Describe the diseases caused by each and the species included in each:

Answer: Nontyphoidal: Salmonella enteritidis and Salmonella choleraesuis cause enterocolitis, osteomyelitis, and septicemia.

Salmonella species are divided into typhoidal or nontyphoidal types?

Answer: Typhoidal: Salmonella typhi and Salmonella paratyphi cause typhoid fever.

What is the treatment of Shigella and what medications should be avoided?

Answer: Treatment includes fluid/electrolyte replacement and antibiotics such as trimethoprim-sulfamethoxazole (TMP-SMX) and ciprofloxacin. Antidiarrhea medications such as loperamide can prolong illness or worsen the severity and should be avoided.

What populations are most often affected by Shigella?

Answer: Nursing home residents and very young children (ages 2-4 years), especially those in developing countries

How is Shigella transmitted?

Answer: Four Fs: fingers, food, flies, feces

What symptoms are often seen with shigellosis?

Answer: Dysentery, bloody diarrhea, fever, and lower abdominal cramps

Why is Shigella nonmotile?

Answer: It lacks the H antigen that codes for motility.

Why does Shigella only cause superficial ulcers and not invade blood vessels?

Answer: Once Shigella enters M cells in the intestine, it uses actin tails to travel among cells without entering the extracellular matrix and remains contained only within the epithelial intestinal cells.

What are the reservoirs for Shigella?

Answer: Only humans, there are no animal carriers

What are the mechanisms of the two subunits of Shiga toxin?

Answer: Subunit A: Inhibits 60S ribosome, stopping protein synthesis, killing the intestinal cell Subunit B: Helps subunit A enter cells by binding to the microvillus membrane in the large intestine

What other bacteria besides Shigella contain the Shiga toxin?

Answer: The hemorrhagic and invasive strains of E. coli

Which is more virulent, Salmonella or Shigella?

Answer: Shigella. Less than 10 organisms are required for Shigella to cause infection because it is very resistant to stomach acid. Salmonella is not as resistant and requires 106 to 109 organisms to cause disease.

Salmonella and Shigella are the two important gram-negative bacteria that do not ferment lactose and cause enterocolitis. How are they differentiated?

Answer: Salmonella produces gas from glucose fermentation, produces H2S, and is motile (can disseminate hematogenously)

Mnemonic:

Salmon require energy (glucose) to swim (motile) and smell bad (H2S)

Escherichia coli is the most common cause of UTIs, what is the key virulence factor?

Answer: P-pili that mediate adhesion to urinary epithelium

Who does EPEC commonly affect?

Answer: Children, associated with nursery breakouts

EPEC adheres to but does not invade intestinal cells and results in flattening of the intestinal villi. What is the consequence of this and how does it present?

Answer: Flattening of the villi leads to malabsorp-tion. Patients present with fever and bloody diarrhea.

How do patients with EIEC present?

Answer: Fever and bloody diarrhea with inflammatory white blood cells (compare to EHEC)

How do these plasmid-encoded proteins act?

Answer: These plasmid-encoded proteins allow for adherence and direct invasion of epithelial cells in the gut. Note that this is not toxin-mediated like ETEC and EHEC.

The main virulence factors of EIEC are encoded by a plasmid shared by what other diarrhea causing bacteria?

Answer: Shigella

How is EHEC treated?

Answer: Fluids and supportive therapy. Antibiotics are not useful and may predispose to HUS.

How are patients typically exposed to EHEC O157:H7?

Answer: Undercooked hamburger meat and direct contact with animals (child presents following a petting zoo visit)

What is the mechanism that causes hemolytic uremic syndrome (HUS)? What are the features of HUS?

Answer: HUS occurs when Shiga-like toxin (verocytotoxin) enters the blood stream and damages the vascular endothelium. Cardinal features include thrombocytopenia, anemia, and acute renal failure.

Mnemonic:

You can get HUS from a RAT (Renal failure, Anemia, Thrombocytopenia)

How do patients with EHEC present?

