatic fever may occur, especially following pharyngitis. S. pyogenes also causes another toxin-mediated disease, streptococcal toxic shock syndrome, which has clinical findings similar to those of staphylococcal toxic shock syndrome (see Staphylococcus aureus: Toxin-Mediated Diseases).
However, streptococcal TSS typically has a recognizable site of pyogenic inflammation and blood cultures are often positive, whereas staphylococcal TSS typically has neither a site of pyogenic inflammation nor positive blood cultures.
Group A streptococci cause skin and soft tissue infections, such as cellulitis, erysipelas, necrotizing fasciitis (streptococcal gangrene), and impetigo. Impetigo, a form of pyoderma, is a superficial skin infection characterized by “honey-colored” crusted lesions. Group A streptococci also cause endometritis (puerperal fever), a serious infection of pregnant women, and sepsis. Immune-mediated poststreptococcal acute glomerulonephritis can also occur, especially following skin infections caused by certain M protein types of S. pyogenes.
Group B streptococci cause neonatal sepsis and meningitis. The main predisposing factor is prolonged (longer than 18 hours) rupture of the membranes in women who are colonized with the organism. Children born prior to 37 weeks’ gestation have a greatly increased risk of disease. Also, children whose mothers who lack antibody to group B streptococci and who consequently are born without transplacentally acquired IgG have a high rate of neonatal sepsis caused by this organism. Group B streptococci are an important cause of neonatal pneumonia as well.
Although most group B streptococcal infections are in neonates, this organism also causes such infections as pneumonia, endocarditis, arthritis, and osteomyelitis in adults. Postpartum endometritis also occurs. Diabetes is the main predisposing factor for adult group B streptococcal infections.
Viridans streptococci (e.g., S. mutans, S. sanguis, S. salivarius, and S. mitis) are the most common cause of infective endocarditis. They enter the bloodstream (bacteremia) from the oropharynx, typically after dental surgery. Signs of endocarditis are fever, heart murmur, anemia, and embolic events such as splinter hemorrhages, subconjunctival petechial hemorrhages, and Janeway lesions. It is 100% fatal unless effectively treated with antimicrobial agents. About 10% of endocarditis cases are caused by enterococci, but any organism causing bacteremia may settle on deformed valves. At least three blood cultures are necessary to ensure recovery of the organism in more than 90% of cases.
Viridans streptococci, especially S. anginosus, S. milleri, and S. intermedius, also cause brain abscesses, often in combination with mouth anaerobes (a mixed aerobic-anaerobic infection). Dental surgery is an important predisposing factor to brain abscess because it provides a portal for the viridans streptococci and the anaerobes in the mouth to enter the bloodstream (bacteremia) and spread to the brain. Viridans streptococci are involved in mixed aerobic-anaerobic infections in other areas of the body as well, e.g., abdominal abscesses.
Enterococci cause urinary tract infections, especially in hospitalized patients. Indwelling urinary catheters and urinary tract instrumentation are important predisposing factors. Enterococci also cause endocarditis, particularly in patients who have undergone gastrointestinal or urinary tract surgery or instrumentation. They also cause intra-abdominal and pelvic infections, typically in combination with anaerobes. S. bovis, a nonenterococcal group D streptococcus, causes endocarditis, especially in patients with carcinoma of the colon. This association is so strong that patients with S. bovis bacteremia or endocarditis should be investigated for the presence of colonic carcinoma.
In August 2005, it was reported that Streptococcus suis caused the death of 37 farmers in China. The illness is characterized by the sudden onset of hemorrhagic shock. This species is known to cause disease in pigs but only rarely in people prior to this outbreak. Spread of the bacteria from the index case to others has not occurred.
Peptostreptococci are one of the most common bacteria found in brain, lung, abdominal, and pelvic abscesses.
