# 34 - 152 Staphylococcal Infections

### 152 Staphylococcal Infections

20-valent pneumococcal conjugate vaccine, PREVNAR 20 (Pfizer). 
Both vaccines are now also licensed for infant immunization and are 
likely to gradually replace PCV10 and PCV13. The additional serotypes 
in the new vaccines account for a variable fraction of the residual IPD 
in children (additional 15–45%) and adults (additional 11–33%) for 
PCV15 and PCV20, respectively, in countries where PCV13 coverage 
is high. For adults the United States Advisory Committee on Immuni­
zation Practices (ACIP) now recommends PCV20 instead of PPSV23 
for all persons ≥65 years of age and for those 2–64 years of age who 
have underlying medical conditions that put them at increased risk 
for pneumococcal disease or, if infected, disease of increased severity 
(Table 151-1; see also www.cdc.gov/vaccines/schedules). United States 

recommendations for PPSV23 are now limited to sequential use in the 
above age groups receiving the PCV15 vaccine.
The introduction of PCV in high-income settings has resulted in a 
>90% reduction in vaccine-serotype IPD among the whole population. 
This decline has been noted not only in those age groups immunized 
but also in adults and is attributable to the near elimination of vaccine-

serotype nasopharyngeal colonization in immunized infants, which 
reduces spread to adults. This protection of unimmunized community 
members through vaccination of a subset of the community is termed 
the indirect effect. Increases in colonization with—and concomitantly 
in disease due to—non-vaccine-serotype strains (i.e., replacement 
colonization and disease) have been seen. The scale of replacement 
disease has varied geographically with the impact eroding vaccine 
impact significantly in the elderly in the United Kingdom while having 
relatively little impact in the United States (see “Epidemiology,” above). 
Since vaccine-serotype strains are more commonly resistant to anti­
biotics than are non-vaccine serotypes, use of PCV has also resulted 
in substantial declines in the proportion and absolute rates of drugresistant pneumococcal disease. The ACIP recommendations for the 
use of conjugate vaccines can be found at www.cdc.gov/vaccines/hcp/
acip-recs/vacc-specific/pneumo.html. PCV has been shown to prevent 
pneumococcal infection in HIV-infected adults.
Other Prevention Strategies 
Pneumococcal disease can be 
averted through the prevention of illnesses that predispose individu­
als to pneumococcal infections. Relevant measures include smoking 
cessation and influenza vaccination, as well as improved management 
and control of diabetes, HIV infection, heart disease, and lung disease. 
Finally, the reduction of antibiotic misuse is a strategy for the preven­
tion of pneumococcal disease in that antimicrobial resistance directly 
and indirectly perpetuates organism transmission and disease in the 
community.
■
■GLOBAL HEALTH
In 2015, pneumococcal infections were estimated to have caused 
~317,000 annual deaths worldwide among children 1–59 months of 
age, accounting for 9.7% of the 3.2 million all-cause deaths and 38% of 
all pneumonia deaths in this age group. Updated estimates of residual 
pneumococcal disease burden since the widespread introduction of 
PCV have not been published. Reliable estimates of adult cases and 
deaths globally are more difficult to establish because of limited data 
from parts of the world where most disease occurs. Rates of pneumo­
coccal disease and mortality vary substantially across geographic set­
tings, with the highest rates in selected countries of sub-Saharan Africa 
and southern Asia, where risk factors for pneumococcal disease—
including HIV infection, lack of breast feeding of infants and children, 
malnutrition, sickle cell disease, and limited access to medical care—
are prevalent. Serotypes causing disease exhibit some heterogeneity 
across geographic settings, but a small number of serotypes universally 
account for the preponderance of disease in the absence of vaccina­
tion; accordingly, vaccine development and vaccination programs are 
globally relevant. Reductions in disease from pneumococcal infections 
are anchored in prevention through the inclusion of pneumococcal 
vaccines in infant immunization programs, timely assessment and 
appropriate treatment of persons with pneumococcal infections, and 
reduction of risk factors for pneumococcal disease. The use of vaccines 
for the prevention of adult pneumococcal disease, particularly among 

the elderly, is currently implemented in high-income countries, with 
virtually no use in low-income countries where most cases of disease 
exist.

■
■FURTHER READING
Krone CL et al: Immunosenescence and pneumococcal disease: An 
imbalance in host–pathogen interactions. Lancet Respir Med 2:141, 
2014.
Lees JA et al: Fast and flexible bacterial genomic epidemiology with 
PopPUNK. Genome Res 29:304, 2019.
Mackenzie GA et al: The impact of the introduction of pneumococcal 
conjugate vaccination in invasive pneumococcal disease and pneumonia 
in The Gambia: 10 years of population-based surveillance. Lancet 
Infect Dis 21:1293, 2021.
Subramanian K et al: Pneumolysin binds to the mannose recep­
tor C type 1 (MRC-1) leading to anti-inflammatory responses and 
enhanced pneumococcal survival. Nat Microbiol 4:62, 2019.
Van Der Poll T, Opal SM: Pathogenesis, treatment, and prevention of 
pneumococcal pneumonia. Lancet 374:1543, 2009.
■
■WEBSITES
American Academy of Pediatrics: Red Book: The report of the 
Committee on Infectious Diseases. Available at: aapredbook.aap­
publications.org.
Cochrane: Corticosteroids for Bacterial Meningitis. Available at: www.
cochrane.org/CD004405/ARI_corticosteroids-bacterial-meningitis.
U.S. Department of Health and Human Services: Antibiotic 
Resistance Threats in the United States 2019. Available at: www.cdc.
gov/drugresistance/pdf/threats-report/2019-ar-threats-report-508.pdf.
World Health Organization: Summary of WHO Position Paper 
CHAPTER 152
on Pneumococcal conjugate vaccines in infants and children 
under 5 years of age, February 2019. Available at: www.who.int/
publications/i/item/10665-310968.
Staphylococcal Infections
Franklin D. Lowy, Anne-Catrin Uhlemann

Staphylococcal Infections
Staphylococcus aureus, the most virulent of the many (≥40) staphylococ­
cal species, has demonstrated its versatility by remaining a major cause of 
morbidity and mortality worldwide despite the availability of numerous 
effective antistaphylococcal antibiotics. S. aureus is a pluripotent pathogen, 
causing disease through both toxin- and non-toxin-mediated mecha­
nisms. It is responsible for numerous nosocomial and community-based 
infections that range from relatively minor skin and soft tissue infections 
(SSTIs) to life-threatening systemic infections.
The “other” staphylococci, coagulase-negative staphylococci, are less 
virulent than S. aureus but remain important pathogens in select set­
tings, such as infections involving prosthetic devices.
MICROBIOLOGY AND TAXONOMY
Staphylococci, gram-positive cocci in the family Micrococcaceae, 
form grapelike clusters on Gram’s stain (Fig. 152-1). These organisms 
(~1 μm in diameter) are catalase-positive (unlike streptococcal spe­
cies), nonmotile, aerobic, and facultatively anaerobic. They are capable 
of prolonged survival on environmental surfaces under varying condi­
tions. Some species have a relatively broad host range, including mam­
mals and birds, whereas the host range for others is quite narrow—i.e., 
limited to one or two closely related animals.
S. aureus is generally distinguished from other staphylococcal spe­
cies by coagulase production, a surface enzyme that converts fibrinogen 
to fibrin. However, several of the “coagulase-negative staphylococci,”

FIGURE 152-1  Gram’s stain of S. aureus in a sputum sample, illustrating 
staphylococcal clusters. (From ASM MicrobeLibrary.org. © Pfizer, Inc.)
including S. pseudintermedius and S. argenteus, are coagulase-positive. 
As a result, description of these other staphylococci as non–S. aureus 
staphylococci (NSaS) is more accurate.
S. aureus ferments mannitol, is positive for protein A, and produces 
DNAse. On blood agar plates, S. aureus forms golden β-hemolytic colo­
nies; in contrast, most NSaS form small, white nonhemolytic colonies. 
Latex kits that detect both protein A and clumping factor can distin­
guish S. aureus from most other staphylococcal species. Point-of-care 
tests targeting these two proteins also are used for the rapid detection 
of staphylococcal colonization. Newer methods such as matrix-assisted 
laser desorption/ionization time-of-flight mass spectrometry (MALDITOF) are increasingly being used for staphylococcal speciation.
PART 5
Infectious Diseases
Determining whether multiple staphylococcal isolates from differ­
ent patients are the same or different is often relevant when there is 
concern that a nosocomial outbreak of staphylococcal infections is due 
to a common point source (e.g., a contaminated medical instrument). 
Molecular typing methods, such as pulsed-field gel electrophoresis and 
sequence-based techniques (e.g., staphylococcal protein A [SpA] 
typing), have been used for this purpose. More recently, whole-genome 
sequencing has emerged as the gold standard for discrimination among 
different isolates.
S. AUREUS INFECTIONS
■
■EPIDEMIOLOGY
S. aureus is both a commensal and an opportunistic pathogen. Approx­
imately 20–40% of healthy persons are colonized with S. aureus, with 
a smaller percentage (~10%) persistently colonized with the same 
strain. The rate of colonization is elevated among type 1 diabetics, 
HIV-infected patients, patients undergoing hemodialysis, injection 
drug users, and individuals with damaged skin. The anterior nares and 
oropharynx are frequent sites of human colonization, although the 
skin (especially when damaged), axilla, vagina, and perineum also are 
often colonized. These colonization sites serve as potential reservoirs 
for future infections.
Most individuals who develop S. aureus infections become infected 
with a strain that is already a part of their own commensal flora. 
Breaches of the skin or mucosal membrane allow S. aureus to initiate 
infection. Person-to-person transmission of S. aureus also occurs, most 
frequently from direct personal contact with an infected body site. 
Spread of staphylococci in aerosols of respiratory or nasal secretions 
from heavily colonized individuals, although rare, has been reported.
Some diseases increase the risk of S. aureus infection. Diabetes, for 
example, combines an increased rate of S. aureus colonization and 
the use of injectable insulin with the possibility of impaired leuko­
cyte function. Individuals with congenital or acquired qualitative or 
quantitative defects of polymorphonuclear leukocytes (PMNs) are at 
increased risk of S. aureus infections; this group includes neutropenic 
patients (e.g., those receiving chemotherapeutic agents), those with 

