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      "titulo" => "Prognosis of Mono- and Polydrug Resistant Pulmonary Tuberculosis in the City of Santa Cruz, Bolivia"
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    "titulo" => "Comments on Recent Guidelines for the Treatment of Tuberculosis by the American Thoracic Society, the Centers for Disease Control and Prevention, and the Infectious Diseases Society of America"
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    "textoCompleto" => "<p class="elsevierStylePara">The American Thoracic Society &#40;ATS&#41; has just published extensive guidelines on the treatment of tuberculosis &#40;TB&#41;&#46;<span class="elsevierStyleSup">1</span> The document has many positive aspects but others that can be questioned or even criticized&#46; Perhaps the first point in its favor is the fact that these recommendations&#44; which take levels of evidence into consideration&#44; have been accepted and approved by the Centers for Disease Control and Prevention &#40;CDC&#41; and the Infectious Diseases Society of America &#40;IDSA&#41;&#44; making it the document on the treatment of TB most widely accepted by the scientific societies of the United States&#46; Another favorable aspect to mention is that the purpose of the guidelines is highlighted on the first page of the document&#44; in a box under the table of contents&#44; making it clear that they should be followed by countries with substantial economic resources&#46; This is very important and has not been stated in previous ATS guidelines&#44; causing the vast majority of private medical specialists in countries with scarce or middling economic resources &#40;which bear the burden of 95&#37; of the world&#39;s TB cases&#41; to regard the guidelines as the procedures to follow without adapting them to local economic and epidemiologic situations&#44; even when recommendations were inconsistent with those of their own national TB control programs&#46; The measures to be adopted for the treatment and control of TB in rich countries&#44; and for which these recommendations of the ATS are perfectly valid&#44; are quite different from those of poor countries which should follow the guidelines of the World Health Organization<span class="elsevierStyleSup">2</span> and the International Union against Tuberculosis and Lung Diseases&#46;<span class="elsevierStyleSup">3&#44;4</span> Although aspects of treatments may be similar for both &#34;worlds&#44;&#34; methods of diagnosis&#44; follow up&#44; and control have very different protocols&#46; The first point to underline&#44; then&#44; is that these guidelines are only valid for 5&#37; of the world&#39;s TB sufferers&#44; those that come from developed countries&#44; Spain included&#46;</p><p class="elsevierStylePara"> Perhaps the first two comments to make about this document should refer to its length &#40;60 pages of the journal&#41; and the range of treatments recommended&#58; although the best treatment regimen is recognized to be 6 months long &#40;2 months with isoniazid&#44; rifampicin&#44; pyrazinamide&#44; and ethambutol&#44; followed by 4 months with isoniazid and rifampicin&#41; administered daily or intermittently&#44; many different therapeutic strategies are recommended&#46; Consensus documents and official recommendations of scientific societies should be brief and concise to encourage their being read by the largest possible number of people concerned&#44; thereby increasing their impact&#46; Detailed explanations on each and every point can be left to the manuals and treatises of the same scientific societies&#46;<span class="elsevierStyleSup">4</span> Furthermore&#44; if a therapeutic strategy is accepted as optimal&#44; in certain circumstances recommending others can only generate confusion&#44; possible mistakes and&#44; above all&#44; improvisations by some practitioners&#44; a situation that can lead to increased resistance to the drugs&#46;<span class="elsevierStyleSup">4</span></p><p class="elsevierStylePara">The ATS recommendations introduce certain radical changes&#44; 4 of which deserve special attention both for being new and&#44; in some cases&#44; questionable&#46; The 4 changes are detailed below&#58;</p><p class="elsevierStylePara"><span class="elsevierStyleItalic"> 1&#46;</span> Treatment that includes the administration of isoniazid and rifapentine once a week for 4 months in the second phase&#44; in human immunodeficiency virus seronegative patients with