How is Y. pestis typically transmitted?

Answer: Rat-flea bite/contact with infected animal (bubonic plague) or via respiratory aerosols (pneumonic plague)

What diseases does Y. pestis cause?

Answer: Bubonic plague (most common), septicemic plague, and pneumonic plague

Describe the morphology of Yersinia pestis:

Answer: Nonmotile, bipolar staining pleomorphic gram-negative coccobacillus

Which zoonotic organisms are facultative intracellular organisms?

Answer: Francisella, Brucella, and Yersinia

Name the five medically important zoonotic gram-negative rods:

1. Yersinia

2. Francisella

3. Brucella

4. Pasteurella

5. Bartonella

A 70-year-old man with diabetes presents with severe left ear pain and discharge. On physical examination, there is granulation tissue seen in the ear canal.

Answer: Pseudomonas is the most common cause of malignant otitis externa.

A 10-year-old girl with cystic fibrosis presents with 2 days of high fever and a cough productive of purulent green sputum. On chest x-ray (CXR) there is a left upper lobe (LUL) infiltrate. What is the most likely pathogen contributing to her symptoms? Appropriate treatment?

Answer: Pseudomonas aeruginosa. Treatment with an aminoglycoside and antipseudomonal penicillin (eg, tobramycin and piperacillin) or an antipseudomonal cephalosporin

Which bacterium, which has reservoirs in water sources, causes hot tub folliculitis, characterized by pruritic or tender follicular lesions following bathing in a hot tub, whirlpool, or public swimming pool.

Answer: Pseudomonas aeruginosa

A young child presents with a 2-week history of mild upper respiratory symptoms and a severe paroxysmal cough, followed by high-pitched inspiratory whoop. A complete blood count (CBC) reveals marked lymphocytosis. What is the likely diagnosis and causative organism?

Answer: Whooping cough or pertussis caused by B. pertussis

An older man with a significant history of smoking and alcohol consumption presents with a fever, nonproductive cough, and shortness of breath. Several of his coworkers have had similar symptoms over the preceding months, and his workplace is investigating whether the air conditioner may be a source of infection. He also uses a humidifier in his home. What is the likely diagnosis and organism? How is the organism visualized?

Answer: Legionella pneumonia (Legionnaires' disease) caused by L. pneumophila. Visualize with silver stain or fluorescence staining

What population is especially susceptible to K. pneumoniae and what is the characteristic appearance of the sputum?

Answer: Alcoholics, diabetics, hospitalized patients with "red-currant jelly" sputum

Describe the appearance of K. pneumoniae colonies and whatgives them this appearance?

Answer: Appear as mucoid colonies due to large capsule size

Klebsiella pneumoniae causes what diseases?

Answer: Necrotizing lobar pneumonia, nosocomial UTIs, bacteremia, and wound infection

Describe the biochemical characteristics of Klebsiella pneumoniae.

Answer: Lactose-fermenting, encapsulated, nonmotile (ie, lacks H antigen)

What are the signs and symptoms of Pontiac fever and how does it differ from Legionnaires' disease?

Answer: Pontiac fever includes generalized headache, fevers, chills, and myalgias without any respiratory complaints. It is generally a self-limited illness that does not require treatment and resolves within 1 week.

What are the treatment options for Legionnaires' disease?

Answer: Mortality from Legionnaires' disease can approach 30% to 50% in untreated patients, so they need rapid treatment with macrolides (azithromycin, erythromycin), fluoroquinolones, or tetracyclines.

What stain is required to visualize L. pneumophila?

Answer: Silver staining or immunofluorescent staining. Legionella pneumophila stains poorly with Gram staining because it is an intracellular pathogen.

What have been the major sources for Legionnaires' disease?

Answer: Water sources (air conditioners, water distribution systems, and the like) due to inhalation of aerosolized particles. Person-to-person transmission does not occur.

How is Legionnaires' disease diagnosed?

Answer: Most commonly with culture on selective media (buffered charcoal yeast extract agar; iron and cysteine are required growth factors) and urinary antigen test

Where is L. pneumophila found within infected patients? Why?

Answer: Intracellularly in alveolar monocytes/macrophages. It is a facultative intracellular organism that inhibits phagosome-lysosome fusion and replicates within the phagosome.

What are the risk factors for Legionnaires' disease?

