Staphylococcus aureus bacteremia in children

INTRODUCTION — 

Staphylococcus aureus is a leading cause of both community- and healthcare-associated bloodstream infections. S. aureus bacteremia (SAB) is associated with increased morbidity and mortality, even with appropriate therapy.

SAB in children will be reviewed here. Related topics include:

●(See "Staphylococcus aureus in children: Overview of treatment of invasive infections".)

●(See "Methicillin-resistant Staphylococcus aureus (MRSA) in children: Epidemiology and clinical spectrum".)

●(See "Methicillin-resistant Staphylococcus aureus (MRSA) in children: Prevention and control".)

●(See "Methicillin-resistant Staphylococcus aureus (MRSA): Microbiology and laboratory detection".)

EPIDEMIOLOGY

Incidence — Reported incidence rates for pediatric SAB range from 4 to 20 cases per 100,000 children per year [1-5]. The incidence of SAB in children increased throughout the early 2000s to 2010s [3,6-9]. In one study, the increase was attributed largely to methicillin-resistant S. aureus (MRSA) bacteremia [7]. The rate of SAB among hospitalized children ranges from 1.5 to 3.5 per 1000 hospital admissions [7,9-11].

In one study using data from a large administrative database, SAB accounted for 22 percent of all bloodstream infections (excluding neonates) in pediatric patients (excluding neonates) admitted to the participating hospitals in 2014; methicillin-susceptible S. aureus (MSSA) accounted for 16 percent and MRSA for 6 percent [12].

Infection source — Most cases of SAB in children are associated with either:

●A localized infection source (eg, bone and joint infections, skin and soft tissue infections, pneumonia), or

●An invasive device (eg, central venous catheter)

SAB without a focus of infection accounts for <10 percent of SAB episodes, most of which occur in children with comorbidities [13,14].

The source of SAB differs depending on whether the infection is community- or healthcare-associated, as discussed in the following sections.

Community-associated SAB — Community-associated infections are those that occur in patients without risk factors for healthcare-associated infection (eg, no invasive devices or recent hospitalizations) with onset in the community (ie, in a nonhospitalized patient or within first 48 hours of a hospital admission).

Approximately 40 to 50 percent of SAB episodes are community-associated [1,2,8,15-17].

In otherwise healthy children, community-associated SAB is frequently related to a focus of infection, including [2,18,19]:

●Bone and joint infections. (See "Hematogenous osteomyelitis in children: Epidemiology, pathogenesis, and microbiology", section on 'Microbiology' and "Bacterial arthritis: Epidemiology, pathogenesis, and microbiology in infants and children", section on 'Microbiology'.)

●Skin and soft tissue infections. (See "Cellulitis and skin abscess: Epidemiology, microbiology, clinical manifestations, and diagnosis", section on 'Microbiology' and "Skin and soft tissue infections in children >28 days: Evaluation and management".)

●Pneumonia – In particular, SAB may occur in children with influenza who develop a secondary S. aureus pneumonia [20]. (See "Pneumonia in children: Epidemiology, pathogenesis, and etiology", section on 'Etiologic agents' and "Seasonal influenza in children: Clinical features and diagnosis", section on 'Complications'.)

●Infective endocarditis (IE) – IE is an uncommon source of SAB in childhood. Nevertheless, S. aureus remains the predominant causative organism of pediatric IE causing infective endocarditis in children. (See "Infective endocarditis in children", section on 'Microbiology'.)

Community-associated MRSA (CA-MRSA) infection is discussed separately. (See "Methicillin-resistant Staphylococcus aureus (MRSA) in children: Epidemiology and clinical spectrum", section on 'CA-MRSA infection'.)

Healthcare-associated SAB — This category refers to infections that are acquired in a healthcare setting or that are associated with any of the following:

●Invasive devices

●History of surgery, hospitalization, or dialysis within the past year

●Prior history of healthcare-associated S. aureus infection or colonization

Approximately 50 to 60 percent of SAB episodes in children are healthcare-associated [1,2,8,15-17].

Healthcare-associated infections are further classified based upon whether onset is in the community or hospital.