noncavitary chest radiographs and who have negative sputum smears at the end of the second month of treatment&#46; This recommendation is based on 2 fine studies by the CDC<span class="elsevierStyleSup">5&#44;6</span> which found&#44; however&#44; a high relapse rate with single drug resistance to rifamycin in human immunodeficiency virus seropositive patients&#46;<span class="elsevierStyleSup">6</span> This once-weekly treatment did not prove to be more efficacious than the 6-month treatment with rifampicin in 2 phases &#40;2 months with isoniazid&#44; rifampicin&#44; pyrazinamide&#44; and ethambutol&#44; followed by 4 months with isoniazid and rifampicin&#41;&#44; so the only advantage is that it allows medication intake to be supervised in the second phase&#46; The disadvantages&#44; however&#44; include making the overall treatment of TB patients more complicated and the cost much higher&#46; Moreover&#44; rifapentine is difficult to obtain and strict supervision of administration is absolutely essential to assure patients do not miss a single dose of medication&#46;</p><p class="elsevierStylePara"><span class="elsevierStyleItalic"> 2&#46;</span> The recommendation to prolong treatment to 9 months with isoniazid and rifampicin &#40;2 months with isoniazid&#44; rifampicin&#44; pyrazinamide&#44; and ethambutol&#44; followed by 7 months with isoniazid and rifampicin&#41;&#44; in patients who fulfill 2 conditions&#58; cavitary radiography at the start of treatment and positive sputum smear at completion of 2 months of treatment&#46; This recommendation was also based on a study by the CDC&#44;<span class="elsevierStyleSup">5</span> as a consequence of the over 20&#37; relapse rate in patients who fulfilled these 2 conditions and had been treated with the 6-month isoniazid regimen&#46; Patients who had only one of the conditions had relapse rates of under 5&#37; and those with neither condition&#44; less than 2&#37;&#46; Despite the validity of this study&#44;<span class="elsevierStyleSup">5</span> it does not demonstrate that the high relapse rate is corrected with the extension of the treatment to 9 months&#46;</p><p class="elsevierStylePara"><span class="elsevierStyleItalic"> 3&#46;</span> The possibility of suspending the treatment after 4 months completion in patients classified clinically and radiographically as having TB but whose sputum smear and culture are negative&#46; If there is a clinical improvement in these patients by the end of the second month and the initial culture is confirmed as negative&#44; the 2 months with isoniazid&#44; rifampicin&#44; pyrazinamide&#44; and ethambutol&#44; followed by 2 months with isoniazid and rifampicin regimen is recommended&#44; as it was recommended as an alternative for inactive residual TB in the 1994 official ATS guidelines&#46;<span class="elsevierStyleSup">7</span></p><p class="elsevierStylePara"><span class="elsevierStyleItalic"> 4&#46;</span> Treatment with 4 to 6 second line drugs is recommended for patients who are carriers of strains resistant to isoniazid and rifampicin &#40;multi-drug resistant &#91;MDR&#93;&#41; and other first line drugs&#46; This significant&#44; controversial change in the handling of these complicated cases is apparently based on 3 studies<span class="elsevierStyleSup">8-10</span> in which better results were obtained using the increased number of drugs&#46; However&#44; on careful revision of the 3 studies&#44; it is surprising to find that none of them compares treatment regimens or demonstrates that the increased number of drugs led to better results in the treatment of these patients&#46; Thus important changes have been recommended based on 3 references that do not demonstrate that the changes are justified&#46; The first reference is the study carried out by Goble et al<span class="elsevierStyleSup">8</span> at the Department of Medicine&#44; National Jewish Center for Immunology and Respiratory Medicine&#44; Denver &#40;Colorado&#44; USA&#41;&#44; who published the results of treating 171 patients who were resistant to an average of 6 drugs including isoniazid and rifampin&#46; Of the 134 patients that could be followed up&#44; 87 &#40;65&#37;&#41; responded to the treatment administered and 47 &#40;35&#37;&#41; had no response&#46; In the authors&#39; univariate analysis&#44; an unfavorable response was associated with 4 factors&#58; prior administration of a larger number of drugs&#44; treatment regimens with fewer drugs not used previously&#44; resistance <span class="elsevierStyleItalic">in vitro</span> to a greater number of drugs&#44; and male sex&#59; however&#44; only the first and last were statistically significant in a multivariate analysis&#46; The second reference is the study by Park et al<span class="elsevierStyleSup">9</span> on the results of treating 107 Korean patients resistant to an average of 4 drugs including isoniazid and rifampin&#46; There was sufficient follow up in 63 cases&#58; 52 &#40;82&#46;5&#37;&#41; responded to treatment and 11 &#40;17&#46;5&#37;&#41; had no response&#46; Univariate analysis showed that the only factor that was significantly associated with an unfavorable response was resistance to a greater number of drugs in vitro&#44; and that factor continued to be significant in the logistic regression model&#46; Finally&#44; the third reference is the study carried out in the Netherlands by Geerligs et al&#44;<span class="elsevierStyleSup">10</span> on the treatment of 44 patients with resistance to an average of 5 drugs including isoniazid and rifampicin&#46; However&#44; only 3 of the 44 patients were resistant to 5 drugs considered to be first line&#46; The patients were treated with an average of 6 drugs including isoniazid in 36 cases despite the patients&#39; proven resistance&#46; The results were that 33 patients &#40;75&#37;&#41; were cured&#44; 6 &#40;14&#37;&#41; died &#40;only 1 from TB&#41;&#44; and the rest were being followed up&#46; No statistical analysis was made in this study to relate good or bad responses to particular factors&#46;</p><p class="elsevierStylePara"> Thus none of the 3 articles concluded that the use of 4 to 6 drugs was associated with better results&#46;<span class="elsevierStyleSup">1</span> Indeed&#44; the only conclusion that can be drawn is that in these 3 studies acceptable results were obtained using more than 4 drugs&#44; with favorable responses that oscillate between 65&#37;<span class="elsevierStyleSup">8</span> and 82&#46;5&#37;&#46;<span class="elsevierStyleSup">9</span> However&#44; it should be remembered that in the 1950&#39;s and 1960&#39;s&#44; before the discovery of rifampicin&#44; many studies on patients resistant to isoniazid and streptomycin&#44; among other drugs&#44; were published that had very good results using only 3 drugs&#46;<span class="elsevierStyleSup">11-16</span> Many of these studies predated ethambutol&#44; which means that treatment of these patients was just as complex as the MDR cases today that were analyzed in the articles mentioned&#46;<span class="elsevierStyleSup">8-10</span></p><p class="elsevierStylePara"> This unsupported change in the ATS guidelines for the treatment of these patients is remarkable in that the official guidelines of 1965<span class="elsevierStyleSup">17</span> and 1966<span class="elsevierStyleSup">18</span> recommended the use of only 2 or 3 new drugs in these cases&#46; There was a certain shift in the 1994 guidelines&#44;<span class="elsevierStyleSup">7</span> where the use of at least 3 new drugs was recommended&#44; without any references that justified the change&#46; The administration of 4&#44; 6&#44; or more drugs&#44; apart from not being bacteriologically justifiable&#44; insures a high probability of intolerance on the part of the patient&#44; who will abandon treatment or demand that medication be suspended when serious adverse reactions occur&#46;</p><p class="elsevierStylePara"> There are two further comments to be made on the guidelines analyzed here&#46; The first concerns the recommendation to use ethambutol on all initial patients as a fourth first line drug&#46; This was included in the 1994 guidelines&#44;<span class="elsevierStyleSup">7</span> clearly contradicting the 1986 guidelines<span class="elsevierStyleSup">19</span> which had recommended the use of only 3 drugs in the initial phase&#46; The change in the 1994 guidelines was due to the increase in the rate of initial resistance to isoniazid that had been observed in the United States&#46; There is no explanation given for continuing to use the fourth drug in the current guidelines&#46; As regards Spain&#44; there has been no national study carried out on resistances to antituberculosis drugs but the results that have been gathered in different regions of the country<span class="elsevierStyleSup">20-22</span> indicate a low rate of initial resistance to isoniazid&#46; This means that use of ethambutol in the first phase is not justified in Spain&#44; except maybe in