Another therapeutic option, to be used in selected cases and which can not be considered a treatment of first choice, provides for the administration for the months of an association of isoniazid and rifampicin. A meta-analysis of 5 studies that compared this treatment compared with 6-12 months of isoniazid monotherapy did not show significant differences in efficacy and safety (therapeutic failure rates of 4.2, respectively) and 4.1%) Treatment with rifampicin and pyrazinamide is no longer recommended, following the description of cases of severe hepatotoxicity. To minimize the risk of toxicity, these therapies must be used appropriately, with adequate information and education of the patient, which must also be subjected to clinical monitoring. The risk of hepatotoxicity associated with isoniazid administration is between 0.1% and 1%; the risk increases in the presence of chronic hepatopathies (eg alcoholism, viral hepatitis) and in patients of advanced age. Monitoring of liver function tests before starting treatment is only indicated in patients with chronic liver disease, HIV infection or alcoholism, as well as during pregnancy and up to 3 months after delivery. Long-term monitoring of liver function tests is only indicated in patients with abnormal results at initial evaluation and in patients with chronic liver disease. Age by itself is not an indication to monitor liver function tests; in the elderly patient the decision on whether or not to undertake such monitoring should be made by chance. L and pregnant women, patients at high risk for a peripheral neuropathy associated with isoniazid (eg patients with diabetes, alcoholism, pre-existing neuropathies, uremia, malnutrition, HIV infection) and patients with an underlying convulsive disorder must be supplemented with pyridoxine (vitamin B6) in combination with isoniazid therapy. When a latent tuberculosis infection is not treated, the development of impaired immune function increases the risk of reactivation and progression to active disease.
Populations exposed to the highest risk of reactivation or
progression to active disease include:
the children;
• Patients with previous tuberculosis not treated or treated sub-optimal;
• Immunosuppressed patients (eg patients with HIV infection, diabetes, chronic
or terminal kidney disease, silicosis, carcinomas, malnutrition;
• Patients receiving immunosuppressive drugs such as inhibitors
tumor necrosis factor-alpha (tumor necrosis factor, TNF) (eg infliximab,
eranercept, adalimumab).
All patients treated with TNF inhibitors should be tested for latent
tuberculosis before treatment.
The treatment of active tuberculosis with the administration of an association
between several drugs continues to be of fundamental importance for the
elimination of mycobacteria and tissue sterilization. These effects contribute
to the prevention of drug resistance, which is an aspect of growing concern. The
development of drug resistance is can be of two types. In some cavitary lesions
an extensive proliferation of up to 108 tubercles can result in primary drug
resistance. A secondary resistance may instead develop following inappropriate
drug therapy (attributable, for example, to the administration of an
insufficient number of drugs, to the administration of inactive drugs, or to the
achievement of suboptimal concentrations), caused by poor patient adhesion to
therapeutic prescriptions or inadequate prescriptions. Two treatment stages are
recommended for active tuberculosis therapy. The first stage is an initial, or
"intensive" phase, and involves the administration for 2 months of an
association of 4 drugs: isoniazid, rifampicin, pyrazinamide, ethambutol. The
administration of multiple drugs aims to eliminate tubercle bacilli in active
replication and "semi-dormant" bacilli. Most treatment regimens involve drug
administration 5-7 times a week, by direct observation. In the majority of patients with pulmonary or extra-pulmonary tuberculosis sensitive to
drugs, the initial phase is followed by a "maintenance phase". The latter
involves the administration of isoniazid and rifamycin (rifampicin, rifabutin or
rifapentine), administer every day or every other day for 4-7 months. In most
patients the maintenance therapy phase typically lasts 4 months.
This phase should be extended up to 7 months in the following cases:
-patients in whom the initial treatment phase had not provided for the
administration of pyrazinamide;
-patients with tuberculosis disease-related pulmonary pathology sensitive to
drugs, in which the sputum culture examination conducted at the end of the
intensive care phase continues and is positive for M. tuberculosis;
-patients treated with isoniazide plus rifapentine once a week, in which the
sputum culture examination conducted at the end of the intensive care phase
continues and is positive for M. tuberculosis.
In patients free of HIV infection and suffering from non-cavitary lung disease, and with absence of acid-resistant bacilli at the end of the initial treatment phase. The maintenance phase can be carried out by administering rifapentine once a week. The duration of the maintenance phase may be reduced to 2 months in HIV-free patients with tuberculosis negative for culture and presenting, during treatment, a clinical and radiographic improvement; in these cases the total duration of the treatment is therefore equal to 4 months. Many doctors also prefer a total duration of treatment of 6 months in these patients. Recent studies support, in patients with visual toxic effects or drug-resistant tuberculosis, therapy with 400 mg of moxifloxacin as a possible alternative to ethambutol. Moxifloxacin and ethambutol seem to be equally effective in obtaining, after 2 months of treatment, the change from positive to negative of the sputum examination. Moxifloxacin may therefore offer additional sterilization capacity, which could reduce the duration of treatment. Patients with tuberculosis who are negative for sputum examination and who do not suspect drug-resistant tuberculosis can be considered non-infectious after 2-3 weeks of drug therapy.