chronic granulomatous disease, and those with autosomal dominant 
hyperimmunoglobulin E (Job syndrome) or Chédiak-Higashi syn­
drome. Other groups at risk include individuals with end-stage renal 
disease, HIV infection, skin abnormalities, or prosthetic devices.
S. aureus is a leading cause of health care–associated infections 
(Chap. 147). It is the most common cause of surgical wound infections 
and is second only to NSaS as a cause of primary bacteremia. These iso­
lates are often resistant to multiple antibiotics; thus, available therapeutic 
options may be limited. In the community, S. aureus remains an important 
cause of SSTIs, respiratory infections, and, especially among injection drug 
users, infective endocarditis. The increasing use of home infusion therapy 
also poses a risk of community-acquired staphylococcal infections.
In the past three decades, there has been a dramatic change in 
the epidemiology of infections due to methicillin-resistant S. aureus 
(MRSA). In addition to its major role as a nosocomial pathogen, MRSA 
has become an established community-based pathogen. Numerous 
outbreaks of community-associated MRSA (CA-MRSA) infections 
have been reported in both rural and urban settings in widely separated 
regions throughout the world.
This trend appears to be due in part to the dramatic increase in 
MRSA colonization found in the community in different parts of the 
world. Outbreaks of CA-MRSA infections have occurred among such 
diverse groups as children, prisoners, athletes, Native Americans, and 
drug users. Risk factors common to these outbreaks include poor 
hygienic conditions, close contact, contaminated material, and dam­
aged skin. In some geographic regions of the world, the infections have 
been caused by a single CA-MRSA strain, while in others, a variety of 
CA-MRSA strains have been responsible. In the United States, strain 
sequence type 8 (PFGE type USA300) has been the predominant clone 
(Fig. 152-2). Although most infections caused by these strains have 
involved the skin and soft tissue, 5–10% have been invasive and poten­
tially life-threatening. CA-MRSA strains have also been responsible for 
an increasing number of nosocomial infections. Of concern has been 
the enhanced capacity of CA-MRSA to cause disease in immunocom­
petent individuals.
■
■PATHOGENESIS
General Concepts 
S. aureus is a pyogenic pathogen known for its 
capacity to induce abscess formation at both local and distant sites (i.e., 
metastatic infections). This classic pathologic response to S. aureus 
defines the framework within which infections will progress. The bac­
teria elicit an inflammatory response characterized by an initial intense 
infiltration of PMNs and a subsequent infiltration of macrophages and 
fibroblasts. Either the host cellular response (including the deposition 
of fibrin and collagen) contains the infection with the formation of a 
fibrinous capsule, or infection spreads to the adjoining tissue or into 
the bloodstream.
In toxin-mediated staphylococcal disease, infection is not invari­
ably present. For example, in staphylococcal food poisoning, once the 
heat-stable enterotoxin has been released into food, symptoms can 
develop in the absence of viable bacteria. In staphylococcal toxic shock 
syndrome (TSS), conditions allowing toxin elaboration at colonization 
sites (e.g., the presence of a superabsorbent tampon) suffice for initia­
tion of clinical illness.
The S. aureus Genome 
 The complete genomes of S. aureus 
strains are now readily available. Among the interesting revela­
tions are (1) the high degree of nucleotide sequence similarity of 
the core genomes of different strains; (2) the acquisition of a relatively 
large amount of genetic information by horizontal transfer from other 
bacterial species; and (3) the presence of unique “pathogenicity” or 
“genomic” islands—mobile genetic elements that contain clusters of 
enterotoxin and exotoxin genes and/or antimicrobial resistance deter­
minants. Among the genes in these islands is mecA, the gene respon­
sible for methicillin resistance. Methicillin resistance–containing 
islands have been designated staphylococcal cassette chromosome mec 
(SCCmec). There are different SCCmec types that range in size from 
~20 to 60 kb. Among the more common SCCmec types, types 1–3 are

FIGURE 152-2  Global distribution of community-associated MRSA. Dotted lines indicate possible route of dissemination. Estimates of the areas are shown where infection 
with the main strains—i.e., ST1 (green), ST8 (red), ST30 (blue), and ST80 (gray hatched)—have been reported. +, Panton-Valentine leukocidin (PVL)-positive strains; –, 
PVL-negative strains; ±, PVL-positive and -negative strains. (Reproduced with permission from FR DeLeo, M Otto, BN Kreiswirth, HF Chambers: Community-associated 
methicillin-resistant Staphylococcus aureus. Lancet 375:1557, 2010.)
traditionally associated with nosocomial MRSA isolates, whereas types 
4–6 have been associated with epidemic CA-MRSA strains.
A relatively limited number of MRSA clones have been responsible 
for most community- and hospital-associated infections worldwide. A 
comparison of these strains with those from earlier outbreaks (e.g., the 
phage 80/81 strains from the 1950s) has revealed preservation of much 
of the nucleotide sequence over time. This observation suggests that 
these strains possess determinants that facilitate survival and spread.
Regulation of Virulence Gene Expression 
In both toxinmediated and non-toxin-mediated diseases due to S. aureus, the 
expression of virulence determinants associated with infection 
depends on a series of regulatory genes (e.g., accessory gene regulator 
[agr] and staphylococcal accessory regulator [sar]) that coordinately 
control the expression of many virulence genes. The regulatory gene 
agr is part of a quorum-sensing signal transduction pathway that 
senses and responds to bacterial density. Staphylococcal surface pro­
teins are synthesized during the bacterial exponential growth phase in 
vitro. In contrast, many secreted proteins, such as α toxin, the entero­
toxins, and assorted enzymes, are released during the post–exponential 
growth phase in response to transcription of the effector molecule of 
agr, RNAIII.
These regulatory genes appear to serve a similar function in vivo. 
Successful invasion requires the sequential expression of these different 
bacterial elements. Bacterial adhesins are needed to initiate coloniza­
tion of host tissue surfaces. The subsequent release of various enzymes 
enables the colony to obtain nutritional support and permits bacteria 
to spread to adjacent tissues. Studies with strains in which these regu­
latory genes are inactivated show reduced virulence in several animal 
models of S. aureus infection.
Pathogenesis of Invasive S. aureus Infection 
Staphylococci 
are opportunists. For these organisms to invade the host and cause 
infection, some or all of the following steps are necessary: contamina­
tion and colonization of host tissue surfaces, breach of cutaneous or 
mucosal barriers, establishment of a localized infection, invasion, eva­
sion of the host response, and metastatic spread. Colonizing strains or 
strains transferred from other exposures are introduced into damaged 
skin, a wound, or the bloodstream. Recurrences of S. aureus infections 
are common, apparently because of the capacity of these pathogens to 

CHAPTER 152
persist in a quiescent state in various tissues, and then to cause recru­
descent infections when suitable conditions arise.
S. AUREUS COLONIZATION OF BODY SURFACES  The anterior nares 
and oropharynx are primary sites of staphylococcal colonization. In 
the nares, colonization appears to involve the attachment of S. aureus 
to keratinized epithelial cells. Other factors that contribute to colo­
nization include the influence of other resident nasal flora and their 
bacterial density, host factors, and nasal mucosal damage (e.g., that 
resulting from inhalational drug use). Other colonized body sites, such 
as damaged skin, the groin, and the oropharynx, may be particularly 
important reservoirs for CA-MRSA strains.
Staphylococcal Infections
INOCULATION AND COLONIZATION OF TISSUE SURFACES  Staphylo­
cocci may be introduced into tissue as a result of minor abrasions (e.g., 
mosquito bites), administration of medications such as insulin, or estab­
lishment of IV access with catheters. After introduction into a tissue site, 
bacteria replicate and colonize the host tissue surface. A family of struc­
turally related S. aureus surface proteins referred to as MSCRAMMs 
(microbial surface components recognizing adhesive matrix molecules) 
play an important role as mediators of adherence to these different sites. 
By adhering to exposed matrix molecules (e.g., fibrinogen, collagen, 
fibronectin), MSCRAMMs, such as clumping factor and collagen-binding 
protein, enable the bacteria to colonize different host tissue surfaces; 
these proteins contribute to the pathogenesis of invasive infections such 
as endocarditis and septic arthritis by facilitating the adherence of 
S. aureus to surfaces with exposed fibrinogen or collagen.
Although NSaS are classically known for their ability to elaborate 
biofilms and to colonize prosthetic devices, S. aureus also possesses the 
genes responsible for biofilm formation, such as the intercellular adhe­
sion (ica) locus. Binding to these devices occurs in a stepwise fashion, 
involving staphylococcal adherence to serum constituents that have 
coated the device surface and subsequent biofilm elaboration. S. aureus is 
thus a frequent cause of biomedical device–related infections.
INVASION  After colonization, staphylococci replicate at the initial 
site of infection, elaborating enzymes that include serine proteases, 
hyaluronidases, thermonucleases, and lipases. These enzymes facilitate 
bacterial survival and local spread across tissue surfaces. The lipases 
may facilitate survival in lipid-rich areas such as the hair follicles, 
where S. aureus infections are often initiated.

