COMMON BACTERIAL PATHOGENS

Question 1

Endoxtoxic shock

Answer 1

LPS (endotoxin) is a very toxic molecule for humans. The toxic moiety, Lipid A, is embedded in the outer leaflet of the outer membrane of the Gram- negative cell wall. In many cases it is a significant component of the disease process of G- organisms. Even in minute quantities, LPS may cause fever and shock (IL-1 and TNF release). In larger doses, LPS may result in DRAMATIC life-threatening effects:
• Hypotension
• Hemorrhage
• Intravascular coagulation (activates clotting cascade)
Patients encounter LPS e.g., release of cell wall fragments following treatment with certain antibiotics, injection of contaminated materials, bacteremia.

Question 2

General rules for antimicrobial susceptibility

Answer 2

The Gram-negative outer membrane is a permeability barrier that protects the cell from many organic materials, including some antibiotics, e.g., erythromycin.

Question 3

(Gram + cocci) Genus staphylococcus

Answer 3

-Staphylococcus. aureus
Gram + Cocci
-SSNA (“staph species, not aureus” e.g. S. epidermidis)

Question 4

Staphylococcus aureus background

Answer 4

Primary pathogenic species of the genus. Asymptomatic carriage in ~30% of healthy individuals. The sites
of carriage are primarily in the anterior nares and perineum. One’s endogenous infection can be source of bacterial infection to another person.

Question 5

Staphylococcus aureus typical diseases: Cutaneous infection

Answer 5

The characteristic lesion is a localized abscess. Both the bacterium and the host contribute to the formation of a fibrinous capsule which tends to wall off the infection and limit spread to adjacent tissues. The fibrinous capsule also restricts access of phagocytic cells, antibodies, and antimicrobials, etc to the site of infection. Effective treatment typically includes drainage of the abscess. The enzyme “coagulase” is an essential virulence factor that is associated with formation of the fibrin capsule and deposition of fibrin on the cell surface- which interfers with phagocytosis. Alpha-toxin is the major cytotoxic agent released by bacterium Staphylococcus aureus and the first identified member of the pore forming beta-barrel toxin family. Cutaneous S. aureus infections are often associated with the presence of a “foreign body” at the site, e.g., a suture or splinter. The presence of such an object interferes with bacterial clearance by phagocytes and provides a surface for the bacterial to colonize.
 Spread from the initial lesion occurs, and may result in bacteremia, sepsis or metastatic lesions

Question 6

Staphylococcus aureus typical diseases: Toxin mediated diseases

Answer 6

Superantigen toxins are a class of antigens that cause non-specific activation of T-cells, resulting in polyclonal T cell activation and massive cytokine release. SAgs can be produced by pathogenic microbes (including viruses, mycoplasma, and bacteria) as a defense mechanism against the immune system. Compared to a normal antigen-induced T-cell response where .0001-.001% of the body’s T-cells are activated, these SAgs are capable of activating up to 25% of the body’s T- cells. Can lear to STAPHYLOCOCCAL TOXIC SHOCK SYNDROM and STAPHYLOCOCCAL FOOD POISONING

Question 7

Toxic shock syndrome

Answer 7

Patients generally have a localized infection by a toxinogenic S. aureus strain; circulating toxin produced locally by bacteria at the site of infection results in severe systemic manifestations. typically manifests in otherwise healthy individuals with high fever, accompanied by low blood pressure, malaise and confusion, which can rapidly progress to stupor, coma, and multiple organ failure. The characteristic rash, often seen early in the course of illness, resembles a sunburn, and can involve any region of the body, including the lips, mouth, eyes, palms and soles. Toxin expression requires O2 neutral pH, high protein
High fever, shock, vomiting, muscle pain- renal and hepatic injury/failure

Question 8

Staphylococcus aureus typical diseases: Pneumonia

Answer 8

specially in patients with impaired host defenses (particularly high mortality 50%). Although it is not a very common cause of pneumonia in patients who present to the clinic (outpatient), it is common isolate in patients who develop pneumonia once they are in the hospital or are recently or chronically associated with health care (health care-associated pneumonia (HCAP); hospital acquired-pneumonia (HAP); and ventilator-associated pneumonia (VAP).

