Staphylococcal and Streptococcal infections

What are the WBC features of bacterial infection ?

The answer

• Leucocytosis
• Shift to left
• Toxic  granules
• Cytoplasmic vacuoles
• Doehle bodies:  Discrete round or oval density in the periphery of cytoplasm. Stains sky blue with Romanowsky stain
• Disappearance of Eosinophils

What are the types of shock you can encounter with infection?

The answer

• Septic Shock
• Toxic Shock

What are the features of septic shock?

The answer

• Evidence for sepsis
• Low blood pressure
• Multiple organ failure

What are the features of toxic shock syndrome?

The answer

Toxic shock

• Evidence for infection
• Evidence for toxin
  • Erythematous rash
  • GI symptoms 
• Low blood pressure

Which organisms can give rise to Toxic shock syndrome ?

 The answer

• Staphylococcus aureus producing a toxin (TSST-1)
• Streptococcus pyogenes producing pyrogenic exotoxin A, B. or C. 

Describe  toxic shock syndrome toxin (TSST-1) and how it produces the clinical picture?

The answer

• TSST-1 is a true exotoxin 
• It is secreted during cell growth rather than after cell lysis. 
• This toxin is a super antigen which activates T cells by binding antigen-presenting cells to the V$ chains of the T-cell receptor. 
• Super antigens can activate 5-25 % of the total T-cell population rather that 1-2% activated by the more physiological mechanism of processed antigen causing excessive release of cytokines (IL-2, TNF), that leads to many signs and symptoms of the illness.

Who is prone to develop toxic shock syndrome due to staphylococcal infection?

The answer

• The initial epidemic of TSS was that the disease was most severe in women who used super absorbent tampons.

• It is known that TSST-1 is produced under conditions of low magnesium ion concentration. 

• It is speculated that the tampons act to absorb various ions including magnesium, providing optimal conditions for production of TSST-1.

• These strains are found in surgically related infections and at other body sites.

The answer

• In order to prove that an isolate is the etiologic agent of toxic shock syndrome, it should be demonstrated that the isolate produced Toxic Shock Syndrome Toxin-1 (TSST-1).

How do you manage toxic shock syndrome?

The answer

• Therapy consists of fluid and electrolyte replacement 
• Identification and drainage of any focally infected site, such as an abscess.
• Antibiotic therapy should be based on the susceptibility pattern of the isolate. The following antibiotics can be used

Penicillin

• Nafcilllin
• Oxacillin
• Dicloxacillin

Methicillin resistant Staph aureus

• Vancomycin
• Trimethoprim-sulfamethaxazole

What are the clinical presentations of  S. aureus  infection

The answer

• Impetigo
• Deep infections: (Abscess,  Osteomyelitis , Cellulitis, Lung abscess etc) 
• Toxic shock syndrome
• Acute infective endocarditis

Is staph aureus an opportunistic infection or can it affect patients with normal immunity?

The answer

• It can affect patients with normal immunity
• Both Staphylococcus aureus and Streptococcus pyogenes (group A strep) have many enzymes which act as virulence factors allowing these bacteria to invade tissue from patients with normal immunity 
• The toxins enable them to spread from infection at a local site to the bloodstream.   

What are the common causes for Pharyngitis ?

The answer

• Viruses
• Streptococcus pyogenes

Viral pharyngitis occurs at least as frequently as strep pharyngitis.

How do you distinguish viral from streptococcal pharyngitis?

The answer

• It is very difficult to distinguish between the two by physical examination of throat
• You need a culture to establish the diagnosis 
• An antigen screen  for Streptococcus pyogenes is also very useful

10 year old girl is brought to your office with sore throat. Her mother is very concerned about strep throat and is anxious for you to prescribe penicillin. How would you proceed?

The answer

• Pharyngitis is caused by virus or strep with high degree of frequency and they are indistinguishable by physical examination.
• You do not want to prescribe penicillin indiscriminately.
• Throat cultures take about 48 hours.
• It is best to do a throat swab for antigen screen  for Streptococcus pyogenes, the results can be obtained within 45 minutes. 
• Based on the result you can initiate penicillin therapy.

Describe the clinical setting when you will consider Rheumatic fever?

The answer

Patients present with joint pain and history of sore throat about 3 weeks ago. There is a time lag between Pharyngitis and onset of joint pain

• Joint pain and swelling
• History of pharyngitis
  • Throat cultures are negative by the time the joint symptoms are apparent
• Onset of new murmur in heart

How often does rheumatic fever follow Streptococcal pharyngitis.?

