Bacterial Infectious Diseases Flashcards
(112 cards)
1
Q
What are the 6 most medically relevant Gram Positive Bacteria?
A
- Streptococcus (cocci)
- Staphylococcus (cocci)
- Bacillus (rods)
- Clostridium (rods)
- Corynebacterium (rods)
- Listeria (rods)
(Book also mentions Enterococcus)
2
Q
Which Gram Positive Pathogens produce spores?
A
- Bacillus (anthracis)
- Clostridium
3
Q
What is the difference between gram-positive and gram-negative cells?
- Layers?
- Lipid content?
- Endotoxin?
- Periplasmic space?
- Porin channel?
- Lysozyme/penicillin attack?
- Stain color?
A
Gram-Positive: • *** 2 layers: 1. Inner cytoplasmic membrane 2. Outer thick peptidoglycan layer (60-100% peptidoglycan) • Low lipid content • No endotoxin • No periplasmic space • No porin channel • Vulnerable to lysozyme and penicillin attack • Stain violet/blue
Gram-Negative:
• *** 3 layers:
1. Inner cytoplasmic membrane
2. Thin peptidoglycan layer (5-10% peptidoglycan)
3. Outer membrane with lipopolysaccharide (LPS)
• High lipid content
• Endotoxin (LPS) - lipid A
• Periplasmic space
• Porin channel
• Resistant to lysozyme and penicillin attack
• Stain red
4
Q
Are bacteria prokaryotes or eukaryotes?
A
Prokaryotes
5
Q
What are the steps of the Gram stain
A
For any stain you must first smear the substance to be stained onto a slide and then heat it to fix the bacteria on the slide.
1. Pour on crystal violet stain (a blue dye) and wait 60 seconds.
- Wash off with water and flood with iodine solution. Wait 60 seconds.
- Wash off with water and then “decolorize” with 95% alcohol.
- Finally, counter-stain with safranin (a red dye). Wait 30 seconds and wash off with water.
- Gram-positive = cells that absorb the crystal violet so stain BLUE/VIOLET
- Gram-negative= if the crystal violet is washed off by the alcohol, these cells will absorb the safranin and appear RED
6
Q
Which Gram Positive Pathogens do not produce spores?
A
- Corynebacterium
- Listeria
7
Q
Bacilli means the same thing as what?
A
Rods
8
Q
What are the morphological attributes of the cocci?
A
Circular/spherical
9
Q
Clinically, what is the difference between Gram-positive and Gram-negative?
A
- The gram-positive thickly meshed peptidoglycan layer does not block diffusion of low molecular weight compounds, so substances that damage the cytoplasmic membrane (such as antibiotics, dyes, and detergents) can pass through.
- However, the gram negative outer lipopolysaccharide-containing cell membrane blocks the passage of these substances to the peptidoglycan layer and sensitive inner cytoplasmic membrane. Therefore, antibiotics and chemicals that attempt to attack the peptidoglycan cell wall (such as penicillins and lysozyme) are unable to pass through
10
Q
Which of the 6 Gram-positive bacteria are considered Facultative Anaerobes?
A
- Staphylococcus
- Bacillus anthracis
- Corynebacterium
- Listeria
11
Q
Which of the 6 Gram-positive bacteria are considered Obligate Aerobes?
A
Bacillus cereus
12
Q
Which of the 6 Gram-positive bacteria are considered Microaerophilic?
A
- Streptococcus
13
Q
Which of the 6 Gram-positive bacteria are considered Obligate Anaerobes?
A
Clostridium
14
Q
What are obligate aerobes?
A
These critters are just like us in that they use glycolysis, the Krebs TCA cycle, and the electron transport chain with oxygen as the final electron acceptor. They also use the enzymes catalase, peroxidase, and superoxide dismutase.
15
Q
What are Facultative Anaerobes?
A
These bacteria are actually aerobic. They use oxygen as an electron acceptor in their electron transfer chain and have catalase and superoxide dismutase. The only difference is that they can grow in the absence of oxygen by using fermentation for energy. Thus they have the faculty to be anaerobic but prefer aerobic conditions.
16
Q
What are Microaerophilic bacteria/aerotolerant anaerobes?
A
These bacteria use fermentation and have no electron transport system. They can tolerate low amounts of oxygen because they have superoxide dismutase (but they have no catalase).
17
Q
What are obligate anaerobes?
A
These guys hate oxygen and have no enzymes to defend against it.
18
Q
Bacterial Genetics:
What is transformation?
A
- Naked DNA fragments from one bacterium, released during cell lysis, bind to the cell wall of another bacterium.
- The recipient bacterium must be competent, which means that it has structures on its cell wall that can bind the DNA and take it up intracellularly. Recipient competent bacteria are usually of the same species as the donor.
- The DNA that has been brought in can then incorporate itself into the recipient’s genome if there is enough homology between strands (another reason why this transfer can only occur between closely related bacteria).
19
Q
Bacterial Genetics:
What is transduction?
A
Transduction occurs when a virus that infects bacteria, called a bacteriophage, carries a piece of bacterial DNA from one bacterium to another.
20
Q
Bacterial Genetics:
What is conjugation?
How do they acquire antibiotic resistance?
A
- Conjugation is bacterial sex at its best: hot and heavy! In conjugation, DNA is transferred directly by cell-to-cell contact, resulting in an extremely efficient exchange of genetic information.
- For conjugation to occur, one bacterium must have a
self-transmissible plasmid, also called an F plasmid (F for fertility). Plasmids are circular double-stranded DNA molecules that lie outside the chromosome and can carry many genes, including those for drug resistance. F plasmids encode the enzymes and proteins necessary to carry out the process of conjugation. - The self-transmissible plasmid (F plasmid) has a gene that encodes enzymes and proteins that form the sex penis, that is, sex pilus. This long protein structure protrudes from the cell surface of the donor F(+) bacterium and binds to and penetrates the cell membrane ofthe recipient bacterium. Now that a conjugal bridge has formed, a nuclease breaks off one strand of the F plasmid DNA, and this single strand of DNA passes through the sex pilus (conjugal bridge) to the recipient bacterium.
- The exchange can occur between unrelated bacteria and is the major mechanism for transfer of antibiotic resistance.
21
Q
Bacterial Genetics:
What are transposons?
How do they acquire antibiotic resistance?
A
- Transposons are mobile genetic elements. You can visualize them as DNA pieces with legs. These pieces of DNA can insert themselves into a donor chromosome without having DNA homology. They can carry genes for antibiotic resistance and virulence factors.
- The importance of transposons clinically is that a transposon gene that confers a particular drug resistance can move to the plasmids of different bacte rial genera, resulting in the rapid spread of resistant strains.
22
Q
A virus that infects bacteria is called a?
A
Bacteriophage
23
Q
Transduction:
What is lysogenic immunity?
A
- The integrated temperate phage genome is called a prophage. Bacteria that have a prophage inte grated into their chromosome are called lysogenic because at some time the repressed prophage can become activated.
- Lysogenic immunity is the term used to describe the ability of an integrated bacteriophage (prophage) to block a subsequent infection by a similar phage.
- The first temperate phage to infect a bacteria produces a repres sor protein. This “survival of the fittest” adaptation ensures that the first temperate phage is the bacteria’s sole occupant.
24
Q
How are bacteria and other potential pathogenic agents, identified?
A
• Smears
– To visualize
– Gram staining
– “other” techniques and/or other stains
• Culture
– A variety of culture media (and culture “conditions”) utilized
• Molecular techniques
– Often, nucleic acid sequence data (both genomic and ribosomal) is the agent substrate utilized in conjunction with complementary nucleic acid
laboratory probes
• Serology
– There are certain bacteria that do not “culture well”
– “other agents” (e.g. viruses) cannot be cultured by standard
microbiologic (generally aerobic) techniques
– Survey for antibody positivity
– Acute and convalescent samples
25
What are the pros to culture?
- High specificity
- Isolates can be tested for antibiotic sensitivity
- Enables biochemical characterization of phenotype
- Less expensive
- Does not require special workflow
- Does not require specialized instrumentation
- Permits visual inspection of colony morphology
26
NAT Method Pros
- High sensitivity
- Rapid turnaround time
- Permits detection of nonviable bacteria
- Reduced biosafety concern (i.e. bacteria not propagated)
- Permits high res analysis of bacterial isolates for epidemiology purposes
- Permits detection of certain antibiotic-resistant bacteria without an initial culture
27
Culture Cons
- Low sensitivity (low bacterial count)
- Cannot detect nonviable bacteria (i.e., bacteria not viable due to sample processing, pretreatment of patient with antibiotics, etc.)
- Biochemical phenotype may not agree with genotype
- Longer time to result (turnaround time) for slow-growing or fastidious bacteria
- Biosafety concern (i.e., bacteria propagated)
28
NAT Method Cons
- False positive results due to cross reaction with genetically-related bacteria
- False-negatives can occur (inhibitors in sample can cause amplification to fail, genetic changes in bacterial nucleic acid prevent the primer or
probe from binding)
- Genotype may not agree with biochemical results
- Requires special instrumentation or workflow
- Requires special training
- Few tests for antibiotic sensitivity are available
29
Streptococci ???
* Hemolytic reaction on blood agar
* Grp A beta-hemolytic strep (genus/species name?)
* virulence factors
30
Grp B Streptococci
* Streptococcus agalactiae
* Age-group related
```
• The 3 most common pathogens associated
with meningitis in neonates and infants less than three months of age:
- Grp B Strep
- Listeria
- E. coli
```
• Classic presentation
- Children under 3 present with lethargy and nuchal rigidity (can't flex neck forward)
31
Viridans Grp streptococci
• They are normal flora in:
- GI tract
- Nasopharynx
- Gingiva
• Associated infections:
- Dental/caries
- Other
- Endocarditis
• Anginosus species group (or Streptococcus intermedius)
- The clinical significance of blood culture positivity with this type of bacterium is suspect occult abscess
32
Grp D Strep
• Enterococcus and nonenterococci
- Unique characteristic: they have the ability to grow in bile and NaCl
* nosocomial infections
* multiply drug-resistant enterococci
* Non-enterococci, Streptococcus bovis associated with colon cancer
33
Streptococcus pneumoniae (pneumococcus)
* Quellung reaction/optochin sensitivity
* Pneumococcal pneumonia/meningitis
* Otitis media. The 3 organisms associated:
- S. pneumo
- HI
- MC
• Antibiotic resistance has emerged
34
Staphylococci
* Can be colonized and not infected
* 3 types:
- Staphylococcus aureus
- Staphylococcus epidermidis
- Staphylococcus saprophyticus
* All catalase positive
* Normal skin flora = Staphylococcus epidermidis
* Most important type = Staphylococcus aureus
* Coagulase positive = Staphylococcus aureus
35
Staphylococcus aureus
• virulence proteins (especially beta-lactamase)
• enzymatic tissue proteins (numerous tissue enzymes
to degrade stroma and promote tissue spread)
* Cutaneous exotoxin
* Exotoxins (enterotoxins)
• TSST-1, exotoxin (noteworthy also as a potentiator of
endotoxin)
- Usually seen with tampons but can also see it in men (super antigens)
* Diseases, exotoxin release
* Diseases, organ invasion
• MRSA
– general
– Community-acquired type
* Tend to see it as a necrotizing organism
* Sometimes people with lobar pneumonia can get infections like this
• Same thing when it involves the heart
- Seen in IV abusers (if it contaminates needles and will go to cardiac valves and can necrose cardiac valves)
36
Other staphylococci (coagulase neg.)
• S. epidermidis
- Indwelling catheters, prosthetic devices
- Generally normal skin flora
• S. saprophyticus
– A leading cause (but second to E. coli) of community-acquired UTI’s in sexually-active young women
37
Bacillus anthracis
* Gram positive
* Spore former
* The disease is acquired in soil and especially agricultural because it is shed by animals
* Forms a black scar called an eschar
* Exotoxins
* Cutaneous anthrax - usually what we would see. On their skin
* Pulmonary anthrax - if it is aerosol
* Gastrointestinal anthrax = if you swallow anthrax
* “injectional” anthrax = It has been injected in a few cases
* Has potential as a weaponized biologic agent of mass destruction [WMD]
38
Bacillus cereus
* Same genus as anthracis
* Bacillary dysentery
* enterotoxins
39
Clostridium sp.
