Staphlococcus Flashcards
Is S. epidermidis, S. aereus, or S. saprophyticus described as the following:
• Catalase positive, coagulase positive, ß-hemolytic, ferments mannitol
S. aureus
Is S. epidermidis, S. aereus, or S. saprophyticus described as the following:
• Catalase positive, coagulase negative, non-hemolytic, urease positive, does not ferment mannitol, novobiocin resistant
S. saprophyticus
Is S. aereus, S. saprophyticus, or S. epidermidis described as the following:
• Catalase positive, coagulase negative, non-hemolytic, urease positive, does not ferment mannitol, novobiocin sensitive
S. epidermidis
What key factors differentiate staph aureus from S. epidermidis or S. saprophyticus?
S. aureus is coagulase positive and can ferment mannitol (the others cannot)
What key factors differentiate S. saprophyticus from S. epidermidis?
• S. epidermidis is novobiocin sensitive and S. saprophyticus is resistant
Which of the following can staph species do?
• Motility
• Spore Production
• Catalase Production
staph is nonmotile, does not produce spores, but DOES produce catalase
T or F: staphyloccus aureus is a member of the normal flora.
True, mostly in the nose
Here’s a list of what staph aureus can do for you:
• abscessses
• Septic arthritis
• Endocarditis
• Food poisoning
• Scaleded Skin Sydrome
• Toxic Shock Syndrome (TSS)
• Hosptial-acquried PNA
• Septicemia
See back
- Surgical wound infections
- Folliculitis
- Impetigo
- Bacterial Conjunctivitis
What is the primary location that you can find staphlococcus epidermidis?
• Infections that is causes?
Found on the skin and really good at bioflim formation
- Endocarditis (with heart valves)
- Prosthetic joints/Harward
What is the major infection caused by staph. saprophyticus?
UTIs
# Define the Carrier State? • who typically falls in this category?
Carrier state - you harbor the pathogen and pose a risk of infecting others.
This typically refers to those who carry an asymptomatic infection or those who have just recovered from a disease
Define colonization.
The bacteria is on you/ in you but it has not intiated an infection yet but it still might, or your immune system might get rid of it before you ever knew it was there.
Define colonization resistance.
non-pathogenic bacteria occupy the attachment sites where most bacteria would try to infect and thus they prevent colonization by pathogenic bacteria
Staphylococcus aureus
• morphology
• coagulase/catalase characteristics
• Hemolysis on blood agar
• fermination
• Mechanism of resistance to penicillin? methacillin?
Staphylococcus aureus forms gram positvie cocci in cluster that are coagulase and catalase positive and produce beta-hemolysis on blood agar. S. aureus can also ferment mannitol.
MOR penicillin:
• this is intrinsic resistance in the majority of staph strains in which the S. aureus codes for a ß-lactamase
MOR methacillin:
• methacillin has a bulky side group to try to prevent ß-lactamases form working however, methacillin resistant S. aureus has mecA gene that codes for new Penicillin Binding Proteins
T or F: 50% of the hospital strains that are isolated are MRSA
True
**Side note: remember that the coagulase test is done with rabbit serum**
Staph. aureus is a part of our normal flora. Where is it typically found?
• is there an increased risk of infecting yourself if you are colonized?
- 30% of people are colonized by S. aureus in their nasal cavity at any given time => this leads to an increased risk of skin infections in these people
- People often have staph on their hand
• 5% of women have colonized vaginas
What is the underlying pathogenesis of all diseases caused by S. aureus?
Toxin production and pyogenic inflammation
Staphyloxanthin (carotenoid)
• what is it?
Virulence factor of S. aureus that produces the golden color of staph colonies and is responsible for inactivating the microbiocidal effects of Superoxides and other ROS in neutrophils
Coagulase
• what is it?
Virulence factor of S. aureus that causes conversion of prothrombin (II) to thrombin (IIa) that then allows cleavage of fibrinogen to fibrin. Clot formation allows Staph to wall itself off from the immune system.
(Remember the vit K dependent factors? they are II, IX, XI, X, protein S and protein C)
Hemolysins
• what do they do?
Virulence factor of S. aureus that cleaves RBCs to recover iron that is needs to grow.
(Remember: its the job of serum hepcidin and serum ferritin to bind up iron so that this doesn’t happen regularly)
Protein A
• what is it?
