BACTERIAL INFECTIONS CAUSED BY: GRAM-POSITIVE COCCI

STAPHYLOCOCCAL INFECTIONS

Pathogenic staphylococci are ubiquitous; they are carried in the anterior nares of about 30% of healthy adults and on the skin of about 20%. Hospital patients and personnel have slightly higher rates. Antibiotic-resistant strains are common in hospitals and in the community.

Newborns and nursing mothers are predisposed to staphylococcal infections, as are patients with influenza, chronic bronchopulmonary disorders (eg, cystic fibrosis, pulmonary emphysema), leukemia, neoplasms, transplants, prostheses or other foreign bodies, burns, chronic skin disorders, surgical incisions, diabetes mellitus, and indwelling intravascular plastic catheters. Patients receiving adrenal steroids, irradiation, immunosuppressants, or antitumor chemotherapy are also at increased risk. Predisposed patients may acquire antibiotic-resistant staphylococci from other colonized areas of their bodies or from hospital personnel. Transmission via the hands of personnel is the most common means of spread, but airborne spread can also occur.

Some staphylococcal disease is toxin-mediated rather than the result of infection per se. Staphylococcal food poisoning is caused by ingesting a preformed heat-stable staphylococcal enterotoxin. Toxic shock syndrome (below), caused by exotoxin, may occur in association with the use of vaginal tampons or as a complication of a postoperative infection (often minor appearing). Staphylococcal scalded skin syndrome, caused by the toxin exfoliatin, is an exfoliative dermatitis of childhood.

Symptoms and Signs

Neonatal infections usually appear within 6 wk after birth. Pustular or bullous skin lesions are most common, generally located in the axillary, inguinal or neck skin folds; but multiple subcutaneous abscesses (especially in breasts), exfoliation, bacteremia, meningitis, or pneumonia also occur. Microscopic examination of purulent lesions reveals neutrophils and clusters of gram-positive staphylococci, often within the neutrophils. 

Nursing mothers who develop breast abscesses or mastitis 1 to 4 wk. postpartum should be considered to have antibiotic-resistant staphylococcal infections, probably derived from the nursery via their infants.

Postoperative infections, ranging from stitch abscesses to extensive wound involvement, commonly are due to staphylococci. Such infections may appear within a few days or several weeks after surgery; they are likely to be delayed in onset if the patient received antibiotics at the time of surgery.

Furuncles and carbuncles

Staphylococcal pneumonia should be suspected in patients with influenza or who are receiving corticosteroids or immunosuppressive therapy who develop dyspnea, cyanosis, and persistent or recurrent fever and in those hospitalized with chronic bronchopulmonary or other high-risk diseases who develop fever, tachypnea, cough, cyanosis, and leukocytosis. In newborns, staphylococcal pneumonia is characterized by abscess formation in the lung, followed by rapid development of pneumatoceles and empyema. Microscopic examination of patients' sputum reveals grapelike clusters of gram-positive cocci within neutrophils.

Staphylococcal bacteremia may occur with any localized staphylococcal abscess or infection related to intravascular catheters or other foreign bodies; in severely burned patients, it is a common cause of death. Persistent fever is usual and may be associated with shock. Staphylococcus epidermidis and other coagulase-negative staphylococci are increasingly a cause of nosocomial bacteremia associated with catheters and other foreign bodies. They are important causes of morbidity (especially prolongation of hospitalization) and mortality in debilitated patients.

Staphylococcal endocarditis develops, particularly in IV drug users and in patients with prosthetic heart valves. Diagnosis is suspected by the sudden development of a cardiac murmur, septic emboli, and other classic signs and is confirmed by echocardiogram and blood cultures.

Staphylococcal osteomyelitis occurs predominantly in children, causing chills, fever, and pain over the involved bone. Redness and swelling subsequently appear. Periarticular infection frequently results in effusion, suggesting septic arthritis rather than osteomyelitis. The WBC count is usually > 15,000/µL, and blood cultures are often positive. X-ray changes may not be apparent for 10 to 14 days, and bone rarefaction and periosteal reaction may not be detected for even longer. Abnormalities in radionuclide bone scans often are apparent earlier.

