Staphylococcus Aureus Infection 

Updated: Jan 15, 2019
Author: Elizabeth P Baorto, MD, MPH; Chief Editor: Russell W Steele, MD 

Overview

Practice Essentials

Both community-associated and hospital-acquired infections with Staphylococcus aureus have increased in the past 20 years, and the rise in incidence has been accompanied by a rise in antibiotic-resistant strains—in particular, methicillin-resistant S aureus (MRSA) and, more recently, vancomycin-resistant strains.

An example of radiographic findings in S aureus infections is shown in the image below.

Posteroanterior chest radiograph of a 15-year-old Posteroanterior chest radiograph of a 15-year-old with staphylococcal endocarditis and multiple septic emboli, revealing borderline cardiomegaly, multiple nodular infiltrates, and bilateral pleural effusions.

Signs and symptoms

Types and presentation of S aureus infection include the following:

  • Skin and soft tissue (impetigo): 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

  • Scalded skin syndrome (Ritter disease): A relatively rare, toxin-mediated disorder with superficial fragile blisters that burst, leaving a tender base; often accompanied by fever and occasionally by mucopurulent eye discharge

  • Folliculitis: A tender pustule that involves the hair follicle

  • Furuncle: Small abscesses characterized by exuding purulent material from a single opening; involves both the skin and the subcutaneous tissues in areas with hair follicles

  • Carbuncle: An aggregate of connected furuncles, with several pustular openings

  • Bone infections (osteomyelitis): In children, sudden onset of fever and bony tenderness or a limp; pain may be throbbing and severe; however, presentation in neonates can be subtle

  • Septic arthritis: Decreased range of motion, warmth, erythema, and tenderness of the joint with constitutional symptoms and fever; however, these signs may be absent in infants (in whom the hip is the most commonly involved joint)

  • Endocarditis: Initially presents as fever and malaise; peripheral emboli may be present; may involve healthy valves

  • Toxic shock syndrome: Fever, diffuse macular erythema, and hypotension, with involvement of 3 or more organ systems; can be rapidly progressive in previously healthy individuals

  • Pneumonia: Most common in infants, young children, and debilitated patients; a short prodrome of fever followed by rapid onset of respiratory distress; prominent GI symptoms may also occur

  • Thrombophlebitis: Fever, pain, and occasionally erythema at the insertion site of an intravenous catheter; usually affects hospitalized patients

  • Deep tissue abscess and infection: Muscles[1, 2, 3, 4] and organs can become infected, including the parotid gland, eyes, liver, spleen, kidneys, and central nervous system[5] ; deep abscesses also may occur[6] ; fever with or without localizing pain is typical

See Clinical Presentation for more detail.

Diagnosis

Folliculitis, furuncle, and carbuncle

  • Diagnosis based on clinical appearance

  • Aspiration or incision and culture of purulent material from the lesion occasionally diagnostic

Osteomyelitis

  • Cultures of bone aspirate

  • Blood culture results positive in only 30-50% of pediatric patients

  • C-reactive protein levels and erythrocyte sedimentation rate are generally elevated in acute disease

  • Bone scan with increased technetium-99m–labeled diphosphonate uptake supports the clinical diagnosis; 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

  • On plain film radiographs, destructive bone changes are usually observed 2 weeks after infection

Septic arthritis

  • Gram stain and culture of joint fluid is the primary means of diagnosis

  • Direct inoculation of synovial fluid into culture bottles may improve culture yield

  • Median white blood cell count in joint fluid is 60.5 × 109, with neutrophil predominance >75%

  • Synovial fluid glucose levels are often low

  • Plain radiographs show capsular swelling

  • MRI or CT scanning is the imaging method of choice for pyogenic sacroiliitis

Endocarditis

  • Blood culture is the most important diagnostic procedure

  • Inject the blood sample into hypertonic media if the patient has been exposed to antibiotics

  • Obtain 3-5 sets of large-volume blood cultures within the first 24 hours

  • Echocardiography is a valuable adjunct

Pneumonia

  • Blood cultures are more likely to be positive in secondary than primary disease (90% vs 20%)

  • An adequate respiratory tract specimen should be obtained prior to initiating therapy; specimens may include endotracheal sampling, pleural fluid, or lung tap

  • Sputum specimens are inadequate because upper respiratory tract colonization is common

  • No radiologic features are highly specific

  • Typical radiographic features are unilateral consolidation in primary staphylococcal pneumonia and bilateral infiltrates in secondary cases

  • Early in the disease course, the chest radiograph may reveal minimal infiltrates, but within hours, infiltrates progress rapidly

  • Pleural effusion, pneumatoceles, and pneumothorax are also common

  • In oncology patients, S aureus may cause pulmonary nodules[7]

Thrombophlebitis

  • Obtain a blood culture through the intravenous line and a peripheral blood culture

See Workup for more detail.