Virulence factor of S. aureus that binds the Fc region of IgG and thus prevents the activation of complement because there is a reduction in C3b production which greatly reduces phagocytosis of organisms
(note: C3b is needed to complete all paths, it is an important component of C5 convertase (C3bC2aC4b - classic) (C3bx2 + Bb - alt) that generates C5a to work as MAC and chemoattractant, it also can bind to CR1 (complement receptor -1) on macs to directly affect phagocytosis)
Teichioic acids
• what are they?
Virulence factor of S. aureus that mediate adherance of staph to mucosal cells and also induces IL-1 and TNF release from macrophages (via binding to TLR-2)
Polysaccharide Capsule
• what is it?
• Serotypes? most virulent?
Virulence factor of S. aureus that allows bacteria to attach to artificial materials and resist host cell phagocytosis
There are 11 serotypes with type 5 and 8 being to most virulent
Peptidoglycan
• what does it do?
Virulence factor of S. aureus that acts as an endotoxin-like protein that stimulates cytokines production and coagulation/complement cascades leading to gram positivie septic shock (gram + response to Lipid A in LPS of gram negatives?)
**Remember with endotoxins there must be an actual bacteremia for it to have its effects, as opposed to exotoxins or superantigens.
Alpha Toxin
• what does it do?
Virulence factor of S. aureus that forms holes in hosts cells and forms skin necrosis and hemolysis
Panton Valentine (P-V) leukocidin
• what does it do?
• What strains is it produced by?
• Disease manifestations?
Virulence factor of S. aureus that forms pores (like granzymes) and causes leukocyte destruction by damaging cell membranes and causes tissue necrosis leading to SEVERE SKIN/SOFT tissue infection and SEVERE necrotizing PNA.
• Typically this guy is produced by COMMUNITY acquired MRSA
Gamma-toxin/leukotoxin
• what does it do?
Virulence factor of S. aureus that lyses Phagocytes/RBC’s
Why do we end up with Community acquired S. aureus that has PVL toxin and MRSA?
*****This is related to Community Acquired MRSA NOT Hospital acquired MRSA*****
This happens through 2 separate Events:
Methacillin Sensitive S. aureus (MSSA) gets attacked by a bactiophage (phiSLT) that lysogenically implants LukS-PV and LukF-PV genes that encode for PVL.
HORIZONTAL Transfer (see image below) allows for the aquisition of the mecA (methacillin resistant cassette - SCCmec IV, V or VT) gene that is transferred to the MSSA strain that has PVL already
Exfoliatin/Exfoliative toxins A and B
• what do they do?
Virulence factor of S. aureus that cleaves desmoglein in desmosomes, leading to separation of the epidermis at the granular cell layer (stratum granulosum)
These are responsible for scalded skin syndrome (babies) and impetigo (older ppl.)
What is the clinical presentation of scladed skin syndrome in babies?
• what causes it ?
Exfoliatin/Exfoliative toxins A and B are responsible for SSS
Clinical Presentation:
• Typically this is a baby 3-7 days old that begins developing an rash around his mouth and becomes febrile and irritable then 1-2 days later you he develops blisters at a flexural areas, butt, hands and feet.
What are some of the complications of Scalded Skin Syndrome?
• what does the healing processes look like?
• how long does it take to recover?
• are mucous membranes ever involved?
We see lots of serous fluid exudates leading to dehydration and electrolyte imbalance this this then leads to a healing phase where we see flakey desquamation and sloughing as lesions heal. Recovery typically occurs in about 10 days.
Does SSS leave a scar?
• why or why not?
NO - all pealing that takes places is intraepidermal so dermis is never exposed - all skin that is falling off is already dead.
Remember the target of exfoliative toxins A and B is desmoglein in desmosomes
Exfoliative toxins of s. aureus targets desmoglein and so do antibodies in pemphigus vulgaris. But pemphigus attacks both types
Enterotoxin (A)
• what does it do?
• symptoms that its causes?
Virulence factor of S. aureus acts as a superantigen in the GI tract that stimulates IL-1 and IL-2 secretion from macrophages and helper T-cells the result of this is prominents vomitting (induced in CNS) and watery, non-bloody diarrhea.
You just ate some food that contained staph. aureus enterotoxin A. but you cooked it first.
• will you get sick?
• If so, how long before you get sick and how long will it take before it goes away?
Enterotoxin A is heat resistant so unless you cook your food for long enough you aren’t going to get rid of of it. Therefore, you might get sick and if you do it will happen in 1-8 hours and you’ll stay sick for about 24 hours.