Poststreptococcal (Nonsuppurative) Diseases
These are disorders in which a local infection with group A streptococci is followed weeks later by inflammation in an organ that was not infected by the streptococci. The inflammation is caused by an immunologic response to streptococcal M proteins that cross-react with human tissues. Some strains ofS. pyogenes bearing certain M proteins are nephritogenic and cause acute glomerulonephritis, and other strains bearing different M proteins are rheumatogenic and cause acute rheumatic fever.
Acute glomerulonephritis (AGN) typically occurs 2–3 weeks after skin infection by certain group A streptococcal types in children (e.g., M protein type 49 causes AGN most frequently). AGN is more frequent after skin infections than after pharyngitis. The most striking clinical features are hypertension, edema of the face (especially periorbital edema) and ankles, and “smoky” urine (due to red cells in the urine). Most patients recover completely. Reinfection with streptococci rarely leads to recurrence of acute glomerulonephritis.
The disease is initiated by antigen–antibody complexes on the glomerular basement membrane, and soluble antigens from streptococcal membranes may be the inciting antigen. It can be prevented by early eradication of nephritogenic streptococci from skin colonization sites but not by administration of penicillin after onset of symptoms.
ACUTE RHEUMATIC FEVER
Approximately 2 weeks after a group A streptococcal infection—usually pharyngitis—rheumatic fever, characterized by fever, migratory polyarthritis, and carditis, may develop. The carditis damages myocardial and endocardial tissue, especially the mitral and aortic valves. Uncontrollable, spasmodic movements of the limbs or face (chorea) may also occur. ASO titers and the erythrocyte sedimentation rate are elevated. Note that group A streptococcalskin infections do not cause rheumatic fever.
Rheumatic fever is due to an immunologic reaction between cross-reacting antibodies to certain streptococcal M proteins and antigens of joint, heart, and brain tissue. It is an autoimmune disease, greatly exacerbated by recurrence of streptococcal infections. If streptococcal infections are treated within 8 days of onset, rheumatic fever is usually prevented. After a heart-damaging attack of rheumatic fever, reinfection must be prevented by long-term prophylaxis. In the United States, fewer than 0.5% of group A streptococcal infections lead to rheumatic fever, but in developing tropical countries, the rate is higher than 5%.
Gram-stained smears are useless in streptococcal pharyngitis because viridans streptococci are members of the normal flora and cannot be visually distinguished from the pathogenic S. pyogenes. However, stained smears from skin lesions or wounds that reveal streptococci are diagnostic. Cultures of swabs from the pharynx or lesion on blood agar plates show small, translucent beta-hemolytic colonies in 18–48 hours. If inhibited by bacitracin disk, they are likely to be group A streptococci. Group B streptococci are characterized by their ability to hydrolyze hippurate and by the production of a protein that causes enhanced hemolysis on sheep blood agar when combined with beta-hemolysin of S. aureus (CAMP test). Group D streptococcihydrolyze esculin in the presence of bile; i.e., they produce a black pigment on bile-esculin agar. The group D organisms are further subdivided: the enterococci grow in hypertonic (6.5%) NaCl, whereas the nonenterococci do not.
Although cultures remain the gold standard for the diagnosis of streptococcal pharyngitis, a problem exists because the results of culturing are not available for at least 18 hours and it is beneficial to know while the patient is in the office whether antibiotics should be prescribed. For this reason, rapid tests that provide a diagnosis in approximately 10 minutes were developed. The rapid test detects bacterial antigens in a throat swab specimen. In the test, specific antigens from the group A streptococci are extracted from the throat swab with certain enzymes and are reacted with antibody to these antigens bound to latex particles. Agglutination of the colored latex particles occurs if group A streptococci are present in the throat swab.
A rapid test is also available for the detection of group B streptococci in vaginal and rectal samples. It detects the DNA of the organism and results can be obtained in approximately 1 hour.
Viridans group streptococci form alpha-hemolytic colonies on blood agar and must be distinguished from S. pneumoniae (pneumococci), which is also alpha-hemolytic. Viridans group streptococci are resistant to lysis by bile and will grow in the presence of optochin, whereas pneumococci will not. The various viridans group streptococci are classified into species by using a variety of biochemical tests.
