stafilokokus aureus infection

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Introduction

Background

Bacteria of the genus Staphylococcus are gram-positive cocci that are microscopically observed

as individual organisms, in pairs, and in irregular, grapelike clusters. The term Staphylococcus is

derived from the Greek term staphyle, meaning "a bunch of grapes." Staphylococci are nonmotile,

nonspore-forming, and catalase-positive bacteria. The cell wall contains peptidoglycan and

teichoic acid. The organisms are resistant to temperatures as high as 50C, to high salt

concentrations, and to drying. Colonies are usually large (6-8 mm in diameter), smooth, and

translucent. The colonies of most strains are pigmented, ranging from cream-yellow to orange.

The ability to clot plasma continues to be the most widely used and generally accepted criterion for

the identification ofStaphylococcus aureus. One such factor, bound coagulase, also known as

clumping factor, reacts with fibrinogen to cause organisms to aggregate. Another factor,

extracellular staphylocoagulase, reacts with prothrombin to form staphylothrombin, which can

convert fibrinogen to fibrin. Approximately 97% of human S aureus isolates possess both of these

forms of coagulase.

S aureus is ubiquitous and may be a part of human flora found in the axillae, the inguinal and

perineal areas, and the anterior nares. In 2001, von Eiff et al described 3 patterns of carriage:

those who always carry a strain, those who carry the organism intermittently with changing strains,

and a minority of people who never carry S aureus.1Persistent carriage is more common in

children than in adults.

Wenzel and Perl (1995) found that, among healthy adults, carrier rates of 11-32% were detected in

the general population, and a prevalence of 25% was detected in hospital personnel.2Using

pulsed-field gel electrophoresis (PFGE) for molecular typing, von Eiff et al (2001) found that, in

most patients with S aureus bacteremia, the isolate from the patient's blood is identical to thatfound in the anterior nares.1Curiously,community-associated methicillin-resistant S aureus (CA-

MRSA) is rarely found in the anterior nares; rather, it colonizes the skin, particularly in the perineal

area. It may also colonize the pharynx, gut, and vagina.

Pathophysiology

The organism may cause disease through tissue invasion and toxin production. The toxins

liberated by the organism may have effects at sites distant from the focus of infection or

colonization.

Tissue invasion

The postulated sequence of events that leads to infection is initiated with carriage of the organism.

The organism is then disseminated via hand carriage to body sites where infection may occur

(either through overt breaks in dermal surfaces, such as vascular catheterization or operative

incisions, or through less evident breakdown in barrier function, such as eczema or shaving-

associated microtrauma).

The hallmark of staphylococcal infection is the abscess, which consists of a fibrin wall surrounded

by inflamed tissues enclosing a central core of pus containing organisms and leukocytes. From

this focus of infection, the organisms may be disseminated hematogenously, even from the

smallest abscess. The ability to elaborate proteolytic enzymes facilitates the process. This may

result in pneumonia, bone and joint infection, and infection of the heart valves. Inimmunocompromised hosts (eg, patients with cancer who are neutropenic and have a central
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venous line), 20-30% develop serious complications or fatal sepsis following catheter-related S

aureus bacteremia.

Persistent deep-seated infections have now been linked to small-colony variants of the organism.

This population is more resistant to antibiotics and grows slowly. These organisms have been

described in patients with cystic fibrosis and may contribute to the persistence ofS aureus in thesepatients.

Toxin-mediated disease

The organism may also elaborate toxins that can cause specific diseases or syndromes.

Enterotoxin-producing strains ofS aureus cause one of the most common food-borne illnesses.

The most common presentation is acute onset of vomiting and watery diarrhea 2-6 hours after

ingestion. The symptoms are usually self-limited. The cause is the proliferation of toxin-producing

organisms in uncooked or partially cooked food that an individual carrying the staphylococci has

contaminated.

A rare but well-described disorder in neonates and young children is staphylococcal scalded skin

syndrome (Ritter disease). The organism produces an exfoliative toxin produced by strains

belonging to phage group II. Initial features include fever, erythema, and blisters, which eventually

rupture and leave a red base. Gentle shearing forces on intact skin cause the upper epidermis to

slip at a plane of cleavage in the skin, which is known as the Nikolsky sign. How the exfoliative

toxins produce epidermal splitting has not been fully elucidated.

The most feared manifestation ofS aureus toxin production istoxic shock syndrome (TSS).

Although first described in children, it was most frequently associated with women using tampons

during menstruation. Since the early 1990s, at least half of the cases have not been associated

with menstruation. The syndrome is associated with strains that produce the exotoxin TSST-1, but

strains that produce enterotoxins B and C may cause 50% of cases of nonmenstrual TSS. These

toxins are superantigens, T-cell mitogens that bind directly to invariant regions of major

histocompatibility complex class II molecules, causing an expansion of clonal T cells, followed by a

massive release of cytokines. This cytokine release mediates the TSS; the resultant

pathophysiology mimics that of endotoxic shock.

In a recent worldwide trend, the proportion of infections caused by CA-MRSA has increased.

Initially noted in tertiary care centers, these infections are now increasingly common in the

community. Resistance to methicillin confers resistance to all penicillinase-resistant penicillins and

cephalosporins. This high level of resistance requires the mecgene that encodes penicillin-binding

protein 2a. This protein has decreased binding affinity for most penicillins and cephalosporins.

Methicillin resistance has a wide variety of phenotypic expression. Heterogeneous resistance,recognized in the first clinical isolates described, is the typical phenotype. In this case, all cells

carry the genetic markers of resistance but only a small fraction of them express the phenotype.

Less frequent is homogenous resistance, with a single population of cells that are inhibited only

through high concentrations of antibiotics.

