The recommended treatment of new-onset pulmonary tuberculosis, as of 2010, is six months of a combination of antibiotics containing rifampicin, isoniazid, pyrazinamide, and ethambutol for the first two months, and only rifampicin and isoniazid for the last four months. Where resistance to isoniazid is high, ethambutol may be added for the last four months as an alternative.

If tuberculosis recurs, testing to determine which antibiotics it is sensitive to is important before determining treatment. If multiple drug-resistant TB (MDR-TB) is detected, treatment with at least four effective antibiotics for 18 to 24 months is recommended.

The standard treatment recommended by the WHO is with isoniazid and rifampicin for six months, as well as ethambutol and pyrazinamide for the first two months. If there is evidence of meningitis, then treatment is extended to twelve months. The U.S. guidelines recommend nine months' treatment. "Common medication side effects a patient may have such as inflammation of the liver if a patient is taking pyrazinamide, rifampin, and isoniazid. A patient may also have drug resistance to medication, relapse, respiratory failure, and adult respiratory distress syndrome."

It is currently recommended that HIV-infected individuals with TB receive combined treatment for both diseases, irrespective of CD4+ cell count. ART (Anti Retroviral Therapy) along with ATT (Anti Tuberculosis Treatment) is the only available treatment in present time. Though the timing of starting ART is the debatable question due to the risk of immune reconstitution inflammatory syndrome (IRIS). The advantages of early ART include reduction in early mortality, reduction in relapses, preventing drug resistance to ATT and reduction in occurrence of HIV-associated infections other than TB. The disadvantages include cumulative toxicity of ART and ATT, drug interactions leading to inflammatory reactions are the limiting factors for choosing the combination of ATT and ART.

A systematic review investigated the optimal timing of starting antiretroviral therapy in adults with newly diagnosed pulmonary tuberculosis. The review authors included eight trials, that were generally well-conducted, with over 4500 patients in total. The early provision of antiretroviral therapy in HIV-infected adults with newly diagnosed tuberculosis improved survival in patients who had a low CD4 count (less than 0.050 x 109 cells/L). However, such therapy doubled the risk for IRIS. Regarding patients with higher CD4 counts (more than 0.050 x 109 cells/L), the evidence is not sufficient to make a conclusion about benefits or risks of early antiretroviral therapy.

When HIV-negative children take isoniazid after they have been exposed to tuberculosis, their risk to contract tuberculosis is reduced. A Cochrane review investigated whether giving isoniazid to HIV-positive children can help to prevent this vulnerable group from getting tuberculosis. They included three trials conducted in South Africa and Botswana and found that isoniazid given to all children diagnosed with HIV may reduce the risk of active tuberculosis and death in children who are not on antiretroviral treatment. For children taking antiretroviral medication, no clear benefit was detected.

The principles of treatment for MDR-TB and for XDR-TB are the same. Treatment requires extensive chemotherapy for up to two years. Second-line drugs are more toxic than the standard anti-TB regimen and can cause a range of serious side-effects including hepatitis, depression, hallucinations, and deafness. Patients are often hospitalized for long periods, in isolation. In addition, second-line drugs are extremely expensive compared with the cost of drugs for standard TB treatment.

XDR-TB is associated with a much higher mortality rate than MDR-TB, because of a reduced number of effective treatment options. Despite early fears that this strain of TB was untreatable, recent studies have shown that XDR-TB can be treated through the use of aggressive regimens. A study in the Tomsk oblast of Russia, reported that 14 out of 29 (48.3%) patients with XDR-TB successfully completed treatment. Nix-TB regimen, a combination pretomanid, bedaquiline, and linezolid, has shown promise in early clinical trials.

Successful outcomes depend on a number of factors including the extent of the drug resistance, the severity of the disease and whether the patient’s immune system is compromised. It also depends on access to laboratories that can provide early and accurate diagnosis so that effective treatment is provided as soon as possible. Effective treatment requires that all six classes of second-line drugs be available to clinicians who have special expertise in treating such cases.

If left untreated, miliary tuberculosis is almost always fatal. Although most cases of miliary tuberculosis are treatable, the mortality rate among children with miliary tuberculosis remains 15 to 20% and for adults 25 to 30%. One of the main causes for these high mortality rates includes late detection of disease caused by non-specific symptoms. Non-specific symptoms include: coughing, weight loss, or organ dysfunction. These symptoms may be implicated in numerous disorders, thus delaying diagnosis. Misdiagnosis with tuberculosis meningitis is also a common occurrence when patients are tested for tuberculosis, since the two forms of tuberculosis have high rates of co-occurrence.

