Treatment of pulmonary tuberculosis with short course chemotherapy in south India--5-year follow up

A controlled clinical trial of three short-course chemotherapy regimens was undertaken in patients with newly diagnosed bacteriologically positive pulmonary tuberculosis. The patients were randomly allocated to receive one of three regimens: rifampicin, streptomycin, isoniazid and pyrazinamide daily for 2 months, followed by streptomycin, isoniazid and pyrazinamide twice weekly for 3 months (R/5) or for 5 months (R/7), or the same regimen as R/7 but without rifampicin (Z/7). A bacteriological relapse requiring retreatment occurred by 5 years in 7.1% of 126 R/5, 4.0% of 124 R/7 and 6.7% of 253 Z/7 patients with organisms initially sensitive to streptomycin and isoniazid; none of these differences is statistically significant. Of the 31 relapses, 16 occurred within 2 years of the completion of chemotherapy and the remaining 15 between 2 and 5 years. Among 65 patients with initial drug resistance to streptomycin or isoniazid or both, there were six bacteriological relapses requiring retreatment.     

Controlled clinical trial of 4 short-course regimens of chemotherapy (three 6-month and one 8-month) for pulmonary tuberculosis: Final report

The bacteriological relapse rates up to 30 months after the start of chemotherapy have been compared for 4 daily short-course regimens for pulmonary tuberculosis. All 4 had the same initial 2-month intensive phase of streptomycin, isoniazid, rifampicin and pyrazinamide (SHRZ) followed by isoniazid plus rifampicin for 4 months (4HR), or isoniazid plus pyrazinamide for 4 months (4HZ), or isoniazid alone for 4 months (4H), or isoniazid alone for 6 months (6H).In patients with fully sensitive strains pretreatment, the 6-month regimen with rifampicin throughout (4HR) was highly effective, only 2% of 166 patients relapsing bacteriologically in 24 months of follow-up after stopping chemotherapy. This regimen was significantly better than the 4H regimen which had a relapse rate of 10% in 156 patients (P<0.02) and the 4HZ regimen which had a relapse rate of 8% in 164 patients (P=0.05). The 6H regimen was also highly effective, only 3% of the 123 patients relapsing, compared with 10% of the 156 on the 4H regimen (P=0.06). The relapse rate of the regimen with pyrazinamide throughout (4HZ), was not significantly different from that of either of the regimens with isoniazid alone in the continuation phase. All except 3 (1 4HR, 1 4HZ, 1 4H) of the 36 relapses were with fully drug-sensitive strains.In patients with strains resistant to isoniazid alone pretreatment none of the 23 on the 4HR or 4HZ regimens had an unfavourable bacteriological status at the end of chemotherapy compared with 8 of the 17 patients (P<0.005) on 4H or 6H regimens. Of the patients assessed, 3 of 20 receiving rifampicin or pyrazinamide throughout relapsed compared with 2 of 8 who did not.     

Clinical trial of two short-course (6-month) regimens and a standard regimen (12-month) chemotherapy in retreatment of pulmonary tuberculosis in Pakistan. Results 18 months after completion of treatment (Lahore Tuberculosis Study)

This study compared the efficacy and tolerability of two 6-month daily regimens of isoniazid and rifampin in combination with either pyrazinamide or ethambutol (RHZ and RHE regimens) against a standard daily regimen of streptomycin, isoniazid, and ethambutol (SHE regimen) given for 6 months followed by isoniazid and ethambutol for an additional 6 months. Only previously treated sputum positive patients suffering from active pulmonary tuberculosis were entered into the study. Three hundred and fifty-eight patients were admitted to the study and 267 (75%) completed chemotherapy. Eighty-five percent of RHZ-regimen and 82% of RHE-regimen patients achieved sputum culture negativity compared to 55% of patients in SHE regimen. Successfully treated patients were followed up for 18 months, and among these, all 3 treatment regimens showed broadly similar levels of culture negativity at the end of the follow-up period. Final therapeutic outcome was based on sputum culture results obtained throughout the follow-up period, and no statistically significant difference in relapse rate was noticed in the 3 regimens. Severe drug intolerance necessitated discontinuation of therapy in only 2 patients.     