Question 9

Staphylococcus aureus typical diseases: foreig-body associated infections

Answer 9

vascular catheter-related infections, prosthetic joint infections, hardware infections (cardiac pacemakers, vascular grafts).

Question 10

Staphylococcus aureus typical diseases: bacteremia/endocarditis

Answer 10

One of the most common isolates from blood cultures (associated with concurrent foreign-body infections or skin/soft tissue infection) and a common cause of heart valve infection (endocarditis).

Question 11

Staphylococcus aureus Antibiotic Resistance.

Answer 11

The development of antibiotic resistance is of particular concern in this organism. For example, there has been a progressive acquisition of genes which confer resistance to penicillins, followed by resistance to methicillin, and the more recently emerging resistance to vancomycin . The most important of these is methicillin resistance (“methicillin- resistant Staph aureus” MRSA).

Question 12

(Gram + Cocci) Staphylococcus epidermidis

Answer 12

This is the prototype of the group of staphylococcal species collectively termed SSNA (“staph species, not aureus”), or CNS (“coagulase negative staphylococcus”).
• These are generally considered to be normal skin flora and relatively non-pathogenic. However in certain circumstances, it is associated with various sorts of localized infection. Infections are typically associated with various sorts of foreign bodies, e.g., catheters, shunts, hip prostheses, artificial (or damaged) heart valves. The members of this group that are most often associated with disease are those that produce “slime”, an extracellular glycocalyx that allows the organisms to adhere very tenaciously to the various implanted devices, and allows them to grow in a protected biofilm on the surface of the device.
• Infections are quite difficult to treat and often require removal of the device. o Antibiotic resistance (including methicillin) and
o Limited accessibility of the drug to the bacteria within the biofilm

Question 13

The genus Streptococcus (and relatives)

Answer 13

Gram-positive cocci often in chains or pairs
• Catalase negative (Staphylococci are catalase positive)
o Streptococcus pyogenes
o Streptococcus pneumoniae
o “Viridans” streptococci
o Enterococcus faecalis/Enterococcus faecium

Question 14

Streptococcus pyogenes (“Group A Strep”, GAS)

Answer 14

Pharyngeal infection- Strep throat. Streptococcus pyogenes is the causative agent of common “strep throat”. Untreated, this infection of the pharynx generally self-limiting and resolves in a
couple weeks. Among the Group A strep that cause human disease, there are over 70 serotypes based on antigenic differences in the M-protein. Antibody against the M-protein is protective against disease caused by the same streptococcal serotype, but individuals remain susceptible to infection by isolates with serologically distinct M-protein. Transmission is generally by contact with nasal secretions of an infected individual, or by droplets produced by coughing, etc.

Question 15

streptococcus pyogenes: Skin and wound infections

Answer 15

Group A Strep are associated with infections of the skin and wounds. The typical lesion is that of a spreading infection of the cutaneous and subcutaneous tissues (cellulitis). Bacteremia and sepsis are possible. GAS produce a variety of hydrolytic enzymes that act in concert to break down tissue and damage or kill phagocytic cells, thereby facilitating spread of the organism through the tissues.

Question 16

streptococcus pyogenes: Post-streptococcal diseases.

Answer 16

Glomerulonephritis- an immune complex disease that may follow skin or pharyngeal infection by Group A strep. Rheumatic fever- This is an autoimmune inflammatory disease characterized by fever and inflammation of the heart, joints, and other tissues. RF is generally thought to result from the production of self-reactive antibodies produced in response to pharyngeal infection by Group A Strep. In RF, the heart tissue itself is NOT colonized by the infecting Streptococcal organisms, making the disease distinct from infective (bacterial) endocarditis- a true bacterial infection of the heart valves (e.g., Staphylococcus epidermidis).

