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Staphylococcus infections



Staphylococci are spherical bacteria that grow in irregular clusters. They were among the first pathogenic bacteria to be discovered in pus by Koch in 1878, cultivated by Pasteur in 1880, recovered from purulent infection by Ogston in 1881, and characterized in the early 1900’s by Rosenbach. The species of staphylococci are commonly present on the body surfaces of man and animals. They are also found in air, dust, milk, food, and sewage. In man, they are found on the skin, in the nasopharynx, and in the gastrointestinal tract. 

All staphylococci are placed in one common genus, that is, Staphylococcus. The most important species of this genus is Staph. aureus, which is the pathogenic member. Other species include Staph. epidemidis and Staph. saprophyticus, which rarely cause disease. 

Staph. aureus cause a wide variety of pyogenic infectious diseases ranging from localized skin infections (boils and carbuncles) to pneumonia, exfoliative dermatitis, osteomyelitis, and food poisoning. 

CELLULAR MORPHOLOGY 

Staph. aureus are spherical bacteria, 0.5-1.5μm in diameter. They occur singly, in pairs, and in irregular bunches. They are nonmotile, nonsporing, and noncapsulated. There are a few strains, which possess capsule or slime layer. They are Gram-positive. 

CULTURAL CHARACTERISTICS

PHYSICAL REQUIREMENTS 

Staph. aureus are facultative anaerobes, though they may grow in the presence of oxygen. They are mesophilic bacteria growing at temperature ranging from 20-40°C , optimum being 30-37°C. The chromogenic character is more prominent when incubated at room temperature. The optimum pH is 7.0-7.5. 

NUTRITIONAL REQUIREMENTS 

Staph. aureus can grow readily on simple culture media, such as nutrient agar and nutrient broth. Their growth is, however, enhanced when cultivated on meat infusion media with or with out any added carbohydrate. Blood agar, mannitol salt agar, and potassium tellurite agar are used for their isolation and identification. They characteristically produce golden-yellow colonies due to the production of carotenoid pigments; color may vary from white to deep golden-yellow. Many strains, particularly pathogenic, produce clear hemolysis on blood agar. Cultivation on tellurite medium is useful in isolating Staph. aureus from specimens such as feces that are contaminated with other bacteria. 

COLONIAL MORPHOLOGY 

Staph. aureus Usually produce smooth, round, raised, glistening, opaque, golden yellow colonies with entire edge. 

BIOCHEMICAL CHARACTERISTICS 

Staph. aureus ferment many carbohydrates slowly, producing lactic acid but no gas. Significantly, most strains ferment mannitol; other species of staphylococci do not ferment mannitol. They produce catalase, which distinguishes them from streptococci. They usually grow with 10% NaCl.

RESISTANCE 

Staphylococci are more resistant than most vegetative forms of bacteria to heat; drying, and certain disinfectants. Heating at 60°C agar, and potassium tellurite agar are used for their isolation and identification. They characteristically produce golden-yellow colonies due to the production of carotenoid pigments; color may vary from white to deep golden-yellow. Many strains, particularly pathogenic, produce clear hemolysis on blood agar. Cultivation on tellurite medium is useful in isolating Staph. aureus from specimens such as feces that are contaminated with other bacteria. 


EXTRACELLULAR ENZYMES 

COAGULASE 

Staph. aureus produce and release various extracellular enzymes, which are involved in the course of the disease. 

Production of coagulase is a characteristic of Staph. aureus. lndeed, determination of coagulase activity is a particular criterion for designation of a particular staphylococcal strain as being Staph. aureus. This enzyme clots plasma. It is produced in a cell-free form, which is secreted into the medium, and in an immunologically unrelated cell-bound form. Detection of both of these forms of coagulase is easily accomplished in the diagnostic laboratory. Free coagulase is shown by incubating staphylococci at 37°C in a tube containing rabbit plasma. Formation of a plasma clot within 3 to 4 hours is a positive reaction. The bound coagulase on the surface of the bacterial cells is detected by mixing staphylococcal colony with rabbit plasma. Formation of a gelatinous clump of cells is an indication of a positive reaction. 