Methicillin-resistant S aureus (MRSA) was initially described in hospitalized populations. University

affiliation and greater number of beds were institutional risk factors. In pediatric centers, number of

beds, region, and metropolitan population correlated with increased risk. Since 1996, more

patients with CA-MRSA have been described. The strains isolated from these patients are different

from typical nosocomial organisms in their susceptibility patterns and in their PFGE characteristics.

A clonal population, designated USA-300, has become the predominant circulating organism inmost communities. Many of these strains produce the Panton-Valentine leukocidin, which is
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associated with a tendency to produce abscesses, invasiveness, thrombogenesis, and morbidity

and mortality.

More recently, S aureus that is intermediately resistant to vancomycin has been reported in 2

hospitalized patients, which suggests that full resistance to vancomycin may eventually emerge.3

Although the possibility of interspecies transfer of vancomycin-resistance genes from vancomycin-resistant Enterococcus was originally considered as the cause of this phenomenon, none of the

species isolated have carried vanA, vanB, vanC1, vanC2, orvanC3 genes. Of note, the clinical

isolates with intermediate resistance to vancomycin were from patients who had undergone

prolonged vancomycin therapy for MRSA. Morphologically, these isolates were found to have

increased extracellular material associated with the cell wall that may have been selected for

during a prolonged antibiotic course.

Frequency

United States

Numbers of both community-associated and hospital-acquired infections have increased in the

past 20 years. From 1990-1992, data from the National Nosocomial Infections Surveillance

System for the Centers for Disease Control and Prevention (CDC)revealed that S aureus was the

most common cause of nosocomial pneumonia and operative wound infections and the second

most common cause of nosocomial bloodstream infections.

Frequency of antibiotic resistance: In a disturbing trend, antibiotic resistance among these isolates

has increased because of antibiotic pressure. Currently, less than 5% of clinical isolates remain

sensitive to penicillin. Resistance to penicillin was reported as early as 1942 and is mediated by

beta-lactamase, a serine protease that hydrolyzes the lactam ring. In the 1980s, MRSA emerged

as a prominent hospital-based infection; consequently, the use of vancomycin increased. A CDC

survey revealed that the proportion of methicillin-resistant isolates with sensitivity only to

vancomycin increased from 22.8% in 1987 to 56.2% in 1997.4

Mortality/Morbidity

Morbidity and mortality from S aureus infection widely varies depending on the clinical entity.

Although mortality is low in children with scalded skin syndrome, most fatalities are associated with

delay in diagnosis.

Sex

The male-to-female ratio of skeletal infections is 2:1, mostly because boys are more likely to

experience traumatic events.

Clinical

History

Skin and soft tissue (impetigo): Typically, this starts as a small area of erythema that

progresses into bullae (filled with cloudy fluid) that rupture and heal with the formation of a

honey-colored crust. Although group A Streptococcus was once considered the primary

agent, Staphylococcus aureus has become the major pathogen since the 1980s. S

aureus exclusively causes bullous impetigo, which is observed less frequently in the

United States. This form of disease seems to arise from healthy-appearing skin. The

bullae rupture, leaving a denuded area with a varnish-like coating.

Scalded skin syndrome (Ritter disease): An exfoliative toxin (seeToxin-mediated disease)

causes this relatively rare syndrome, which takes the form of superficial fragile blisters
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that burst, leaving a tender base. The patient is often febrile and, occasionally, has

mucopurulent eye discharge. This diagnosis should be made carefully, because scalded

skin syndrome may be mistaken for erythema multiforme or toxic epidermal necrolysis,

which can be treated with corticosteroids. Misdiagnosis delays treatment and allows

exfoliation to progress, and corticosteroid therapy may potentiate bacterial superinfection.

Although the mortality rate is low in children with this entity, most fatalities are associatedwith delay in diagnosis.

Folliculitis, furuncle, and carbuncle: These are increasingly severe staphylococcal skin

infections. Folliculitis is a tender pustule that involves the hair follicle. A furuncle involves

both the skin and the subcutaneous tissues in areas with hair follicles, such as the neck,

axillae, and buttocks. They are actually small abscesses characterized by exuding

purulent material from a single opening. A carbuncle is an aggregate of connected

furuncles and has several pustular openings. Skin infections may be self-limited, but they

can also disseminate hematogenously and cause life-threatening septicemia.

Bone infections (osteomyelitis)

Children often present with sudden onset of fever and bony tenderness or a limp.

The pain may be throbbing and severe; however, presentation in neonates canbe subtle. Infants may appear well except for failure to move an extremity or pain

on movement. Redness or swelling indicates that infection has spread into the

subperiosteal space. Rupture of a focus of osteomyelitis into joint space can

result in septic arthritis. This is often observed in neonates.

Children with vertebral osteomyelitis present with back pain, and those younger

than 3 years present with refusal to walk or with a limp. Occasionally, children

with vertebral osteomyelitis present with incontinence. Children with discitis tend

to present with less fever and often appear less ill than children with vertebral

osteomyelitis.

Septic arthritis: Typical findings include decreased range of motion, warmth, erythema,

and tenderness of the joint with constitutional symptoms and fever. Infants (in whom thehip is the most commonly involved joint) are an exception, as these signs may be absent.

The child typically lies with the involved joint abducted and externally rotated. Because

pain fibers are located within the joint capsule, movements that compress the head of the

femur into the acetabulum (eg, changing a diaper) cause pain. A portal of infection is

almost never found, and the infection is nearly always unilateral. Patients with infection of

the sacroiliac joint present with tenderness elicited during digital rectal examination and

with pain during flexion, abduction, and external rotation of the hip.