Question 17

Streptococcus pneumoniae

Answer 17

G+ cocci in pairs (diplococci; “pneumococcus”). Normal flora in UR tract of up to 40% of healthy people
• Diseases include non-invasive and invasive disease:
o Non-invasive: Pneumonia (one of the most frequent causes of bacterial pneumonia in all age groups, world-wide). Sinusitis, otitis media, bronchitis. o Invasive disease: Meningitis, bacteremia/septicemia, pneumonia with septicemia. Predisposing factors include: young or old, alchollism, respiraroty viral infection

Question 18

Streptococcus pneumoniae Vaccines

Answer 18

Adults- (pneumovax, PPSV23) Commonly refered to as the “pneumonia vaccine”. Provides measurable (but by no means complete) protection against INVASIVE disease in elderly and immunocompromised adults. Ironically, does NOT provide protection against pneumonia. Children- Hepta-valent (Prevnar) and newer 13-valent (Prevnar 13) vaccines in kids are remarkably successful at reducing disease in vaccinated. Confers a degree of “herd immunity” on unvaccinated individuals. Rather unexpectedly, widespread vaccination of kids also reduced vaccine-type pneumococcal carriage across all age groups. Some studies suggest efficacy is threatened by “serotype replacement”.

Question 19

Streptococcus pneumoniae: antibiotic resistance

Answer 19

Emerging pencillin resistance due to alterations of penicillin-binding proteins

Question 20

Viridans streptococci

Answer 20

one of the important causes of infective (bacterial) endocarditis. Particularly abundant in mouth where some are associated with dental caries. The oral viridans streptococci may also gain access to the bloodstream following dental extractions or other dental manipulations, in which case they have the potential to cause infective (bacterial) endocarditis. The production of dextrans also allows them to serendipitously adhere to the fibrin and platelet deposits on damaged heart valves

Question 21

Enterococcus faecalis and Enterococcus faecium

Answer 21

common commensal organisms (normal flora) in the
intestines of healthy humans. Common sites of infection: Urinary tract, surgical wounds, biliary tract, endocarditis. Important to distinguish from streptococci because of its intrinsic and emerging acquired antibiotic resistance

Question 22

Gram-Positive Rods

Answer 22

Most common G+ rods encountered in human disease are members of the genus Clostridium

Question 23

Clostridium

Answer 23

are characterized as:
o Strict anaerobes- growing cells are KILLED by molecular oxygen
o Endospore-formers- Endospores are extremely resilient, metabolically inactive developmental
stage of these bacteria. The spores are difficult to kill with sanitizing agents and, unlike the growing forms of the bacteria, are largely insensitive to oxygen. As such they are critical to the persistence of these bacteria in the environment.
• Diseases and organisms considered in this section:
o Hospital-acquired diarrhea and colitis (C. difficile)
o tetanus (C. tetani),
o botulism (C. botulinum),
o gangrene and other tissue infections (C. perfringens and others)

Question 24

Clostridium difficile

Answer 24

typically a hospital-acquired (nosocomial) infection, and the Clostridia that is most likely to be
encountered in the hospital.
o diarrhea
o Pseudomembranous colitis.
Constituent of the normal flora of the GI tract in ~10% of healthy individuals. Relatively resistant to most common antibiotics. Most frequently associated with diarrhea and colitis following antibiotic treatment for unrelated conditions. Source can be patients own flora, or transmitted from another infected Pt or hospital staff. spores nore killed by alcohol based handsantitizers. Clindamycin, and nearly every other antibiotic have been implicated.

Question 25

Clostridium tetani:

Answer 25

Common organism in soil and GI tract of animals (importance of spores)
• Local infection (anaerobic) and toxin production
• Retrograde axonal transport of toxin to CNS
• Toxin blocks inhibitory interneurons in CNS resulting in “spastic paralysis”
• Vaccine (inactive toxoid) used to induce production of protective anti-toxin antibody. Compare to
passive immunization with antitoxin (tetanus-immune human gamma globulin) to treat non-immune individuals with clinical signs of tetanus