* Does not tolerate oxygen well
* Gram positive
```
• Diseases (role of toxins)
– botulism; adult vs. infant
– tetanus (immunization and clinical features)
– gangrene
– pseudomembranous colitis
```
40
Corynebacterium diphtheriae
• Clinical presentation:
- Upper respiratory manifestation and pseudomembrane in the back of the throat
* Antitoxin
* Vaccine
* Rhodococcus equi
41
Listeria monocytogenes
* pregnancy association/diet advice?
* placentitis
* relationship to neonatal meningitis
* immunocompromised hosts
* facultative intracellular organism
* cell mediated immunity issues
* Increasingly seen in compromised elderly
42
Streptococcus Pyogenes: Lancefield group A
* Metabolism?
* Virulence?
* Toxins?
* Pathology?
* Treatment?
* Diagnostics?
* Miscellaneous?
```
• Metabolism:
1.) Catalase-negative
2.) Microaerophilic
3.) Beta-hemolytic, due to enzymes that destroy red and white blood cells
A. Streptolysin O:
a. Oxygen labile
b. Antigenic
B. Streptolysin-S
a. Oxygen stable
b. Non-antigenic
```
• Virulence:
1. ) M-protein (70 types)
a. Adherence factor
b. Anti-phagocytic
c. Antigenic: Induces antibodies which can lead to phagocytosis
2. ) Lipoteichoic acid: adherence factor
3. ) Streptokinase
4. ) Hyaluronidase
5. ) DNAase
6. ) Anti-C5a peptidase
• Toxins:
1. ) Erythrogenic or Pyrogenic Toxin (produced only by lysogenized Group A Streptococci): responsible for scarlet fever
2. ) Toxic shock syndrome toxin (similar to, but different from the staph exotoxin TSST-1)
• Pathology:
Direct Invasion/Toxin:
```
1.) Pharyngitis:
A. Red, swollen tonsils and pharynx
B. Purulent exudate on tonsils
C. Fever
D. Swollen lymph nodes
2.) Skin Infections:
A. Folliculitis
B. Cellulitis
C. Impetigo
D. Necrotizing fasciitis
3.) Scarlet fever:
fever and scarlet red rash on body
4.) Toxic shock syndrome
```
Antibody Mediated:
1.) Rheumatic fever (may follow streptococcal pharyngitis):
A. Fever
B. Myocarditis: heart inflammation
C. Arthritis: migratory polyarthritis
D. Chorea
E. Rash: erythrema marginatum
F. Subcutaneous nodules
- 10-20 years after infection, may develop permanent heart valve damage
2.) Acute post-streptococcal glomerulonephritis:
tea-colored urine, following streptococcal skin or pharynx infection
• Treatment:
1.) Penicillin G
2.) Penicillin V
3.) Erythromycin
4.) Penicillinase-resistant penicillin: in skin infections, where staphylococci could be the responsible organism
- Following rheumatic heart:
A. Patients are placed on continuous prophylactic antibiotics to prevent repeat strep throat infections that could potentially lead to a repeat case of rheumatic fever
- For invasive streptococcus pyogenes infections, such as necrotizing fasciitis or streptococcal toxic shock syndrome, consider adding clindamycin
• Diagnostics:
1. ) Gram positive cocci in chains
2. ) Culture on standard lab media. Growth is inhibited by BACITRACIN (only beta-hemolytic strep sensitive to bacitracin)
3. ) Pharyngitis: Throat swab rapid antigen detection test (RADT) is specific for it and immunologically detects group A carbohydrate antigen.
• Miscellaneous
1. ) Dick Test: once commonly used to confirm Scarlet Fever diagnosis
2. ) C-Carbohydrate: used for Lancefield groupings
43
Streptococcus Agalactiae: Lancefield group B
* Metabolism?
* Virulence? (None)
* Toxins? (None)
* Pathology?
* Treatment?
* Diagnostics?
* Miscellaneous?
• Metabolism:
1. ) Catalase-negative
2. ) Facultative anaerobe
3. ) Beta-hemolytic
• Pathology:
1. Neonatal meningitis
2. Neonatal pneumonia
3. Neonatal sepsis
4. Sepsis in pregnant women (with secondary infection of fetus)
5. Increasing incidence of infections in elderly >65 years of age and patients with diabetes or neurological disease: causes sepsis and pneumonia
• Treatment:
- Penicillin G
• Diagnostics:
1. Gram stain of CSF or urine
2. Culture of CSF, urine or blood
• Miscellaneous:
- Part of normal flora (25% of pregnant women carry Group B streptococci in their vagina)
44
Streptococcus: Lancefield group D
* Metabolism?
* Virulence?
* Toxins? (None)
* Pathology?
* Treatment?
* Diagnostics?
* Miscellaneous?
Lancefield group D: 2 sub-types:
1. Enterococci
- Streptococcus faecalis
- Streptococcus faecium
2. Non-enterococci
- Streptococcus bovis
- Streptococcus equinus
• Metabolism:
1. Catalase-negative
2. Facultative anaerobe
3. Usually gamma-hemolytic, but may be alpha-hemolytic
• Virulence:
- Extracellular dextran helps them bind to heart valves
• Pathology:
1. Subacute bacterial endocarditis
2. Biliary tract infections
3. Urinary tract infections (especially the enterococci)
• Treatment:
1. Ampicillin, sometimes combined with an aminoglycoside
2. Resistant to penicillin G
3. Emerging resistance to vancomycin
4. For vancomycin resistant organisms (VRE) consider linezolid, daptomycin, and nitrofurantoin
```
• Diagnostics:
1. Gram stain
2. Culture:
A. Enterococci can be cultured in:
1.) 40% bile
2.) 6.5% sodium chloride
B. Nonenterococci can only grow in bile
```
• Miscellaneous:
- S. Bovis associated with colonic malignancies
45
Streptococcus Viridans:
* Metabolism?
* Virulence?
* Toxins? (None)
* Pathology?
* Treatment?
* Diagnostics?
* Miscellaneous?
• Metabolism:
1. Catalase-negative
2. Facultative anaerobe
3. Alpha-hemolytic
• Virulence:
- Extracellular dextran helps them bind to heart valves
• Pathology:
1. Subacute bacterial endocarditis
2. Dental caries (cavities): caused by Streptococcus mutans
3. Brain or liver abscesses: caused by Streptococcus intermedius group
• Treatment:
- Penicillin G
• Diagnostics:
1. Gram stain
2. Culture
3. Resistant to optochin
• Miscellaneous:
- Part of the normal oral flora (found in the nasopharynx and gingival crevices) and GI tract
46
Streptococcus Pneumoniae (pneumococci):
* Metabolism?
* Virulence?
* Toxins?
* Pathology?
* Treatment?
* Diagnostics?
* Miscellaneous?
• Metabolism:
1. Catalase-negative
2. Facultative anaerobe
3. Alpha-hemolytic
• Virulence:
- Capsule (83 serotypes)
• Toxins:
- Pneumolysin: binds to cholesterol in host-cell membranes (but its actual effect is unknown)
• Pathology:
1. Pneumonia
2. Meningitis
3. Sepsis
4. Otitis media (in children)
• Treatment:
1. ) Penicillin G (IM)
2. ) Erythromycin
3. ) Ceftriaxone
4. ) Vaccine: made against the 23 most common capsular antigens. Vaccinate individuals who are susceptible, such as elderly folk or asplenic individuals (including being functionally asplenic due to sickle cell anemia)
5. ) Heptavalent and the newer 13 valent conjugated vaccines are effective at preventing otitis media and pneumonia
• Diagnostics:
A. Gram stain: reveals gram-positive diplococci
B. Culture: does not grow in presence of:
1.) Optochin
2.) Bile
C. Positive Quellung test: swelling when tested against antiserum containing anti-capsular antibodies
• Miscellaneous:
- Quellung reaction: technique used to detect encapsulated bacteria (such as S. pneumoniae and H. influenzae)
47
Staphylococcus Aureus:
* Metabolism?
* Virulence?
* Toxins?
* Clinical?
* Treatment?
* Diagnostics?
* Miscellaneous?
• Metabolism:
1. Catalase-positive
2. Coagulase-positive **
3. Facultative anaerobe
```
• Virulence:
Protective Proteins:
1. Protein A: binds IgG, preventing opsonization and phagocytosis
2. Coagulase: allows fibrin
3. Hemolysins
4. Leukocidins
5. Penicillinase
```
Tissue-Destroying Proteins:
1. Hyaluronidase: breaks down connective tissue
2. Staphylokinase: lyses formed clots
3. Lipase
```
• Toxins:
Assault Weaponry
1. Exfoliatin: scalded skin syndrome
2. Enterotoxin: food poisoning
3. Toxic shock syndrome toxin (TSST-1)
```
```
• Clinical:
A. Exotoxin Dependent
1. Gastroenteritis (food poisoning): Rapid onset of vomiting and diarrhea, with rapid recovery
2. Toxic shock syndrome:
A. High fever
B. Nausea and vomiting
C. Watery diarrhea
D. Erythematous rash
E. Hypotension
F. Desquamation of palms and soles
3. Scalded skin syndrome
B. Direct Invasion
1. Pneumonia
2. Meningitis
3. Osteomyelitis (in children)
4. Acute bacterial endocarditis
5. Septic arthritis
6. Skin infection
7. Bacteremia/sepsis
8. Urinary tract infection
```
• Treatment:
1. Penicillinase-resistant penicillins: nafcillin (IV) and dicloxacillin (oral)
2. 1st generation cephalosporins: cefazolin (IV), cephalexin (oral) treat with intravenous
3. Clindamycin (IV and oral)
If MRSA:
1. Vancomycin (IV)
2. Daptomycin (IV)
3. Clindamycin (IV and oral)
4. Trimethaprim-sulfamethoxazole (IV and oral)
5. Linezolid (IV and oral)
6. Ceftaroline (IV)
7. Telavancin (IV)
8. Dalbavancin (IV)
9. Oritavancin (IV)
10. Tedizolid (IV and po)
11. Tigecycline
• Diagnostics:
1. Gram stain: reveals gram-positive cocci in clusters
2. Culture:
A. Beta-hemolytic
B. Produces a golden yellow pigment.
3. Metabolic
A. Catalase-positive
B. Coagulase-positive
4. Polymerase chain reaction (PCR) detection of ribosomal RNA
48
Staphylococcus Epidermidis:
* Metabolism?
* Virulence?
* Toxins?
* Clinical?
* Treatment?
* Diagnostics?
* Miscellaneous?
• Metabolism:
1. Catalase-positive
2. Coagulase-negative **
3. Facultative anaerobe
• Virulence:
1. Polysaccharide capsule: adheres to a variety of prosthetic devices. Forms a biofilm.
2. Highly resistant to antibiotics!
```
• Clinical:
A. Nosocomial infections:
1. Prosthetic joints
2. Prosthetic heart valves
3. Sepsis from intravenous lines
4. Urinary tract infections
B. Frequent skin contaminant in blood cultures!
```
• Treatment:
- Vancomycin (since resistant to multiple antibiotics)
```
• Diagnostics:
1. Gram stain; reveals gram-positive cocci in clusters
2. Culture
3. Metabolic
A. Catalase-positive
B. Coagulase-negative
```
49
Staphylococcus Saprophyticus:
* Metabolism?
* Clinical?
* Treatment?
* Diagnostics?
• Metabolism:
1. Catalase-positive
2. Coagulase- negative **
3. Facultative anaerobe
• Clinical:
- Urinary tract infections in sexually active women
• Treatment:
- Penicillin
```
• Diagnostics:
1. Gram stain: reveals gram-positive cocci in clusters
2. Culture: gamma-hemolytic
3. Metabolic
A. Catalase-positive
B. Coagulase-negative
```
50
Bacillus Anthracis:
* Reservoir?
* Transmission?
* Metabolism?
* Virulence?
* Toxins?
* Clinical?
* Treatment?
* Diagnostics?