Endocarditis: The initial presentation of patients with S aureus endocarditis is fever and

malaise. However, the disease has a more rapid onset than that caused by less virulent

pathogens. Notably, on initial presentation, the usual physical stigmata are absent.

Endocarditis may also involve healthy valves. For more detail, please see Endocarditis,Bacterial.

Toxic shock syndrome (TSS)

Staphylococcal TSS is a potentially life-threatening systemic bacterial

intoxication. Case definition includes fever, diffuse macular erythema, and

hypotension, with involvement of 3 or more of the following organ systems:

GI - Emesis or diarrhea appears at the time of illness. Diarrhea is

secretory and profuse, and is found in almost all patients with TSS but is

uncommon in patients in septic shock.

Muscular - Severe myalgia or elevated creatine kinase (CK) levels are

observed. Myalgia may be one of the earliest manifestations of the

disease.
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Renal - Elevation of BUN or creatinine levels or more than 5 WBCs per

high-power field in the absence of a urinary tract infection is observed.

Hepatic levels of bilirubin, serum glutamic-oxaloacetic transaminase

(aspartate aminotransferase), and serum glutamic-pyruvic transaminase

(alanine aminotransferase) are twice the upper limit of the reference

range. Hematologic The platelet count is less than 100,000/ L.

Nervous system Features include disorientation and alteration in

consciousness with the absence of focal neurologic signs when fever

and hypotension are absent.

A probable case of TSS involves 5 of the above 6 findings.

A confirmed case of TSS involves all 6 findings.

The most striking aspect of the disease is the rapidity with which it can progress

in a previously healthy individual of any age. This is especially true in postsurgical

patients, particularly following nasal surgery, because this is an area commonly

colonized with S aureus. Late-onset dermatologic findings include a red and

pruritic maculopapular rash, desquamation of the fingers and toes, and telogeneffluvium (see Toxic Shock Syndrome).

Pneumonia: Cases of rapidly progressive and fatal staphylococcal pneumonia still occur,

although they were much more common in the 1950s and early 1960s, when S aureus

phage type 80/81 caused frequent disease in infants. Staphylococcal pneumonia most

commonly occurs in infants, young children, and patients who are debilitated. This is a

rapidly progressive disease. Patients with primary staphylococcal pneumonia present with

a short prodrome of fever followed by rapid onset of respiratory distress, which may

include tachypnea, retractions, and cyanosis. Patients may also have prominent GI tract

symptoms. Staphylococcal pneumonia may also develop after influenza infection, which

seems to occur preferentially among young adults (in whom mortality reaches 50%).

Typically, the child seems to recover from a febrile illness only to once again develop anincreasing fever and the symptoms mentioned above.

Thrombophlebitis: Usually occurring in a hospitalized patient, thrombophlebitis is

characterized by fever, pain, and, occasionally, erythema at the insertion site of an

intravenous catheter. Occasionally, pus is expressed. Severe suppurative

thrombophlebitis may occur in burn patients, with fewer than half of diagnoses made while

the patients are alive.

Deep tissue abscess and infection: Muscles (myositis and pyomyositis) and organs can

become infected, including the parotid gland, eyes, liver, spleen, and kidneys. These

infections typically cause fever with or without localizing pain.

Physical

Skin and soft tissue (impetigo): The infection initially appears as a small area of erythema.

Bullae (ie, blister-like lesions filled with cloudy fluid) appear as the disease progresses. As

bullae heal, a honey-colored crust develops.

Scalded skin syndrome (Ritter disease): Examination reveals superficial, fragile blisters

that burst, leaving a tender base. Skin sloughs easily when touched, a condition termed

the Nikolsky sign. Fever is often present, and mucopurulent eye discharge may be

observed. As discussed above, the infection is often mistaken for erythema multiforme or

toxic epidermal necrolysis. Misdiagnosis must be avoided.

Folliculitis, furuncle, and carbuncle: Folliculitis is the appearance of a tender pustule

involving a hair follicle. A furuncle is an apparent small abscess that exudes purulent
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material from a single opening. A carbuncle is an aggregate of furuncles with several

openings.

Bone infections (osteomyelitis): Fever, bony tenderness, or a limp indicate bone

infections. Infants may appear well except for failure to move an extremity or pain on

movement. Children with vertebral osteomyelitis present with back pain, and those

younger than 3 years present with refusal to walk or with a limp. Occasionally, childrenwith vertebral osteomyelitis have incontinence as a presenting symptom. Children with

discitis tend to present with less fever and often appear less ill than children with vertebral

osteomyelitis.

Septic arthritis: Examination reveals warmth, erythema, and tenderness of the joint.

Constitutional symptoms and fever are frequently observed. These findings may be

absent in an infant. Children with infection of the sacroiliac joint present with tenderness

elicited during digital rectal examination.

Endocarditis: The clinical syndrome widely varies and may involve multiple organs. S

aureus infection usually results in an acute course but may involve subacute disease.

Most patients present with high fever. Chills and sweats and a new or worsened murmur

may occur. Peripheral emboli such as Osler nodes, subungual hemorrhages, Janewaylesions, and Roth spots may be present. Other embolic phenomena may occur.

TSS: TSS involves a fever of 38.9C or higher. Hypotension occurs, either with blood

pressure below the fifth percentile for age or with an orthostatic (lying to sitting) drop in

diastolic blood pressure greater than or equal to 15 mm Hg. A diffuse, erythroderma-like

rash is present. Conjunctival or vaginal hyperemia may be present. Patients may have

altered sensorium, even when normotensive, or may be delirious, disoriented, or agitated

without focal signs. Reddened lips and tongue may be observed. Later, on recovery,

desquamation of hands and feet may occur; occasionally, alopecia occurs later.

