The Staphylococci Gram-positive, cluster-forming coccus nonmotile, nonsporeforming facultative anaerobe fermentation of glucose produces mainly

lactic acid catalase positive coagulase positive golden yellow colony on agar normal flora of humans found on nasal passages, skin and mucous membranes pathogen of humans, causes a wide range of suppurative infections, as well as food poisoning and toxic shock syndrome

Staphylococci are Gram-positive spherical bacteria that occur in microscopic clusters resembling grapes. Bacteriological culture of the nose and skin of normal humans invariably yields staphylococci. S. aureus colonizes mainly the nasal passages, but it may be found regularly in most other anatomical locales. S epidermidis is an inhabitant of the skin. Staphylococcus aureus forms a fairly large yellow colony on rich medium, S. epidermidis has a relatively small white colony. S. aureus is often hemolytic on blood agar; S. epidermidis is non hemolytic. Staphylococci are facultative anaerobes that grow by aerobic respiration or by fermentation that yields principally lactic acid. The bacteria are catalase-positive and oxidase-negative. S. aureus can grow at a temperature range of 15 to 45 degrees and at NaCl concentrations as high as 15 percent. Nearly all strains of S. aureus produce the enzyme coagulase: nearly all strains of S. epidermidis lack this enzyme. S. aureus should always be considered a potential pathogen; most strains of S. epidermidis are nonpathogenic and may even play a protective role in their host as normal flora. Staphylococcus epidermidis may be a pathogen in the hospital environment. NOTE: Catalase Test A colony is placed on a glass slide. A drop of 3% hydrogen peroxide is added. The catalase- producing organism catalyzes the breakdown of H2O2 to oxygen and water. O2 is released as bubbles. The catalase test is used to differentiate Staphylococcus sp. from Streptococcus sp. Staphylococcus sp. are positive for catalase production. Streptococcus sp. are negative for catalase production NOTE: Coagulase Test Add a generous loopful of the organism to be tested to a tube of citrated rabbit plasma. Thoroughly homogenize the inoculum with the loop and incubate the tube at 37o C for one to four hours. Examine the tube at 30 minute to hourly intervals for the first couple of hours for the presence of a clot by tipping the tube gently on its side. A test that shows any degree of clotting within 24 hours is considered coagulase positive NOTE: Fermentation of Mannitol Mannitol Salt Agar (MSA) is a selective and differential medium. The high concentration of salt (7.5%) selects for members of the genus Staphylococcus, since they can tolerate high saline levels. Organisms from other genera may grow, but they typically grow very weakly.

MSA also contains the sugar mannitol and the pH indicator phenol red. If an organism can ferment mannitol, an acidic byproduct is formed that will cause the phenol red in the agar to turn yellow. Most pathogenic staphylococci, such as Staphylococcus aureus, will ferment mannitol. Most non-pathogenic staphylococci will not ferment mannitol. Staphylococci are perfectly spherical cells about 1 micrometer in diameter. They grow in clusters because staphylococci divide in two planes. The configuration of the cocci helps to distinguish staphylococci from streptococci, which are slightly oblong cells that usually grow in chains (because they divide in one plane only). Pathogenesis of S. aureus infections Staphylococcus aureus causes a variety of suppurative (pus-forming) infections and toxinoses in humans. It causes superficial skin lesions such as boils, styes and furunculosis; more serious infections such as pneumonia, mastitis, phlebitis, meningitis, and urinary tract infections; and deep-seated infections, such as osteomyelitis and endocarditis. S. aureus is a major cause of hospital acquired (nosocomial) infection of surgical wounds and infections associated with indwelling medical devices. S. aureus causes food poisoning by releasing enterotoxins into food, and toxic shock syndrome by release of superantigens into the blood stream.

