STAPHYLOCOCCAL

INFECTION

NONTAPAK THIANGPAK
OUTLINE
•  Introduction
•  Microbiology
•  Staphylococcus aureus infections
•  Coagulase-negative staphylococcal infections
•  Treatment
INTRODUCTION
•  Staphylococcus aureus, the most virulent of the many
staphylococcal species.
•  S. aureus is a pluripotent pathogen, toxin-mediated and
non-toxin-mediated mechanisms.
•  Nosocomial and community-based infections; minor skin
and soft tissue infections to life-threatening systemic
infections.
•  The “other” staphylococci; coagulase-negative
staphylococci (CoNS), less virulent, important pathogens
in infections associated with prosthetic devices.
MICROBIOLOGY
•  Gram-positive cocci in the family Micrococcaceae.
•  Grapelike clusters on Gram’s stain.
•  Catalase-positive (unlike streptococcal species),
nonmotile, aerobic, and facultatively anaerobic.
•  Prolonged survival on environmental surfaces.
•  More than 30 staphylococcal species are pathogenic.
•  S. aureus is distinguished from other staphylococcal
species by its production of coagulase.
•  S. aureus tends to form golden β-hemolytic colonies.
•  CoNS produce small white nonhemolytic colonies.
COLONIES
Right; S. aureus
Left; CoNS
S. AUREUS
S. AUREUS
•  S. aureus is one of the most common bacterial pathogens
and a part of the normal human flora.
•  Colonization is higher among IDDM, HIV, hemodialysis
patients, and skin damage.
•  The anterior nares are the most frequent site.
•  Most individuals who develop S. aureus infections are
infected with their own colonizing strains.
•  Numerous outbreaks of community-based infection
caused by methicillin-resistant S. aureus (MRSA)
PATHOGENESIS
GENERAL CONCEPTS
•  Induce abscess formation; both local and metastatic
infections.
•  Toxin-mediated staphylococcal disease.
THE S. AUREUS
GENOME
•  The interesting revelations
1.  High degree of nucleotide sequence similarity among the
different strains.
2.  Large amount of genetic information by horizontal transfer
from other bacterial species.
3.  Presence of unique "pathogenicity" or "genomic" island;
contain clusters of enterotoxin and exotoxin genes or
antimicrobial resistance determinants.

“mecA gene”
REGULATION OF VIRULENCE
GENE EXPRESSION
•  The expression of virulence determinants associated with
infection depends on a series of regulatory genes
•  Accessory gene regulator (agr)
•  Staphylococcal accessory regulator (sar)
•  Staphylococcal surface proteins are synthesized during
exponential growth phase.
•  Secreted proteins are released during the post
exponential growth phase.
PATHOGENESIS OF INVASIVE
S. AUREUS INFECTION
•  Staphylococci are opportunists.
•  Inoculation and local colonization of tissue surfaces.
•  Invasion.
•  Evasion of the host response.
•  Metastatic spread.
•  Requires a breach in cutaneous or mucosal barriers.
PATHOGENESIS OF INVASIVE
S. AUREUS INFECTION
•  Nasal Colonization
•  Anterior nares is the principal site of staphylococcal
colonization.
•  Inoculation and Colonization of Tissue Surfaces
•  Introduced into tissue as a result of trauma.
•  Replicate and colonize the host tissue surface.
•  MSCRAMMs (microbial surface components recognizing
adhesive matrix molecules); a mediator of adherence such
as clumping factor and collagen-binding protein.
•  S. aureus also possesses genes for biofilm formation, such
as the intercellular adhesion (ica) locus.
 Pathogenic factors of Staphylococcus aureus, with structural and secreted products both
playing roles as virulence factors.