Pneumonia: Fever is present. Findings of respiratory distress include tachypnea,

cyanosis, grunting, and retractions. Vomiting and abdominal distension occur. Clinical

deterioration is rapid. Thrombophlebitis: Patients usually have a fever and, occasionally, have cutaneous

involvement such as erythema, induration, or tenderness. Occasionally, pus is expressed

at the insertion site of the catheter. The exit site often does not show signs of infection.

Establishing infection of an intravascular device as the cause of fever in a hospitalized

patient is a diagnosis of exclusion.

Deep tissue abscess and infection: Localizing tenderness may be present, as may signs

of inflammation.

Causes

Skin and soft tissue (impetigo): Often occurring in young children, impetigo is spreadwithin families and through close physical contact. Impetigo is more prevalent in warm,

humid climates because of more opportunities for insect bites and cutaneous trauma.

Impetigo may also be a complication ofvaricella. Diagnosis is usually made based on the

characteristic appearance of the lesions. Bullous impetigo may also occur in endemic and

epidemic patterns. Nursery outbreaks have been described, and some cases in infants

have progressed to scalded skin syndrome or Ritter disease (described in History).

Folliculitis, furuncle, and carbuncle: Recurrent staphylococcal skin infections develop in

certain patients, such as those with impaired neutrophil function (eg, those with chronic

granulomatous disease), patients with atopy and chronic eczema, and those with impaired

circulation and diabetes mellitus. However, most patients with recurrent furunculosis are

colonized with CA-MRSA but are otherwise healthy. Thus, an evaluation of the immunesystem in these individuals is seldom useful.
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Bone and joint infections (osteomyelitis): Osteomyelitis typically occurs in children prior to

the age of epiphyseal closure. Osteomyelitis typically originates in the metaphysis of long

bones in the region of most rapid growth. Osteomyelitis usually involves (in order of

frequency) the lower end of the femur, the upper end of the tibia and humerus, and the

radius. Most bone and joint infections result from hematogenous spread, but significant

blunt trauma is a preceding event in approximately one third of cases. In addition,penetrating wounds, compound fractures, and orthopedic appliances may introduce

microbial infection directly into bone. Notably, the male-to-female ratio of skeletal

infections is 2:1, mostly because boys are more likely to experience traumatic events.

Septic arthritis: Staphylococci are frequent etiologic agents of septic arthritis and, since

the era of successful vaccination forHaemophilus influenzae, are now more predominant

in younger age groups . Bacteria can enter the joint space through hematogenous spread,

direct inoculation, or contiguous spread of infection. Because the synovial membrane has

a high effective blood flow, a large number of bacteria may be delivered to the joint during

a period of bacteremia. Inoculation can occur when a joint is punctured with a

contaminated object, and many clinical studies reveal that the knee is more likely to be

punctured. In the postantibiotic era, contiguous spread has been rare, with the exceptionof neonatal osteomyelitis.

Endocarditis: Fortunately, S aureus endocarditis is rare in pediatric patients. It often

involves adolescent intravenous drug users who do not have antecedent valvular disease.

These patients usually present with right-sided disease with evidence of pulmonary

disease, such as pulmonary abscesses or shifting infiltrates. In children with preexisting

heart disease, endocarditis is often temporally related to cardiac surgery or

catheterization. Children with prosthetic valves are particularly vulnerable because of the

organisms propensity to adhere to foreign materials. In addition, patients with indwelling

vascular access devices are at risk, because infections from the skin can seed the

catheter.

TSSo Infection with toxin-producing S aureus in the absence of protective antibody is

an antecedent. Younger patients may be at increased risk because they lack the

protective antibodies to the enterotoxins and other exotoxins responsible for

producing this clinical syndrome. However, other factors may be involved;

Jacobsen et al (1989) demonstrated in a small study that not all patients without

antibody develop true TSS when infected with a toxin-producing strain of the

organism.5

o Approximately 25% of all S aureus strains are toxigenic, and, at any time, roughly

4-10% of healthy individuals are colonized with these strains. In the 1980s, the

disease was associated with the use of highly absorbent tampons in women

during menstruation. Currently, many cases observed are nonmenstrual (eg,localized infections, surgery, infected varicella lesions, insect bites), and these

now account for one third of all cases. These patients carry a higher mortality rate

than those with menstrual TSS.

Pneumonia: The primary form occurs without an extrapulmonary focus, presumably

through direct inoculation to the lungs, and the secondary form results from

hematogenous seeding of the lungs during endocarditis or bacteremia. Predisposing

factors include infancy, chronic illness, and viral respiratory disease such as influenza.

Patients with head injury and trauma who have nasopharyngeal carriage ofS aureus are

at increased risk ofS aureus pneumonia.

Thrombophlebitis: The causes are associated with infusion, including infected intravenous

catheters and needles. The common point of entry for infection related to intravasculardevices is the insertion site along the outside of the device.


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Deep tissue abscess and infection: These typically result from hematogenous seeding,

although myositis or pyomyositis can result from contiguous spread of infection and

endophthalmitis can follow trauma (injury or iatrogenic), for example.