Answer: Cigarette smoking, alcoholics, chronic lung disease, and immunosuppressed states

How does Legionnaires' disease present?

Answer: Severe atypical lobar pneumonia with neurologic (mental confusion) and gastrointestinal (nonbloody diarrhea) complaints (may see hyponatremia)

What diseases does Legionella pneumophila cause?

Answer: Legionnaires' disease and Pontiac fever

What is the treatment of P. aeruginosa?

Answer: For severe infections, typically a pseudomonas-specific penicillin (ticarcillin, piperacillin) or cephalosporin (ceftazidime, cefepime) plus an aminoglycoside (gentamicin, tobramycin, amikacin; recall excellent for aerobic bacteria) or a pseudomonas-specific fluoroquinolone (ciprofloxacin)

What characteristics of P. aeruginosa allow it aggressively invade tissues?

Answer: Elastases allow P. aeruginosa to invade skin creating erythema gangrenosum and progress to sepsis.

What is the clinical significance of ecthyma gangrenosum?

Answer: An ulcerated lesion with black eschar. It appears almost exclusively in Pseudomonas sepsis (typically in neutropenic patients) and requires immediate medical attention and antibiotic coverage.

Why is P. aeruginosa one of the most feared bacteria?

Answer: It is ubiquitous, causes a large variety of diseases, can be very virulent in compromised hosts, and is relatively antibiotic resistant.

What is a common source of P. aeruginosa?

Answer: Pseudomonas aeruginosa is a water-loving organism and its common sources include hospital respiratory equipment, sinks, basins, AC units, and plants.

What three groups of patients are extremely susceptible to P. aeruginosa infections?

1. Burn patients

2. Cystic fibrosis patients

3. Neutropenic patients

A toxin produced by which other bacteria also inhibits EF-2?

Answer: Corynebacterium diphtheriae

What is the mechanism of exotoxin A produced by P. aeruginosa?

Answer: Exotoxin A inhibits elongation factor 2 (EF-2), thereby inhibiting protein synthesis.

How is P. aeruginosa differentiated from Enterobacteriaceae?

Answer: All will grow on MacConkey agar, but P. aeruginosa is oxidase positive and lactose negative.

What is the characteristic smell of P. aeruginosa?

Answer: Grapelike scent (another description is the smell of wet corn tortillas)

Describe the important biochemical characteristics of P. aeruginosa:

Answer: Obligate aerobe that grows on blood or MacConkey agar; does not ferment lactose (colorless on MacConkey); oxidase positive; produces pyoverdin (green pigment fluoresces under ultraviolet light); pyocyanin (blue); and polar flagella.

What diseases are commonly associated with Pseudomonas aeruginosa?

Answer: Pneumonia (cystic fibrosis patients, mechanically ventilated patients), otitis externa (elderly diabetics), wound infections (burn patients), urinary tract infections (hospital patients), corneal ulcers (contact lens wearers), sepsis, endocarditis (intravenous [IV] drug users), osteomyelitis (IV drug users), osteochondritis (following penetration injury to foot), ecthyma gangrenosum, and hot tub folliculitis (hot tub user)

What vaccines are available for B. pertussis?

Answer: A killed-whole cell vaccine and an acellular vaccine are available for children under 7 years. Two booster vaccines are also available for adolescents and adults.

The majority of whooping cough cases occur in whom today?

Answer: Classically unimmunized infants younger than 1 year. However, in the last 10 years adolescent and adult infections are more common than infant infections.

What is the treatment of whooping cough and when should it be given?

Answer: Macrolides (eg, azithromycin) should be given in the prodromal or catarrhal stage to render the patient noninfectious and prevent spread to contacts.

However, treatment does not alter the clinical course of the disease in the source patient.

What is the clinical significance of increased cAMP?

Answer: Impaired cell function (especially neutrophils, macrophages, lymphocytes) and chemotaxis. Impaired chemotaxis leads to lymphocytosis because lymphocytes stay in circulation instead of migrating into lymphoid tissue.

What is the mechanism of action of pertussis toxin?

Pertussis toxin inactivates Gi via adenosine diphosphate (ADP) ribosylation. Inactivated Gi cannot inhibit adenylate cyclase; therefore there is increased cyclic adenosine monophosphate (cAMP).

