Staphylococcus aureus bacteremia in children:

Epidemiology and clinical features

Authors:
Vance G Fowler, Jr, MD
Daniel J Sexton, MD
Sheldon L Kaplan, MD
Section Editor:
Morven S Edwards, MD
Deputy Editor:
Carrie Armsby, MD, MPH

Contributor Disclosures

All topics are updated as new evidence becomes available and our peer review process is
complete.
Literature review current through: Apr 2018. | This topic last updated: May 11, 2017.

INTRODUCTION — Staphylococcus aureus is a leading cause of both community- and

healthcare-associated bacteremia. S. aureusbacteremia (SAB) is associated with
increased morbidity and mortality, even with appropriate therapy.

The epidemiology and clinical features of SAB in children will be reviewed here. The
management and outcome of SAB in children are discussed separately.
(See "Staphylococcus aureus bacteremia in children: Management and outcome".)

EPIDEMIOLOGY — Bacteremia caused by S. aureus can be divided into the following

categories:

●Community-associated, and

●Healthcare-associated, which includes both:

•Hospital-onset (previously known as hospital-acquired or nosocomial), and

•Community-onset (previously called non-nosocomial healthcare-associated

infection [eg, related to outpatient intravascular therapy or underlying chronic
conditions that affect host response to infection])

Fifty to 60 percent of episodes of S. aureus bacteremia (SAB) in children are healthcare

associated, and 40 to 50 percent are community associated [1-4]. However, the rate of
community-onset healthcare-associated SAB has risen as the role of outpatient
intravenous (IV) therapies has expanded [2,5-8]. (See 'Intravascular catheters' below.)

Most cases of SAB in children are associated with a localizing infection source (eg,
pneumonia, skin and soft tissue infection, bone and joint infection) or invasive device (eg,
central venous catheter). SAB without a focus of infection accounted for only 6 percent of
SAB episodes at Texas Children's Hospital between 2001 and 2012; almost 90 percent of
these episodes occurred in children with comorbidities [9].

Incidence — The overall incidence of pediatric SAB varies somewhat by region, ranging
from 6 to 20 per 100,000 [10,11]. The incidence of SAB in children increased throughout
the early 2000s to 2010s [4,10,12-14]. In one study, the increase was attributed largely to
methicillin-resistant S. aureus (MRSA) bacteremia [13]. The rate of SAB among
hospitalized children ranges from 1.5 to 3.5 per 1000 hospital admissions [13-15].

Community-associated — In otherwise healthy children, community-associated SAB is

frequently related to a focus of infection, especially musculoskeletal infections, while
infective endocarditis is unusual. In one 10-year review of 58 children with S.
aureus sepsis who were admitted to a pediatric intensive care unit (55 of which were
community associated), 79 percent had musculoskeletal symptoms, and 10 percent had
pneumonia; 95 percent had normal cardiac valves [16]. Nonetheless, S. aureus remains
the predominant organism causing infective endocarditis in children. (See "Infective
endocarditis in children", section on 'Microbiology'.)

SAB may occur in a small percentage of children with influenza, primarily those who
develop a secondary S. aureus pneumonia [17]. (See "Seasonal influenza in children:
Clinical features and diagnosis", section on 'Complications'.)

CA-MRSA infection is discussed below. (See 'Community-associated MRSA' below.)

Hospital-onset healthcare-acquired — SAB is a leading cause of nosocomial

bloodstream infections (BSIs) in children in the United States [12,18-20]. In a prospective
study of 3432 episodes nosocomial BSIs in children at 49 hospitals in the United States
between 1995 and 2002, the most frequently isolated organisms were coagulase-negative
staphylococci (43 percent), S. aureus (9 percent), enterococci (9 percent),
and Candida spp (9 percent) [20].

Hospital-onset healthcare-acquired SAB is more frequent in infants (<1 year) than in older
children [2,21,22], and particularly in premature infants [23]. In a seven-year Danish
surveillance study, 74 to 91 percent of SAB in infants was hospital acquired, compared
with 39 to 50 percent of SAB in the older age groups [21].

In a 10-year review from a single institution in the United States, all episodes of SAB in
neonates were hospital acquired, compared with 20 percent in older children [22]. In
another children's hospital, 41 percent of 242 episodes of nosocomial S. aureus infection
were bacteremias primarily related to catheters [24]. However, other centers have reported
community-associated SAB in otherwise normal neonates, particularly related to
community-associated methicillin-resistant S. aureus (CA-MRSA) [25]. (See "Methicillin-
resistant Staphylococcus aureus infections in children: Epidemiology and clinical
spectrum", section on 'Epidemiology and risk factors'.)
Risk factors for nosocomial SAB in infants and children are similar to those described in
adults and relate mainly to intravascular devices, respiratory illness, and surgical wounds
[2,8,26,27]. Premature infants are especially likely to suffer from SAB [23].
(See "Epidemiology, pathogenesis, and microbiology of intravascular catheter infections".)

