What component of Mycoplasma cell membrane is unique?

Answer: It contains sterols like cholesterol and is the cell's only protective layer. Mycoplasma requires cholesterol for growth.

Why do penicillins and cephalosporins not work against Mycoplasma?

Answer: Mycoplasma has no cell wall, therefore, penicillins and cephalosporins which target the cell wall are ineffective.

How is nocardiosis treated?

Answer: Trimethoprim-sulfamethoxazole (TMP-SMX)

What risk factors predispose to Nocardia infection?

Answer: Immunosuppression and cancer

How does a Nocardia infection manifest?

Answer: Infection with Nocardia can produce pneumonia, lung abscesses, and can spread systemically. Abscesses can form throughout the body, especially in the brain.

How is Nocardia transmitted?

Answer: Transmitted via inhalation, producing lung abscesses and cavitations (it can be confused with Mycobacterium tuberculosis)

Does Nocardia require oxygen?

Answer: Yes. Nocardia is aerobic, in contrast to Actinomyces, an anaerobe.

Where is Nocardia normally found?

Answer: In the soil with transmission via inhalation. Nocardia is never a normal flora.

Describe the appearance of Nocardia asteroides on light microscopy:

Answer: Gram-positive rods forming branching, beaded filament S. Nocardia is also slightly acid-fast due to the mycolic acid in its cell walls.

How are Actinomyces infections treated?

Answer: Penicillin G (often for a prolonged course) +/- surgical drainage

How does an Actinomyces infection manifest?

Answer: Actinomyces causes eroding abscesses with draining sinus tracts. Main forms are cervicofacial (lumpy jaw) and thoracic. Also may cause pelvic pathology in females.

Can Actinomyces grow without oxygen?

Answer: Yes. Actinomyces is an anaerobe.

What are sulfur granules of Actinomyces?

Answer: Yellow-colored colonies and cellular debris (do not actually contain sulfur) that are visible within the purulent discharge

Where is Actinomyces normally found?

Answer: In the gingival crevices of the teeth, especially in patients with poor oral hygiene. It forms part of the normal oral flora.

Describe the appearance of Actinomyces israelii on light microscopy:

Answer: Gram-positive rods forming branching, beaded filaments. Colonies in pus appear as yellow granules called sulfur granules.

A 30-year-old woman from Southeast Asia presents with a hypopigmented, macular forearm lesion and associated with loss of sensation (decreased pin prick). The arm shows significant muscle atrophy. What is the most likely diagnosis?

Answer: Tuberculoid leprosy

A 34-year-old male immigrant presents to the physician with a cough and fever. On his last visit 12 months ago, his PPD was positive and chest x-ray showed likely active tuberculosis. He was treated with INH and rifampin and his symptoms abated. On this visit, he appears very sick and has hard time breathing. He denies night sweats and hemoptysis. His temperature is 102.1°F. Chest x-ray reveals infiltrates in the right middle and lower lobes and a Ghon complex. He is still taking INH and rifampin, which do not seem to help. What is the most likely diagnosis?

Answer: TB relapse; note that the Ghon complex is consistent with primary healed TB and does not exclude reactivation on relapse.

A patient presents with low-grade fever, chills, night sweats, weight loss, and a cough productive of blood-tinged sputum for 2 months. You suspect tuberculosis (TB) and order a chest x-ray. What findings on chest x-ray would be consistent with your suspected diagnosis?

Answer: Active tuberculosis pneumonia with cavitary lesions and posterior upper lobe involvement (past exposure would show isolated granuloma, Ghon focus, Ghon complex, old scarring in the upper lobes)

A 22-year-old woman is taking isoniazid prophylaxis for tuberculosis exposure. After 1 month of therapy she develops tingling in both her hands. What is the term for what she is experiencing and how would you treat her?

Answer: Peripheral neuropathy due to vitamin B6 depletion by the isoniazid (INH). Treat with vitamin B6, otherwise known as pyridoxine

What causes fish-tank or swimming-pool granuloma?