The answer

• Rheumatic fever occurs in about 3% of times following Streptococcal pharyngitis.
• Rheumatic fever is a non-suppurative sequela of Streptococcus pyogenes infections

What are the characteristics of rheumatic fever?

The answer

Rheumatic fever is characterized by

• Migratory ployarthritis

• Carditis

• Sub Q nodules

• Erythema marginatum

• Sydenham Chorea

Describe the hemolysins of Streptococcus pyogenes 

The answer

Colonies of Streptococcus pyogenes are beta hemolytic due to two distinct hemolysins: 

• streptolysin S

• streptolysin O 

  • Cytotoxin, lyses RBC's and WBC's

  • streptolysin O is oxygen labile, unlike streptolysin S. 

  • Cultures must be incubated anaerobically or the blood agar plates must be stabbed to demonstrate the streptolysin O 

How can we link rheumatic fever to streptococcal infection ?

The answer

There is a time lag between pharyngitis and onset of joint pain and by that time throat cultures are negative.

• An elevated ASO titer in individuals with appropriate clinical symptoms supports the diagnosis of RF

• Patients with RF will frequently mount (80%) a humoral immune response to streptolysin O. 

• The test used to measure antibodies against this hemolysin is called an ASO (anti-streptolysin O) titer. 

Describe the pathogenesis of rheumatic fever

The answer

• The cell wall (Pili) of Streptococcus pyogenes contains M protein an important virulence factor 

• M protein has been found to be antiphagocytic and it also has epitopes which are antigenically similar to one found in the cardiac myosin and sarcolemmal membrane proteins.

• Acute RF is thought to be an auto-immune disease. 

  • Antibodies directed against M protein cross-react with cardiac tissue. 

  • These antibodies bind to the cross-reactive antigens in muscle and damage the muscle tissue. 

  • Other group A strep antigens may also cross-react with other cardiac antigens causing damage to the heart valves. 

How does Rheumatic fever manifest pathologically?

The answer

• Acute : Causes Pancarditis (Pericardium, Myocardium and endocardium)

• Chronic: Progressive valvular fibrosis with thickening and sclerosis of valves, adhesion of commisures, thickening, shortening and adhesions of chordee, calcification.

What are the other virulence factors of  Streptococcus pyogenes ?

The answer

• Hyaluronidase

• DNase

• Streptokinase : Lyses fibrin clots

• Erythrogenic toxin.

These enzymes help spread infection further into tissue.

What are the clinical presentations of group A streptococcal  infection?

The answer

Infective

• Pharyngitis: Sorethroat, fever, cervical lymphadenopathy, swollen red tonsils with white or yellow patches

• Necrotizing Fascitis: Bacterial infection of fibrous tissue that covers the body beneath the skin. "Flesh eating bacteria" . Significant mortality.

Auto-immune

• Rheumatic fever: Auto-immune process. Systemic inflammation affecting Heart, Joints and Skin.

• Acute Glomerulonephritis: Auto-immune process.

Toxic

• Toxic shock syndrome:  Pyrogenic exotoxins A,B or C. Stimulates T cells to release of Cytokines. Shock and failure of multiple organs. Superantigens

• Scarlet fever is a manifestation of group A streptococcal pharyngitis in which the infecting strain produces a specific virulence factor called erythrogenic toxin, which is coded for by a phage.

  • Production of this toxin is manifested clinically by the appearance of a scarlatinal (bright red) rash beginning on the chest and spreading to the trunk and neck, then to the extremities. The rash is not seen on the face, or the palms or soles. 

  • A "strawberry" tongue is frequently seen with this disease as well. 

  • Rheumatic fever can be a post-streptococcal sequela of scarlet fever just as it may be follow strep throat caused by strains which do not produce erythrogenic toxin. 

How would you treat group A streptococcal  infection?

The answer

Depends on the clinical presentation

• Penicillin for 10 days to prevent recurrence or complications
• Symtomatic therapy (Tylenol, Fluids and electrolytes)
• Complications ( Acute glomerulonephritis, Carditis etc)
• Surgical debridement: in Necrotizing fascitis

Infective endocarditis

What do you understand by the terms acute and subacute infective endocarditis?

The answer

• Acute infective endocarditis.

  • Normal intact endothelium resists implantation by organisms. 

  • Very virulant pathogens may be able to cause endovascular infection. 

• Sub acute infective endocarditis:

  • If there is damaged valves the organisms can implant on them. 

  • Endothelial injury inflicted by the organisms release tissue factors to activate platelets and fibrin-platelet vegetaions ( clot ) forms.  