Usually, multidrug-resistant tuberculosis can be cured with long treatments of second-line drugs, but these are more expensive than first-line drugs and have more adverse effects. The treatment and prognosis of MDR-TB are much more akin to those for cancer than to those for infection. MDR-TB has a mortality rate of up to 80%, which depends on a number of factors, including

1. How many drugs the organism is resistant to (the fewer the better)

2. How many drugs the patient is given (patients treated with five or more drugs do better)

3. Whether an injectable drug is given or not (it should be given for the first three months at least)

4. The expertise and experience of the physician responsible

5. How co-operative the patient is with treatment (treatment is arduous and long, and requires persistence and determination on the part of the patient)

6. Whether the patient is HIV positive or not (HIV co-infection is associated with an increased mortality).

The majority of patients suffering from multi-drug-resistant tuberculosis do not receive treatment, as they are found in underdeveloped countries or in poverty. Denial of treatment remains a difficult human rights issue, as the high cost of second-line medications often precludes those who cannot afford therapy.

A study of cost-effective strategies for tuberculosis control supported three major policies. First, the treatment of smear-positive cases in DOTS programs must be the foundation of any tuberculosis control approach, and should be a basic practice for all control programs. Second, there is a powerful economic case for treating smear-negative and extra-pulmonary cases in DOTS programs along with treating smear-negative and extra-pulmonary cases in DOTS programs as a new WHO “STOP TB” approach and the second global plan for tuberculosis control. Last, but not least, the study shows that significant scaling up of all interventions is needed in the next 10 years if the millennium development goal and related goals for tuberculosis control are to be achieved. If the case detection rate can be improved, this will guarantee that people who gain access to treatment facilities are covered and that coverage is widely distributed to people who do not now have access.

In general, treatment courses are measured in months to years; MDR-TB may require surgery, and death rates remain high despite optimal treatment. However, good outcomes for patients are still possible.

The treatment of MDR-TB must be undertaken by physicians experienced in the treatment of MDR-TB. Mortality and morbidity in patients treated in non-specialist centers are significantly higher to those of patients treated in specialist centers. Treatment of MDR-TB must be done on the basis of sensitivity testing: it is impossible to treat such patients without this information. When treating a patient with suspected MDR-TB, pending the result of laboratory sensitivity testing, the patient could be started on SHREZ (Streptomycin+ isonicotinyl Hydrazine+ Rifampicin+Ethambutol+ pyraZinamide) and moxifloxacin with cycloserine. There is evidence that previous therapy with a drug for more than a month is associated with diminished efficacy of that drug regardless of "in vitro" tests indicating susceptibility. Hence, a detailed knowledge of the treatment history of each patient is essential. In addition to the obvious risks (i.e., known exposure to a patient with MDR-TB), risk factors for MDR-TB include HIV infection, previous incarceration, failed TB treatment, failure to respond to standard TB treatment, and relapse following standard TB treatment.

A gene probe for "rpoB" is available in some countries. This serves as a useful marker for MDR-TB, because isolated RMP resistance is rare (except when patients have a history of being treated with rifampicin alone). If the results of a gene probe ("rpoB") are known to be positive, then it is reasonable to omit RMP and to use SHEZ+MXF+cycloserine. The reason for maintaining the patient on INH is that INH is so potent in treating TB that it is foolish to omit it until there is microbiological proof that it is ineffective (even though isoniazid resistance so commonly occurs with rifampicin resistance).

When sensitivities are known and the isolate is confirmed as resistant to both INH and RMP, five drugs should be chosen in the following order (based on known sensitivities):

- an aminoglycoside (e.g., amikacin, kanamycin) or polypeptide antibiotic (e.g., capreomycin)

- pyrazinamide

- ethambutol

- a fluoroquinolone (e.g., moxifloxacin (ciprofloxacin) should no longer be used);

- rifabutin

- cycloserine

- a thioamide: prothionamide or ethionamide

- PAS

- a macrolide: e.g., clarithromycin

- linezolid

- high-dose INH (if low-level resistance)

- interferon-γ

- thioridazine

- Ampicillin

"Note:" Drugs placed nearer the top of the list are more effective and less toxic; drugs placed nearer the bottom of the list are less effective or more toxic, or more difficult to obtain.