Community onset — This category refers to infection in a patient with one or more of the above risk factors for healthcare-associated infection with onset in the community (ie, in a nonhospitalized patient or within first 48 hours of a hospital admission). Approximately one-third to one-half healthcare-associated SAB episodes are community onset [1,2,21].

Community-onset healthcare-associated SAB typically affects children with chronic illnesses (eg, cancer, neurologic disorders, gastrointestinal disorders requiring home parenteral nutrition) [16]. The rate of community-onset healthcare-associated SAB has risen with increasing use of outpatient intravenous therapies [16,22-25]. (See 'Intravascular catheters' below.)

In one large multicenter study from Australia and New Zealand, the source of bacteremia among children with community-onset healthcare-associated SAB was as follows [2]:

●Central venous catheter (CVC) or other device infection (26 percent)

●Skin or soft tissue infection (21 percent)

●Bone and joint infection (14 percent)

●No identified source (19 percent)

Hospital onset — Hospital-onset (or nosocomial) healthcare-associated infections are those that occur >48 hours after hospital admission. One-half to two-thirds of healthcare-associated SAB episodes are hospital onset [1,2,21,26].

SAB is a leading cause of nosocomial BSIs in children, particularly among children with CVCs [6,27-30]. Preterm neonates are at particularly high risk of nosocomial SAB, which most commonly occurs in association with an indwelling CVC [16,26,31,32].

Other risk factors for nosocomial SAB in children are similar to those described in adults and relate mainly to intravascular devices, respiratory illness, and surgical wounds [16,25,33,34]. (See "Epidemiology of Staphylococcus aureus bacteremia in adults", section on 'Risk factors'.)

Nosocomial SAB is a serious infection with mortality ranging from 4 to 9 percent in children [2,10,31]. Nosocomial SAB also may be associated with metastatic complications, including septic pulmonary emboli, pneumonia/pneumatoceles, osteomyelitis, and, rarely, infective endocarditis [21]. (See 'Outcome' below and "Infective endocarditis in children".)

RISK FACTORS — 

Risk factors for developing SAB include:

●Intravascular catheters (see 'Intravascular catheters' below)

●Indwelling foreign body or prosthesis (see 'Implanted foreign body' below)

●Underlying medical conditions (see 'Underlying medical conditions' below)

●Nasal S. aureus colonization (see 'Nasal colonization' below)

●Injection drug use (see 'Injection drug use' below)

Intravascular catheters — Intravascular catheters serve as a direct conduit into the intravascular space, allowing easy access for pathogens such as S. aureus into the bloodstream.

Intravascular catheters are the most common predisposing cause for SAB in hospitalized patients and an increasingly important contributor to community-onset healthcare-associated infections [16,21-24,27,30,33].

In a report from the National Nosocomial Infections Surveillance System, >90 percent of episodes of nosocomial bacteremia detected in patients in the pediatric intensive care unit (PICU) setting were associated with central venous catheters [27]. In 144 PICUs reporting data to the Centers for Disease Control and Prevention from 1997 through 2007, methicillin-resistant S. aureus (MRSA) and methicillin-susceptible S. aureus (MSSA) accounted for 2.6 and 5.3 percent of all catheter-associated bloodstream infections (BSIs), respectively [35]. Catheter-associated infections account for approximately one-third of pediatric SAB episodes overall and up to three-quarters of nosocomial episodes [14,16,30].

The risk of bacteremia varies depending on the type of catheter (eg, peripherally inserted versus centrally inserted, tunneled versus nontunneled), insertion site (upper versus lower extremity, internal jugular versus femoral vein), and duration of catheterization. These issues are discussed in greater detail separately. (See "Intravascular catheter-related infection: Epidemiology, pathogenesis, and microbiology".)

Implanted foreign body — Any implanted foreign body that becomes infected is a potential source for SAB. Implanted devices include vascular, urologic, neurologic, and orthopedic prostheses and devices. In a report of 47 episodes of implant-associated S. aureus infection in pediatric patients, three cases (7 percent) had associated bacteremia; all three were associated with spinal instrumentation [36].