Answer: Mycobacterium marinum.

Granulomatous, ulcerating lesions at the site of breaks in the skin exposed to these environments

What is Mycobacterium avium complex (MAC) and what are its symptoms?

Answer: A mycobacterium ubiquitous in water and soil, but has become a common pathogen in late-stage AIDS patients (CD4 count <50). Symptoms include chronic wasting, fever, weight loss, marrow suppression, and chronic watery diarrhea. May also cause respiratory disease mimicking tuberculosis especially in chronic obstructive pulmonary disease (COPD) patients.

How are close contacts prophylactically treated?

Answer: Dapsone

What are potential toxicities associated with dapsone treatment?

Answer: Methemoglobinemia and hemolysis

What is the treatment of leprosy?

Answer: Dapsone and rifampin for tuberculoid form. Add clofazimine for lepromatous form. Because of slow growth rate, must treat for at least 2 years

What is the main host defense against leprosy?

Answer: Cell-mediated immunity (CD4+ T cells and macrophages) because M. leprae is a facultative intracellular pathogen

How is M. leprae cultured or grown?

Answer: Mycobacterium leprae cannot be cultured on artificial media, and has been grown on mouse footpads and in armadillos (doubling time of 14 days).

What conditions favor the growth of M. leprae?

Answer: Low temperature (30°C). Mycobacterium leprae preferentially affects cool areas of the body (surface of the skin in distal extremities and the nose).

How is leprosy transmitted?

Answer: Respiratory secretions or contact with skin lesions of infected individual. However, not all individuals are susceptible to infection (reasons unknown).

What laboratory test distinguishes between lepromatous and tuberculoid leprosies?

Answer: Lepromin skin test is Negative in lepromatous leprosy. Positive in tuberculoid leprosy

What is tuberculoid leprosy?

Benign form of leprosy that is mild and sometimes self-limiting disease in a person with intact cell-mediated immunity. Usually only one or two hypopigmented, hairless macular skin lesions with diminished sensation. Enlarged nerves near the skin may be palpable (greater auricular, ulnar, posterior tibial, peroneal). In contrast to lepromatous leprosy, there is usually asymmetric nerve involvement. In tuberculoid leprosy biopsies of lesions may show small numbers of organisms and vigorous granuloma formation.

What is lepromatous leprosy?

Malignant, progressive form of leprosy that results from failure of cell-mediated immunity and primarily affects the nerves, skin, eyes, and testes, leading to loss of sensation in symmetric stocking-glove distribution, leonine facies (thickened facial skin), nodular skin lesions, saddle-nose deformity, blindness, and infertility. Sensory loss can lead to repetitive trauma and secondary infection, eventually leading to loss of fingers and toes. In lepromatous leprosy biopsies of lesions may show large numbers of organisms and minimal host inflammatory response.

What are the two main clinical manifestations of leprosy?

1. Lepromatous leprosy

2. Tuberculoid leprosy

What is the most common cause of adrenal insufficiency worldwide?

Answer: Adrenal TB

What is the most common extrapulmonary manifestation of tuberculosis?

Answer: Scrofula or cervical mycobacterial lymphadenitis

What is Pott disease?

Answer: Tuberculous infection of the thoracic/lumbar spine leading to destruction of intervertebral discs/bodies and compression fractures

Who gets miliary tuberculosis?

Answer: Those with weakened cell-mediated immunity (HIV positive, elderly, children)

What is miliary tuberculosis?

Answer: Disseminated TB infection leading to millet seed-sized granulomas in the lungs, liver, spleen, bone, kidneys, spine, and other organs

What percentage of primary infections progress to active tuberculosis?

Answer: Five percent of those primarily infected will develop reactivation tuberculosis in the first 1 to 2 years. Another 5% will develop reactivation infection sometime later in life. Normal infected individuals have a 10% lifetime risk of active infection, while immunocompromised patients are at substantially higher risk.

What are the main toxicities of anti-tuberculous therapy?

