Gram-positive cocci

Dr. Ayat Mostafa

Lecturer of Microbiology and Immunology
Faculty of Pharmacy- Assiut University
Gram positive cocci
1-Staphylococci

• Morphology: G +Ve cocci arranged in

grape like clusters, non-motile, and non-
spore forming.
 Classification of Staphylococci

1-Coagulase production:
a-Coagulase positive Staph:
Staph. aureus (pathogenic Staph)
b-Coagulase negative Staphylococci:
Staph.epidermidis, Staph.saprophyticus.
- They are potential pathogen ( cause disease in
immunocompromised or when displaced from
normal site to abnormal site)
2-Endopigments production:

• Staph aureus : golden yellow endopigments.

• Staph citrus (saprophyticus) : lemon yellow
endopigments
• Staph albus (epidermidis) : white
endopigments
 1-Staph aureus

• Morphology: G +Ve cocci arranged in grape like clusters, non-motile,

and non-spore forming, some have microcapsule.

• Culture characters:
➢ Facultative anaerobes.
➢ Can grow on nutrient agar producing golden yellow colonies.
➢ They produce yellow colonies on mannitol salt agar.
• Virulence factors:
A-cell wall components
1-Protein A: anticomplementary ,anti-opsonic and antiphagocytic; as it binds to the Fc of
IgG at the complement binding site thus preventing complement fixation, Opsonization
and phagocytosis.
2-Teichoic acid: adherence to mucosal surfaces.
3-Peptidoglycan-Teichoic acid complex has endotoxin like characters … septic shock.
4- Polysaccharide microcapsule: antiphagocytic, anticomplementary ,anti-opsonic
 B-enzymes:
1-Coagulase enzyme:
• Differentiate Staph. aureus from other Staphylococci
• Causes coagulation of plasma by converting Fibrinogen to fibrin --- deposited around staph
making them resistant to phagocytosis
-----(localized pyogenic infections (pus)??
• ex. Abscess, boils.
2-Bound Coagulase (Clumping factor): adherence.
3-Catalase enzyme: 2H2O2 2H2O+O2. So Its antiphagocytic
• All staphylococci are catalase positive (differentiated from streptococci which are
catalase negative).
4- Other enzymes:
-Fibrinolysin (Staphylokinase):converts plasminogen to plasmin so dissolve fibrin clots.
-Hyaluronidase: Breakdown hyaluronic acid.
-DNAase
-Beta lactamases (penicillinases): destroy B- lactam antibiotics as penicillins
 C-Toxins:
1-Exfoliative toxin (epidermolytic toxin):
➢ They are two distinct proteins A and B that are epidermolytic and cause the desquamation in scaled skin
syndrome in young children.
➢ They are superantigens and produced only by certain strains of Staphylococcus aureus lysogenized by a
bacteriophage carrying the gene for the toxin (temperate phage).
2-Toxic shock syndrome Toxin (TSST 1):
➢ It is superantigen and causes toxic shock by stimulating the release of large amounts of cytokines from T cells.
➢ causes Toxic shock syndrome
3-Enterotoxins:
➢ (6 major antigenic types A,B,C,D,E and G): cause food poisoning.
➢ Resistant to heat and to gut enzymes
➢ They are superantigens and produced only by certain strains of Staphylococcus aureus lysogenized by a bacteriophage carrying
the gene for the toxin (temperate phage).
4- Haemolysins (α, β, γ, delta).
5- Leucocidins: kills white blood cells (pus cells).
NB: Exfoliative, TSST, Enterotoxins are superantigen (they cause non-specific stimulation of T cells and the
activated T cells release cytokines that mediate shock and tissue injury) and produced only by certain strains of
Staph aureus lysogenized by a bacteriophage carrying the gene for the toxin .
 A- Localized superficial infections (pyogenic infection): due to
coagulase.
Diseases e.g. Folliculitis, boil or Furuncle, abscess, ,carbuncles .
B- Deep seated infections:
-Bacteremia, Septicemia, endocarditis, septic arthritis,
osteomyelitis, Pneumonia, meningitis, Nosocomial Infections
(hospital acquired infection).
C-Toxigenic staphylococcal disease:
 C-Toxigenic staphylococcal disease:
1-food poisoning:
• Results from ingestion of preformed enterotoxin A,C,D, not the organism,
• in contaminated food that is improperly cocked and kept unrefrigerated
for some time.
• The type of the toxin: enterotoxin (Exotoxin) its heat stable
• They cause CNS stimulation of the vomiting center after it act on the neural
receptor in the gut.
• The source of contamination is the hands or the nose of cook or food handlers
(carriers).
• Type of food: carbohydrate rich food as Koshari, cakes, milk and milk products.
• The I.P is short (1-6 h). Why fast???..........................................................
• Signs: nausea, vomiting, watery non bloody diarrhea and general malaise with no
fever???? Because it’s caused by exotoxin not endotoxin and not toxemia or
bacteremia
 2-Toxic shock syndrome:

• caused by TSST-1 = It is a superantigen and causes toxic shock by

stimulating the release of large amounts of cytokines from T cells and
macrophages.
• Observed in localized and wound infections, first observed in menstruating females using tampons.
• The toxin enters into the circulation in the absence of true infection. it’s a superantigen.
• Signs: acute onset of fever, hypotension, multi-organ failure and erythematous rash with
desquamation occurring during convalescence
3-Scalded skin syndrome (Bullos Impetigo)

• It is due to exfoliative toxin A, B

• it occurs in babies
• Signs: desquamation of the skin
and generalized bullae
formation.
Diagnosis of Staph aureus
infections

1-Sample: According to site of infection, Pus in

case of abscess, sputum, C. S .F, stool.
2-Film: G +ve cocci arranged in grape-like
clusters, Non motile,
non spore forming, some have microcapsule.
Diagnosis of Staph aureus
infections

3-Culture: Facultative anaerobic.

1-Nutrient agar (simple media) or milk
agar (Enriched media):
Staph aureus = golden yellow
endopigments.
2-Blood agar (enriched media):
-B-haemolysis (complete
haemolysis)With Clear zone around the
colonies due to production of
haemolysins (Staph β- lysine).
 Diagnosis of Staph aureus infections

3- Mannitol salt agar (selective media- Selective substance:

7.5% NaCl)
-Staph is Halophilic, tolerate 7.5 % NaCl
- Staph.aureus : pale yellow colonies surrounded by a yellow
zone due to fermentation of mannitol= Acid=Change the colour
of phenol red indicator to yellow.
- Coagulase -ve staph produce pink colonies
 Diagnosis of Staph aureus infections + ve

- ve
4-Biochemical reactions:

1-Coagulase +ve (only pathogenic Staph aureus).

Add few drops of a broth culture of the test organism to .5
ml of human or rabbit plasma …..Coagulation occurs within
few hours
2-Clumping factor: when mix a drop of bacterial
suspension with a drop of human plasma on a slide,
clumping occurs.

3-Catalse +ve (# streptococci :catalase -ve) Few drops of

H2O2 + bacterial colonies= effervescence occurs indicating
O2 production & +ve test.
Diagnosis of Staph aureus infections

4-Liquify gelatin
• Gelatinase is a proteolytic enzyme that hydrolyzes gelatin
5- Ferment mannitol.
5- Serology: ELISA for detection of antibodies.
6-Typing methods:
a-Phage typing: It is used for epidemiological tracing of the
source of infections in outbreaks of wound infections & food
poisoning.
Principle: Different strains of Staphylococci show lysis to
different types of phages. The source of infection can be
identified by comparing the isolated strains from patients with
that of suspected carrier.
b- Genotyping: by PCR,
C- serotyping
D-antibiotyping
 Treatment

• Antibiotic sensitivity test should be done.

Why??? due to rapid development of resistance
.
• 90% of S.aureus strains are resistant to
penicillin. .
• Mech of resistance: due to production of B-
lactamase (penicillinase) Origin: plasmid
encoded
• they could be treated with B- lactamase
resistant penicillins as methicillin.
• MRSA = methicillin resistant S aureus
-Mechanism of action: chromosomal mutation results in formation of Mec A gene
leading to alteration in Penicillin binding proteins PBP (transpeptidase enzymes) to
PBP2a with very low affinity to Methicillin
-Origin: chromosome encoded
-the drug of choice for MRSA is vancomycin
• VRSA: Vancomycin resistant staph aureus.
- Origin of resistance: Resistance in VRSA results from plasmid transfer of the VanA
gene from VRE (vancomycin resistant Enterococci).
-Mechanism:
1-Target alteration (alteration of cell wall D-alanin –D- alanine into D-alanin-D-
lacatate).
2- Increased Cell-wall thickness.
-Treatment of VRSA: linezolid (Zyvox) and combination ot two streptogramines
quinopristin and daflopristin (synercid) .
 Infection control:

• certain measures should be taken in hospitals to control spread of

staphylococcal infections including:
-Frequent hand washing and aseptic management of lesions.
-Treatment of nasal carriers or their removal from high risk areas, e.g.
operating rooms, intensive care units and newborn nurseries...etc.
-Antibiotic sensitivity testing to avoid empirical treatment.
Comparison between the 3 species of staphylococci?
Streptococci

• Gram positive cocci arranged in chains.

Non- motile and non- spore forming.
• Catalase - ve
 Classification of streptococci:

1- According to gaseous requirements:

All are facultative anaerobic except peptostreptococci which is obligate anaerobes.
2- According to hemolytic effect on blood agar:

B-hemolytic streptococci α - hemolytic streptococci Gama hemolytic

Produces complete haemolysis with a produces greenish discoloration of non-haemolytic

clear zone around the colonies due to
the beta haemolysin.
Ex. Str pyogenes and Str agalactiae.
blood agar due to production of
H2O2 that changes the hemoglobin
to met-hemoglobin (green)
Ex. Streptococcus viridans and Str. Strep faecalis
Pneumoniae (pneumococci)
 Classification of streptococci:

3- Lancefield classification:
Β- hemolytic streptococci are classified according to the cell wall carbohydrates antigen into
different serogroups.

g Organism C antigen
Group A Str. pyogenes. rhamnose N-acetylgulcosamine.
Group B Str. agalactia. Rhamnose-gulcosamine
polysaccharide.
Group C Str. mutans. rhamnose N-acetylgalactosamine.
Group D e.g. Str. fecalis. Glycerol teichoic acid containing
D-alanine and glucose.
4- Type-specific M-protein (Griffith's classification): (serotyped using known
antibodies the M-protein for Strept. pyogenes)
According to M protein there are more than 80 types of Str. pyogenes. A
person can have repeated infections with group A ??
5-The most recent classification is based on 16s rRNA sequencing classifies
strept. into 6 groups
1- Pyogens group: includes Str pygens and Str agalactiae. They are B-
hemolytic.
2- The other 5 groupes (Mitis group, Mutans, Bovis, Anginosus and Slivarius
group).
They are α or non-haemolytic.
Collectively named Viridans streptococci
 1- Group A β-hemolytic streptococci
Streptococcus pyogenes

• Group A, β –hemolytic streptococci, facultative anaerobic,

Bacitracin sensitive.

• Virulence factors
A) Cell wall structure
1-M protein: It is anti-phagocytic, but antibodies against M
protein may cross react with cardiac muscle → rheumatic fever.
2-Hyaluronic acid capsule: Anti-phagocytic, non-
immunogenic??? Because hyaluronic acid is a normal body
component so not identified as foreign and so not used in
vaccination.
3-Lipoteichoic acid; is another surface component that covers
the pili (consist of M protein)and mediates adherence of the
organism to mucosal surfaces.
B) Enzymes (spreading factors):

a) Streptokinase (Fibrinolysin): It converts plasminogen to plasmin which

dissolves fibrin clots.
-used in treatment of embolism and thrombus.
b) DNase (Streptodornase):4 types (A-D), DNase B is common in pyoderma
(skin infection)
c) Hyaluronidase: destroys hyaluronic acid and helps spreading of skin
infections (cellulites).
 C) Toxins

1-Streptolysins (haemolysins): There are 2 types:

-Streptolysin "O" (oxygen labile); is immunogenic, and antibodies to it [ASO] develop in Str. pyogenes infections.
-Streptolysin "S" (oxygen stable): not immunogenic. Cause B-hemolysis on blood agar.
2- Pyrogenic toxins
• Pyrogenic exotoxin A (erythrogenic toxin):-
-Produced by lysogenized streptococci carrying the gene for the toxin.
-It is a superantigen that leads to STSS and scarlet fever
• Pyrogenic exotoxin B
• It is a protease that destroy tissues causing necrotizing fasciitis.
• These strains are referred to as “flesh eating bacteria”
• Pyrogenic exotoxin C: causes STSS.
*Not all types of streptococci cause Scarlet fever?
Scarlet fever occurs by strains producing the Erythrogenic toxin. These strains are lysogenised by bacteriophage carrying the toxin
gene.
Diseases