Gordon R J , Lowy F D Clin Infect Dis. 2008;46:S350-S359

© 2008 by the Infectious Diseases Society of America

PATHOGENESIS OF INVASIVE
S. AUREUS INFECTION

Invasion
PATHOGENESIS OF TOXIN-
MEDIATED DISEASE
•  Three types of toxin
•  Cytotoxins.
•  Pyrogenic-toxin superantigens.
•  Exfoliative toxins.
•  Antitoxin antibodies are protective against; TSS,
staphylococcal food poisoning, and staphylococcal
scalded-skin syndrome (SSSS).
PATHOGENESIS OF TOXIN-
MEDIATED DISEASE
Enterotoxin and Toxic Shock Syndrome Toxin 1 (TSST-1)
•  The pyrogenic toxin superantigens: TSS and food
poisoning.
•  TSS results from the ability of enterotoxins and TSST-1 to
function as T cell mitogens. “Cytokine storm”
•  A different region of the enterotoxin molecule is
responsible for the symptoms of food poisoning.
•  Heat stable.
•  Short incubation period(1-6 hrs.)
•  Stimulate vagus nerve.
PATHOGENESIS OF TOXIN-
MEDIATED DISEASE
Exfoliative Toxins and the Staphylococcal Scalded-Skin
Syndrome
•  Exfoliative toxins are responsible for SSSS.
•  Two serotypes: ETA and ETB.
•  Mechanism of skin disruption remains uncertain
DIAGNOSIS
•  Gram's stain.
•  Routine culture of infected material usually yields positive
results.
•  Blood cultures are sometimes positive
CLINICAL SYNDROME
SKIN AND SOFT
TISSUE INFECTIONS
•  Common predisposing factors; skin disease, skin
damage, injections, and poor personal hygiene.
•  Characterized by the formation of pus-containing blisters;
begin in hair follicles and spread to adjoining tissues.
•  Folliculitis; involves the hair follicle.
•  Furuncles are more extensive, painful lesions.
•  Carbuncles are most often located in the lower neck and
are more severe and painful.
•  Mastitis generally presents within 2–3 weeks after delivery.
•  One of the most common causes of surgical wound
infection.
FOLLICULITIS
FURUNCLES
CARBUNCLES
MUSCULOSKELETAL
INFECTIONS
•  The most common causes of bone infections.
•  Vertebral bone infections are most often seen in patients
with endocarditis, hemodialysis, diabetics, and injection
drug users.
•  S. aureus is the most common cause of epidural abscess.
•  Surgical intervention in this setting often constitutes a
medical emergency.
•  MRI most reliably establishes the diagnosis.
VERTEBRAL
OSTEOMYELITIS
MUSCULOSKELETAL
INFECTIONS
•  Osteomyelitis
MUSCULOSKELETAL
INFECTIONS
•  S. aureus is the most common cause of septic arthritis in
native joints.
•  Rapidly progressive and extensive joint destruction if left
untreated.
•  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 OA or RA.
MUSCULOSKELETAL
INFECTIONS
RESPIRATORY TRACT
INFECTIONS
•  Nosocomial S. aureus pulmonary infections are commonly
seen in intubated patients in ICU.
•  Community-acquired respiratory tract infections most
commonly follow viral infections or septic pulmonary
emboli.
•  Influenza is the most common cause.
•  Present with fever, bloody sputum, and midlung-field
pneumatoceles or multiple, patchy pulmonary infiltrates.
•  Diagnosis is made by sputum Gram's stain and culture.
•  Blood cultures are usually negative.
BACTEREMIA, SEPSIS, AND
INFECTIVE ENDOCARDITIS
•  S. aureus bacteremia may be complicated by sepsis,
endocarditis, vasculitis, or metastatic seeding(31%).
•  Risk of complications; diabetes, HIV, and renal
insufficiency.
•  S. aureus sepsis presents in a manner similar to other
bacteria.
•  The microbiologic diagnosis is established by positive
blood cultures.
BACTEREMIA, SEPSIS, AND
INFECTIVE ENDOCARDITIS
•  S. aureus is now the leading cause of endocarditis
worldwide, 25–35% of cases.
•  Risk of endocarditis; injection drug use, hemodialysis, the
presence of intravascular prosthetic devices, and
immunosuppression.
•  Mortality rates 20 to 40%.
•  Complications of S. aureus endocarditis; cardiac valvular
insufficiency, peripheral emboli, metastatic seeding, CNS
involvement.
BACTEREMIA, SEPSIS, AND
INFECTIVE ENDOCARDITIS
•  S. aureus endocarditis is encountered in four clinical
settings
•  Right-sided endocarditis in association with injection drug
use.
•  Left-sided native-valve endocarditis.
•  Prosthetic-valve endocarditis.
•  Nosocomial endocarditis.
URINARY TRACT
INFECTIONS
•  UTIs are infrequently caused by S. aureus.
•  The presence of S. aureus in the urine suggests
hematogenous dissemination.
•  Ascending S. aureus infections occasionally result from
instrumentation of the genitourinary tract.
PROSTHETIC DEVICE
RELATED INFECTIONS
•  These infections often involve intravascular catheters,
prosthetic valves, orthopedic devices, peritoneal or
intraventricular catheters, LV assist devices, and vascular
grafts.
•  S. aureus device-related infections often present more
acutely.
•  Most prosthetic-device infections, successful therapy
usually involves removal of the device.
INFECTIONS ASSOCIATED
WITH COMMUNITY
ACQUIRED MRSA
•  Necrotizing fasciitis.
•  Necrotizing pneumonia.
•  Sepsis with Waterhouse-Friderichsen syndrome
TOXIN-MEDIATED
DISEASES
Toxic Shock Syndrome
•  First recognized as a disease in children in 1978.
•  Outbreak occurred among young healthy menstruating
women.
•  Subsequent studies established the role of TSST-1 in
these illnesses.
•  TSS results from the elaboration of an enterotoxin or the