Management

Antibiotic regimens include the following:

  • Empiric therapy with penicillins or cephalosporins may be inadequate because of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA)[8]

  • Combination therapy with a penicillinase-resistant penicillin or cephalosporin (in case the organism is methicillin-sensitive S aureus [MSSA])[9] and clindamycin or a quinolone

  • Clindamycin, trimethoprim-sulfamethoxazole (TMP-SMX), rifampin, doxycycline, or a quinolone

  • TMP-SMX and rifampin in combination, rather than singly

  • Clindamycin (rather than TMP-SMX) may become the preferred outpatient antibiotic therapy in regions with a relatively low incidence of clindamycin resistance[10]

  • The Infectious Diseases Society of America has published treatment guidelines for MRSA infection[11]

Treatment of specific infections

Impetigo, folliculitis, furuncle, carbuncle:

  • Superficial or localized skin infections: 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: Oral antistaphylococcal agents[12]

  • Drainage of pus collections is of paramount importance[13]

Scalded skin syndrome (Ritter disease):

  • Eradication of the focal infection to end toxin production

  • Large doses of intravenous antistaphylococcal agents such as oxacillin or a first-generation cephalosporin such as cefazolin, combined with clindamycin

Osteomyelitis:

  • Empiric semisynthetic penicillin and clindamycin

  • In patients with allergy to penicillin, a first-generation cephalosporin and clindamycin

  • Vancomycin or linezolid when the other drugs mentioned are absolutely not tolerated or when resistance or the clinical course dictates

  • Minimum effective treatment time is 4-6 weeks; therapy can be completed orally[14]

  • Surgery to drain purulent material from the subperiosteal space or remove infected foreign material

Septic arthritis:

  • A parenteral antistaphylococcal drug (eg, oxacillin, which is penicillinase resistant; clindamycin; cefazolin)

  • Therapy usually continues for at least 4 weeks; duration of parenteral therapy is debated

  • Joint fluid that reaccumulates should be removed and a sample should be cultured

  • Hip or shoulder infections in infants require prompt drainage to prevent bony destruction

  • Surgical drainage is indicated if needle drainage is inadequate

Endocarditis:

  • The combination of a beta-lactam and an aminoglycoside (eg, nafcillin and gentamicin)

  • In patients with MRSA, combinations of vancomycin with aminoglycosides

  • Rifampin can be added to combination therapy, especially for prosthetic valve endocarditis

  • Duration of therapy is at least 4 weeks

  • Bacteremia, fever, and leukocytosis for at least a week after therapy is initiated

Toxic shock syndrome:

  • Surgical exploration and drainage of all potential foci of infection

Thrombophlebitis:

  • Removal of the infected intravenous line in patients who are immunocompromised or severely ill or when infection cannot be eradicated medically

Bacteremia :

  • Daptomycin, with or without beta-lactams, controls S aureus bacteremia without worsening renal dysfunction. In a cohort of patients with mild or moderate renal insufficiency, more than 80% responded to treatment, with no detrimental effect on their kidneys. Currently, the combination of daptomycin with beta-lactams is recommended only as salvage therapy for refractory MRSA bacteremia.[15]

See Treatment and Medication for more detail.

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, non–spore-forming, and catalase-positive bacteria. The cell wall contains peptidoglycan and teichoic acid. The organisms are resistant to temperatures as high as 50°C, 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 of Staphylococcus 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. 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.[16] Persistent carriage is more common in children than in adults. Nasal carriers may be divided into persistent carriers with high risk of infection and intermittent or noncarriers with low risk of infection.[17]

Wenzel and Perl 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.[18] Using pulsed-field gel electrophoresis (PFGE) for molecular typing, von Eiff et al found that, in most patients with S aureus bacteremia, the isolate from the patient's blood is identical to that found in the anterior nares.[16] Persistent nasal carriage depends on host genetic determinants.[19]

Curiously, community-associated methicillin-resistant S aureus (CA-MRSA) is less often found in the anterior nares than are methicillin-sensitive S aureus (MSSA) and hospital-acquired methicillin-resistant S aureus (HA-MRSA)[20, 21, 22, 23] ; rather, it colonizes the skin, particularly in the perineal area[24] and the rectum.[25] It also colonizes the pharynx,[26] gut,[27] and vagina.[28, 29] Another interesting finding is the protective effect of consumption of hot coffee or tea for nasal carriage of MRSA.[30] In contrast, hormonal contraceptive use is a significant risk factor for nasal carriage of S aureus.[31] [#IntroductionPathophysiology]

Pathophysiology

The organism may cause disease through tissue invasion and toxin production.[32] 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. 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.

Persistent deep-seated infections have now been linked to small-colony variants of the organism.[33] 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 of S aureus in these patients.

Toxin-mediated disease

The organism also elaborates toxins that can cause specific diseases or syndromes and likely participate in the pathogenesis of staphylococcal infection.[34] Enterotoxin-producing strains of S 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.[35]

The most feared manifestation of S aureus toxin production is toxic 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.