  • These start off as non-bacterial thrombotic endocarditis (NBTE).

  • Organisms of low virulence colonize these NBTE and cause endovascular infection.

What are the common organisms leading to acute infective endocarditis?

The answer

Very virulant pathogens

• Staphylococcus aureus

• Psudomonas aeruginosa

• Streptococcus pneumoniae

• Neisseria Gonorroheae

What are the common organisms leading to sub acute infective endocarditis?

The answer

Low virulant pathogens

• Strep viridans

• Enterococus

What are the signs and symptoms of infective endocarditis ?

The answer

The manifestations of infective endocarditis are protean since any organ can be involved.

• Infective: Fever, Weight loss, anorexia, malaise, splenomegaly, leucocytosis

• Vegetations: New murmurs, destruction of valve leading to insufficiency followed by hear failure

• Embolic: 

  • Stroke

  • Janeway lesions (erythematous macules and papules on the palms and sole)

  • Osler nodes (tender raised erythematous lesions on the finger and toe pads ) 

  • Splinter hemorrhage in the nail beds

  • Roth spots (Petechiae in retina with white centers)

• Clubbing

What is the best way to demonstrate vegetations on the valve?

The answer

• An echocardiogram  

How do enterococci cause infection?

The answer

• The enterococci  require a breakdown of host's defenses or mucosal barriers to cause infection. 

• The enterococci do not have M protein, hemolysins, or toxins 

What are the common infections caused by enterococci ? Why are they significant infections?

The answer

• urinary tract infections

• mixed bacterial wound infections

• sub-acute bacterial endocarditis

• can cause sepsis and rarely meningitis. 

The enterococci are normal flora of the gastrointestinal tract and are present in the gastrointestinal tract . They lack the virulence factors of the staphylococci and beta hemolytic streptococci, but are significant pathogens because of their intrinsic antimicrobial resistance.

How effective are antibiotics when sbe is due to enterococcal infection?

The answer

• Enterococcus is not susceptible to vancomycin and ampicillin

• Most likely species is E. faecium, which is intrinsically resistant to ampicillin and has acquired a gene to change its cell wall composition so that vancomycin can not disrupt cell wall synthesis and inhibit the growth of the bacteria.

• In addition the orgnims are inside avascular vegetations,  Antibiotis and Phagocytes do not have easy access. 

• They are also in lower metabloic state.

What are the preventive measures to be undertaken with Vancomycin resistant enterococcal infections (VRE)?

The answer

Prevention

• Patient  must be placed on barrier precautions, which entails gloves and gown for anyone handling the patient or objects in their environment.

  • When a patient has VRE, most likely they are carrying the organism in their GI tract. 

  • Items in their room readily become colonized so that VRE can be isolated from bed rails, call buttons, etc

• Hand washing is an important means by which the transmission of VRE can be reduced.

• A mask is not required. 

S. epidermidis 

What is an opportunistic pathogen?

The answer

• Organisms requiring a breakdown of the host's skin or mucosal barriers to cause infection. 

How does staph epidermis cause infection ?

The answer

• Opportunistic pathogen

  • S. epidermidis and other coagulase negative species of staphylococci are normal commensals of the skin, anterior nares, and external ears in humans and animals. 

  • This organism that does not produce the virulence factors that more pathogenic organisms do. 

  • S. epidermidis, require a breakdown of the host's skin or mucosal barriers to cause infection. 

  • The introduction of central lines, venous catheters, or prosthetic devices provide an entrance route to the body for these organisms

• Once the barrier has been compromised, S. epidermidis may produce "slime", a biofilm that aids in the adherence of the bacteria to the synthetic surface of the device and protects the bacteria from phagocytosis and antimicrobials.

• Neonates and neutropenic patients are particularly at risk. 

What is the significance of positive blood culture for staph epidermis ?

The answer

• Because coagulase negative staphylococci are present on the skin, identification of staphylococci in blood cultures may represent either contamination or a clinically significant finding. 

• Distinguishing between the two is often difficult.

How would you treat staph epidermis infections?

The answer

• Antimicrobial therapy may eliminate the organisms from the blood stream. 

  • Coagulase negative staphylococci are usually resistant to oxacillin, nafcillin, and methicillin.

  • If the isolate is methicillin resistant, treatment with the first generation cephalosporins is not effective. 

  • Vancomycin is usually the drug of choice for methicillin resistant staph infections.

• If bacteremia persists inspite of appropriate antibiotics, the catheter or the prostehtic devise must be removed for eradication of the infection.