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PubMed2003

Multidrug-resistant tuberculosis in pregnancy: case report and review of the literature.

A woman at 23 weeks' gestation was treated with rifampin, isoniazid, and ethambutol for cavitary tuberculosis (TB). She did not respond within 3 weeks, and multidrug-resistant (MDR) TB was suspected. Direct plating on susceptibility media was performed immediately. Treatment was initiated with IV capreomycin, levofloxacin, para-aminosalicylic acid, pyrazinamide, cycloserine, and high-dose vitamin B(6) at 26 weeks' gestation. The patient delivered vaginally at week 35. The newborn was not infected. Following delivery, ethionamide was added as a sixth drug, and levofloxacin was replaced with moxifloxacin. The patient's sputum became smear-negative and culture-negative for TB. All reported cases of MDR-TB during pregnancy are reviewed.

Adult↗
PubMed2003

Comparative roles of levofloxacin and ofloxacin in the treatment of multidrug-resistant tuberculosis: preliminary results of a retrospective study from Hong Kong.

OBJECTIVE: To compare levofloxacin and ofloxacin in the treatment of multidrug-resistant tuberculosis (MDR-TB). PATIENTS AND METHODS: A retrospective analysis of 106 patients with MDR-TB (February 1990 through December 2000) receiving directly observed therapy with fluoroquinolone and accompanying drugs, which mainly included aminoglycosides, cycloserine, ethionamide/prothionamide, and pyrazinamide, was performed. Clinical data from 99 suitable patients were subjected to univariate analysis, stratification, and multiple logistic regression to compare the roles of levofloxacin and ofloxacin in multidrug regimens. RESULTS: Forty patients received 612.5 +/- 79.0 mg qd levofloxacin (mean +/- SD), and 59 patients received 628.8 +/- 101.8 mg qd ofloxacin together with similar active second-line drugs for similar durations. The times to sputum smear (both 1.8 months) and culture conversion (both 2.1 months) were equivalent. Adverse reactions occurred at similar rates (10.0% vs 11.9%). The combined treatment success rate was 83.8%, being higher among ofloxacin-susceptible than ofloxacin-resistant cases (90.5% vs 64.0%, p < 0.01). The success rates for the levofloxacin group were 90.0% (overall), 96.2% (ofloxacin-susceptible cases), and 78.6% (ofloxacin-resistant cases) in comparison with 79.7%, 87.5%, and 45.5%, respectively, for the ofloxacin group (Mantel-Haenszel common odds ratio estimate, 4.0; p < 0.05). Bacillary susceptibility to ofloxacin, good adherence, radiographic extent of one lung or less, and use of levofloxacin were independent predictors of favorable outcome (odds ratios, 7.6 to 21.3). One patient each from both groups relapsed. CONCLUSION: Levofloxacin was found to be more efficacious than ofloxacin when incorporated into multidrug regimens used for treatment of MDR-TB.

Anti-Infective Agents↗
PubMed2005

A cholesterol-rich diet accelerates bacteriologic sterilization in pulmonary tuberculosis.

BACKGROUND: Hypocholesterolemia is common among tuberculous patients and is associated with mortality in miliary cases. Some in vitro studies have shown that cholesterol is necessary for the good functioning of macrophages and lymphocytes. STUDY OBJECTIVES: To determine whether a cholesterol-rich diet could accelerate sputum sterilization in patients with pulmonary tuberculosis. DESIGN: An 8-week follow-up, randomized, controlled trial carried out from March 2001 to January 2002. SETTING: A third-level hospital for respiratory diseases in Mexico City. PATIENTS AND INTERVENTIONS: Adult patients with newly diagnosed pulmonary tuberculosis were hospitalized for 8 weeks and randomly assigned to receive a cholesterol-rich diet (800 mg/d cholesterol [experimental group]) or a normal diet (250 mg/d cholesterol [control group]). All patients received the same four-drug antitubercular regimen (ie, isoniazid, rifampin, pyrazinamide, and ethambutol). MEASUREMENTS AND RESULTS: Every week, a quantitative sputum culture and laboratory tests were done and respiratory symptoms were recorded. Patients in the experimental group (10 patients) and the control group (11 subjects) were HIV-negative and harbored Mycobacterium tuberculosis that was fully sensitive to antitubercular drugs. Sterilization of the sputum culture was achieved faster in the experimental group, as demonstrated either by the percentage of negative culture findings in week 2 (80%; control group, 9%; p = 0.0019) or by the Gehan-Breslow test for Kaplan-Meier curves (p = 0.0037). Likewise, the bacillary population decreased faster (p = 0.0002) in the experimental group. Respiratory symptoms improved in both groups, but sputum production decreased faster in the experimental group (p < 0.05). Laboratory test results did not differ between the groups. CONCLUSIONS: A cholesterol-rich diet accelerated the sterilization rate of sputum cultures in pulmonary tuberculosis patients, suggesting that cholesterol should be used as a complementary measure in antitubercular treatment.