Underlying medical conditions — Underlying medical conditions that are associated with an increased risk of SAB in pediatric patients include [16,19,37-39]:

●Malignancy

●Congenital heart disease

●Sickle cell disease

●Prematurity

●End-stage kidney disease (ie, dialysis dependent or transplant recipient)

●Severe eczema or other dermatologic conditions

●Inflammatory bowel disease

Rare inherited defects in white blood cell function or immune responses can also predispose patients to recurrent staphylococcal infections [40]. These include:

●Hyperimmunoglobulin E recurrent infection syndrome (HIES; previously called Job syndrome) (see "Autosomal dominant hyperimmunoglobulin E syndrome")

●Chronic granulomatous disease (see "Chronic granulomatous disease: Pathogenesis, clinical manifestations, and diagnosis")

●Leukocyte adhesion deficiency (see "Leukocyte-adhesion deficiency")

●Chediak-Higashi syndrome (see "Chediak-Higashi syndrome")

●Wiskott-Aldrich syndrome (see "Wiskott-Aldrich syndrome")

Nasal colonization — Colonization with S. aureus, particularly MRSA, is a risk factor for subsequent infection. Similarly, several studies have found that a negative nasal MRSA PCR test at the time of hospital admission provides a strong indication (>95 percent negative predictive value) that the patient is unlikely to have MRSA infection [41-45]. This issue is discussed in greater detail separately. (See "Methicillin-resistant Staphylococcus aureus (MRSA) in children: Epidemiology and clinical spectrum", section on 'Colonized individuals'.)

Injection drug use — The role of injection drug use in SAB is discussed separately. (See "Epidemiology of Staphylococcus aureus bacteremia in adults", section on 'Injection drug use'.)

ANTIMICROBIAL RESISTANCE

Methicillin resistance — Methicillin-resistant S. aureus (MRSA) was initially a healthcare-associated pathogen, with only small numbers of community-acquired cases, but it has become a prevalent community-acquired pathogen.

The epidemiology, microbiologic characteristics, and risk factors for methicillin resistance are discussed in detail separately. (See "Methicillin-resistant Staphylococcus aureus (MRSA) in children: Epidemiology and clinical spectrum".)

Clindamycin resistance — Resistance to clindamycin may be constitutive or inducible via the macrolide-lincosamide-streptogramin B (MLS[B]) resistance mechanism. Isolates with constitutive clindamycin resistance are fully resistant to both erythromycin and clindamycin and can be detected with routine susceptibility testing. MRSA isolates with inducible resistance via the MLS(B) mechanism can develop resistance during therapy; these isolates appear susceptible to clindamycin and resistant to erythromycin by most standard techniques but can be detected using the "D test" (picture 1). Automated systems are available that can screen for inducible resistance to clindamycin, with results comparable with the standard D test [46]. (See "Overview of antibacterial susceptibility testing", section on 'Inducible clindamycin resistance testing'.)

Clindamycin resistance in community-associated S. aureus can have considerable regional and temporal variation. The proportion of MRSA isolates that are resistant to clindamycin has increased since the early 2000s [47]. Clinicians must remain vigilant for increasing clindamycin resistance among community-associated methicillin-susceptible S. aureus (MSSA) and MRSA, especially since clindamycin is commonly used to treat these infections in children [47-50]. We suggest not using clindamycin to complete therapy for selective invasive infections associated with SAB until or unless the isolate is known to be susceptible to this agent and blood cultures are negative [51,52]. (See 'Definitive therapy' below.)

Vancomycin resistance — S. aureus isolates with intermediate susceptibility or resistance to vancomycin are much less common than MRSA. Bacteremia has been described [53]. These infections are discussed elsewhere. (See "Staphylococcus aureus bacteremia with reduced susceptibility to vancomycin".)

Reduced susceptibility to ceftaroline — Although ceftaroline is not widely used in the treatment of MRSA bacteremia in children, in one report, reduced susceptibility to ceftaroline (minimum inhibitory concentration ≥2 mcg/mL) was found in almost 3 percent of 201 invasive MRSA isolates from children between the years 2015 to 2018. All isolates with reduced susceptibility were from children with healthcare-associated infections; none had received ceftaroline prior to the recovery of the MRSA isolate [54].