Staphylococcal coagulase contributes in the pathological course of the disease by inhibiting the bactericidal activity of normal serum and by inhibiting phagocytosis. 

HYALURONIDASE 

LIPASES 

Hyaluronic acid is a ground substance of tissues. Staphs cannot spread into the tissues without disintegrating this complex. They produce an enzyme, called hyaluronidase, that depolymerizes hyaluronic acid and facilitates spread of the organism in tissues. 

Staph. aureus produce a group of enzymes that can hydrolyze lipids, including the fats and oils of the skin. These enzymes presumably facilitate invasion by pathogenic staphs of cutaneous and subcutaneous tissue.

STAPHYLOKINASE 

Pathogenic strains of staphs produce an enzyme that can dissolve fibrin clots. 
This enzyme is called staphylokinase. 

STAPHYLOOOCCAL TOXINS 

Staph. aureus strains produce few toxins that have been proved significant in the pathogenesis. 

STAPHYLOCOCCAL LEUCOCIDIN 

This exotoxin increases the permeability of leucocytes to cations. This leads to the swelling and eventually cell disruption. The leucocidin is also known as Panton-Valentine leucocidin. 

STAPHYLOLYSINS 

These toxins are produced by a vast majority of strains of Staph. aureus and are believed to play a significant role in the pathogenesis of staphylococcal diseases. They are active not only against erythrocytes but also against leucocytes and platelets. There are four main types of staphylolysins: alpha, beta, gamma, and delta. The alpha-lysin is responsible for the lysis of rabbit, sheep, and calf erythrocytes. It causes necrosis of the dermis and epidermis. The beta-lysin is strongly active against ovine and bovine erythrocytes but weakly active against human erythrocytes. The delta-lysin also serves as hemolytic and dermonecrotic toxin. The gamma-lysin is toxic for the human erythrocytes. 

EXFOLIATIN 

There are two serologically distinct types of this toxin: A and B. Exfoliatin A is relatively heat-stable, retaining activity after heating to 100°C for 20 minutes. Exfoliatin B is heat-Iabile, losing activity upon heating to 60°C for 30 minutes. Both of them disrupt the intracellular cement of epidermal cells, resulting in exfoliation. It is involved in scalded skin syndrome. 

TOXIC SHOCK SYNDROME TOXIN 

Many pathogenic strains of staphs produce an exotoxin called toxic shock syndrom toxin-t. It stimulates the production of interieukin-t (IL-1) and tumor necrosis factor (TNF) by macrophages. It is pyrogenic, increases susceptibility of human host to the bacterial endotoxins, and causes damage to a variety of host organs. 

ENTEROTOXIN 

There are a few strains of the staphs, which produce immunologically distinct enterotoxins, designated A to E. The ingestion of preformed enterotoxins in food causes an acute gastroenteritis, usually within 2-5 hours of food ingestion. These toxins are low molecular weight proteins that are colorless, odorless, tasteless, heat-stable, and relatively resistant to proteolytic enzymes. 

PATHOGENESIS 

Staphs are the normal microflora of the human body. The human skin serves as an important habitat for Staph. aureus. These bacteria are present around the 
nose and in the anterior nares in 20% of the general population and up to 70% of hospital staff. They may also be present on the male perineum and not infrequently in the groins and axillae. Twenty five to 30% of the population is the permanent carrier of Staph. aureus

Staphyiococcal carriage can result in infection of the individual carrier or dissemination and resultant cross-infection of others. Transfer on hands is the most important mode of spread but skin scale dispersion from the face and perineum of carriers can be significant in operation theatre and special care unit outbreaks. Transfer of staphs is also possible by clothing and fomites. Approximately 20% of all human staphylococcal infections are autogenous. 