ASO titers are high soon after group A streptococcal infections. In patients suspected of having rheumatic fever, an elevated ASO titer is typically used as evidence of previous infection because throat culture results are often negative at the time the patient presents with rheumatic fever. Titers of anti-DNase B are high in group A streptococcal skin infections and serve as an indicator of previous streptococcal infection in patients suspected of having AGN.
All group A streptococci are susceptible to penicillin G, but neither rheumatic fever nor AGN patients benefit from penicillin treatment after onset. In mild group A streptococcal infections, oral penicillin V can be used. In penicillin-allergic patients, erythromycin or one of its long-acting derivatives, e.g., azithromycin, can be used. However, erythromycin-resistant strains of S. pyogenes have emerged that may limit the effectiveness of the macrolide class of drugs in the treatment of streptococcal pharyngitis.
Endocarditis caused by most viridans streptococci is curable by prolonged penicillin treatment. However, enterococcal endocarditis can be eradicated only by a penicillin or vancomycin combined with an aminoglycoside.
Enterococci resistant to multiple drugs, e.g., penicillins, aminoglycosides, and vancomycin, have emerged. Vancomycin-resistant enterococci (VRE) are now an important cause of nosocomial infections; there is no reliable antibiotic therapy for these organisms. At present, two investigational drugs are being used to treat infections caused by VRE: linezolid (Zyvox) and quinupristin/dalfopristin (Synercid). Nonenterococcal group D streptococci, e.g., S. bovis, are not highly resistant and can be treated with penicillin G.
The drug of choice for group B streptococcal infections is either penicillin G or ampicillin. Some strains may require higher doses of penicillin G or a combination of penicillin G and an aminoglycoside to eradicate the organism. Peptostreptococci can be treated with penicillin G.
Rheumatic fever can be prevented by prompt treatment of group A streptococcal pharyngitis with penicillin. Prevention of streptococcal infections (usually with benzathine penicillin once each month for several years) in persons who have had rheumatic fever is important to prevent recurrence of the disease. There is no evidence that patients who have had AGN require similar penicillin prophylaxis.
In patients with damaged heart valves who undergo invasive dental procedures, endocarditis caused by viridans streptococci can be prevented by using amoxicillin perioperatively. In patients with damaged heart valves who undergo gastrointestinal or urinary tract procedures, endocarditis caused by enterococci can be prevented by using ampicillin and gentamicin perioperatively.
The incidence of neonatal sepsis caused by group B streptococci can be reduced by a two-pronged approach: (1) All pregnant women should be screened by doing vaginal and rectal cultures at 35–37 weeks. If cultures are positive, then penicillin G (or ampicillin) should be administered intravenously at the time of delivery. (2) If the patient has not had cultures done, then penicillin G (or ampicillin) should be administered intravenously at the time of delivery to women who experience prolonged (longer than 18 hours) rupture of membranes, whose labor begins before 37 weeks’ gestation, or who have a fever at the time of labor. If the patient is allergic to penicillin, either cefazolin or vancomycin can be used. Oral ampicillin given to women who are vaginal carriers of group B streptococci does not eradicate the organism. Rapid screening tests for group B streptococcal antigens in vaginal specimens can be insensitive, and neonates born of antigen-negative women have, nevertheless, had neonatal sepsis. Note, however, that as group B streptococcal infections have declined as a result of these prophylactic measures, neonatal infections caused by E. coli have increased.
There are no vaccines available against any of the streptococci except S. pneumoniae (see below).
Pneumococci cause pneumonia, bacteremia, meningitis, and infections of the upper respiratory tract such as otitis media and sinusitis. Pneumococci are the most common cause of community-acquired pneumonia, meningitis, sepsis in splenectomized individuals, otitis media, and sinusitis.
