|Year : 2005 | Volume
| Issue : 1 | Page : 5-12
Chemotherapy of osteoarticular tuberculosis
Avijit Hazra1, Baisakhi Laha2
1 Department of Pharmacology, Institute of Postgraduate Medical Education and Research, 244B Acharya J.C. Bose Road, Calcutta - 700 020, India
2 Department of Anesthesiology, Institute of Postgraduate Medical Education and Research, 244B Acharya J.C. Bose Road, Calcutta - 700 020, India
|Date of Submission||01-May-2004|
|Date of Decision||01-Jul-2004|
|Date of Acceptance||17-Sep-2004|
Department of Pharmacology, Institute of Postgraduate Medical Education and Research, 244B Acharya J.C. Bose Road, Calcutta - 700 020
Source of Support: None, Conflict of Interest: None
Tuberculosis (TB) of the bones and joints is rampant in India with the dorsolumbar spine as the most common site of osseous involvement. For diagnosis, clinical suspicion needs to be confirmed through appropriate laboratory and imaging investigations, and increasingly nowadays, nucleic acid amplification techniques. Chemotherapy remains the cornerstone of management complemented by rest, nutritional support and splinting, as necessary. Operative intervention is required if response to chemotherapy is unsatisfactory and for spinal stabilization. The drugs and regimens are fundamentally similar to those for pulmonary TB. However, there is lack of consensus on the appropriate duration of treatment. The prevailing practice of extending treatment till radiological evidence of healing is complete, may be unnecessary in view of recent reports that 6-9 months of therapy is sufficient for the majority of cases. Relapse rates are not drastically improved by extending treatment to 12 months or even longer, except perhaps in pediatric cases. However, prolonged treatment may be required if surgical debridement is indicated but cannot be done. Multidrug-resistant TB should be suspected if disease activity shows no signs of abating after 4-6 months of uninterrupted therapy. These cases are therapeutically challenging and will require second line or experimental antiTB drugs, supported by resistance testing where feasible. Coexistent HIV/AIDS may also necessitate prolonged treatment. Interactions between first line antiTB drugs and antiretroviral medication can complicate matters. Close monitoring is essential in all cases, with dechallenge and cautious reinstitution of drugs in the event of toxicity. While awaiting the arrival of long overdue new antiTB medication, existing drugs and regimens must be used in an informed manner with emphasis on patient compliance.
Keywords: Bone tuberculosis, caries spine, antitubercular drugs, MDR-TB
|How to cite this article:|
Hazra A, Laha B. Chemotherapy of osteoarticular tuberculosis. Indian J Pharmacol 2005;37:5-12
Tuberculosis (TB) remains one of the major killer infections worldwide. About 2.2 million new cases of TB occur every year. As per the World Health organization (WHO) 1999 report on global tuberculosis control, South East Asia accounts for approximately 40% - two out of five cases of TB in the world. Within South-East Asia, more than 95% of cases are found in India, Indonesia, Bangladesh, Thailand, and Myanmar. It is estimated that there are about 60 lakh active pulmonary TB cases in India and annual death rate due to TB is about 500,000. Of the various secondary forms of the disease, TB of the bones and joints is a common orthopedic problem in India and in many other developing countries. Indeed, after decades of consistent decline in incidence, a resurgence of TB is occurring in developed countries, partly linked to the prevalence of human immunodeficiency virus (HIV) infection, and this includes osteoarticular TB.,
| » Sites of infection and etiopathology|| |
In India, the incidence of osteoarticular TB appears to be higher in children, adolescents and young adults, than in the elderly.
The spine is probably the most common site of osseous involvement, followed by the hip and knee. Spinal disease is found in about 1% of all TB cases. In the spine, the usual involvement is vertebral bodies and intervertebral disks in the dorsolumbar regions. Less commonly the cervical vertebrae, craniovertebral junction,, sacrum and sacroiliac joints may be involved. Atypical presentations of spinal TB, such as intradural spinal TB, may occur and may be misdiagnosed as neoplasm without a high index of clinical suspicion. Other sites of involvement reported in the literature are ribs, pelvic bones, small bones of the foot, long bones, sternoclavicular joint, sternum, calvarial bones and bursae.,
Multifocal skeletal TB is an uncommon entity but has been reported from India and other countries.,,
The human subtype of Mycobacterium tuberculosis is almost invariably the causative organism in India. The skeletal focus is always secondary to another focus, usually in the lungs or in the mediastinal lymph nodes. The spread is via the blood stream and the infection settles in bone usually near the epiphyseal cartilage in proximity to the synovial membrane.