Pertussis toxin turns off the cAMP off mechanism.

What is the mechanism of action of tracheal cytotoxin?

Answer: Ciliostasis and epithelial cell death diminishing mucociliary clearance

What is the mechanism of action of filamentous hemagglutinin (FHA)?

Answer: FHA facilitates attachment to the cilia of respiratory epithelial cells.

What are the virulence factors of B. pertussis?

Answer: Attachment virulence factors (filamentous hemagglutinin [FHA]) and toxins (pertussis toxin, tracheal cytotoxin, and invasive adenylate cyclase)

What are the three stages of whooping cough?

1. Catarrhal (1-2 weeks with sympto: similar to a viral upper respiratory infection [URI]; most contagious stage)

2. Paroxysmal (following 1-6 weeks with characteristic burst of cough with inspiratory "whoop")

3. Convalescent (2-3 weeks with decreased coughing attacks; not contagious)

What culture media does B. pertussis require for growth?

Answer: 

Bordet-Gengou (potato) agar.

Note that B. pertussis is difficult to culture.

How is B. pertussis diagnosed?

Answer: Bacterial culture (on Bordet-Gengou agar) or polymerase chain reaction (PCR) from nasopharyngeal swab or serology

BORDETELLA PERTUSSIS What disease does Bordetella pertussis cause?

Answer: Pertussis or whooping cough

What drug is used for prophylaxis for close contacts?

Answer: Rifampin achieves a high concentration in secretions, thereby reducing spread.

What are the treatment options for H. influenzae!

Answer: Local infections are treated with amoxicillin with clavulanate or second-or third-generation cephalosporin. Invasive infections are treated with third-generation cephalosporins such as ceftriaxone that can cross the blood-brain barrier to treat meningitis.

Why are patients with sickle cell disease especially susceptible to H. influenzae infection?

Answer: The spleen is necessary to clear encapsulated organisms and sickle cell disease results in functional asplenia.

What diseases are seen in the nonencapsulated strains versus encapsulated type B H. influenzae?

Answer: Nonencapsulated (nontypeable) strains cause local infections such as pneumonia, otitis media, and sinusitis. Encapsulated strains (usually type B) cause invasive infections such as meningitis, acute epiglottitis, septic arthritis, and sepsis.

Why has H. influenzae remained the second most common cause of otitis media in children vaccinated with Hib?

Answer: Ninety percent of otitis media is caused by a nonencapsulated (nontypeable) type, thus antibodies against type B are not protective.

Haemophilus influenzae is known for causing epiglottitis in children. How does this present?

Answer: An initial sore throat with fever that progresses to airway obstruction, stridor, dysphagia, and drooling due to an inability to swallow. The epiglottis is red and swollen.

What is the pathognomonic radiographic sign seen with epiglottitis?

Answer: "Thumbprint sign" seen on lateral cervical x-ray

What is the H. influenzae vaccine composed of?

Answer: The H. influenzae type B (Hib) vaccine is made of type B capsular polysaccharide conjugated to a protein (eg, diphtheria toxoid) that allows for a T-dependent immune response providing greater protection than T-independent immune response.

How is H. influenzae diagnosed?

Answer: Culture in chocolate agar enriched with NAD (factor V) and hemin (factor X) and latex agglutination against PRP. Meningitis with Hib can be diagnosed by antigen detection in the cerebrospinal fluid (CSF).

What is unique about capsule serotype B of H. influenzae?

Answer: Associated with invasive infections in children. B capsule is composed of repeating polyribosylribitol phosphate (PRP, pentose sugars); other serotypes have hexose sugars.

What are the virulence factors of H. influenzae?

Answer: Capsule (six serotypes), lipopolysaccharide (LPS), attachment factors (pili, fibrils, protein H. influenzae adhesin [Hia]), immunoglobulin A (IgA) protease

What does Haemophilus mean? (It is a clue to its culture requirements.)

Answer: Blood loving

What special culture requirements does H. influenzae have?

Answer: Chocolate agar with factors V (nicotinamide adenine dinucleotide [NAD]) and X (hematin) Coculture H. influenzae with Staphylococcus aureus on blood agar because S. aureus hemolyzes red blood cells (RBCs) releasing factors V and X.

Describe the morphology of H. influenzae:

Answer: Encapsulated gram-negative pleomorphic coccobacillus

What other organisms should be in the differential when considering H. influenzae infection of the head and neck?