Answer: Afebrile and bloody diarrhea without inflammatory white blood cells. EHEC strain O157:H7 is associated with hemolytic uremic syndrome (HUS)

What toxin mediates EHEC diarrhea? What is the mechanism of action?

Answer: Shiga-like toxin (verocytotoxin) inhibits 28S component of the 60S ribosome subunit, inhibiting protein synthesis leading to cell necrosis of the intestinal epithelium and hemorrhagic colitis.

Mnemonic:

Shiga-like it's the 1960s

Which other bacterial toxin is similar to LT toxin?

Answer: Cholera toxin

What is the mechanism of action for ST?

Answer: Constitutively activates guanylate cyclase leading to increased cyclic guanosine monophosphate (cGMP) and ultimately decreased water absorption from the GI lumen

What is the mechanism of heat LT?

Answer: Constitutively activates Gs via adenosine diphosphate (ADP) ribosylation leading to constant activation of adenylate cyclase and high levels of cyclic adenosine mono-phosphate (cAMP). This causes increased secretion of Cl− ions from intestinal cells into the gastrointestinal (GI) lumen. Negative Cl− ions cause positively charged Na+ ions to follow. Water follows Na+ into the lumen leading to diarrhea.

What two toxins does ETEC traveler's diarrhea produce?

1. Heat-labile toxin (LT)

2. Heat-stable toxin (ST)

What are five strains of virulent enteric E. coli?

1. Enterotoxigenic E. coli (ETEC)

2. Enterohemorrhagic E. coli (EHEC)

3. Enteroinvasive E. coli (EIEC)

4. Enteropathogenic E. coli (EPEC)

5. Enteroaggregative E. coli (EAEC)

Why would E. coli with the K1 antigen be troubling to physicians?

Answer: K1 strains cause neonatal meningitis, bacteremia, and urinary tract infection.

What does the lack of H antigen signify?

Answer: H antigen is part of the flagellae. Strains without it lack flagellae and are nonmotile.

What larger structure is the O antigen a part of?

Answer: O antigen is part of lipopolysaccharide (LPS) (endotoxin).

Escherichia coli is classically associated with what three antigens? Which two are commonly used for serology?

1. O antigen (somatic antigen)

2. K antigen (capsular antigen)

3. H antigen (flagellar antigen)

O and H are used for serology.

How is an E. coli infection diagnosed?

Answer: Laboratory culture. Escherichia coli is gram negative, oxidase negative, lactose fermenting, and β-hemolytic (although not all strains are lactose fermenting or β-hemolytic).

Where does E. coli normally colonize and how is it transmitted?

Answer: Escherichia coli is considered normal flora of the colon that is transmitted via fecal-oral route.

Name the common diseases caused by Escherichia coli:

Escherichia coli can cause diarrhea (bloody and nonbloody), urinary tract infections (UTIs) (most common cause), neonatal meningitis (second most common after group B streptococci), gram-negative sepsis (most common cause), and nosocomial pneumonia.

An 18-year-old woman presents with a sore throat. She is sexually active with a new boyfriend who was recently treated for an unknown sexually transmitted disease (STD). What is the most likely diagnosis? How do you diagnose this?

Answer: Gonococcal pharyngitis. Diagnose by pharyngeal culture.

A 19-year-old college student presents to the ER with headache, malaise, and fever (102°F). On examination, there is nuchal rigidity and on the lower extremities there are petechiae and purpura. What is the most likely diagnosis?

Answer: Meningitis with petechiae is most often associated with meningococcal meningitis.

A 23-year-old college student presents to his school's student health office complaining of painful urination and purulent urethral discharge for the last 3 days. Analysis of the discharge reveals gram-negative diplococci. What is the offending pathogen and what is the treatment of choice?

Answer: Neisseria gonorrhoeae, ceftriaxone (and azithromycin for presumed coinfection with Chlamydia)

What is the treatment of N. meningitidis infection?

Answer: Penicillin G (it does not eradicate N. meningitidis from the nasopharynx) or a cephalosporin with good CNS penetration (eg, ceftriaxone)

How are N. meningitidis infections prevented?