The 'tubercle' is the microscopic pathological lesion with central necrosis surrounded by epithelioid cells, giant cells and mononuclear cells. Two types of microscopic lesions have been described - (a) the caseating exudative type where caseating necrosis and cold abscess formation predominate, and (b) the proliferating type where cellular proliferation predominates with minimal caseation. The tuberculous granuloma is the extreme form of this type.
In children the lesion is commonly of the caseating type with rapid and extensive destruction of bone and cartilage, whereas in adults the proliferating type with less bone destruction is usual.
| » Clinical features and investigations|| |
Clinically the onset of TB in any bone or joint is insidious. Constitutional symptoms like low-grade fever, anorexia and weight loss usually precede localizing symptoms and signs such as pain, tenderness and swelling of the affected part. Other local features may be muscle spasms and discharging sinuses. There may be additional features referable to the primary site of involvement, such as the lungs, but these may be minor or even absent.
In addition to the usual array of diagnostic tests for TB, advanced imaging modalities such as computerized tomography (CT),, magnetic resonance imaging (MRI),, and bone scans can be very helpful. Indeed, MRI, with gadolinium enhancement if necessary, is considered an ideal modality for making the diagnosis, demonstrating the extent of disease, identifying complications and assessing response to treatment. It provides better delineation of vertebral lesions with adjoining soft tissue involvement and nerve compressions, than CT. The imaging modalities can guide aspiration cytology and the tissue aspirates can be subjected to smear examination and culture., Biopsy of the bony lesion, synovium or soft tissue masses may be needed to clear up diagnostic confusion.,
Molecular diagnostic techniques like the polymerase chain reaction (PCR) and other forms of nucleic acid amplification tests are being applied nowadays to tissue samples. Although DNA-based PCR can be quite sensitive, it may not distinguish between viable and non-viable bacilli. Messenger-RNA based reversed transcription PCR may be more specific in this regard.
Testing for HIV may also be needed if the clinical circumstances so dictate.
| » General principles of management|| |
If osteoarticular TB is diagnosed and treated at an early stage, the large majority of patients are expected to achieve healing with near normal function. The mainstay of treatment is multidrug antitubercular chemotherapy and active or assisted non-weightbearing exercises of the involved joint throughout the period of healing. An initial period of rest is to be followed by supervised gradual mobilization. In caries spine, various types of spinal support in the form of collars, braces and corsets, may need to be used. Adequate nutritional support is also essential, as in all forms of TB. The goals of treatment are to:
- Contain and eradicate the infection
- Relieve pain
- Preserve and restore bone and joint function
An initial period of hospitalization enables supervised treatment. Continuation treatment can be on a domiciliary basis. However, it is always advisable to follow the principle of directly observed treatment wherever feasible. Intermittent (thrice weekly) regimens have not received adequate trials in skeletal TB. Intermittent regimens, if resorted to for logistical reasons, should be directly supervised.
Operative intervention is required when the patient is not responding to an adequate trial of chemotherapy (e.g. synovectomy and debridement); if the therapeutic outcome is not satisfactory (e.g. excisional arthroplasty of the hip or the elbow); or the healed status has resulted in a painful ankylosis (e.g. arthrodesis for the ankle, the wrist, or the knee). It is also required for an unstable spine. Joint replacement can be considered only if the disease process has remained quiescent for at least a year or more. Multidrug resistance should be suspected if the disease activity does not subside after 4 to 6 months of uninterrupted combination chemotherapy. Such patients (an estimated 5-10%) or those unable to tolerate first-line antitubercular drugs require specialist intervention.
| » Principles of antiTB chemotherapy|| |
As in other forms of TB, multidrug therapy is the norm in bone and joint TB. Mycobacterium tuberculosis is a complex pathogen. It produces at least 250 distinct enzymes compared to only 50 for Escherichia More Details coli. Mutations capable of conferring drug resistance occur frequently. Multiple drugs used in combination will reduce the possibility of selecting drug-resistant strains and hence chances of relapse. Among the first-line drugs, pyrazinamide, being active in an acidic environment, takes care of the persistent intracellular bacilli.