What other disease besides scalded skin syndrome is caused by s. aureus exfoliative toxins A and B?
• what are some characteristics of this disease? be specific.
• Exfoliative toxin is localized at the site of infection in Bullous impetigo as opposed to SSS where it disseminates over the entire epidermis. The site of infection is typically on the trunk. This causes the formation of bullae with clear yellow fluid that later become darker and more turbid. Ruptured bullae leave a thin brown crust.
How can you tell the difference in impetigo that is cause by staph. aureus and GAS just on the basis of anatomic location?
Staph aureus impetigo is localized to the trunk typically, while GAS is found around the mouth.
What are some signs and symptoms that may indicate that someone is getting toxic shock syndrome?
All the typical signs of shock: Fever, hypoTN, end-organ failure (renal failure, transaminitis or hyperbilirubinemia), DIC (thrombocytopenia), Altered mental status
Signs more specific to Toxic Shock: Severe myalgia with CPK elevation, Vomitting/diarrhea, Diffuse macular erythroderma that desquamates 1-2 weeks after onset.
***Note: this may be more likely to happen in white people***
What is the pathogenesis of toxic shock syndrome?
TSST (toxic shock syndrome toxin) produced locally in the vagina/nose/post-op wounds by S. aureus enters the bloodstream and induces polyclonal activation and proliferation of CD4+ T cells (by locking the alpha chaing of MHC class II to the Beta-chain of any random TCR). This stimulates the release of cytokines like IL-1, IL-2, and TNF.
**The advantage to activating random T cells is that it prevents the appropriate oligoclonal response that is specific to pathogen antigens**
Studies show that 5-25% of S. aureus isolates have the TSST gene. Why don’t more people get TSS with S. aureus infections?
• what if you do blood cultures on these people?
TSS only occurs when people don’t have antibodies against TSST
**Blood cultures would be negative**
T or F: to diagnose someone with TSS you much isolate the bacteria.
False, the cause should be fairly obvious like a tampon, nasal packing, or infected surgical wound. BUT things may not look AS infected as you might expect
How do you treat MSSA?
- Nafcillin/Oxacillin
- Some cephalosporins (cefazolin, ceftriaxone, cefepime, ceftaroline)
- Vancomycin
- Augmentin (amoxi/clav) if infection is mild
How do you treat MRSA?
- Vancomycin
- Daptomycin
- Linezolid
- Ceftaroline
- Bactrim/Clinda/Doxycylcine => for mild infections
How do we treat VISA/VRSA?
- Daptomycin
- Linezolid
- Ceftaroline
How do we treat patients with TSS?
• 3 general ways.
Supportive - 10-20 liters of fluid with vasopressors like dopamine and norepinephrine (helps prevent hypotension)
Surgical - look for and remove tampons from vaginal canal or explore surgical wounds (remember they may not look as bad as you would think)
Antibiotics - Vanc/Oxacillin (depending on resistance) + CLINDAMYCIN
Why is clindamycin a must-have in Toxic Shock Syndrome?
• what other drug a
• Clindamycin and Linezolid are able to supress protein synthesis and thus STOP THE SYNTHESIS of the SUPERANTIGEN
What mechansims or resitance are used in the following stains of staph. aureus.
• MRSA
• VRSA
• VISA
MRSA - altered PBPs that have oxicillin/napicillin as substraits
VRSA - changes D-ala-D-ala bond for a D-ala-D-lac in the cell wall
VISA - synthesisizes a very thick cell wall
What is the D-test to evaluate for Clindamycin susceptibility?
• why is it needed?
We need the D-test because it may look up front on the sensitivities like the bug is sensitive to Clindamycin BUT if you expose the bug to erythromycin (left) and clindamycin on the right, you might see a D shape. This indicates that the erythromycin disk has induced resistance in the bacteria surrouding it. If you see this then DO NOT USE CLINDAMYCIN.
How do we keep people from getting S. aureus in the perioperative period?
• Give them Cefazolin +/- Vanc depending on teh MRSA rate in the area
What should you do to prevent S. aureus infections in people that get recurrent boils?
• how long do you continue the therapy?
- Intranasal Mupirocin to reduce colonization + Hibiclen (chlorhexidine gluconate) for bathing ± Abx (doxy and TMX/SMX)
- This is done for a week
S. epidermidis
• morphology?