Question 26

Clostridium botulinum

Answer 26

Common organism in soil and GI tract of animals (importance of spores)
• Bacteria grow in contaminated food under anaerobic conditions (e.g., home canned foods). During
growth, bacteria produce botulinum toxin, which is secreted into the food. People ingest the preformed toxin by eating the under-cooked, contaminated food. (Compare and contrast this scenario with Staphylococcal food poisoning and ETEC).
• Toxin blocks acetylcholine transmission at neuro-muscular junctions, resulting in “flaccid paralysis”

Question 27

Clostridium perfringens: Wound infections

Answer 27

Wound infections. especially crushing-type injuries, and others that lead to compromised blood
flow to tissues and creation of a low-oxygen environment in the devitalized tissue conducive to growth of this anaerobic bacterium. While growing in the wound, the bacterium produces “alpha toxin” (phospholypase enzyme), and several other damaging enzymes and toxins. Alpha toxin kills phagocytic cells and muscle tissue. Disease can range from cellulitis to myonecrosis to gas gangrene.

Question 28

clostridium perfringens: clostridial food poisoning

Answer 28

Some strains of C. perfringens produce enterotoxin. Large numbers are ingested with contaminated food; the enterotoxin is produced in vivo when the bacteria sporulate in the gut. The action of the toxin disrupts tight junctions between endothelial cells in the ilium resulting in a dysregulation of fluid transport.

Question 29

(Aerobic and facultative) Gram-Negative Rods

Answer 29

Organisms considered in this section: E. coli (Escherichia coli) Pseudomonas aeruginosa

Question 30

E. coli - the “prototypical” Gram-negative bacterium

Answer 30

Normal flora in large intestine
• Disease may be caused by endogenous organisms or acquisition (ingestion)
• Although normally sensitive to most antibiotics, this is one of the most common organisms to
acquire resistance thru acquisition of drug-resistant plasmids
• Many different strains of E. coli with varying pathogenic potential. Three types of E. coli disease
are considered here: gastrointestinal disease, urinary tract infections and abdominal infections.

Question 31

E. coli GI disease:

Answer 31

Many strains which vary in type and severity of disease
• Typically from drinking contaminated food and water
• ETEC- typical traveler’s diarrhea- (Enterotoxigenic E. coli). Disease is self-limiting and patient
management may only require fluid replacement. Two properties of the bacteria are essential for disease:
o Adherence to the intestinal mucosa (pili)
o Toxin(s) that disrupts the electrolyte balance in gut

Question 32

E. coli Urinary tract infections

Answer 32

Isolates are typically endogenous from GI tract
• Access the UT via urethra -> bladder -> kidney
• “Special” strains getting into the “wrong” place. The typical urinary tract isolate has the
following properties, which are rather uncommon in the bulk of the intestinal population: o Adherence to bladder epithelium
o Specific interactions with bladder epithelial cells
o UTIstrainsaretypicallyβ-hemolytic

Question 33

E. coli Abdominal infections

Answer 33

Release/escape of contents of colon to peritoneal cavity and adjacent tissues, e.g.,
o Surgical wounds, traumatic wounds, etc
o Colon cancer
• Such infections are often bacteriologically mixed cultures
• Often associated with anaerobic bacteria to form anaerobic abscess.

Question 34

Pseudomonas aeruginosa

Answer 34

Very common environmental bacterium, to which most individuals are highly resistant to infection.
• Three types of disease are considered here:
a. Infections of traumatic injuries, surgical wounds, and especially BURNS. Opportunistic
pathogen often affecting immunocompromised patients
b. Chronic lung infection of patients with Cystic fibrosis
c. Hospital-acquired infections (UTIs, pneumonia, less frequently associated with intravascular
catheter-related infections).