Staphylococcal enterocolitis, which is now rare, is suggested when hospitalized patients develop fever, ileus, abdominal pain and distention, hypotension, or diarrhea--especially if they underwent abdominal surgery recently or received antibiotics. The diagnosis is likely if microscopic examination of the stools reveals sheets of neutrophils and gram-positive cocci. Infection with toxigenic Clostridium difficile, the most common cause of antibiotic-associated colitis, must be ruled out.

Toxic Shock Syndrome

A syndrome caused by staphylococcal exotoxin, characterized by high fever, vomiting, diarrhea, confusion, and skin rash that may rapidly progress to severe and intractable shock.

Toxic shock syndrome occurred predominantly in menstruating women who used tampons. After widespread publicity of the role played by tampons and diaphragms as well as the withdrawal of some tampons from the market, the incidence in women dropped precipitously. Less severe cases that lack some manifestations are fairly common. Estimates made from small series suggest about 3 cases/100,000 menstruating women still occur, and cases are still reported in women who do not use tampons and in postoperative and postpartum women. About 15% of cases occur postpartum or as postoperative staphylococcal wound infections, which frequently appear insignificant. Cases have also been reported in association with influenza, osteomyelitis, and cellulitis.

Etiology and Pathogenesis

The exact cause of toxic shock syndrome is unknown, but almost all cases have been associated with exotoxin-producing strains of phage-group 1 Staphylococcus aureus that elaborate the toxic shock syndrome toxin-1 or related exotoxins. The organisms have been found in mucosal sites (nasopharynx, vagina, trachea) or sequestered (empyema, abscess), and in menstruating women in the vagina. Presumably, women most at risk for toxic shock syndrome are those with preexisting colonization of the vagina who use tampons. It is likely that mechanical or chemical factors related to tampon use result in enhanced production of the bacterial exotoxin, which enters the bloodstream through a mucosal break or via the uterus.

Symptoms, Signs and Diagnosis

Onset is sudden, with fever (39 to 40.5° C [102 to 105° F], which remains elevated), headache, sore throat, nonpurulent conjunctivitis, profound lethargy, intermittent confusion without focal neurologic signs, vomiting, profuse watery diarrhea, and a diffuse sunburn-like erythroderma. The syndrome may progress within 48 h to orthostatic hypotension, syncope, shock, and death. Between the 3rd and 7th days after onset, desquamation of the skin begins and leads to epidermal sloughing, particularly of the palms and soles.

Other organ systems are frequently involved, resulting in mild nonhemolytic anemia, moderate leukocytosis with a predominance of immature granulocytes, and early thrombocytopenia followed by thrombocytosis. Although clinically important bleeding phenomena are rare, the prothrombin time and partial thromboplastin time tend to be prolonged. Laboratory evidence of hepatocellular dysfunction (hepatitis) and skeletal myolysis is common during the first week of illness. Cardiopulmonary involvement may occur, manifested by peripheral and pulmonary edema (with abnormally low central venous pressures, suggesting adult respiratory distress syndrome). Especially in children, profound hypotension and impaired perfusion of the extremities may occur, and renal dysfunction, characterized by diminished urine output and increases in BUN and creatinine levels, almost always occurs.

Toxic shock syndrome resembles Kawasaki syndrome (mucocutaneous lymph node syndrome but can usually be differentiated on clinical grounds. Kawasaki syndrome generally occurs in children < 5 yr of age; it does not cause shock, azotemia, or thrombocytopenia; and the skin rash is maculopapular. Other disorders to be considered are scarlet fever, Reye's syndrome, the staphylococcal scalded skin syndrome, meningococcemia, Rocky Mountain spotted fever, leptospirosis, and viral exanthematous diseases. These are ruled out by specific clinical differences, by cultures, and by serologic studies.