S. aureus expresses many potential virulence factors: 1) surface proteins that promote colonization of host tissues; (2) invasins that promote bacterial spread in tissues (leukocidin, kinases, hyaluronidase); (3) surface factors that inhibit phagocytic engulfment (capsule, Protein A); (4) biochemical properties that enhance their survival in phagocytes (carotenoids, catalase production); (5) immunological disguises (Protein A, coagulase, clotting factor); and (6) membrane-damaging toxins that lyse eukaryotic cell membranes (hemolysins, leukotoxin, leukocidin; (7) exotoxins that damage host tissues or otherwise provoke symptoms of disease (, TSST) (8) inherent and acquired resistance to antimicrobial agents.

Human staphylococcal infections are frequent, but usually remain localized at the portal of entry by the normal host defenses. The portal may be a hair follicle, but usually it is a break in the skin which may be a minute needle-stick or a surgical wound. Foreign bodies, including sutures, are readily colonized by staphylococci, which may makes infections difficult to control. Another portal of entry is the respiratory tract. Staphylococcal pneumonia is a frequent complication of influenza. The localized host response to staphylococcal infection is inflammation, characterized by an elevated temperature at the site, swelling, the accumulation of pus, and necrosis of tissue. Around the inflamed area, a fibrin clot may form, walling off the bacteria and leukocytes as a characteristic pus-filled boil or abscess. More serious infections of the skin may occur, such as furuncles or impetigo. Localized infection of the bone is called osteomyelitis. Serious consequences of staphylococcal infections occur when the bacteria invade the blood stream. A resulting septicemia may be rapidly fatal; a bacteremia may result in seeding other internal abscesses, other skin lesions, or infections in the lung, kidney, heart, skeletal muscle or meninges.

Adherence to Host Cell Proteins S. aureus cells express on their surface proteins that promote attachment to host proteins such as laminin and fibronectin that form the extracellular matrix of epithelial and endothelial surfaces. In addition, most strains express a fibrin/fibrinogen binding protein (clumping factor) which promotes attachment to blood clots and traumatized tissue. Most strains of S. aureus express both fibronectin and fibrinogen-binding proteins. In addition, an adhesin that promotes attachment to collagen has been found in strains that cause osteomyelitis and septic arthritis. Interaction with collagen may also be important in promoting bacterial attachment to damaged tissue where the underlying layers have been exposed. Invasion The invasion of host tissues by staphylococci apparently involves the production of a huge array of extracellular proteins, some of which may occur also as cell-associated proteins Membrane-damaging toxins aplha-toxin (alpha-hemolysin) The best characterized and most potent membrane-damaging toxin of S. aureus is alpha-toxin. It is expressed as a monomer that binds to the membrane of susceptible cells. Subunits then oligomerize to form heptameric rings with a central pore through which cellular contents leak. In humans, platelets and monocytes are particularly sensitive to alpha-toxin. Susceptible cells have a specific receptor for alpha-toxin which allows the toxin to bind causing small pores through which monovalent cations can pass. The mode of action of alpha hemolysin is likely by osmotic lysis. ß-toxin is a sphingomyelinase which damages membranes rich in this lipid. The classical test for ß-toxin is lysis of sheep erythrocytes. The majority of human isolates of S. aureus do not express ß-toxin. A lysogenic bacteriophage is known to encode the toxin. Leukocidin is a multicomponent protein toxin produced as separate components which act together to damage membranes. Leukocidin forms a hetero-oliogmeric transmembrane pore composed of four LukF and four LukS subunits, thereby forming an octameric pore in the affected mwembrane. Leukocidin is hemolytic, but less so than alpha hemolysin.