Question 35

P. aeruginosa and CF

Answer 35

CF patients produce copious, viscous bronchial secretions. This tends to result in stasis in the lungs and predisposes the patient to infection. nearly all CF patients become chronically infected with P. aeruginosa by age 15 - 20. Within the lungs of the chronically infected patient, the bacteria are relatively protected from phagocytosis by the patient’s viscous lung secretions, the mucoid exopolysaccharide made by the bacterium and the production of bacterial toxins. The consequences of chronic lung infection with P. aeruginosa is very frequently the cause of death in CF patients

Question 36

P. aeruginosa and hospital-acquired infections

Answer 36

This is a big player to think about for most all hospital- acquired infections, (especially UTIs, pneumonias). The point not only is that it is relatively common, but given its high intrinsic antibiotic resistance, many empiric regimens won’t cover it.

Question 37

Gram negative (diplo)cocci: Neisseria gonorrhoeae (gonococcus)

Answer 37

Causative agent of gonorrhea and of conjunctivitis leading to blindness in infants born to
infected mothers. Key to infectivity is the pilus. This structure is required for adherence and interferes with bacterial killing by neutrophils. rowth on mucosal surface incites a robust inflammatory response, resulting in a purulent discharge and local tissue invasion. Prolonged infection may lead to scarring and fibrosis

Question 38

Neisseria gonorrhoeae

Answer 38

Males range from asymptomatic to urethritis.

o Females: infection of cervix, urethra. More often asymptomatic than in males. Ascending infection including uterine tubes may result in fibrosis and infertility

• Antibiotic resistance
o N. gonorrhoeae isolates are almost always resistant to penicillin and strains with reduced
sensitivity to cephalosporins are emerging.
o Fluroquinolone resistance is also highly prevalent and use of these agents to treat N.
gonorrhoeae is no longer recommended.

Question 39

Anaerobic Bacteria

other than the clostridia

Answer 39

The most common anaerobic bacteria (other than the Clostridia) that are implicated in human disease are members of the normal flora that inhabit the many anaerobic nitches in/on the human body. These anaerobic sites include Colon, Mouth (e.g., gums, tongue), Female genital tract and Skin. Anaerobic bacteria are KILLED by the presence of molecular oxygen in their environment

Question 40

Anaerobic Bacteria properties

Answer 40

Infective organisms are generally of endogenous origin- normal flora getting into the wrong place. The typical lesion is an abscess.
• A hallmark is that of a mixed infection containing both aerobic and anaerobic bacteria. Aerobes
may play a role in metabolizing the local oxygen, making the site more conducive to growth of the anaerobes.

Question 41

Bacteroides fragilis:

Answer 41

Despite the abundance and diversity of anaerobic bacteria in the human normal flora, most endogenous anaerobic abscesses are caused by relatively anaerobic few species. Members of the Bacteroides group are among the most frequently encountered; Bacteroides fragilis is considered to be the prototypical endogenous anaerobic pathogen. making up only 1- 2% of the total bacteria of the colon, it is associated with greater than 80% of intra-
abdominal infections

Question 42

Obligate intracellular bacteria

Answer 42

Rickettsia and Chlamydia. These are organisms that grow only within an infected eukaryotic cell.

Question 43

Rickettsia

Answer 43

have lost the capacity to synthesize their own ATP and rely on the infected host cell to supply this essential compound

Question 44

Chlamydia trachomatis

Answer 44

An obligate, intracellular bacterium. Diseases: Trachoma (infection of conjunctiva), Genital infections, NNeonatal infections.

Question 45

Bacteria without cell walls

Answer 45

“Mycoplasmas” (family designation) includes two genera of bacteria lacking cell walls and containing sterols in the plasma membrane:
Mycoplasma and Ureaplasma

Question 46

Mycoplasma pneumoniae.

Answer 46

Mycoplasma pneumoniae adheres to respiratory epithelial cells. Bacterial growth remains extracellular. Bacteria produce hydrogen peroxide and superoxide radicals, which damages host tissue.
One of the common causes of pneumoniae, especially in ages 5-20
• Mycoplasma pneumonia is generally mild.
• Person to person transmission by direct contact with infected respiratory secretions
• Fever, headache, sore throat, non-productive cough, chest and body aches, fatigue.
• Resolution and recovery occurs slowly over 1-4 weeks
Because the bacteria lack a rigid cell wall, shape is highly pleomorphic and penicillins are not effective.