Constitutional findings may result from either localized or systemic 
infections. The staphylococcal cell wall—consisting of alternating 
N-acetyl muramic acid and N-acetyl glucosamine units in combination 
with an additional cell wall component, lipoteichoic acid—can initiate 
an inflammatory response that includes the sepsis syndrome. Staphy­
lococcal alpha (α) toxin is a critical staphylococcal toxin. It causes pore 
formation in various eukaryotic cells and can also initiate an inflam­
matory response with findings suggestive of sepsis. The S. aureus toxin 
Panton-Valentine leukocidin is cytolytic to PMNs, macrophages, and 
monocytes. Strains elaborating this toxin have been epidemiologically 
linked with cutaneous and more serious infections (i.e., pneumonia) 
caused by strains of CA-MRSA.

EVASION OF HOST DEFENSE MECHANISMS  Staphylococci have many 
host immune evasion strategies that are crucial to their survival. They 
possess an antiphagocytic polysaccharide microcapsule. Most human 
S. aureus infections are due to strains with capsular types 5 and 8. 
The zwitterionic (both negatively and positively charged) S. aureus 
capsule also plays a critical role in the induction of abscess formation. 
Protein A, an MSCRAMM unique to S. aureus, acts as an Fc receptor, 
binding the Fc portion of IgG subclasses 1, 2, and 4 and preventing 
opsonophagocytosis by PMNs. Both chemotaxis inhibitory protein of 
staphylococci (CHIPS, a secreted protein) and extracellular adherence 
protein (EAP, a surface protein) interfere with PMN migration to sites 
of infection. There are several cytolytic toxins, including α toxin and 
Panton-Valentine toxin, that are secreted by staphylococci that cause 
lysis of different host cells and contribute to host tissue damage.
An additional potential mechanism of S. aureus evasion is its capac­
ity for intracellular survival. Both professional and nonprofessional 
phagocytes internalize staphylococci. Internalization by these cells may 
provide a sanctuary that protects bacteria against the host’s defenses. 
This phenomenon appears to be especially relevant for hepatic Kupffer 
cells during staphylococcal bacteremias. The intracellular environment 
favors the phenotypic expression of S. aureus small-colony variants, 
which are found in patients receiving antimicrobial therapy (e.g., with 
aminoglycosides) and in those with cystic fibrosis or osteomyelitis. 
These variants, whether intra- or extracellular, may facilitate prolonged 
staphylococcal survival in different tissue sites and enhance the likeli­
hood of recurrences. Finally, S. aureus can survive within PMNs and 
may use these cells to spread and seed other tissue sites.
PART 5
Infectious Diseases
PATHOGENESIS OF COMMUNITY-ACQUIRED MRSA INFECTIONS  A 
number of specific virulence determinants contribute to the patho­
genesis of CA-MRSA infections. A strong epidemiologic association 
links the presence of the gene for the Panton-Valentine leukocidin 
with SSTIs and with necrotizing postinfluenza pneumonia. Other 
determinants that play a role in the pathogenesis of these infections 
and contribute to the unique virulence of these clones include the 
arginine catabolic mobile element (ACME), a cluster of unique genes 
that may facilitate evasion of host defense mechanisms; phenol-soluble 
modulins, a family of cytolytic peptides; and α toxin.
Host Response to S. aureus Infection 
The primary host response 
to S. aureus infection is the recruitment of PMNs. These cells are 
attracted to infection sites by bacterial components such as formylated 
peptides or peptidoglycan as well as by the cytokines tumor necrosis 
factor (TNF) and interleukins (ILs) 1 and 6, which are released by 
activated macrophages and endothelial cells.
Although most individuals have antibodies to staphylococci, it is not 
clear that antibody levels are qualitatively or quantitatively sufficient to 
protect against infection. Anticapsular and anti-MSCRAMM antibod­
ies facilitate opsonization in vitro and have been protective against 
infection in several animal models; however, vaccines with these com­
ponents have not yet successfully prevented staphylococcal infections 
in clinical trials.
Pathogenesis of Toxin-Mediated Disease 
S. aureus produces 
three types of toxins: cytotoxins, pyrogenic toxin superantigens, and 
exfoliative toxins. Both epidemiologic data and studies in animals 
suggest that antitoxin antibodies are protective against illness in 
TSS, staphylococcal food poisoning, and staphylococcal scalded-skin 

syndrome (SSSS). Illness develops after toxin synthesis and absorption 
and the subsequent toxin-initiated host response.
ENTEROTOXIN AND TOXIC SHOCK SYNDROME TOXIN 1 (TSST-1)  The 
pyrogenic toxin superantigens are a family of small-molecular-size, 
structurally similar proteins that are responsible for two diseases: 
TSS and food poisoning. TSS results from the ability of TSST-1 and 
enterotoxins to function as T-cell mitogens. In the normal process of 
antigen presentation, the antigen is first processed within the cell, and 
peptides are then presented in the major histocompatibility complex 
(MHC) class II groove, initiating a measured T-cell response. In con­
trast, TSST-1 and enterotoxins bind directly to the invariant region of 
MHC—outside the MHC class II groove. TSST-1 and the enterotoxins 
can then bind T-cell receptors via the vβ chain; this binding results 
in a dramatic overexpansion of T-cell clones (up to 20% of the total 
T-cell population). The consequence of this T-cell expansion is a cyto­
kine storm, with the release of inflammatory mediators that include 
interferon γ, IL-1, IL-6, TNF-α, and TNF-β. The resulting multisystem 
disease produces a constellation of findings that mimic those found in 
endotoxin shock; however, the pathogenic mechanisms differ.
A different region of the enterotoxin molecule is responsible for 
the symptoms of food poisoning. The enterotoxins are heat stable and 
can survive conditions that kill the bacteria. Illness results from the 
ingestion of preformed toxin; as a result, the incubation period is short 
(1–6 h). The toxin stimulates the vagus nerve and the vomiting center 
of the brain. It also appears to stimulate intestinal peristaltic activity.
EXFOLIATIVE TOXINS AND SSSS  The exfoliative toxins are responsible 
for SSSS, most commonly seen in newborns. The toxins that produce 
disease in humans are of two serotypes: ETA and ETB. These toxins 
are serine proteases that cleave desmosomal cadherins in the superfi­
cial layer of the skin, triggering exfoliation. The result is a split in the 
epidermis at the granular level, which is responsible for the superficial 
desquamation of the skin that typifies this illness.
■
■DIAGNOSIS
Staphylococcal infections are readily diagnosed by Gram’s stain 
(Fig. 152-1) and microscopic examination of abscess contents or 
of infected tissue. Routine cultures of infected material usually are 
positive; blood cultures are sometimes positive even when infections 
are localized to extravascular sites. S. aureus is rarely a blood culture 
contaminant. Polymerase chain reaction (PCR)–based assays are now 
often used for the rapid diagnosis of S. aureus infection. A number of 
point-of-care tests are available to screen patients for colonization with 
MRSA. Determining whether patients with documented S. aureus 
bacteremia also have infective endocarditis or a metastatic focus of 
infection remains a diagnostic challenge. Uniformly positive cultures 
of blood collected over time suggest an endovascular infection such 
as endocarditis (see “Bacteremia, Sepsis, and Infective Endocarditis,” 
below).
■
■CLINICAL SYNDROMES
(Table 152-1)
Skin and Soft Tissue Infections 
S. aureus causes a variety of 
cutaneous infections. Common factors predisposing to S. aureus cuta­
neous infection include chronic skin conditions (e.g., eczema), skin 
damage (e.g., insect bites, minor trauma), injections (e.g., in diabetes, 
injection drug use), and poor personal hygiene. These infections are 
characterized by the formation of pus-containing blisters, which often 
begin in hair follicles and spread to adjoining tissues. Folliculitis is a 
superficial infection that involves the hair follicle, with a central area 
of purulence (pus) surrounded by induration and erythema. Furuncles 
(boils) are more extensive, painful lesions that tend to occur in hairy, 
moist regions of the body and extend from the hair follicle to become 
a true abscess with an area of central purulence. Carbuncles are most 
often located in the lower neck and are even more severe and painful, 
resulting from the coalescence of other lesions that extend to a deeper 
layer of the subcutaneous tissue. In general, furuncles and carbuncles 
are readily apparent, with pus often expressible or discharging from 
the abscess. Other cutaneous S. aureus infections include impetigo