Hospital-onset healthcare-acquired SAB is a serious infection with mortality ranging from 4

to 9 percent in children [15,21]. Hospital-onset SAB also may be associated with
metastatic complications, including infective endocarditis. (See "Staphylococcus aureus
bacteremia in children: Management and outcome", section on 'Outcome' and "Infective
endocarditis in children".)

Community-onset healthcare-associated — Community-onset healthcare-associated

infection is defined as infection diagnosed at the time of admission or before the fourth
calendar day of hospitalization in an outpatient with extensive healthcare contact, as
defined by [4,28]:

●IV therapy, wound care, or specialized nursing care at home, or IV chemotherapy

within the prior 30 days

●Hospitalization in an acute-care hospital within the prior year

●An underlying chronic condition associated with frequent medical care

●Dialysis

●Residence in a nursing home or other long-term care facility (least common in

children)

Community-onset healthcare-associated SAB typically affects children with chronic

illnesses (eg, neurologic disorders, diabetes, malignancy) [2]. Prospective surveillance at
Texas Children's Hospital identified 899 episodes of community-onset healthcare-
associated S. aureusinfection between 2001 and 2004 [29]. Compared to community-
associated S. aureus infection, community-onset healthcare-associated S. aureus infection
is more often associated with invasive disease (9 versus 5 percent for MRSA and 24
versus 9 percent for methicillin-susceptible S. aureus [MSSA]).

Intravascular catheters play an increasingly important role in healthcare-associated

community-onset SAB [5-7]. In the Texas Children's surveillance study described above,
IV catheters were present in 74 of 899 episodes of S. aureus infection (8.2 percent) [29].
(See 'Intravascular catheters' below.)

ANTIMICROBIAL RESISTANCE

Methicillin resistance — There has been a considerable rise in the rate of methicillin
resistance since 1990 for all types of S. aureusbacteremia (SAB) [2,20,26,30]. In several
large series of bloodstream infections (BSIs) in children, 13 to 19 percent of S.
aureus isolates were resistant to methicillin [2,20,26,30]. Methicillin resistance was an
independent risk factor for mortality in neonates in a meta-analysis of seven cohort studies
of SAB-related mortality in children [31].

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

Community-associated MRSA — In a number of locations in the United States and

worldwide, an increasing proportion of S. aureusisolates associated with community-
acquired infections are methicillin-resistant [32,33]. In a study from the Centers for Disease
Control and Prevention (CDC) Active Bacterial Core Surveillance of 692 MRSA BSIs in
infants and children from 2005 to 2010, 36 percent were hospital-onset, 23 percent were
community-onset healthcare-associated, and 42 percent were community-acquired [4]. At
Texas Children's Hospital, MRSA has accounted for >65 percent of community-
acquired S. aureus isolates since 2004 [34,35].

Community-associated methicillin-resistant S. aureus (CA-MRSA) is genetically distinct

from traditional strains of hospital-acquired MRSA. USA300 is the predominant clone of
CA-MRSA associated with S. aureus bacteremia (SAB) in most studies from the United
States [24,32,33]. However, in one study, USA300 was also the predominant clone for
nosocomial MRSA isolates, accounting for 73 percent of such isolates since 2003, and
several reports have emphasized the growing frequency of the USA300 clone as a cause
of healthcare-associated SAB [24]. However, clindamycin susceptibility rates are generally
higher for true USA300 CA-MRSA isolates compared with healthcare associated USA300
MRSA isolates. (See "Methicillin-resistant Staphylococcus aureus infections in children:
Epidemiology and clinical spectrum", section on 'Epidemiology and risk factors'.)

Although CA-MRSA typically causes skin and soft-tissue infections [36,37], it can cause
invasive disease at any site, including hematogenous osteomyelitis, septic arthritis,
pneumonia, myositis and pyomyositis, and fasciitis; hematogenous osteomyelitis is the
most common invasive infection [35]. Septic thrombophlebitis, often of the lower
extremities or pelvis, is an increasingly recognized clinical manifestation of pediatric
community-associated S. aureus bacteremia due to CA-MRSA, usually in association with
a contiguous site of osteomyelitis [38].

Healthcare contact (particularly prior hospitalization) is an important risk factor for MRSA,
but there are numerous reports of patients with no identifiable healthcare contacts or other
risk factors [34,39-41]. In a prospective surveillance study at a tertiary-care children's
hospital where 60 to 67 percent of community-associated S. aureus isolates were
methicillin resistant, the presence of known risk factors for methicillin resistance did not
differentiate children with CA-MRSA from those with community-associated methicillin-
susceptible S. aureus (CA-MSSA) [34].
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 to
the standard D test [42]. (See "Overview of antibacterial susceptibility testing", section on
'Inducible clindamycin resistance testing'.)