SPECTRUM OF DISEASE — 

SAB is frequently associated with the following conditions and clinical syndromes, each of which is discussed in greater detail separately.

●Catheter-associated bloodstream infections – Clinical manifestations may include fever, inflammation or purulence at the insertion site, hemodynamic instability, and/or catheter dysfunction. (See "Intravascular catheter-related infection: Epidemiology, pathogenesis, and microbiology" and "Intravascular non-hemodialysis catheter-related infection: Clinical manifestations and diagnosis".)

●Sepsis – Septic shock is characterized by signs of inadequate tissue perfusion with evidence of systemic inflammation (ie, abnormal temperature, white blood cell count, heart rate, and/or respiratory rate). (See "Children with sepsis in resource-abundant settings: Rapid recognition and initial resuscitation (first hour)" and "Sepsis in children: Definitions, clinical manifestations, and diagnosis".)

●Toxic shock syndrome – Toxic shock syndrome (TSS) can be due to streptococcal or staphylococcal infections. Bacteremia is common in the former but rare in staphylococcal TSS. Manifestations of TSS include fever, hypotension, and erythroderma (picture 2). (See "Staphylococcal toxic shock syndrome".)

●Osteomyelitis – Children with osteomyelitis usually present acutely with fever, constitutional symptoms (eg, irritability, decreased appetite or activity), focal findings of bone inflammation (warmth, swelling, point tenderness), and limitation of function (eg, limp, limited use of extremity). (See "Hematogenous osteomyelitis in children: Clinical features and complications".)

●Septic arthritis – Bacterial arthritis classically presents with acute onset (two to five days) of fever and joint pain, swelling, and limited range of motion. However, the presentation varies depending upon the age of the child and the site of infection. Osteomyelitis contiguous to the septic arthritis is common. (See "Bacterial arthritis: Clinical features and diagnosis in infants and children", section on 'Clinical features'.)

●Pneumonia – S. aureus pneumonia may be associated with SAB. S. aureus pneumonia is usually severe and often associated with complications such as necrotizing pneumonia, parapneumonic effusion, empyema, and lung abscess. (See "Community-acquired pneumonia in children: Clinical features and diagnosis" and "Epidemiology, clinical presentation, and evaluation of parapneumonic effusion and empyema in children".)

●Skin and soft tissue infections – Skin and soft tissue infections in children, particularly infections that are purulent/fluctuant, are commonly caused by S. aureus. Bacteremia is uncommon in uncomplicated skin and soft tissue infections but may occur in certain settings (eg, surgical wound infections, burns, patients with underlying risk factors). (See "Skin and soft tissue infections in children >28 days: Evaluation and management".)

●Infective endocarditis – Infective endocarditis, especially in community-acquired SAB, is much less frequent in children than in adults (1.4 percent in children compared with up to 30 percent in adults) [15]. The risk is higher in children with congenital heart disease and/or indwelling central venous catheters [55,56]. Clinical symptoms of infective endocarditis include a new or changing murmur and/or septic emboli. (See "Infective endocarditis in children".)

MANAGEMENT

Antibiotic therapy

Empiric therapy — Empiric antistaphylococcal antibiotic therapy may be warranted in any of the following circumstances:

●Patients diagnosed with an invasive focal or systemic infections for which S. aureus is a likely pathogen – An antistaphylococcal agent is often included in the empiric regimen in patients with clinical findings suggestive of a syndrome or invasive focal infection for which S. aureus is an important potential pathogen (eg, toxic shock syndrome, severe skin and soft tissue infections, bone and joint infections, severe pneumonia/empyema, endocarditis) (see 'Spectrum of disease' above). The initial empiric antimicrobial regimens for these conditions generally include broader coverage for S. aureus as well as other likely pathogens. (See "Staphylococcus aureus in children: Overview of treatment of invasive infections", section on 'When to suspect S. aureus infection'.)

●Patients with documented bacteremia – Empiric antistaphylococcal therapy may be warranted based on preliminary Gram stain results (if Gram stain shows gram-positive cocci in clusters).

●Clinical concern for bacteremia in an at-risk patient – In children without an apparent clinical syndrome or focal source, SAB may be suspected on the basis of fever or signs of systemic infection in a child with underlying risk factors for SAB (eg, intravascular catheter or other invasive device, intravenous drug use).