Operational evaluation of treatment for tuberculosis. Results of 8- and 12-month regimens in Peru

To measure the effectiveness of treatment for pulmonary tuberculosis in Peru we evaluated the fate of 2,669 patients who had tuberculosis diagnosed in 1981. Two regimens were used: (1) isoniazid, rifampin, pyrazinamide, and streptomycin daily for 2 months, then either isoniazid and streptomycin twice a week or isoniazid and thiacetazone daily for 6 months; and (2) isoniazid, streptomycin, and thiacetazone daily for 2 months, then either isoniazid and streptomycin twice weekly or isoniazid and thiacetazone daily for 10 months. Patients were not assigned at random to the 2 treatment regimens; thus, the results cannot be directly compared. In the 8-month group, 70% had a favorable outcome, 14% abandoned, 9% failed, 3% died, and 3% relapsed. In the 12-month group, 53% had a favorable outcome, 34% abandoned, 6% failed, 4% died, and 2% relapsed. In patients who did not abandon treatment, the results of both regimens were nearly identical. Patients in both groups who had been treated previously had significantly lower rates of cure than those not treated previously.     

Effectiveness and problems of PZA-containing 6-month regimen for the treatment of new pulmonary tuberculosis patients

One third of the world population has been infected with Mycobacterium tuberculosis, and the number of tuberculosis will increase worldwide without more effective programs of tuberculosis control. Despite of the presence of very potent anti-tuberculosis drugs the global tuberculosis situation is still very serious, and such gloomy feature are caused, at least partly, by the failures in the treatment of tuberculosis. The most important factor for the failure in chemotherapy is incompliance of the patients to the regimens. History of the chemotherapy of tuberculosis can be said as the history of the efforts to reduce such defaulters. Modern chemotherapy of tuberculosis has started from the discovery of streptomycin. Streptomycin monotherapy could improve temporally symptoms and bacteriological status, but could not cure the patients with moderately advanced pulmonary tuberculosis because of the emerge of drug-resistant tuberculosis. This problem was overcome by combining use of para-aminosalicylate and/or isoniazid developed later on. About 97% of patients with pulmonary tuberculosis became bacteriologically quiescent by the 12 months of streptomycin, para-aminosalicylate and isoniazid. Since 1950s through 1970s three drug combination of streptomycin, para-aminosalicylate and isoniazid had been the standard regimen for the treatment of tuberculosis. By the introduction of rifampicin, the duration of chemotherapy could be shortened to 9 months. Subsequent to the successful animal experiments carried out by Grosset which demonstrated that the addition of pyrazinamide for initial 2 months to the standard two-drug combination (isoniazid and rifampicin) could remarkably shorten the duration of chemotherapy, many clinical trials have been done all over the world to compare the efficacy and safety of pyrazinamide-containing intensified short-course regimen with those of standard regimen without pyrazinamide. Sputum negative conversion rates after 2 months of treatment with PZA-regimen was 70-95%, and the relapse rates after the completion of the treatment course were less than 4%. The incidence of adverse events was less than 4%. The pyrazinamide-containing 6 months short-course regimens has been established as a new standard regimen for the initial treatment of pulmonary tuberculosis worldwide. But, in Japan, this regimen had not been adapted as the standard until April 1996 because of undue fear for high incidence of liver toxicity induced by pyrazinamide. However, in many clinical trials carried out in various parts of the world did not show any causative relationship between the higher incidence of liver toxicity and pyrazinamide. According to our own experience in Fukujuji Hospital, Japan Anti-tuberculosis Association, the frequency of drug induced hepatitis among 632 patients with normal liver function at the onset of chemotherapy was 7.9 percent (50/632) when treated with pyrazinamide-containing regimens, and was similar to that among 412 patients treated with other regimens without pyrazinamide (7.3 percent 30/412). These figures were higher than those reported in the literatures. The risk factors of drug-induced hepatitis so far reported included elderly, positive hepatitis C virus antibody, low serum albumin and so on. Such known risk factors could not wholly explain the higher rate of liver dysfunction observed among our Japanese patients. We have examined additional factors affecting the frequency of drug-induced hepatitis in our hospital, and noticed that the past history of gastrectomy and over-dosing of isoniazid (> or = 7.5 mg/kg) and/or pyrazinamide (> or = 30 mg) were relating to the higher incidence of drug-induced hepatitis. Another important finding is that the relapse rate among patients complicated with diabetes mellitus is significantly higher than that of the patients without diabetes mellitus (6.31/100 person-years vs 0.90/100 person-years, P < 0.001). Further research will need whether the patients complicated with diabetes mellitus have any immunological deficient to kill Mycobacterium tuberculosis. WHO, CDC and ATS recommended that 4-drug regimen including pyrazinamide for the initial treatment of all cases of tuberculosis. Considering that the incidence of initial resistance to isoniazid is 4.4% in Japan, we should start to treat all cases of newly diagnosed tuberculosis with pyrazinamide-containing regimen (isoniazid, rifampicin, pyrazinamide, plus streptomycin or ethambutol). To do this, further studies on the risk factors of drug-induced hepatitis are urgently needed.     