Only 2% of all of S. aureus isolates express leukocidin, but nearly 90% of the strains isolated from severe dermonecrotic lesions express this toxin, which suggests that it is an important factor in necrotizing skin infections. Coagulase and clumping factor Coagulase is an extracellular protein which binds to prothrombin in the host to form a complex called staphylothrombin. The protease activity characteristic of thrombin is activated in the complex, resulting in the conversion of fibrinogen to fibrin. Coagulase is a traditional marker for identifying S aureus in the clinical microbiology laboratory. However, there is no overwhelming evidence that it is a virulence factor. Staphylokinase Many strains of S aureus express a plasminogen activator called staphylokinase. This factor lyses fibrin.The genetic determinant is associated with lysogenic bacteriophages. A complex formed between staphylokinase and plasminogen activates plasmin-like proteolytic activity which causes dissolution of fibrin clots. Other extracellular enzymes S. aureus can express proteases, a lipase, a deoxyribonuclease (DNase) and a fatty acid modifying enzyme (FAME). The first three probably provide nutrients for the bacteria, and it is unlikely that they have anything but a minor role in pathogenesis. However, the FAME enzyme may be important in abscesses, where it could modify anti-bacterial lipids and prolong bacterial survival. Avoidance of Host Defenses S. aureus expresses a number of factors that have the potential to interfere with host defense mechanisms. This includes both structural and soluble elements of the bacterium. Capsular Polysaccharide The majority of clinical isolates of S aureus express a surface polysaccharide of either serotype 5 or 8. This has been called a microcapsule because it can be visualized only by electron microscopy unlike the true capsules of some bacteria which are readily visualized by light microscopy. S. aureus strains isolated from infections express high levels of the polysaccharide but rapidly lose the ability when cultured in the laboratory. The function of the capsule in virulence is not entirely clear. Although it does impede phagocytosis in the absence of complement, it also impedes colonization of damaged heart valves, perhaps by masking adhesins. Protein A Protein A is a surface protein of S. aureus which binds IgG molecules by their Fc region. In serum, the bacteria will bind IgG molecules in the wrong orientation on their surface which disrupts opsonization and phagocytosis. Mutants of S. aureus lacking protein A are more efficiently phagocytosed in vitro, and mutants in infection models have diminished virulence.

Leukocidin S. aureus can express a toxin that specifically acts on polymorphonuclear leukocytes. Phagocytosis is an important defense against staphylococcal infection so leukocidin should be a virulence factor. Exotoxins S. aureus can express several different types of protein toxins which are probably responsible for symptoms during infections Some will lyse erythrocytes, causing hemolysis, but it is unlikely that hemolysis is a relevant determinant of virulence in vivo. Leukocidin causes membrane damage to leukocytes, but is not hemolytic. Systemic release of aplha-toxin causes septic shock, while enterotoxins and TSST-1 are superantigens that may cause toxic shock. Staphylococcal enterotoxins cause emesis (vomiting) when ingested and the bacterium is a leading cause of food poisoning. The exfoliatin toxin causes the scalded skin syndrome in neonates, which results in widespread blistering and loss of the epidermis. There are two antigenically distinct forms of the toxin, ETA and ETB. The toxins have esterase and protease activity and apparently target a protein which is involved in maintaining the integrity of the epidermis.

Superantigens: enterotoxins and toxic shock syndrome toxin and their diseases STAPHYLOCOCCAL FOOD POISONING S. aureus secretes two types of toxin with superantigen activity, enterotoxins, of which there are six antigenic types (named SE-A, B, C, D, E and G), and toxic shock syndrome toxin (TSST-1). Enterotoxins cause diarrhea and vomiting when ingested and are responsible for staphylococcal food poisoning. Staphylococcal food poisoning is a gastrointestinal illness. It is caused by eating foods contaminated with toxins produced by Staphylococcus aureus . The most common way for food to be contaminated with Staphylococcus is through contact with food workers who carry the bacteria or through contaminated milk and cheeses. Staphylococcus is salt tolerant and can grow in salty foods like ham. As the bacteria multiplies in food, it produces toxins that can cause illness. Staphylococcal toxins are resistant to heat and cannot be destroyed by cooking. Foods at highest risk of contamination with Staphylococcus aureus and subsequent toxin production are those that are made by hand and require no cooking. Some examples of foods that have caused staphylococcal food poisoning are sliced meat, puddings, some pastries and sandwiches. Signs and symptoms Staphylococcal toxins are fast acting, sometimes causing illness in as little as 30 minutes. Symptoms usually develop within one to six hours after eating contaminated food. Patients typically experience several of the following: nausea, vomiting, stomach cramps, and diarrhea. The illness is usually mild and most patients recover after one to three days. In a small minority of patients the illness may be more severe.