Once the decision has been made to provide empiric antibiotic coverage for invasive S. aureus infection, the choice of agent(s) depends upon the source and severity of the infection, whether the infection is community- or healthcare-acquired, and, if community-acquired, what the prevalence of methicillin-resistant S. aureus (MRSA) is in the community. The approach is outlined in the table (table 1) and discussed in detail separately. (See "Staphylococcus aureus in children: Overview of treatment of invasive infections", section on 'Choice of therapy'.)

Definitive therapy — Once susceptibilities have been determined, the antimicrobial regimen can be modified. Consultation with a pediatric infectious disease specialist is advised for all children with SAB, especially those with persistent SAB despite presumed adequate source control and the administration of appropriate antibiotic therapy [57].

Confirmed invasive MRSA infections are commonly treated with vancomycin or one of the alternative options as summarized in the table (table 2) and discussed in greater detail separately. (See "Staphylococcus aureus in children: Overview of treatment of invasive infections", section on 'Definitive antimicrobial therapy'.)

For SAB associated with musculoskeletal infections or pneumonia caused by clindamycin-susceptible isolates (including testing for inducible resistance), clindamycin is an appropriate choice to complete therapy once bacteremia is cleared if endovascular sites are not a concern [58]. Clindamycin is bacteriostatic for S. aureus and thus is not routinely used for the initial treatment of SAB.

Although vancomycin is generally efficacious for the treatment of MRSA, it is less effective than beta-lactams for MSSA. Thus, once results of susceptibility testing are known, S. aureus isolates that are methicillin- or penicillin-susceptible should be treated with beta-lactams rather than vancomycin (table 3).

If MRSA is not isolated within 72 hours after antibiotics are initiated, the vancomycin (or other empiric MRSA-targeting antibiotics) can be discontinued; commercial methods for rapid detection of MSSA may allow for earlier discontinuation [59]. This approach requires that clinicians be aggressive in obtaining cultures from all appropriate sites in addition to blood cultures (eg, aspiration or surgical incision and drainage of bone or joint infections). (See "Hematogenous osteomyelitis in children: Evaluation and diagnosis" and "Bacterial arthritis: Clinical features and diagnosis in infants and children", section on 'Synovial fluid'.)

Duration of therapy — The duration of therapy for SAB depends upon the source of infection:

●No source identified – Uncomplicated SAB without an identified source in otherwise healthy infants (excluding neonates) and children is typically treated with 10 to 14 days of parenteral antibiotics; however, the optimal duration of antibiotic therapy in this setting is not established. A shorter or longer duration of therapy may be reasonable depending on the severity of the infection. In nonsevere cases, it may be reasonable to transition to an appropriate oral antibiotic once cultures are negative and the patient has defervesced.

●Osteomyelitis or septic arthritis – SAB associated with osteomyelitis or septic arthritis is usually treated for at least three weeks. The initial treatment is with parenteral antibiotics. Most patients can be converted to an oral regimen once they have clinically improved and blood cultures are sterile. Treatment is often continued until the erythrocyte sedimentation rate is <25 to 30 mm/hour, which may take four to six weeks. This is discussed in greater detail separately. (See "Bacterial arthritis in infants and children: Treatment and outcome", section on 'Total duration' and "Hematogenous osteomyelitis in children: Management", section on 'Total duration'.)

●Skin and soft tissue infection – SAB associated with skin and soft tissue infection is usually treated for 7 to 10 days. Parenteral therapy is continued until two consecutive blood cultures are negative and the patient has clinically improved; then, treatment is completed with an oral agent based on the susceptibility of the isolate. Longer courses may be necessary depending upon clinical response. (See "Skin and soft tissue infections in children >28 days: Evaluation and management", section on 'Total duration'.)

●Catheter-related infection – Catheter-related SAB is treated with 10 to 14 days of parenteral antibiotics [60]. If the catheter is removed and bacteremia clears promptly, no further studies are necessary unless new clinical concerns arise. Longer duration of therapy may be warranted if bacteremia persists or if there are complications.