STREPTOCOCCAL INFECTIONS

When grown on sheep blood agar, beta-hemolytic streptococci produce zones of clear hemolysis around each colony; beta-hemolytic streptococci (commonly called Streptococcus viridans) are surrounded by green discoloration resulting from incomplete hemolysis; and beta-hemolytic streptococci are nonhemolytic. Another classification, based on carbohydrates present in the cell wall, divides streptococci into the Lancefield groups A through H and K through T.

Group A beta-hemolytic streptococci (S. pyogenes) are the most virulent species for humans, causing pharyngitis, tonsillitis, wound and skin infections, septicemia, scarlet fever, pneumonia, rheumatic fever, and glomerulonephritis.

Group B beta-hemolytic streptococci, also known as S. agalactiae, cause serious infections, particularly neonatal sepsis, postpartum sepsis, endocarditis, and septic arthritis.

Groups C and G beta-hemolytic streptococci are S. pyogenes-like organisms that are distinguished by their serogrouping and resistance to bacitracin. They are often carried by animals and also colonize the human pharynx, intestinal tract, vagina, and skin. They can cause severe suppurative infections, including pharyngitis, pneumonia, cellulitis, pyoderma, erysipelas, impetigo, wound infections, puerperal sepsis, neonatal sepsis, endocarditis, septic arthritis, and poststreptococcal glomerulonephritis. Penicillin, vancomycin, the cephalosporins, and erythromycin are useful in therapy, but susceptibility tests can guide therapy, especially in very ill, immunocompromised, or debilitated hosts or in those with foreign bodies at the site of the infection. Surgery as an adjunct to antimicrobial therapy may be lifesaving.

Group D (usually alpha- or beta-hemolytic) includes the enterococci E. faecalis, E. durans, and E. faecium (formerly S. faecalis, S. durans, S. faecium), and the nonenterococcal group D streptococci, of which S. bovis and S. equinus are the most common. Most infections of humans caused by group D are caused by E. faecalis, E. faecium, or S. bovis. Like the enterococci, S. bovis is commonly found in the GI tract. S. bovis is an important cause of bacterial endocarditis, particularly when an intestinal neoplasm or other significant lesion is present. S. bovis is relatively susceptible to antibiotics, whereas enterococci are very resistant unless exposed to a combination of a cell wall-active drug such as penicillin, ampicillin, or vancomycin plus an aminoglycoside such as gentamicin or streptomycin. E. faecalis and E. faecium cause endocarditis, UTIs, intra-abdominal infections, cellulitis, and wound infection as well as concurrent bacteremia.

Viridans streptococci consist of five main species: S. mutans, S. sanguis, S. salivarius, S. mitior, and A. milleri; the latter is further subdivided into S. constellatus, S. intermedius, and S. anginosus. There is still disagreement about their classification and identification. Although defined as beta-hemolytic, some are actually alpha-hemolytic, and many of these organisms are nongroupable. Colonization of the oral cavity and its components appears to play an important role in preventing colonization by other more pathogenic organisms, such as Pseudomonas and enteric organisms. Most viridans streptococci are susceptible to lysis by serum and do not produce exotoxins or traditional virulence factors; however, they are important causes of bacterial endocarditis because they can adhere to cardiac valves, especially in persons with underlying valvular disease. Members of the S. milleri group are variably hemolytic, microaerophilic, or anaerobic, and tend to produce serious invasive infections or localized abscesses in almost any part of the body.

S. iniae, a pathogen in fish, is capable of causing outbreaks of cellulitis and invasive infections in patients with skin injuries who handled live or freshly killed aquacultured fish, usually tilapia or trout.

Symptoms and Signs

Streptococcal infections can be divided into three groups: (1) the carrier state, in which the patient harbors streptococci without apparent infection; (2) acute infection, often suppurative, caused by streptococcal invasion of tissues; and (3) delayed, nonsuppurative complications, which occur most commonly about 2 wk after a clinically overt streptococcal infection, but the infection may be asymptomatic and the interval may be longer than 2 wk.