```
• Reservoir:
- Herbivores (zoonotic)
A. Sheep
B. Goats
C. Cattle
```
• Transmission:
- Endospores
1. Cutaneous
2. Inhalation
3. Ingestion
• Metabolism:
- Aerobic (but since it can grow without oxygen, it is classified as a facultative anaerobe)
• Virulence:
1. Unique protein capsule (polymer of gamma-D-glutamic acid): antiphagocytic
2. Non-motile **
3. Virulence depends on acquiring 2 plasmids. One carries the gene for the protein capsule; the other carries the gene for its exotoxin
```
• Toxins:
Exotoxin: 3 proteins
a. Protective antigens (PA)
b. Edema factor (EF)
c. Lethal factor (LF)
```
• Clinical:
Anthrax
1. Cutaneous (95%):
painless black vesicles; Can be fatal if untreated
2. Pulmonary (woolsorter's disease)
3. GI: abdominal pain, vomiting and bloody diarrhea
- Infection results in permanent immunity (if the patient survives)
• Treatment:
1. Ciprofloxacin
2. Doxycycline
3. Raxibacumab (monoclonal antibody for use in inhalation anthrax)
4. Vaccine: for high-risk individuals
A. Vaccine is composed of the protective antigen (PA)
B. Animal vaccine is composed of a live strain, attenuated by loss of its protein capsule
• Diagnostics:
1. Gram stain
2. Culture
3. Serology
4. PCR of nasal swab
51
Bacillus cereus:
* Transmission?
* Metabolism?
* Virulence?
* Toxins?
* Clinical?
* Treatment?
* Diagnostics?
• Transmission:
- Endospores
• Metabolism:
- Aerobic
• Virulence:
1. No capsule **
2. Motile
• Toxins:
Enterotoxins
A. Heat labile: similar to enterotoxin of cholera and E. coli
B. Heat stable: produces syndrome similar to that of Staphylococcus aureus food poisoning, but with limited diarrhea
• Clinical:
- Food poisoning: nausea, vomiting, and diarrhea
• Treatment:
1. Vancomycin
2. Clindamycin
3. Resistant to beta-lactam antibiotics
4. No treatment for food poisoning ("Be serious, Dr. Goofball: food poisoning is caused by the pre-formed enterotoxin)
• Diagnostics:
- Culture specimen from suspected food source
52
Clostridium botulinum:
* Reservoir?
* Transmission?
* Metabolism?
* Virulence?
* Toxins?
* Clinical?
* Treatment?
* Diagnostics?
• Reservoir:
1. Soil
2. Stored vegetables:
- Home-canned
- Zip-lock storage bags
3. Smoked fish
4. Fresh honey: associated with infant botulism
• Transmission:
- Endospores (heat resistant)
• Metabolism:
- Anaerobic **
• Virulence:
- Motile: flagella (so H-antigen positive)
• Toxins:
1. Neurotoxin: inhibits release of acetylcholine from peripheral nerves
2. Toxin is not secreted. Rather it is released upon the death of the bacterium
```
• Clinical:
Food-borne botulism:
1. Cranial nerve palsies
2. Muscle weakness
3. Respiratory paralysis
```
Infant botulism:
1. Constipation
2. Flaccid paralysis
Wound botulism:
1. Similar to Food-borne except absence of GI prodromal symptoms
• Treatment:
1. Antitoxin (for food-borne and wound botulism)
2. Human botulism immunoglobulin (for infant botulism)
3. Penicillin
4. Hyperbaric oxygen
5. Supportive therapy: including incubation and ventilatory assistance
• Diagnostics:
1. Gram stain
2. Culture: requires anaerobic conditions
3. Patient's serum injected into mice results in death
53
Clostridium tetani:
* Reservoir?
* Transmission?
* Metabolism?
* Virulence?
* Toxins?
* Clinical?
* Treatment?
* Diagnostics?
• Reservoir:
- Soil
• Transmission:
- Endospores: introduced through wound
• Metabolism:
- Anaerobic
• Virulence:
- Motile: flagella (so H-antigen positive)
• Toxins:
- Tetanospasmin: inhibits release of GABA and glycine (both inhibitory neurotransmitters) from nerve cells, resulting in sustained muscle contraction
```
• Clinical:
Tetanus
1. Muscle spasms
2. Lockjaw (trismus)
3. Risus sardonicus
4. Respiratory muscle paralysis
```
• Treatment:
1. Tetanus toxoid: vaccination with formalin-inactivated toxin (toxoid). Part of the DPT vaccine
2. Antitoxin: human tetanus immune globulin (preformed anti-tetanus antibodies)
3. Clean the wound
4. Metronidazole or penicillin
5. Supportive therapy: may require ventilatory assistance
- Vaccine: DTap
1. Diphtheria
2. Tetanus
3. Acellular Pertussis
• Diagnostics:
1. Gram stain:
gram-positive rods, often with an endospore at one end, giving them the appearance of a drumstick
2. Culture: requires anaerobic conditions
54
Clostridium difficile:
* Reservoir?
* Transmission?
* Metabolism?
* Virulence?
* Toxins?
* Clinical?
* Treatment?
* Diagnostics?
• Reservoir:
1. Intestinal tract
2. Endospores found in hospitals and nursing homes
• Transmission:
- Fecal-oral: ingestion of endospores
• Metabolism:
- Anaerobic
• Virulence:
- Motile: flagella (so H-antigen positive)
• Toxins:
1. Toxin A: diarrhea
2. Toxin B: cytotoxic to colonic epithelial cells
• Clinical:
- Pseudomembranous enterocolitis: antibiotic-associated diarrhea
• Treatment:
1. Metronidazole
2. Oral vancomycin
3. Fidaxomicin
4. Fecal transplant
5. Discontinue unnecessary antibiotics
• Diagnostics:
1. Immunoassay for C. difficile toxin
2. PCR for toxin A and B genes
55
Clostridium Perfringens
* Reservoir?
* Transmission?
* Metabolism?
* Virulence?
* Toxins?
* Clinical?
* Treatment?
* Diagnostics?
• Reservoir:
- Ubiquitous:
1. Soil
2. GI tract of humans and mammals
• Transmission:
- Endospores
• Metabolism:
- Anaerobic
• Virulence:
- NON-motile
• Toxins:
1. Alpha toxin: lecithinase (splits lecithin into phosphocholine and diglyceride)
2. 11 other tissue destructive enzymes
• Clinical:
Gaseous Gangrene
A. Cellulitis/wound infection
B. Clostridial myonecrosis: fatal if untreated
C. Watery diarrhea: associated with food-borne ingestion
• Treatment:
1. Radical surgery (may require amputation)
2. Penicillin
3. Hyperbaric oxygen
• Diagnostics:
1. Gram stain
2. Culture: requires anaerobic conditions
56
Corynebacterium Diphtheriae:
* Morphology?
* Transmission?
* Metabolism?
* Virulence?
* Toxins?
* Clinical?
* Treatment?
* Diagnostics?
* Miscellaneous?
• Morphology:
1. Gram-positive rods (very pleomorphic and club-shaped)
2. Non-spore-forming
3. Non-motile
• Transmission:
- Respiratory droplets from a carrier
• Metabolism:
1. Facultative anaerobe
2. Catalase-positive
• Virulence:
- Pseudomembrane forms in the pharynx, which serves as a base from where it secretes its toxin
• Toxins:
- Exotoxin (coded by a bacteriophage):
A subunit: blocks protein synthesis by inactivating EF2
B subunit: provides entry into cardiac and neural tissue
- This exotoxin is like an anti-human antibiotic, as it inhibits eucaryotic protein synthesis, just as tetracycline inhibits protein synthesis in bacteria
• Clinical:
Diphtheria
1. Mild sore throat with fever initially
2. Pseudomembrane forms on pharynx
3. Myocarditis causing A-V conduction block and dysrhythmia
4. Neural involvement
a. Peripheral nerve palsies
b. Guillain Barre-like syndrome
c. Palatal paralysis and cranial neuropathies
```
• Treatment:
1. Antitoxin
2. Penicillin or erythromycin
3. Vaccine: DPT
- Diphtheria: formalin
Inactivated exotoxin, as antibodies to the B-subunit are protective
- Pertussis
- Tetanus
```
• Diagnostics:
1. Gram stain:
gram-positive pleomorphic rods (sometimes described as looking like Chinese letters)
2. Culture:
A. Potassium tellurite: get dark black colonies
B. Loeffler's medium: after 12 hours of growth, stain with methylene blue. Reddish (Babes-Ernst) granules can be seen
• Miscellaneous:
1. Obtains exotoxin from a temperate bacteriophage by lysogenic conversion
2. Schick test: Injection of diphtheria exotoxin into the skin, to determine whether a person is susceptible to infection by C. diphtheriae
57
Listeria Monocytogenes:
* Morphology?
* Transmission?
* Metabolism?
* Virulence?
* Toxins?
* Clinical?
* Treatment?
* Diagnostics?
* Miscellaneous?
• Morphology:
1. Gram-positive rods
2. Non-spore-forming
3. Motile: tumbling motility is seen when grown at 25 C
• Transmission:
1. Ingestion of contaminated raw milk or cheese from infected cows
2. Vaginally (during birth)
3. Transplacental infection of fetus from bacteremic mother
• Metabolism:
1. Facultative anaerobe
2. Catalase-positive
3. Beta-hemolytic on blood agar
• Virulence:
1. Motile (via flagella): so has H-antigen
2. Hemolysin: (like streptolysin O)
a. Heat labile
b. Antigenic
• Toxins:
- Listeriolysin O and phospholipases: allows escape from the phagolysosomes of macrophages
• Clinical:
1. Neonatal meningitis
2. Meningitis in immune-suppressed patients and the elderly (>50)
3. Septicemia in pregnant women
• Treatment:
1. Ampicillin
2. Trimethoprim/sulfamethoxazole
• Diagnostics:
1. Gram stain: gram-positive rods
2. Culture: can grow at temperatures as low as 0 C. So use cold enrichment technique to isolate from mixed flora
• Miscellaneous:
- Facultative intracellular parasite
- Cell-mediated immunity is protective
58
Neisseria Meningitidis:
* Reservoir?
* Morphology and Metabolism?
* Virulence?
* Toxins?
* Clinical?
* Treatment?
* Diagnostics?
* Miscellaneous?
• Reservoir:
1. Nasopharynx of humans ONLY.
- Immunity can develop to particular strains
- Strict human parasite
2. Spread by respiratory transmission
• Morphology and Metabolism:
1. Kidney bean shaped with concave sides facing each other, forming the appearance of a doughnut
2. Gram-negative diplococci
3. Facultative-anaerobe
4. Grows best in high CO2 environment
5. Ferments maltose and glucose - easy to remember, since there is both an "m" and "g" in meningitidis
• Virulence:
1. Capsule:
a. 13 serotypes based on antigenicity of capsule polysaccharides
b. Serotypes A, B, and C are associated with epidemics of meningitis (usually type B)
2. IgA1 protease
3. Have unique proteins that can extract iron from transferrin, lactoferrin and hemoglobin
4. Pili: for adherence
• Toxins:
1. Endotoxin: Lipopolysaccharide (LPS)
2. NO exotoxins
```
• Clinical:
1. Asymptomatic carriage in the nasopharynx
2. Meningitis:
A. Fever
B. Stiff neck (nuchal rigidity)
C. Vomiting
D. Lethargy or altered mental status
E. Petechial rash
3. Septicemia (meningococcemia)
A. Fever
B. Petechial rash
C. Hypotension
D. Fulminant
meningococcemia (Waterhouse-Friderichsen Syndrome): hemorrhage of the adrenal glands along with hypotension and the petechial rash
```
• Treatment:
1. There are two separate vaccines- one against capsular antigens: A, C, Y and W-135; the second is against capsular antigen B
2. Antibiotics:
A. Penicillin G
B. Ceftriaxone (or other third generation cephalosporins)
C. Rifampin and ciprofloxacin are used for prophylaxis of close contacts of infected persons
• Diagnostics:
1. Gram-stain
2. Culture
A. Culture specimen on blood agar that has been heated to 80 C for 15 minutes (called chocolate agar)
B. Selective media: prevents growth of bacteria
- Thayer Martin VCN
V= Vancomycin
C= Colistin
N = Nystatin
C. Cell wall contains cytochrome oxidase which oxidizes dye tetramethylphenylene diamine from colorless to deep pink. Used to ID colonies
D. PCR of bacteria DNA in clinical specimens
• Miscellaneous:
1. Neonates are very susceptible from 6 to 24 months, when protective antimeningococcal IgG is low
2. Army recruits are also at high risk (with carriage rates of greater than 40%)
59
Neisseria gonorrhoeae:
* Reservoir?
* Morphology and Metabolism?
* Virulence?
* Toxins?
* Clinical?
* Treatment?
* Diagnostics?
* Miscellaneous?