Influence of initial drug resistance on the response to short-course chemotherapy of pulmonary tuberculosis

The response to short-course chemotherapy of patients with pulmonary tuberculosis caused by drug-resistant Mycobacterium tuberculosis was examined in 12 controlled trials carried out during the past decade in Africa, Hong Kong, and Singapore. Among those with initial resistance to isoniazid and/or streptomycin, failures during chemotherapy were encountered in 17% of 23 patients given a 6-month regimen of isoniazid and rifampin and in 12% of 264 patients given rifampin only in an initial 2-month intensive phase of their regimen. The proportion of failures fell as the number of drugs in the regimen and the duration of treatment with rifampin were increased, to reach 2% of 246 patients receiving 4 or 5 drugs including rifampin in 6-month regimens. The sterilizing activity of the regimens, whether these included rifampin or pyrazinamide, was little influenced by initial resistance, because the sputum conversion rate at 2 months was similar to that in patients with initially sensitive bacilli, and the relapse rates after chemotherapy were only a little higher. The response in the 11 patients with initial rifampin resistance was, however, much less good, failure during chemotherapy occurring in 5 and relapse afterwards in a further 3 patients. This review demonstrates the value of rifampin in preventing failure caused by the emergence of resistance during treatment and the greater sterilizing activity of rifampin and pyrazinamide compared with that of isoniazid and streptomycin.     

Rifapentine and isoniazid in the continuation phase of a 6-month regimen. Final report at 5 years: prognostic value of various measures.

SETTING: Clinical trial in 672 patients with newly diagnosed pulmonary tuberculosis in Hong Kong. After an initial 2 months of a four-drug intensive phase consisting of thrice-weekly streptomycin, isoniazid, rifampicin and pyrazinamide (SHRZ), a random allocation was made to a continuation phase of once-weekly 600 mg rifapentine + 15 mg/kg isoniazid (HRp1), HRp1 given in 2 of every 3 weeks (HRp1.2/3), or to thrice-weekly isoniazid + rifampicin (HR3), the standard treatment in Hong Kong. OBJECTIVE: Final report evaluating adverse events (46 relapses and one failure) after 5 years and the prognostic influence of various factors. METHODS: Kaplan-Meier analysis of adverse events and Cox proportional hazards analysis of prognostic factors. RESULTS: The two rifapentine regimens, HRp1 and HRp1.2/3 had similar final rates of adverse events of 10.8% and 11.7%, respectively, compared to 4.2% for the HR3 regimen (P = 0.02 and 0.009, respectively). In the initial univariate proportional hazards analysis, adverse events were significantly related to the regimen, age, sex, pretreatment radiographic extent of disease and cavitation, and also to sputum culture at 2 months. In the final multivariate analysis, after step-wise removal of non-significant factors, adverse events were related only to the regimen, patients' sex and pretreatment radiographic extent of disease. Elderly male patients were more at risk of an adverse event, as were those with more severe disease. Adverse events occurred at life table rates of 9.0% in patients with drug-sensitive strains and in 8.9% of those with initially isoniazid-resistant organisms at 5 years. CONCLUSIONS: The two rifapentine regimens were unsatisfactory because of their high incidence of adverse events. Isoniazid appeared not to contribute to preventing relapse. Further studies with increased rifapentine dosage are necessary.     

Rifapentine and isoniazid in the continuation phase of a 6-month regimen. Interim report: no activity of isoniazid in the continuation phase.

SETTING: Clinical trial amongst 762 patients with newly diagnosed pulmonary tuberculosis in Hong Kong. After an initial 2 months of a four-drug intensive phase consisting of streptomycin, isoniazid, rifampicin and pyrazinamide (SHRZ), a random allocation in continuation to once-weekly rifapentine + isoniazid (HRp1), HRp1 given in 2 of every 3 weeks (HRp1.2/3), or to three times weekly isoniazid + rifampicin (HR3). OBJECTIVE: Interim report evaluating progress of study and the role of isoniazid in the continuation phase. METHODS: Kaplan-Meier analysis and response of patients related to susceptibility of pretreatment organisms to isoniazid and to rate of isoniazid acetylation determined by NAT2 genotyping. RESULTS: In the 30-month follow-up, rates for adverse treatment events (failure and relapse) were 4.2% in the HR3, 10.2% in the HRp1 and 11.2% in the HRp1.2/3 series (P = 0.02 for HR3 vs HRp1 and P = 0.01 for HR3 vs HRp1.2/3). Occurrence of adverse events was not related to initial susceptibility to isoniazid nor to the rate of acetylation of isoniazid. CONCLUSIONS: The two rifapentine regimens had similar final rates of adverse events which were unsatisfactory. Isoniazid had little or no activity in the continuation phase, indicating that no improvement of the continuation regimen is likely to be obtained by alteration of the isoniazid dosage.     