Answer: 

Rifampin → orange discoloration of urine/tears, hepatitis, drug interactions

Isoniazid → hepatitis, peripheral neuropathy, lupus-like syndrome

Pyrazinamide → hepatitis, hyperuricemia

Ethambutol → optic neuritis

Streptomycin → nephro- and ototoxicity

What is the treatment of active tuberculosis?

Answer: Cough with hemoptysis, low-grade six-month regimen: initially four drugs (rifampin, isoniazid, pyrazinamide, ethambutol) for 2 months, followed by 4 months of isoniazid and rifampin. Multiple drugs should always be used to prevent the emergence of multidrug-resistant strains.

What are the signs and symptoms of active pulmonary tuberculosis?

Answer: Cough with hemoptysis, low-grade fever, night sweats, and weight loss. Chest x-ray showing upper lobe infiltrates, cavitary lesions, calcifications

What is secondary tuberculosis?

Answer: Reactivation of a prior infection due to weakened immunity (months to years later). Most adult cases of active tuberculosis are secondary tuberculosis.

Pathology Correlate: The Ghon complex is the hallmark of primary tuberculosis, what is it?

Answer: Ghon complex = a Ghon focus (calcified TB granuloma forming a nodule in the middle or lower lung) + an associated hilar or perihilar lymph node

What is the pathology of symptomatic primary tuberculosis?

Answer: In the lungs and other organs, large caseous granulomas develop and eventually liquefy, creating cavitary lesions with air-fluid levels (air-fluid levels in the lungs only).

What groups are at risk for symptomatic primary tuberculosis?

Answer: Those with deficient cell-mediated immunity (children, elderly, immunocom-promised or immunosuppressed)

What are the clinical manifestations of most primary infections with tuberculosis?

Answer: No symptoms (asymptomatic 90%), positive PPD, Ghon complex

Pathology Correlate: Describe the pathogenesis of primary tuberculosis:

Answer: Mycobacteria ingested by phagocytes trigger cell-mediated immunity leading to caseating granulomas.

What is primary tuberculosis?

Answer: An infection in the lungs of a previously unexposed individual

How is tuberculosis transmitted?

Answer: Inhalation of infected respiratory droplets

How is M. tuberculosis cultured?

Answer: Lowenstein-Jensen agar. However, it is important to remember that TB is very difficult to culture and takes weeks to grow.

What can cause a false-positive PPD?

Answer: Bacillus Calmette-Guérin (BCG) vaccine, prior treated tuberculosis (once exposed, the PPD remains positive even after treatment), exposure to nontuberculosis mycobacteria

What medication must be coadministered to all patients on isoniazid therapy and why?

Answer: Vitamin B6 (pyridoxine) to prevent a peripheral neuropathy

How is latent tuberculosis (TB) infection detected and how is it treated?

Answer: Latent infection is conversion to positive PPD with no signs or symptoms of active disease and no signs of disease on chest x-ray (CXR). First-line treatment is 9 months of isoniazid.

What are the criteria for a positive PPD skin test?

Answer: A positive test is defined based on the size of the red, raised in duration after 48 hours: greater than 15 mm for persons with no known exposure, greater than 10 mm in high-risk patients (including health-care workers), greater than 5 mm in HIV patients or those with recent known exposure

Purified protein derivative (PPD) is a skin test for tuberculosis. How does it work?

Answer: Intradermally injected proteins from M. tuberculosis initiate a local delayed-type hypersensitivity reaction (type IV hyper-sensitivity) in previously infected individuals.

What is the main host defense against M. tuberculosis?

Answer: Cell-mediated immunity (CD4+ T cells and macrophages)

What populations are most at risk for TB?

Answer: Elderly persons, immunocompromised, human immunodeficiency virus (HIV)/immunosuppressed (transplant patients), and people from lower socioeconomic status

What two classic "ancient" diseases are caused by mycobacteria?