• Reservoir:
1. Humans only (no immunity to repeated infections)
2. Sexually transmitted
• Morphology and Metabolism:
1. Kidney bean shaped with concave sides facing each other, forming the appearance of a doughnut
2. Gram-negative diplococci
3. Facultative-anaerobe
4. Grows best in high CO2 environment
5. Ferments only glucose (not maltose) - easy to remember, since there is only a "g" (no "m") in gonorrhoeae
• Virulence:
1. Pill
A. Adherence to epithelial cells
B. Antigenic variation
C. Antiphagocytic: binds bacteria tightly to host cell, protecting from phagocytosis
2. IgA protease
3. Outer membrane proteins: Protein I: porin Protein II (opacity protein): presence associated with dark, opaque colonies
- for adherence
4. Have unique proteins that can extract iron from transferrin, lactoferrin and hemoglobin
• Toxins:
1. Endotoxin: Lipopolysaccharide (LPS)
2. NO exotoxins
• Clinical:
1. Asymptomatic (but still infectious)
2. Men : urethritis
3. Women: cervical gonorrhea, which can progress to pelvic inflammatory disease (PID)
Complications of PID
A. Sterility
B. Ectopic pregnancy
C. Abscess
D. Peritonitis
E. Perihepatitis
4. Both men and women:
A. Gonococcal bacteremia
B. Septic arthritis: gonococcal arthritis is the most common cause of septic arthritis in sexually active individuals
5. Neonates: Ophthalmia neonatorum conjunctivitis in newborns.
N. gonorrhoeae is acquired during passage through an infected birth canal. Conjunctivitis usually erupts within the first 5 days
• Treatment:
1. Antibiotic of choice: Ceftriaxone 250 mg IM and Azithromycin 1 gm orally x 1
2. Second line:
A. Cefixime + azithromycin or doxycycline
B. Spectinomycin (not available in the US)
3. For ophthalmia neonatorum:
- Erythromycin eye drops should be given immediately following birth, for prophylaxis against both N. gonorrhoeae and Chlamydia trachomatis conjunctivitis
- Infants with ophthalmia neonatorum require systemic treatment with ceftriaxone. Erythromycin syrup should also be provided to cover for possible concurrent Chlamydial disease (This is important, as failure to treat neonatal Chlamydia conjunctivitis can lead to Chlamydial pneumonia)
• Diagnostics:
1. Gram-stain of urethral pus reveals the tiny gram-negative doughnut-shaped diplococci within white blood cells
2. Culture
A. Culture specimen on chocolate agar
B. Selective media: prevents growth of other bacteria
- Thayer Martin VCN
V= Vancomycin
C= Colistin
N= Nystatin
C. Cell wall contains cytochrome oxidase which oxidizes dye tetramethylphenylene diamine from colorless to deep pink. Used to ID colonies
D. PCR of bacterial DNA in clinical specimens
• Miscellaneous:
- No immunity following infection: a person can be reinfected numerous times
60
Moraxella (Branhamella) catarrhalis:
* Reservoir?
* Clinical?
* Treatment?
* Miscellaneous?
• Reservoir:
- Part of the normal respiratory flora
• Clinical:
1. Otits media in children
2. Can cause other respiratory tract infections, such as sinusitis, bronchitis, and pneumonia
3. COPD exacerbations
• Treatment:
1. Azithromycin or clarithromycin
2. Amoxicillin with clavulanate
3. Oral second or third generation cephalosporin
4. Trimethoprim/sulfamethoxazole
• Miscellaneous:
- Resistant to penicillin
61
Enterobacteriaceae Generalities:
* Reservoir?
* Transmission?
* Metabolism?
* Virulence?
* Toxins?
* Clinical?
* Treatment? (None)
* Diagnostics?
* Miscellaneous?
• Reservoir:
- All are Gram-negative rods
• Transmission:
1. Fecal-oral
2. Migration up the urethra
3. Colonization of catheters in hospitalized patients (Foley catheters, central lines, etc.)
• Metabolism:
1. Catalase-positive
2. Oxidase-negative
3. Ferments glucose
4. Facultative anaerobic
• Virulence:
- Many of these organisms can acquire antibiotic resistance
• Toxins:
1. Many have enterotoxins
2. All have endotoxin: lipopolysaccharide (LPS)
• Clinical:
1. Many organisms cause diarrhea
2. Various other infections including urinary tract infections, pneumonia and sepsis especially (in debilitated hospitalized patients)
• Diagnostics:
1. Eosine methylene blue agar (EMB): inhibitory to gram-positive bacteria
2. MacConkey agar: Contains bile salts in the media that inhibit gram-positive bacteria
```
• Miscellaneous:
Antigenic Classification:
1. O-antigen: Outer portion of LPS
2. K-antigen: Kapsule
3. H-antigen: Flagella
```
62
Escherichia coli: (Enterobacteriaceae)
* Reservoir?
* Transmission?
* Metabolism?
* Virulence?
* Toxins?
* Clinical?
* Treatment?
* Diagnostics?
* Miscellaneous?
• Reservoir:
- Humans: GI and urinary tract
• Transmission:
1. Fecal-oral
2. Migration up the urethra
3. Colonization of catheters in hospitalized patients (Foley catheters, central lines, etc.)
4. Aspiration of oral E.coli
• Metabolism:
1. Indole-positive (makes indole from tryptophan)
2. Beta-hemolytic
3. Ferments lactose
• Virulence:
1. Fimbriae (pili): colonization factor
2. Siderophore
3. Adhesins
4. Capsule (K-antigen)
5. Flagella (H-antigen)
• Toxins:
Enterotoxins
1. LT (Heat labile): increases cAMP (same as cholera toxin)
2. ST (heat stable): increases cGMP
3. Shiga-like toxin (verotoxin): inhibits protein synthesis by inactivating the 60S ribosomal subunit
• Clinical:
1. Newborn meningitis
2. Urinary tract infection
3. Hospital acquired sepsis
4. Hospital acquired pneumonia
5. Diarrhea
A. Noninvasive strain (Enterotoxigenic): releases LT and ST toxins, causing traveler's diarrhea
B. Enterohemorrhagic: bloody diarrhea; no fever, no pus in stool; secretes Shiga-like toxin: causes hemorrhagic colitis and hemolytic uremic syndrome (E.coli strain O157:H7)
C. Enteroinvasive: bloody diarrhea (with pus in stool) and fever. Also secretes small amounts of Shiga-like toxin.
• Treatment:
1. Cephalosporins
2. Aminoglycosides
3. Trimethoprim and sulfamethoxazole
4. Fluoroquinolones
• Diagnostics:
1. Gram stain
2. Culture (specimen may be urine, sputum, CSF, or blood). Can grow at 45.5 C.
3. Pathogenic strains may be isolated from stool
- E. coli ferments lactose. Its colonies produce a green metallic sheen on EMB agar and are pink-purple on MacConkey agar.
• Miscellaneous:
- Index organism for fecal contamination of water
63
Klebsiella pneumoniae: (Enterobacteriaceae)
* Metabolism?
* Virulence?
* Clinical?
* Treatment?
• Metabolism:
- Indole-negative
- Ferments lactose
• Virulence:
1. Capsule
2. Non-motile
• Clinical:
1. Pneumonia, with significant lung necrosis and bloody sputum, commonly in alcoholics, or those with underlying lung disease
2. Hospital acquired urinary tract infections and sepsis
• Treatment:
1. Third generation cephalosporin
2. Ciprofloxacin
64
Proteus Mirabilis: (Enterobacteriaceae)
* Metabolism?
* Virulence?
* Toxins?
* Clinical?
* Treatment?
* Diagnostics?
* Miscellaneous?
• Metabolism:
1. Urease: splits urea into NH3 and CO2
2. Indole-negative
3. Does not ferment lactose
• Virulence:
- Motile (swarming)
• Toxins:
- No toxin
• Clinical:
1. Urinary tract infection: urine has a high pH due to urease. May get stones in the bladder.
2. Sepsis
• Treatment:
1. Ampicillin
2. Trimethoprim and sulfamethoxazole
• Diagnostics:
1. Culture: colonies swarm over entire culture plate
2. Examination of urine shows a high pH (from splitting urine into NH3 and CO2)
• Miscellaneous:
- Weil-Felix test: a test that uses antibodies against certain strains of proteus to diagnose rickettsial diseases (as certain rick-ettsiae share similar antigens)
65
Shigella dysenteriae: (Enterobacteriaceae)
* Reservoir?
* Transmission?
* Metabolism?
* Virulence?
* Toxins?
* Clinical?
* Treatment?
* Diagnostics?
* Miscellaneous?
• Reservoir:
- Humans
• Transmission:
- Fecal-oral transmission
• Metabolism:
1. No H2S production
2. Does not ferment lactose
• Virulence:
1. Invades submucosa of intestinal tract, but not the lamina propria
2. NON-motile: No H-antigen (since no flagella)
• Toxins:
- Shiga toxin: Inactivates the 60S ribosome, inhibiting protein synthesis and killing intestinal epithelial cells
• Clinical:
- BLOODY diarrhea with mucus and pus (similar to enteroin-vasive E.coli)
• Treatment:
1. Fluoroquinolones
2. Azithromycin
3. Trimethoprim and sulfamethoxazole
• Diagnostics:
- Stool culture: never part of the normal intestinal flora
• Miscellaneous:
- IgA is best for immunity
66
Salmonella typhi: (Enterobacteriaceae)
Non-typhi groups of Salmonella
* Reservoir?
* Transmission?
* Metabolism?
* Virulence?
* Clinical?
* Treatment?
* Diagnostics?
* Miscellaneous?
• Reservoir:
- S. typhi is found only in humans
- Zoonotic: (Non-typhi)
1. Pet turtles
2. Chickens
3. Uncooked eggs
• Transmission:
- S. typhi is transmitted via fecal-oral route
• Metabolism:
1. Produces H2S
2. Does not ferment lactose.
• Virulence:
1. Motile (H-antigen)
2. Capsule (called the VI antigen): protects from intracellular killing
3. Siderophore
```
• Clinical:
1. Enteric fever
A. Typhoid fever:
1. Fever
2. Abdominal pain
3. Liver or spleen enlargement
4. Rose spots on abdomen
B. Paratyphoid fever (similar to typhoid fever, but caused by non-typhoid Salmonella)
2. Chronic carrier state
3. Gastroenteritis
4. Sepsis
5. Osteomyelitis: especially in sickle cell patients
```
• Treatment:
1. Ciprofloxacin
2. Ceftriaxone
3. Trimethoprim and sulfamethoxazole
4. Azithromycin
* Salmonella gastroenteritis: there is little benefit from antibiotic treatment - can prolong carrier state
• Diagnostics:
- Culture: blood, stool, or urine may contain S. typhi
- Never part of the normal intestinal flora
• Miscellaneous:
A. Facultative intracellular parasite:
1. Lives within macrophages in lymph nodes
2. Can live in gallbladder for years (carriers secrete S.typhi in stools)
B. Persons who are asplenic or have nonfunctioning spleens (sickle cell anemia) are at increased risk of infection by this organism
67
Yersinia enterocolitica: (Enterobacteriaceae)
* Reservoir?
* Transmission?
* Metabolism?
* Virulence?
* Toxins?
* Clinical?
* Treatment?
* Diagnostics?
* Miscellaneous?
• Reservoir:
- Zoonotic: can be found in pigs
• Transmission:
1. Ingestion of contaminated food or water
2. Unpasteurized milk
• Metabolism:
1. Non-lactose fermenter
2. Virulence factors are temperature sensitive; expressed at 37 C
• Virulence:
1. V and W antigens
2. Motile
• Toxins:
- Enterotoxin similar to the heat stable toxic of E.coli: increases cGMP levels
• Clinical:
- Acute enterocolitis, with fever, diarrhea and abdominal pain
• Treatment:
- Antibiotics do not alter the course of the diarrhea. However, patients with positive blood culture should be treated with antibiotics
• Diagnostics:
1. Stool or blood cultures may be positive
2. Examination of the terminal ilium with colonoscopy will reveal mucosal ulceration
• Miscellaneous:
1. Can survive refrigeration.
2. Closely related to Yersinia pestis, which is the cause of bubonic plague
68
Vibrio cholerae: (Vibrionaceae):
* Transmission?
* Metabolism?
* Virulence?
* Toxins?
* Clinical?
* Treatment?