• Catalase/coagulase characteristics
• Hemolysis
• Urease ability
• Mannitol fermentation
• Novobiocin Sensitive
S. epidermidis is a gram positive cocci that forms in clusters and is catalase positive and coagulase negative. It is non-hemolytic on blood agar and does not ferment mannitol. It is also sensitive to Novobiocin and has urease activity.
What reaction does urease in S. epidermidis catalyze and what human enzyme catalyzes a similar reverse reaction?
Urease catalyzes the following reaction:
Urea –> NH3 + H2O
A positive test will be Bright Pink in solution
**human enzyme that catalyzes the reverse reaction is carbomyl phosphate synthetase 1 (CPS1) - makes carbomyl-phosphate that reacts with orinithine to become citruline via (OTC) then arginine so that nitrogen waste can get moved out of the blood**
If you swabbed your whole body, where would S. epidermidis show up?
S. epidermidis would show up as Normal Skin flora and on Mucous membranes
While S. epidermidis has the ability to cause osteomyelitis, what is the most prominent infection that it causes?
S. epidermidis is good at forming biofilms (probably via quorum sensing) so it forms infections in prostheses at the time of implant (e.g. IV catheters, heart valves, joints)
Explain how S. epidermidis adheres to material and forms biofilms.
Once the prosthesis is inserted into the body it is coated in host protein like fibrinogen and fibronectin that serve as adhesion sites for Staph species via adhesins. After adherence the S. epidermidis species begins to secrete polysaccarides that shield the bacteria from our immune system and drugs.
**S. aureus can form a biofilm as well, but this is not its primary virulence factor**
You get preliminary gram stains on bacteria isolated via blood culture and it indicates gram positive cocci in clusters. Why should you wait until all tests are run and assess the patient before freaking out?
S. epidermidis is normal skin flora so it commonly contaminates cultures and before coagulase and mannitol tests are run it may even look like the patient has S. aureus. Assess the patient and look at the test (how many cultures showed growth).
Additionally, if the patient doesn’t have any hardware its unlikely that they have S. epidermidis even with positive tests
What are the drugs of choice in the treatment of S. epidermidis?
• how does this change depending on if strains are MSSE or MRSE?
#1 remove the device if possible.
- Vancomycin (D-ala/D-ala blocker - red man) for MRSE or Oxacilllin/nafcillin (PBP inhibitors w/ penicillinase resistance - macolopapular rash/renal elimination) for MSSE
- Rifampin (RNA pols inhibition - orange pee) and Gentimicin (16s unit blockage in 30S ribosome - hearing loss) should be use for prosthetic valve endocarditis
S. saprophyticus
• Morphology
• Hemolysis
• Urease ability
• Mannitol Fermenation
• Novobiocin
S. saprophyticus is a gram positive cocci that is gamm-hemolytic (no hemolysis). It has urease abilities but lacks the ability to ferment mannitol. It is novobiocin resistant.
**Note that novobiocin resistance is key to distinguishing this from S. epidermidis, which is sensistive to novobiocin**
A women comes in with a UTI that is not E. coli, her history indicates that she has had sex in the last 24 hours. What is the most likely cause of infection?
• how would you treat her?
S. saprophyticus is the second most common cause of UTIs in women and most have had sex in the last 24 hours.
Treatment:
• Ciprofloxacin (fluroquinolone -> topoisomerase inhibitor, tendon rupture)
• Bactrim (TMX/SMX -> DHFR inhibition and Dihydropteroate synthetase inhbition -> synergy, G6PD deficiency contraindication)
S. aureus
Catalase positive, coagulase positive, Beta-hemolytic, ferments mannitol
S. epidermidis
Catalase positive, coagulase negatvie, gamma-hemolytic, urease positive, does not ferment mannitol, novobiocin sensitive
S. saprophyticus
Catalase positive, coagulase negative, gamma-hemolytic, urease positive, no fermentation of mannitol, novobiocin resistant
What is the importance of Catalase as a virulence factor?
H2O2 is part of what makes neutrophils such good killers
**Remember: H2O2 is generated by Myeloperoxidase in neutrophils (only neutrophils) and lack of this enzyme may be detected by recurrent infections with Candida**
**Don’t confuse myeloperoxidase deficiency with NADPH oxidase deficiency (x-linked) that causes chronic granulomatous disease leading to recurrent infections**
The coagulase test is performed with __________.
The coagulase test is performed with Rabbit Serum
