Tuberculosis (pulmonary): Clinical sciences

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Introduction0:00–0:52

Pulmonary tuberculosis, or pulmonary TB, is an infectious disease of the lungs caused by Mycobacterium tuberculosis. Primary infection with M.
tuberculosis in adults is usually asymptomatic and followed by a latent phase, which, in some cases, can progress to active pulmonary tuberculosis, also called reactivation or post-primary tuberculosis.
The gold standard for diagnosing pulmonary tuberculosis is mycobacterial culture, but preliminary diagnosis can be made with acid-fast bacilli smear and rapid nucleic acid amplification testing.
Diagnostic testing should also include drug susceptibility testing, to identify cases of multi- and extensively-drug resistant tuberculosis.

Unstable patient0:52–1:20

Now, if you suspect pulmonary TB, first, you should perform an ABCDE assessment to determine if your patient is unstable or stable.
If the patient is unstable, stabilize their airway, breathing, and circulation, which might require intubation. Additionally, obtain IV access, administer supplemental oxygen, and put your patient on continuous vital sign monitoring, including heart rate, blood pressure, and pulse oximetry.Now, let’s go back to the ABCDE assessment and take a look at the stable patients.

Stable patient1:20–4:10

In this case, perform a focused history and physical examination and get a chest x-ray. History typically reveals respiratory involvement, such as chronic cough and hemoptysis, but also systemic symptoms, like unintentional weight loss, anorexia, fever, and night sweats.
Additionally, the individual might present with risk factors for exposure to tuberculosis, such as living in a facility like a nursing home, homeless shelter, or correctional facility; having a family member or close contact with tuberculosis; or spending time in a country with a high prevalence of TB.
Also, the patient could report risk factors for developing active tuberculosis, like being immunocompromised due to HIV, malignancy, or immunosuppressive therapy.
Now, here’s one clinical pearl to keep in mind! Individuals with HIV are much more likely to develop active tuberculosis compared to people without HIV.
Patients who are diagnosed with active tuberculosis should be tested for HIV, and HIV positive patients should be started on antiretroviral therapy, in addition to treatment for TB.
On the other hand, physical exam might reveal lung findings, such as dullness to percussion; low-pitched, hollow breath sounds; and rales, or crackles.
The chest x-ray will typically show a solitary cavitary lesion, called a Ghon focus, in addition to other scattered consolidation or nodularity.
On the other hand, a Ghon complex is when a Ghon focus presents together with ipsilateral hilar lymphadenopathy. Lastly, a Ranke complex is a later manifestation of a Ghon complex, where the lesion undergoes calcification and has an ipsilateral calcified lymph node.
As a clinical pearl, a CT scan is not usually required to diagnose TB, but it can be ordered in unclear cases to obtain a more precise resolution of the cavitary lesions.Here’s a high-yield fact for your tests!
The cavitary lung lesions, in patients with tuberculosis, classically involve the upper lobes, but less frequently may involve the lower lobes too.
Also, remember that several differential diagnoses should come to mind when a question stem mentions cavitary lung lesions, such as aspergillus infection, sarcoidosis, or even cancer, so the clinical history is what will help you narrow down the diagnosis.If these findings are present, you should suspect pulmonary TB and order laboratory testing of the patient’s sputum.

Suspect pulmonary TB4:10–5:36

Check rapid diagnostic tests including smear microscopy for acid fast bacilli, or AFB, on 3 separate sputum samples, and order nucleic acid amplification testing or NAAT for short.
In addition, send a sputum sample for mycobacterial culture. Mycobacterial culture of sputum, bronchoalveolar lavage, pleural fluid, or even pleural or lung biopsy is the gold standard for diagnosing tuberculosis, but culture results may not be available for weeks.
On the other hand, results of the AFB smear and nucleic acid amplification testing are ready in 1 to 2 days, which can help expedite diagnosis and treatment.
Ok, let’s say the sputum AFB is positive and NAAT is positive. Then, you can diagnose the patient with pulmonary TB.
On the other hand, if the sputum AFB is negative and NAAT is negative, or there are discordant results, then pulmonary tuberculosis is still possible, and you should assess the mycobacterial culture results.
If the culture is negative for Mycobacterium tuberculosis, consider alternative diagnoses, but if the culture comes back positive, then the patient has pulmonary TB.Ok, once you have diagnosed the patient with pulmonary tuberculosis, the next step is drug susceptibility testing.