Adult↗
PubMed2005

Ulcerative cutaneous mycobacteriosis due to Mycobacterium ulcerans: report of two Mexican cases.

We report two patients from Central Mexico, with ulcerated cutaneous lesions containing acid-fast bacilli (AFB) and ultimately diagnosed as Mycobacterium ulcerans disease. The first patient had a long history (11 years) of disease involving multiple lesions of both upper and lower extremities. Histopathological changes included necrosis of the subcutaneous tissue with large numbers of extracellular AFB. Cultures at 32 degrees C were "positive for mycobacteria," but were not further identified. The polymerase chain reaction for M. ulcerans performed on skin bopsies was positive. The lesions improved after treatment with rifampin and isoniazid (INH) for one month, followed by ethambutol and streptomycin. The second case followed trauma to the right hand, which spread over 2 years to the right upper extremity, the back, and both legs, with a loss of digits and metacarpal bones of the right hand. The histopathological findings were similar to the first case, including presence of AFB. PCR for M. ulcerans on extracts of skin biopsies was positive. Rifampin, INH, pyrazinamide, and levofloxacin resulted in marked improvement of the ulcer; ethambutol and streptomycin were later used, also. We report these cases because they are rare (approximately 6 previous cases were reported from Mexico), and both are unusually disseminated. They are significant in alerting the medical community to M. ulcerans infection, which is still active in Mexico, and the treatment used has not been reported previously.

Adult↗
PubMed2003

Recent developments in the treatment of tuberculosis.

The history of chemotherapy of tuberculosis commenced in 1944 with the discovery of streptomycin. Currently, short-course chemotherapy comprising rifampicin, isoniazid, pyrazinamide and ethambutol/streptomycin administered under directly observed settings for 6 months (initially all four drugs followed by the former two drugs), constitutes the cornerstone treatment for pulmonary tuberculosis. Multi-drug resistant tuberculosis requires alternative chemotherapy, ideally in the form of individualised regimens, for management. To improve on the duration of chemotherapy for drug-susceptible tuberculosis and to achieve better treatment for multi-drug resistant tuberculosis as well as latent tuberculosis infection, there arises a genuine need for new drugs. The quest for new agents is, however, impeded by obstacles. Hopefully, tackling these through collaborative public-private partnerships on an international scale will lead to a fruitful outcome.

Animals↗
PubMed2005

New drugs being developed for the treatment of tuberculosis.

More than one-third of the world is infected with tuberculosis (TB) and 5000 people die of TB everyday. Of the many diarylquinolones shown to be effective at inhibiting the multiple-cycle growth of Mycobacterium tuberculosis, R-207910 was the most active and was chosen as the lead compound. In the non-established infection mouse TB model, a single dose of R-207910 50 mg/kg had a bacteriostatic effect, and a bactericidal effect was observed at 100 mg/kg. In the established infection mouse model, treatment was started 12-14 days after infection, and when added to the triple therapy of isoniazid, rifampin and pyrazinamide or substituted for any component of the triple therapy, R-207910 increased the effectiveness. As ethambutol is chemically simple, and only has modest potency in treating TB, it was considered to be amenable to optimisation by combinatorial chemistry, and from the analogues synthesised that inhibited the growth of M. tuberculosis, SQ-109 was eventually selected as the lead compound for further testing. In female mice infected with M. tuberculosis H37Rv by tail-vein injection, treatment with SQ-109 25 mg p.o. initiated 20 days later for 5 days/week for 4 weeks reduced the counts by 1.87 log units, which was slightly more than with ethambutol 100 mg (1.67 log units). These results indicate that exciting new drugs are under development for the treatment of TB.

Animals↗
PubMed2006

Adverse reactions to first-line antituberculosis drugs.