Answer: Purified polysaccharide vaccine for groups A, C, Y, and W135. A conjugate vaccine for those four capsular polysaccharides is also available. Group B, is not immunogenic and not covered by the vaccine, therefore, even vaccinated individuals are at risk for meningococcal meningitis.

How is N. meningitidis spread to close contacts? How can N. meningitidis infection be prevented in close contacts?

Answer: Spread via asymptomatic nasopharyngeal carriers. Contact prophylaxis with rifampin or ciprofloxacin

What is Waterhouse-Friderichsen syndrome and what are its most common manifestations?

Answer: Fulminant meningococcemia leading to septic shock and bilateral adrenal hemorrhage causing a catastrophic adrenal insufficiency and death in hours

What are typical lumbar puncture findings in bacterial meningitis?

Answer: Increased intracranial pressure, turbid cerebrospinal fluid (CSF) with greater than 1000 WBC/uL (predominantly polymorphonuclear [PMN]), increased total protein, decreased glucose, and characteristic bacteria on Gram stain

What are the key signs of meningitis associated with N. meningitidis infection?

Answer: Fever, nuchal rigidity, vomiting, lethargy, altered mental status. In young children, irritability, seizures, and they may not have nuchal rigidity

What virulence factor causes the petechiae seen in meningococcal infections?

Answer: Endotoxin-mediated blood vessel destruction leading to blood vessel hemorrhage

What are the key clinical aspects of a patient who leads to a diagnosis of meningococcemia?

Answer: Prodrome of fever, headache, nausea followed by vomiting, hypotension, myalgias, discrete pink macules, papules, petechiae distributed over the trunk, extremities, and palate

What type of immunodeficiency has the greatest risk of N. meningitidis bacteremia?

Answer: Persons deficient in terminal complement components C6 to C9

What are the two highest risk groups for N. meningitidis infection?

1. Infants 6 months to 2 years (<6 months protected by maternal antibodies)

2. Young adults brought into crowded conditions such as military recruits and college students in dorms or during the Hajj. Frequent epidemics in sub-Saharan Africa

Name one mechanism that allows N. meningitidis to escape host defenses.

Answer: Antiphagocytic polysaccharide capsule

How does N. meningitidis spread?

Answer: Spread via respiratory secretions

Name the most important clinical diseases caused by N. meningitidis:

Answer: Meningitis, meningococcemia (fulminant form: Waterhouse-Friderichsen syndrome)

Which part of N. gonorrhoeae undergoes antigenic variation making it difficult to completely eradicate or develop a vaccine?

Answer: Pili, outer membrane proteins (Opa), lipooligosaccharide (LOS)

What other bacterial coinfection must be considered in treating N. gonorrhoeae infections?

Answer: Chlamydial infection is a common coinfection with gonorrhea, so antibiotic treatment should cover both organisms. Sexual partners also need to be evaluated for treatment.

How is N. gonorrhoeae treated?

Answer: Ceftriaxone or a fluoroquinolone. Prophylaxis for neonatal conjunctivitis with silver nitrate or erythromycin into both eyes immediately after birth

Describe the key symptoms of both forms of disseminated gonococcal infection.

1. Fever, petechial lesions, and arthralgias with erythematous macules over arms and legs that evolve into hemorrhagic painful pustules over 2 to 3 days

2. Monoarticular large joint septic arthritis (eg, pain, swelling of one knee)

What complication of pelvic inflammatory disease often caused by N. gonorrhoeae involves perihepatitis?

Answer: Fitz-Hugh and Curtis syndrome. Patients complain of right upper quadrant pain and tenderness. "Violin strings" adherent to the liver capsule

What are the major long-term complications of N. gonorrhoeae- induced pelvic inflammatory disease?

Answer: Sterility, ectopic pregnancy, abscess, peritonitis, perihepatitis (liver capsule)

What are the most common complications in men of gonococcal urethritis?

Answer: Epididymitis, prostatitis, urethral strictures

Identification of gram-negative diplococci in urethral discharge within which cell type is sufficient for the diagnosis of gonorrhea in men?

Answer: Neutrophils

Is vaginal and penile discharge caused by N. gonorrhoeae usually purulent or clear and why?