CA-MRSA

In a worldwide trend,[36] the proportion of infections caused by CA-MRSA has increased.[37] Initially noted in tertiary care centers, these infections are now increasingly common in the community.[38, 39] Resistance to methicillin confers resistance to all penicillinase-resistant penicillins and cephalosporins. This high level of resistance requires the mec gene 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. Homogenous resistance is less frequent, 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.[40] 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 in most communities.[41, 42] Many of these strains produce the Panton-Valentine leukocidin, which is associated with a tendency to produce abscesses, invasiveness, thrombogenesis, and morbidity and mortality.[43, 44, 45, 46]

A 2012 report corroborates earlier reports which describe an increased prevalence of USA300 strains causing invasive infections.[47] High levels of antibody to the leukocidin are not protective,[48] however, so the role of this and other virulence factors and immunomodulatory bacterial products remains under investigation.[49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65]

A dose-dependent increase in risk of infection due to CA-MRSA with exposure to antibiotics has been reported.[66]

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,[67] although that has not yet occurred in the pediatric population.[68] 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, or vanC3 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. Some virulence genes appear to be linked to decreased susceptibility to vancomycin.[69, 70]

Most recently, the emergence of newly described mec genes and chromosomal cassettes from bovine sources has been described.[71, 72] Thus, the issue of antimicrobial resistance in S aureus continues to evolve.[73]

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.

A recent analysis of laboratory-confirmed MRSA cases in the Active Bacterial Core Surveillance database (which covers 9 geographic regions and represents some 4.4 million children younger than 18 years of age) indicates that community-acquired invasive MRSA infection is increasing among children, particularly among black children and infants younger than 90 days of age. The incidence of community-acquired MRSA increased from 1.1 case per 100,000 children in 2005 to 1.7 cases per 100,000 in 2010. The yearly increase in incidence, adjusted for race and age, was 10.2%. The adjusted incidence of invasive MRSA among black children was 6.7 cases per 100,000 in 2010, compared with 1.6 cases per 100,000 for children of other races.[74, 75]

An analysis of 148 consecutive patients with acute musculoskeletal S aureus infection (111 with MSSA and 37 with MRSA) found that the proportion of pediatric MRSA infections increased from 11.8% to 34.8% between 2001 and 2009, resulting in longer mean hospitalizations (13 vs 8 days).[76] . In addition, children with MRSA infection more often required surgical procedures (38% vs. 15%), experienced more infection-related complications (24% vs 6%), and were more often admitted to the intensive care unit (16% vs 3%).

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.[77] Scattered reports of vancomycin resistance have been noted.[78] Community-onset MRSA infections are increasingly common,[79, 80] although geographic variations persist.[81] Recent data suggest that the incidence of MRSA infection may have peaked.[82, 83]

A study by Sutter et al analyzed 41,745 S aureus isolates from 39,207 pediatric patients and found that like recent trends seen in adults, the proportion of pediatric S aureus infections secondary to methicillin-resistant S aureus appear to be decreasing, as is variability in US geographical resistance rates. The authors also added S aureus susceptibility to clindamycin declined from 90% to 83% over a 10-year period.[84]

A large population based case-control study by Smit et al indicated that diabetes patients are almost three times more likely to contract community-acquired Staphylococcus aureus bacteremia, with the risk escalating with worsening disease.[85, 86]

 

International

The USA300 lineage of community-associated MRSA has become widespread in Latin America.[87] Incidence of staphylococcal skin and complicated infections among children in the United Kingdom has increased over the past decade or so as well[88, 89] , although the incidence of community-associated MRSA blood stream infection in the United Kingdom is less than that seen in the United States.[90] Other strains of community-associated MRSA have been described in Canada,[91, 92, 93, 94] Australia, Asia,[95, 96] and elsewhere in Europe.[97, 98, 99, 100, 101, 102, 103, 104, 105]

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.

 

Presentation

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.[105] 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 (see Toxin-mediated disease) causes this relatively rare syndrome, which takes the form of superficial fragile blisters 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 associated with 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.[106, 107]

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 can be 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 the hip 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 Pediatric Bacterial Endocarditis.

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 organ systems.

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.

Severe myalgia or elevated creatine kinase (CK) levels are observed. Myalgia may be one of the earliest manifestations of the disease.

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.

The platelet count is less than 100,000/μL.

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 telogen effluvium (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 an increasing fever and the symptoms mentioned above. In the CA-MRSA era, staphylococcal pneumonia is becoming more prevalent.[108]

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)[109, 1, 2, 3] and organs can become infected, including the parotid gland, eyes, liver, spleen, kidneys, and central nervous system.[4] Deep abscesses also may occur.[5] 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 material from a single opening. A carbuncle is an aggregate of furuncles with several openings. Blistering distal dactylitis is a superficial infection of the pad of the distal digit.[110]

Bone infections (osteomyelitis)

Fever, bony tenderness, or a limp indicates 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, children with 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, Janeway lesions, and Roth spots may be present. Other embolic phenomena may occur.

TSS

TSS involves a fever of 38.9°C 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 spread within 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 of varicella. 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 immune system in these individuals is seldom useful.

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 for Haemophilus influenzae, are now more predominant in younger age groups. The USA300 genotype is the most common clone in staphylococcal septic arthritis in children.[111] 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 exception of 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 organism’s 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, resulting in catheter-related blood stream infection and its consequences.[112]

TSS

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 demonstrated in a small study that not all patients without antibody develop true TSS when infected with a toxin-producing strain of the organism.[113]

The erythroderma of TSS depends on preexisting T-cell hypersensitivity and the toxin superantigen for amplification.[114]

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 of S aureus are at increased risk of S aureus pneumonia.