Answer: Moraxella catarrhalis and Streptococcus pneumoniae

Name the diseases caused by Haemophilus influenzae:

Answer: Bronchitis, sinusitis, pneumonia, otitis media, conjunctivitis, epiglottitis, bacterial meningitis

Name the five medically important respiratory Gram-negative rods:

1. Klebsiella

2. Bordetella

3. Legionella

4. Haemophilus

5. Pseudomonas

A 15-year-old girl presents with abdominal pain and diarrhea after eating a hamburger at a barbeque the day before. She is afebrile but on rectal examination there is gross blood. Stool analysis is positive for RBCs and negative for fecal leukocytes. What is the most likely diagnosis? How do you confirm the diagnosis? What is a possible sequela of this infection?

Answer: Enterohemorrhagic E. coli O157:H7. Confirm with stool culture. May lead to hemolytic uremic syndrome (HUS)

A 30-year-old man presents with fever, abdominal cramps and watery diarrhea after consuming raw oysters on the prior day. On stool examination, there are RBCs and WBCs. What is the most likely diagnosis?

Answer: Vibrio parahaemolyticus

CLINICAL VIGNETTES A 10-year-old girl with sickle cell disease presents with left knee pain, leukocytosis, and an increased erythrocyte sedimentation rate (ESR). What is the most likely diagnosis and what pathogen is most likely responsible?

Answer: Osteomyelitis caused by Salmonella

What is given as antimicrobial prophylaxis prior to abdominal surgery to prevent pathologic infection with B. fragilis among other GI pathogens?

Answer: Used to be anti-anaerobic cephalosporins or oral metronidazole, but these have largely been replaced by ertapenem

Bacteroides fragilis is normal colonic flora, but under what conditions does it cause disease?

Answer: Bacteroides fragilis has very low virulence; however, intestinal perforation may lead to secondary peritonitis and abscess formation. Bacteroides fragilis may also be pathogenic in situations of gyn pathology (pelvic inflammatory disease [PID], septic abortion).

Note that 1° peritonitis = spontaneous bacterial peritonitis, 2° = peritonitis due to perforation/necrosis

What is the combination of medications used to treat H. pylori infection?

Answer: Triple therapy originally included bismuth salts, metronidazole, and either ampicillin or tetracycline. The current regimen of choice is a proton pump inhibitor, amoxicillin, and clarithromycin.

What are the long-term consequences of H. pylori infection?

Answer: Chronic gastritis, gastric adenocarcinoma, and mucosa-associated lymphoid tumor (MALT) type B-cell lymphoma

How is H. pylori diagnosed?

Answer: Invasive (endoscopy with biopsy) or noninvasive (serology or urease breath test in which patients drink C14-labeled urea which is then hydrolyzed to ammonia and labeled CO2 that is detected in their breath)

How can H. pylori be biochemically characterized?

Answer: Catalase positive, oxidase positive, and urease positive. Urease, an important pathogenic factor, produces ammonia and bicarbonate that neutralizes gastric acids.

HELICOBACTER PYLORI What disorder does H. pylori most commonly cause?

Answer: Duodenal ulcers. Ninety percent of duodenal ulcers are associated with H. pylori. (Chronic nonsteroidal anti-inflammatory drug [NSAID] use accounts for the other 10%.)

What neurological disorder is associated with C. jejuni infection?

Answer: Guillain-Barré syndrome, an autoimmune, demyelinating ascending motor paralysis

What is the most common cause of bloody diarrhea in the United States?

Answer: Campylobacter

What are the common sources of C. jejuni and how is it transmitted?

Answer: Poultry (infrequently red meats) and in many domestic animals. Commonly transmitted via cross-contamination (eg, unwashed cutting board)

What is the clinical progression of disease in an individual infected with Campylobacter jejuni?

Answer: After incubation of approximately 3 days, patients usually present with abdominal pain and diarrhea. However, approximately one-third of patients present with an influenza-like prodrome (ie, fever, malaise), followed a day later by severe loose, watery, or bloody stools.

Describe the morphology of Campylobacter?

Answer: Corkscrew shaped with long bipolar flagellae. Similar to Helicobacter pylori, its specialized shape helps drill through mucous membranes.