INTRODUCTION: Tuberculosis continues to be a major cause of morbidity and mortality worldwide. Currently available drugs are effective for treatment of the disease or latent infection, but may cause serious adverse effects. METHODS: The authors reviewed the literature for side effects of five first-line antituberculous medications (isoniazid, rifampin, pyrazinamide, ethambutol and streptomycin). Incidence of the major side effects were compiled with particular attention to the incidence of isoniazid hepatotoxicity. RESULTS: Hepatotoxicity to isoniazid is a serious problem. Although overall incidence may be decreasing, incidence averaged 9.2 per 1000 patients who were compliant, in multiple studies, with a case fatality rate of 4.7%. The incidence is higher with increasing age. Other serious adverse effects include dermatological, gastrointestinal, hypersensitivity, neurological, haematological and renal reactions. They can lead to drug discontinuation (in up to 10% of patients) or even more serious morbidity or mortality. CONCLUSIONS: Side effects to antituberculosis drugs are common, and include hepatitis, cutaneous reactions, gastrointestinal intolerance, haematological reactions and renal failure. These adverse effects must be recognised early, to reduce associated morbidity and mortality.

Age Factors↗
PubMed1998

Central nervous system tuberculosis in children: a review of 214 cases.

OBJECTIVE: To study the clinical, laboratory, and treatment features observed in pediatric patients with tuberculous meningitis in Turkey. Study Design. Retrospective case review study. METHODS: Review of medical records for demographic data, medical history, clinical manifestations, auxiliary test results, complications, and treatment of 214 children with central nervous system tuberculosis (TB) admitted to Dicle University's hospital between August 1988 and February 1996. RESULTS: Of the 214 patients with tuberculous meningitis, 112 (52%) were male. The mean age at presentation was 4. 1 years, with 165 patients (77%) younger than 5 years. Twenty-two patients (10%) were in the first stage of the disease, 120 (56%) in the second, and 72 (34%) in the third. Our epidemiologic data showed that 141 (66%) of the patients had a family history of TB, and 64 (30%) had a Mantoux skin test result of >10 mm of induration. Radiographic studies demonstrated abnormal chest findings in 187 patients (87%) (hilar adenopathy, 33%; infiltrates, 33%; miliary pattern, 20%; and pleural effusions, 1%, and 172 (80%) cases with hydrocephalus, 26% with parenchymal disease, 15% with basilar meningitis, and 2% with tuberculomas. Only 22 (13%) of 164 children had a positive acid-fast bacilli smear in cerebrospinal fluid, and Mycobacterium tuberculosis was isolated in 49 patients (30%). All the patients were treated with Isoniazid, rifampin, and streptomycin or pyrazinamide for 2 months, followed by 10 months of Isoniazid and rifampin alone. Also, all the patients received adjuvant treatment with steroids early in the course of treatment, and 140 of 172 cases with hydrocephalus had surgical intervention. The overall mortality rate was 23%. CONCLUSION: One or more of these findings: a family history of TB, positive tuberculin skin test results, abnormal cranial computed tomography, and/or cerebrospinal fluid analysis compatible with TBM were found in all but 3 children in our study. central nervous system, tuberculous meningitis, diagnosis, hydrocephalus, children.

Adolescent↗
PubMed2006

Pulmonary thromboembolism in AIDS patient with chronic venous insufficiency, pulmonary tuberculosis and breast cancer: a case report and pathophysiology review.

Recent literature reports thrombotic episodes occurring in patients with HIV infection associated with other abnormalities including neoplasms and infections predisposing to a hypercoagulable state. We report a 47-year-old woman who developed pulmonary thromboembolism in association with HIV infection, pulmonary tuberculosis and breast cancer. She was treated with rifampin, isoniazid, pyrazinamide; heparin, phenprocoumon, zidovudine, lamivudine and efavirenz. Acid fast bacilli were visualized in a sputum smear and three months after, Mycobacterium tuberculosis was isolated from lymph node biopsy during a episode of immune reconstitution. The isolated mycobacteria showed sensitivity to all first-line drugs. HIV infection, breast cancer and pulmonary tuberculosis have several mechanisms that induce hypercoagulable state and can lead to thromboembolic complications. Pulmonary thromboembolism in this patient was a diagnostic challenge because of all the other severe diseases that she experienced at the same time.