The differential diagnoses of staphylococcal infections include the following:

Impetigo - None

Bullous impetigo

o Pemphigus

o Pemphigoid

o Burn

o Stevens-Johnson syndrome

o Dermatitis herpetiformis

Scalded skin syndrome (Ritter disease)

o Nonaccidental injury

o Scalding

o Abrasion traumao Sunburn

o Erythema multiforme

o Toxic epidermal necrolysis

Bone and joint infections

o Bone infarction (in patients with sickle cell disease)

o Toxic synovitis

o Leukemia

Septic arthritis

o Trauma

o Deep cellulitis

o Henoch-Schnlein purpurao Slipped capital femoral epiphysis

o Legg-Calve-Perthes disease

o Leukemia

o Toxic synovitis

o Metabolic diseases affecting joints (Ochronosis)

Endocarditis - Bacteremia

TSS

o Staphylococcal scalded skin syndrome

o Meningococcemia

o Rubeola

o Adenoviral infectionso Dengue fever

o Severe allergic drug reactions

Differential Diagnoses

Bacteremia Leptospirosis

Burns, Chemical Osteomyelitis

Endocarditis, Bacterial Parvovirus B19 Infection

Enteroviral Infections Rheumatic Fever

Impetigo Rocky Mountain Spotted Fever

Irritable Bowel Syndrome Serum Sickness
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Juvenile Rheumatoid Arthritis Streptococcal Infection, Group A

Kawasaki Disease Toxic Shock Syndrome

Workup

Laboratory Studies

An erythromycin-induction test, or D-test, should always be performed with staphylococcal

sensitivities to reveal inducible clindamycin resistance among community-associated methicillin-

resistant Staphylococcus aureus (CA-MRSA).

Folliculitis, furuncle, and carbuncle: Make the diagnosis based on clinical appearance and,

occasionally, on results of aspiration or incision and culture of purulent material from the

lesion.

Osteomyelitis: Blood culture results are positive in only 30-50% of pediatric patients.

Therefore, cultures of bone aspirate are useful in obtaining the organism and planning for

long-term therapy. In addition, C-reactive protein levels and erythrocyte sedimentation

rate are generally elevated in acute disease. Septic arthritis: Examination of joint fluid, when obtained, is the primary means of

diagnosis; the fluid should be sent to the laboratory for Gram stain and culture. In addition,

the number and type of leukocytes should be determined. Median cell count in bacterial

arthritis is 60.5 X 109 cells with a neutrophil predominance of greater than 75%. Often,

synovial fluid glucose levels are low. Yield of culture may be improved by directly

inoculating synovial fluid into blood culture bottles.

Endocarditis: The most important diagnostic procedure is the blood culture. Blood should

be injected into hypertonic media if the patient has been exposed to antibiotics. Obtaining

3-5 sets of large-volume blood cultures within the first 24 hours is recommended.

Pneumonia: Blood culture findings forS aureus are more likely to be positive in secondary

disease than in primary disease (90% vs 20%). Because blood culture results are oftennegative, an adequate respiratory tract specimen should be obtained prior to initiating

therapy; specimens may include endotracheal sampling, pleural fluid, or lung tap. Sputum

is not considered adequate because the organism is frequently present in the upper

respiratory secretions of healthy individuals.

Thrombophlebitis: Although treatment is occasionally controversial, obtaining a blood

culture through the intravenous line and a peripheral blood culture is usually

recommended.

Imaging Studies

Osteomyelitis: On plain film radiographs, destructive bone changes are usually observed2 weeks after infection. This is because a 30-50% reduction in bone calcium content is

required before an osteolytic lesion is visible. The clinical diagnosis of osteomyelitis is

most often supported by findings on bone scan with technetium Tc99mlabeled

diphosphonate. Increased tracer uptake reflects the inflammatory process in the bone

lesion. However, this modality is not as useful in neonates or after trauma or surgery. MRI

is the best imaging modality for defining purulent collections and for planning surgery.

Septic arthritis: Plain radiographs show capsular swelling. They are most useful in

revealing other causes of hip pain, such as Legg-Calve-Perthes disease. Radiographs

should be obtained with the child in the frog leg position as well as with the legs extended

and slightly internally rotated. Displacement of gluteal fat lines because of the swelling of

the joint capsule is an early radiologic sign of septic arthritis. If a bone scan is performed,
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increased uptake on either side of the joint is visible. As pyogenic sacroiliitis is difficult to

diagnose, the radiologic method of choice is MRI or CT scanning.

Endocarditis: Echocardiography is a valuable adjunct. Two-dimensional echocardiography

is more sensitive than the M-mode technique, and it has been used to reveal vegetations

in patients with negative culture results. However, because of variable sensitivity, a

negative finding does not exclude endocarditis. Transesophageal echocardiography ismore sensitive than transthoracic echocardiography in the detection of intracardiac

vegetations.

Pneumonia: No radiologic features are highly specific, but the chest radiograph may

provide information, especially in demonstrating its progression. Radiographs of patients

with primary staphylococcal pneumonia may reveal unilateral consolidation, while patients

with secondary staphylococcal pneumonia are more likely to demonstrate bilateral

infiltrates on radiographs. Early in the disease course, the chest radiograph may reveal

minimal infiltrates, but, within hours, they rapidly progress. Pleural effusion,

pneumatoceles, and pneumothorax are also common.

Histologic Findings

For scalded skin syndrome (Ritter disease), histologic examination of a skin biopsy

specimen is the most helpful, because demonstration of midepidermal separation at the

zona granulosa is diagnostic of this entity and excludes erythema multiforme in which

dermoepidermal cleavage occurs.

Treatment

Medical Care

Because community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) causes

more than one half of all staphylococcal infections in most communities, empiric therapy with

penicillins or cephalosporins is inadequate. Some experts recommend combination therapy with a

penicillinase-resistant penicillin or cephalosporin (in case the organism is methicillin-sensitive S

aureus [MSSA]) and clindamycin or a quinolone. Others suggest use of clindamycin, trimethoprim-

sulfamethoxazole (TMP-SMX), rifampin, or a quinolone. Finally, because of concerns about

induction of resistance, some recommend using TMP-SMX and rifampin in combination, rather

than singly.