Thrombophlebitis

The causes are associated with infusion, including infected intravenous catheters and needles. The common point of entry for infection related to intravascular devices is the insertion site along the outside of the device.

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.

Differential diagnosis

The differential diagnoses of staphylococcal infections include the following:

  • Impetigo - None

  • Bullous impetigo

    • Pemphigus

    • Pemphigoid

    • Burn

    • Stevens-Johnson syndrome

    • Dermatitis herpetiformis

  • Scalded skin syndrome (Ritter disease)

    • Nonaccidental injury

    • Scalding

    • Abrasion trauma

    • Sunburn

    • Erythema multiforme

    • Toxic epidermal necrolysis

  • Bone and joint infections

    • Bone infarction (in patients with sickle cell disease)

    • Toxic synovitis

    • Leukemia

  • Septic arthritis

    • Trauma

    • Deep cellulitis

    • Henoch-Schönlein purpura

    • Slipped capital femoral epiphysis

    • Legg-Calve-Perthes disease

    • Leukemia

    • Toxic synovitis

    • Metabolic diseases affecting joints (Ochronosis)

  • Endocarditis - Bacteremia

  • TSS

    • Staphylococcal scalded skin syndrome

    • Meningococcemia

    • Rubeola

    • Adenoviral infections

    • Dengue fever

    • Severe allergic drug reactions

 

DDx

 

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 for S aureus are more likely to be positive in secondary disease than in primary disease (90% vs 20%). Because blood culture results are often negative, 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

Ultrasonography may have value in identifying drainable skin and soft tissue foci of infection.[115, 116] Examples of radiographic findings in S aureus infections are shown in the images below.

Posteroanterior chest radiograph of a 15-year-old Posteroanterior chest radiograph of a 15-year-old with staphylococcal endocarditis and multiple septic emboli, revealing borderline cardiomegaly, multiple nodular infiltrates, and bilateral pleural effusions.
Lateral chest radiograph of a 15-year-old with sta Lateral chest radiograph of a 15-year-old with staphylococcal endocarditis and multiple septic emboli, revealing borderline cardiomegaly, multiple nodular infiltrates, and bilateral pleural effusions.

Examples of CT scan findings in S aureus infections are shown in the images below.

CT scan of the thorax (mediastinal windows) of a 1 CT scan of the thorax (mediastinal windows) of a 15-year-old with staphylococcal endocarditis and multiple septic emboli, revealing bilateral pleural effusions.
CT scan of the thorax (lung windows) of a 15-year- CT scan of the thorax (lung windows) of a 15-year-old with staphylococcal endocarditis and multiple septic emboli, demonstrating multiple nodular infiltrates (some with cavitation) consistent with septic emboli, volume loss on the right, and pleural effusions.
CT scan of the thorax (lung windows) of a 15-year- CT scan of the thorax (lung windows) of a 15-year-old with staphylococcal endocarditis and multiple septic emboli, revealing multiple nodular infiltrates (some with cavitation) consistent with septic emboli, volume loss on the right, and pleural effusions.
CT scan of the thorax (lung windows) of a 15-year- CT scan of the thorax (lung windows) of a 15-year-old with staphylococcal endocarditis and multiple septic emboli, revealing multiple nodular infiltrates (some with cavitation) consistent with septic emboli, volume loss on the right, and pleural effusions.
CT scan of the thorax (lung windows) of a 15-year- CT scan of the thorax (lung windows) of a 15-year-old with staphylococcal endocarditis and multiple septic emboli, revealing multiple nodular infiltrates (some with cavitation) consistent with septic emboli, volume loss on the right, and pleural effusions.
Follow-up CT scan of the thorax (lung windows) of Follow-up CT scan of the thorax (lung windows) of a 15-year-old with staphylococcal endocarditis and multiple septic emboli, revealing multiple nodular infiltrates (some with cavitation) consistent with septic emboli, volume loss on the right, and pleural effusions.
Follow-up CT scan of the thorax (lung windows) of Follow-up CT scan of the thorax (lung windows) of a 15-year-old with staphylococcal endocarditis and multiple septic emboli, revealing multiple nodular infiltrates (some with cavitation) consistent with septic emboli and evolution of the lesions over time.
Follow-up CT scan of the thorax (lung windows) of Follow-up CT scan of the thorax (lung windows) of a 15-year-old with staphylococcal endocarditis and multiple septic emboli, revealing multiple nodular infiltrates (some with cavitation) consistent with septic emboli and evolution of the lesions over time.