Lab diagnosis of S. aureus food poisoning Toxin-producing Staphylococcus aureus can be identified in stool or vomit, and toxin can be detected in food items. Diagnosis of staphylococcal food poisoning in an individual is generally based only on the signs and symptoms of the patient. Testing for the toxin-producing bacteria or the toxin is not usually done in individual patients. Testing is usually reserved for outbreaks involving several persons. Treatment Supportive Antibiotics are not useful in treating this illness. The toxin is not affected by antibiotics. Patients with this illness are not contagious. Toxins are not transmitted from one person to another.

TOXIC SHOCK SYNDROME TSST-1 is expressed systemically and is the cause of toxic shock syndrome (TSS). When expressed systemically, enterotoxins can also cause toxic shock syndrome. In fact, enterotoxins B and C cause 50% of non-menstrual cases of TSS. TSST-1 is weakly related to enterotoxins, but it does not have emetic activity. TSST-1 is responsible for 75% of TSS, including all menstrual cases. TSS can occur as a sequel to any staphylococcal infection if an enterotoxin or TSST-1 is released systemically and the host lacks appropriate neutralizing antibodies. Superantigens stimulate T cells non-specifically without normal antigenic recognition . Up to one in five T cells may be activated, whereas only 1 in 10,000 are stimulated during a usual antigen presentation. Cytokines are released in large amounts, causing the symptoms of TSS. Superantigens bind directly to class II major histocompatibility complexes of antigen-presenting cells outside the conventional antigen-binding grove. This complex recognizes only the Vb element of the T cell receptor. Thus any T cell with the appropriate Vb element can be stimulated, whereas normally, antigen specificity is also required in binding. SIGNS AND SYPMTOMS The Centers for Disease Control and Prevention (CDC) criteria for the diagnosis of staphylococcal TSS are as follows: • • • Fever, hypotension, and rash (as defined above) Involvement of 3 or more organ systems Absence of serologic evidence of Rocky Mountain spotted fever, leptospirosis, measles, hepatitis B, antinuclear antibody, positive Venereal Disease Research Laboratory (VDRL) test results, and antibodies at Monospot testing

Prodromal period of 2-3 days followed by: Pain at site of infection (most common symptom of streptococcal TSS) Fever and/or chills Nausea and/or vomiting Profuse watery diarrhea with abdominal pain Lightheadedness and/or syncope Myalgias and/or arthralgias Pharyngitis and/or headache Confusion (more common with staphylococcal TSS than with streptococcal TSS) At physical examination, findings may include the following: Fever higher than 102°F Hypotension - Systolic BP less than 90 mm Hg or orthostatic decrease in systolic BP of 15 mm Hg Skin findings o o Diffuse rash, occasionally patchy and erythematous, with desquamation occurring approximately 1-2 weeks later Rash initially appearing on trunk, spreading to arms and legs, and involving palms and soles

Signs of multiorgan involvement o o o o o o Physical findings associated with ventricular arrhythmias, renal failure, or hepatic failure Disseminated intravascular coagulation (DIC) Acute respiratory distress syndrome Necrotizing fasciitis and/or myositis Altered consciousness (CNS involvement) Mucosal inflammation (eg, vaginitis, conjunctivitis, pharyngitis)