the cases of immigrants who come from areas where TB is highly endemic and of other groups at risk of being carriers of resistant strains&#46;</p><p class="elsevierStylePara">The second comment concerns extrapulmonary TB&#44; which is thoroughly analyzed in the document&#59; the same 6-month treatment &#40;2 months with isoniazid&#44; rifampicin&#44; pyrazinamide&#44; and ethambutol&#44; followed by 4 months with isoniazid and rifampicin&#41; as for pulmonary TB is recommended except in the case of meningeal TB where the recommended treatment is extended to 9 to 12 months&#46;<span class="elsevierStyleSup">1</span> Although there are no randomized controlled trials that compare the 6-month treatment with longer ones in the treatment of meningeal TB&#44; there are trials that demonstrate the validity of the 6-month regimen&#44;<span class="elsevierStyleSup">23</span> so&#44; in order to simplify and standardize the treatment of all forms of TB&#44; it might be better to recommend the 6-month regimen for the treatment of meningeal TB&#46;</p><p class="elsevierStylePara">To conclude these comments and criticisms on the fine recommendations for TB treatment issued by the ATS&#47;CDC&#47;IDSA&#44;<span class="elsevierStyleSup">1</span> this author believes that all initial forms of TB should be treated with the same 6-month regimen&#44; which in Spain should not include ethambutol in the first phase &#40;2 months with isoniazid&#44; rifampicin&#44; and pyrazinamide&#44; followed by 4 months with isoniazid and rifampicin&#41;&#46; Moreover&#44; patients who are carriers of MDR strains should have a retreatment schedule of only 3 drugs that they have never received and to which they are susceptible&#46;</p><hr></hr><p class="elsevierStylePara">Correspondence&#58; Dr&#46; J&#46;A&#46; Caminero Luna&#46;<br></br> Servicio de Neumolog&#237;a&#46; Hospital de Gran Canaria Dr&#46; Negr&#237;n&#46;<br></br> Barranco de la Ballena&#44; s&#47;n&#46; 35020 Las Palmas de Gran Canarias&#46; Spain&#46;</p><p class="elsevierStylePara">Manuscript received May 6&#44; 2003&#46; Accepted for publication May 13&#44; 2003&#46;</p>"
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Comments on Recent Guidelines for the Treatment of Tuberculosis by the American Thoracic Society, the Centers for Disease Control and Prevention, and the Infectious Diseases Society of America
Comentarios a la reciente normativa de tratamiento de la tuberculosis de la ATS/CDC/IDS
JA. Caminero Lunaa
a Servicio de Neumología, Hospital de Gran Canaria Dr. Negrín, Las Palmas de Gran Canarias, Spain.
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        "titulo" => "Comentarios a la reciente normativa de tratamiento de la tuberculosis de la ATS&#47;CDC&#47;IDS"
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    "textoCompleto" => "<p class="elsevierStylePara">The American Thoracic Society &#40;ATS&#41; has just published extensive guidelines on the treatment of tuberculosis &#40;TB&#41;&#46;<span class="elsevierStyleSup">1</span> The document has many positive aspects but others that can be questioned or even criticized&#46; Perhaps the first point in its favor is the fact that these recommendations&#44; which take levels of evidence into consideration&#44; have been accepted and approved by the Centers for Disease Control and Prevention &#40;CDC&#41; and the Infectious Diseases Society of America &#40;IDSA&#41;&#44; making it the document on the treatment of TB most widely accepted by the scientific societies of the United States&#46; Another favorable aspect to mention is that the purpose of the guidelines is highlighted on the first page of the document&#44; in a box under the table of contents&#44; making it clear that they should be followed by countries with substantial economic resources&#46; This is very important and has not been stated in previous ATS guidelines&#44; causing the vast majority of private medical specialists in countries with scarce or middling economic resources &#40;which bear the burden of 95&#37; of the world&#39;s TB cases&#41; to regard the guidelines as the procedures to follow without adapting them to local economic and epidemiologic situations&#44; even when recommendations were inconsistent with those of their own national TB control programs&#46; The measures to be adopted for the treatment and control of TB in rich countries&#44; and for which these recommendations of the ATS are perfectly valid&#44; are quite different from those of poor