Acquired Immunodeficiency Syndrome↗
PubMedDate not supplied

Standardization of broth microdilution method for Mycobacterium tuberculosis.

Indirect drug susceptibility tests of Mycobacterium tuberculosis was done to investigate the accuracy and feasibility of a broth microdilution method (BMM) for determining minimal inhibitory concentrations of conventional drugs against M. tuberculosis. Test drugs included isoniazid (H), rifampicin (R), ethambutol (E), streptomycin (S) and pyrazinamide (Z). Fifty isolates of M. tuberculosis from patients who had never received drug therapy, and H37Rv strain for control, were evaluated in the system. When comparing this method with the gold standard proportional method in Lowenstein-Jensen medium, sensitivity of 100% for all drugs and specifities of 91, 100, 96, 98 and 85% were observed respectively for H, R, E, S and Z. The BMM was read faster (14-20 days) than the proportional method (20-28 days). The microdilution method evaluated allows the testing of multiple drugs in multiple concentrations. It is easy to perform and does not require special equipment or expensive supplies. In contrast to radiometric method it does not use radioactive material.

Antibiotics, Antitubercular↗
PubMed2003

Evaluation of indirect susceptibility testing of Mycobacterium tuberculosis to the first- and second-line, and alternative drugs by the newer MB/BacT system.

In order to evaluate the Organon Teknika MB/BacT system used for testing indirect susceptibility to the alternative drugs ofloxacin (OFLO), amikacin (AMI), and rifabutin (RIF), and to the usual drugs of standard treatment regimes such as rifampin (RMP), isoniazid (INH), pyrazinamide (PZA), streptomycin (SM), ethambutol (EMB), and ethionamide (ETH), cultures of clinical specimens from 117 patients with pulmonary tuberculosis under multidrug-resistant investigation, admitted sequentially for examination from 2001 to 2002, were studied. Fifty of the Mycobacterium tuberculosis cultures were inoculated into the gold-standard BACTEC 460 TB (Becton Dickinson) for studying resistance to AMI, RIF, and OFLO, and the remaining 67 were inoculated into Lowenstein Jensen (LJ) medium (the gold standard currently used in Brazil) for studying resistance to RMP, INH, PZA, SM, EMB, and ETH. We observed 100% sensitivity for AMI (80.8-100), RIF (80.8-100), and OFLO (78.1-100); and 100% specificity for AMI (85.4-100), RIF (85.4-100), and OFLO (86.7-100) compared to the BACTEC system. Comparing the results obtained in LJ we observed 100% sensitivity for RMP (80-100), followed by INH-95% (81.8-99.1), EMB-94.7% (71.9-99.7), and 100% specificity for all drugs tested except for PZA-98.3 (89.5-99.9) at 95% confidence interval. The results showed a high level of accuracy and demonstrated that the fully automated, non-radiometric MB/BacT system is indicated for routine use in susceptibility testing in public health laboratories.

Antitubercular Agents↗
PubMed2003

[Educational strategy for improving patient compliance with the tuberculosis treatment regimen in Chiapas, Mexico].

OBJECTIVE: To implement a training program for physicians and patients and assess its effectiveness in terms of patient compliance with the pulmonary tuberculosis treatment regimen in the border region of Chiapas, Mexico. METHODS: A controlled intervention study was performed with patients over 15 years of age who had pulmonary tuberculosis diagnosed by direct microscopy (bacilloscopy) between 1 February 2001 and 31 January 2002 in health units randomly selected in the border region of Chiapas, Mexico. The sample was made up of patients who sought consultation at 23 and 25 health units over that period (intervention and control group, respectively). The intervention group took part in a training program for health personnel in which the following were discussed: the social, cultural, and economic aspects of tuberculosis; the theoretical and practical underpinnings of the diagnosis and treatment of the illness, and the establishment of self-help groups. Selfhelp groups were also created for all patients at the 23 units where the intervention group sought consultation. All patients were given a short-term treatment regimen with isoniazid, rifampin, pyrazinamide, and ethambutol for a total of 25 weeks, until completing a total of 105 doses. Patient follow-up was extended through December 2003. The intervention and control groups were compared by means of the chi square test, and Student's t test was used to compare means. The relative risk of non-compliance (RR) was calculated along with 95% confidence intervals (95% CI). RESULTS: Eighty-seven patients participated in the study; 44 were exposed to the intervention, and 43 made up the control group. Compliance with treatment was considerably greater in the intervention group than in the control group (97.7% vs. 81.4%, respectively; RR = 1.20; 95% CI: 1.03 to 1.39; P = 0.0015). It was noted that physicians in the border region of Chiapas gear their activities toward curative medicine, rather than preventive medicine or understanding the social determinants of disease. CONCLUSIONS: As a result of the educational activities that were part of the intervention, there was an increase in the proportion of patients who complied with treatment. Health services can improve tuberculosis control in Chiapas with the resources that are available to them at present. Physicians should be taught to view health problems in Chiapas as part of an integral set of conditions, and efforts should be made to improve the doctor-patient relationship. Steps should also be taken to incorporate educational activities and community participation in health services in order to address public health problems in a comprehensive way.

