regimen; the us recommendation is therefore not supported by the evidence. up to 25% of patients with tb of the lymph nodes (tb lymphadenitis) will get worse on treatment before they get better and this usually happens in the first few months of treatment. a few weeks after starting treatment, lymph nodes often start to enlarge, and previously solid lymph nodes may soften and develop into tuberculous cervical lymphadenitis. this should not be interpreted as failure of therapy and is a common reason for patients (and their physicians) to panic unnecessarily. with patience, two to three months into treatment the lymph nodes start to shrink again and re-aspiration or re-biopsy of the lymph nodes is unnecessary: if repeat microbiological studies are ordered, they will show the continued presence of viable bacteria with the same sensitivity pattern, which further adds to the confusion: physicians inexperienced in the treatment of tb will then often add second-line drugs in the belief that the treatment is not working. in these situations, all that is required is re-assurance. steroids may be useful in resolving the swelling, especially if it is painful, but they are unnecessary. additional antibiotics are unnecessary and the treatment regimen does not need to be lengthened. there is no evidence that 6 months regimen is inadequate in treating abdominal tb and there is no additional benefits for 9-month regimen for preventing relapse. however, more large scale studies are needed to confirm the above conclusion. tuberculosis of the central nervous system central nervous system tuberculosis takes two major forms: tuberculous meningitis and tuberculoma. tuberculosis may affect the central nervous system (meninges, brain or spinal cord) in which case it is called tb meningitis, tb cerebritis, and tb myelitis respectively; the standard treatment is 12 months of drugs (2hrez/10hr) and steroid are mandatory. diagnosis is difficult as csf culture is positive in less than half of cases, and therefore a large proportion of cases are treated on the basis of clinical suspicion alone. pcr of csf does not significantly improve the microbiology yield; culture remains the most sensitive method and a minimum of 5 ml (preferably 20 ml) of csf should be sent for analysis. tb cerebritis (or tb of the brain) may require brain biopsy to make the diagnosis, because the csf is commonly normal: this is not always available and even when it is, some clinicians would debate whether it is justified putting a patient through such an invasive and potentially dangerous procedure when a trial of anti-tb therapy may yield the same answer; probably the only justification for brain biopsy is when drug-resistant tb is suspected. it is possible that shorter durations of therapy (e.g., six months) may be sufficient to treat tb meningitis, but no clinical trial has addressed this issue. the csf of patients with treated tb meningitis is commonly abnormal even at 12 months; the rate of resolution of the abnormality bears no correlation with clinical progress or outcome, and is not an indication for extending or repeating treatment; repeated sampling of csf by lumbar puncture to monitor treatment progress should therefore not be done. although tb meningitis and tb cerebritis are classified together, the experience of many clinicians is that their progression and response to treatment is not the same. tb meningitis usually responds well to treatment, but tb cerebritis may require prolonged treatment (up to two years) and the steroid course needed is often also prolonged (up to six months). unlike tb meningitis, tb cerebritis often required repeated ct or mri imaging of the brain to monitor progress. central nervous system tb may be secondary to blood-borne spread: therefore some experts advocate the routine sampling of csf in patients with miliary tb. the anti-tb drugs that are most useful for the treatment of central nervous system tb are: inh (csf penetration 100%) rmp (10–20%) emb (25–50% inflamed meninges only) pza (100%) stm (20% inflamed meninges only) lzd (20%) cycloserine (80–100%) ethionamide (100%) pas (10–50%) (inflamed meninges only) the use of steroids is routine in tb meningitis (see section below). there is evidence from one poorly designed trial that aspirin may be beneficial, but further work is required before this can be recommended routinely. steroids the usefulness of corticosteroids (e.g., prednisolone or dexamethasone) in the treatment of tb is proven for tb meningitis and tb pericarditis. the dose for tb meningitis is dexamethasone 8 to 12 mg daily tapered off over six weeks (for those who prefer more precise dosing should refer to thwaites et al., 2004). the dose for pericarditis is prednisolone 60 mg daily tapered off over four to eight weeks. steroids may be of temporary benefit in pleurisy, extremely advanced tb, and tb in children: pleurisy: prednisolone 20 to 40 mg daily tapered off over 4 to 8 weeks extremely advanced tb: 40 to 60 mg daily tapered off over 4 to 8 weeks tb in children: 2 to 5 mg/kg/day for one week, 1 mg/kg/day the next week, then tapered off over 5 weeks steroids may be of benefit in peritonitis, miliary disease, tubercular osteomyelitis, tb osteomyelitis, laryngeal tb, lymphadenitis and genitourinary disease, but the evidence is scant and the routine use of steroids cannot be recommended. steroid treatment in these patients should be considered on a case-by-case basis by the attending physician. the long-term impact of pleural tb on respiratory function is unknown. therefore, such impact should be quantified first before assessing the need of further clinical trials of corticosteroids with pleural tb. thalidomide may be of benefit in tb meningitis and has been used in cases where patients have failed to respond to steroid treatment. non-compliance patients who take their tb treatment in an irregular and unreliable way are at greatly increased risk of treatment failure, relapse and the development of drug-resistant tb strains. there are variety of reasons why patients fail to take their medication. the symptoms of tb commonly resolve within a few weeks of starting tb treatment and many patients then lose motivation to continue taking their medication. regular follow-up is important to check on compliance and to identify any problems patients are having with their medication. patients need to be told of the importance of taking their tablets