Lab Studies • • The CBC may reveal leukocytosis (77% of cases) with , mild anemia with abnormal cells on smears, and/or thrombocytopenia. Electrolyte levels may indicate hyponatremia, hypokalemia, hypocalcemia out of proportion to hypoalbuminemia, hypophosphatemia, and

hyperbilirubinemia (76% of cases), an elevated aspartate aminotransferase (SGOT) level (75% of cases), and an elevated alanine aminotransferase (SGPT) level (50% of cases). • Coagulation studies may reveal an elevated activated partial thromboplastin time (aPTT) (46% of cases) and fibrin split products. Fibrinogen levels and prothrombin times (PTs) usually are normal. • Azotemia and/or acute tubular necrosis may be present. • Urinalysis may reveal sterile pyuria, myoglobinuria, and red cell casts. • Creatine Exfoliatin toxin (ET)kinase levels may indicate rhabdomyolysis (63% of cases). • ABG findings may indicate metabolic acidosis secondary to hypotension and/or hypoxia. The exfoliatin toxin, associated with scalded skin syndrome, causes separation within the epidermis, between theCulturelayers and the superficial dead layers. The separation is through of stratum granulosum living all potentially infected sites (including blood). More than 50% the • of the epidermis. This is probably why TSS have a positive little scarring although the risks of fluid loss and patients with streptococcal healing occurs with blood culture result. Recent secondary infections are suggested that early and definitive diagnosis can be made by to specifically studies have increased. Staphylococcal exfoliative toxin B has been shown cleave desmoglein 1, athe expansion of found in desmosomes in the epidermis. receptors observing cadherin that is TSS-1 reactive V beta2-positive T-cell in peripheral blood mononuclear cells. Staphylococcal scalded skin syndrome (SSS) or Ritter Disease Imaging Studies Scalded skin syndrome is a skin infection characterized by damage to the skin, with marked shedding (exfoliation). It usually affects infants and evidence under therespiratory distress • A chest radiograph may show children of acute age of 5. syndrome or pulmonary edema. Scalded•skin syndrome isof the infected site may show soft-tissue swelling. children. Radiographs found most commonly in infants and very young • An echocardiogram may show wall-motion abnormality suggestive of toxic SIGNSAND SYMPTOMS cardiomyopathy. • A CT scan should be obtained if the diagnosis is in question. Findings fever should be normal in TSS. redness of the skin (erythema) which spreads to cover most of the body TREATMENT Fluid resuscitation Crystalloids may be administered. As much as 10-20 L/d often is necessary. Some authors suggest that colloids may decrease the risk of pulmonary edema. Oxygen therapy skin slips off with gentle pressure leaving wet red areas (Nikolsky sign) Administer supplemental oxygen therapy to maximize tissue oxygenation and to correct hypoxia and/or acidosis. large areas of skin peel or fall away (exfoliation or desquamation) painful skin Assisted ventilation may be required if acute respiratory distress syndrome develops. LAB EXAMS Hyperbaric oxygen therapy has been used in necrotizing soft-tissue infections, but the • Complete blood count benefit of this intervention has not been proven. • cultures of the skin and throat (often yield staphylococci) • skin biopsy (done only performed, where diagnosis high-grade arrhythmias. Cardiac monitoring should bein rare cases with treatment ofis in question, such as when the skin condition may be due to a drug reaction known as toxic epidermal necrolysis or TEN) •Foley catheter should be placed to monitor urine output (assess adequacy of Serum electrolytes A resuscitation). TREATMENT Tampons and packing materials, if present, should be removed. • Patients need fluid rehydration, topical wound care similar to the care for thermal burns, and parenteral menstruation-related TSS, irrigation of vagina with isotonic sodium For patients withantibiotics to cover S aureus. • Consideration must be given for the sharply increasing rates chloride solution or povidone-iodine solution has been advocated. of community-acquired S aureus infection (CA-MRSA).