* Diagnostics?
* Miscellaneous?
• Transmission:
1. Fecal-oral transmission
2. Morphology: short comma shaped, gram-negative rod, with a single polar flagellum
• Metabolism:
1. Oxidase-positive
2. Ferments sugars (except lactose)
• Virulence:
1. Motile (H-antigen)
2. Mucinase: digests mucous layer so V. cholerae can attach to cells.
3. Fimbriae: helps with attachment to cells.
4. Non-invasive !!!
• Toxins:
- Choleragen (enterotoxin): like LT of E.coli; increases levels of cAMP, causing secretion of electrolytes from the intestinal epithelium. This results in secretion of fluid into the intestinal tract.
• Clinical:
- Cholera: severe diarrhea with rice water stools. No pus in stools.
• Treatment:
1. Replace fluids
2. Doxycycline
3. Fluoroquinolone
• Diagnostics:
1. Dark field microscopy of stool reveals motile organisms that are immobilized with antiserum
2. Grows as flat yellow colonies on selective media: thiosulfate-citrate-bile salts-sucrose (TCBS) agar
• Miscellaneous:
- Death by dehydration; children affected in endemic areas
1991: Latin America epidemic
1993: Epidemic in Bangladesh and India
69
Vibrio Parahaemolyticus: (Vibrionaceae)
* Reservoir?
* Transmission?
* Metabolism?
* Virulence?
* Toxins?
* Clinical?
* Treatment?
* Diagnostics?
• Reservoir:
- Fish
• Transmission:
1. Consumption of raw fish
2. Morphology: short comma shaped, with a single polar flagellum
• Metabolism:
- Halophilic (likes salt)
• Virulence:
1. Motile (H-antigen)
2. Capsule
• Toxins:
- Hemolytic cytotoxin
• Clinical:
- Cause of 25% of food poisoning in Japan (diarrhea for 3 days)
• Treatment:
1. Doxycycline
2. Fluoroquinolone
* (unclear if antibiotics change clinical course)
• Diagnostics:
- Requires thiosulfate and bile salts
70
Campylobacter jejuni (Vibrionaceae)
* Reservoir?
* Transmission?
* Metabolism?
* Virulence?
* Toxins?
* Clinical?
* Treatment?
* Diagnostics?
* Miscellaneous?
• Reservoir:
- Zoonotic: wild and domestic animals, and poultry
• Transmission:
1. Uncooked meat (especially poultry)
2. Unpasteurized milk
3. Fecal-oral
4. Morphology: curved gram-negative rods, with a single polar flagellum
• Metabolism:
1. Microaerophilic
2. Oxidase positive
3. Optimum temperature is 42C
• Virulence:
1. Motile (H-antigen)
2. Invasive
• Toxins:
1. Enterotoxin:
similar to cholera toxin and the LT of E. coli
2. Cytotoxin: destroys mucosal cells
• Clinical:
- Secretory or bloody diarrhea
• Treatment:
1. Fluoroquinolone
2. Erythromycin
• Diagnostics:
1. Microscopic exam of stool reveals motile, curved gram-negative rods
2. Selective media with antibiotics at 42C
• Miscellaneous:
- One of the three most common causes of diarrhea in the world
71
Helicobacter pylori: (Vibrionaceae)
* Transmission?
* Metabolism?
* Toxins?
* Clinical?
* Treatment?
* Diagnostics?
* Miscellaneous?
• Transmission:
- Morphology: curved gram-negative rods, with a tuft of polar flagellum
• Metabolism:
1. Microaerophilic
2. Urease-positive
• Toxins:
- No toxin
• Clinical:
1. Duodenal ulcers
2. Chronic gastritis
• Treatment:
1. Bismuth, ampicillin, metronidazole and tetracycline
2. Clarithromycin and omeprazole
- Both regimens reduce duodenal ulcer relapse
72
Bacteroides fragilis: (Bacteroidaceae)
* Transmission?
* Metabolism?
* Toxins?
* Clinical?
* Treatment?
* Diagnostics?
* Miscellaneous?
• Transmission:
- Part of the normal flora of the intestine
• Metabolism:
1. Anaerobic
2. Gram-negative rod
3. Non-spore former
4. Polysaccharide capsule
• Toxins:
- Does not contain lipid A (NO endotoxin)
• Clinical:
- Abscesses in the gastrointestinal tract, pelvis, and lungs
• Treatment:
1. Metronidazole
2. Clindamycin
3. Chloramphenicol
4. Surgically drain abscesses
• Diagnostics:
1. Gram-stain
2. Anaerobic culture
• Miscellaneous:
- Infection occurs when the organism enters into the peritoneal cavity
73
Bacteroides melaninogenicus: (Bacteroidaceae)
* Transmission?
* Metabolism?
* Toxins?
* Clinical?
* Treatment?
* Diagnostics?
• Transmission:
- Part of the normal flora of the intestine
• Metabolism:
1. Anaerobic
2. Gram-negative rod
3. Non-spore former
4. Polysaccharide capsule
• Toxins:
- Does not contain lipid A (so NO Endotoxin)
• Clinical:
1. Necrotizing anaerobic pneumonia
2. Periodontal disease
3. Abdominal and pelvic abscess
4. Otitis media
• Treatment:
- Penicillin G
• Diagnostics:
1. Gram-stain
2. Anaerobic culture
74
Fusobacterium: (Bacteroidaceae)
* Metabolism?
* Toxins?
* Clinical?
* Treatment?
* Diagnostics?
• Metabolism:
1. Anaerobic
2. Gram-negative rod
3. Non-spore former
• Clinical:
1. Necrotizing anaerobic pneumonia
2. Periodontal disease
3. Abdominal and pelvic abscess
4. Otitis media
• Treatment:
- Penicillin G
• Diagnostics:
1. Gram-stain
2. Anaerobic culture
75
Pseudomonas Aeruginosa
* Reservoir?
* Transmission?
* Metabolism?
* Virulence?
* Toxins?
* Clinical?
* Treatment?
* Diagnostics?
* Miscellaneous?
• Reservoir:
- Soil
- Water
- Plants
- Animals
- Intestinal flora
- Skin
• Transmission:
- Medical devices
- Hands of healthcare workers
• Metabolism:
1. Obligate aerobe
2. Non-lactose fermenter
3. Oxidase-positive
• Virulence:
1. Motile (polar flagella)
2. Hemolysin
3. Collagenase
4. Elastase
5. Fibrinolysin
6. Phospholipase C
7. DNAse
8. Antiphagocytic capsule (some strains)
• Toxins:
1. Exotoxin A (similar to diphtheria toxin): inhibits protein synthesis by blocking EF2
• Clinical:
1. Burns
2. Endocarditis
3. Pneumonia
4. Sepsis
5. External Malignant otitis media
6. UTI
7. Diabetic Osteomyelitis
• Treatment:
1. Timentin
2. Piperacillin
3. Imipenem
4. Doripenem
5. Aminoglycosides
6. Aztreonam
7. Ciprofloxacin
8. Ceftazidime
9. Cefepime
10. Polymixins
• Diagnostics:
1. Culture: greenish metallic appearing colonies on blood agar, which have fruity (grape) smell
• Miscellaneous:
1. Common etiology for infection in neutropenic patients
2. Produces pigments when cultured:
a. Pyocyanin (blue pigment)
b. Pyoverdin (green pigment)
76
Burkholderia cepacia (COLE SPROUSE HAD THIS)
* Reservoir?
* Transmission?
* Metabolism?
* Virulence?
* Clinical?
* Treatment?
* Diagnostics?
• Reservoir:
- Soil
- Water
- Plants
- Animals
- Lungs of cystic fibrosis patients
• Transmission:
- Medical devices
- Hands of healthcare workers
- Between cystic fibrosis patients?
• Metabolism:
1. Oxidase-positive
2. Non-lactose fermenter
• Virulence:
- Extremely antibiotic and disinfectant resistant
• Clinical:
1. Pneumonia in Cystic fibrosis patients
2. Infections in patients with chronic granulomatous disease
• Treatment:
1. Trimethoprim-sulfamethoxazole
2. Timentin
3. Ciprofloxacin
4. Ceftazidime
5. Carbapenems
• Diagnostics:
1. May use selective media with colistin to select for growth
77
Stenotrophomonas maltophilia
* Reservoir?
* Transmission?
* Metabolism?
* Virulence?
* Toxins?
* Clinical?
* Treatment?
* Miscellaneous?
• Reservoir:
- Soil
- Water
- Skin
- Secretions
• Transmission:
- Medical devices
- Hands of healthcare workers
• Metabolism:
1. Obligate aerobe
2. Oxidase-negative
3. Non-lactose fermenter
• Virulence:
- Multiple acquired mechanisms of antibiotic resistance
• Toxins:
1. Bacteriocin production
2. Protective capsule (inhibits phagocytosis)
• Clinical:
1. Pneumonia
2. Line-related bacteremia
3. UTI
4. Burn/wound infections
5. Eye infections
• Treatment:
1. Aminoglycosides
2. Carbapenems
3. Polymixins
4. Tigecyline
5. Sulbactam
• Miscellaneous:
1. May be mistaken for Neisseria
2. Guide therapy with antibiotic susceptibilities
78
Haemophilus Influenzae:
* Reservoir?
* Virulence?
* Toxins?
* Clinical?
* Treatment?
* Diagnostics?
* Miscellaneous?
• Reservoir:
- Man only (obligate human parasite)
- Transmitted via respiratory route
• Virulence:
1. Capsule: 6 types, a-f (b is most virulent)
2. Attachment pili
3. IgA1 protease
• Toxins:
- Cytolethal distending toxin (CDT)
- Hemolysin
```
• Clinical:
Encapsulated
H. influenzae (usually type B capsule)
1. Meningitis: Haemophilus influenzae type b is the primary cause of meningitis in infants from 3 to 36 months of age. Complications include mental retardation, seizures, deafness, and death.
2. Acute epiglottitis
3. Septic arthritis in infants
4. Sepsis: especially in patients without functioning spleens
5. Pneumonia
```
```
Nonencapsulated
H. influenzae
1. Otitis media
2. Sinusitis
3. COPD exacerbation and pneumonia
```
• Treatment:
1. Second or third generation cephalosporins (since H. influenzae can acquire ampicillin resistance by plasmids)
2. Hib vaccine: H. influenzae polysaccaride capsule of type b strain (Hib) is conjugated to diphtheria toxoid and given to children at 2,4, 6, and 15 months (DTaP and oral polio are given at the same time.) This has resulted in solid immunity during the critical 3 month to 3 year age, and has dramatically reduced the incidence of Hib infection (acute epiglottis, meningitis, etc.) in the US
3. Passive immunization: mother is immunized during 8th month of pregnancy to increase passive antibody transfer in breast milk
• Diagnostics:
1. Gram stain
2. Culture specimen on blood agar that has been heated to 80 C for 15 minutes (now called chocolate agar). This high temperature lyses the red blood cells, releasing both hematin (called X factor) and NAD+ (called V factor). Like the Neisseria, H. influenzae organisms grow best when the chocolate agar is placed in a high CO2 environment at 37 C.
3. Fluorescently labeled antibodies (ELISA and latex particle agglutination)
4. Positive Quellung test: due to its capsule (just like Streptococcus pneumoniae)
• Miscellaneous:
1. Haemophilus influenzae requires two factors for growth (both found in blood):
- X factor: Hematin
- V factor: NAD +
2. Note:
Haemophilus stands for "blood loving"
79
Haemophilus ducreyi:
* Reservoir?
* Toxins?
* Clinical?
* Treatment?
* Diagnostics?
* Miscellaneous?
• Reservoir:
- Sexually transmitted disease
• Toxins:
- No exotoxins
• Clinical:
- Chancroid: painful genital ulcer, often associated with unilateral swollen lymph nodes that can rupture releasing pus
• Treatment:
1. Azithromycin or erythromycin
2. Ceftriaxone (IM)
3. Ciprofloxacin
• Diagnostics:
- Gram stain and culture of ulcer exudate and pus released from swollen lymph node
• Miscellaneous:
1. A sexually transmitted disease
2. Requires X factor (hematin) only
80
Gardnerella Vaginalis:
* Reservoir?
* Virulence?
* Toxins?
* Clinical?
* Treatment?
* Diagnostics?
* Miscellaneous?