A-Pyogenic Local infections

1-Sore throat and follicular tonsillitis : the most
common
• Mode of infection: by droplet infection
• May be followed by rheumatic fever
2-Pyoderma (impetigo)
local infection of the skin with pus formation
• Transmission : Contact with infected skin
• may be followed by acute glomerulonephritis.
Diseases
B-Invasive diseases:
1) Erysipelas:( red skin) , edema on the face.
2) Puerperal sepsis: ‫حمي النفاس‬
Infection of the uterus after delivery or abortion leading to
endometritis, septicemia and toxic shock
3-Acute bacterial endocarditis
The organism reaches the heart valve through the blood stream as a
complication of any of the primary lesions mentioned above. The
presence of a deformed or rheumatically affected valve encourages the
condition.
 Diseases
C- Toxigenic diseases
1-Streptococcus toxic shock syndrome
-mediated by production of Str. pyogenes exotoxins that
function as superantigens.

2-Scarlet fever: ‫الحمي االقرمزيه‬a disease of children

characterized by sore throat and an erythematous rash,
fever , tonsillitis , strawberry tongue It is produced by
streptococci that produce erythrogenic toxin in susceptible
individuals (i.e. have no antitoxin).
 Diseases
D-Post streptococcal immunologic diseases:
 Diagnosis of PUERPERAL SEPSIS

• Puerperal sepsis: infection of the uterus after delivery or abortion and associated with septicemia.
• Causative agent: Streptococcus pyogenes.
• Transmission: by droplet infection or from doctors, nurses, or use of non-sterile instruments
1-Sample: Uterine swab or Blood for blood culture, which is more reliable than uterine swab (WHY?)
because the swab is often contaminated by normal flora.
2- Blood culture: Addition of 5-10 ml of patient blood to 50-100 ml of nutrient broth and incubated for
7 days at 37c.
–Subculture on blood agar each 48 hours → B-haemolysis
-N.B: the large volume of broth has the following advantages:
1-Increase the multiplication of the organism which is present in few numbers in blood
2-Dilute antibodies naturally occurring in serum
 Diagnosis of PUERPERAL SEPSIS

3- Film: shows G+Ve cocci arranged in chains.

4- B.R: catalase –ve
5- Bacitracin sensitive
6- Serology: Detection of group A streptococcal carbohydrate Ag by agglutination or ELISA.
Treatment: penicillin is the drug of choice (Erythromycin & azithromycin in case of allergy)
• Blood culture is the most reliable test for diagnosis of puerperal sepsis?
N.B : Blood culture is more reliable than uterine swab in diagnosis of puerperal sepsis?
• Uterine swab may be contaminated with the normal commensals of vagina as strept
agalactia, so it will interfere with diagnosis giving false positive results while with blood
culture there is no interference.
 Diagnosis of SCARLET FEVER
• Causative agent: Streptococcus pyogenes.
• Mode of infection: droplet infection
• Pathogenesis:
• -M.o remain localized in the throat and produce erythrogenic toxin that diffuses to the
blood (toxemia), then skin producing skin rash, fever , tonsillitis , strawberry tongue.
1-Specimen:throat swab.
2-Film:stained by Gram's stain shows G+Ve cocci arranged in chains.
3-Culture:produces B- haemolysis on blood agar
4- B.R: catalase –ve
5- Bacitracin sensitive
6-Serology: Detection of group A streptococcal carbohydrate Ag by agglutination or ELISA.
 Diagnosis of SCARLET FEVER