Impetigo, folliculitis, furuncle, carbuncle: Impetigo and other minor skin infections (ie,

superficial or localized infections) may be treated with a topical agent such as mupirocin

or retapamulin. However, most CA-MRSA strains are or readily become resistant to

mupirocin. More extensive or serious skin disease and bullous impetigo are treated with

oral antistaphylococcal agents, as noted above.

Scalded skin syndrome (Ritter disease): As with any S aureus toxinmediated disease,

treatment should aim to eradicate the focus of infection and end toxin production.

Administer large doses of intravenous antistaphylococcal agents, such as oxacillin (150

mg/kg/d), or a first-generation cephalosporin, such as cefazolin (100 mg/kg/d). In vitro,

clindamycin has been shown to inhibit the synthesis of TSST-1 and is extremely effective

in combination with one of the agents mentioned above. Children with denuded skin

should be touched as little as possible. Topical antimicrobial agents have little use,

because skin damage is self-limited once systemic antibiotics are administered.

Osteomyelitis: Empirically, initiating a semisynthetic penicillin (eg, oxacillin [150 mg/kg/d])

and clindamycin (30-40 mg/kg/d) is a good choice for most cases of community-acquired

osteomyelitis. In patients with allergy to penicillin, a first-generation cephalosporin and


11/22

clindamycin (30-40 mg/kg/d) are an excellent alternative. Use vancomycin or linezolid

when the other drugs mentioned are absolutely not tolerated or when resistance or the

clinical course dictates. The duration of therapy is a controversial topic in the literature, but

the consensus among multiple authors is that the minimum effective treatment time is 4-6

weeks. A switch to oral therapy is acceptable if the child is able to take oral antibiotics, is

afebrile, and if he or she has demonstrated a good clinical response to parenteralantibiotics.

Septic arthritis: As in osteomyelitis, initiate an appropriate antistaphylococcal drug (eg,

oxacillin, which is penicillinase resistant; clindamycin; cefazolin) parenterally. These

antibiotics readily reach joint fluid, and the concentration in the joint fluid is 30% of the

serum value. Therapy usually continues for at least 4 weeks. Duration of parenteral

therapy is often debated. Some authors have demonstrated efficacy with 1 week of

parenteral therapy followed with 3 weeks of oral therapy. Consider a switch to oral therapy

based on the considerations mentioned above. Joint fluid that reaccumulates should be

removed, and a sample should be cultured to assess the efficacy of therapy and to make

the patient more comfortable.

Endocarditis Duration of therapy for endocarditis, which is a life-threatening infection, is at

least 4 weeks.

The combination of a beta-lactam and an aminoglycoside is advocated, because

it increases bacterial killing in vitro and in animal models of endocarditis. In

patients with MRSA, combinations of vancomycin with aminoglycosides should

be used.

Rifampin, because of its lipid solubility, is another potent agent when used in

combination with nafcillin and gentamicin or vancomycin and gentamicin,

especially in patients with prosthetic valve endocarditis. Rifampin should never be

used alone because resistance can develop.

The response to therapy is usually slow, and patients may continue to havebacteremia, fever, and leukocytosis for at least a week after therapy is initiated.

Some authors recommend obtaining blood cultures after the end of therapy.

Treatment with antibiotics is specific to the etiologic agent and its characteristics.

For more information, seeEndocarditis, Bacterial.

Surgical Care

Osteomyelitis: Surgery is usually indicated to drain purulent material from the

subperiosteal space or if infected foreign material is present.

Septic arthritis: In an infant, septic arthritis of the hip and shoulder is a surgical

emergency; these joints should be drained as soon as possible to prevent bonydestruction. In addition, if a large amount of fibrin, tissue debris, or loculation is present,

preventing adequate drainage with needle aspiration, the joint should be surgically

drained.

Endocarditis: If endocarditis occurs in the presence of an intracardiac foreign body, it may

require removal.

Toxic shock syndrome (TSS): All potential foci of infection should be explored and

surgically drained.

Thrombophlebitis: Remove the infected intravenous line in patients who are

immunocompromised or severely ill or when infection is impossible to eradicate medically.

Medication
http://emedicine.medscape.com/article/896540-overviewhttp://emedicine.medscape.com/article/896540-overviewhttp://emedicine.medscape.com/article/896540-overview


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The major antibiotics active against the staphylococcal organism are presented here.

Antistaphylococcal antibiotics

Serious staphylococcal infections require treatment with parenteral penicillinase-resistant penicillin

(eg, nafcillin, oxacillin) or first-generation or second-generation cephalosporins (eg, cephalexin,

cefuroxime) plus clindamycin. Vancomycin is reserved for staphylococcal strains that are resistant

to penicillinase-resistant penicillins (ie, MRSA) and clindamycin, or for when the patient has

potentially life-threatening infection or intoxication. Mupirocin or retapamulin may be used for

superficial localized infections (ie, impetigo).

Dicloxacillin

Binds to one or more penicillin-binding proteins, which, in turn, inhibits synthesis of bacterial cell

walls. For treatment of infections caused by penicillinase-producing staphylococci. May be used to

initiate therapy when staphylococcal infection is suspected.

Dosing

Interactions

Contraindications

Precautions

Adult

125-500 mg PO q6h

Pediatric

40 kilograms: Administer as in adults

Dosing

Interactions

Contraindications

Precautions

Dosing

Interactions

Contraindications

Precautions

Dosing

Interactions Contraindications

Precautions

Oxacillin

Bactericidal antibiotic that inhibits cell wall synthesis. Used in the treatment of infections caused by

penicillinase-producing staphylococci.