structurally related enterotoxin-like TSST-1.
•  TSS begins with relatively nonspecific flulike symptoms.
TOXIN-MEDIATED
DISEASES
Food Poisoning
•  S. aureus is the most common causes of food-borne
outbreaks of infection.
•  Results from the inoculation of toxin-producing S. aureus
into food by colonized food handlers.
•  Heat-stable toxin.
•  Onset is rapid; within 1–6 h of ingestion.
•  N/V, diarrhea, hypotension, and dehydration.
•  Symptoms generally resolve within 8–10 h.
TOXIN-MEDIATED
DISEASES
Staphylococcal Scalded-Skin Syndrome
•  SSS most often affects newborns and children.
•  The illness may vary from localized blister formation to
exfoliation.
•  SSSS is much less common among adult.
COAGULASE-NEGATIVE
STAPHYLOCOCCAL INFECTIONS
COAGULASE-NEGATIVE
STAPHYLOCOCCAL
INFECTIONS
•  CoNS are the most common causes of prosthetic-device
infections.
•  S. epidermidis is the most common human pathogen.
•  S. saprophyticus, a novobiocin-resistant species, is a
pathogen in UTIs.
PATHOGENESIS
•  Among CoNS, S. epidermidis is the species most
commonly associated with prosthetic-device infections.
•  Infection is a two-step process, with initial adhesion to the
device followed by colonization.
•  S. epidermidis is uniquely adapted to colonize by its
capacity to elaborate the extracellular polysaccharide
(glycocalyx or slime); formation of biofilm.
•  The capacity of S. saprophyticus to cause UTIs in young
women related to its capacity to adhere to uroepithelial
cells.
DIAGNOSIS
•  These organisms are present in large numbers on the skin,
they often contaminate cultures.
•  Only 10–25% of blood cultures positive for CoNS reflect true
bacteremia.
•  Clinical findings suggestive of true bacteremia
•  Fever.
•  Evidence of local infection.
•  Leukocytosis.
•  Systemic signs of sepsis.
•  Laboratory findings suggestive of true bacteremia
•  Multiple isolations of the same strain.
•  Growth of the strain within 48 h.
•  Bacterial growth in both aerobic and anaerobic bottles.
CLINICAL
SYNDROMES
•  CoNS cause diverse prosthetic device–related infections.
•  The signs of localized infection are often subtle.
•  Rate of disease progression is slow.
•  Systemic findings are often limited.
TREATMENT
GENERAL PRINCIPLES
OF THERAPY
•  Surgical incision and drainage; the most important
therapeutic intervention.
•  Prosthetic-device infections are unlikely to be
successfully managed unless the device is removed.
•  If removal is not possible or the infection is due to CoNS,
an initial attempt at medical therapy without device
removal may be warranted.
•  Because risk of complications associated with S.
aureus bacteremia, therapy is generally prolonged (4–8
weeks).
DURATION OF
ANTIMICROBIAL THERAPY
•  Debate continues regarding the duration of therapy for
bacteremic S. aureus infections.
•  A meta-analysis studies; concluded that insufficient
information was available to determine which patients
were candidates for short-course therapy (2 weeks rather
than 4–8 weeks).
CHOICE OF
ANTIMICROBIAL AGENTS
•  Dramatic increase in the number of MDR strains
susceptible only to vancomycin.
•  Widespread dissemination of plasmids containing
penicillinase.
•  Penicillin-resistant isolates are treated with semisynthetic
penicillinase-resistant penicillins.
•  The carbapenem imipenem has excellent activity against
MSSA.
•  Production of a novel penicillin-binding protein (PBP 2a or
2') is responsible for methicillin resistance.
CHOICE OF
ANTIMICROBIAL AGENTS
•  Vancomycin remains the drug of choice for the treatment
of MRSA infections.
•  Less bactericidal than the β–lactams.
•  In 1997, VISA was reported from Japan.
•  The mechanism of VISA resistance is due to an abnormal
cell wall.
•  In 2002, the first clinical isolate of fully vancomycin-
resistant S. aureus was reported.
•  Resistance was due to the presence of vanA gene.
•  The vanA gene is responsible for the synthesis of the
dipeptide D-Ala-D-Lac in place of D-Ala-D-Ala.
CHOICE OF
ANTIMICROBIAL AGENTS
•  Alternatives to the β-lactams and vancomycin have less
antistaphylococcal activity.
•  Quinolones have reasonable in vitro activity against
staphylococci.
•  Other antibiotics, such as minocycline and TMP-SMX have
been successfully used to treat MRSA infections.
•  Parenteral streptogramin quinupristin/dalfopristin displays
bactericidal activity against all staphylococci.
•  Linezolid is bacteriostatic against staphylococci.
CHOICE OF
ANTIMICROBIAL AGENTS
•  Daptomycin is approved for the treatment of bacteremias
and complicated skin infections, not effective in
respiratory infections.
•  Tigecycline has bacteriostatic activity against MRSA; use
in skin and soft tissue infections and intraabdominal
infections caused by S. aureus.
•  Combinations: enhance bactericidal activity in the
treatment of serious infections such as endocarditis or
osteomyelitis.
•  Combination; rifampin, aminoglycoside, fusidic acid.
CHOICE OF
ANTIMICROBIAL AGENTS
In vitro studies have demonstrated synergy against
staphylococci with the following combinations:
•  β-lactams and aminoglycosides.
•  Vancomycin and gentamicin.
•  Vancomycin, gentamicin and rifampin (against CoNS).
•  Vancomycin and rifampin.
FURTHER READINGS