In general, regimens that are adequate for treating pulmonary TB are also effective for treating extrapulmonary TB. The problem lies in deciding on the appropriate duration of treatment for various osteoarticular sites and in selecting appropriate drugs when resistance to the first-line drugs is encountered. The general dosage recommendations for first-line antiTB drugs are presented in [Table - 1].
For the purpose of rationalizing and initiating treatment, WHO categorizes TB patients into four categories depending upon clinical severity and priority. Treatment in a category is divided into initial, intensive, and subsequent continuation phases. The intensive phase comprises maximum number of drugs given daily (preferably under supervision) and is intended to bring about rapid clinical amelioration and achieve non-infectivity. Treatment is then continued with 2 or 3 drugs given daily or intermittently to eliminate residual bacilli and prevent relapse. These regimens are presented in [Table - 2]. It may be noted that apart from newly diagnosed TB spine patients being placed in Category I, there is no specific categorization of other sites of osteoarticular involvement.
[Table - 3] and [Table - 4] summarize the characteristics of standard first-line and current second-line antiTB drugs.
Duration of chemotherapy
Although the first-line regimens are now standardized, the problem lies in deciding upon the appropriate duration of chemotherapy in osteoarticular TB. This is an area where there is no consensus. WHO categorizes caries spine as a severe form of extrapulmonary TB with new cases assigned to Category I. Therefore, by WHO criteria, all caries spine cases should be treated for a minimum of 6 months. Many surgeons in India prefer to continue treatment till there is adequate radiological evidence of healing, which can take much longer than 6 months. It is a moot point whether treatment really needs to be so long.
In various studies, the duration of therapy has varied widely - 6 months in sacral TB, 12-18 months in afflictions of various spinal sites,,, 12-18 months in TB of craniovertebral junction,, 14 -18 months in sternoclavicular joint involvement, 12-20 months in TB affecting the talus,, etc. However, certain suggestions can be made from a perusal of the literature:
- The initial intensive phase drugs may need to be maintained into the continuation phases, in the same doses, particularly in the absence of surgical debridement. Triple therapy regimens, with either pyrazinamide or ethambutol, with appropriate precautions to avoid drug-related toxicity, appear to achieve satisfactory results in caries spine.,
- The minimum duration of therapy should be 6 months. In a systematic review of chemotherapeutic treatment for spinal TB, it was concluded that 6 months of therapy is probably sufficient for the majority of patients. Both 6 and 9-month treatment regimens appear to give acceptable relapse rates of within 2%.
- The United States Centers for Disease Control recommend that for infants and children with miliary TB or bone and joint TB treatment should last at least 12 months. For adults with these forms of extrapulmonary TB, the patient's response to therapy should be monitored closely. If response is slow or inadequate, treatment may be prolonged on a case-by-case basis.
Treatment in HIV-positive individuals
The treatment regimens as outlined above are also effective in the presence of HIV infection. However, HIV-positive patients should be closely monitored and should be re-evaluated if response appears inadequate. Unfortunately, complex interactions between rifampicin and antiretroviral drugs may force withdrawal of conventional regimens. Rifabutin has been used as an alternative to rifampicin in such situations.
Treatment of MDR-TB
Multi-drug-resistant TB (MDR-TB) is defined as resistance to both isoniazid and rifampicin, with or without resistance to any other antituberculosis drugs. As already stated, resistance to multiple first-line antiTB drugs should be suspected if disease activity does not show signs of subsiding after 4-6 months of uninterrupted multidrug therapy. Many crucial management issues in MDR-TB treatment remain unanswered and the existing primary literature consists almost entirely of retrospective cohort studies., There are no standardized regimens or guidelines. Second-line and potential antitubercular drugs will have to be tried. If reliable laboratory facilities are available, drug susceptibility should be determined and treatment commenced with relevant second-line or experimental drugs. It has been suggested that four or five (at least three) antitubercular drugs, including the fluoroquinolones, must be included in the regimen and that, if needed, these drugs should be changed at the same time, not one by one. Further, treatment with these drugs takes 2 years or longer, as opposed to 6 to 9 months with isoniazid-rifampicin-containing regimens., However, studies have also reported reasonably satisfactory responses in shorter periods through regimens incorporating fluoroquinolones like ofloxacin and sparfloxacin.,,
In general, second-line drugs are more expensive and toxic and treatment, at least in the initial part, should therefore be supervised in a hospital. Therapeutic drug monitoring has been employed. Immunomodulatory therapy with levamisole and Mycobacterium vaccae has been disappointing. Other immunomodulators, such as recombinant human interleukin-2 and recombinant interferon-alpha2b, are being tried., Unfortunately, no separate guidelines exist for managing multidrug-resistant osteoarticular TB.