Dosing

Interactions

Contraindications

Precautions

Adult


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0.25-1 g IV q6h

Pediatric

150 mg/kg/d IV divided qid

Dosing Interactions

Contraindications

Precautions

Dosing

Interactions

Contraindications

Precautions

Dosing

Interactions

Contraindications

Precautions

Nafcillin

Initial therapy for suspected penicillin Gresistant staphylococcal infections. Use parenteral

therapy initially in severe infections. Change to PO therapy as condition warrants.

Dosing

Interactions

Contraindications

Precautions

Adult

0.5-1 g IV/IM q4-6h

Pediatric

Neonates:

7 days and >2000 grams: 100 mg/kg/d IV divided q6h

Children:

100-200 mg/kg/d IV divided qid; not to exceed 12 g/d

Reduce dose by 50% in renal or hepatic impairment

Dosing

Interactions

Contraindications

Precautions

Dosing

Interactions

Contraindications

Precautions

Dosing

Interactions

Contraindications

Precautions


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Cephalexin (Keflex)

First-generation cephalosporin that arrests bacterial growth by inhibiting bacterial cell wall

synthesis. Bactericidal activity against rapidly growing organisms. Primary activity against skin

flora.

Dosing

Interactions

Contraindications

Precautions

Adult

250-500 mg PO q6h; not to exceed 4 g/d

Pediatric

25-100 mg/kg/d PO divided q6h; not to exceed 4 g/d

Dosing

Interactions

Contraindications

Precautions

Dosing

Interactions

Contraindications

Precautions

Dosing

Interactions

Contraindications Precautions

Cefuroxime (Ceftin oral, Kefurox injection)

Broad-spectrum cephalosporin most closely resembling the second-generation cephalosporins.

Cefuroxime is stable against beta-lactamaseproducing organisms.

Dosing

Interactions

Contraindications

Precautions

Adult

250-500 mg PO bid; alternatively, 1 g IV q8h

Pediatric

Serious infections: 150 mg/kg/d IV divided q8h

Impetigo:

250-mg tab PO q12h

30 mg/kg/d PO susp divided bid; not to exceed 1 g/d

Dosing

Interactions

Contraindications

Precautions


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Dosing

Interactions

Contraindications

Precautions

Dosing


Precautions

Cefazolin

First-generation semisynthetic cephalosporin that arrests bacterial cell wall synthesis, inhibiting

bacterial growth. Primarily active against skin flora, including S aureus. Typically used alone for

skin and skin structure coverage.

Dosing

Interactions

Contraindications

Precautions

Adult

0.5-2 g IV q6-8h; not to exceed 12 g/d

Pediatric

50-100 mg/kg/d IV divided q8h; not to exceed 6 g/d

Dosing

Interactions


Dosing

Interactions

Contraindications

Precautions

Dosing

Interactions

Contraindications

Precautions

Amoxicillin and clavulanate (Augmentin)

Drug combination treats bacteria resistant to beta-lactam antibiotics. For children >3 mo, base

dosage regimen on amoxicillin content. Because of different amoxicillin/clavulanic acid ratios in

250-mg tab (ie, 250/125) versus 250-mg chewable tab (ie, 250/62.5), do not use 250-mg tab until

child is >40 kg.

Dosing

Interactions

Contraindications

Precautions

Adult

250-500 mg PO q8h; not to exceed 2 g/d


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Pediatric

3 months and 40 kilograms: Administer as in adults

Dosing

Interactions

Contraindications

Precautions

Dosing

Interactions

Contraindications

Precautions

Dosing

Interactions


Vancomycin (Lyphocin, Vancocin, Vancoled)

Potent antibiotic directed against gram-positive organisms and active against Enterococcus

species. Useful in the treatment of septicemia and skin structure infections. Indicated in patients

who are unable to receive or who have not responded to penicillins and cephalosporins or for

infections with resistant staphylococci. Use CrCl to adjust dose in patients diagnosed with renal

impairment.

Dosing

Interactions

Contraindications

Precautions

Adult

0.5 g IV q6h or 1 g IV q24h

Pediatric

Neonates:

2000 grams: 30 mg/kg/d IV divided q12h

>7 days and >2000 grams: 45 mg/kg/d IV divided q8h


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Contraindications

Precautions

Dosing

Interactions

Contraindications

Precautions

Clindamycin (Cleocin)

Lincosamide for treatment of serious skin and soft tissue staphylococcal infections. Also effective

against aerobic and anaerobic streptococci (except enterococci). Inhibits bacterial growth, possibly

by blocking dissociation of peptidyl tRNA from ribosomes, arresting RNA-dependent protein

synthesis.

Dosing

Interactions

Contraindications

Precautions

Adult

150-450 mg PO q6h

1.2-1.8 g/d IV divided bid/qid; may increase dose, not to exceed 4.8 g/d

Pediatric

10-30 mg/kg/d PO divided q6-8h

25-40 mg/kg/d IV divided q6-8h; not to exceed 4.8 g/d

Dosing


Precautions

Dosing

Interactions

Contraindications

Precautions

Dosing

Interactions

Contraindications

Precautions

Daptomycin (Cubicin)

First of new antibiotic class termed cyclic lipopeptides. Binds to bacterial membranes and causes

rapid membrane potential depolarization, thereby inhibiting protein, DNA, and RNA synthesis, and,

ultimately, causing cell death. Indicated to treat complicated skin and skin structure infections

caused by S aureus (including methicillin-resistant strains), S pyogenes, S agalactiae, S

dysgalactiae, and E faecalis (vancomycin-susceptible strains only). Indicated for skin and skin

structure infections.

Dosing

Interactions

Contraindications

Precautions


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Adult

CrCl >30 mL/min: 4 mg/kg IV q24h infused over 30 min

CrCl


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Rifampin (Rifadin injection/oral, Rimactane oral)

Inhibits RNA synthesis in bacteria by binding to beta subunit of DNA-dependent RNA polymerase,

which, in turn, blocks RNA transcription.