Adolescent↗
PubMed2003

Evaluation of disease patterns, treatment and prognosis of tuberculosis in AIDS patient.

Patterns of disease, diagnosis, treatment and prognosis of tuberculosis in 100 patients co-infected with AIDS at Casa da AIDS clinic was studied. Demographic characteristics were as follows: 76 male patients, 24 female patients, 67 caucasian, average 35.8 years-old (SD +/- 8.5). Sexual transmission of HIV was reported in 68 patients. Pulmonary tuberculosis was seen in 40 patients, extrapulmonary in 11, and combined in 49 patients. In 63 patients, TCD(4)(+) counts were below 200/mm(3) when tuberculosis was diagnosed. Fifty-five patients had their diagnoses confirmed by bacteriological identification of Mycobacterium; either through direct observation and/or culture. Tuberculosis was treated with rifampin, isoniazid and pyrazinamide in 60 patients, reinforced treatment in 14 and alternative treatment in the other 13 patients. Tuberculosis therapy lasted up to 9 months in 66% of the patients. Fifty-four patients were treated with a two-drug antiretroviral regimen and the remaining 46 patients received a triple regimen, which included a protease inhibitor. Among the latter, 35 patients were co-treated with rifampin. The occurrence of hepatic liver enzyme abnormalities was statistically related to alternative antiretroviral regimens (p = 0.01) and to the co-administration of rifampin and protease inhibitor (p = 0.019). Clinical resolution of tuberculosis was obtained in 74 patients. Twelve patients died during tuberculosis treatment. Resolution of tuberculosis was statistically significant related to antituberculosis treatment adherence (p = 0.001). The risk of no response to the treatment was 1.84 times more frequent among patients treated with alternative regimens regardless of the duration of the therapy. We conclude that the characteristics of tuberculosis in HIV infected patients requires that special attention be directed to the types and duration of both antiretroviral and anti-TB therapy in order to achieve the highest level of care.

AIDS-Related Opportunistic Infections↗
PubMed2003

Reiter's syndrome associated with the Acquired Immunodeficiency Syndrome: a case report.

The association of Reiter's Syndrome (RS) with the Acquired Immunodeficiency Syndrome (AIDS) is seldom mentioned in the medical literature. This report illustrates this relationship in a 46 years old male patient suffering from AIDS (CD(4)(+) = 240 cells/mm(3), CD(8)(+) = 1,301 cells/mm(3) and viral load = 330,000 copies/ml), pulmonary tuberculosis (positive catarrhal bacilluscopy), and RS. The diagnosis of RS was based on the combination of dermatological and articular alterations. The patient s cutaneous lesions were characterized by exfoliation and the formation of crusts located on the face, scalp, genitals, hands, and feet; onychodystrophy with opacity; yellowish coloring; and hyperkeratosis of the nails. Articular lesions led to progressive deformity of phalangeal joints of the hands, and intensive arthralgia, mainly of the larger joints (shoulders, elbows, hips and knees). AIDS treatment was administered with anti-retroviral drugs (zidovudine and didanosine); for tuberculosis (isoniazid, rifampicine, and pyrazinamide); and (prednisone and inometacine) for the RS. The patient recovered with the improvement of articular symptoms; however, on the eighth day of treatment, the patient showed significant hemoptysis and hypovolemic shock, and died. The association of RS and HIV infection is reviewed.

Acquired Immunodeficiency Syndrome↗
PubMed2003

Pseudotumoral form of primary progressive tuberculosis: a diagnosis to be considered.