●Infective endocarditis – S. aureus infective endocarditis is treated parenterally for a minimum of four to six weeks, as discussed separately. (See "Infective endocarditis in children", section on 'Treatment'.)

Removal of infectious foci

Intravascular catheter removal — For children with catheter-related SAB, optimal management of the infection includes removal of the catheter [60]. However, the benefits of catheter removal must be weighed against the potential difficulty of obtaining alternative venous access. It is reasonable to attempt to clear the infection without removing the catheter in select children, particularly those who require central venous access for survival and those in whom alternative sites for catheter placement are limited [61,62]. Antimicrobial treatment without catheter removal is reasonable if the child is not in shock, responds promptly to medical therapy (ie, fever resolves and bacteremia clears), and has no evidence of an infected thrombus or distant sites of infection. If the catheter remains in place, both systemic antibiotics and antibiotic lock therapy may be warranted [60]. Observational studies have reported successful management in 50 to 80 percent of children treated without catheter removal [63-67]. Close monitoring is required, and the device should be removed in the event of clinical deterioration or if SAB persists for >2 days [68]. In a study of catheter-related SAB, catheter removal >4 days after infection or failure to remove the catheter, prolonged bacteremia (>4 days), and thrombocytopenia at presentation were independent predictors of complications [21]. Treatment of intravascular catheter-related infections is discussed in greater detail separately. (See "Intravascular non-hemodialysis catheter-related infection: Treatment", section on 'Selecting a catheter management strategy'.)

Surgical intervention — Surgical intervention may be warranted in children with infectious foci. Indications for surgical intervention are discussed separately:

●Parapneumonic effusion, empyema, or lung abscess (see "Management and prognosis of parapneumonic effusion and empyema in children", section on 'Chest tubes' and "Management and prognosis of parapneumonic effusion and empyema in children", section on 'Surgical therapy')

●Osteomyelitis (see "Hematogenous osteomyelitis in children: Management", section on 'Indications for surgery')

●Septic arthritis (see "Bacterial arthritis in infants and children: Treatment and outcome", section on 'Drainage')

●Skin abscesses (see "Skin abscesses in adults: Treatment", section on 'Incision and drainage')

●Infective endocarditis (see "Infective endocarditis in children", section on 'Surgical intervention')

Monitoring

Repeat blood cultures — Blood cultures should be repeated every 24 to 48 hours until two consecutive blood cultures are sterile [69,70]. Positive cultures persisting beyond 48 to 72 hours should prompt evaluations for unidentified foci of infection, such as septic thrombophlebitis, infective endocarditis, or undrained abscess.

In a retrospective study of 122 pediatric patients with SAB managed at a single institution, only one patient (0.8 percent) had a positive blood culture after two documented negative cultures (and this patient had clinical evidence of disease recurrence with new onset of septic shock on the day that the cultures reverted back to positive) [69]. Thus, documenting sterility with two consecutive blood cultures obtained at least 24 hours apart is generally sufficient.

Drug levels — For children treated with vancomycin, we generally favor trough-guided monitoring. Although area under the curve-guided dosing is suggested by consensus guidelines [71], the advantages and feasibility of this approach may differ among pediatric facilities. We aim to achieve trough concentrations of 5 to 15 mcg/mL and modify the dose or dosing interval if the trough is ≥15 mcg/mL. Therapeutic monitoring of vancomycin in children is discussed in greater detail separately. (See "Staphylococcus aureus in children: Overview of treatment of invasive infections", section on 'Therapeutic monitoring for vancomycin'.)

Toxicity — A complete blood count should be monitored weekly for patients receiving beta-lactam antibiotics. If neutropenia occurs, it typically develops after the first 10 days of therapy. Neutropenia can also be associated with vancomycin treatment. Elevated transaminase (ie, aspartate aminotransferase [AST] or alanine aminotransferase [ALT]) concentrations also can occur [72]. Some authorities follow AST and ALT levels weekly, though they are rarely markedly elevated (ie, >5 times normal) and patients typically have no associated symptoms. Hypersensitivity rashes may be severe enough to require discontinuation of the beta-lactam antibiotic, although similar rashes may be encountered with clindamycin.