TABLE 152-1  Common Illnesses Caused by Staphylococcus aureus
Skin and Soft Tissue Infections
  Folliculitis
  Abscess, furuncle, carbuncle
  Cellulitis
  Impetigo
  Mastitis
  Surgical wound infections
Musculoskeletal Infections
  Septic arthritis
  Osteomyelitis (hematogenous or contiguous spread)
  Pyomyositis
  Psoas abscess
Respiratory Tract Infections
  Ventilator-associated or nosocomial pneumonia
  Septic pulmonary emboli
  Postviral pneumonia (e.g., influenza)
  Empyema
Bacteremia and Its Complications
  Sepsis, septic shock
  Metastatic foci of infection (kidney, joints, bone, lung)
  Infective endocarditis
Infective Endocarditis
  Injection drug use–associated
  Native-valve
  Prosthetic-valve
  Nosocomial
Device-Related Infections (e.g., intravascular catheters, prosthetic 
joints)
Toxin-Mediated Illnesses
  Toxic shock syndrome
  Food poisoning
  Staphylococcal scalded-skin syndrome
Invasive Infections Associated with Community-Acquired MethicillinResistant S. aureus
  Necrotizing fasciitis
  Waterhouse-Friderichsen syndrome
  Necrotizing pneumonia
  Purpura fulminans
and cellulitis. S. aureus is one of the most common causes of surgical 
wound infections.
Mastitis develops in 1–3% of nursing mothers. This infection of 
the breast, which generally presents within 2–3 weeks after delivery, is 
characterized by findings that range from cellulitis to abscess forma­
tion. Systemic signs, such as fever and chills, are often present in more 
severe cases.
Musculoskeletal Infections 
S. aureus is a common cause of bone 
infections—both those resulting from hematogenous dissemination 
and those arising from contiguous spread from a soft tissue site. Hema­
togenous osteomyelitis in children most often involves the long bones. 
Infections present with fever and bone pain or with a child’s reluctance 
to bear weight. The white blood cell count and erythrocyte sedimen­
tation rate are often elevated. Blood cultures are positive in ~50% of 
cases. When necessary, bone biopsies for culture and histopathologic 
examination are usually diagnostic.
In adults, hematogenous osteomyelitis involving the long bones is 
less common. However, vertebral osteomyelitis is among the more com­
mon clinical presentations. Vertebral bone infections are most often 

seen in patients with endocarditis, those undergoing hemodialysis, 
diabetics, and injection drug users. These infections may present with 
intense back pain and fever but may also be clinically occult, present­
ing as chronic back pain with low-grade fever. S. aureus is the most 
common cause of epidural abscess, a complication that can result in 
neurologic compromise. Patients report difficulty voiding or walking 
and radicular pain in addition to the symptoms associated with their 
osteomyelitis. Surgical intervention in this setting often constitutes a 
medical emergency.

Magnetic resonance imaging (MRI) is the most reliable imaging 
modality to help establish the diagnosis of osteomyelitis (Fig. 152-3). 
Routine x-rays are an appropriate first step, but findings may be normal 
for up to 14 days after the onset of symptoms. If an MRI is not possible, 
computed tomography (CT) is an acceptable alternative.
Bone infections that result from contiguous spread tend to develop 
from soft tissue infections, such as those associated with diabetic 
or vascular ulcers, surgery, or trauma. Exposure of bone, a draining 
fistulous tract, failure to heal, or continued drainage suggests involve­
ment of underlying bone. Bone involvement is established by bone 
culture and histopathologic examination (revealing evidence of PMN 
infiltration). Contamination of culture material from adjacent tissue 
can make the diagnosis of osteomyelitis difficult in the absence of 
pathologic confirmation. Samples obtained during surgery are the 
most reliable. An MRI is the most reliable radiologic test to distinguish 
between osteomyelitis and overlying soft tissue infection with underly­
ing osteitis.
In both children and adults, S. aureus is the most common cause of 
septic arthritis in native joints. If left untreated, this infection is rapidly 
progressive and may be associated with extensive joint destruction. It 
presents with intense pain on motion of the affected joint, swelling, 
and fever. Aspiration of the joint reveals turbid fluid, with >50,000 
PMNs/μL and gram-positive cocci in clusters seen on Gram’s stain 
(Fig. 152-1). In adults, septic arthritis may result from trauma, surgery, 
or hematogenous dissemination. The most commonly involved joints 
include the knees, shoulders, hips, and phalanges. Infection frequently 
develops in joints previously damaged by osteoarthritis or rheumatoid 
CHAPTER 152
Staphylococcal Infections
FIGURE 152-3  S. aureus vertebral osteomyelitis and epidural abscess involving 
the thoracic disk between T9 and T10. Sagittal postcontrast magnetic resonance 
imaging of the spine illustrates destruction of the T9–T10 intervertebral space with 
enhancement (long arrow). There is impingement on the thoracic cord and an 
epidural collection extending from T9 through T11 (short arrows).

arthritis. Iatrogenic infections resulting from aspiration or injection of 
agents into the joint also occur. In these settings, the patient experi­
ences increased pain and swelling in the involved joint in association 
with fever.

Pyomyositis is an unusual infection of skeletal muscles that is seen 
primarily in tropical climates but also occurs in immunocompromised 
(e.g., HIV-infected) patients. It is believed to arise from occult bacte­
remia. Pyomyositis presents as fever, swelling, and pain overlying the 
involved muscle. Aspiration of fluid from the involved tissue yields pus. 
Although a history of trauma may be associated with the infection, its 
pathogenesis is poorly understood.
Respiratory Tract Infections 
Respiratory tract infections caused 
by S. aureus occur in selected clinical settings. S. aureus is a cause of 
serious respiratory tract infections in newborns and infants; these 
infections present with shortness of breath, fever, and respiratory 
failure. Chest x-ray may reveal pneumatoceles (shaggy, thin-walled 
cavities). Pneumothorax and empyema are recognized complications.
In adults, nosocomial S. aureus pulmonary infections are common 
among intubated patients in intensive care units. Nasally colonized 
patients are at increased risk of these infections. The clinical presenta­
tion is no different from pulmonary infections caused by other bacterial 
pathogens. Patients produce increased volumes of purulent sputum and 
develop respiratory distress, fever, and new pulmonary infiltrates. Dis­
tinguishing bacterial pneumonia from respiratory failure or other causes 
of new pulmonary infiltrates in critically ill patients is difficult and relies 
on a constellation of clinical, radiologic, and laboratory findings.
Community-acquired respiratory tract infections due to S. aureus 
often follow viral infections—most commonly influenza. Patients 
may present with fever, bloody sputum production, and midlung-field 
pneumatoceles or multiple, patchy pulmonary infiltrates. Diagnosis is 
made by sputum Gram’s stain and culture. Blood cultures, although 
useful, are usually negative.
Bacteremia, Sepsis, and Infective Endocarditis 
S. aureus 
bacteremia may be complicated by sepsis, endocarditis, vasculitis, or 
metastatic seeding (establishment of suppurative collections at other 
tissue sites). Among the more commonly seeded tissue sites are bones, 
joints, kidneys, and lungs. The frequency of metastatic seeding during 
bacteremia has been estimated to be as high as 31%. The incidence of 
these complications increases with the duration of the bacteremia.
PART 5
Infectious Diseases
Recognition of these complications by clinical criteria alone is chal­
lenging. Comorbid conditions that are frequently seen in association 
with S. aureus bacteremia and that increase the risk of complications 
include diabetes, HIV infection, and renal insufficiency. Other host 
factors that increase the risk of complications include presentation 
with community-acquired S. aureus bacteremia, lack of an identifiable 
primary focus of infection, and the presence of prosthetic devices or 
material.
Clinically, S. aureus sepsis presents in a manner similar to that docu­
mented for sepsis due to other bacteria. The well-described progres­
sion of hemodynamic changes—beginning with respiratory alkalosis 
and clinical findings of hypotension and fever—is commonly seen. 
The microbiologic diagnosis is established by positive blood cultures.
The overall incidence of S. aureus endocarditis has increased over 
the past 20 years. S. aureus is now the leading cause of endocarditis 
worldwide, accounting for 25–35% of cases. This increase is due, at 
least in part, to the increased use of intravascular devices and, more 
recently, the upsurge in injection drug use. Studies using transesopha­
geal echocardiography found an endocarditis incidence of ~25% 
among patients with intravascular catheter–associated S. aureus bacte­
remia. Other factors associated with an increased risk of endocarditis 
are hemodialysis, the presence of intravascular prosthetic devices at the 
time of bacteremia, and immunosuppression. Patients with implant­
able cardiac devices (e.g., permanent pacemakers) are at increased risk 
of endocarditis or device-related infections. Despite the availability of 
effective antibiotics, mortality rates from these infections continue to 
range from 20 to 40%, depending on both the host and the nature of 
the infection. Complications of S. aureus endocarditis include cardiac 
valvular insufficiency, peripheral emboli, metastatic seeding, vasculitis, 

and central nervous system (CNS) involvement (e.g., mycotic aneu­
rysms, embolic strokes).
S. aureus endocarditis is encountered in four clinical settings: (1) 
right-sided endocarditis in association with injection drug use; (2) leftsided native-valve endocarditis; (3) prosthetic-valve endocarditis; and 
(4) nosocomial endocarditis. In each of these settings, the diagnosis 
is suspected from the patient’s history and the recognition of physical 
signs suggestive of endocarditis. These findings include cardiac mani­
festations, such as new or changing cardiac valvular murmurs; cuta­
neous evidence, such as vasculitic lesions, Osler’s nodes, or Janeway 
lesions; evidence of right- or left-sided embolic disease; and a history 
suggesting a risk for S. aureus bacteremia. In the absence of anteced­
ent antibiotic therapy, blood cultures are almost uniformly positive. 
Transthoracic echocardiography, while less sensitive than transesopha­
geal echocardiography, is less invasive and often identifies valvular 
vegetations. The Duke criteria (Chap. 133) are commonly used to help 
establish this diagnosis.
Acute right-sided tricuspid valvular S. aureus endocarditis is most 
often seen in patients who inject drugs. The classic presentation 
includes a high fever, a toxic clinical appearance, pleuritic chest pain, 
and the production of purulent, sometimes bloody, sputum. Chest 
x-rays or CT scans reveal evidence of septic pulmonary emboli (small, 
peripheral, circular lesions that may cavitate with time) (Fig. 152-4). A 
high percentage of affected patients have no history of antecedent val­
vular damage. At the outset of their illness, patients may present with 
fever alone, without cardiac or other localizing findings. As a result, a 
high index of clinical suspicion is essential for diagnosis.
Individuals with antecedent cardiac valvular damage more com­
monly present with left-sided native-valve endocarditis involving the 
damaged valve. These patients tend to be older than those with rightsided endocarditis, their prognosis is worse, and their incidence of 
complications (including peripheral emboli, cardiac decompensation, 
cerebrovascular events, and metastatic seeding) is increased.
S. aureus is one of the more common causes of prosthetic-valve 
endocarditis. This infection is especially fulminant in the early post­
operative period and is associated with increased morbidity and mor­
tality. In most instances, medical therapy alone is not sufficient and 
urgent valve replacement is necessary. Patients are prone to develop 
valvular insufficiency or myocardial abscesses originating from the 
region of valve implantation.
The increased frequency of nosocomial endocarditis (15–30% of 
cases, depending on the series) reflects in part the increased use of 
intravascular devices. This form of endocarditis is most commonly 
caused by S. aureus. These patients are often critically ill, are receiving 
antibiotics for various other indications, and have comorbid condi­
tions. As a result, blood cultures may be negative, and the diagnosis 
missed.
Prosthetic Device–Related Infections 
S. aureus accounts for 
a large proportion of prosthetic device–related infections. These 
infections include intravascular and peritoneal catheters, prosthetic 
valves, orthopedic devices, pacemakers, left ventricular assist devices, 
or vascular grafts. In contrast with the more indolent presentation of 
FIGURE 152-4  Computed tomography scan illustrating septic pulmonary emboli in 
a patient with methicillin-resistant Staphylococcus aureus bacteremia.