Pulmonary TB5:36–6:04

This can be done through rapid molecular tests and whole-genome sequencing. Drug susceptibility testing for first-line treatments should be performed whenever possible.
It is particularly important for patients at high risk of drug resistance, such as people with a history of travel to a country with a high prevalence of drug-resistant TB.If the testing reveals no drug resistance, begin the intensive phase of treatment with antimicrobial therapy.

No drug resistance6:04–7:39

Keep in mind that you always need to use a combination of antimicrobials during the intensive phase, because Mycobacterium tuberculosis can quickly develop drug resistance if you don’t.You should begin treatment with RIPE therapy, which stands for rifampin, isoniazid, pyrazinamide, and ethambutol for 2 months.
Next, assess the patient’s response to therapy by checking sputum AFB and mycobacterial culture monthly. If there are two consecutive negative culture results by the end of the intensive phase of treatment, then the continuation phase of treatment will consist of isoniazid and rifampin for 4 months.
On the other hand, if there are positive cultures at the end of the intensive phase of treatment, then the continuation phase with isoniazid and rifampin should be extended to seven months.
Now, here’s another clinical pearl to keep in mind! Symptoms of pulmonary tuberculosis usually begin to improve within a few weeks of treatment.
However, patients with TB and HIV coinfection may develop immune reconstitution inflammatory syndrome, or IRIS for short.
This is a paradoxical reaction where symptoms and imaging findings get worse after starting antituberculosis therapy or antiretroviral therapy.
Common clinical manifestations include fever, lymphadenopathy, and worsening respiratory symptoms. Ok, now let’s go back to drug susceptibility testing and take a look at patients that have drug-resistant tuberculosis.

Drug resistance7:39–9:10

If there is resistance to isoniazid only, then the isoniazid can be replaced by a fluoroquinolone. So, isoniazid-resistant TB can be treated with rifampin, a fluoroquinolone, pyrazinamide, and ethambutol for 6 months.However, if the drug susceptibility testing reveals rifampin-resistant TB, or even multidrug-resistant TB, meaning there’s resistance to both rifampin and isoniazid, then the patient can be treated with bedaquiline, pretomanid, linezolid, and a fluoroquinolone for 6 months.
Finally, if testing reveals extensive drug resistance, then tailor therapy based on susceptibility for a prolonged treatment course.
Here’s one last clinical pearl to keep in mind! In the United States, TB is a nationally notifiable disease, which means that cases of tuberculosis should be reported to a public health office.
Incomplete treatment of pulmonary TB can lead to continued transmission of disease, and the development of drug-resistant TB.
For this reason, most states have laws authorizing public health officials to take disease control measures, and may require patients to participate in directly observed therapy, called DOT, where a healthcare provider observes the patient taking each dose of antituberculosis medication.
Alright, as a quick recap… If you suspect pulmonary TB, test the patient’s sputum for acid fast bacilli, NAAT, and mycobacterial culture.

Review9:10–10:23

Next, obtain drug susceptibility testing. In cases of drug-sensitive tuberculosis, treat with RIPE therapy for 2 months.
During treatment, send sputum samples for mycobacterial culture to assess the patient’s response. If you get two consecutive negative cultures, then continue treatment with 4 months of rifampin and isoniazid.
If the cultures are positive, then they need a longer course of treatment. On the other hand, if the patient has drug-resistant TB, then use second-line antituberculosis medications.
In isoniazid-resistant TB, a fluoroquinolone can replace the isoniazid in RIPE. If the patient has rifampin- or multidrug-resistant TB, then treatment is usually bedaquiline, pretomanid, linezolid, and a fluoroquinolone for 6 months.
Finally, if testing reveals extensive drug resistance, tailor therapy based on susceptibility for a prolonged treatment course.