Clindamycin should be avoided in the treatment of patients with serious infections caused
by S. aureus isolates with the inducible MLS(B) form of resistance [43-45].

Clinicians must remain vigilant for the emergence of clindamycin resistance among
community-associated MRSA [46,47], as more clindamycin is being used for treating these
infections in children.

Vancomycin resistance — S. aureus isolates with intermediate susceptibility or

resistance to vancomycin are much less common than MRSA. Bacteremia has been
described [48]. These infections are discussed elsewhere. (See "Staphylococcus aureus
bacteremia with reduced susceptibility to vancomycin".)

RISK FACTORS — The following clinical conditions predispose patients to develop S.

aureus bacteremia (SAB):

●Intravascular catheters

●Indwelling foreign body or prosthesis

●Underlying medical conditions (eg, malignancy, end-stage renal disease [ie, dialysis-
dependent], eczema and other dermatologic conditions)

●Nasal colonization

●Injection drug use

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 both the most common predisposing cause for SAB in
hospitalized patients and an increasingly important cause of community-onset healthcare-
associated SAB [2,5-7,18,24,26,49].
 ●In a seven-year prospective review of bloodstream infections (BSIs) in children, 49
percent of infections were associated with intravascular catheters [26].

●More than 90 percent of episodes of nosocomial bacteremia reported to the National

Nosocomial Infections Surveillance System (NNIS) from pediatric intensive care units
occurred in patients with central venous lines [18]. In 144 pediatric ICUs reporting
data to the Centers for Disease Control and Prevention (CDC) 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 central line associated
bloodstream infections [50].

●In single-institution studies, approximately 75 percent of nosocomial SAB episodes

were related to catheters [2,24].

●An increasing proportion of intravenous (IV) catheter-related SAB is caused by

USA300 MRSA. In one tertiary-care children's hospital, MRSA caused 26 percent of
IV catheter-related SAB; 41 percent of the MRSA isolates were USA300 [49].

The increasing role of outpatient IV therapies in the pathogenesis of SAB is illustrated by

an investigation that found that 22 percent of community-onset SAB cases were related to
intravascular catheters in 1990-1993 compared with no cases in 1980-1983 [5]. In
prospective surveillance, 5.7 percent of 279 peripherally inserted central venous catheters
in 271 children were removed for BSI, and another 5.4 percent were removed for
presumed BSI (fever in the absence of an identified focus of infection) [51]. These findings
are consistent with those of a retrospective review in which 11 percent of 75 children who
received ≥2 weeks of IV therapy via a central venous catheter for the treatment of
osteomyelitis developed a catheter-related BSI [7].

Tunneled venous catheters (eg, Hickman and perm catheters) and central venous
catheters account for a significant percentage of cases of catheter-associated SAB.
Peripheral venous and midline catheters have much lower risk of infection, and
peripherally inserted central catheters have an intermediate risk of causing SAB [52,53].
(See "Epidemiology, pathogenesis, and microbiology of intravascular catheter infections".)

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.

A classic experiment demonstrated that subcutaneous injection of up to one million colony-

forming units of S. aureus did not produce clinically apparent infection in normal human
volunteers [54]. However, in the presence of a subcutaneous suture, subcutaneous
injection of 300 colony-forming units of S. aureus invariably led to infection.

Underlying medical conditions — Underlying medical conditions are associated with an

increased risk of SAB in children. In a retrospective review of 164 episodes of SAB in 151
children, 74 percent of patients had an underlying medical condition, including heart
disease (24 percent), malignancy (18 percent), premature birth (12 percent),
gastrointestinal disorder (7 percent), transplant recipient (7 percent), and end-stage renal
disease (5 percent) [2]. Approximately one-half of cases had onset in hospital.

Hemodialysis-dependent and diabetic patients have high rates of nasal and skin
colonization with S. aureus [55-57]. Such patients are more prone to S. aureus infection
[55,57], including SAB [55,58]. (See "Tunneled, cuffed hemodialysis catheter-related
bacteremia".)

Inherited defects in white-blood-cell function or immune responses such as Job syndrome,

chronic granulomatous disease, leukocyte adhesion deficiency, Chediak-Higashi
syndrome, and Wiskott-Aldrich syndrome also predispose patients to recurrent
staphylococcal infections [59]. However, these conditions are extremely uncommon. (See
appropriate topic reviews).