In the event of toxicity
As evident from [Table - 3] and [Table - 4], a number of adverse drug reactions are possible from the use of antiTB drugs. If a reaction occurs but its nature does not single out a particular drug, cautious rechallenge is the only way to identify the offending drug or drugs; starting with the one least likely to be responsible for the symptoms. Rechallenge is started with one drug in a small challenge dose, which is increased stepwise to full therapeutic dose over a few days. This procedure is repeated, with one drug added at a time. The step-up should be even more gradual if the initial reaction is severe. Needless to say that if the reaction recurs, the offending drug has been identified, it must be withdrawn. Combination tablets are not suitable for this purpose and rechallenge should not be attempted if the patient is uncooperative or if a close watch is not possible. Any reaction to thioacetazone, even if it is simple itching, should prompt immediate withdrawal of the drug and rechallenge should not be attempted with this drug. Treatment may be continued by replacing the offending drug with a suitable alternative, or with a reduced number of drugs if none is suitable. Specialist advice may be sought. It is also noteworthy that the resumed regimen is considered to be a new start to the treatment. This prolongs the duration of therapy but, on the other hand, reduces the chance of recurrence.
Most antiTB drugs, particularly pyrazinamide, rifampicin, and isoniazid, can cause hepatotoxicity, while ethambutol is seldom responsible. If a patient on antiTB drugs develops hepatitis, and no other cause is likely, drug-induced hepatitis must be presumed and the drugs stopped. Once the hepatitis has resolved, the same regimen may be cautiously reintroduced. If the hepatitis has been severe, then it is probably safer to avoid pyrazinamide, and possibly also rifampicin, altogether. An alternative regimen in such patients can be a 2-month initial phase of daily isoniazid, ethambutol and streptomycin followed by a 10-month continuation phase of isoniazid plus ethambutol. A severely ill TB patient with drug-induced hepatitis may die without antiTB treatment. In this case the patient may be treated with the two least hepatotoxic drugs, namely streptomycin and ethambutol instead of interrupting TB treatment. Isoniazid may be cautiously reintroduced after the hepatitis has resolved.
| » Follow-up and prognosis|| |
Chemotherapy in osteoarticular TB not only helps to control the infection per se but timely surgery can also be done safely, if efficient conservative treatment is carried out in the first instance with rest and chemotherapy. Whatever the goal the importance of regular follow-up to assess disease activity and to ensure patient compliance cannot be overemphasized. Supervised drug treatment programs will facilitate the latter. The diagnosis of quiescence is as important as the diagnosis of the lesion itself and has to be judged through clinical (local and systemic), radiological and laboratory criteria.
The prognosis in general is good with adequate treatment regimens sustained for an appropriate length of time. In some series children appear to fare better than adults. In spinal TB, established deformity and neurological deficits are more difficult to reverse,, which points to the importance of stabilization surgery.
| » Conclusion|| |
TB continues to kill approximately two million people each year around the globe. Yet, according to WHO estimates based on 2001 data, worldwide, only 30% of active TB cases are being diagnosed and treated under directly observed therapy, short-course (DOTS) programs. The global targets of 70% case detection and 85% cure rates for those detected must be reached by 2005 in order to halve TB prevalence and deaths by 2010. The opportunity provided by the World TB Day (March 24) should be taken for increasing awareness of various stakeholders on the importance of effective TB control and for social mobilization.