Answer: Purulent due to a neutrophilic exudate

Name a mechanism by which N. gonorrhoeae evades host defenses:

Answer: Antigenic and phase variation of its surface proteins (pili)

Which growth media is used for the isolation and identification of N. gonorrhoeae?

Answer: Thayer-Martin vancomycin, colistin, and nystatin (VCN) media

Name the most common pathologic manifestations of infection by N. gonorrhoeae:

Answer: Purulent urethritis, cervicitis, epididymitis, pelvic inflammatory disease, neonatal conjunctivitis, disseminated gonococcal infection (two forms: tenosynovitis and skin lesions or septic arthritis most commonly involving the knee)

What enzyme common to both N. gonorrhoeae and N. meningitidis allows them to colonize mucosal surfaces?

Answer: IgA protease

Describe the sugar fermentation patterns of N. gonorrhoeae and N. meningitidis:

Answer: N. gonorrhoeae ferments only glucose whereas N. meningitidis ferments both glucose and maltose.

What is the characteristic appearance of both Neisseria gonorrhoeae and Neisseria meningitidis under the microscope?

Answer: Gram-negative kidney-shaped diplococci

A 55-year-old drum maker presents with nonspecific respiratory symptoms, low-grade fever, and substernal discomfort. Chest x-ray reviews a widening mediastinum. What is the likely diagnosis?

Answer: "Woolsorter's disease" or inhalational anthrax caused by B. anthracis, a life-threatening pneumonia, which can progress from nonspecific respiratory symptoms to hemorrhagic mediastinitis, bloody pleural effusions, septic shock, and death

A young girl presents with fever, sore throat, and regurgitating fluids through her nose. Physical examination reveals cervical lymphadenopathy and a thick, gray, adherent pseudomembrane over the tonsils and throat, and paralysis of the soft palate. What is the likely diagnosis and causative organism?

Answer: Diphtheria caused by C. diphtheriae

Spores of this bacterium enter the body through a traumatic wound, causing pain, edema, and cellulitis. Degenerative enzymes produce gas in tissues, evident by crepitation. Hemolysis, jaundice, and bloody exudates are common. Mortality rates are high. What is the causative organism and disease?

Answer: Clostridium perfringens causing gas gangrene (myonecrosis), early surgical debridement, antibiotics (penicillin, clindamycin), and hyperbaric oxygen

CLINICAL VIGNETTES A 43-year-old man who has been taking amoxicillin for 3 weeks to treat an upper respiratory tract infection suddenly develops low-grade fever and diarrhea. What has he most likely developed, which pathogen is causing his new symptoms, and what is the treatment of choice?

Answer: He has developed pseudomembranous colitis from overgrowth of C. difficile due to broad-spectrum antibiotic therapy. Treat with metronidazole and stop the amoxicillin.

How is Listeria treated?

Answer: Ampicillin (with gentamicin for serious cases or trimethoprim-sulfamethoxazole for penicillin-allergic patients). Listeria is always resistant to cephalosporins.

How is Listeria transmitted?

Answer: Most commonly via unpasteurized dairy, meats, and vegetables. Also transplacental spread during delivery

What patient populations are typically affected by Listeria monocytogenes? Why?

Answer: Pregnant women, newborns of infected mothers, elderly, and immunosuppressed patient S. Listeria is a facultative intracellular organism and requires an intact cell-mediated immunity to clear.

What diseases are caused by Listeria?

Answer: Meningoencephalitis, sepsis, infections in pregnancy (leading to premature birth or fetal death), and gastroenteritis are the most common manifestations of Listeria.

What type of motility does Listeria display?

Answer: Tumbling motility

What is unique about the mechanism in which Listeria infects cells?

Answer: Listeria has the ability to spread from cell to cell without entering the extracellular environment by using an actin polymerization propulsion system called "actin rockets."

What is the most prominent virulence factor in Listeria? How does it work?

Answer: Listeriolysin O toxin penetrates host cell's phagocytic vacuole to facilitate bacterial entry into the cytoplasm.