• • • • •

Fluid rehydration is initiated with Lactated Ringer solution at 20 cc/kg initial bolus. Repeat the initial bolus as clinically indicated followed by maintenance therapy with consideration for fluid losses from exfoliation of skin being similar to a burn patient. Topical wound care should begin with saline, followed by topical antibiotic ointment. Cultures from the exfoliated sites as well as nose, throat, and other potential sites of the original focus of infection should be performed. A chest radiograph should be considered to rule out pneumonia as the original focus of infection. Steroids are not indicated at this time.

Healing begins in about 10 days following treatment. The prognosis is usually excellent. A full recovery is expected. Possible Complications • • • • severe bloodstream infection (septicemia) fluid regulation problems causing dehydration or electrolyte imbalance poor temperature control (in young infants) spread to deeper skin infection (cellulitis)

The disorder may not be preventable. Prompt treatment of any staphylococcus infection may be helpful.

S. epidermidis accounts for all 75% of clinical isolates, and this relates to its abundance in the skin of normal persons. Other species include: S, haemolyticus S. hominis S. capitis S. saprophyticus The emergence of these species as pathogens refelects the increased use of implants such as CSF shunts, IV lines, cardiac valves, pacemakers, artificial joints, urinary catheters and the increasing number of severely debilitated patients in the hospitals. They are morphologically similar to S.aureus, however they form white colonies, and are coagulase negative.

Diseases caused: Prosthetic valve endocarditis Meningitis Peritonitis UTI in pregnant women(S. saprophyticus) Treatment is with Vancomycin, if not resistant. S. saprophyticus responds to trimethoprim or to quinolones.

Staphylococcus epidermidis In contrast to S. aureus, little is known about mechanisms of pathogenesis of S. epidermidis infections. Adherence is obviously a crucial step in the initiation of foreign body infections. Bacteria-plastic interactions are probably important in colonization of catheters, and a polysaccharide adhesion (PS/A) has been identified. In addition, when host proteins deposit on the implanted device S. epidermidis will bind to fibronectin. A characteristic of many pathogenic strains of S. epidermidis is the production of a slime resulting in biofilm formation. The slime is predominantly a secreted teichoic acid, normally found in the cell wall of the staphylococci. This ability to form a biofilm on the surface of a prosthetic device is probably a significant determinant of virulence for these bacteria.

Resistance of Staphylococci to Antimicrobial Drugs Hospital strains of S. aureus are usually resistant to a variety of different antibiotics. A few strains are resistant to all clinically useful antibiotics except vancomycin, and vancomycin-resistant strains are increasingly-reported. The term MRSA refers to Methicillin resistant Staphylococcus aureus. Methicillin resistance is widespread and most methicillin-resistant strains are also multiply resistant. A plasmid associated with vancomycin resistance has been detected in Enterococcusfaecalis which can be transferred to S. aureus in the laboratory, and it is speculated that this transfer may occur naturally (e.g. in the gastrointestinal tract). In addition, S. aureus exhibits resistance to antiseptics and disinfectants, such as quaternary ammonium compounds, which may aid its survival in the hospital environment. S aureus responded to the introduction of antibiotics by the usual bacterial means to develop drug resistance: (1) mutation in chromosomal genes followed by selection of resistant strains and (2) acquisition of resistance genes as extrachromosomal plasmids, transducing particles, transposons, or other types of DNA inserts. Host Defense against Staphylococcal Infections

Phagocytosis is the major mechanism for combatting staphylococcal infection. Antibodies are produced which neutralize toxins and promote opsonization. However, the bacterial capsule and protein A may interfere with phagocytosis. Biofilm growth on implants is also impervious to phagocytosis. Staphylococci may be difficult to kill after phagocytic engulfment because they produce catalase which neutralize singlet oxygen and superoxide which are primary phagocytic killing mechanisms within the phagolysosome. Treatment Hospital acquired infection is often caused by antibiotic resistant strains (MRSA) and can only be treated with vancomycin or an alternative. Until recently, infections acquired outside hospitals have been treated with penicillinase-resistant ß-lactams. However, many of the community acquired (CA) Staphylococcal infections are now methicillin resistant. Particularly in Georgia, Texas, and California, the prevalence of CA-MRSA is widespread. OTHER DISEASE CAUSED BY STAPHYLOCOCCI boils and pimples (folliculitis) pneumonia septicemia osteomyelitis surgical wound infections