On the chemotherapy front, we continue to fight with the available drugs against the formidable challenges posed by MDR-TB and the HIV-TB vicious cycle. It is sad but true that there have been no new antitubercular drugs for at least the past three decades. However, the Global Alliance for TB Drug Development has been set up and is committed to delivering its first new drug by 2010. The total funding is expected to exceed US$ 150 million. The Alliance also seeks to make antiTB drugs available, particularly in the countries worst hit by the disease, at prices that are affordable to their populations. Cost-effective new antiTB drugs are badly needed to shorten the duration of TB treatment, simplify the regimens, improve the treatment of latent TB infection and overcome the resilience of MDR-TB. Till then we must continue to apply existing drugs and regimens in an informed manner with the maximum emphasis on patient adherence to treatment.
| » References|| |
|1.||Al-Matar MJ, Cabral DA, Petty RE. Isolated tuberculous monoarthritis mimicking oligoarticular juvenile rheumatoid arthritis. J Rheumatol 2001;28:204-6. [PUBMED] |
|2.||Andronikou S, Jadwat S, Douis H. Patterns of disease on MRI in 53 children with tuberculous spondylitis and the role of gadolinium. Pediatr Radiol 2002;32:798-805. [PUBMED] [FULLTEXT]|
|3.||Teklali Y, El Alami ZF, El Madhi T, Gourinda H, Miri A. Peripheral osteoarticular tuberculosis in children: 106 case-reports. Joint Bone Spine 2003;70:282-6. [PUBMED] [FULLTEXT]|
|4.||Mazza O, Logroscino G, Pola E, Aulisa AG, Mastantuoni G, Aulisa L. Pott's disease: Current diagnostic and therapeutic approaches. Clin Ter 2001;152:369-76. [PUBMED] |
|5.||Rasit AH, Razak M, Ting FS. The pattern of spinal tuberculosis in Sarawak General Hospital. Med J Malaysia 2001;56:143-50. [PUBMED] |
|6.||Behari S, Nayak SR, Bhargava V, Banerji D, Chhabra DK, Jain VK. Craniocervical tuberculosis: Protocol of surgical management. Neurosurgery 2003;52:72-80;80-1. |
|7.||Krishnan A, Patkar D, Patankar T, Shah J, Prasad S, Bunting T, et al. Craniovertebral junction tuberculosis: A review of 29 cases. J Comput Assist Tomogr 2001;25:171-6. [PUBMED] [FULLTEXT]|
|8.||Wellons JC, Zomorodi AR, Villaviciencio AT, Woods CW, Lawson WT, Eastwood JD. Sacral tuberculosis: A case report and review of the literature. Surg Neurol 2004;61:136-9;139-41. |
|9.||Tanriverdi T, Kizilkilic O, Hanci M, Kaynar MY, Unalan H, Oz B. Atypical intradural spinal tuberculosis: Report of three cases. Spinal Cord 2003;41:403-9. [PUBMED] [FULLTEXT]|
|10.||Dhillon MS, Nagi ON. Tuberculosis of the foot and ankle. Clin Orthop 2002;(398):107-13. [PUBMED] [FULLTEXT]|
|11.||Eren A, Atay EF, Omeroglu H, Altintas F. Solitary cystic tuberculosis of long tubular bones in children. J Pediatr Orthop B 2003;12:72-5. [PUBMED] [FULLTEXT]|
|12.||Dhillon MS, Gupta RK, Bahadur R, Nagi ON. Tuberculosis of the sternoclavicular joints. Acta Orthop Scand 2001;72:514-7. [PUBMED] [FULLTEXT]|
|13.||Kato Y, Horikawa Y, Nishimura Y, Shimoda H, Shigeto E, Ueda K. Sternal tuberculosis in a 9-month-old infant after BCG vaccination. Acta Paediatr 2000;89:1495-7. [PUBMED] |
|14.||Mukherjee KK, Kaushik R, Nada R, Khosla VK, Khandelwal N, Kak VK. Calvarial tuberculosis. Surg Neurol 2002;57:195-202;202-3. |