What is unique about the growth characteristic of Listeria?

Answer: It grows well in cold temperature (4°-10°C).

LISTERIA MONOCYTOGENES Describe the morphology and special characteristics of Listeria:

Answer: Small gram-positive bacillus, facultative intracellular, β-hemolysis, catalase positive, tumbling motility at room temperature

How is diphtheria treated? Prevented?

Answer: Immediate administration of horse serum antitoxin and antibiotics (penicillin G and erythromycin). Prevented with diphtheria, tetanus, and acellular pertussis (DTaP) vaccine

How is C. diphtheriae diagnosed?

Answer: Laboratory diagnosis is based on gram-positive rods with metachromatic (blue and red) granules.

What type of agar is used for culturing C. diphtheriae?

Answer: Tinsdale potassium tellurite agar

What are the major complications of diphtheria?

Answer: Physical airway obstruction, myocarditis, demyelination/paralysis of peripheral nerves

Mnemonic:

Diphtheria affects MAN (Myocarditis, Airway, Nerves).

What is exotoxin's mechanism of action?

Answer: ADP ribosylation of elongation factor-2 (EF-2) which blocks tRNA translocation causing inhibition of host protein synthesis

How is C. diphtheriae's exotoxin encoded?

Answer: β-Prophage DNA

How is C. diphtheriae transmitted?

Answer: Via airborne droplets

What disease is caused by C. diphtheriae? Name its typical symptoms:

Answer: Diphtheria. Lymphadenopathy (bull neck) and pseudomembrane pharyngitis (ie, thick, gray exudative pseudomembrane in the throat and nasopharynx)

CORYNEBACTERIUM DIPHTHERIAE Does Corynebacterium diphtheriae form spores or have a capsule?

Answer: No, it is nonspore forming and nonencapsulated.

What is in a diphtheria, tetanus, and pertussis (DTaP) childhood vaccine?

Answer: Diphtheria toxin, tetanus toxoid, and acellular pertussis antigen

What is the tetanus vaccine made of?

Answer: Formalin-inactivated tetanus toxoid

How is tetanus treated?

Answer: Antitoxin, antibiotics, sedatives, and muscle relaxants to prevent spasms, and debridement of wound

What are the symptoms of tetanus? Why?

Answer: Spastic paralysis due to prolonged muscle contracture results from lack of inhibition (ie, loss of glycine), resulting in dysphagia (early), trismus (lockjaw), risus sardonicus (grimace), and respiratory failure.

Mnemonic:

Tricks a Good Spine (Tetanus, Glycine, Spastic paralysis)

CLOSTRIDIUM TETANI How does Clostridium tetani cause tetanus?

Clostridium tetani acquired from traumatic wound releases tetanus toxin (exotoxin), which blocks the release of inhibitory neurotransmitter glycine and γ-aminobutyric acid (GABA) from Renshaw cells in spinal cord.

How is C. perfringens food poisoning treated?

Answer: Supportive care treatment because it is a self-limiting disease

How does C. perfringens food poisoning usually present?

Answer: Abdominal cramps, diarrhea, and fever that presents 8 to 18 hours after ingestion of contaminated beef, poultry, pork, and fish. It takes more time than Staphylococcus aureus to develop symptoms because C. perfringens has to grow and produce enterotoxin in vivo.

How is gas gangrene treated?

Answer: Surgical debridement of necrotic tissue, antibiotics (penicillin plus clindamycin), and hyperbaric oxygen chamber may disrupt anaerobic progression of myonecrosis.

What is the role of α-toxin in myonecrosis?

Answer: α-Toxin lyses red blood cells, endothelial cells, leukocytes, and platelets. This facilitates invasion of muscles near the infected wounds, leading to the production of subcutaneous gas (hence the name gas gangrene).

Name two major toxins by C. perfringens:

1.α-Toxin (lecithinase)

2. Enterotoxin (heat-labile toxin)

CLOSTRIDIUM PERFRINGENS Name the conditions most often associated with Clostridium perfringens:

Answer: Myonecrosis (gas gangrene), cellulitis, food poisoning, necrotizing enteritis