NSaS infections, S. aureus device-related infections are often acute, 
have both local and systemic manifestations, and tend to progress more 
rapidly. It is relatively common for a pyogenic collection to be present 
at the device site. Aspiration of these collections and performance 
of blood cultures are important components in establishing a diag­
nosis. S. aureus infections tend to occur more commonly soon after 
implantation unless the device is used for access (e.g., intravascular or 
hemodialysis catheters). In the latter instance, infections can occur at 
any time. As in most prosthetic-device infections, successful therapy 
usually involves removal of the device. Left in place, the device serves 
as a potential nidus for either persistent or recurrent infections.
Urinary Tract Infections 
Urinary tract infections (UTIs) are 
infrequently caused by S. aureus. The presence of S. aureus in the urine 
often suggests hematogenous dissemination. Ascending S. aureus 
infections occasionally result from instrumentation of the genitouri­
nary tract.
Infections 
Associated 
with 
Community-Acquired 
MRSA 
Although skin and soft tissues are by far the most common 
sites of infection associated with CA-MRSA, 5–10% of these infections 
are invasive and can be life-threatening. The latter unique infections, 
including necrotizing fasciitis, necrotizing pneumonia, and sepsis with 
Waterhouse-Friderichsen syndrome or purpura fulminans, were rarely 
associated with S. aureus prior to the emergence of CA-MRSA. These 
life-threatening infections reflect the increased virulence of CA-MRSA 
strains.
Toxin-Mediated Diseases 
• 
FOOD POISONING  S. aureus is 
among the most common causes of foodborne outbreaks in the United 
States. Staphylococcal food poisoning results from the inoculation of 
toxin-producing S. aureus into food by colonized food handlers. Toxin 
is then elaborated in such growth-promoting food as custards, potato 
salad, or processed meats. Even if the bacteria are killed by warming, 
the heat-stable toxin is not destroyed. The onset of illness is rapid, 
occurring within 1–6 h of ingestion; it is characterized by nausea 
and vomiting, although diarrhea, hypotension, and dehydration may 
occur. The differential diagnosis includes diarrhea of other etiologies, 
especially that caused by similar toxins (e.g., the toxins elaborated by 
Bacillus cereus). The rapidity of onset, the absence of fever, and the 
epidemic nature of the presentation (without secondary spread) should 
arouse suspicion of staphylococcal food poisoning. Symptoms gener­
ally resolve within 8–10 h. The diagnosis can be established by the 
demonstration of bacteria or the documentation of enterotoxin in the 
implicated food. Treatment is entirely supportive.
TOXIC SHOCK SYNDROME  TSS gained attention in the early 1980s, 
when a nationwide outbreak occurred among young, otherwise healthy, 
menstruating women. Epidemiologic investigation demonstrated that 
these cases were associated with the use of a highly absorbent tampon 
recently introduced to the market. Subsequent studies established the 
role of TSST-1 in these illnesses. Withdrawal of the tampon from the 
market resulted in a rapid decline in the incidence of this disease. 
However, menstrual and nonmenstrual cases continue to be reported. 
Nonmenstrual cases are seen in patients with surgical or postpartum 
wound infections, especially when packing of the wound occurs.
The clinical presentation is similar in menstrual and nonmenstrual 
TSS. Evidence of clinical S. aureus infection is not a prerequisite. 
TSS results from the elaboration of an enterotoxin or the structurally 
related enterotoxin-like TSST-1. More than 90% of menstrual cases 
are caused by TSST-1, whereas a high percentage of nonmenstrual 
cases are caused by enterotoxins (e.g., enterotoxin B). TSS begins with 
relatively nonspecific flulike symptoms. In menstrual cases, the onset 
usually comes 2 or 3 days after the start of menstruation. Patients 
present with fever, hypotension, and erythroderma of variable inten­
sity. Mucosal involvement is common (e.g., conjunctival hyperemia). 
The illness can rapidly progress to symptoms that include vomiting, 
diarrhea, confusion, myalgias, and abdominal pain. These symptoms 
reflect the multisystemic nature of the disease, with involvement of the 
liver, kidneys, gastrointestinal tract, and/or CNS. Desquamation of the 
skin occurs during convalescence, usually 1–2 weeks after the onset of 

TABLE 152-2  Case Definition of Staphylococcus aureus Toxic Shock 
Syndrome
Clinical Criteria
An illness with the following clinical manifestations:
• Fever: temperature ≥102.0°F (≥38.9°C)
• Rash: diffuse macular erythroderma
• Desquamation: 1–2 weeks after rash onset
• Hypotension: systolic blood pressure ≤90 mmHg for adults or less than the fifth 
percentile, by age, for children <16 years old
• Multisystem involvement (≥3 of the following organ systems)
• Gastrointestinal: vomiting or diarrhea at illness onset
• Muscular: severe myalgia or creatine phosphokinase level at least twice 
ULN
• Mucous membrane: vaginal, oropharyngeal, or conjunctival hyperemia
• Renal: blood urea nitrogen or creatinine level at least twice ULN for 
laboratory or urinary sediment with pyuria (≥5 leukocytes per high-power 
field) in the absence of urinary tract infection
• Hepatic: total bilirubin or aminotransferase level at least twice ULN for 
laboratory
• Hematologic: platelet count <105/μL
• Central nervous system: disorientation or alterations in consciousness 
without focal neurologic signs in the absence of fever and hypotension
Laboratory Criteria
Negative results in the following tests, if obtained:
• Blood or cerebrospinal fluid cultures for another pathogena
• Serologic tests for Rocky Mountain spotted fever, leptospirosis, or measles
CHAPTER 152
Case Classification
Probable: a case that meets the laboratory criteria and in which four of the five 
clinical criteria are fulfilled
Confirmed: a case that meets the laboratory criteria and in which all five of the 
clinical criteria are fulfilled, including desquamation (unless the patient dies 
before desquamation occurs)
Staphylococcal Infections
aBlood cultures may be positive for S. aureus.
Abbreviation: ULN, upper limit of normal.
Source: Centers for Disease Control and Prevention (www.cdc.gov/nndss/
conditions/toxic-shock-syndrome-other-than-streptococcal/case-definition/2011/).
illness. Laboratory findings may include azotemia, leukocytosis, hypo­
albuminemia, thrombocytopenia, and liver function abnormalities.
Diagnosis of TSS still depends on a constellation of findings rather 
than one specific finding and on a lack of evidence of other possible 
infections (Table 152-2). These other diagnoses include drug toxicities, 
viral exanthems, Rocky Mountain spotted fever, sepsis, and Kawasaki 
disease. Illness occurs only in persons who lack antibody to TSST-1. 
Recurrences are possible if antibody fails to develop after the illness.
STAPHYLOCOCCAL SCALDED-SKIN SYNDROME  SSSS primarily affects 
newborns and children. The illness may vary from a localized blister to 
exfoliation of much of the skin surface. The skin is usually fragile and 
often tender, with thin-walled, fluid-filled bullae (Fig. 152-5). Gentle 
pressure results in rupture of the lesions, leaving denuded underlying 
skin. The mucous membranes are usually spared. In more generalized 
infection, there are often constitutional symptoms, including fever, 
lethargy, and irritability with poor feeding. Significant amounts of fluid 
can be lost in more extensive cases. Illness usually follows localized 
infection at one of several possible sites. SSSS is much less common 
among adults but can follow infections caused by exfoliative toxin–
producing strains.
NON–S. AUREUS STAPHYLOCOCCAL 
INFECTIONS
Although less virulent than S. aureus, NSaS are among the most com­
mon causes of prosthetic-device infections, including endocarditis. 
They also are increasingly a cause of native-valve endocarditis and 
life-threatening bloodstream infections in neonates and in neutropenic 
patients. Approximately half of the identified NSaS species have been 
associated with human infections. Of these species, Staphylococcus

