Clinical Infectious Diseases: An Introduction

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Clinical Infectious Diseases An Introduction

• Charles S. Bryan, M.D.
• November 19, 2007

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What do you see in this picture?
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Infectious Diseases Mortality/100,000
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Case 70 year old WM

• September 29 Cold caught while returning from
  Scotland
• October Bronchopneumonia
• November Pneumonia Type 3 pneumococcus and M.
  catarrahalis isolated later Pfeiffers
  bacillus (Haemophilus influenzae) isolated
• December Surgery for empyema and lung abscess
  foul odor to pus
• December 29 Hemorrhage from wound, expired

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Parade of pathogens
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Staphylococcus aureus

• Gram-positive cocci in clusters
• Distinguished from other staphylococci on basis
  of gold pigmentation of colonies and positive
  results of coagulase, mannitol-fermentation, and
  deoxyribonuclease tests

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S. aureus pathogenesis

• 30 to 50 of humans have nasal colonization with
  10 to 20 being persistently colonized
  (colonization seems to involve staphylococcal
  protein and mucin carbohydrate)
• Colonization increases risk of infection
• Foreign bodies increase risk of infection

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S. aureus
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S. aureus epidemiologic trends

• Increasing incidence of nosocomial disease due
  especially to device utilization
• Methicillin-resistant strains have increased both
  in hospitals and in the community

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Panton-Valentine Leukocidin

• An exotoxin that induces pore formation in
  polymorphonuclear neutrophils and monocytes,
  leading to activation, degranulation, and release
  of inflammatory mediators
• Associated with skin abscesses, furuncles, and
  severe necrotizing pneumonia

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Outbreak of MRSA infection in a profootball team
(NEJM 2005 352 468-475)

• Eight MRSA infections among 5 of 58 players, all
  at sites of turf abrasions
• All had Panton-Valentine leukocidin and genes for
  mec type IVa resistance

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Classifications of streptococci

• Vancomycin-resistant strains a distinct
  possibility
• Hemolysis patterns alpha, beta, gamma
• Growth patterns aerobic, anaerobic,
  microaerophilic
• Antigenic components Lancefield groups (A, B, C,
  D, etc.)
• Biochemical reactions specific species
• DNA analysis

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Viridans streptococci

• One-half of all cases of endocarditis
• However, up to one-half of blood isolates may be
  contaminates, since organisms can be transient
  skin flora
• Nutritionally-deficient variants require B6,
  satellite around staphylococci

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Viridans streptococci (2)

• S. mutans dental caries
• S. sanguis, S. mitis, S. salivarius endocarditis
• S. anginosus abscesses
• S. bovis association with colon tumors

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Lancefield groups highlights

• Group A (S. pyogenes) Pharyngitis, scarlet
  fever, cellulitis, glomerulonephritis, rheumatic
  fever, toxic shock syndrome, fasciitis
• Group B (S. agalactiae) Septicemia in newborn
  infants and their mothers
• Group D S. bovis (carcinoma of the colon)
• Groups C, F, G assorted syndromes

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Streptococcus pyogenes (1)

• Fimbriae external to cell wall constitute major
  virulence factor and contain M protein of which
  there are 70 types
• Facultative anaerobes. Beta-hemolysis. Usually
  sensitive to bacitracin (A disk)
• Lancefield grouping C polysaccharide
• T antigens slide agglutination
• Hemolysins streptolysin O (ASO titer) and
  streptolysin S explain beta-hemolysis

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Streptococcus pyogenes (2)

• Erythrogenic toxin synthesized as result of
  infection by a temperate bacteriophage
• Nucleases extracellular enzymes produced by most
  strains. Antibodies to DNAse B useful in
  serologic diagnosis
• Streptokinase catalyses conversion of
  plasminogen to plasmin (thus, fibrinolytic)
• Hyaluronidase hydrolyzes hyaluronic acid

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Streptococcal M protein

• Identified by Rebecca Lancefield (1928)
• Enables organism to resist phagocytosis by PMNs
  in the absence of type-specific antibody
• At least 85 serotypes have been identified
• Appearance of type-specific opsonizing antibodies
  correlates with the elimination of streptococcal
  pharyngitis

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Streptococcus pyogenes
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Whats your diagnosis?

• 39-year-old truck driver with sensory loss in
  right leg due to sciatic nerve surgery for
  neuroma
• Presents with cellulitis with bullae,
  hypotension, renal failure, and a low platelet
  count

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Answer Streptococcal toxic shock syndrome

• Blood cultures positive for
• Streptococcus pyogenes

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Enterococci

• Enterococcus faecalis (80 to 90), E. faecium,
  E. durans, other
• Cause community-acquired endocarditis and UTI but
  are mainly important for nosocomial infections
• Resistance to antibiotics is becoming a major
  problem

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Anaerobic Bacteria Questions

• What are the major clues to anaerobic infection?
• What are the major anaerobic resident flora of
  the skin? Oral cavity? Colon?
• What types of specimens are appropriate for
  anaerobic culture? Inappropriate?
• What is the significance of soft tissue gas?
• Define the major features of tetanus. Botulism.
  Clostridial myonecrosis. Actinomycosis.