Which groups of patients are especially sensitive to V. vulnificus septicemia?

Answer: Cirrhotic and immunocompromised patients are very susceptible (>40% mortality rate).

How is Vibrio vulnificus transmitted and what are its symptoms?

Answer: Direct inoculation of contaminated brackish water causes necrotizing wound infections (hand injuries related to opening oysters). Ingestion of raw shellfish causes gastroenteritis and sepsis with necrotizing skin lesions.

How is Vibrio parahaemolyticus transmitted and what are its symptoms?

Answer: Vibrio parahaemolyticus is transmitted by ingestion of undercooked seafood (shrimp, sushi, and the like) and is a frequent cause of seafood-associated diarrhea.

How are V. cholerae infections treated?

Answer: Rehydration with intravenous (IV) fluid and electrolytes. In milder cases, treat with oral rehydration with electrolyte and glucose solution (eg, WHO oral rehydration solution). Antibiotics such as doxycycline, tetracycline, and ciprofloxacin may shorten the duration of the illness.

What is the relationship between cholera and stomach acid?

Answer: Vibrio cholerae is acid-sensitive, therefore, individuals taking medications to reduce stomach acid (eg, proton pump inhibitors) may be at increased risk for cholera.

What are the physical findings in an individual infected with V. cholerae?

Answer: Severe dehydration from continuous watery diarrhea with a rice water appearance. Look for sunken eyes, poor skin turgor (skin tenting), and diminished pulses.

What is the mechanism of action of cholera toxin?

Answer: Constitutively activates Gs via ADP ribosylation leading to constant activation of adenylate cyclase and high levels of cAMP. This causes increased secretion of Cl~ ions from intestinal cells into the GI lumen followed by positively charged Na+ ions. Water follows Na+ into the lumen leading to watery diarrhea (recall ETEC LT).

What does V. cholerae require in order to cause the clinical disease cholera?

Answer: Infection of V. cholerae with the CTX phage that encodes the cholera toxin

VIBRIO Describe the characteristic appearance of Vibrio cholerae:

Answer: Gram-negative rod with a single polar flagellum, giving it a comma shape

What patients are at increased risk for Salmonella osteomyelitis and sepsis?

Answer: Sickle cells disease patients due to functional asplenia

How do you treat Salmonella enterocolitis?

Answer: Fluid/electrolyte replacement as the disease resolves within a week

How does nontyphoidal Salmonella cause enterocolitis and describe the type of diarrhea?

Answer: Salmonella directly invades epithelial cells of the small and large intestines. Presents with fever and bloody diarrhea with inflammatory white blood cells (similar to EIEC).

What are some sources of Salmonella?

Answer: Undercooked poultry, meat, eggs, greens

What disease is typhoid fever often mistaken for? Why?

Answer: Appendicitis, patients present with right lower quadrant abdominal pain without rash.

What is the appropriate therapy for S. typhi infection?

Answer: Ciprofloxacin, ceftriaxone, or azithromycin

Describe the location and appearance of the rash seen in week 2:

Answer: Rose spots, small, transient, pink rash located on the abdomen (seen in 30% of patients)

Typhoid fever is a protracted disease of about 3 weeks. Describe the pathogenesis and symptoms seen in each week:

Week 1

Bacteremia with fever/chills

Week 2

Monocyte involvement with organ inflammation, abdominal pain, and rash

Week 3

Ulceration of Peyer patches, intestinal bleeding, and shock

What cells in particular harbor S. typhi and facilitate its dissemination?

Answer: Monocytes, those in Peyer patches in the ileocecal intestines are the initial target

What organ harbors S. typhi in a chronic carrier state?

Answer: Gallbladder (remember Typhoid Mary)

Where does infection with S. typhi begin and where does it spread to?

Answer: Salmonella typhi begins in the ileocecal intestine and spreads hematogenously and through the lymphatic system to the liver, bone marrow, gallbladder, and spleen.

What makes S. typhi resistant to macrophage killing?

Answer: Inhibits phagolysosome fusion and defensins resist O2-dependent and independent killing.

How do typhoidal strains differ from nontyphoidal strains of Salmonella in terms of reservoirs?

Answer: Salmonella typhi and S. paratyphi have only human reservoirs, while nontyphoidal strains have both human and animal reservoirs (chickens and turtles).