FIGURE 152-5  Staphylococcal scalded skin syndrome in a 6-year-old boy. 
Nikolsky’s sign, with separation of the superficial layer of the outer epidermal layer, 
is visible. (Adapted from LA Schenfeld: Staphylococcal scalded skin syndrome: 
N Engl J Med 342:1178, 2000.)
epidermidis is the most common human pathogen. It is part of the 
normal human flora and is found on the skin (where it is the most 
abundant bacterial species) as well as in the oropharynx and vagina. 
Staphylococcus saprophyticus, a novobiocin-resistant species, is a com­
mon pathogen in UTIs.
■
■PATHOGENESIS
S. epidermidis is the NSaS species most often associated with pros­
thetic-device infections. Infection is a two-step process, with initial 
adhesion to the device followed by colonization. S. epidermidis is 
uniquely adapted to colonize these devices because of its capacity to 
elaborate the extracellular polysaccharide (glycocalyx or slime) that 
facilitates formation of a protective biofilm on the device surface.
PART 5
Infectious Diseases
Implanted prosthetic material is rapidly coated with host matrix 
molecules such as fibrinogen or fibronectin. These molecules serve 
as potential bridging ligands, facilitating initial bacterial attachment 
to the device surface. A number of staphylococcal surface-associated 
proteins, such as autolysin (AtlE), fibrinogen-binding protein, and 
accumulation-associated protein (AAP), appear to play a role in attach­
ment to either modified or unmodified prosthetic surfaces. The poly­
saccharide intercellular adhesin facilitates subsequent staphylococcal 
colonization, aggregation, and accumulation on the device surface. 
Intercellular adhesin (ica) genes are more commonly found in strains 
of S. epidermidis that are associated with device infections than in 
strains associated with colonization of mucosal surfaces. Biofilm acts 
as a barrier, protecting bacteria from host defense mechanisms as well 
as from antibiotics while providing a suitable environment for bacterial 
maturation, survival, and potential spread to other tissue sites.
Two additional NSaS species, Staphylococcus lugdunensis and Staph­
ylococcus schleiferi, produce more serious infections (native-valve 
endocarditis and osteomyelitis) than do other NSaS. The basis for this 
enhanced virulence is not known, although both species appear to 
share more virulence determinants with S. aureus (e.g., clumping factor 
and lipase) than do other NSaS.
The capacity of S. saprophyticus to cause UTIs in young women 
appears related to the presence of adhesins that facilitate adherence to 
uroepithelial cells. A 160-kDa hemagglutinin/adhesin may contribute 
to this affinity.
■
■DIAGNOSIS
Although the detection of NSaS at sites of infection or in the blood­
stream by standard microbiologic culture methods is not difficult, 
interpretation of these results is frequently problematic. Because these 
organisms are present in large numbers on the skin, they often con­
taminate cultures. It has been estimated that only 10–20% of blood cul­
tures positive for NSaS reflect true bacteremia. Similar problems arise 
with cultures obtained from other sites. Among the clinical findings 

suggestive of true bacteremia are fever, evidence of local infection (e.g., 
erythema or purulent drainage at the IV catheter site), leukocytosis, 
and systemic signs of sepsis. Laboratory findings suggestive of true 
bacteremia include repeated isolation of the same strain (i.e., the same 
species with the same antibiogram or with a closely related DNA fin­
gerprint) from separate cultures, growth of the strain within 48 h, and 
bacterial growth in both aerobic and anaerobic bottles.
■
■CLINICAL SYNDROMES
NSaS cause a variety of prosthetic device–related infections, including 
those that involve prosthetic cardiac valves and joints, vascular grafts, 
intravascular devices, and CNS shunts. In all of these settings, the 
clinical presentation is similar. The signs of localized infection are often 
subtle, the rate of disease progression is slow, and the systemic findings 
are often limited. Signs of infection, such as purulent drainage, pain 
at the site, or loosening of prosthetic implants, are sometimes evident. 
Fever is frequently but not always present, and there may be mild leu­
kocytosis. Acute-phase reactant levels, erythrocyte sedimentation rate, 
and C-reactive protein concentration may be elevated.
Infections that are not associated with prosthetic devices include, 
as noted, native-valve endocarditis due to NSaS, which accounts for 
~5% of cases. Infections in preterm infants and neutropenic patients 
are often associated with the need for intravascular devices. S. lugdunensis 

appears to be a more aggressive pathogen in this setting, causing 
greater mortality and rapid valvular destruction with abscess formation 
than other NSaS.
TREATMENT
Staphylococcal Infections 
GENERAL PRINCIPLES OF THERAPY
Source control (e.g., incision and drainage of suppurative collec­
tions or removal of infected prosthetic devices), coupled with rapid 
institution of appropriate antimicrobial therapy, is essential for the 
management of all staphylococcal infections. The emergence of 
MRSA as a community-based pathogen has increased the impor­
tance of culturing all sites of infection to determine antimicrobial 
susceptibility and optimize oral treatment regimens. 
DURATION OF ANTIMICROBIAL THERAPY
Therapy for S. aureus bacteremia is generally prolonged (4–6 weeks) 
because of the high risk of complications (e.g., endocarditis, meta­
static foci of infection). Among the findings associated with com­
plicated bacteremias are (1) persistently positive blood cultures 
96 h after institution of therapy, (2) failure to promptly remove or 
drain an identified focus of infection (i.e., an intravascular cathe­
ter), (3) the presence of deep-seated infections, and (4) acquisition 
of the infection in the community. Patients with uncomplicated 
bacteremias are defined by a removable focus of infection, prompt 
response to antimicrobial therapy (i.e., no fever or positive blood 
cultures after 3–4 days), no evidence of metastatic foci of infection, 
and no implanted prostheses. In these latter infections, shortcourse therapy (2 weeks) can be given; however, these findings 
are not always predictive of an uncomplicated bacteremia. Given 
these concerns, caution is therefore needed in instituting a short 
course of therapy. Transesophageal echocardiography to rule out 
endocarditis is generally necessary because neither clinical nor 
laboratory findings can reliably detect cardiac involvement. A 
thorough radiologic investigation to identify potential metastatic 
collections is also indicated. All symptomatic body sites must be 
carefully evaluated.
Recent studies have demonstrated that parenteral therapy is not 
always necessary to complete a course of treatment for invasive 
staphylococcal infections such as endocarditis or osteomyelitis for 
carefully selected patients. These include patients with uncompli­
cated staphylococcal bacteremia.
NSaS treatment is complicated by the possibility that a single iso­
late may be a contaminant. Therapy for 7–14 days is recommended

for documented infections (i.e., blood cultures of the same strain 
≥24 h apart) in the absence of endocarditis or additional sites of 
infection. 
CHOICE OF ANTIMICROBIAL AGENTS
The choice of antimicrobial agents to treat both coagulase-positive 
and coagulase-negative staphylococcal infections is often difficult 
because of the prevalence of multidrug-resistant strains and the 
limited number of clinical trials that have compared the available 
TABLE 152-3  Antimicrobial Therapy for Staphylococcal Infectionsa
SENSITIVITY/
RESISTANCE OF ISOLATE
DRUG OF CHOICE
ALTERNATIVE(S)
COMMENTS
Parenteral Therapy for Serious Infections
Sensitive to penicillin
Penicillin G (4 mU q4h)
Nafcillin or oxacillin (2 g q4h), cefazolin (2 g q8h), 
vancomycin (15–20 mg/kg q8hb)
Sensitive to methicillin; 
resistant to penicillin
Nafcillin or oxacillin (2 g q4h), 
cefazolin (2 g q8h)
Daptomycin (6–10 mg/kg IV q24hb,d), vancomycin 
(15–20 mg/kg q8hb), ceftobiprole (500 mg IV q6hg)
Resistant to methicillin
Vancomycin (15–20 mg/kg

q8–12hb), daptomycin 
(6–10 mg/kg IV q24hb,d) for 
bacteremia, endocarditis, 
osteomyelitis, and 
complicated skin infections
Linezolid (600 mg q12h PO or IV), ceftaroline (600 mg IV 
q8–12h), telavancin (7.5–10 mg/kg IV q24h)b,
TMP-SMX (5 mg [based on TMP]/kg IV q8–12h)f
Additional agents include tedizolid (200 mg once daily 
IV), oritavancin (single dose of 1200 mg), dalbavancin 
(single dose of 1500 mg), delafloxacin (300 mg q 12 h 
IV), omadacycline 100 mg OD).
Ceftobiprole (500 mg IV q6hg)
Resistant to methicillin 
with intermediate or 
complete resistance to 
vancomycine
Daptomycin (6–10 mg/kg 
q24hb,d) for bacteremia, 
endocarditis, osteomyelitis, 
and complicated skin 
infections
Same as for methicillin-resistant strains (check 
antibiotic susceptibilities)
or
 
 
Ceftaroline (600 mg IV q8–12h)
Newer agents include tedizolid (200 mg once daily 
IV or PO), oritavancin (single dose of 1200 mg), and 
dalbavancin (single dose of 1500 mg). These drugs 
are approved only for the treatment of skin and soft 
tissue infections.
Not yet known (i.e., 
empirical therapy)
Vancomycin (15–20 mg/kg 
q8–12hb), daptomycin 

(6–10 mg/kg q24hb,d) for 
bacteremia, endocarditis, 
osteomyelitis, and 
complicated skin infections
—
Empirical therapy is given when the susceptibility 
of the isolate is not known. Vancomycin with or 
without a b-lactam is recommended for suspected 
community- or hospital-acquired Staphylococcus 
aureus infections because of the increased 
frequency of methicillin-resistant strains in the 
community. If isolates with an elevated MIC to 
vancomycin (≥1.5 μg/mL) are common in the 
community, daptomycin may be preferable.
Oral Therapy for Skin and Soft Tissue Infections
Sensitive to methicillin
Dicloxacillin (500 mg qid), 
cephalexin (500 mg qid), or 
cefadroxil (1 g q12h)
Minocycline or doxycycline (100 mg q12hb), TMPSMX (1 or 2 DS tablets bid), clindamycin (300–450 mg 
tid), linezolid (600 mg PO q12h), tedizolid 