Pneumococci are gram-positive lancet-shaped cocci arranged in pairs (diplococci) or short chains. (The term “lancet-shaped” means that the diplococci are oval with somewhat pointed ends rather than being round.) (see Color Plate 3). On blood agar they produce alpha-hemolysis. In contrast to viridans streptococci, they are lysed by bile or deoxycholate and their growth is inhibited by optochin (see Color Plate 18).
Color Plate 3
Streptococcus pneumoniae—Gram stain. Arrows point to typical gram-positive diplococci. Note that the clear area around the organism is the capsule. Provider: Professor Shirley Lowe, University of California, San Francisco School of Medicine. With permission.
Color Plate 18
Optochin test—Arrow points to zone of inhibition of growth of Streptococcus pneumoniae caused by optochin that has diffused from the disk labeled P. In the lower half of the blood agar plate, there is alpha hemolysis caused by Streptococcus pneumoniae, except in the region around the optochin disk. The arrow points to the outer limit of the zone of inhibition. Upper half of blood agar plate shows alpha hemolysis caused by a viridans streptococcus and there is no zone of inhibition around the optochin disk. Provider: Professor Shirley Lowe, University of California, San Francisco School of Medicine. With permission.
Pneumococci possess polysaccharide capsules of more than 85 antigenically distinct types. With type-specific antiserum, capsules swell (quellung reaction), and this can be used to identify the type. Capsules are virulence factors; i.e., they interfere with phagocytosis and favor invasiveness. Specific antibody to the capsule opsonizes the organism, facilitates phagocytosis, and promotes resistance. Such antibody develops in humans as a result either of infection (asymptomatic or clinical) or of administration of polysaccharide vaccine. Capsular polysaccharide elicits primarily a B-cell ( i.e., T-independent) response.
Another important surface component of S. pneumoniae is a carbohydrate in the cell wall called C-substance. This carbohydrate is medically important, not for itself, but because it reacts with a normal serum protein made by the liver called C-reactive protein (CRP). CRP is an “acute-phase” protein that is elevated as much as a 1000-fold in acute inflammation. CRP is not an antibody (which are gamma globulins) but rather a beta-globulin. (Plasma contains alpha, beta, and gamma globulins.) Note that CRP is a nonspecific indicator of inflammation and is elevated in response to the presence of many organisms, not just S. pneumoniae. Clinically, CRP in human serum is measured in the laboratory by its reaction with the carbohydrate of S. pneumoniae.The medical importance of CRP is that an elevated CRP appears to be a better predictor of heart attack risk than an elevated cholesterol level.
Humans are the natural hosts for pneumococci; there is no animal reservoir. Because a proportion (5–50%) of the healthy population harbor virulent organisms in the oropharynx, pneumococcal infections are not considered to be communicable. Resistance is high in healthy young people, and disease results most often when predisposing factors (see below) are present.
The most important virulence factor is the capsular polysaccharide, and anticapsular antibody is protective. Lipoteichoic acid, which activates complement and induces inflammatory cytokine production, contributes to the inflammatory response and to the septic shock syndrome that occurs in some immunocompromised patients. Pneumolysin, the hemolysin that causes alpha-hemolysis, may also contribute to pathogenesis. Pneumococci produce IgA protease that enhances the organism’s ability to colonize the mucosa of the upper respiratory tract. Pneumococci multiply in tissues and cause inflammation. When they reach alveoli, there is outpouring of fluid and red and white blood cells, resulting in consolidation of the lung. During recovery, pneumococci are phagocytized, mononuclear cells ingest debris, and the consolidation resolves.
Factors that lower resistance and predispose persons to pneumococcal infection include (1) alcohol or drug intoxication or other cerebral impairment that can depress the cough reflex and increase aspiration of secretions; (2) abnormality of the respiratory tract (e.g., viral infections), pooling of mucus, bronchial obstruction, and respiratory tract injury caused by irritants (which disturb the integrity and movement of the mucociliary blanket); (3) abnormal circulatory dynamics (e.g., pulmonary congestion and heart failure); (4) splenectomy; and (5) certain chronic diseases such as sickle cell anemia and nephrosis. Trauma to the head that causes leakage of spinal fluid through the nose predisposes to pneumococcal meningitis.