Dosing

Interactions

Contraindications

Precautions

Adult

S aureus: 600 mg/d PO/IV with other antibiotics

Pediatric

S aureus: 15 mg/kg/d PO/IV divided q12h with other antibiotics

Dosing

Interactions

Contraindications

Precautions

Dosing

Interactions

Contraindications

Precautions

Dosing

Interactions

Contraindications

Precautions

Sulfamethoxazole and trimethoprim (Bactrim, Septra)

Inhibits bacterial growth by inhibiting synthesis of dihydrofolic acid.

Dosing

Interactions

Contraindications

Precautions

Adult

160/800 mg PO q12h

Pediatric

2 years: 6-12 mg of trimethoprim/kg/d in 2 doses

Dosing

Interactions

Contraindications

Precautions

Dosing

Interactions

Contraindications

Precautions

Dosing


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Interactions

Contraindications

Precautions

Mupirocin (Bactroban)

For elimination ofS aureus. Inhibits bacterial growth by inhibiting RNA and protein synthesis.

Dosing

Interactions

Contraindications

Precautions

Adult

Apply small amount topically to affected area 2-5 times per d for 5-14 d

Apply intranasal ointment 2-4 times per d and topical cream or ointment 3-5 times per d

Pediatric

Apply as in adults

Dosing

Interactions

Contraindications

Precautions

Dosing

Interactions

Contraindications

Precautions

Dosing Interactions

Contraindications

Precautions

Retapamulin (Altabax)

Topical antibiotic available as a 1% ointment. First of new antibiotic class called pleuromutilins.

Inhibits protein synthesis by binding to 50S subunit on ribosome. Indicated for impetigo caused by

Staphylococcus aureus orStreptococcus pyogenes.

Dosing

Interactions

Contraindications

Precautions

Adult

Apply topically to affected site bid for 5 d

Pediatric

9 months: Apply as in adults

Dosing

Interactions

Contraindications


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Precautions

Dosing

Interactions

Contraindications

Precautions

Dosing Interactions

Contraindications

Precautions

Blood products

These agents stimulate an immune response and offer transient protection while the host immune

system develops antibodies.

Immune globulin, intravenous (Carimune, Gamunex, Polygam S/D)

Actions include neutralizing circulating myelin antibodies through anti-idiotypic antibodies, down-regulating proinflammatory cytokines (including interferon gamma), blocking Fc receptors on

macrophages, suppressing inducer T and B cells, and augmenting suppressor T cells. Also blocks

the complement cascade and promotes remyelination. May increase CSF IgG (10%).

IVIG has been shown to have high concentration of TSST-1 and the staphylococcal enterotoxins

implicated in the pathogenesis of TSS. These antibodies may interfere with the binding of toxins

that cause TSS.

Dosing

Interactions

Contraindications

PrecautionsAdult

400 mg/kg IV as single dose infused over several hours

Pediatric

Administer as in adults

Dosing

Interactions

Contraindications

Precautions

Dosing Interactions

Contraindications

Precautions

Dosing

Interactions

Contraindications

Precautions

Follow-up

Further Outpatient Care


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Appropriately monitor renal function, CBC count, and serum hepatic transaminase levels

while patients with Staphylococcus aureus infection are undergoing therapy.

Complications

S aureus infection may result in pneumonia, bone and joint infection, and infection of theheart valves.

In immunocompromised hosts (eg, patients with cancer who are neutropenic and have a

central venous line), 20-30% develop serious complications or fatal sepsis following

catheter-related S aureus bacteremia.

Community-associated methicillin-resistant S aureus (CA-MRSA) infection is more serious

and is associated with thrombogenesis.

Patient Education

For excellent patient education resources, visit eMedicine'sWomen's Health Centerand

Skin, Hair, and Nails Center. Also, see eMedicine's patient education articlesToxic ShockSyndromeandBoils.

Miscellaneous

Medicolegal Pitfalls

Scalded skin syndrome (Ritter disease) is often mistaken for erythema multiforme or toxic

epidermal necrolysis, which may be treated with steroids. Misdiagnosis delays treatment

and allows exfoliation to progress, and steroid therapy may potentiate bacterial

superinfection. Most fatalities are associated with delay in diagnosis.

Another potential medical pitfall is failure to realize that, in an infant, septic arthritis of thehip and shoulder is a surgical emergency. These joints should be drained as soon as

possible to prevent bony destruction. In addition, if a large amount of fibrin, tissue debris,

or loculation is present, which prevents adequate drainage with needle aspiration, the joint

should be surgically drained
http://www.emedicinehealth.com/collections/SU310.asphttp://www.emedicinehealth.com/collections/SU310.asphttp://www.emedicinehealth.com/Collections/SU306.asphttp://www.emedicinehealth.com/Collections/SU306.asphttp://www.emedicinehealth.com/Articles/15911-1.asphttp://www.emedicinehealth.com/Articles/15911-1.asphttp://www.emedicinehealth.com/Articles/15911-1.asphttp://www.emedicinehealth.com/Articles/15911-1.asphttp://www.emedicinehealth.com/articles/20077-1.asphttp://www.emedicinehealth.com/articles/20077-1.asphttp://www.emedicinehealth.com/collections/SU310.asphttp://www.emedicinehealth.com/Collections/SU306.asphttp://www.emedicinehealth.com/Articles/15911-1.asphttp://www.emedicinehealth.com/Articles/15911-1.asphttp://www.emedicinehealth.com/articles/20077-1.asp

stafilokokus aureus infection

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