The treatment for pulmonary tuberculosis is based on the standard TB treatment and it is done using the world health organization (WHO) classification of TB patients to different categories.:
Category 1: a new TB case
Category 2: Re-treatment case
Category 3: sputum smear negative; not seriously ill but with Extrapulmonary
Tuberculosis
Category 4: a multidrug resistance TB (MDR TB)
The DOTS - Directly Observed Therapy Short course is used and it has 2 Phases of
treatment: the Intensive phase and Continuation phase.
Pulmonary Tuberculosis Treatment Guideline for Category 1
Patients
Intensive Phase: this lasts for 2 months (8 weeks) and the drugs used
include Rifampicin, Isoniazid, Ethambutol and Pyrazinamide.
Continuation Phase: this lasts for 4 months (16 weeks) and drugs used include
Rifampicin and Isoniazid
Intensive Phase: this phase for category 2 patients lasts for 3 months
– Streptomycin is used for the first 2 months and Rifampicin, Isoniazid,
Ethambutol and Pyrazinamide in the 3rd month.
Continuation Phase: this lasts for 5 months (20 weeks) and drugs used include
Rifampicin, Isoniazid and Ethambutol
Multi drug resistant Tuberculosis (MDR TB) is the resistance to at least Rifampicin and Isoniazid. Treatment of this type of TB requires the use of second-line TB drugs and should be supervised by a specialist. The Treatment duration for MDR TB is between 18 and 24 months.
In each patient, tests to determine the susceptibility to drugs of the M.
tuberculosis isolates are carried out. In the United States, 1.1% of M.
tuberculosis infections are attributable to multiple drug-resistant strains (isoniazid
rifampicin). In these patients the treatment should be carried out with 4-6
drugs against which the responsible strain is sensitive. The average cost of
this type of treatment is equal, in the United States, to about $ 250,000 per
patient, ie more than 10 times higher than the average cost for patients
infected with non-resistant strains. In 2006 the definition of drug-resistant
tuberculosis was revised to include isoniazid-resistant and rifampicin-resistant
strains, fluoroquinolones, and at least one drug administered by injection (amikacin,
capreomycin or kanamycin). Tuberculosis resistant to multiple drugs and
tuberculosis extensively resistant to drugs require, depending on the patient's
response to treatment, at least 18-24 months of therapy. The surgical resection
of pulmonary lesions is often taken into account as adjunctive therapy. The
small outbreaks of tuberculosis largely resistant to drugs, so far of limited
extent, are nevertheless characterized by low survival rates. The spread of air
travel has facilitated the spread of pathogenic germs. Other important factors
that have contributed to the spread of multi-drug resistant tuberculosis and
extensively drug-resistant tuberculosis include poor patient compliance with
current or previous treatments, inappropriate drug choices, and the selection of
particularly virulent strains. In order to optimize patient compliance and
treatment tolerance, close monitoring of the treatments by the local health
authorities is particularly useful; Experts in the treatment of tuberculosis
should help the doctor in the choice of therapies that use multiple
second-choice drugs.
Every patient with tuberculosis should be tested for HIV infection. In patients
with co-infection with tuberculosis and HIV, treatment of tuberculous infection
or active disease should be undertaken promptly. HIV infection significantly
increases the risk of developing active tuberculosis, regardless of CD4 cell
count. Immunosuppression mediated by HIV infection leads to an increased risk of
extrapulmonary tuberculosis and miliary tuberculosis, as well as abnormal
radiological and clinical presentation of pulmonary tuberculosis. Tuberculosis
is an acquired immunodeficiency syndrome (AIDS, acquired immunodeficiency
syndrome), which becomes a disease in patients with HIV infection; the diagnosis
of one of the two conditions imposes the execution of screening exams for the
research of the other.) In patients with HIV infection the once or twice weekly
administration of isoniazide plus rifapentine is not advisable, as a consequence
of the higher rates. high levels of therapeutic failure and relapse, often
caused by rifamicin-resistant M. tuberculosis strains. For similar reasons, in
patients with HIV infection and CD4 cell counts below 100 / mm3 it is not
recommended a maintenance therapy with isoniazid and rifampicin given twice a
week. Immediate administration of antiretroviral therapy may be considered in
patients with AIDS-associated conditions of severity such as to endanger
survival. the decision to delay antiretroviral therapy for up to 2 weeks or 2
months after the start of tuberculosis therapy can also optimize patient
tolerance and compliance with treatment. In patients with CD4 cell counts below
2O0 / mm3, highly active antiretroviral therapy reduces the risk of progression
to active tuberculosis and reduces the mortality rates associated with
tuberculosis; the therapy can however be associated with complications such as
an inflammatory syndrome due to immune reconstitution, or drug toxicity.
Rifampicin exerts an enzymatic induction of hepatic drug metabolism, and this
effect may decrease the efficacy of an antiretroviral therapy associated in
particular when protease inhibitors and non-nucleoside reverse transcriptase
inhibitor drugs are used. To reduce the risk of interactions with antiretroviral
drugs, rifamputin can be replaced with rifabutin. Treatment of HIV and
tuberculosis often requires collaboration between multiple specialists.
Pregnancy per se is not a significant risk factor for progression from latent tuberculosis to active disease. Pregnant women with positive results on the tuberculin skin test or on the examination based on the release of the interferon gamma should be promptly subjected to a clinical evaluation and to a chest radiograph with abdominal protection. If the risk of active tuberculosis is important, treatment is also indicated during pregnancy.