Pneumonia often begins with a sudden chill, fever, cough, and pleuritic pain. Sputum is a red or brown “rusty” color. Bacteremia occurs in 15–25% of cases. Spontaneous recovery may begin in 5–10 days and is accompanied by development of anticapsular antibodies. Pneumococci are a prominent cause of otitis media, sinusitis, purulent bronchitis, pericarditis, bacterial meningitis, and sepsis, especially in immunocompromised patients.
In sputum, pneumococci are seen as lancet-shaped gram-positive diplococci in Gram-stained smears. They can also be detected by using the quellung reaction with multitype antiserum. On blood agar, pneumococci form small alpha-hemolytic colonies. The colonies are bile-soluble, i.e., are lysed by bile, and growth is inhibited by optochin. Blood cultures are positive in 15–25% of pneumococcal infections. Culture of cerebrospinal fluid is usually positive in meningitis. Rapid diagnosis of pneumococcal meningitis can be made by detecting its capsular polysaccharide in spinal fluid using the latex agglutination test. A rapid test that detects urinary antigen (capsular polysaccharide) is also available for the diagnosis of pneumococcal pneumonia and bacteremia. Because of the increasing numbers of strains resistant to penicillin, antibiotic sensitivity tests must be done on organisms isolated from serious infections.
Most pneumococci are susceptible to penicillins and erythromycin. In severe pneumococcal infections, penicillin G is the drug of choice, whereas in mild pneumococcal infections, oral penicillin V can be used. In penicillin-allergic patients, erythromycin or one of its long-acting derivatives, e.g., azithromycin, can be used. In the United States, about 25% of isolates exhibit low-level resistance to penicillin, primarily as a result of changes in penicillin-binding proteins. An increasing percentage of isolates, ranging from 15% to 35% depending on location, show high-level resistance, which is attributed to multiple changes in penicillin-binding proteins. They do not produce -lactamase. Vancomycin is the drug of choice for the penicillin-resistant pneumococci. However, strains of pneumococci tolerant to vancomycin have emerged. (Tolerance to antibiotics is described in Specific Mechanisms of Resistance.) Strains of pneumococci resistant to multiple drugs have also emerged.
Despite the efficacy of antimicrobial drug treatment, the mortality rate is high in elderly ( i.e., persons older than 65 years), immunocompromised (especially splenectomized), or debilitated persons. Such persons should be immunized with the polyvalent (23-type) polysaccharide vaccine. The vaccine is safe and fairly effective and provides long-lasting (at least 5 years) protection. A booster dose is recommended for (1) people over the age of 65 who received the vaccine more than 5 years ago and who were less than 65 when they received the vaccine and (2) people between the ages of 2 and 64 who are asplenic, HIV-infected, receiving cancer chemotherapy, or receiving immunosuppressive drugs to prevent transplant rejection. Oral penicillin is given to young children with hypogammaglobulinemia or splenectomy because such children are prone to pneumococcal infections and respond poorly to the vaccine.
A different pneumococcal vaccine containing pneumococcal polysaccharide coupled (conjugated) to a carrier protein (diphtheria toxoid) is given to children under the age of 2 years. This “conjugate” vaccine is effective in young children in preventing both bacteremic infections, such as meningitis, and mucosal infections, such as otitis media. The vaccine contains the capsular polysaccharide of the seven most common pneumococcal serotypes. Immunization of children reduces the incidence of pneumococcal disease in adults because children are the main source of the organism for adults and immunization reduces the carrier rate in children.
A potential problem regarding the use of the pneumococcal vaccine containing 7 serotypes is that of serotype replacement. Will the vaccine reduce the incidence of disease caused by the serotypes in the vaccine but not the overall incidence of pneumococcal disease because other serotypes that are not in the vaccine will now cause disease? This important question is being evaluated at this time.
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