USMLE® Step 1 style questions USMLE
A 30-year-old man presents to the emergency department due to shortness of breath and cough. The patient’s symptoms started one week ago and have progressively worsened. The patient also has chest pain on the right side. Past medical history is significant for poorly-controlled HIV which was diagnosed 3 years ago. Temperature is 39.0 ºC (102.2 ºF), pulse is 120/min, blood pressure is 110/78 mmHg, respirations are 25/minute, and SpO2 is 88% of room air. Chest radiography shows cavitations in the right side of the chest. Sputum and blood cultures grow a Gram-positive bacterium that forms branching filaments and is weakly acid-fast. Which of the following is a feature of the bacterium causing this patient’s condition?
Content Reviewers:Viviana Popa, MD
Contributors:Evan Debevec-McKenney, Alexandru Duhaniuc, MD
Nocardia is a genus of Gram-positive branching filamentous rods that are often found in soil.
There are over 80 species of Nocardia and around 30 of them causes disease in humans, and the most notable ones are Nocardia asteroides, Nocardia brasiliensis, Nocardia cyriacigeorgica, Nocardia farcinica and Nocardia nova.
Nocardia causes a disease called nocardiosis which has three major forms - pulmonary, cutaneous and disseminated.
OK, Nocardia is a rod-shaped Gram-positive bacteria, we’ve got that part down, and this means it goes purple when Gram-stained.
When there’s many of them, they arrange themselves in the shape of purple branching filaments.
They are obligate aerobes, meaning they need oxygen to grow, they are also non-motile, and don’t form spores.
But wait… that sounds exactly like Actinomyces israelii, another group of rod shaped, gram-positive, filamentous bacteria with a lot of other similar features.
To distinguish them, an acid-fast stain, also called Ziehl-Neelsen stain is done.
With this test, a red dye called carbon fuchsin, binds to lipids in the cell wall, coloring them red.
Then alcohol is applied to wash out any dye that hasn’t colored bacteria, and a second dye, methylene blue, is applied.
Now, Nocardia is a weak acid-fast bacteria which means that a less concentrated solution of alcohol is needed during staining and that’s because the mycolic acids in its cell wall have intermediate-length.
So, because it has plenty of lipids in its cell wall, it retains the carbon fuchsin, and it looks red under the microscope, making it an acid-fast bacteria.
On the other hand, in bacteria who don’t have a lot of lipids in their cell wall, like A. Israelii, all the red dye is washed off by alcohol, so it looks blue under the microscope, making it a non-acid-fast bacteria.
Also, Nocardia can be visualized with auramine-rhodamine stain using fluorescence microscopy, which can show a reddish-yellow fluorescence.
This stain is not as specific as Ziehl-Neelsen stain, so it has more false-positive results, but it’s more sensitive, so it has less false-negative results, and it’s also inexpensive.
So the auramine-rhodamine stain is often used for screening.
Another difference is that Nocardia is catalase positive, so it makes an enzyme called catalase which converts hydrogen peroxide to water and oxygen, and also urease positive which means that it produces an enzyme called urease that can break urea into ammonia and carbon dioxide, whereas A. israelii is catalase and urease negative.
Finally, Nocardia species grows on routine media, like blood agar or chocolate agar, on selective media, such as modified Thayer-Martin agar or BCYE agar, on mycobacterial media, like Lowenstein Jensen agar and on fungi media, like Sabouraud dextrose agar.
Nocardia forms white, yellow or orange long branching filamentous colonies with a powdered aspect, which usually takes 3 to 5 days to grow, but sometimes it may take as long as 2 to 3 weeks.
Now, Nocardia has a low virulence and therefore nocardiosis occurs more often as an opportunistic infection in immunocompromised people.
It enters the body through inhalation or skin trauma and once inside, it’s ingested by macrophages.
Inside macrophages, it gets wrapped in a vesicle called a phagosome, which normally merges with lysosomes, to form a phagolysosome inside which bacteria are killed by lysosomal enzymes.
However, the cell wall of Nocardia contains a cord factor, or trehalose dimycolate, which is a glycolipid that inhibits phagolysosomal fusion.
Ok, now, another immune system weapon is that neutrophils and macrophages destroy invading bacteria by generating a bunch of toxic oxygen radicals, such as superoxide, which results from oxidative metabolic burst.
But, Nocardia makes two enzymes that break these toxic oxygen radicals.
First, there’s superoxide dismutase which breaks superoxide radicals into oxygen and hydrogen peroxide.
And since hydrogen peroxide is still harmful, Nocardia also makes catalase, which breaks hydrogen peroxide into water.
Now, in pulmonary nocardiosis, the presence of Nocardia triggers an inflammatory response that calls more macrophages to the site of battle.
As more of them make their way there, they surround the bacteria from all sides, and form a granuloma, which prevents it from spreading.
Nocardia is a gram-positive rod, filamentous, branching bacteria commonly found in soil. It is known to cause nocardiosis, a nocardia infection that can affect different parts of the body, including the skin, respiratory tract, and central nervous system
Nocardia infections are more common in people with weakened immune systems, such as those who have HIV/AIDS, organ transplants, or certain types of cancer. People with conditions that cause a deficiency in their immune system, such as diabetes, are also at an increased risk for Nocardia infections.
Symptoms vary depending on the location of the infection but commonly include fever, cough, chest pain, difficulty breathing, redness, swelling, and pain at the site of the infection. Nocardiosis of the central nervous system can cause symptoms such as headache, fever, seizures, and changes in mental function.
Diagnosis is done by identifying bacteria in a smear or a culture from respiratory secretions, skin biopsy samples, aspirates from abscesses or CSF and blood in case of disseminated disease and treatment is with antibiotics, preferably trimethoprim-sulfamethoxazole.