Osteomyelitis

On plain film radiographs, destructive bone changes are usually observed 2 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 Tc99m–labeled 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, 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 is more sensitive than transthoracic echocardiography in the detection of intracardiac vegetations.[117, 118, 119]

A multicenter study concluded that clinical risk stratification combined with a normal transthoracic echocardiogram (TTE) may be adequate to rule out infective endocarditis (IE) in most patients with Staphylococcus aureus bacteremia (SAB).[120, 121]

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. In oncology patients, S aureus may cause pulmonary nodules.[6]

Procedures

Needle aspiration for culture may have utility.[122]

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 may be inadequate.[7] Some experts recommend combination therapy with a penicillinase-resistant penicillin or cephalosporin (in case the organism is methicillin-sensitive S aureus [MSSA])[8] and clindamycin or a quinolone. Others suggest use of clindamycin, trimethoprim-sulfamethoxazole (TMP-SMX), rifampin, doxycycline, or a quinolone. Finally, because of concerns about induction of resistance, some recommend using TMP-SMX and rifampin in combination, rather than singly. As data accumulate, clindamycin may become the preferred outpatient antibiotic therapy (compared with TMP-SMX) in regions with a relatively low incidence of clindamycin resistance.[9] Recently, treatment guidelines have been published.[10]

A randomized, double-blind study by Thwaites et al that included 758 patients with S aureus bacteremia assigned adjunctive rifampicin or a placebo, reported no overall benefit in adjunctive rifampicin over standard antibiotic therapy.[194]

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.[11, 123, 124, 125, 126]

Scalded skin syndrome (Ritter disease)

As with any S aureus toxin–mediated 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 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 parenteral antibiotics.[13]

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.[127]

The combination of a beta-lactam and an aminoglycoside (usually gentamicin) 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. In all cases the aminoglycoside is only added for the first 3 days.

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 have bacteremia, 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, see Endocarditis, Bacterial.

Surgical Care

Skin and soft tissue infections

Drainage of any collections of pus is of paramount importance.[12] For small abscesses in afebrile toddlers and children, drainage alone may suffice, since treatment with efficacious and nonefficacious systemic antibacterial therapy was equivalent if adequate drainage had occurred.[128] Placement of a subcutaneous drain, rather than formal incision and drainage, has proven successful.[129]

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 bony destruction. 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.

Prevention

In a 5-year multicenter study, the introduction of practices to eliminate Staphylococcus aureus significantly reduced the rate of complex S aureus infection at surgical sites, from 0.36% to 0.20%. The study included 38,049 patients who underwent 42,534 operations (cardiac surgery or hip or knee arthroplasty); 28,218 operations were performed before the intervention was implemented and 14,316 were performed during the intervention period.[130, 131]

For the intervention, patients were screened for S aureus in the month before surgery. Those with positive screens were asked to apply intranasal mupirocin and to bathe with chlorhexidine for 5 days before surgery. Patients with methicillin-sensitive S aureus received perioperative prophylactic cefazolin, and those with MRSA received cefazolin and vancomycin. Patients who were negative for S aureus bathed with chlorhexidine the night before and the morning of surgery, and received cefazolin.[130, 131]

A population-based study by Smit et al reported that current statin users had a 27% lower risk of community-acquired Staphylococcus aureus bacteremia and that long-term use was particularly associated with lower risk.[132, 133]

 

Medication

Medication Summary

The major antibiotics active against the staphylococcal organism are presented below.[134, 135]

A human chimeric monoclonal antilipoteichoic acid antibody (pagibaximab) has shown encouraging results for the prevention of staphylococcal infection in premature newborns in a phase 2 randomized, controlled trial.[136]

Antistaphylococcal Antibiotics

Class Summary

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. In these situations, minimum inhibitory concentrations of vancomycin should be monitored.[137, 138, 139, 140, 141, 142, 143]

Data for use of daptomycin in pediatrics are accruing. Linezolid is an alternative to vancomycin,[144, 145] although resistance has begun to appear.[146, 147] Tedizolid, an oxazolidinone, was approved by the FDA in June 2014 for adults. Approval for tedizolid was based on 2 clinical trials that included more than 1300 participants and showed it to be equivalent to linezolid.[148, 149, 150, 151, 152] Telavancin is a lipoglycopeptide derivative of vancomycin for use in complicated skin and skin-structure infections and pneumonia.[134, 153] Newer derivatives include dalbavancin and oritavancin (both FDA approved for adults).[154, 155] Ceftaroline is a broad-spectrum cephalosporin with activity against MRSA that is in clinical trials.[156, 157, 158, 159, 160]

An old antibiotic, fusidic acid, is receiving renewed attention in the United States for treatment of MRSA infections.[161, 162, 163] Topical antibiotics such as mupirocin or retapamulin may be used for superficial localized infections (ie, impetigo), although development of resistance may limit their utility.[164]

Telavancin (Vibativ)

Lipoglycopeptide antibiotic that is a synthetic derivative of vancomycin. Inhibits bacterial cell wall synthesis by interfering with polymerization and cross-linking of peptidoglycan. Unlike vancomycin, telavancin also depolarizes the bacterial cell membrane and disrupts its functional integrity. Indicated for complicated skin and skin structure infections caused by susceptible gram-positive bacteria, including S aureus (both methicillin-resistant and methicillin-susceptible strains), S pyogenes, S agalactiae, S anginosus group, and E faecalis (vancomycin-susceptible isolates only).

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.

Oxacillin (Bactocill)

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

Nafcillin (Nallpen)

Initial therapy for suspected penicillin G–resistant staphylococcal infections. Use parenteral therapy initially in severe infections. Change to PO therapy as condition warrants.

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.