The diversity of clinical presentations of primary progressive tuberculosis (TB) and the difficulty in establishing the diagnosis of paucibacillary forms is the subject of painstaking research, as well as a cause of delay in therapy. We report the case of a 10-year-old black child who presented with chest pain and progressive widening of the upper mediastinum. Computerized tomography of the chest revealed multiple calcifications that were not identified with X-rays. Biopsy through mediastinoscopy was compatible with a diagnosis of tuberculosis. Despite exhaustive investigation that included direct examination, culture for mycobacteria and PCR (Polymerase Chain Reaction) of tissue samples, the etiologic agent was not revealed. Tuberculin conversion was observed during the follow-up and resolution period of the lesion, after administration of isoniazid, rifampicin and pyrazinamide. The nodal pseudotumoral form of tuberculosis is rare in immunocompetent children and it may simulate neoplastic disease; therefore, it should be included in the list of differential diagnoses of masses located in the anterosuperior mediastinum.

Biopsy↗
PubMed2003

Miliary tuberculosis with positive acid-fast bacilli in a pediatric patient.

CONTEXT: Tuberculosis is an important public health issue. The Brazilian government reported 78,460 new cases in 1999. Miliary tuberculosis is a severe form of this disease. OBJECTIVE: To report on an uncommon clinical presentation of miliary tuberculosis in a child. CASE REPORT: A 5-year old boy presented in the emergency room with fatigue and weight loss. He had had Staphylococcus aureus pneumonia 7 months before. Chest radiography revealed lobar consolidation and miliary pattern associated with small cavities in both upper lobes. Antibiotic therapy was started. The sputum was positive for acid-fast bacilli and hence the treatment recommended for tuberculosis (rifampicin, isoniazid [INH], pyrazinamide) was started. The patient was treated for 9 months and at the end of the follow-up period he had made a complete clinical recovery. CONCLUSION: Although in some particular cases sputum can be positive for acid-fast bacilli in children, limitations to the sputum test have forced pediatricians to base tuberculosis diagnosis on epidemiological data, clinical findings and radiographic pattern. In this particular case, we hypothesize that the sputum bacillus test was positive because bacilli grew inside residual pneumatoceles that were produced during previous pneumonia.

Bacteriological Techniques↗
PubMed2006

Mycobacterium szulgai in a patient with advanced acquired immunodeficiency syndrome: an unusual pathogen with unusual multidrug resistance.

A 37-year-old Hispanic man with advanced acquired immunodeficiency syndrome developed extensive pulmonary disease with persistent cough, fever, night sweats, worsening dyspnea, and weight loss. Sputum samples showed scant growth of acid-fast bacilli. He failed to respond to the standard tuberculosis regimen of isoniazid, rifampin, ethambutol, and pyrazinamide. Subsequently, Mycobacterium szulgai was identified, and susceptibility tests showed it to be resistant to all four of those agents. Therapy was changed to clarithromycin, doxycycline, ciprofloxacin, and amikacin. Within 2 weeks, the patient's condition improved significantly, and 6 months after treatment, extensive pulmonary infiltrates had nearly resolved. Fewer than 1% of all human isolates of mycobacteria consist of M. szulgai, which is relatively susceptible to standard antimycobacterial agents. To our knowledge, this is the first reported case of M. szulgai with resistance to all primary antituberculosis drugs.

AIDS-Related Opportunistic Infections↗
PubMed2000

Factors influencing response to treatment of pulmonary tuberculosis.

We analyzed 150 patients with pulmonary tuberculosis from 1990 to 1996 (i) to evaluate the frequency of drug resistance, (ii) to elucidate factors influencing the response to chemotherapy, and (iii) to attempt to improve the therapeutic approach. Multidrug-resistant tuberculosis strains were not found. By univariate analysis, there were 8 factors associated with an increased sputum conversion time: male gender, prior treatment, complications, progressive chest radiographic findings, a high Ziehl-Neelsen stain score, lymphocytopenia, a high erythrocyte sedimentation rate (ESR), and hypoproteinemia. Complications, prior treatment, a high Ziehl-Neelsen stain score, and a high ESR were independent predictive factors in a Cox proportional hazard model. Recursive partitioning and amalgamation (RPA) defined 3 subgroups that responded to treatment. In order to reduce the time to sputum conversion, poor responders according to the RPA should be treated with a 4-drug regimen containing pyrazinamide.

Aged↗