|15.||Yamamoto T, Iwasaki Y, Kurosaka M. Tuberculosis of the greater trochanteric bursa occurring 51 years after tuberculous nephritis. Clin Rheumatol 2002;21:397-400. [PUBMED] [FULLTEXT]|
|16.||Kim RS, Lee JY, Jung SR, Lee KY. Tuberculous subdeltoid bursitis with rice bodies. Yonsei Med J 2002;43:539-42. [PUBMED] [FULLTEXT]|
|17.||Dhammi IK, Jain AK, Singh S, Aggarwal A, Kumar S. Multifocal skeletal tuberculosis in children: A retrospective study of 18 cases. Scand J Infect Dis 2003;35:797-9. [PUBMED] |
|18.||Turgut M. Multifocal extensive spinal tuberculosis (Pott's disease) involving cervical, thoracic and lumbar vertebrae. Br J Neurosurg 2001;15:142-6. [PUBMED] |
|19.||Zhang H, Jin D. Multiple cystic tuberculous lesions in the skeleton (Jungling disease): A case report. Spine 2003;28:155-7. |
|20.||Amogne W, Abubaker A. Multifocal vertebral tuberculosis with the involvement of the ribs: Case report. Ethiop Med J 2002;40:397-405. [PUBMED] |
|21.||Alothman A, Memish ZA, Awada A, Al-Mahmood S, Al-Sadoon S, Rahman MM, et al. Tuberculous spondylitis: Analysis of 69 cases from Saudi Arabia. Spine 2001;26:565-70. |
|22.||Benli IT, Acaroglu E, Akalin S, Kis M, Duman E, Un A. Anterior radical debridement and anterior instrumentation in tuberculosis spondylitis. Eur Spine J 2003;12: 224-34. [PUBMED] [FULLTEXT]|
|23.||Pande KC, Babhulkar SS. Atypical spinal tuberculosis. Clin Orthop 2002;(398):67-74. [PUBMED] [FULLTEXT]|
|24.||Dass B, Puet TA, Watanakunakorn C. Tuberculosis of the spine (Pott's disease) presenting as 'compression fractures'. Spinal Cord 2002;40:604-8. [PUBMED] [FULLTEXT]|
|25.||Pan KL, Ibrahim S. Tuberculosis of the distal end of the radius mimicking a giant-cell tumour. Med J Malaysia 2000;55:105-6. [PUBMED] |
|26.||Schluger NW. The diagnosis of tuberculosis: What's old, what's new. Semin Respir Infect 2003;18:241-8. [PUBMED] [FULLTEXT]|
|27.||Tuli SM. General principles of osteoarticular tuberculosis. Clin Orthop 2002;(398):11-9. [PUBMED] [FULLTEXT]|
|28.||Tay BK, Deckey J, Hu SS. Spinal infections. J Am Acad Orthop Surg 2002;10:188-97. [PUBMED] |
|29.||Standardised treatment regimens. In: Maher D, Chaulet P, Spinaci S, Harries A for the Global Tuberculosis Programme. Treatment of tuberculosis: Guidelines for national programs. 2nd Ed. Geneva: World Health Organization; 1997. p. 25-31. |
|30.||Wellons JC, Zomorodi AR, Villaviciencio AT, Woods CW, Lawson WT, Eastwood JD. Sacral tuberculosis: A case report and review of the literature. Surg Neurol 2004;61:136-9; discussion 139-41. [PUBMED] [FULLTEXT]|
|31.||Moon MS, Moon YW, Moon JL, Kim SS, Sun DH. Conservative treatment of tuberculosis of the lumbar and lumbosacral spine. Clin Orthop 2002;(398):40-9. [PUBMED] [FULLTEXT]|
|32.||Chen YC, Chang MC, Wang ST, Yu WK, Liu CL, Chen TH. One-stage posterior surgery for treatment of advanced spinal tuberculosis. J Chin Med Assoc 2003;66:411-7. [PUBMED] |
|33.||Anand A, Sood LK. Isolated tuberculosis of talus without ankle and subtalar joint involvement. Med J Malaysia 2002;57:371-3. [PUBMED] |
|34.||Boussouga M, Tanane M, Bousselmame N, Lazrak K, Taobane H. Tuberculosis of the talus: A rare localization of Koch's bacillus [Article in French]. Rev Chir Orthop Reparatrice Appar Mot 2002;88:522-5. [PUBMED] [FULLTEXT]|