countries which should follow the guidelines of the World Health Organization<span class="elsevierStyleSup">2</span> and the International Union against Tuberculosis and Lung Diseases&#46;<span class="elsevierStyleSup">3&#44;4</span> Although aspects of treatments may be similar for both &#34;worlds&#44;&#34; methods of diagnosis&#44; follow up&#44; and control have very different protocols&#46; The first point to underline&#44; then&#44; is that these guidelines are only valid for 5&#37; of the world&#39;s TB sufferers&#44; those that come from developed countries&#44; Spain included&#46;</p><p class="elsevierStylePara"> Perhaps the first two comments to make about this document should refer to its length &#40;60 pages of the journal&#41; and the range of treatments recommended&#58; although the best treatment regimen is recognized to be 6 months long &#40;2 months with isoniazid&#44; rifampicin&#44; pyrazinamide&#44; and ethambutol&#44; followed by 4 months with isoniazid and rifampicin&#41; administered daily or intermittently&#44; many different therapeutic strategies are recommended&#46; Consensus documents and official recommendations of scientific societies should be brief and concise to encourage their being read by the largest possible number of people concerned&#44; thereby increasing their impact&#46; Detailed explanations on each and every point can be left to the manuals and treatises of the same scientific societies&#46;<span class="elsevierStyleSup">4</span> Furthermore&#44; if a therapeutic strategy is accepted as optimal&#44; in certain circumstances recommending others can only generate confusion&#44; possible mistakes and&#44; above all&#44; improvisations by some practitioners&#44; a situation that can lead to increased resistance to the drugs&#46;<span class="elsevierStyleSup">4</span></p><p class="elsevierStylePara">The ATS recommendations introduce certain radical changes&#44; 4 of which deserve special attention both for being new and&#44; in some cases&#44; questionable&#46; The 4 changes are detailed below&#58;</p><p class="elsevierStylePara"><span class="elsevierStyleItalic"> 1&#46;</span> Treatment that includes the administration of isoniazid and rifapentine once a week for 4 months in the second phase&#44; in human immunodeficiency virus seronegative patients with noncavitary chest radiographs and who have negative sputum smears at the end of the second month of treatment&#46; This recommendation is based on 2 fine studies by the CDC<span class="elsevierStyleSup">5&#44;6</span> which found&#44; however&#44; a high relapse rate with single drug resistance to rifamycin in human immunodeficiency virus seropositive patients&#46;<span class="elsevierStyleSup">6</span> This once-weekly treatment did not prove to be more efficacious than the 6-month treatment with rifampicin in 2 phases &#40;2 months with isoniazid&#44; rifampicin&#44; pyrazinamide&#44; and ethambutol&#44; followed by 4 months with isoniazid and rifampicin&#41;&#44; so the only advantage is that it allows medication intake to be supervised in the second phase&#46; The disadvantages&#44; however&#44; include making the overall treatment of TB patients more complicated and the cost much higher&#46; Moreover&#44; rifapentine is difficult to obtain and strict supervision of administration is absolutely essential to assure patients do not miss a single dose of medication&#46;</p><p class="elsevierStylePara"><span class="elsevierStyleItalic"> 2&#46;</span> The recommendation to prolong treatment to 9 months with isoniazid and rifampicin &#40;2 months with isoniazid&#44; rifampicin&#44; pyrazinamide&#44; and ethambutol&#44; followed by 7 months with isoniazid and rifampicin&#41;&#44; in patients who fulfill 2 conditions&#58; cavitary radiography at the start of treatment and positive sputum smear at completion of 2 months of treatment&#46; This recommendation was also based on a study by the CDC&#44;<span class="elsevierStyleSup">5</span> as a consequence of the over 20&#37; relapse rate in patients who fulfilled these 2 conditions and had been treated with the 6-month isoniazid regimen&#46; Patients who had only one of the conditions had relapse rates of under 5&#37; and those with neither condition&#44; less than 2&#37;&#46; Despite the validity of this study&#44;<span class="elsevierStyleSup">5</span> it does not demonstrate that the high relapse rate is corrected with the extension of the treatment to 9 months&#46;</p><p class="elsevierStylePara"><span