For patients treated with vancomycin, kidney function (blood urea nitrogen and creatinine levels) should be monitored twice weekly in hospitalized patients and weekly in outpatients. More frequent monitoring may be warranted in children with kidney function impairment. However, in children with more significant kidney function impairment, it may be prudent to use an alternative agent that is not nephrotoxic, such as ceftaroline.

Echocardiography — Patients with risk factors or signs of infective endocarditis should undergo transthoracic echocardiography. (See "Infective endocarditis in children", section on 'Echocardiography'.)

The Infectious Diseases Society of America clinical practice guideline recommends echocardiography for children with SAB and any of the following [58]:

●Underlying congenital heart disease (CHD) or acquired valve disease

●Persistent bacteremia more than two to three days' duration

●Clinical findings suggestive of endocarditis (eg, new or changing murmur, septic emboli) (see "Infective endocarditis in children", section on 'Clinical manifestations')

Routine echocardiography is not necessary in all children with SAB. This is in contrast with the practice in adults patients, wherein routine echocardiography is recommended for all patients with SAB. (See "Clinical approach to Staphylococcus aureus bacteremia in adults", section on 'Echocardiography'.)

Infective endocarditis, especially in community-acquired SAB, occurs far less frequently in children than in adults (1.4 percent in children compared with up to 30 percent in adults) [15]. (See 'Endocarditis' below.)

OUTCOME

Mortality — In the contemporary era, mortality associated with SAB in children is approximately 2 to 3 percent [6,9,14,15,17,19,31].

In a large surveillance study from Denmark, the mortality rate associated with pediatric SAB fell from 20 percent in the early 1970s to 2.5 percent by the late 1990s [31].

Mortality is highest among infants <1 year of age, particularly premature neonates [6,31,73]. Other reported risk factors for mortality include comorbid conditions, hospital-acquired infection, and associated pulmonary infection or endocarditis [31,34]. In one study, the duration of time to positive blood culture was independently associated with mortality, with increased risk in patients with shorter time to positivity [74].

Rarely, patients may present with severe and rapidly progressing S. aureus sepsis, a presentation that can be fatal [75,76]. Severe sepsis can occur in previously healthy children, particularly adolescents, and may be caused by methicillin-susceptible and methicillin-resistant isolates.

Endocarditis — Patients with SAB who have underlying congenital heart disease (CHD) and those with persistent bacteremia are at increased risk of endocarditis and should undergo echocardiography. Echocardiography is also warranted if there are suggestive clinical findings (eg, new or changing murmur, septic emboli). (See 'Echocardiography' above.)

In children without CHD, infective endocarditis is a rare complication of SAB, especially in community-acquired SAB.

In seven observational studies including data on 839 episodes of pediatric SAB, endocarditis was diagnosed in 5 percent, most of which (31 of 41 episodes) occurred in children with CHD [15,21,34,55,56,77,78]. Other risk factors for endocarditis identified in these studies included prolonged bacteremia and prematurity. Management of endocarditis is discussed separately. (See "Infective endocarditis in children".)

SOCIETY GUIDELINE LINKS — 

Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Sepsis in children and adults".)

SUMMARY AND RECOMMENDATIONS

●Epidemiology – Staphylococcus aureus is an important cause of both community- and healthcare-associated bacteremia. Most episodes of S. aureus bacteremia (SAB) in children are associated with a localized infection source (eg, bone and joint infections, pneumonia, skin and soft tissue infections) or invasive device (eg, central venous catheter). (See 'Epidemiology' above.)

●Antibiotic resistance – Methicillin-resistant S. aureus (MRSA) has become a prevalent community-acquired pathogen. S. aureus isolates have also developed resistance to clindamycin and, in rare cases, vancomycin. (See 'Antimicrobial resistance' above and "Methicillin-resistant Staphylococcus aureus (MRSA) in children: Epidemiology and clinical spectrum".)