MRSA AND VRSA Methicillin-resistant Staphylococcus aureus (MRSA) is a type of bacteria that is resistant to certain antibiotics. These antibiotics include methicillin and other more common antibiotics such as oxacillin, penicillin and amoxicillin. Staph infections, including MRSA, occur most frequently among persons in hospitals and healthcare facilities (such as nursing homes and dialysis centers) who have weakened immune systems. MRSA infections that occur in otherwise healthy people who have not been recently (within the past year) hospitalized or had a medical procedure (such as dialysis, surgery, catheters) are known as communityassociated (CA)-MRSA infections. These infections are usually skin infections, such as abscesses, boils, and other pus-filled lesions Methicillin-resistant Staphylococcus aureus (MRSA) has become a prevalent nosocomial pathogen in the United States. In hospitals, the most important reservoirs of MRSA are infected or colonized patients. Although hospital personnel can serve as reservoirs for MRSA and may harbor the organism for many months, they have been more commonly identified as a link for transmission between colonized or infected patients.

The main mode of transmission of MRSA is via hands (especially health care workers' hands) which may become contaminated by contact with a) colonized or infected patients, b) colonized or infected body sites of the personnel themselves, or c) devices, items, or environmental surfaces contaminated with body fluids containing MRSA. Approximately 10% of S. aureus isolates in the United States are susceptible to penicillin. However, many S. aureus strains, while resistant to penicillin, remain susceptible to penicillinase-stable penicillins, such as oxacillin and methicillin. Strains that are oxacillin and methicillin resistant, historically termed methicillinresistant S. aureus (MRSA), are resistant to all ß-lactam agents, including cephalosporins and carbapenems. Hospital-associated MRSA isolates often are multiply resistant to other commonly used antimicrobial agents, including erythromycin, clindamycin, and tetracycline, while community-associated MRSA isolates are often resistant only to ß-lactam agents and erythromycin. Since 1996, MRSA strains with decreased susceptibility to vancomycin (minimum inhibitory concentration [MIC], 8-16 μg/ml) and strains fully resistant to vancomycin (MIC ≥ 32 μg/ml) have been reported . FEATURES OF MRSA

1. Pathogenicity.
MRSA have many virulence factors that enable them to cause disease in normal hosts. For example, MRSA are frequent causes of healthcare-associated bloodstream and catheter-related infections. MRSA are also an emerging cause of community-associated infections, especially skin and soft tissue infections and necrotizing pneumonia. Limited treatment options. Vancomycin and two newer antimicrobial agents, linezolid and daptomycin, are among the drugs that are used for treatment of severe healthcare-associated MRSA infections. Although some strains remain susceptible to trimethoprim/sulfamethoxazole, gentamicin, or rifampin, these drugs are not typically used as first-line agents. Because of the rapid emergence resistance to rifampin, this drug should never be used as a single agent to treat MRSA infections.


3. MRSA are transmissible.
An MRSA outbreak can occur when one strain is transmitted to other patients or close contacts of the infected persons in the community. Often this occurs when a patient or health-care worker is colonized with an MRSA strain (i.e., carries the organism but shows no clinical signs or symptoms of infection) and, through contact, spreads the strain to another person. Handwashing and screening patients for MRSA should be performed to decrease transmission and reduce the number of patients infected with MRSA. Lab EXAMS The cefoxitin disk screen test, the latex agglutination test for PBP2a, or a plate containing 6 μg/ml of oxacillin in Mueller-Hinton agar supplemented with NaCl (4% w/v; 0.68 mol/L) as alternative methods of testing for MRSA. Accurate detection of oxacillin/methicillin resistance can be difficult due to the presence of two subpopulations (one susceptible and the other resistant) that may coexist within a culture of staphylococci .