In general, resistance to one drug within a class means resistance to all drugs within that class, but a notable exception is rifabutin: Rifampicin-resistance does not always mean rifabutin-resistance, and the laboratory should be asked to test for it. It is possible to use only one drug within each drug class. If it is difficult finding five drugs to treat then the clinician can request that high-level INH-resistance be looked for. If the strain has only low-level INH-resistance (resistance at 0.2 mg/l INH, but sensitive at 1.0 mg/l INH), then high dose INH can be used as part of the regimen. When counting drugs, PZA and interferon count as zero; that is to say, when adding PZA to a four-drug regimen, another drug must be chosen to make five. It is not possible to use more than one injectable (STM, capreomycin or amikacin), because the toxic effect of these drugs is additive: If possible, the aminoglycoside should be given daily for a minimum of three months (and perhaps thrice weekly thereafter). Ciprofloxacin should not be used in the treatment of tuberculosis if other fluoroquinolones are available.

There is no intermittent regimen validated for use in MDR-TB, but clinical experience is that giving injectable drugs for five days a week (because there is no-one available to give the drug at weekends) does not seem to result in inferior results. Directly observed therapy helps to improve outcomes in MDR-TB and should be considered an integral part of the treatment of MDR-TB.

Response to treatment must be obtained by repeated sputum cultures (monthly if possible). Treatment for MDR-TB must be given for a minimum of 18 months and cannot be stopped until the patient has been culture-negative for a minimum of nine months. It is not unusual for patients with MDR-TB to be on treatment for two years or more.

Patients with MDR-TB should be isolated in negative-pressure rooms, if possible. Patients with MDR-TB should not be accommodated on the same ward as immunosuppressed patients (HIV-infected patients, or patients on immunosuppressive drugs). Careful monitoring of compliance with treatment is crucial to the management of MDR-TB (and some physicians insist on hospitalisation if only for this reason). Some physicians will insist that these patients remain isolated until their sputum is smear-negative, or even culture-negative (which may take many months, or even years). Keeping these patients in hospital for weeks (or months) on end may be a practical or physical impossibility, and the final decision depends on the clinical judgement of the physician treating that patient. The attending physician should make full use of therapeutic drug monitoring (in particular, of the aminoglycosides) both to monitor compliance and to avoid toxic effects.

Some supplements may be useful as adjuncts in the treatment of tuberculosis, but, for the purposes of counting drugs for MDR-TB, they count as zero (if four drugs are already in the regimen, it may be beneficial to add arginine or vitamin D or both, but another drug will be needed to make five).

- arginine (peanuts are a good source)

- vitamin D

- Dzherelo

- V5 Immunitor

The drugs listed below have been used in desperation, and it is uncertain as to whether they are effective at all. They are used when it is not possible to find five drugs from the list above.

- imipenem

- co-amoxiclav

- clofazimine

- prochlorperazine

- metronidazole

On December 28, 2012 the U.S. Food and Drug Administration (FDA) approved bedaquiline (marketed as Sirturo by Johnson & Johnson) to treat multi-drug resistant tuberculosis, the first new treatment in 40 years. Sirturo is to be used in a combination therapy for patients who have failed standard treatment and have no other options. Sirturo is an adenosine triphosphate synthase (ATP synthase) inhibitor.

The following drugs are experimental compounds that are not commercially available, but may be obtained from the manufacturer as part of a clinical trial or on a compassionate basis. Their efficacy and safety are unknown:

- pretomanid (manufactured by Novartis, developed in partnership with TB Alliance)

- delamanid

In cases of extremely resistant disease, surgery to remove infection portions of the lung is, in general, the final option. The center with the largest experience in this is the National Jewish Medical and Research Center in Denver, Colorado. In 17 years of experience, they have performed 180 operations; of these, 98 were lobectomies and 82 were pneumonectomies. There is a 3.3% operative mortality, with an additional 6.8% dying following the operation; 12% experienced significant morbidity (in particular, extreme breathlessness). Of 91 patients who were culture-positive before surgery, only 4 were culture-positive after surgery.

The resurgence of tuberculosis in the United States, the advent of HIV-related tuberculosis, and the development of strains of TB resistant to the first-line therapies developed in recent decades—serve to reinforce the thesis that Mycobacterium tuberculosis, the causative organism, makes its own preferential option for the poor. The simple truth is that almost all tuberculosis deaths result from a lack of access to existing effective therapy.