Nasal colonization — The role of nasal colonization in the development of SAB was
prospectively evaluated in a study in which more than 14,000 nonbacteremic, nonsurgical
adults were screened for nasal S. aureus carriage on hospital admission [60]. Nosocomial
SAB occurred significantly more often in the 24 percent of patients who were nasal carriers
(1.2 versus 0.4 percent in noncarriers). Genotyping demonstrated that 80 percent of
strains causing SAB in nasal carriers were endogenous. On the other hand, nasal carriers
had significantly lower rates of SAB-related mortality (3 of 40 versus 13 of 41 (8 versus 32
percent)), a difference that could not be explained by differences in age or comorbidities.

Differences in the immune response of S. aureus carriers and noncarriers may help to
explain the lower mortality among carriers. Support for this hypothesis comes from an
observational study in which nasal swabs and serum samples were obtained from healthy
blood donors [61]. Carriers of S. aureus demonstrated effective antibody response against
the colonizing strain, whereas the antibody response against other strains was similar to
that of noncarriers. This strain-specific immunity may contribute to the improved mortality
outcome for nasal carriers compared to noncarriers. How these findings relate to children
is unknown.

A more marked increase in the risk of infection has been described in patients who are
colonized with methicillin-resistant S. aureus (MRSA) at hospital admission. What role
nasal carriage of S. aureus plays in the pathogenesis of SAB with onset in the community
as opposed to the hospital is not clear. (See "Methicillin-resistant Staphylococcus aureus
infections 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'.)
CLINICAL FEATURES — S. aureus bacteremia (SAB) frequently occurs in association
with fever and other symptoms related to the source of infection.

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 "Septic shock in children: Rapid recognition and initial
resuscitation (first hour)" and "Systemic inflammatory response syndrome (SIRS) and
sepsis in children: Definitions, epidemiology, clinical manifestations, and diagnosis".)

Toxic shock syndrome — Manifestations of staphylococcal toxic shock syndrome include

fever, hypotension, and skin manifestations (erythroderma (picture 2)).
(See "Staphylococcal toxic shock syndrome".)

Osteomyelitis — Children with hematogenous 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. Children
<3 years are affected most frequently. (See "Bacterial arthritis: Clinical features and
diagnosis in infants and children", section on 'Clinical features'.)

Pneumonia — SAB may be associated with pneumonia with typical symptoms of fever,
cough, and tachypnea. Complications such as necrotizing pneumonia, parapneumonic
effusion, empyema, and lung abscess are frequently associated with S.
aureus pneumonia. (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 "Suspected Staphylococcus aureus and streptococcal skin and soft tissue infections
in children >28 days: Evaluation and management".)

Intravascular catheter infection — Patients with indwelling intravascular catheters are at

risk for developing SAB. Clinical manifestations may include fever, inflammation or
purulence at the insertion site, hemodynamic instability, and/or catheter dysfunction.
(See "Epidemiology, pathogenesis, and microbiology of intravascular catheter
infections" and "Diagnosis of intravascular catheter-related infections".)
 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) [1]. Children with congenital heart disease and/or indwelling central
venous catheters are at increased risk for infective endocarditis. Clinical symptoms of
infective endocarditis include a new or changing murmur and/orseptic emboli.
(See "Infective endocarditis in children".)

SUMMARY

●Staphylococcus aureus is a leading cause of both community- and healthcare-

associated bacteremia. Most cases of S. aureus bacteremia (SAB) in children are
associated with a localizing infection source (eg, bone and joint infections,
pneumonia, skin and soft tissue infections) or invasive device (eg, central venous
catheter). (See 'Introduction' above and 'Epidemiology' above.)

●In otherwise healthy children, community-associated SAB is frequently related to a

focus of infection, especially musculoskeletal infections, while infective endocarditis is
unusual. (See 'Community-associated' above.)

●Risk factors for nosocomial SAB in infants and children relate mainly to intravascular
devices, respiratory illness, and surgical wounds. Premature infants are at particularly
high risk. Hospital-acquired SAB is also associated with metastatic complications,
including infective endocarditis. (See 'Hospital-onset healthcare-acquired' above.)

●Community-onset healthcare-associated infection typically affects chronically ill

children; intravascular catheters play an important role. Community-onset healthcare-
associated S. aureus infection is more often associated with invasive disease than
community-associated S. aureus infection. (See 'Community-onset healthcare-
associated' above.)

●S. aureus isolates have developed resistance to methicillin, clindamycin, and, in rare
cases, vancomycin. The rate of methicillin resistance has significantly increased since
1990 for all types of SAB. (See 'Antimicrobial resistance' above.)

●Risk factors for SAB include intravascular catheters, indwelling foreign body or
prosthesis, underlying medical conditions, nasal colonization, and injection drug use.
(See 'Risk factors' above.)

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