class="elsevierStyleItalic"> 3&#46;</span> The possibility of suspending the treatment after 4 months completion in patients classified clinically and radiographically as having TB but whose sputum smear and culture are negative&#46; If there is a clinical improvement in these patients by the end of the second month and the initial culture is confirmed as negative&#44; the 2 months with isoniazid&#44; rifampicin&#44; pyrazinamide&#44; and ethambutol&#44; followed by 2 months with isoniazid and rifampicin regimen is recommended&#44; as it was recommended as an alternative for inactive residual TB in the 1994 official ATS guidelines&#46;<span class="elsevierStyleSup">7</span></p><p class="elsevierStylePara"><span class="elsevierStyleItalic"> 4&#46;</span> Treatment with 4 to 6 second line drugs is recommended for patients who are carriers of strains resistant to isoniazid and rifampicin &#40;multi-drug resistant &#91;MDR&#93;&#41; and other first line drugs&#46; This significant&#44; controversial change in the handling of these complicated cases is apparently based on 3 studies<span class="elsevierStyleSup">8-10</span> in which better results were obtained using the increased number of drugs&#46; However&#44; on careful revision of the 3 studies&#44; it is surprising to find that none of them compares treatment regimens or demonstrates that the increased number of drugs led to better results in the treatment of these patients&#46; Thus important changes have been recommended based on 3 references that do not demonstrate that the changes are justified&#46; The first reference is the study carried out by Goble et al<span class="elsevierStyleSup">8</span> at the Department of Medicine&#44; National Jewish Center for Immunology and Respiratory Medicine&#44; Denver &#40;Colorado&#44; USA&#41;&#44; who published the results of treating 171 patients who were resistant to an average of 6 drugs including isoniazid and rifampin&#46; Of the 134 patients that could be followed up&#44; 87 &#40;65&#37;&#41; responded to the treatment administered and 47 &#40;35&#37;&#41; had no response&#46; In the authors&#39; univariate analysis&#44; an unfavorable response was associated with 4 factors&#58; prior administration of a larger number of drugs&#44; treatment regimens with fewer drugs not used previously&#44; resistance <span class="elsevierStyleItalic">in vitro</span> to a greater number of drugs&#44; and male sex&#59; however&#44; only the first and last were statistically significant in a multivariate analysis&#46; The second reference is the study by Park et al<span class="elsevierStyleSup">9</span> on the results of treating 107 Korean patients resistant to an average of 4 drugs including isoniazid and rifampin&#46; There was sufficient follow up in 63 cases&#58; 52 &#40;82&#46;5&#37;&#41; responded to treatment and 11 &#40;17&#46;5&#37;&#41; had no response&#46; Univariate analysis showed that the only factor that was significantly associated with an unfavorable response was resistance to a greater number of drugs in vitro&#44; and that factor continued to be significant in the logistic regression model&#46; Finally&#44; the third reference is the study carried out in the Netherlands by Geerligs et al&#44;<span class="elsevierStyleSup">10</span> on the treatment of 44 patients with resistance to an average of 5 drugs including isoniazid and rifampicin&#46; However&#44; only 3 of the 44 patients were resistant to 5 drugs considered to be first line&#46; The patients were treated with an average of 6 drugs including isoniazid in 36 cases despite the patients&#39; proven resistance&#46; The results were that 33 patients &#40;75&#37;&#41; were cured&#44; 6 &#40;14&#37;&#41; died &#40;only 1 from TB&#41;&#44; and the rest were being followed up&#46; No statistical analysis was made in this study to relate good or bad responses to particular factors&#46;</p><p class="elsevierStylePara"> Thus none of the 3 articles concluded that the use of 4 to 6 drugs was associated with better results&#46;<span class="elsevierStyleSup">1</span> Indeed&#44; the only conclusion that can be drawn is that in these 3 studies acceptable results were obtained using more than 4 drugs&#44; with favorable responses that oscillate between 65&#37;<span class="elsevierStyleSup">8</span> and 82&#46;5&#37;&#46;<span class="elsevierStyleSup">9</span> However&#44; it should be remembered that in the 1950&#39;s and 1960&#39;s&#44; before the discovery of rifampicin&#44; many studies on patients