Answer: Tuberculosis ("consumption") by Mycobacterium tuberculosis and leprosy (Hansen disease) by Mycobacterium leprae

What other bacteria are acid-fast? Why?

Answer: Nocardia species are acid-fast because their cell walls are also high in mycolic acid.

What is the principal dye in acid-fast stain and what component of the cell wall does it bind?

Answer: Carbolfuchsin binds to mycolic acid (long-chain fatty acid), which is present in abundance in the cell wall.

How are mycobacteria visualized under light microscope?

Answer: Appear red with Ziehl-Neelsen acid-fast stain. Stain is positive for AFB = "acid-fast bacillus"

Tuberculosis (TB) stain poorly with Gram stain; technically gram positive but not useful in clinical practice

What are some characteristics of mycobacteria?

Answer: Obligate aerobes, acid-fast bacilli, intracellular growth, and multiple-drug resistance

A 30-year-old human immunodeficiency virus (HlV)-positive man presents with 1 week of fever and malaise. On his forearm there is a 2-cm round, vascular, nontender, friable exophytic lesion. What is the diagnosis? Pathogen? Appropriate treatment?

Answer: Bacillary angiomatosis caused by Bartonella Oral erythromycin, doxycycline, or azithromycin

A 5-year-old girl presents to the emergency department (ED) with a deep puncture wound on her hand from a cat bite. There is considerable pain, erythema, and swelling noted. What is required for prophylaxis?

Answer: Amox-clavulanate for Pasteurella prophylaxis

A 25-year-old woman presents with a painful rash on her hand and tender axillary adenopathy for 2 days. She owns two cats. On examination, she has multiple pruritic erythematous vesicles and papules on her right hand with suppurative axillary adenopathy. What is the diagnosis? Treatment?

Answer: Cat scratch disease. Azithromycin

A patient of yours kills a deer infected with F. tularensis; he then skins it. His wife then prepares the deer for dinner but undercooks it. The deer is served at her office for lunch the next day. What type of infection will the husband present with? What type will his wife and her coworkers present with?

Answer: Hunter: pneumonia through inhalation of aerosolized bacteria from skinning or ulceroglandular from inoculation Wife and coworkers: typhoidal tularemia with fever and abdominal pain

What is trench fever?

Answer: Disease that affected up to 1 million soldiers during World War I. Typically presents with flu-like illness with bone pain, splenomegaly, and a maculopapular rash. It is spread by human body louse.

What diseases does Bartonella quintana cause?

Answer: Trench fever, bacillary angiomatosis (several species of Bartonella are known to cause bacillary angiomatosis) and endocarditis in homeless patients

What is the treatment of bacillary angiomatosis?

Answer: Oral erythromycin or doxycycline. Newer macrolides such as azithromycin and clarithromycin probably effective but not as well studied

What is bacillary angiomatosis? What patient population is affected?

Answer: Systemic disease that often presents with cutaneous vascular lesions that easily bleed in AIDS patients

What is the treatment of cat scratch disease?

Answer: Azithromycin, quinolones, or doxycycline

What is seen on a lymph node biopsy of cat scratch disease?

Answer: Stellate granulomas

What is cat scratch disease? What patient population is most often affected?

Answer: Cutaneous lesion at the site of cat scratch/bite with regional lymphadenopathy, fever, and malaise. Eighty-five to ninety percent of cases occur in children.

What diseases does Bartonella henselae cause?

Answer: Cat scratch disease and bacillary angiomatosis

What drugs are used as treatment and prophylaxis for P. multocida?

Answer: Treat with penicillin G and prophylaxis with amoxicillin/clavulanate. Pasteurella multocida is resistant to first-generation cephalosporins.

Why shouldn't wounds from animal bites be sutured up?

Answer: Pasteurella multocida is a facultative anaerobe and suturing the wound would provide a better growth environment for the bacteria.

How does P. multocida most commonly present?

Answer: Painful wound infection with rapid swelling within 24 hours of bite

What is the typical source of Pasteurella multocida in human infections?