• Reservoir:
- Sexually transmitted disease
• Virulence:
- No capsule
• Toxins:
- No exotoxins
• Clinical:
- Bacterial vaginitis: foul smelling vaginal discharge (with fishy odor), vaginal pruritus, and often dysuria
• Treatment:
- Metronidazole
• Diagnostics:
- Clue cells**: vaginal epithelial cells that contain tiny pleomorphic gram-negative bacilli within the cytoplasm
• Miscellaneous:
- Does not require X factor or V factor for growth
81
Bordetella Pertussis:
* Reservoir?
* Virulence?
* Toxins?
* Clinical?
* Treatment?
* Diagnostics?
* Miscellaneous?
• Reservoir:
- Man: highly contagious
- Transmitted via respiratory route
• Virulence:
1. Capsule
2. Beta-lactamase
3. Filamentous hemagglutinin (FHA): A pili rod that extends from the surface of B. pertussis, enabling the bacteria to bind to ciliated epithelial cells of the bronchi
• Toxins:
1. Pertussis toxin**: activates G proteins that increase cAMP, resulting in:
A. Increased sensitivity to histamine
B. Increased insulin release
C. Increased number of lymphocytes in blood
2. Extracytoplasmic adenylate cyclase: "weakens" neutrophils, lymphocytes, and monocytes
3. Filamentous hemagluttinin: allows binding to ciliated epithelial cells
4. Tracheal cytotoxin: kills ciliated epithelial cells
• Clinical:
Whooping Cough **
1. Catarrhal phase: patient is highly contagious (1-2 weeks)
A. Low grade fever, runny nose and mild cough
B. Antibiotic susceptible during this stage
2. Paroxysmal phase (2-10 weeks)
A. Whoop (bursts of non-productive cough)
B. Increased number of lymphocytes in blood smear
C. Antibiotics ineffective during this stage
3. Convalescent stage
• Treatment:
1. Erythromycin (most effective if given in catarrhal stage)
2. Vaccine: DaPT
1. Diptheria
2. acellular Pertussis
3. Tetanus (Given routinely at ages 2, 4, 6, 15 months and between 4-6 years)
3. Treat household contacts with erythromycin
• Diagnostics:
1. Bordet-Gengou media: potatoes, blood and glycerol agar, with penicillin added
2. Rapid serologic tests (ELISA)
- Collect specimen from posterior pharynx on a calcium alginate swab since B. pertussis will not grow on cotton
3. Direct fluorescein-labeled antibodies applied to nasopharyngeal specimens for rapid diagnosis.
4. PCR detection of bacterial DNA in respiratory secretions
• Miscellaneous:
- High risk groups:
1. Infants less than one year old
2. Adults (as immunity acquired from vaccine wears off)
82
Legionella pneumophila:
* Reservoir?
* Virulence?
* Toxins?
* Clinical?
* Treatment?
* Diagnostics?
* Miscellaneous?
• Reservoir:
- Ubiquitous in man and natural water environments
1. Air conditioning systems
2. Cooling towers
• Virulence:
1. Facultative intracellular parasite: Dot/Icm type IV secretion system inhibits macrophage phagosome/endo/lysosome fusions
2. Cu-Zn superoxide dismutase and catalase-peroxidase protects bacteria from macrophage superoxide and hydrogen peroxide oxidative burst
3. Pili and flagella promote attachment and invasion
4. Secretion of protein toxins like RNAase, phospholipase A and phospholipase C
• Toxins:
- Cytotoxin: kills hamster ovary cells
• Clinical:
1. Pontiac fever**: headache, fever, muscle aches and fatigue, Self-limiting; recovery in a week is common
2. Legionnaire's Disease **: pneumonia: fever and non-productive cough
• Treatment:
1. Azithromycin
2. Levofloxacin
3. Doxycycline
• Diagnostics:
1. Culture on buffered charcoal yeast extract agar (L-cysteine is a critical ingredient)
2. Serology (IFA and ELISA)
3. Urinary antigen can be detected by radioimmunoassay with high sensitivity and specificity and will remain positive for months after infection. Urine antigen test only detects L. pneumophila serogroup 1, but this accounts for 90% of cases.
• Miscellaneous:
1. Facultative intracellular parasite: inside alveolar macrophages
2. Persons with compromised immune systems are especially susceptible
83
Yersinia pestis:
* Reservoir?
* Transmission?
* Metabolism?
* Virulence?
* Toxins?
* Clinical?
* Treatment?
* Diagnostics?
* Miscellaneous?
• Reservoir:
1. Wild rodents
2. City rats
3. Squirrels and prairie dogs in the SW U.S.
• Transmission:
1. Flea bite
2. Contact with infected animal tissue
3. Inhaled aerosolized organisms: human to human transmission occurs during epidemics
• Metabolism:
1. Facultative Anaerobe
2. Virulence factors are temperature sensitive: only expressed at 37 C (temp inside macrophages)
3. Virulence is plasmid mediated
• Virulence:
1. Fraction 1 (F1): This capsular antigen is antiphagocytic
2. V and W proteins
3. Non-motile
4. Requires calcium at 37 C. If insufficient calcium, Y.pestis alters its metabolism and protein production. This trait assists with its intracellular state.
• Toxins:
1. Pesticin: kills other bacteria (including E.coli)
2. Intracellular murine toxin: lethal to mice
• Clinical:
1. Bubonic plague**:
A. regional lymph nodes (usually groin) swell, and become red, hot and tender (called a bubo)
B. High fever
C. Conjunctivitis
2. Sepsis: ** bacteria survive in macrophages, and spread to blood and organs. Death occurs in 75% if untreated
3. Pneumonic plague**: during epidemics, pneumonia occurs, as bacteria are spread from person to person by aerosolized respiratory secretions: 100% fatal if untreated
• Treatment:
1. Streptomycin or gentamicin
2. Doxycycline
3. Killed vaccine is effective only for a few months (attenuated vaccine is more effective but also has more side effects)
• Diagnostics:
1. Gram stain will reveal gram-negative rods with bipolar staining: the ends of these rod shaped bacteria take up stain more than the center
2. Blood culture
3. Culture of bubo aspirate
4. Serology
5. Rapid diagnostic test: antibody against F1 (capsular antigen)
• Miscellaneous:
1. Facultative intracellular parasite
2. Yersinia can accept plasmids from E.coli, and shares many antigens with enteric bacteria
3. Subcutaneous hemorrhage results in a blackish skin discoloration, giving the name "Black Death"
84
Francisella tularensis:
* Reservoir?
* Transmission?
* Metabolism?
* Virulence?
* Clinical?
* Treatment?
* Diagnostics?
* Miscellaneous?
• Reservoir:
1. Rabbits and squirrels
2. Ticks can serve as a reservoir
• Transmission:
1. Bile of tick, deerfly or infected animals
2. Direct contact with infected animal tissue (usually rabbit)
3. Inhaled aerosolized organisms
4. Ingestion of contaminated meat or water
5. Easily transmitted to lab personnel
• Metabolism:
1. Obligate aerobe
2. Requires cysteine
• Virulence:
1. Capsule: antiphagocytic
2. Non-motile
• Clinical:
Tularemia **
1. Ulceroglandular: at the site of tick bite or direct contact with contaminated rabbit, an ulcer develops, with swelling of local lymph nodes
2. Pneumonia: inhalation, or through the blood
3. Oculoglandular: direct inoculation into eyes
4. Typhoidal: ingestion results in GI symptoms (abdominal pain) and fever
• Treatment:
1. Gentamicin or streptomycin
2. Doxycycline
3. Attenuated vaccine: only for high risk individuals
• Diagnostics:
1. Culture (but very dangerous due to its high infectivity): requires addition of cysteine to blood agar media
2. Skin test
3. Measure rise in IgG antibody titer (IgM is not very good)
• Miscellaneous:
- Facultative intracellular parasite
85
Brucella:
* Reservoir?
* Transmission?
* Metabolism?
* Virulence?
* Clinical?
* Treatment?
* Diagnostics?
* Miscellaneous?
• Reservoir:
- Goats (Brucella melitensis)
- Cattle (Brucella abortus)
- Pigs (Brucella suis)
- Dogs (Brucella canis)
• Transmission:
1. Direct contact with contaminated live-stock or aborted placentas
2. Ingestion of infected milk products
3. Aerosolization in laboratory or possibly due to bioterrorism
• Metabolism:
- Obligate aerobe
• Virulence:
1. Capsule
2. Non-motile
3. Tropism for erythritol, a sugar found in animal placentas
• Clinical:
1. Brucellosis**:
- Undulating fever (fever peaks in the evening, and returns to normal by morning)
- Weakness
- Loss of appetite
2. Induces abortions in animals
• Treatment:
1. Pasteurization of milk
2. Treat with combination of doxycycline and one other drug (gentamicin, streptomycin, or rifampin)
3. All cattle are immunized with a living attenuated strain of Brucella abortus
• Diagnostics:
1. Culture of blood, bone marrow (best yield), liver, or lymph nodes
2. Serologic test
3. Skin test: indicates exposure only
• Miscellaneous:
- Facultative intracellular parasite
86
Pasteurella multocida:
* Reservoir?
* Transmission?
* Metabolism?
* Virulence?
* Clinical?
* Treatment?
* Diagnostics?
* Miscellaneous?
• Reservoir:
- Part of the normal flora of domestic and wild animals
• Transmission:
- Bite from dog or cat
• Metabolism:
- Facultative anaerobe
• Virulence:
1. Capsule
2. Non-motile
• Clinical:
- Wound infections (following dog or cat bites): may progress to infection of nearby bones and joints
• Treatment:
1. Penicillin G
2. Doxycycline
3. Third generation cephalosporin
• Diagnostics:
- Culture specimen on standard lab media
• Miscellaneous:
- NOT a facultative intracellular organism!
87
Chlamydia trachomatis:
* Reservoir?
* Transmission?
* Metabolism?
* Virulence?
* Clinical?
* Treatment?
* Diagnostics?
• Reservoir:
- Humans
- Morphological note: gram-negative, but lacks peptidoglycan layer and muramic acid
```
• Transmission:
1. Direct personal contact
2. Primarily affects the:
A. Eyes
B. Genitals
C. Lungs
3. Note that trachoma is found in underdeveloped countries, and transmission occurs due to poor hygiene
```
• Metabolism:
Life Cycle
1. Elementary body (EB): dense spherule that infects cells
2. Initial (reticulate) body: After EB enters cell, it transforms into an initial body
A. Larger and osmotically fragile
B. Can reproduce via binary fission
C. Requires ATP from the host
D. The initial body transforms back into EB, which leaves the cell to infect other cells
- Note: Clamydia are obligate Intracellular parasites - steal ATP from host with ATP/ADP translocator
• Virulence:
1. Resistant to lysozyme (since their cell wall lacks muramic acid)
2. Prevents phagosome - lysosome fusion
3. Non-motile
4. No pili
5. No exotoxins
• Clinical:
Serotypes A, B, and C:
- Trachoma: causes scarring of the inside of the eyelid, resulting in redirection of the eyelashes onto the corneal surface. This results in corneal scarring and blindness
Serotypes D through K:
1. Inclusion conjunctivitis (ophthalmia neonatorum)
2. Infant pneumonia
3. Urethritis, cervicitis, and pelvic inflammatory disease (PID) in women
4. Nongonococcal urethritis, epididymitis and prostatitis in men
Complications of chlamydial genital tract infections:
1. Sterility, ectopic pregnancy and chronic pain may occur after pelvic inflammatory disease
2. Reiter's syndrome: triad of conjunctivitis, urethritis, and arthritis
3. Fitz-Hugh-Curtis Syndrome: perihepatitis
Serotypes L1, L2, and L3
- Lymphogranuloma venereum
• Treatment?
- Genital and eye infections:
1. Doxycycline (use only for adults)
2. Erythromycin (especially for infants and pregnant woman)
3. Azithromycin
- Note: Systemic treatment is required for any chlamydial eye infection!! This is especially true for infants, who can develop chlamydial pneumonia following chlamydial conjunctivitis
• Diagnostics:
1. Can NOT be grown on artificial media. Can classically be grown in chick yolk sacs. More commonly, Chlamydia is cultured in certain cell lines (McCoy cells, for example)
2. For inclusion conjunctivitis, (ophthalmia neonatorum): Scrapings from the surface of the conjunctiva will show intracytoplasmic inclusion bodies within conjunctival epithelial cells. The inclusion bodies contain glycogen, and thus stain with iodine or giemsa
3. Gram stain of genital secretions will NOT show gram-negative intracellular diplococci
4. Urethritis: most commonly diagnosed by polymerase chain reaction of urethral swab or urine sample
5. Immunofluorescent slide test: place infected genital or ocular secretions on a slide and stain with fluorescein-conjugated anti-chlamydial antibody
6. Serologic: Examine blood for elevated titers of anti-chlamydial antibodies with complement fixation and immunofluorescence tests
7. Lymphogranuloma venereum:
A. Serologic tests
B. Frei test, which is rarely used, is similar to the PPD skin test for tuberculosis
88
Chlamydophila psittaci:
* Reservoir?