resistant to isoniazid and streptomycin&#44; among other drugs&#44; were published that had very good results using only 3 drugs&#46;<span class="elsevierStyleSup">11-16</span> Many of these studies predated ethambutol&#44; which means that treatment of these patients was just as complex as the MDR cases today that were analyzed in the articles mentioned&#46;<span class="elsevierStyleSup">8-10</span></p><p class="elsevierStylePara"> This unsupported change in the ATS guidelines for the treatment of these patients is remarkable in that the official guidelines of 1965<span class="elsevierStyleSup">17</span> and 1966<span class="elsevierStyleSup">18</span> recommended the use of only 2 or 3 new drugs in these cases&#46; There was a certain shift in the 1994 guidelines&#44;<span class="elsevierStyleSup">7</span> where the use of at least 3 new drugs was recommended&#44; without any references that justified the change&#46; The administration of 4&#44; 6&#44; or more drugs&#44; apart from not being bacteriologically justifiable&#44; insures a high probability of intolerance on the part of the patient&#44; who will abandon treatment or demand that medication be suspended when serious adverse reactions occur&#46;</p><p class="elsevierStylePara"> There are two further comments to be made on the guidelines analyzed here&#46; The first concerns the recommendation to use ethambutol on all initial patients as a fourth first line drug&#46; This was included in the 1994 guidelines&#44;<span class="elsevierStyleSup">7</span> clearly contradicting the 1986 guidelines<span class="elsevierStyleSup">19</span> which had recommended the use of only 3 drugs in the initial phase&#46; The change in the 1994 guidelines was due to the increase in the rate of initial resistance to isoniazid that had been observed in the United States&#46; There is no explanation given for continuing to use the fourth drug in the current guidelines&#46; As regards Spain&#44; there has been no national study carried out on resistances to antituberculosis drugs but the results that have been gathered in different regions of the country<span class="elsevierStyleSup">20-22</span> indicate a low rate of initial resistance to isoniazid&#46; This means that use of ethambutol in the first phase is not justified in Spain&#44; except maybe in the cases of immigrants who come from areas where TB is highly endemic and of other groups at risk of being carriers of resistant strains&#46;</p><p class="elsevierStylePara">The second comment concerns extrapulmonary TB&#44; which is thoroughly analyzed in the document&#59; the same 6-month treatment &#40;2 months with isoniazid&#44; rifampicin&#44; pyrazinamide&#44; and ethambutol&#44; followed by 4 months with isoniazid and rifampicin&#41; as for pulmonary TB is recommended except in the case of meningeal TB where the recommended treatment is extended to 9 to 12 months&#46;<span class="elsevierStyleSup">1</span> Although there are no randomized controlled trials that compare the 6-month treatment with longer ones in the treatment of meningeal TB&#44; there are trials that demonstrate the validity of the 6-month regimen&#44;<span class="elsevierStyleSup">23</span> so&#44; in order to simplify and standardize the treatment of all forms of TB&#44; it might be better to recommend the 6-month regimen for the treatment of meningeal TB&#46;</p><p class="elsevierStylePara">To conclude these comments and criticisms on the fine recommendations for TB treatment issued by the ATS&#47;CDC&#47;IDSA&#44;<span class="elsevierStyleSup">1</span> this author believes that all initial forms of TB should be treated with the same 6-month regimen&#44; which in Spain should not include ethambutol in the first phase &#40;2 months with isoniazid&#44; rifampicin&#44; and pyrazinamide&#44; followed by 4 months with isoniazid and rifampicin&#41;&#46; Moreover&#44; patients who are carriers of MDR strains should have a retreatment schedule of only 3 drugs that they have never received and to which they are susceptible&#46;</p><hr></hr><p class="elsevierStylePara">Correspondence&#58; Dr&#46; J&#46;A&#46; Caminero Luna&#46;<br></br> Servicio de Neumolog&#237;a&#46; Hospital de Gran Canaria Dr&#46; Negr&#237;n&#46;<br></br> Barranco de la Ballena&#44; s&#47;n&#46; 35020 Las Palmas de Gran Canarias&#46; Spain&#46;</p><p class="elsevierStylePara">Manuscript received May 6&#44; 2003&#46; Accepted for publication May 13&#44; 2003&#46;</p>"
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