(200 mg PO q24h)
Resistant to methicillin
Clindamycin (300–450 mg 
tid), TMP-SMX (1 or 2 DS 
tablets bid), minocycline or 
doxycycline (100 mg q12hb), 
linezolid (600 mg bid), or 
tedizolid (200 mg once daily)
Delafloxacin 450 mg q12 h, omadacycline 300 mg 
once a day
aRecommended dosages are for adults with normal renal and hepatic function. bThe dosage must be adjusted for patients with reduced creatinine clearance. cFor the 
treatment of prosthetic-valve endocarditis, the addition of gentamicin (1 mg/kg q8h) and rifampin (300 mg PO q8h) is recommended, with adjustment of the gentamicin 
dosage if the creatinine clearance rate is reduced. dDaptomycin cannot be used for the treatment of pneumonia. eVancomycin-resistant S. aureus isolates from clinical 
infections have been reported. fTMP-SMX may be less effective than vancomycin. gAdditional studies are needed.
Abbreviations: DS, double-strength; TMP-SMX, trimethoprim-sulfamethoxazole; VISA, vancomycin-intermediate S. aureus; VRSA, vancomycin-resistant S. aureus.
Source: Modified from C Liu et al: Clin Infect Dis 52:285, 2011; DL Stevens et al: Clin Infect Dis 59:148, 2014; DL Stevens et al: Med Lett Drugs Ther 56:39, 2014; and LM 
Baddour et al: Circulation 132:1435, 2015.

agents. Staphylococcal resistance to most antibiotic families, includ­
ing β-lactams, aminoglycosides, fluoroquinolones, and (to a lesser 
extent) glycopeptides, has increased. This trend is even more appar­
ent with NSaS; >80% of nosocomial isolates are resistant to methi­
cillin, and these methicillin-resistant strains are often resistant to 
other antibiotics. Because the selection of antimicrobial agents for 
S. aureus infections is similar to that for NSaS infections, treatment 
options for these pathogens are discussed together and are sum­
marized in Table 152-3.

Fewer than 5% of isolates are sensitive to penicillin. 
The clinical microbiology laboratory must verify 
that the strain is not a b-lactamase producer.
Patients with a penicillin allergy can be treated 
with a cephalosporin if the allergy does not 
involve an anaphylactic or accelerated reaction; 
desensitization to b-lactams may be indicated in 
selected cases of serious infection when maximal 
bactericidal activity is needed (e.g., prostheticvalve endocarditisc). Vancomycin is a less effective 
option than a b -lactam.
Sensitivity testing is necessary before an 
alternative drug is selected. The efficacy of 
adjunctive therapy is not well established in many 
settings. Linezolid, ceftaroline, and telavancin 
have in vitro activity against most VISA and VRSA 
strains. See footnote for treatment of prostheticvalve endocarditis.c
CHAPTER 152
Staphylococcal Infections
Same as for methicillin-resistant strains; check 
antibiotic susceptibilities. Ceftaroline is used either 
alone or in combination with daptomycin.
 
It is important to know the antibiotic susceptibility 
of isolates in the specific geographic region. All 
collections should be drained, and drainage should 
be cultured.
It is important to know the antibiotic susceptibility 
of isolates in the specific geographic region. All 
collections should be drained, and drainage should 
be cultured.

Few strains of staphylococci (≤5%) remain susceptible to peni­
cillin. This is a result of the widespread dissemination of plasmids 
containing the enzyme penicillinase. Penicillin-resistant isolates are 
treated with semisynthetic penicillinase-resistant penicillins (SPRPs), 
such as oxacillin or nafcillin. Methicillin, the first of the SPRPs, is 
no longer used. Cephalosporins are alternative therapeutic agents 
for these infections. In patients with a history of serious β-lactam 
allergies, alternatives to SPRPs for the treatment of invasive infec­
tions should be used only after careful consideration. Desensitiza­
tion to β-lactams remains an option for life-threatening infections. 
Second- and third-generation cephalosporins offer no therapeutic 
advantage over first-generation cephalosporins for the treatment of 
staphylococcal infections, and some third-generation cephalosporins 
(e.g., ceftazidime, ceftriaxone) have considerably less activity and 
should be avoided. The carbapenems have excellent activity against 
methicillin-sensitive S. aureus but not against MRSA.

The isolation of MRSA was reported within 1 year of the intro­
duction of methicillin. Since then, the prevalence of MRSA has 
steadily increased. In many U.S. hospitals and elsewhere, 40–50% of 
S. aureus isolates are resistant to methicillin. Resistance to methicil­
lin indicates resistance to all SPRPs as well as to all cephalosporins 
(except ceftaroline). Production of a novel penicillin-binding pro­
tein (PBP2a) is responsible for methicillin resistance. This protein 
is synthesized by the mecA gene, which (as stated above) is part 
of a large mobile genetic element—a pathogenicity or genomic 
island—called SCCmec. It is hypothesized that mecA was acquired 
via horizontal transfer from related staphylococcal species. Phe­
notypic expression of methicillin resistance may be constitutive 
(i.e., expressed in all cells in a population) or heterogeneous (i.e., 
displayed by only a proportion of the total cell population). Detec­
tion of methicillin resistance is enhanced by growth of cultures at 
reduced temperatures (≤35°C for 24 h) and with increased concen­
trations of salt in the medium. Culture techniques are increasingly 
being replaced by PCR-based or other methods (e.g., latex aggluti­
nation) that allow for the rapid detection of methicillin resistance.
PART 5
Infectious Diseases
Either vancomycin or daptomycin is recommended as the drug 
of choice for the treatment of invasive MRSA infections. MRSA 
susceptibility to vancomycin has decreased in many areas of the 
world. It is important to note that vancomycin is less effective than 
SPRPs for the treatment of infections due to methicillin-susceptible 
strains.
Three types of staphylococcal resistance to vancomycin have 
emerged. (1) Minimal inhibitory concentration (MIC; an in vitro 
measure of susceptibility) “creep” refers to the incremental increase 
in vancomycin MICs that has been detected in various geographic 
areas. Studies suggest that morbidity and mortality may be increased 
in infections due to S. aureus strains with vancomycin MICs of 
≥1.5 μg/mL. (2) In 1997, an S. aureus strain with reduced suscepti­
bility to vancomycin (vancomycin-intermediate S. aureus [VISA]) 
was reported from Japan. Subsequently, additional VISA clinical 
isolates were reported. These strains were resistant to methicillin 
and many other antimicrobial agents. The VISA strains appear 
to evolve (under vancomycin selective pressure) from strains that 
are susceptible to vancomycin but are heterogeneous, with a small 
proportion of the bacterial population expressing the resistance 
phenotype. The mechanism of VISA resistance is in part due to an 
abnormally thick cell wall. Vancomycin is trapped by the abnormal 
peptidoglycan cross-linking and is unable to gain access to its target 
site. Regulatory genes involved in cell wall metabolism appear to 
play an important role in this type of resistance. (3) In 2002, the 
first clinical isolate of fully vancomycin-resistant S. aureus (VRSA) 
was reported. Resistance in this and several additional clinical 
isolates was due to the presence of vanA, the gene responsible for 
expression of vancomycin resistance in enterococci. This observa­
tion suggested that resistance was acquired as a result of horizontal 
conjugal transfer from a vancomycin-resistant strain of Enterococcus 
faecalis. Several of the patients infected with the VRSA strain had 
both MRSA and vancomycin-resistant enterococci cultured from 
infection sites. The vanA gene is responsible for the synthesis of 

the dipeptide d-Ala-d-Lac in place of d-Ala-d-Ala. Vancomycin 
cannot bind to the altered peptide. While isolates with MICs of 
≥1.5 μg/mL have been relatively common in some areas, VISA and 
VRSA isolates are uncommon.
Daptomycin, a parenteral bactericidal agent with antistaphylo­
coccal activity, is approved for the treatment of bacteremia (includ­
ing right-sided endocarditis) and complicated skin infections. It 
is not effective in respiratory infections. This drug has a unique 
mechanism of action: it disrupts the cytoplasmic membrane. Staph­
ylococcal resistance to daptomycin has been reported. Resistance 
can emerge during therapy; patients previously treated with van­
comycin may have elevated daptomycin MICs. Patients need to be 
monitored for rhabdomyolysis with creatine phosphokinase mea­
surement and for eosinophilic pneumonia.
Linezolid—the first oxazolidinone—is bacteriostatic against 
staphylococci; it offers the advantage of comparable bioavailability 
after oral or parenteral administration. Cross-resistance with other 
inhibitors of protein synthesis has not been detected. Resistance to 
linezolid is rare but has been reported. Serious adverse reactions 
to linezolid include thrombocytopenia, occasional cases of neutro­
penia, and rare instances of lactic acidosis or peripheral and optic 
neuropathy. These reactions tend to occur after relatively prolonged 
courses of therapy.
Tedizolid, a second oxazolidinone, is available as both oral 
and parenteral preparations. It exhibits enhanced in vitro activity 
against antibiotic-resistant gram-positive bacteria, including staph­
ylococci. Tedizolid is administered once a day. Data on its efficacy 
for the treatment of deep-seated infections are limited.
Ceftaroline is a fifth-generation cephalosporin with bactericidal 
activity against MRSA (including strains with reduced susceptibil­
ity to vancomycin and daptomycin). It is generally well tolerated. 
Ceftaroline is approved for use in nosocomial pneumonias and for 
SSTIs. It has increasingly been used to treat invasive MRSA infec­
tions with or without glycopeptides.
Telavancin is a parenteral lipoglycopeptide derivative of van­
comycin that is approved for the treatment of complicated SSTIs 
and for nosocomial pneumonias. The drug has two targets: the 
cell wall and the cell membrane. It remains active against VISA 
strains. Because of its potential nephrotoxicity, telavancin should be 
avoided in patients with renal disease.
Dalbavancin and oritavancin are long-acting, parenterally 
administered lipoglycopeptides that have been used to treat com­
plicated SSTIs. Because of their long half-lives, they can be admin­
istered on a weekly basis. Both have been used as single-dose 
regimens for the treatment of SSTIs. Emerging data support their 
use for the treatment of invasive staphylococcal infections.
Although the quinolones are active against staphylococci in 
vitro, the frequency of staphylococcal resistance to these agents 
has increased, especially among methicillin-resistant isolates. Of 
particular concern in MRSA is the possibility of quinolone resis­
tance emerging during therapy. Therefore, quinolones are not 
recommended for the treatment of MRSA infections. Resistance to 
the quinolones is most commonly chromosomal and results from 
mutations of the topoisomerase IV or DNA gyrase genes, although 
multidrug efflux pumps also may contribute. Although the newer 
quinolones exhibit increased in vitro activity against staphylococci, 
it is uncertain whether this increase translates into enhanced in 
vivo activity. Delafloxacin, a fluoroquinolone with broad-spectrum 
activity, has excellent activity against MRSA, retaining activity 
against some isolates resistant to other fluoroquinolones.
Tigecycline, a broad-spectrum minocycline analogue, has bac­
teriostatic activity against MRSA and is approved for use in SSTIs 
as well as intraabdominal infections caused by S. aureus. It is not 
recommended for the treatment of invasive infections.
Other older antibiotics, such as minocycline, doxycycline, 
clindamycin, and trimethoprim-sulfamethoxazole, continue to be 
successfully used to treat MRSA infections.
Ceftobiprole is a new antibiotic with excellent activity against 
both MRSA and methicillin-susceptible S. aureus (MSSA). It has