* Transmission?
* Metabolism?
* Virulence?
* Clinical?
* Treatment?
* Diagnostics?
• Reservoir:
- birds and poultry
• Transmission:
1. Bird feces dry out
2. Fecal particles are inhaled, infecting the lungs
• Metabolism:
- Life cycle is similar to Chlamydia trachomatis
• Virulence:
- same
• Clinical:
- Psittacosis: a viral-like atypical pneumonia, with fever and dry, non-productive cough (similar to a Mycoplasma pneumonia)
• Treatment:
1. Doxycycline
2. Erythromycin
• Diagnostics:
1. Serologic: Examine blood for elevated titers of antibodies with complement fixation and immunofluorescence tests
2. Intracytoplasmic inclusion bodies do not stain with iodine
89
Chlamydophila pneumoniae (strain TWAR):
* Reservoir?
* Transmission?
* Metabolism?
* Clinical?
* Treatment?
* Diagnostics?
• Reservoir:
- Humans (spread from human to human)
• Transmission:
- Respiratory route
• Metabolism:
- Life cycle is similar to Chlamydia trachomatis
• Clinical:
- Atypical pneumonia: viral-like atypical pneumonia (similar to a Mycoplasma pneumonia) in young adults
• Treatment:
1. Doxycycline
2. Erythromycin
• Diagnostics:
1. Serologic: Examine blood for elevated titers of antibodies with complement fixation and immunofluorescence tests
2. Intracytoplasmic inclusion bodies do not stain with iodine
90
Rickettsia generalities:
* Transmission?
* Metabolism?
* Virulence?
* Clinical?
* Treatment?
* Diagnostics?
• Transmission:
- Arthropod vector (except Q fever)
• Metabolism:
1. Rickettsiae are obligate intracellular parasites: They can not make their own ATP
2. Grow in cytoplasm (in contrast to Chlamydia, which replicates in endosomes)
• Virulence:
1. Non-motile
2. No exotoxins
• Clinical:
- Damages ENDOthelial cells lining blood vessels
• Treatment:
1. Doxycycline
2. Chloramphenicol
• Diagnostics:
1. Culture: chick yolk sac
- Can NOT be grown on artificial media (except for Bartonella species)
2. Serology: identify antibodies against the rickettsial organism
3. Weil-Felix reaction
91
Rickettsia rickettsii:
* Reservoir?
* Transmission?
* Clinical?
* Treatment?
* Diagnostics?
• Reservoir:
- Dogs, rabbits, and wild rodents
• Transmission:
1. Wood tick: In Western U.S. (Dermacentor andersoni)
2. Dog tick: In Eastern U.S. (Dermacentor viariabilis)
```
• Clinical:
Rocky Mountain Spotted Fever**:
1. Fever
2. Conjunctival injection (redness)
3. Severe headache
4. Rash on wrists, ankles, soles, and palms initially, becomes more generalized later
```
• Treatment:
1. Doxycycline
2. Chloramphenicol
```
• Diagnostics:
1. Clinical exam
2. Direct immunofluorescent exam of skin biopsy from rash site
3. Serology
4. Weil-Felix reaction:
A. Positive OX-19
B. Positive OX-2
```
92
Rickettsia akari:
* Reservoir?
* Transmission?
* Clinical?
* Treatment?
* Diagnostics?
• Reservoir:
- House mice
• Transmission:
- Mites (which live on the house mice)
• Clinical:
Rickettsial Pox:
Vesicular rash similar to chicken pox. It resolves over 2 weeks.
• Treatment:
1. Doxycycline
2. Chloramphenicol
• Diagnostics:
- Weil-Felix reaction negative
93
Rickettsia prowazekii:
* Reservoir?
* Transmission?
* Clinical?
* Treatment?
* Diagnostics?
• Reservoir:
1. Humans
2. Flying squirrels
• Transmission:
- Human body louse (Pediculus corporis)
• Clinical:
1. Epidemic Louse-borne Typhus
A. Abrupt onset of fever and headache
B. Rash, which spares the palms, soles, and face
C. Delirium/stupor
D. Gangrene of hands or feet
2. Brill-Zinsser Disease
A. Reactivation of Rickettsia prowazekii
B. Mild symptoms
C. NO rash
• Treatment:
1. Doxycycline
2. Chloramphenicol
3. Eradicate human lice
• Diagnostics:
1. Weil-Felix reaction: positive OX-19
2. Serology
94
Rickettsia typhi:
* Reservoir?
* Transmission?
* Metabolism?
* Virulence?
* Clinical?
* Treatment?
* Diagnostics?
• Reservoir:
1. Rats
2. Small rodents
• Transmission:
- Rat flea (Xenopsylla cheopis)
• Clinical:
- Endemic (or Murine)
Typhus: fever, headache, and rash
• Treatment:
1. Doxycycline
2. Chloramphenicol
• Diagnostics:
- Weil-Felix reaction: positive OX-19
95
Rickettsia tsutsugamushi:
* Reservoir?
* Transmission?
* Clinical?
* Treatment?
* Diagnostics?
• Reservoir:
1. Rats
2. Shrew
3. Mongooses
4. Birds
• Transmission:
- Mite larvae (chiggers)
• Clinical:
- Scrub Typhus:
1. Fever and headache
2. Eschar (scab) at bite site
3. Followed by a rash
• Treatment:
1. Doxycycline
2. Chloramphenicol
• Diagnostics:
- Weil-Felix reaction: positive OX-K
96
Bartonella quintana:
* Reservoir?
* Transmission?
* Metabolism?
* Clinical?
* Treatment?
* Diagnostics?
• Reservoir:
- Humans
• Transmission:
- Body louse
• Metabolism:
- Not an obligate intracellular parasite
• Clinical:
1. Trench Fever: fever, headache and back pain. It lasts for 5 days and recurs at 5 day intervals
2. Bacteremia, endocarditis, and bacillary angiomatosis
• Treatment:
1. Doxycycline
2. Chloramphenicol
3. Azithromycin
• Diagnostics:
1. Serology
2. PCR
97
Bartonella henselae:
* Metabolism?
* Clinical?
* Treatment?
* Diagnostics?
• Metabolism:
- Not an obligate intracellular parasite
• Clinical:
1. Cat-scratch disease
2. Bacillary angiomatosis
3. Bacteremia
4. Endocarditis ("culture negative")
• Treatment:
1. Azithromycin
2. Doxycycline
• Diagnostics:
1. Serology
2. PCR
98
Coxiella burnetii:
* Reservoir?
* Transmission?
* Metabolism?
* Clinical?
* Treatment?
* Diagnostics?
• Reservoir:
- Cattle, sheep, and goats
• Transmission:
Exception:
- No arthropod vector required. Direct airborne transmission of endospore from cow hide or dried placenta, or via consumption of endospore-contaminated unpasteurized cow milk
• Metabolism:
Exception:
1. Can grow at a pH of 4.5 within phagolysosomes
2. Has an endospore form
• Clinical:
1. Q fever: fever, headache, and viral-like pneumonia. No rash!! (This is the only rickettsial disease without a skin rash!!)
2. Complications:
1. Hepatitis
2. Endocarditis
• Treatment:
1. Doxycycline
2. Erythromycin
- Pasteurize milk to 60 C
• Diagnostics:
1. Complement fixation test demonstrating a rise in antibody
2. PCR
99
```
Ehrlichia chaffeensis (HME)
Anaplasma phogocytophilum (HGA)
Ehrlichia ewingii
```
* Reservoir?
* Transmission?
* Clinical?
* Treatment?
* Diagnostics?
• Reservoir:
- Deer, dogs, coyotes = Chaffeensis
- Deer, white-footed mouth = The other two
• Transmission:
- Ticks
• Clinical:
- Human Ehrlichiosis: similar to Rocky Mountain spotted fever, but rash is rare
• Treatment:
1. Doxycycline
2. Rifampin
- Resistant to chloramphenicol
• Diagnostics:
1. Rise in acute and convalescent antibody titers
2. Characteristic ehrlichial inclusion bodies are sometimes seen in leukocytes on blood smears
3. PCR
100
Spirochete generalities:
* Metabolism and morphology?
* Virulence?
* Treatment?
* Diagnostics?
• Metabolism and morphology:
1. Multiply by transverse fission.
2. Motile: six axial filaments* wind around the organism between the peptidoglycan layer and the outer cell membrane. Contraction of axial filaments conveys spinning motion
• Virulence:
- No exotoxins!!
• Diagnostics:
- Can not culture on artificial media (except for Leptospira)
101
Treponema pallidum:
* Reservoir?
* Transmission?
* Metabolism and Morphology?
* Virulence?
* Clinical?
* Treatment?
* Diagnostics?
• Reservoir:
- Humans only
• Transmission:
- Sexual
• Metabolism and Morphology:
1. Microaerophilic
2. Morphology: thick rigid spirals
3. Highly sensitive to elevated temperatures
• Virulence:
- Motile
• Clinical:
SYPHILIS ***
A. Primary stage: painless chancre (skin ulcer)
B. Secondary stage:
1. Rash on palms and soles
2. Condyloma latum: painless, wartlike lesion which occurs in warm, moist places (vulva or scrotum)
3. CNS, eyes, bones, kidneys and/or joints can be involved
C. Latent stage: 25% may relapse back to the secondary stage
D. Tertiary stage (33%):
1. Gummas of skin and bone
2. Cardiovascular syphilis
3. Neurosyphilis: may get the Argyll-Robertson pupil
E. Congenital syphilis: contracted in-utero
• Treatment:
1. Penicillin G
2. Erythromycin
3. Doxycycline
- Jarisch-Herxheimer reaction: acute worsening of symptoms after antibiotics are started
• Diagnostics:
1. Cutaneous lesions examined by dark field microscopy, immunofluorescence, ELISA, or silver stain
2. Non-specific treponemal test: VDRL; RPR
3. Specific treponemal test: FTA-ABS, MHA-TP
- All pregnant women should be screened with VDRL because antibiotic treatment prior to 4 months of gestation prevents congenital syphilis
4. Polymerase chain reaction (PCR) detection of bacterial DNA is available
102
Treponema pallidum subspecies endemicum:
* Reservoir?
* Transmission?
* Metabolism and Morphology?
* Virulence?
* Clinical?
* Treatment?
* Diagnostics?
• Reservoir:
- Desert zones of Africa and the Middle East
• Transmission:
- Sharing of drinking and eating utensils
• Metabolism and Morphology:
- Morphologically and serologically indistinguishable from T. pallidum
• Virulence:
- Motile
• Clinical:
BEJEL
A. Primary and secondary lesions: occur in oral mucosa
B. Tertiary lesions: gummas of skin and bone
• Treatment:
- Penicillin
• Diagnostics:
- VDRL and FTA-ABS are positive
103
Treponema pertenue:
* Reservoir?
* Transmission?
* Metabolism and Morphology?
* Virulence?
* Clinical?
* Treatment?
* Diagnostics?
• Reservoir:
- Moist tropical regions
• Transmission:
- Person-to-person contact or via flies
• Metabolism and Morphology:
- Morphologically, genetically and serologically indistinguishable from T. Pallidum
• Virulence:
- Motile
• Clinical:
YAWS
A. Primary and secondary lesions: ulcerative skin lesions near initial site of infection - often looks like condyloma lata
B. Tertiary lesions: gummas of skin and bone (resulting in severe facial disfigurement)
• Treatment:
1. Azithromycin
2. Penicillin
3. Plastic surgery to correct facial disfigurement
• Diagnostics:
- VDRL and FTA-ABS are positive
104
Treponema carateum:
* Reservoir?
* Transmission?
* Metabolism and Morphology?
* Virulence?
* Clinical?
* Treatment?
* Diagnostics?