Vancomycin (Vancocin)

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.

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.

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.

Linezolid (Zyvox)

Prevents formation of functional 70S initiation complex, which is essential for bacterial translation process. Bacteriostatic against staphylococci.

The FDA warns against the concurrent use of linezolid with serotonergic psychiatric drugs, unless indicated for life-threatening or urgent conditions. Linezolid may increase serotonin CNS levels as a result of MAO-A inhibition, increasing the risk of serotonin syndrome.

Tedizolid (Sivextro)

Not approved for children. Tedizolid is an oxazolidinone antibiotic indicated for skin and skin structure infections caused by susceptible isolates of Gram-positive bacteria including Staphylococcus aureus (including methicillin-resistant [MRSA] and methicillin-susceptible [MSSA] isolates), Streptococcus pyogenes, S agalactiae, S anginosus Group (including S anginosus, S intermedius, and S constellatus), and Enterococcus faecalis. Its action is mediated by binding to the 50S subunit of the bacterial ribosome resulting in inhibition of protein synthesis.

Dalbavancin (Dalvance)

Not approved for children. Dalbavancin is lipoglycopeptide antibiotic that prevents cross-linking by interfering with cell wall synthesis. It is bactericidal in vitro against S aureus and S pyogenes at concentrations observed in humans at recommended doses. It is indicated for treatment of acute bacterial skin and skin structure infections caused by Gram-positive bacteria including S aureus (including methicillin-susceptible and methicillin-resistant S aureus [MRSA]), S pyogenes, Streptococcus agalactiae, and the Streptococcus anginosus group (including S anginosus, S intermedius, S constellatus).

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.

Sulfamethoxazole and trimethoprim (Bactrim, Septra)

Inhibits bacterial growth by inhibiting synthesis of dihydrofolic acid.

Mupirocin (Bactroban)

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

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 or Streptococcus pyogenes.

Cephalosporins

Class Summary

Newer beta-lactam cephalosporins have improved activity against aerobic and anaerobic gram-positive and aerobic gram-negative bacteria, including MRSA.

Ceftaroline (Teflaro)

Beta-lactam cephalosporin with activity against aerobic and anaerobic gram-positive and aerobic gram-negative bacteria. Demonstrates activity in vivo against resistant methicillin-resistant Staphylococcus aureus (MRSA) strains and in vitro against vancomycin-resistant and linezolid-resistant S aureus.

It is indicated in adults and children aged ≥2 months for treatment of acute bacterial skin and skin structure infections (ABSSSI) caused by susceptible isolates of: Staphylococcus aureus (including methicillin-susceptible and -resistant isolates), Streptococcus pyogenes, Streptococcus agalactiae, Escherichia coli, Klebsiella pneumoniae, and Klebsiella oxytoca. It is also indicated for community-acquired bacterial pneumonia caused by Staphylococcus aureus (methicillin-susceptible isolates only).

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.

Cefuroxime (Ceftin oral, Zinacef injection)

Broad-spectrum cephalosporin most closely resembling the second-generation cephalosporins. Cefuroxime is stable against beta-lactamase–producing organisms.

Cefazolin (Kefzol)

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.

Blood Products

Class Summary

These agents stimulate an immune response and offer transient protection while the host immune system develops antibodies.

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

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.

 

Follow-up

Further Outpatient Care

Appropriately monitor renal function, CBC count, and serum hepatic transaminase levels while patients with Staphylococcus aureus infection are undergoing therapy.

Deterrence/Prevention

A large study in adult inpatients has demonstrated that universal surveillance, appropriate use of contact precautions and hand hygiene, and institutional culture change can decrease infections with MRSA.[165] Another approach likely to be cost-saving and to decrease infection in the intensive care unit is targeted screening and nasal decolonization,[166] although the benefits of nasal decolonization outside this setting remain undefined.[167, 168, 169]

Results of a 2-phase interventional study presented at the 23rd European Congress of Clinical Microbiology and Infectious Diseases in April 2013 suggest that in patients at risk for MRSA, PCR screening followed by isolation reduces the frequency of hospital-acquired infections and is cost-effective.[170]

During phase 1 of the study, 1209 newly admitted patients were screened with a microbiology assay. MRSA-positive patients were placed in contact isolation after the assay result was received (mean, 62.8 ± 15.7 hours). During phase 2, 1200 patients were screened with rapid real-time PCR followed by microbiology assays. Patients were placed in contact isolation if their preliminary PCR test result was positive. All high-risk patients with a preliminary positive PCR result were placed in contact isolation from admission onward.

The numbers of admitted MRSA cases in phase 1 and 2 were about the same (2.1 vs 1.96 per 100 patients). The nosocomial MRSA infection and colonization rates were reduced in phase 2 compared to phase 1 (nosocomial infection rates, 0.10 vs 0.20 per 1000 patient days, P< .05; colonization rates, 0.35 vs. 0.66; P< .01) and remained so or decreased further in 4 consecutive subsequent 6-month periods. Treatment costs were lower in phase 2, despite increased costs for preventive measures, but might vary with differing reimbursement systems.