CLINICAL MANIFESTATIONS 

Staph. aureus can cause a wide clinical spectrum of diseases. These are usually localized causing an abscess, but infection may spread, resulting in bacteremia or metastatic infection. The infections are characterized by severe suppuration, and necrosis of local tissues.

INVASIVE INFECTIONS OF SKIN AND SOFT TISSUE 

Skin sepsis caused by Staph. aureus occurs more frequently in patients with skin disease, and in diabetic patients and those receiving high-dose corticosteroid therapy, in whom defects in phagocytosis predispose to such infections. 

FURUNCLE

The most common endogenous infection caused by Staph. aureus is the furuncle, or simple boil. It is a superficial infection that can develop any where on the body but commonly affect the face, neck, axillae, buttocks, or perineum. The infection usually involves the hair follicles, sebaceous glands, or sweat glands. One of the predisposing factors of furuncles is blockage of the gland duct. Establishment of a focus of infection triggers an inflammatory response, with migration and subsequent accumulation of phagocytes, deposition of fibrin in the area, and formation of fibrous tissue around the lesion. 

CARBUNCLE

The lesion is characterized by the formation of a purulent abscess. The center of the lesion becomes necrotic, and pus is formed, which contains dead bacteria and dead leucocytes. The pus usually discharges spontaneously with subsequent resolution and intradermal scarring. Furuncles are not a major concern, except for the area of the nose, where such lesions should be treated as potentially life threatening because the staphs may have direct access to the CNS. 

Carbuncles are in fact the extensions of furuncles to the subcutaneous tissues with one or more abscesses. They are characteristically more chronic with pus discharging through a number of sinus tracks to the skin. The most common 
sites for the development of carbuncle are back of the neck and buttocks but they can develop on other parts of the body. If untreated, the carbuncle may invade the blood circulation causing bacteremia. 

STAPHYLOCOCCAL CELLULITIS 

It is a spreading inflammation of celluIar or connective tissue of the skin. There may be an obvious pre-existing focus, for example an infected wound or chronic ulcer, but the entry site is frequently inapparent. The affected area, usually a limb, is red, swollen and tender, the advancing edge being rather diffuse in comparison with the clear cut edge of streptococcal erysipelas. Systemic upset, including fever, rigors, and toxemia, can be severe. Untreated cellulitis may be complicated by bacteremia and metastatic infection, such as endocarditis, osteomyelitis, and abscess formation in kidneys and brain. The patient should be treated promptly with parenteral antibiotics as cellulitis is a life threatening disease. 

PYOMYOSITIS 

Pyomyositis is predominantly a childhood disease of the tropics in which the muscles of the lower limbs are most commonly affected. Local pain and tenderness within one or more muscle groups is followed by rupture of the intramuscular abscess through fascia into the subcutaneous tissue. Pyrexia and rigors are common. Treatment requires surgical drainage and administration of antibiotics. 

TOXlN-INDUCED STAPHYLOCOCCAL SKIN DISEASE 

These skin manifestations of staphylococcal infection are caused by the effects of exfoliatin, a specific epidermolytic toxin produced by Staph. aureus. The diseases represent a spectrum of toxin-induced disease, collectively called either 
toxic epidermal necrolysis (TEN), staphylococcal scalded skin syndrome (SSSS) or Ritter’s disease. They are commonly seen in neonates and children although immunosuppressed adults may also be involved. Exfoliatin, produced in a staphylococcal lesion, enters the blood circulation and causes erythema and widespread superficial epidermal shedding at remote sites from which staphs cannot be isolated. The shedding reveals denuded oozing epidermis (the scalded skin appearance). The patients are frequently febrile and often lose copious amounts of fluid. A variant termed staphylococcal scarlet fever appears to be a mild form of SSSS, due to minimal amounts of circulating exfoliatin and characterized by a generalized erythema and subsequent desquamation in the absence of the classical oral lesions of streptococcal disease. 