• Reservoir:
- Latin America
• Transmission:
- Person-to-person contact
• Metabolism and Morphology:
- Morphologically and serologically indistinguishable from T. pallidum
• Virulence:
- Motile
• Clinical:
PINTA
- Flat red or blue lesions which do NOT ulcerate
• Treatment:
- Penicillin
• Diagnostics:
- VDRL and FTA-ABS are positive
105
Borrelia burgdorferi:
* Reservoir?
* Transmission?
* Metabolism and Morphology?
* Clinical?
* Treatment?
* Diagnostics?
• Reservoir:
1. White-footed mouse
2. White-tailed deer
• Transmission:
- Vector = lxodes ticks
1. Ixodes scapularis: East and Midwest
2. Ixodes pacificus: West coast
• Metabolism and Morphology:
- Microaerophilic
• Clinical:
LYME DISEASE
A. Early localized stage (stage 1): Erythema chronicum migrans (ECM)
B. Early disseminated stage (stage 2)
1. Multiple smaller ECM
2. Neurologic: aseptic meningitis, cranial nerve palsies (Bell's palsy), and peripheral neuropathy
3. Cardiac: transient heart block or myocarditis
4. Brief attacks of arthritis of large joints (knee)
C. Late stage (stage 3)
1. Chronic arthritis
2. Encephalopathy
• Treatment:
1. Doxycycline
2. Amoxicillin
3. Ceftriaxone for neurologic disease
• Diagnostics:
1. Elevated levels of antibodies against Borrelia burgdorferi can be detected by ELISA
2. Western immunoblotting
106
18 other species of Borrelia:
* Reservoir?
* Transmission?
* Metabolism and Morphology?
* Virulence?
* Clinical?
* Treatment?
* Diagnostics?
• Reservoir:
- Wild rodents in remote undisturbed areas in the Western U.S.
• Transmission:
Vectors
1. Borrelia recurrentis: louse
2. The other species of Borrelia: ticks
• Metabolism and Morphology:
- Microaerophilic
• Virulence:
1. Antigenic variation: variable expression of outer membrane Vmp lipoproteins* allows Borrelia to escape opsonization and phagocytosis
2. No toxins!!
```
• Clinical:
RELAPSING FEVER **
A. Recurring fever about every 8 days
B. Fevers break with drenching sweats
C. Rash and splenomegaly
D. Occasionally meningeal involvement
```
• Treatment:
1. Doxycycline
2. Erythromycin
3. Penicillin G
• Diagnostics:
1. Blood culture during febrile periods
2. Dark field examination of blood drawn during febrile periods
3. Wright's or giemsa - stained peripheral blood smear reveals organism 70% of the time
4. Serologic
107
Leptospira interrogans
23 serogroups
250 serovars
* Reservoir?
* Transmission?
* Metabolism and Morphology?
* Clinical?
* Treatment?
* Diagnostics?
• Reservoir:
- Zoonotic (dogs, cats, livestock, and wild animals)
• Transmission:
- Direct contact with infected urine or animal tissue. Organisms penetrate broken skin (i.e. on feet) and mucous membranes (swallowing urine-contaminated water)
• Metabolism and Morphology:
1. AEROBIC
2. Spiral shaped, with hooks on both ends ("ice tongs")
3. Two axial flagella wrap around and run along the length of the organism under the outer membrane (periplasmic flagella).
• Clinical:
1. First phase (leptospiremic): organisms in blood and CSF causes high spiking temperatures, headache and severe muscle aches (thighs and lower back)
2. Second phase (immune): correlates with emergence of IgM and involves recurrence of the above symptoms, often with meningismus (neck pain)
3. WEIL'S DISEASE: severe case of leptospirosis with renal failure, hepatitis (and jaundice), mental status changes, and hemorrhage in many organs
• Treatment:
1. Penicillin G
2. Doxycycline
• Diagnostics:
1. First week: culture blood or cerebral spinal fluid (on lab media, or by inoculation into animals)
2. Second week to months: culture urine
3. Rarely, dark field microscopy is successful (not recommended)
4. Antibody based ELISA to detect Leptospira antigens in the urine
5. Polymerase Chain Reaction (PCR) to detect bacterial DNA in serum, CSF, and urine
108
Mycobacterium tuberculosis:
* Morphology?
* Metabolism?
* Virulence?
* Toxins?
* Clinical?
* Treatment?
* Diagnostics?
* Miscellaneous?
• Morphology:
1. 40% of total cell dry weight is lipids
2. Composed of mycolic acids
3. Thin rods
4. Non-motile
- Remember, mycolic acids are also found in Nocardia (which also is acid fast)
• Metabolism:
1. Aerobic
2. Catalase-positive
3. Slow growth rate
• Virulence:
1. Mycosides
A. Cord factor: only found in virulent strains (May be responsible for release of tumor necrosis factor (cachectin), causing weight loss)
B. Sulfatides: Inhibit phagosome-lysosome fusion
C. Wax D: acts as an adjuvant
2. Iron siderophore (Mycobactin)
3. Facultative intracellular growth: M. tuberculosis can survive and multiply in macrophages
- Notice!!!
- Non-motile
- No capsule
- No attachment pili
• Toxins:
- No exotoxin nor endotoxin. (It has lipopolysaccharide, but no Lipid A)
```
• Clinical:
Tuberculosis
A. Primary tuberculosis:
1. Asymptomatic
2. Overt disease, involving the lungs or other organs
B. Reactivation or secondary tuberculosis:
1. Pulmonary
2. Pleural or pericardial
3. Lymph node infection
4. Kidney
5. Skeletal
6. Joints
7. Central nervous system
8. Military tuberculosis
```
```
• Treatment:
First line drugs:
1. Isoniazid (INH)
2. Rifampin
3. Pyrazinamide
4. Ethambutol
5. Streptomycin
```
• Diagnostics:
1. Acid-fast stain of specimen
2. RAPID CULTURE: Bactec radiometric culture, a liquid broth in a bottle, with radioactive palmitate as a carbon source. Mycobacteria grow and use the carbon, allowing early detection (in 1-2 weeks) even before colonies can be seen.
3. PPD skin test
4. IGRA (Interferon gamma release assay)
5. Chest X-ray
6. Gene Xpert MTB/Rif (and similar PCR based studies)
```
• Miscellaneous:
Purified Protein Derivative (PPD) Test
1. Measure zone of induration:
- Positive reaction:
1. >5 mm (immunocompromised host)
2. >10 mm (have chronic disease or risk factors for exposure to TB)
3. >15 mm (all others)
```
2. A positive reaction does not mean active disease.
3. Can get false negatives in patients with AIDS or malnourished individuals
109
Mycobacterium tuberculosis:
* Morphology?
* Metabolism?
* Virulence?
* Toxins?
* Clinical?
* Treatment?
* Diagnostics?
* Miscellaneous?
• Morphology:
1. 40% of total cell dry weight is lipids
2. Composed of mycolic acids
3. Thin rods
4. Non-motile
- Remember, mycolic acids are also found in Nocardia (which also is acid fast)
• Metabolism:
1. Aerobic
2. Catalase-positive
3. Slow growth rate
• Virulence:
1. Mycosides
A. Cord factor: only found in virulent strains (May be responsible for release of tumor necrosis factor (cachectin), causing weight loss)
B. Sulfatides: Inhibit phagosome-lysosome fusion
C. Wax D: acts as an adjuvant
2. Iron siderophore (Mycobactin)
3. Facultative intracellular growth: M. tuberculosis can survive and multiply in macrophages
- Notice!!!
- Non-motile
- No capsule
- No attachment pili
• Toxins:
- No exotoxin nor endotoxin. (It has lipopolysaccharide, but no Lipid A)
```
• Clinical:
Tuberculosis
A. Primary tuberculosis:
1. Asymptomatic
2. Overt disease, involving the lungs or other organs
B. Reactivation or secondary tuberculosis:
1. Pulmonary
2. Pleural or pericardial
3. Lymph node infection
4. Kidney
5. Skeletal
6. Joints
7. Central nervous system
8. Military tuberculosis
```
```
• Treatment:
First line drugs:
1. Isoniazid (INH)
2. Rifampin
3. Pyrazinamide
4. Ethambutol
5. Streptomycin
```
• Diagnostics:
1. Acid-fast stain of specimen
2. RAPID CULTURE: Bactec radiometric culture, a liquid broth in a bottle, with radioactive palmitate as a carbon source. Mycobacteria grow and use the carbon, allowing early detection (in 1-2 weeks) even before colonies can be seen.
3. PPD skin test
4. IGRA (Interferon gamma release assay)
5. Chest X-ray
6. Gene Xpert MTB/Rif (and similar PCR based studies)
```
• Miscellaneous:
Purified Protein Derivative (PPD) Test
1. Measure zone of induration:
- Positive reaction:
1. >5 mm (immunocompromised host)
2. >10 mm (have chronic disease or risk factors for exposure to TB)
3. >15 mm (all others)
```
2. A positive reaction does not mean active disease.
3. Can get false negatives in patients with AIDS or malnourished individuals
110
M. avium complex (includes M. avium and M. intracellulare): (Nontuberculosis Mycobacteria)
* Common Clinical Presentations?
* Treatment?
* Miscellaneous?
• Common Clinical Presentations:
1. In AIDs patients: disseminated infection with fever, weight loss, hepatitis, and diarrhea.
2. Immunocompetent hosts:
a. Upper lung cavitary disease in elderly smokers
b. Middle and lower lung nodular and bronchiectatic disease in middle-aged female non-smokers
3. Lymphadenitis- most commonly in children
• Treatment:
1. Disseminated disease in AIDS patients: clarithromycin, rifampin or rifabutin, and ethambutol
2. Pulmonary: clarithromycin, rifampin, ethambutol
3. Lymphadenitis: excisional surgery
• Miscellaneous:
1. Common cause of Fever of Unknown Origin (FUO) in AIDS patients
2. Most common cause of NTM lung disease
111
Mycoplasma pneumoniae (Eaton's Agent):
* Morphology?
* Metabolism?
* Virulence?
* Toxins?
* Clinical?
* Treatment?
* Diagnostics?
* Miscellaneous?
• Morphology:
1. NO CELL WALL
2. Pleomorphic: can appear round to oblong shaped.
3. Smallest bacteria capable of growth and reproduction outside a living cell (smaller than some viruses: .1-.2 microns)
4. Motile (glides)
• Metabolism:
1. Requires CHOLESTEROL for membrane formation
2. Facultative anaerobe
• Virulence:
- Protein P1: adheres to epithelial cells of the respiratory tract
* Toxins: NONE
* Clinical:
1. Tracheobronchitis
2. Walking pneumonia (also called atypical pneumonia): fever with a dry, non-productive hacking cough
• Treatment:
1. Macrolides (azithromycin, clarithromycin)
2. Tetracyclines (doxycycline)
3. Quinolones (ciprofloxacin, levofloxacin)
- Penicillin and cephalosporins do NOT work, as Mycoplasma does not have a cell wall
• Diagnostics:
1. Cold agglutinins
2. Complement fixation test
3. Culture: Takes 2-3 weeks
A. Requires cholesterol and nucleic acids
B. Add penicillin to inhibit growth of contaminating bacteria
C. Dome-shaped colonies with "fried egg" appearance or "mulberry" appearance (in the case of Mycoplasma pneumoniae)
4. Rapid identification tests: sputum can be tested with DNA probes (nucleic acid hybridization). PCR of sputum samples.
• Miscellaneous:
1. Chest X-ray will show patchy infiltrates that look worse than physical exam and clinical symptoms suggest
2. Disease usually occurs in children, adolescents, and young adults
112
Ureaplasma urealyticum:
* Morphology?
* Metabolism?
* Virulence?
* Toxins?
* Clinical?
* Treatment?
* Diagnostics?
* Miscellaneous?
• Morphology:
1. NO CELL WALL
2. Pleomorphic
• Metabolism:
1. Requires cholesterol
2. Urease: metabolizes urea into ammonia and CO2
• Toxins:
- NONE
• Clinical:
- Non-gonococcal urethritis: burning on urination, with a yellow mucoid discharge from the urethra
• Treatment:
1. Erythromycin
2. Tetracycline
• Diagnostics:
1. Requires cholesterol and urea for growth
2. Colonies are extremely tiny (thus called T-strain)
• Miscellaneous:
- T-Form Mycoplasma (T= Tiny)