●Risk factors – Important risk factors for SAB include (see 'Risk factors' above):

•Intravascular catheters (see 'Intravascular catheters' above)

•Indwelling foreign body or prosthesis (see 'Implanted foreign body' above)

•Underlying medical conditions (see 'Underlying medical conditions' above)

•Nasal S. aureus colonization (see 'Nasal colonization' above)

•Injection drug use (see 'Injection drug use' above)

●Spectrum of disease – SAB can be associated with many types of invasive focal and systemic infections, including catheter-associated bloodstream infections, sepsis, toxic shock syndrome, skin and soft tissue infections, osteomyelitis, septic arthritis, pneumonia, and endocarditis. (See 'Spectrum of disease' above.)

●Management

•Empiric therapy – Empiric antibiotic therapy for S. aureus may be warranted either because the child has an infection for which S. aureus is an important potential pathogen, because there is clinical concern for bacteremia in a child with underlying risk factors for S. aureus infection (eg, intravascular catheter or other invasive device, intravenous drug use), or because preliminary Gram stain results suggest S. aureus. (See "Staphylococcus aureus in children: Overview of treatment of invasive infections", section on 'When to suspect S. aureus infection'.)

Once the decision has been made to provide empiric antibiotic coverage for invasive S. aureus infection, the choice of agent(s) depends upon the source and severity of the infection, whether the infection is community- or healthcare-acquired, and, if community-acquired, what the prevalence of methicillin-resistant S. aureus (MRSA) is in the community. The approach is outlined in the table (table 1) and discussed in detail separately. (See "Staphylococcus aureus in children: Overview of treatment of invasive infections", section on 'Choice of therapy'.)

•Definitive therapy – Once susceptibilities have been determined, the antimicrobial regimen can be modified. The choice of regimen is summarized in the table (table 3) and discussed in detail separately. (See "Staphylococcus aureus in children: Overview of treatment of invasive infections", section on 'Definitive antimicrobial therapy'.)

•Duration of therapy – The duration of therapy for SAB depends upon the source of infection (see 'Duration of therapy' above):

-No source identified – Parenteral therapy for 10 to 14 days generally is adequate for uncomplicated SAB in otherwise healthy infants (excluding neonates) and children if no source is identified.

-Osteomyelitis or septic arthritis – SAB associated with osteomyelitis or septic arthritis is usually treated for at least three weeks. The initial treatment is with parenteral antibiotics; most patients can transition to oral antibiotics once they have clinically improved. (See "Bacterial arthritis in infants and children: Treatment and outcome", section on 'Total duration' and "Hematogenous osteomyelitis in children: Management", section on 'Total duration'.)

-Skin and soft tissue infection – SAB associated with skin and soft tissue infection is usually treated for 7 to 10 days. Patients can be transitioned to oral antibiotics 48 to 72 hours after blood cultures have become negative. (See "Skin and soft tissue infections in children >28 days: Evaluation and management", section on 'Total duration'.)

-Catheter-related infection – Catheter-related SAB is treated with 10 to 14 days of parenteral antibiotics. (See "Intravascular non-hemodialysis catheter-related infection: Treatment", section on 'Staphylococcus aureus'.)

-Infective endocarditis – S. aureus infective endocarditis is treated parenterally for a minimum of four to six weeks. (See "Infective endocarditis in children", section on 'Treatment'.)

●Monitoring

•Repeat blood cultures – Blood cultures should be repeated every 24 to 48 hours until two consecutive blood cultures are sterile and the patient is stable. Positive cultures persisting beyond 72 hours should prompt evaluations for unidentified foci of infection, such as septic thrombophlebitis, infective endocarditis, or undrained abscess. A complete blood count should be monitored weekly for patients receiving beta-lactam antibiotics. (See 'Repeat blood cultures' above.)

•Echocardiography – Echocardiography should be performed in children with SAB who have any of the following (see 'Echocardiography' above):

-Underlying congenital heart or valve disease

-Bacteremia lasting >2 to 3 days

-Clinical findings suggestive of endocarditis (eg, new or changing murmur, septic emboli)

●Outcome – The mortality associated with SAB in children is approximately 2 to 3 percent. The risk of mortality is increased in infants <1 year of age and in children with pulmonary infection, endocarditis, hospital-acquired infections, and comorbid conditions. (See 'Outcome' above.)

ACKNOWLEDGMENT — 

The UpToDate editorial staff acknowledges Daniel Sexton, MD, who contributed to earlier versions of this topic review.