Primary and secondary infections can spread through the affected tissues and along lymphatic channels to regional lymph nodes; they can also produce bacteremia. The development of suppuration depends on the severity of infection and the susceptibility of tissue.

In acute infection, symptoms and signs depend on the affected tissue, the organism, the state of the host, and the host's response.

Streptococcal pharyngitis, the most common streptococcal disease, is a primary pharyngeal infection with group A beta-hemolytic streptococci. About 20% of patients with group A infections present with sore throat, fever, a beefy red pharynx, and a purulent tonsillar exudate. The remainder are asymptomatic, have fever or mild sore throat alone (resembling viral pharyngitis), or have nonspecific symptoms such as headache, malaise, nausea, vomiting, or tachycardia. Seizures may occur in children. The cervical and submaxillary nodes may enlarge and become tender. In children < 4 yr, rhinorrhea is common and sometimes the only symptom. Cough, laryngitis, and stuffy nose are uncharacteristic of streptococcal pharyngeal infection, and their presence suggests another cause (usually viral or allergic) or coexisting complications. Definitive diagnosis rests on the laboratory techniques described below.

Scarlet fever (scarlatina) is uncommon today, presumably because antibiotic therapy prevents the infection from progressing or causing epidemics. Scarlet fever is caused by group A streptococcal (and occasionally other) strains that produce an erythrogenic toxin, leading to a diffuse pink-red cutaneous flush that blanches on pressure. The rash is seen best on the abdomen, on the lateral chest, as dark red lines in skinfolds (Pastia's lines), or as circumoral pallor. A strawberry tongue (inflamed papillae protruding through a bright red coating) also occurs and must be differentiated from that seen in the toxic shock (see above) and Kawasaki syndromes. The upper layer of the previously reddened skin often desquamates after fever subsides. The other symptoms are similar to those in streptococcal pharyngitis, and the course and management of scarlet fever are the same as for other group A infections.

Streptococcal pyoderma or Impetigo can also be caused by S. aureus.

Streptococcal toxic shock syndrome, similar to that caused by S. aureus, has recently been attributed to group A beta-hemolytic streptococci strains capable of producing pyrogenic exotoxins. Patients are usually otherwise healthy children or adults with skin and soft tissue infections.

Laboratory Findings

The ESR is usually > 50 mm/h in acute infection, and WBC count is about 12,000 to 20,000/µL, with 75 to 90% neutrophils, many of which are young forms. The urine commonly shows no specific changes except those attributable to fever (eg, proteinuria).

The presence of streptococci in specimens taken from the infected site can be established by overnight incubation on a sheep blood agar plate or, for group A organisms, immediate staining with fluorescent antibodies. The fluorescent method obviates the need for serologic testing to differentiate group A from other beta-hemolytic streptococci, but false-positive reactions with hemolytic staphylococci often occur. Many other inexpensive tests are available for rapid detection of group A streptococci in throat swabs.

Evidence of infection can be obtained indirectly by demonstrating antistreptococcal antibodies in serum during convalescence. 

PNEUMOCOCCAL INFECTIONS

Streptococcus pneumoniae (formerly called Diplococcus pneumoniae) is a gram-positive encapsulated diplococcus, with adjacent surfaces being rounded and the ends pointed to give a lancet shape. It sometimes appears as short chains; in old cultures or purulent exudates, some of the organisms may stain gram-negative. The capsule, visible in smears stained with methylene blue, consists of a complex polysaccharide that determines serologic type and contributes to virulence and pathogenicity. There are > 85 types.

In the Neufeld quellung reaction, the best method for determining type, the capsule swells in the presence of type-specific rabbit antiserum. For diagnosis, polyvalent antisera against some groups of specific types are available commercially or from the CDC, and sera against all types are available from the Danish Serum Institute in Copenhagen. Typing may also be carried out by specific agglutination or by immunoelectrophoresis against specific antisera. A type-specific antipneumococcal antibody may be identified in serum or other body fluids by counterimmunoelectrophoresis.