Prevention of transmission of MRSA among hospitalized children is a significant priority.[171] Increasingly, universal decolonization of ICU patients has been recommended.[172, 173]

Daily washing of ICU patients with chlorhexidine-impregnated cloths reduced positive cultures of MRSA by 37% and reduced bloodstream infection by any pathogen by 44%, according to a study of 74,256 patients in 74 adult ICUs.[172, 174]

In the study, hospitals were randomized to 18 months of either screening for MRSA followed by isolation of positive patients, targeted decolonization of MRSA-positive patients and isolation, or universal decolonization of all ICU patients without screening. Decolonization was achieved via daily cleansing with chlorhexidine-impregnated cloths and 5 days of twice-daily intranasal mupirocin treatments. At baseline, there was no significant difference in the rate of MRSA infections between the 3 groups.[172, 174]

However, patients who underwent universal decolonization showed a significantly larger decline between baseline and intervention periods than those in either of the targeted interventions. Universal decolonization led to a 37% drop in the rate of MRSA infections, while targeted decolonization led to a 25% decline and no significant change was seen in the screening and isolation group. There was no significant difference in outcomes between the targeted decolonization and the screening and isolation groups, while the difference between the universal decolonization and the screening and isolation groups was significant (P = .003). Universal decolonization also significantly reduced ICU-attributed bloodstream infections from any pathogen.[172, 174]

Compared with passive screening, active screening in hospitalized patients for MRSA was shown to result in a higher incidence of discontinuation of MRSA contact precautions. Patients were randomized to observation with either local standard of care (passive screening; n=202) or screening with culture and commercial polymerase chain reaction (PCR) testing (active screening, n=405). In the active screening group, sensitivity, specificity, and positive and negative predictive values of the first PCR were compared to cultures.

The researchers showed that contact precautions were discontinued significantly more often in the active screening group (rate ratio [RR], 4.1; 95% confidence interval [CI], 2.3%-7.1%), including in an intent-to-screen analysis (RR, 2.6; 95% CI, 1.5%-4.7%). Compared with 3 cultures, the first PCR detected MRSA with a sensitivity of 93.9% (95% CI, 85.4%-97.6%), a specificity of 92.0% (95% CI, 85.9%-95.6%), a positive predictive value of 86.1% (95% CI, 75.9%-93.1%), and a negative predictive value of 96.6% (95% CI, 91.6%-99.1%).[175]

Various vaccine candidates are being evaluated.[176, 177, 178, 179, 180, 181, 182]

Complications

S aureus infection may result in pneumonia, bone and joint infection, and infection of the heart 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 or other S aureus infections.[183]

Community-associated methicillin-resistant S aureus (CA-MRSA) infection is more serious and is associated with thrombogenesis. It is becoming endemic in many pediatric and neonatal intensive care units.[184, 185, 186, 187]

Multiple brain abscesses have been reported in premature infants.[188, 189]

S aureus infection complicating influenza infection is associated with significant morbidity and mortality.[190]

Prognosis

Morbidity and mortality associated with staphylococcal bacteremia in children seem to be less significant than observed in bacteremic adults.[191, 192]

Patient Education

Parents of infected children may require additional information/education.[193] For patient education resources, see the Women's Health Center and Skin, Hair, and Nails Center, as well as Toxic Shock Syndrome and Boils.

 

Questions & Answers

Overview

Which strains of Staphylococcus aureus infection are on the rise?

How is Staphylococcus aureus bacteremia treated?

Which conditions are caused by Staphylococcus aureus infection?

How are Staphylococcus aureus folliculitis, furuncle, and carbuncle diagnosed?

How is Staphylococcus aureus osteomyelitis diagnosed?

How is Staphylococcus aureus septic arthritis diagnosed?

How is Staphylococcus aureus endocarditis diagnosed?

How is Staphylococcus aureus pneumonia diagnosed?

How is Staphylococcus aureus thrombophlebitis diagnosed?

Which antibiotics are used in the treatment of Staphylococcus aureus infection?

How are Staphylococcus aureus folliculitis, furuncle, and carbuncle treated?

How is Staphylococcus aureus scalded skin syndrome (Ritter disease) treated?

How is Staphylococcus aureus osteomyelitis treated?

How is Staphylococcus aureus septic arthritis treated?

How is Staphylococcus aureus endocarditis treated?

How is Staphylococcus aureus toxic shock syndrome (TSS) treated?

How is Staphylococcus aureus thrombophlebitis treated?

What is Staphylococcus aureus infection?

How does Staphylococcus aureus infection cause disease?

What is the pathophysiology of Staphylococcus aureus tissue invasion?

What is the pathophysiology of Staphylococcus aureus toxin-mediated disease?

What is the pathophysiology of community associated methicillin-resistant Staphylococcus aureus (CA-MRSA)?

What is the prevalence of Staphylococcus aureus infection in the US?

What is the global prevalence of Staphylococcus aureus infection?

What is the mortality and morbidity associated with Staphylococcus aureus infection?

What are the sexual predilections of Staphylococcus aureus infection?

Presentation

Which clinical history findings are characteristic of Staphylococcus aureus impetigo?

Which clinical history findings are characteristic of Staphylococcus aureus scalded skin syndrome (Ritter disease)?

