tuberculosis management tuberculosis management tuberculosis management describes the techniques and procedures utilized for treating tuberculosis (tb). tuberculosis managementvarious pharmaceutical tuberculosis treatments and their actionsspecialtyinfectious diseases the medical standard for active tb is a short course treatment involving a combination of isoniazid, rifampicin (also known as rifampin), pyrazinamide, and ethambutol for the first two months. during this initial period, isoniazid is taken alongside pyridoxal phosphate to obviate peripheral neuropathy. isoniazid is then taken coincident with rifampicin for the remaining four months of treatment. a patient is considered free of all living tb bacteria after six months. latent tuberculosis or latent tuberculosis infection (ltbi) is treated with three to nine months of isoniazid alone. this long-term treatment often risks the development of hepatotoxicity. a combination of isoniazid plus rifampicin for a period of three to four months is shown to be an equally effective method for treating ltbi, while mitigating risks to hepatotoxicity. treatment of ltbi is essential in preventing the spread of active tb. drugs first line tuberculosis drugs drug 3-letter 1-letter ethambutol emb e isoniazid inh h pyrazinamide pza z rifampicin rmp r streptomycin stm s second line tuberculosis drugs ciprofloxacin cip (none) moxifloxacin mxf (none) p-aminosalicylic acid pas p first line all first-line anti-tuberculous drug names have semi-standardized three-letter and single-letter abbreviations: ethambutol is emb or e isoniazid is inh or h pyrazinamide is pza or z rifampicin is rmp or r, streptomycin is sm or s first-line anti-tuberculous drug names are often remembered with the mnemonic "ripe," referring to the use of rifamycin (like rifampin), isoniazid, pyrazinamide, and ethambutol. in us practice, names and abbreviations that are not universally accepted are used. for example, rifampicin is referred to as rifampin and is abbreviated as rif, while streptomycin is referred to as stm. the notations rif, rfp, and rmp have all been frequently used for rifampicin, and the notations irpe, hrze, ripe, and irep for combination regimens are all synonyms or nearly synonyms depending on dosage schedules. other abbreviations have also been widely used). in this system, which the world health organization (who) supports, "ripe" is "rhze". (both have mnemonic potential, as tuberculosis is named after tubercles (small tubers), and a tuber can be ripe and can be a rhizome.) drug regimens are similarly abbreviated in a semi standardized manner. the drugs are listed using their single letter abbreviations (in the order given above, which is roughly the order of introduction into clinical practice). a prefix denotes the number of months the treatment should be given for; a subscript denotes intermittent dosing (so 3 means three times a week) and no subscript means daily dosing. most regimens have an initial high-intensity phase, followed by a continuation phase (also called a consolidation phase or eradication phase): the high-intensity phase is given first, then the continuation phase, the two phases divided by a slash. so, 2hrez/4hr3 means isoniazid, rifampicin, ethambutol, pyrazinamide daily for two months, followed by four months of isoniazid and rifampicin given three times a week. several studies have shown that the combination of rifampicin, isoniazid, pyrazinamide has increase the risk of drug-induced liver injury. in the us only, streptomycin is not considered a first line drug by ats/idsa/cdc because of high rates of resistance. who has made no such recommendation. second line the second line drugs (who groups 2, 3 and 4) are only used to treat disease that is resistant to first line therapy (i.e., for extensively drug-resistant tuberculosis (xdr-tb) or multidrug-resistant tuberculosis (mdr-tb)). a drug may be classified as second-line instead of first-line for one of three possible reasons: 1) it may be less effective than the first-line drugs (e.g., p-aminosalicylic acid), 2) it may have toxic side-effects (e.g., cycloserine), or 3) it may be effective, but unavailable in many developing countries (e.g., fluoroquinolones): aminoglycosides (who group 2): e.g., amikacin (amk), kanamycin (km) polypeptides (who group 2): e.g., capreomycin, viomycin, enviomycin fluoroquinolones (who group 3): e.g., ciprofloxacin (cip), levofloxacin, moxifloxacin (mxf) thioamides (who group 4): e.g. ethionamide, prothionamide cycloserine (who group 4) terizidone (who group 5) third line third-line drugs (who group 5) include drugs that may be useful, but have doubtful or unproven efficacy: rifabutin macrolides: e.g., clarithromycin (clr); linezolid (lzd); thioacetazone (t); thioridazine; arginine; vitamin d; bedaquiline. these drugs are listed here either because they are not very effective (e.g., clarithromycin) or because their efficacy has not been proven (e.g., linezolid, r207910). rifabutin is effective, but is not included on the who list because, for most developing countries, it is impractically expensive. standard regimen rationale and evidence tuberculosis has been treated with combination therapy for over fifty years. treatments consisting of a single drug are not used (except in latent tb or chemoprophylaxis), and regimens that use only single drug result in the rapid development of resistance and treatment failure. the rationale for using multiple drugs to treat tb is based on simple probability. the rate of spontaneous mutations that confer resistance to an individual drug are well known: 1 mutation for every 107 cell divisions for emb, 1 for every 108 divisions for stm and inh, and 1 for every 1010 divisions for rmp. patients with extensive pulmonary tb have approximately 1012 bacteria in their body, and therefore will likely be harboring approximately 105 emb-resistant bacteria, 104 stm-resistant bacteria, 104 inh-resistant bacteria and 10² rmp-resistant bacteria. resistance mutations appear spontaneously and independently, so the chances of them harbouring a bacterium that is spontaneously resistant to both inh and rmp is 1 in 108 × 1 in 1010 = 1 in 1018, and the chance of them harbouring a bacterium that is spontaneously resistant to all four drugs is 1 in 1033. this is, of course, an oversimplification, but it is a useful way of explaining combination therapy. there are other theoretical reasons for supporting combination therapy. the different drugs in the regimen have different modes of action. inh are bacteriacidal against replicating bacteria. emb is bacteriostatic at low doses, but is used in tb treatment at higher bactericidal doses. rmp is bacteriacidal and has a sterilizing effect. pza is only weakly bactericidal, but is very effective against bacteria located in acidic environments, inside macrophages, or