All cells in a culture may carry the genetic information for resistance, but only a small number may express the resistance in vitro. This phenomenon is termed heteroresistance and occurs in staphylococci resistant to penicillinase-stable penicillins, such as oxacillin. Cells expressing heteroresistance grow more slowly than the oxacillin-susceptible population and may be missed at temperatures above 35°C. This is why it is recommended incubating isolates being tested against oxacillin, methicillin, or nafcillin at 33-35° C (maximum of 35°C) for a full 24 hours before reading . Additional tests to detect oxacillin/methicillin resistance Nucleic acid amplification tests, such as the polymerase chain reaction (PCR), can be used to detect the mecA gene, which mediates oxacillin resistance in staphylococcus. mecA gene involved in the mechanism of resistance Staphylococcal resistance to oxacillin/methicillin occurs when an isolate carries an altered penicillinbinding protein, PBP2a, which is encoded by the mecA gene. The new penicillin-binding protein binds beta-lactams with lower avidity, which results in resistance to this class of antimicrobial agents. Methicillin is no longer commercially available in the United States. Oxacillin maintains its activity during storage better than methicillin and is more likely to detect heteroresistant strains. However, cefoxitin is an even better inducer of the mecA gene and disk diffusion tests using cefoxitin give clearer endpoints and are easier to read than tests with oxacillin. If oxacillin is tested, why are the isolates called “MRSA” instead of “ORSA”? When resistance was first described in 1961, methicillin was used to test and treat infections caused by S. aureus. However, oxacillin, which is in the same class of drugs as methicillin, was chosen as the agent of choice for testing staphylococci in the early 1990s. . The acronym MRSA is still used by many to describe these isolates because of its historic role.

VISA and VRSA VISA and VRSA are specific types of antimicrobial-resistant staph bacteria. While most staph bacteria are susceptible to the antimicrobial agent vancomycin some have developed resistance. VISA and VRSA cannot be successfully treated with vancomycin because these organisms are no longer susceptibile to vancomycin Staph bacteria are classified as VISA or VRSA based on laboratory tests. Laboratories perform tests to determine if staph bacteria are resistant to antimicrobial agents that might be used for treatment of infections. For vancomycin and other antimicrobial agents, laboratories determine how much of the agent it requires to inhibit the growth of the organism in a test tube. The result of the test is usually expressed as a minimum inhibitory concentration (MIC) or the minimum amount of antimicrobial agent that inhibits bacterial growth in the test tube. Therefore, staph bacteria are classified as VISA if the MIC for vancomycin is 4-8µg/ml, and classified as VRSA if the vancomycin MIC is >16µg/ml.

Persons that developed VISA and VRSA infections had several underlying health conditions (such as diabetes and kidney disease), previous infections with methicillin-resistant Staphylococcus aureus (MRSA), tubes going into their bodies (such as intravenous [IV] catheters), recent hospitalizations, and recent exposure to vancomycin and other antimicrobial agents. TREATMENT There are limited treatment options for VISA/VRSA infections. Some possible options include rifampin, gentamicin, imipenem, chloramphenicol, trimethoprim-sulfamethoxazole, and tetracycline. PREVENTION Use of appropriate infection control practices (such as wearing gloves before and after contact with infectious body substances and adherence to hand hygiene) by healthcare personnel can reduce the spread of VISA and VRSA. VISA and VRSA are types of antibiotic-resistant staph bacteria. Therefore, as with all staph bacteria, spread occurs among people having close physical contact with infected patients or contaminated material like bandages. Therefore, persons having close physical contact with infected patients while they are outside of the healthcare setting should: (1) keep their hands clean by washing thoroughly with soap and water, (2) avoid contact with other people’s wounds or material contaminated from wounds

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