7- Intradermal skin test

A-Schultz-Charlton reaction
-0.1ml of anti-toxin is injected directly in the skin rash: local fading and disappearance of the rash
occurs within 6-12 hours is diagnostic
-B-Dick test: to detect immunity or susceptibility against scarlet fever
-0.1 ml of a standard diluted toxin is injected in one forearm<test arm>
• Results:
-If no reaction detected in the test arm: individual is immune.
-If erythema develops within 6-12hours: individual is susceptible
Post streptococcal immunologic diseases:
Rheumatic fever
Jones criteria for diagnosis of rheumatic fever:
• Diagnosis of rheumatic fever is supported by the evidence of preceding group A streptococcal infection plus two major criteria or one
major criteria and two minor criteria.
Evidence of preceding group A streptococcal infection:
• Positive throat culture.
• Positive streptococcal antigen test.
• Elevated or rising ASO titer.
Major criteria:
• Carditis.
• Fleeting polyarthritis.
• Chorea.
• Erythema marginatum.
• Subcutaneous nodules.
Minor criteria:
• Clinical findings; fever and arthralgia.
• Laboratory findings:
➢ Elevated acute phase reactants; ESR & CRP.
➢ Prolonged PR interval on ECG.
 Post streptococcal immunologic diseases:
Rheumatic fever, acute glomerulonephritis (AGN)

• Causative agent: Streptococcus pyogenes

• Diagnosis is (mainly Serological): sample: serum
A-Specific test of diagnosis :
1-Antistreptolysin "O" test (ASOT) : specific for RF
• Principle : in vitro toxin –anti-toxin neutralization test.
• Result : Titre of Ab above 200 Todd units /ml indicates active rheumatic fever
2-Anti-DNAase B test: Specific for AGN
• High titre of Anti-DNAase B antibodies is diagnostic for acute glomerulonephritis
 Post streptococcal immunologic diseases:
Rheumatic fever, acute glomerulonephritis (AGN)

B-Non-Specific Tests:
1 - C-reactive protein (CRP): detected by agglutination
CRP is acute phase protein synthesized in the liver and appears elevated in the serum in cases of RF
,AGN and other inflammatory conditions.
2- High Erythrocyte Sedimentation Rate (ESR).
Treatment
Long-acting penicillin (as a monthly injection for several years) should be given as chemoprophylaxis to
children who had an attack of RF to prevent recurrence
**Streptococci can’t be isolated in AGN and ARF??
• ARF: autoimmune disease occur 1-4 weeks after throat infection with rheumatogenic strains of
group A , β-haemolytic strept. Pyogenes (post streptococcal).no organism in blood but only
antibodies. Strept has M.protein similar to proteins in the heart muscle (Myosin),so antibodies
against M.protein can cross react with the heart muscle leading to damage of the heart muscle.
• In AGN: post streptococcal immunologic disease occur 3-weaks of skin infection with nephritogenic
strains of str.pyogenes….it is type III hypersensitivity due to antigen antibody complex deposition
2-Group β -hemolytic Streptococci
Streptococcus agalactia

• Group B, β-haemolytic streptococci, Bacitracin resistant.

- Have Polysaccharide capsule …antiphagocytic.
- Hydrolyze Hippurate and CAMP factor positive.
- Normal commensal in vagina and can pass to infant from the birth canal
during labor.
Diseases
• It is the most common causative agent of neonatal septicemia and
meningitis
 CAMP test

• On blood agar: Strept agalactia is streaked

perpendicular to Staph aureus.
• Str. agalactia produce CAMP factor which
potentiate hemolytic activity of S. aureus β-
lysine
• Arrow-head shaped hemolysis in the
junction between staph β- &lysine CAMP
factor.
3- α-hemolytic Streptococci

• A-Streptococcus Viridans
-They are normal commensals of the oral cavity.
• Pathogenicity: ( Biofilm –mediated infection & endogenous infection)
1-Dental plaque and dental caries (mediated infection –Biofilm):
• Str. mutans adhere to teeth by slime or glycocalyx and causes dental caries.
2-Subacute bacterial endocarditis (endogenous infection)
 Subacute bacterial endocarditis
• Causative agent: viridans Streptococci
• Mode of infections:
• Predisposing factors: deformed or prosthetic heart valves
• The infection is endogenous; the organism is commensal of the oral cavity and may
reaches the blood stream during tooth extraction or tonsillectomy →settles on the
deformed valve →inflammation.
1-Sample: blood for blood culture.
2-Blood Culture.
• Subculture on blood agar → α-haemolysis.
3-Film from the culture: shows G+Ve cocci arranged in chains.
• due to close similarity between Pneumococci and strept viridans in morphology on
culture, differentiation should be done by biochemical reaction.
 Pneumococci Viridans streptococci
4-B.R:
1. Solubility in bile Soluble Not soluble
2. Inulin fermentation Fermented with acid Not fermented
3. Sensitivity to optochin Sensitive Not sensitive
4. Pathogenicity to mice Pathogenic Not pathogenic
5. Quellung test Positive Negative