The most common types of pneumococcus in serious infections have been types 1, 3, 4, 7, 8, and 12 in adults and types 6, 14, 19, and 23 in infants and children, but these patterns are slowly changing, in part because of the wide use of polyvalent vaccine.

Recovery from pneumococcal infection is usually associated with development of circulating type-specific antibodies.

Epidemiology

Pneumococci commonly inhabit the human respiratory tract, particularly in winter and early spring, when they may be cultured from up to half of the population. The organisms spread from person to person in droplets. Isolating patients is not generally required but seems wise if the organism is highly resistant to penicillin. True epidemics of pneumococcal pneumonia or other infections are rare.

The patients most susceptible to serious and invasive pneumococcal infections are those with lymphoma, Hodgkin's disease, multiple myeloma, splenectomy, other serious debilitating diseases or immunologic deficiencies, and sickle cell disease. Damage to the respiratory epithelium by chronic bronchitis or common respiratory viruses, notably influenza virus, may predispose to pneumococcal invasion. Pneumococcal pneumonia is highly prevalent among gold and diamond miners in South Africa and New Guinea.

Diseases Caused by Pneumococcus

Pneumonia is the most frequent serious infection caused by pneumococci. It is usually lobar but often presents as bronchopneumonia or tracheobronchitis without clearly defined parenchymal involvement. Empyema complicates < 3% of cases of pneumococcal pneumonia. The exudate may resolve spontaneously or during treatment of the pneumonia; conversely, it may become thick and fibrinopurulent, is sometimes loculated, and may require surgical drainage.

Pneumococci cause about 50% of acute otitis media in infants (after the newborn period) and children. About 1/3 of children in most populations have an attack of acute pneumococcal otitis media in the first 2 yr of life, and recurrent otitis due to pneumococcus is common. Mastoiditis, meningitis, and lateral sinus thrombosis, fairly common complications of otitis media in the preantibiotic era, are now rare.

Pneumococcus may infect the paranasal sinuses. Infection of the ethmoidal or sphenoidal sinus may extend into the meninges, producing bacterial meningitis. Sinusitis may become chronic and polymicrobic.

Pneumococcus is one of the most frequent causes of acute purulent meningitis in all age groups. Pneumococcal meningitis may be secondary to bacteremia from other foci (notably pneumonia); infection of the ear, mastoid process, or paranasal sinuses (notably the ethmoidal or sphenoidal sinus); or basilar fracture of the skull involving one of these sites or the cribriform plate. 

Bacteremia may accompany the acute phase of pneumococcal pneumonia, meningitis, endocarditis, or infection of paranasal sinus, internal ear, or mastoid. It may even occur in an otherwise normal patient during the course of a simple, febrile, viral URI (common cold). Pneumococcal bacteremia may be a primary infection in susceptible patients.

Pneumococcal endocarditis may result from the bacteremia even in patients without previous valvular heart disease. A new murmur may develop or pneumococcal endocarditis may produce a corrosive valvular lesion, with sudden rupture or fenestration leading to rapidly progressive heart failure. Rarely, the illness is fatal without having produced changing murmurs, petechiae, or embolic phenomena. Valvular lesions and vegetations may be visualized by echocardiography.

Pneumococcal arthritis, an uncommon form of acute purulent (septic) arthritis, is usually a complication of bacteremia from another focus. The clinical picture and therapy are similar to those of septic arthritis caused by other gram-positive cocci. Pneumococci can usually be demonstrated by direct smear and by culture of the aspirated purulent synovial fluid.

Pneumococcal peritonitis is rare, occurring most often in young women, presumably as an ascending infection from the vagina through the fallopian tubes, or in patients with nephrotic syndrome. The symptoms are similar to those of acute bacterial peritonitis of other causes; the infection responds rapidly to treatment with penicillin.

Source: Merck