in areas of acute inflammation. all tb regimens in use were 18 months or longer until the appearance of rifampicin. in 1953, the standard uk regimen was 3sph/15ph or 3sph/15sh2. between 1965 and 1970, emb replaced pas. rmp began to be used to treat tb in 1968 and the bts study in the 1970s showed that 2hre/7hr was efficacious. in 1984, a bts study showed that 2hrz/4hr was efficacious, with a relapse rate of less than 3% after two years. in 1995, with the recognition that inh resistance was increasing, the british thoracic society recommended adding emb or stm to the regimen: 2hrez/4hr or 2shrz/4hr, which are the regimens currently recommended. the who also recommend a six-month continuation phase of hr if the patient is still culture-positive after 2 months of treatment (approximately 15% of patients with fully sensitive tb) and for those patients who have extensive bilateral cavitation at the start of treatment. monitoring, dots, and dots-plus dots stands for "directly observed treatment, short-course" and is a major plank in the world health organization (who) global plan to stop tb. the dots strategy focuses on five main points of action. the first element involves creating increased sustainable financial services and a short and long-term plan provided by the government, dedicated to eliminating tuberculosis. the world health organization helps encourage mobilized funding to reduce poverty standards that will prevent tuberculosis. the second component of the dots strategy is case detection, which involves improving the accuracy of laboratory tests for bacteriology and improving communication from labs to doctors and patients. case detection means that laboratories that detect and test for bacteriology are accurate and communicative to its doctors and patients. the third strategy is to provide standard treatment and patient support. the guidelines to adhere to adequate treatment is to provide pharmaceutical drugs that will help eliminate tuberculosis and follow-up check-ups to ensure that tuberculosis is not a deterring factor in a patient's life. there are many cultural barriers as many patients might continue to work under unsanitary living conditions or not have enough money to pay for the treatments. programs that provide stipends and incentives to allow citizens to seek treatment are also necessary. the fourth element to dots is to have a management program that supplies a sustainable long-term supply of reliable antibiotics. lastly, the fifth component is to record and monitor treatment plans to ensure that the dots approach is effective. dots not only aims to provide structure for tuberculosis programs, but also to ensure that citizens diagnosed with tuberculosis adhere to protocols which will prevent future bacterial infections. these include government commitment to control tb, diagnosis based on sputum-smear microscopy tests done on patients who actively report tb symptoms, direct observation short-course chemotherapy treatments, a definite supply of drugs, and standardized reporting and recording of cases and treatment outcomes. the who advises that all tb patients should have at least the first two months of their therapy observed (and preferably the whole of it observed): this means an independent observer watching patients swallow their anti-tb therapy. the independent observer is often not a healthcare worker and may be a shopkeeper or a tribal elder or similar senior person within that society. dots is used with intermittent dosing (thrice weekly or 2hrez/4hr3). twice weekly dosing is effective but not recommended by the world health organization (who), because there is no margin for error (accidentally omitting one dose per week results in once weekly dosing, which is ineffective). treatment with properly implemented dots has a success rate exceeding 95% and prevents the emergence of further multi-drug resistant strains of tuberculosis. administering dots, decreases the possibilities of tuberculosis from recurring, resulting in a reduction in unsuccessful treatments. this is in part due to the fact that areas without the dots strategy generally provide lower standards of care. areas with dots administration help lower the number of patients seeking help from other facilities where they are treated with unknown treatments resulting in unknown outcomes. however, if the dots program is not implemented or done so incorrectly positive results will be unlikely. for the program to work efficiently and accurately health providers must be fully engaged, links must be built between public and private practitioners, health services must be available to all, and global support is provided to countries trying to reach their tb prevention, and treatment aims. some researchers suggest that, because the dots framework has been so successful in the treatment of tuberculosis in sub-saharan africa, dots should be expanded to non-communicable diseases such as diabetes mellitus, hypertension, and epilepsy. dots-plus strategy the who extended the dots programme in 1998 to include the treatment of mdr-tb (called "dots-plus"). implementation of dots-plus requires the capacity to perform drug-susceptibility testing (not routinely available even in developed countries) and the availability of second-line agents, in addition to all the requirements for dots. dots-plus is therefore much more resource-expensive than dots, and requires much greater commitment from countries wishing to implement it. community engagement is a new approach that is being initiated alongside the dots individualized treatment. by creating a community for health workers to give support to patients and hospital faculty, the dots-plus model also incorporates psychological structural support treatments to help accommodate patients to ensure completion of treatment. treatment with the new strategy is a total duration of 18–24 months. monthly surveillance until cultures convert to negative is recommended for dots-plus, but not for dots. if cultures are positive or symptoms do not resolve after three months of treatment, it is necessary to re-evaluate the patient for drug-resistant disease or nonadherence to drug regimen. if cultures do not convert to negative despite three months of therapy, some physicians may consider admitting the patient to hospital so as to closely monitor therapy. extra-pulmonary tuberculosis tuberculosis not affecting the lungs is called extra-pulmonary tuberculosis. disease of the central nervous system is specifically excluded from this classification. the united kingdom and the world health organization (who) recommendation is 2hrez/4hr; the us recommendation is 2hrez/7hr. there is good evidence from randomised-controlled trials to say that in tuberculous lymphadenitis and in tb of the spine, the six-month regimen is equivalent to the nine-month