5-Detection of group specific streptococcal carbohydrate Ag by

agglutination or ELISA.
Chemoprophylaxis: the infection can be prevented by giving amoxicillin
before dental extraction
 B-Pneumococci(Streptococcus pneumoniae)

• Morphology: G+ ve cocci arranged in

pairs (diplococci), capsulated
• Diseases: (Typical pneumonia) =Lobar
pneumonia otitis media, Sinusitis and
meningitis.
• Bacteremia, septicemia and Endocarditis
(must differentiate it from
Strept.viridans).
Virulence factors:

1-polysaccharide capsule: it is antiphagocytic and helps invasion.

- Capsulated organisms are virulent, no capsulated are non-virulent.
-Capsule swelling test is used for typing of pneumococci (Quellung reaction)
- Pneumococci can be classified into more than 80 serotypes according to the
capsular polysaccharide substance. Capsules may appear as unstained halos around
the organism.
2-IgA1 protease: destroys secretory IgA thus enabling the organism to colonize the
mucosa of the upper respiratory tract.
3-Penumolysin O : it attack phagocytes and mammalian cell membranes causing
lysis .
4-Lipoteichoic acid: mediate adherence & causes septic shock in
immunocompromised patients.
Diagnosis of lobar Pneumonia
• Mode of transmission: respiratory droplet
1- sample: sputum
2- Film: shows G+Ve cocci arranged in pairs
(diplococci), capsulated
3-Culture:
• Chocolate agar: small grayish white colonies
• Blood agar (5-10%CO2): α-haemolysis (greenish
discoloration) similar to viridans streptococci ------
aerobic conditions
• B-haemolysis ------ anaerobic conditions
Diagnosis of lobar Pneumonia
Pneumococci Viridans streptococci
4-B.R: • Solubility in bile Soluble Not soluble
• Inulin fermentation Fermented with acid Not fermented
• Sensitivity to optochin Sensitive Not sensitive
• Pathogenicity to mice Pathogenic Not pathogenic
• Quellung test Positive Negative

5- Serology: detection of pneumococcal capsular polysaccharide Ag by

agglutination & ELISA.
Treatment : penicillin ,Vancomycin for penicillin
resistant pneumococci.

• Prophylaxis:
1- PNEUMOVAX : A polyvalent (23 type) polysaccharide capsule vaccine .
-Effective and provides long lasting protection recommended for susceptible
immunosuppressed individuals
2- PREVNAR 13: A pneumococci conjugate capsule vaccine:
Contain polysaccharide capsule of the 13 most common pneumococcal serotypes
coupled to carrier protein.
-It’s recommended for children at 2, 4, 6 months and at 12-15 months
 Enterococci (Lancefield group D)

• Ex. E. faecalis (E. faecium).

• Pathogenicity: Enterococci are normal inhabitants of the intestine,
• Predisposing factors: GIT or urinary tract surgery or instrumentation (catheters)
• Disease: nosocomial infections particularly in intensive care units as
-urinary tract infections ,Endocarditis, intra-abdominal and pelvic infections
(peritonitis)in combination with anaerobes, Wound infections, meningitis and
bacteraemia in neonates.
- The organism is transmitted from patient to patient by the hands of hospital
personnel.
 Diagnosis:

• Sample: urine , blood , pus , wound , ……….etc

• Morphology: They are gram positive cocci in short chains.
• Culture: grow well between 10-45°c
- Bile esculin media contain 6.5% NaCI→ black colonies (hydrolyze esculin)
- Bile esculin media containing vancomycin is used to detect VRE (vancomycin resistant enterococci).

- MacConkey's agar →rose pink colonies.

- Blood agar →non-haemolytic or alpha hemolytic .
• Biochemical test : Catalase –ve
Treatment:
• A major problem with enterococci is that they can be very
resistant to several antibiotics.
• They are intrinsically resistant to cephalosporins,
penicillinase-resistant penicillins and mono-bactams
a-Combined penicillin and aminoglycosides
b- Vancomycin for treatment of penicillin resistant strains
c- Vancomycin resistant enterococci VRE by Linezolid, a
combination of two streptogramins, quinupristin / dalfopristin
(synercid)….as VRSA