|35.||Prasad RS, Fraser MH, Urquhart GD, McLean AN. Rupture of tuberculous spinal abscess resulting in tuberculous empyema and chylothorax. Spinal Cord 2003;41:410-2. [PUBMED] [FULLTEXT]|
|36.||van Loenhout-Rooyackers JH, Verbeek AL, Jutte PC. Chemotherapeutic treatment for spinal tuberculosis. Int J Tuberc Lung Dis 2002;6:259-65. [PUBMED] |
|37.||Treatment of TB Infection and Disease. CDC Module 4. Available at: http://www.phppo.cdc.gov/phtn/tbmodules/modules1-5/m4/4-m-05.htm [Accessed Mar 20th 2004]. |
|38.||Sequeira W, Co H, Block JA. Osteoarticular tuberculosis: Current diagnosis and treatment. Am J Ther 2000;7:393-8. [PUBMED] |
|39.||Mukherjee JS, Rich ML, Socci AR, Joseph JK, Viru FA, Shin SS, et al. Programmes and principles in treatment of multidrug-resistant tuberculosis. Lancet 2004;363:474-81. [Comment in: Lancet 2004;363:1240]. |
|40.||Espinal MA. The global situation of MDR-TB. Tuberculosis (Edinb) 2003;83:44-51. [PUBMED] [FULLTEXT]|
|41.||Nakajima Y. Treatment for multidrug-resistant tuberculosis in Japan [Article in Japanese]. Kekkaku 2002;77:805-13. [PUBMED] |
|42.||Bastian I, Colebunders R. Treatment and prevention of multidrug-resistant tuberculosis. Drugs 1999;58:633-61. [PUBMED] |
|43.||Ormerod P. The clinical management of the drug-resistant patient. Ann N Y Acad Sci 2001;953:185-91. [PUBMED] [FULLTEXT]|
|44.||Singla R, Gupta S, Gupta R, Arora VK. Efficacy and safety of sparfloxacin in combination with kanamycin and ethionamide in multidrug-resistant pulmonary tuberculosis patients: Preliminary results. Int J Tuberc Lung Dis 2001;5:559-63. [PUBMED] |
|45.||Mangunnegoro H, Hudoyo A. Efficacy of low-dose ofloxacin in the treatment of multidrug-resistant tuberculosis in Indonesia. Chemotherapy 1999;45:19-25. [PUBMED] [FULLTEXT]|
|46.||Van Deun A, Salim MA, Das AP, Bastian I, Portaels F. Results of a standardised regimen for multidrug-resistant tuberculosis in Bangladesh. Int J Tuberc Lung Dis 2004;8:560-7. [PUBMED] |
|47.||Peloquin CA. Therapeutic drug monitoring in the treatment of tuberculosis. Drugs 2002;62:2169-83. [PUBMED] |
|48.||Johnson BJ, Bekker LG, Rickman R, Brown S, Lesser M, Ress S, et al. rhuIL-2 adjunctive therapy in multidrug resistant tuberculosis: A comparison of two treatment regimens and placebo. Tuber Lung Dis 1997;78:195-203. [PUBMED] |
|49.||Palmero D, Eiguchi K, Rendo P, Castro Zorrilla L, Abbate E, Gonzalez Montaner LJ. Phase II trial of recombinant interferon-alpha2b in patients with advanced intractable multidrug-resistant pulmonary tuberculosis: Long-term follow-up. Int J Tuberc Lung Dis 1999;3:214-8. [PUBMED] |
|50.||Adverse effects of antiTB drugs. In: Maher D, Chaulet P, Spinaci S, Harries A for the Global Tuberculosis Programme. Treatment of tuberculosis: Guidelines for national programmes. Geneva: World Health Organization; 1997. p. 37-9. |
|51.||Shembekar A, Babhulkar S. Chemotherapy for osteoarticular tuberculosis. Clin Orthop 2002;(398):20-6. [PUBMED] [FULLTEXT]|
|52.||Moon MS, Moon JL, Moon YW, Kim SS, Kim SS, Sun DH, et al. Pott's paraplegia in patients with severely deformed dorsal or dorsolumbar spines: Treatment and prognosis. Spinal Cord 2003;41:164-71. [PUBMED] [FULLTEXT]|
[Table - 1], [Table - 2], [Table - 3], [Table - 4]
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| ||Neurosurgery Quarterly. 2006; 16(4): 169 |
|[Pubmed] | [DOI]|