Answer: Cat or dog bites (their normal oral flora) or cat scratch

What is the treatment of choice for Brucella?

Answer: Doxycycline plus rifampin or doxycycline plus streptomycin

Who is most likely to acquire brucellosis?

Answer: Those with close contact with livestock (farmers, veterinarians, meat packers) and those who drink unpasteurized milk

What is the most characteristic symptom of brucellosis?

Answer: Undulant (a diurnal rising and falling) fever actually occurs in a minority of patients. Fever is normal in the AM, has slow rise throughout day, and peaks in the PM. Most patients have nonspecific symptoms (fever, malaise), myalgias, lymphadenitis hepatosplenomegaly, and pancytopenia. The presentation may also be dominated by chronic pain in affected tissues such as the spine.

What type of cells does Brucella infect?

Answer: Reticuloendothelial system (lymph nodes, spleen, liver, and bone marrow)

What is the drug of choice for the treatment of F. tularensis?

Answer: Streptomycin

How is F. tularensis diagnosed?

Answer: Serological tests since laboratory culture is dangerous

What is required for host defense against F. tularensis?

Answer: Cell-mediated immunity as F. tularensis is an intracellular pathogen

Francisella tularensis has what special culture requirement?

Answer: Most strains require cysteine.

How virulent is F. tularensis?

Answer: Highly virulent. Requires only 10 to 50 organisms to cause disease. Most diagnostic laboratories will not culture it, and there is concern over its use as a bioterrorism agent.

How is F. tularensis spread?

Answer: Via vectors (wood ticks, deerflies, mosquitoes) and handling of infected animals (especially rabbits and deer). In the United States, it is most commonly acquired from ticks. Hunters often acquire the pneumonic form of the infection due to aerosolization of the pathogen during skinning of animals.

Francisella tularensis causes two forms of tularemia, describe both forms:

1. Ulceroglandular form (70%-80%; handling of infected animals) presents with ulcers at the site of infection, lymphadenopathy at the draining lymph nodes, and fever.

2. The more severe typhoidal form (10%-15%; ingestion) often includes pneumonia and symptoms of bacteremia (fevers, chills, myalgias, malaise, and weight loss).

How is Y. enterocolitica treated?

Answer: Treat with either fluoroquinolones or trimethoprim-sulfamethoxazole (TMP-SMX). It is resistant to cephalosporins.

Yersinia enterocolitica infection is often confused with what condition?

Answer: Appendiciti S. Yersinia enterocolitica causes mesenteric adenitis (focal ulcerations in the ileum with swelling of the with fever, right lower quadrant pain, and leukocytosis).

How is Yersinia enterocolitica transmitted to humans and what does it cause?

Answer: Consumption of contaminated meat, animal feces, and unpasteurized milk leads to enterocolitis (fever and bloody diarrhea), similar to Salmonella and Shigella infections.

What type of vaccine against Y. pestis is available? What is its limitation?

Answer: A killed whole-cell vaccine protects against bubonic plague and not pneumonic plague.

How is Y. pestis infection treated?

Answer: Streptomycin, gentamicin, or doxycycline

Why is the bubonic plague referred to as the Black Death?

Answer: Cutaneous hemorrhage and disseminated intravascular coagulation cause a black skin discoloration.

What is the progression of disease in a person infected with Y. pest

Answer: Initially lymph nodes will swell and become erythematous, warm, and painful (buboes). Then fever and myalgia begin. Next, lung infection (pneumonic plague, virtually fatal) and sepsis may occur.

What is the purpose of the F1 envelope antigen?

Answer: Inhibits phagocytosis and allows Y. pestis to survive intracellularly in the lymph nodes causing necrosis and buboes

Name the important virulence factors for Y. pestis:

Answer: F1 envelope antigen, V antigen, W antigen, endotoxin

How virulent is Y. pestis?

Answer: Extremely. One to ten organisms can cause disease.

What are the important animal reservoirs for Y. pestis?

Answer: Rats (worldwide) and prairie dogs (United States)