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Some definitions

• Anaerobic bacteria require reduced oxygen
  tension for growth fail to grow on surface of
  solid media in 10 C02 in air
• Microaerophilic bacteria Can grow in 10 C02 in
  air, but grow best in the presence of only a
  small amount of atmospheric oxygen
• Facultative bacteria can grow in the presence or
  absence of air

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Anaerobes in normal flora

• Gingival crevices 1012/mL, ratio
  (anaerobesaerobes) 10001
• Stool 10 11-12/mL, ratio 10001
• Female genital tract 109/mL, ratio 101
• Diverse up to 500 anaerobic species found in
  stool alone

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Some principles of anaerobic disease

• Common and often overlooked
• Frequently polymicrobial
• Typically due to contamination or extension from
  indigenous microflora to adjacent submucosal
  tissues
• Complex interaction involving synergism and
  antagonism among bacterial species

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Oxidation-reduction potential (Eh)

• Oxidation loss of electrons, reduction gain
  of electrons
• Eh, expressed by the positive or negative
  electrical potential across a calomel half cell,
  can be measured in vivo or in vitro
• In vivo, Eh is usually related to the distance
  from oxygen-carrying RBCs

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Eh (2)

• Eh in most tissues is 0.126 to
  0.246, depending on blood supply
• Most anaerobes require an Eh of -1.00 to - 0.250
  for growth
• Areas of body with large populations of anaerobes
  are those removed from active capillary blood
  supply or areas kept warm and moist
  
  

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Eh (3)

• Interruption of capillary blood flow causes fall
  in Eh to negative values, promoting
  multiplication of anaerobes
• Examples surgery, trauma, atherosclerosis,
  tumors with tissue necrosis
• Experimental ischemia reduces the number of
  Clostridium perfringens cells needed to cause
  infection by 1000-fold.

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Surgical measures in anaerobic infection

• Debridement of dead tissue
• Removal of foreign bodies
• Drainage of pus
• Elimination of obstruction
• Release of trapped gas
• Excision of malignancy
• Improvement of circulation and oxygenation

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My wounds stink and are corrupt because of my
foolishness.

• -- Psalm 385

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Experimental model simulating fecal peritonitis

• Mix colonic contents with barium and place in a
  gelatin capsule
• Drop the capsule into a rats abdomen sew up
• Natural history during the first 4 days,
  peritonitis with bacteremia (usually E. coli)
  50 mortality
• After 7 days all survivors develop abscesses
  (mainly anaerobes)

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Major anaerobes causing disease

• Peptostreptococci (gram cocci)
• Clostridia (gram rods)
• Bacteroides fragilis group (gram - rods)
• Prevotella and Porphyromonas (gram - rods)
• Fusobacteria (long gram - rods)
• Bilophila wadworthia (gram - rods)

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Oral cavity

• Prevotella (formerly Bacteroides) melaninogenicus
• Bacteroides fragilis
• Peptostreptococci
• Fusobacteria

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Gastrointestinal tract

• Bacteroides fragilis group B. fragilis, B.
  thetaiotaomicron, B. distasonis, B. vulgatus, B.
  uniformis, B. ovatus
• Clostridia species
• Peptostreptococci
• Bilophila wadsworthia
• Fusobacteria

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Female genital tract

• Prevotella bivia
• Prevotella disiens
• Bacteroides fragilis
• Peptostreptococci

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Specimens inappropriate for anaerobic cultures

• Superficial wounds, body surfaces
• Expectorated sputum, tube secretions bronchoscopy
  aspirates, nasopharyngeal or throat swabs
• Voided or catheter-collected urine
• Swabs from surfaces of abscesses swabs after
  incision and drainage (I D)

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Clinical clues to anaerobic infection

• Foul-smelling discharge
• Location of infection in proximity to a mucosal
  surface
• Necrotic tissue, gangrene, pseudomembranes
• Gas in tissues or in discharges
• Failure to grow pathogens despite multiple
  bacteria on Grams stain

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Clinical reasoning

• Pattern recognition
• Probabilistic thinking
• Pathophysiology

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Terms related to diagnostic tests

• Sensitivity positive in disease
• Specificity negative in health
• Positive predictive value likelihood that a
  person with a positive test result HAS the
  disease.
• Negative predictive value likelihood that a
  person with a negative test result DOES NOT HAVE
  the disease.

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Bayess theorem
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Disease transmission

• Contact transmission (e.g., S. aureus)
• Droplet transmission (e.g., influenza virus)
• Airborne transmission (e.g., M. tuberculosis)
• Vehicle transmission (e.g., contaminated items or
  foods)
• Vector transmission (e.g., by insects or animals)