Treatment depends on the underlying cause. Treatments include iced saline, and topical vasoconstrictors such as adrenalin or vasopressin. Selective bronchial intubation can be used to collapse the lung that is bleeding. Also, endobronchial tamponade can be used. Laser photocoagulation can be used to stop bleeding during bronchoscopy. Angiography of bronchial arteries can be performed to locate the bleeding, and it can often be embolized. Surgical option is usually the last resort, and can involve, removal of a lung lobe or removal of the entire lung. Non–small-cell lung cancer can also be treated with erlotinib or gefitinib. Cough suppressants can increase the risk of choking.

Countries aim to prevent XDR-TB by ensuring that the work of their national TB control programmes, and of all practitioners working with people with TB, is carried out according to the International Standards for TB Care. These emphasize providing proper diagnosis and treatment to all TB patients, including those with drug-resistant TB; assuring regular, timely supplies of all anti-TB drugs; proper management of anti-TB drugs and providing support to patients to maximize adherence to prescribed regimens; caring for XDR-TB cases in a centre with proper ventilation, and minimizing contact with other patients, particularly those with HIV, especially in the early stages before treatment has had a chance to reduce the infectiousness. Also an effective disease control infrastructure is necessary for the prevention of XDR tuberculosis. Increased funding for research, and strengthened laboratory facilities are much required. Immediate detection through drug susceptibility testing's are vital, when trying to stop the spread of XDR tuberculosis.

While antibiotics with activity specifically against "M. pneumoniae" are often used (e.g., erythromycin, doxycycline), it is unclear if these result in greater benefit than using antibiotics without specific activity against this organism in those with an infection acquired in the community.

Broadspectrum antibiotic to cover mixed flora is the mainstay of treatment. Pulmonary physiotherapy and postural drainage are also important. Surgical procedures are required in selective patients for drainage or pulmonary resection.

In the majority of immunocompetent individuals, histoplasmosis resolves without any treatment. Antifungal medications are used to treat severe cases of acute histoplasmosis and all cases of chronic and disseminated disease. Typical treatment of severe disease first involves treatment with amphotericin B, followed by oral itraconazole.

Liposomal preparations of amphotericin B are more effective than deoxycholate preparations. The liposomal preparation is preferred in patients that might be at risk of nephrotoxicity, although all preparations of amphotericin B have risk of nephrotoxicity. Individuals taking amphotericin B are monitored for renal function.

Treatment with itraconazole will need to continue for at least a year in severe cases, while in acute pulmonary histoplasmosis, 6 to 12 weeks treatment is sufficient. Alternatives to itraconazole are posaconazole, voriconazole, and fluconazole. Individuals taking itraconazole are monitored for hepatic function.

There are several ways that drug resistance to TB, and drug resistance in general, can be prevented:

1. Rapid diagnosis & treatment of TB: One of the greatest risk factors for drug resistant TB is problems in treatment and diagnosis, especially in developing countries. If TB is identified and treated soon, drug resistance can be avoided.

2. Completion of treatment: Previous treatment of TB is an indicator of MDR TB. If the patient does not complete his/her antibiotic treatment, or if the physician does not prescribe the proper antibiotic regimen, resistance can develop. Also, drugs that are of poor quality or less in quantity, especially in developing countries, contribute to MDR TB.

3. Patients with HIV/AIDS should be identified and diagnosed as soon as possible. They lack the immunity to fight the TB infection and are at great risk of developing drug resistance.

4. Identify contacts who could have contracted TB: i.e. family members, people in close contact, etc.

5. Research: Much research and funding is needed in the diagnosis, prevention and treatment of TB and MDR TB.

"Opponents of a universal tuberculosis treatment, reasoning from misguided notions of cost-effectiveness, fail to acknowledge that MDRTB is not a disease of poor people in distant places. The disease is infectious and airborne. Treating only one group of patients looks inexpensive in the short run, but will prove disastrous for all in the long run."- Paul Farmer

Most cases respond to antibiotics and prognosis is usually excellent unless there is a debilitating underlying condition. Mortality from lung abscess alone is around 5% and is improving.

The 2007 guideline “Official American Thoracic Society (ATS) and Infectious Diseases Society of America (IDSA) statement: diagnosis, treatment, and prevention of non-tuberculosis mycobacterial diseases”, notes that M. fortuitum isolates are usually susceptible to multiple oral antimicrobial agents, including the macrolides and quinolones, doxycycline and minocycline, and sulfonamides. Isolates of this mycobacterium are susceptible to the beta-lactam antibiotics, belonging to the carbopenam subgroup, such as Imipenem. Imipenem is a broad spectrum antibiotic produced by the bacteria Streptomyces cattleya. Ondansetron HCL (Zofran) is an antiemetic often given to offset the nausea and vomiting that are a common side effect of Imipenem. Severe infections require IV treatment combined with oral antibiotics for a prolonged period, up to several months. The guideline recommends “for serious skin, bone, and soft tissue M fortuitum disease, a minimum of 4 months of therapy with at least two agents with in vitro activity against the clinical isolate is necessary to provide a high likelihood of cure. Surgery is generally indicated with extensive disease, abscess formation, or where drug therapy is difficult.”