STAPHYLOCOCCAL TOXIC SHOCK SYNDROME 

lt is a serious disease caused by the absorption of a specific toxin produced by Staph. aureus. This toxin is called toxic shock syndrome toxin-1 (TSST-1). The disease is most common in women who use absorptive tampons during menstruation. However, it can occur in other situations, such as with the use of female barrier contraceptives. The staphs grow massively in vagina and around the tampons and liberate TSST-1. The onset is abrupt. The illness is characterized by high fever, toxemia, and rigors, which are accompanied by vomiting, diarrhea and myalgia. The disease progresses in the next 48 hours to severe shock with generalized erythroderma and the vulva and conjunctiva are commonly hyperaemic. Hepatorenal involvement, sensorial disturbance and persistent hypetension are frequently present. Leucocytosis, moderate uremia and disturbances of yet and muscle enzymes are typical. Treatment is supportive. 

Antibiotics are usually given, although the syndrome is produced by exotoxins . Antitoxin therapy is not available at present. 

LABORATORY DIAGNOSIS 

The diagnosis of staphylococcal infections depends on the isolation and identification of Staph. aureus from the lesion. 

CLINICAL SPECIMENS 

Common specimens include wound exudates or aspirations, tissues or bones, urine, blood, and cerebrospinal fluid. The specimens should be collected from the offending site prior to antibacterial therapy and so as to exclude normal microflora as much as possible. 

MICROSCOPIC EXAMINATION OF SPECIMENS 

The examination of Gram-stained smears of the specimens may provide rapid, useful, presumptive evidence of staphylococcal infection. Staphylococci usually appear as pairs or small clusters of Gram-positive cocci, often associated with host phagocytic cells. 

ISOLATION OF STAPHS 

Clinical specimens should be inoculated on to sheep blood agar. On blood agar, Staph. aureus produce abundant growth within 18-24 hours at 35-37°C . Colonies will be 1-3 mm in diameter and usually circular, smooth, and raised, with a butyrous consistency. On sheep blood agar, colonies are usually surrounded by zones of hemolysis. Specimens from potentially contaminated sources, such as wounds, should be inoculated on a selective medium, such as SK agar, mannitol salt agar, Columbic colistin-nalidixic acid agar, or tellurite glysine agar. These media inhibit Gram-negative bacteria but allow growth of staphylococci and certain other Gram-positive cocci. 

IDENTIFICATION 

Staph. aureus can be identified on the basis of colony morphology, coagulase activity, oxygen requirements, hemolysis, novobiocin susceptibility, acetylmethylcarbinol production, fermentation of mannitol without gas, and certain enzyme activities. 

PREVENTION 

Staphs are widely distributed in the nature and have very close association with man. It, therefore, appears impossible to eliminate them completely, The controlling measures should, thus, be aimed at controlling the spread of the organisms both in and outside of the hospital environment. Because of the frequency and seriousness of hospital acquired staphylococcal diseases, it is there that control efforts have been concentrated. These efforts are as given under. 

* Good hygienic care and proper disposal of hospital wastes. 

* lsolation of patients with staphylococcal diseases, particularly those with open wounds or pneumonia. 

* Barring contact of known carriers, with highly susceptible individuals, such as newborn infants or compromised patients. 

* Avoiding indiscriminate use of antibiotics. 

* Strict adherence to proper operating room procedures. 

* Clothes and bedding that may cause reinfection should be washed at a sufficiently high temperature to destroy staphs (70-80°C) or dry-cleaned. 

* Chemoprophylactic measures should be taken into consideration in surgical procedures to avoid any risk of staphylococcal infection. 

THERAPY 

lt is very important to take a serious care of the local lesion, such as abscess. It should be perfectly drained and antibiotic ointment be applied. Antibiotic therapy alone is unlikely to be effective if collections of infected material are undrained. For all staphylococcal infections, oral therapy is highly recommended. Penicillin or cephalosporin, such as dicloxacillin or cephalexin, is the drug of choice. In penicillin-allergic patients, erythromycin is commonly prescribed, although the prevalence of erythromycin-resistant strains makes this regimen less attractive empirically. 


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