been shown in clinical trials to be effective in treating complicated 
staphylococcal bacteremias, SSTIs, and pneumonia.
The benefit of antistaphylococcal combinations to enhance 
bactericidal activity in the treatment of deep-seated infections 
remains controversial. Clinical studies have not documented a 
therapeutic benefit from the addition of gentamicin to single-drug 
regimens; recent reports have raised concern about the potential 
nephrotoxicity of gentamicin and adverse reactions from, or drug 
interactions with, rifampin. As a result, the use of gentamicin in 
combination with β-lactams or other antimicrobial agents is no 
longer routinely recommended for the treatment of invasive infec­
tions such as native-valve endocarditis. Rifampin continues to be 
used for the treatment of prosthetic device–related infections and 
for osteomyelitis.
Omadacycline and eravacycline are broad-spectrum semisyn­
thetic tetracycline derivatives with activity against MRSA. They are 
currently approved for the treatment of SSTIs.
The use of bacteriophages with activity against staphylococci 
is now being investigated in clinical trials as adjunctive therapy in 
invasive infections. 
ANTIMICROBIAL THERAPY FOR SELECTED SETTINGS 
Empirical Therapy  Empirical coverage for MRSA is indicated when 
antibiotic susceptibility is not known. Vancomycin or daptomycin is 
generally recommended. It remains uncertain whether daptomycin is 
preferable when elevated vancomycin MICs (>1.5 μg/mL) are com­
mon in a specific locale. 
Salvage Therapy  Salvage therapy for complicated S. aureus infec­
tions is sometimes needed when the bacteremia persists (i.e., for 
3 days) despite appropriate treatment. The risk of a poor outcome 
(i.e., increased mortality, metastatic infections) is increased with the 
duration of bacteremia. Prolonged bacteremia can occur with both 
MRSA and MSSA. There is limited high-quality evidence to serve 
as a guide to salvage therapy. The combination of daptomycin or 
vancomycin with a β-lactam antibiotic (e.g., ceftaroline) has been 
successfully used to treat patients with persistent MRSA bactere­
mia, even those patients with isolates displaying reduced suscep­
tibility to these antimicrobial agents. This combination appears to 
enhance the bactericidal activity of daptomycin by reducing the 
bacterial cell-surface charge and thus allowing enhanced dapto­
mycin binding. For vancomycin, the combination may allow more 
strategic binding to the target site with reduced cell-wall thickness. 
Other combinations have included trimethoprim-sulfamethoxazole 
or rifampin combined with daptomycin. Linezolid and ceftaroline 
have also been used as single alternative agents. 
Endocarditis  S. aureus endocarditis is usually an acute, lifethreatening infection. Thus, prompt collection of blood for cul­
tures should be followed by immediate institution of empirical 
antimicrobial therapy. For native-valve endocarditis, therapy with a 
β-lactam is recommended. If a MRSA strain is isolated, vancomycin 
(15–20 mg/kg every 8–12 h, given in equal doses up to a total of 2 g, 
with the dose adjusted in the case of renal disease) or daptomycin 
(6–10 mg/kg every 24 h) is recommended. The vancomycin dose 
should be adjusted based on area under the curve (AUC)-based 
dosing, although measurement of trough levels may also be used. 
Patients are generally treated for 6 weeks. For prosthetic-valve 
endocarditis, surgery in addition to antibiotic therapy is often nec­
essary. The combination of a β-lactam agent—or, if the isolate is 
β-lactam-resistant, vancomycin or daptomycin—with an aminogly­
coside (gentamicin, 1 mg/kg IV every 8 h) for 2 weeks and rifampin 
(300 mg orally or IV every 8 h) for ≥6 weeks is recommended. 
Infectious diseases and, if necessary, surgical consultation should 
be considered. 
Bone and Joint Infections  For hematogenous osteomyelitis or 
septic arthritis in children, a 4-week course of therapy is usually 
adequate. In adults, treatment is often more prolonged. For chronic 
forms of osteomyelitis, surgical debridement is necessary in com­
bination with antimicrobial therapy. For joint infections, a critical 

component of therapy is the repeated aspiration or arthroscopy of 
the affected joint to prevent damage from leukocytes. The combi­
nation of rifampin with ciprofloxacin has been used successfully 
to treat or suppress prosthetic-joint infections, especially when the 
device cannot be removed. The efficacy of this combination may 
reflect enhanced activity against staphylococci in biofilms as well as 
the attainment of effective intracellular concentrations. 

Skin and Soft Tissue Infections  The increase in SSTIs caused 
by CA-MRSA has drawn attention to the need for initiation of 
appropriate empirical therapy. Even small abscesses appear to ben­
efit from antibiotic therapy in addition to incision and drainage. 
Antibiotics are selected depending on local antibiotic susceptibility 
data; several oral agents have been used to treat these infections, 
including clindamycin, trimethoprim-sulfamethoxazole, doxycy­
cline, linezolid, and tedizolid. Parenteral therapy is reserved for 
more complicated infections. 
Toxic Shock Syndrome  Treatment of shock is the mainstay of 
therapy for TSS. Both fluids and pressors may be necessary. Tam­
pons or other packing material should be promptly removed. Some 
investigators recommend therapy with a combination of clindamy­
cin and a semisynthetic penicillin or (if the isolate is resistant to 
methicillin) vancomycin. Clindamycin is advocated because, as a 
protein synthesis inhibitor, it reduces toxin production. Linezolid 
also appears to be effective. A semisynthetic penicillin or a glyco­
peptide is recommended to eliminate any potential focus of infec­
tion as well as to eradicate persistent carriage that might increase 
the possibility of recurrence. Intravenous immunoglobulin to treat 
TSS is of uncertain benefit. Glucocorticoids are not recommended 
for the treatment of this disease. 
CHAPTER 152
Other Toxin-Mediated Diseases  Therapy for staphylococcal food 
poisoning is entirely supportive. For SSSS, antistaphylococcal 
therapy targets the primary site of infection. 
NONTRADITIONAL APPROACHES TO 
ANTISTAPHYLOCOCCAL THERAPY
In addition to the development of new antibiotics, new and non­
traditional approaches to therapy are currently being investigated. 
These include the use of phages or phage-derived peptides, as well 
as probiotics and antivirulence strategies that target selected viru­
lence determinants.
Staphylococcal Infections
■
■PREVENTION
Primary prevention of S. aureus infections in the hospital setting 
involves hand washing and careful attention to appropriate isolation 
procedures. Through careful screening for MRSA carriage and strict 
isolation practices, several Scandinavian countries have been remark­
ably successful at preventing the introduction and dissemination of 
MRSA in hospitals.
Decolonization strategies, using both universal and targeted 
approaches with topical agents (e.g., mupirocin) to eliminate nasal 
colonization and/or chlorhexidine to eliminate colonization of addi­
tional body sites with S. aureus, have been successful in some clinical 
settings where the risk of infection is high (e.g., intensive care units). 
An analysis of clinical trials suggests that decolonization can reduce the 
incidence of postsurgical infections among people nasally colonized 
with S. aureus. The risk of recurrent admissions among patients with 

S. aureus bacteremia following discharge is high (~22% within 30 days). 
Decolonization following discharge with mupirocin and chlorhexidine 
can lower the incidence of recurrent infections.
“Bundling” (the application of selected medical interventions in a 
sequence of prescribed steps) has reduced rates of nosocomial infec­
tions related to procedures such as the insertion of intravenous cath­
eters, in which staphylococci are among the most common pathogens 
(see Table 147-1). A number of immunization strategies to prevent S. 
aureus infections—both active (e.g., capsular polysaccharide–protein 
conjugate vaccine) and passive (e.g., clumping factor antibody)—have 
been investigated. However, to date, none has been successful for either 
prophylaxis or therapy in clinical trials.