The treatment of TB meningitis is isoniazid, rifampicin, pyrazinamide and ethambutol for two months, followed by isoniazid and rifampicin alone for a further ten months. Steroids help reduce the risk of death in those without HIV. Steroids can be used in the first six weeks of treatment, A few people may require immunomodulatory agents such as thalidomide. Hydrocephalus occurs as a complication in about a third of people with TB meningitis. The addition of aspirin may reduce or delay mortality, possibly by reducing complications such as infarcts.

Controlling the spread of tuberculosis infection can prevent tuberculous spondylitis and arthritis. Patients who have a positive PPD test (but not active tuberculosis) may decrease their risk by properly taking medicines to prevent tuberculosis. To effectively treat tuberculosis, it is crucial that patients take their medications exactly as prescribed.

Tuberculoma is commonly treated through the HRZE drug combination (Isoniazid, Rifampin, Pyrazinamide, Ethambutol) followed by maintenance therapy.

Therapy for cutaneous tuberculosis is the same as for systemic tuberculosis, and usually consists of a 4-drug regimen, i.e., isoniazid, rifampin, pyrazinamide, and ethambutol or streptomycin.

Tuberculous pericarditis is a form of pericarditis.

Pericarditis caused by tuberculosis is difficult to diagnose, because definitive diagnosis requires culturing "Mycobacterium tuberculosis" from aspirated pericardial fluid or pericardial , which requires high technical skill and is often not diagnostic (the yield from culture is low even with optimum specimens). The Tygerberg scoring system helps the clinician to decide whether pericarditis is due to tuberculosis or whether it is due to another cause: night sweats (1 point), weight loss (1 point), fever (2 point), serum globulin > 40g/l (3 points), blood total leucocyte count <10 x 10/l (3 points); a total score of 6 or more is highly suggestive of tuberculous pericarditis. Pericardial fluid with an interferon-γ level greater than 50/ml is highly specific for tuberculous pericarditis.

There are no randomized trials which evaluate the length of anti-tuberculosis treatment required for tuberculous pericarditis. There is a small but not conclusive benefit for treatment with a schedule of steroids with anti-tuberculosis drugs. Open surgical drainage of fluid though effective in preventing cardiac tamponade was associated with more deaths.

The treatment in viral or idiopathic pericarditis is with aspirin, or non-steroidal anti-inflammatory drugs (NSAIDs such as ibuprofen). Colchicine may be added to the above as it decreases the risk of further episodes of pericarditis.

Severe cases may require one or more of the following:

- pericardiocentesis to treat pericardial effusion/tamponade

- antibiotics to treat tuberculosis or other bacterial causes.

- steroids are used in acute pericarditis but are not favored because they increase the chance of recurrent pericarditis.

- in rare cases, surgery

- in cases of constrictive pericarditis, pericardiectomy

Urogenital tuberculosis may cause strictures of the ureter, which, however, may heal when infection is treated.

The definitive treatment for constrictive pericarditis is pericardial stripping, which is a surgical procedure where the entire pericardium is peeled away from the heart. This procedure has significant risk involved, with mortality rates of 6% or higher in major referral centers.

A poor outcome is almost always the result after a pericardiectomy is performed for constrictive pericarditis whose origin was radiation-induced, further some patients may develop heart failure post-operatively.

A diagnosis of latent tuberculosis (LTB), also called latent tuberculosis infection (LTBI) means a patient is infected with "Mycobacterium tuberculosis", but the patient does not have active tuberculosis. Active tuberculosis can be contagious while latent tuberculosis is not, and it is therefore not possible to get TB from someone with latent tuberculosis. The main risk is that approximately 10% of these patients (5% in the first two years after infection and 0.1% per year thereafter) will go on to develop active tuberculosis. This is particularly true, and there is added risk, in particular situations such as medication that suppresses the immune system or advancing age.

The identification and treatment of people with latent TB is an important part of controlling this disease. Various treatment regimens are in use to treat latent tuberculosis, which generally need to be taken for several months.