Which clinical history findings are characteristic of Staphylococcus aureus folliculitis, furuncle, and carbuncle?

Which clinical history findings are characteristic of Staphylococcus aureus osteomyelitis?

Which clinical history findings are characteristic of Staphylococcus aureus septic arthritis?

Which clinical history findings are characteristic of Staphylococcus aureus endocarditis?

Which clinical history findings are characteristic of Staphylococcus aureus toxic shock syndrome (TSS)?

Which clinical history findings are characteristic of Staphylococcus aureus pneumonia?

Which clinical history findings are characteristic of Staphylococcus aureus thrombophlebitis?

Which clinical history findings are characteristic of Staphylococcus aureus infection in the muscles and organs?

Which physical findings are characteristic of Staphylococcus aureus impetigo?

Which physical findings are characteristic of Staphylococcus aureus scalded skin syndrome?

Which physical findings are characteristic of Staphylococcus aureus folliculitis, furuncle, and carbuncle?

Which physical findings are characteristic of Staphylococcus aureus osteomyelitis?

Which physical findings are characteristic of Staphylococcus aureus septic arthritis?

Which physical findings are characteristic of Staphylococcus aureus endocarditis?

Which physical findings are characteristic of Staphylococcus aureus toxic shock syndrome (TSS)?

Which physical findings are characteristic of Staphylococcus aureus pneumonia?

Which physical findings are characteristic of Staphylococcus aureus thrombophlebitis?

Which physical findings are characteristic of Staphylococcus aureus infection in the muscles?

How does Staphylococcus aureus infection cause endocarditis?

How does Staphylococcus aureus infection cause impetigo?

How does Staphylococcus aureus infection cause folliculitis, furuncle and carbuncle?

How does Staphylococcus aureus infection cause osteomyelitis?

How does Staphylococcus aureus infection cause septic arthritis?

How does Staphylococcus aureus infection cause toxic shock syndrome (TSS)?

How does Staphylococcus aureus infection cause pneumonia?

How does Staphylococcus aureus infection cause thrombophlebitis?

How does Staphylococcus aureus infection cause deep tissue abscesses?

Which conditions are included in the differential diagnoses of Staphylococcus aureus infection?

DDX

What are the differential diagnoses for Staphylococcus Aureus Infection?

Workup

Which lab tests are included in the workup of Staphylococcus aureus infection?

What is the role of lab tests in the workup of Staphylococcus aureus folliculitis, furuncle, and carbuncle?

What is the role of lab tests in the workup of Staphylococcus aureus osteomyelitis?

What is the role of lab tests in the workup of Staphylococcus aureus septic arthritis?

What is the role of lab tests in the workup of Staphylococcus aureus endocarditis?

What is the role of lab tests in the workup of Staphylococcus aureus pneumonia?

What is the role of lab tests in the workup of Staphylococcus aureus thrombophlebitis?

What is the role of imaging studies in the workup of Staphylococcus aureus infection?

What is the role of imaging studies in the workup of Staphylococcus aureus osteomyelitis?

What is the role of imaging studies in the workup of Staphylococcus aureus septic arthritis?

What is the role of imaging studies in the workup of Staphylococcus aureus endocarditis?

What is the role of imaging studies in the workup of Staphylococcus aureus pneumonia?

What is the role of needle aspiration in the workup of Staphylococcus aureus infection?

Which histologic findings are characteristic of Staphylococcus aureus infection?

Treatment

How are Staphylococcus aureus infections treated?

How are Staphylococcus aureus impetigo, folliculitis, furuncle, and carbuncle treated?

How is Staphylococcus aureus scalded skin syndrome (Ritter disease) treated?

How is Staphylococcus aureus osteomyelitis treated?

How is Staphylococcus aureus septic arthritis treated?

How is Staphylococcus aureus endocarditis treated?

What is the role of surgery in the treatment of Staphylococcus aureus skin and soft tissue infections?

What is the role of surgery in the treatment of Staphylococcus aureus osteomyelitis?

What is the role of surgery in the treatment of Staphylococcus aureus septic arthritis?

What is the role of surgery in the treatment of Staphylococcus aureus endocarditis?

What is the role of surgery in the treatment of Staphylococcus aureus toxic shock syndrome (TSS)?

What is the role of surgery in the treatment of Staphylococcus aureus thrombophlebitis?

How are Staphylococcus aureus infection at surgical sites prevented?

What is the role of statins in Staphylococcus aureus infection prevention?

Medications

Which medications are used in Staphylococcus aureus infection treatment?

Which medications in the drug class Blood Products are used in the treatment of Staphylococcus Aureus Infection?

Which medications in the drug class Cephalosporins are used in the treatment of Staphylococcus Aureus Infection?

Which medications in the drug class Antistaphylococcal Antibiotics are used in the treatment of Staphylococcus Aureus Infection?

Follow-up

What is included in long-term monitoring of Staphylococcus aureus infections?

How are Staphylococcus aureus infections prevented?

What are the possible complications of Staphylococcus aureus infection?

What is the prognosis of Staphylococcus aureus infection?

What is included in patient education about Staphylococcus aureus infection?