regularly, and the importance of completing treatment, because of the risk of relapse or drug-resistance developing otherwise. one of the main complaints is the bulkiness of the tablets. the main offender is pza (the tablets being the size of horse tablets). pza syrup may be offered as a substitute, or if the size of the tablets is truly an issue and liquid preparations are not available, then pza can be omitted altogether. if pza is omitted, the patient should be warned that this results in a significant increase in the duration of treatment (details of regimens omitting pza are given below). the other complaint is that the medicines must be taken on an empty stomach to facilitate absorption. this can be difficult for patients to follow (for example, shift workers who take their meals at irregular times) and may mean the patient waking up an hour earlier than usual everyday just to take medication. the rules are actually less stringent than many physicians and pharmacists realise: the issue is that the absorption of rmp is reduced if taken with fat, but is unaffected by carbohydrate, protein, or antacids. so the patient can in fact have his or her medication with food as long as the meal does not contain fat or oils (e.g., a cup of black coffee or toast with jam and no butter). taking the medicines with food also helps ease the nausea that many patients feel when taking the medicines on an empty stomach. the effect of food on the absorption of inh is not clear: two studies have shown reduced absorption with food but one study showed no difference. there is a small effect of food on the absorption of pza and of emb that is probably not clinically important. it is possible to test urine for isoniazid and rifampicin levels to check for compliance. the interpretation of urine analysis is based on the fact that isoniazid has a longer half-life than rifampicin: urine positive for isoniazid and rifampicin – patient probably fully compliant urine positive for isoniazid only – patient has taken his medication in the last few days preceding the clinic appointment, but had not yet taken a dose that day. urine positive for rifampicin only – patient has omitted to take his medication the preceding few days, but did take it just before coming to clinic. urine negative for both isoniazid and rifampicin – patient has not taken either medicine for a number of days in countries where doctors are unable to compel patients to take their treatment (e.g., the uk), some say that urine testing only results in unhelpful confrontations with patients and does not help increase compliance. in countries where legal measures can be taken to force patients to take their medication (e.g., the us), then urine testing can be a useful adjunct in assuring compliance. rmp colours the urine and all bodily secretions (tears, sweat, etc.) an orange-pink colour and this can be a useful proxy if urine testing is not available (although this colour fades approximately six to eight hours after each dose). in study on cases of extra-pulmonary tb (eptb), researchers at the university of the philippines manila found that similarity of symptoms of eptb to other diseases results to delayed identification of the disease and late provision of medication. this, ultimately contribute to increasing rates of mortality and incidence rates of eptb. the world health organization (who) recommends prescription of fixed-dose combination drugs, to improve adherence to treatment by reducing the number of tablets that need to be taken by people, and also possibly reducing prescribing errors. a cochrane review, published in 2016, found moderate quality evidence that "there is probably little or no difference in fixed-dose combination drugs compared to single-drug formulations". treatment adherence strategies as stated above, non-compliance to anti-tuberculin treatment can result in treatment failure or development of drug-resistant tuberculosis. therefore, overall treatment strategies should be focused on promoting adherence. who and the centers for disease control and prevention (cdc) recommend a multi-faceted patient centered care approach. public health and private sector practitioners can promote tb treatment adherence by allowing patients to be active partners in making their own treatment decisions; improving patient's knowledge and understanding of tuberculosis disease, treatment and potential spread; and by discussing expected interim and long-term outcomes with patients. cdc also recommends use of incentives and enablers. incentives are monetary rewards for a healthy behavior (e.g.transport or food vouchers), while enablers function to remove economic burdens impeding healthcare access (e.g. grouping clinic visits, providing after hours clinic visits, or home visits). however, more research is needed to determine whether incentives and enablers have a significant effect on long-term treatment adherence for tb. smartphones are considered to have potential to improve compliance. individuals with tuberculosis may also benefit from the emotional support of peers and survivors. advocacy organizations and patient support groups such as stop tb, tb alert, treatment action group (tag) and others work to connect tb survivors. adverse effects for information on adverse effects of individual anti-tb drugs, please refer to the individual articles for each drug. the relative incidence of major adverse effects has been carefully described: inh 0.49 per hundred patient months rmp 0.43 emb 0.07 pza 1.48 all drugs 2.47 this works out to an 8.6% risk that any one patient will need to have his drug therapy changed during the course of standard short-course therapy (2hrez/4hr). the people identified to be most at risk of major adverse side effects in this study were: age >60, females, hiv positive patients, and asians. it can be extremely difficult identifying which drug is responsible for which side effect, but the relative frequency of each is known. the offending drugs are given in decreasing order of frequency: thrombocytopenia: rifampicin (rmp) neuropathy: isoniazid (inh) vertigo: streptomycin (stm) hepatitis: pyrazinamide (pza), rmp, inh rash: pza, rmp, ethambutol (emb) thrombocytopenia is only caused by rmp and no test dosing need be done. regimens omitting rmp are discussed below. please refer to the entry on rifampicin for further details. the most frequent cause of neuropathy is inh. the peripheral neuropathy