Replacement of streptomycin by ethambutol in the intensive phase of tuberculosis treatment: no effect on compliance.

SETTING: Seven tuberculosis clinics in the National Tuberculosis Programme of Madagascar. OBJECTIVE: To compare the treatment efficacy and tolerance of regimens including either streptomycin or ethambutol for patient compliance during initial treatment of smear-positive tuberculosis. DESIGN: The 1023 patients included in the study were randomly divided into two treatment groups-one to receive streptomycin (S), isoniazid (H), rifampicin (R) and pyrazinamide (Z) (SHRZ), and the other to receive EHRZ, where streptomycin was replaced by ethambutol (E). During the 2-month intensive phase, drug delivery was completely supervised. The same 6-month continuation regimen was then given in both groups. Follow-up consisted of a clinical and bacteriological examination at the end of the second, fifth and eighth months. RESULTS: There was no significant difference between the two regimens as regards compliance with treatment, the number of patients lost or who died, or for bacteriological response during the intensive phase. EHRZ was better tolerated. During the continuation phase, the results of the two groups remained comparable, but treatment failures occurred earlier in the patients who had received streptomycin. CONCLUSION: Patient compliance was not better with streptomycin. The ethambutol-containing regimen was as efficient as the other, and better tolerated. There is no argument for preferring streptomycin in the intensive phase of treatment of smear-positive tuberculosis.     

High initial drug resistance in pulmonary tuberculosis in Ghana

Between July 1985 and March 1987, initial sensitivity to anti-tuberculosis drugs was studied in patients presenting at the Chest Clinic of Agogo Hospital in the forest area of Ghana. Culture and sensitivity test results were obtained in 99 out of 123 consecutive patients with pulmonary tuberculosis who claim not to have received previous treatment. Isoniazid resistance was alarmingly high in the isolates of M. tuberculosis: 21 out of 57 (37%), and thiacetazone resistance was very high in the M. africanum isolates: 20 out of 42 (47%). Overall resistance was high: 27% to isoniazid, 23% to streptomycin, 29% to thiacetazone, 16% to both streptomycin and isoniazid, and 5% to all of these three drugs. Only 45% of the isolates were sensitive to all three drugs. Primary drug resistance to rifampicin, pyrazinamide or ethambutol was not observed. Besides the standard treatment of isoniazid, streptomycin and thiacetazone, rifampicin and pyrazinamide were usually added for the first two months of treatment. Of 13 patients who received standard treatment only, 4 of the 5 patients with resistant organisms who could be followed up failed to respond, whereas there were no failures to respond in the 5 corresponding patients with initially sensitive organisms; 3 patients could not be assessed because they defaulted.     

Assessment of a combined preparation of isoniazid, rifampicin and pyrazinamide (Rifater) in the initial phase of chemotherapy in three 6-month regimens for smear-positive pulmonary tuberculosis: a five-year follow-up report.

SETTING: Singapore Tuberculosis Service. OBJECTIVE: To assess the acceptability, efficacy and relapse rate of a combined formulation of three drugs--isoniazid, rifampicin and pyrazinamide (Rifater)--given in the initial phase of chemotherapy in three 6-month regimens (2SHRZ/4H3R3, 1SHRZ/5H3R3 and 2HRZ/4H3R3) under direct observation for all patients. DESIGN: A randomised, controlled, unblinded study comparing a group of patients treated with Rifater and another given the three component drugs as separate formulations. RESULTS: The 310 patients admitted to the study were divided into two groups of 155 patients. The frequency of side effects was similar in both groups. Of 271 patients with drug-sensitive strains who had completed treatment without interruption, sputum cultures converted in all patients. At the end of 5 years, there were 15 relapses: three (2.2%) in the separate drugs group and 12 (9.3%) in the Rifater group. Exclusion of two cases in the Rifater group, one with silicotuberculosis and another with no bacteriological confirmation of diagnosis, gave a relapse rate of 7.9% (P = 0.03 for the comparison of relapse rates in the two groups). CONCLUSION: A combined formulation of three drugs given daily in the initial phase of 6-month short-course therapy, followed by intermittent treatment with isoniazid and rifampicin given three times a week under direct observation for all patients, appears to be less effective than treatment with the component drugs given as separate formulations.     

Evidence of 'amplifier effect' in pulmonary multidrug-resistant tuberculosis: report of three cases.

INTRODUCTION: A cluster of three related cases of tuberculosis (TB) with primary multidrug resistance was investigated at the Centre Hospitalier Universitaire of Kigali (CHUK) in Rwanda. The patients were HIV-1/2 seronegative. Patients 1 and 2 were hospitalized in the same room of CHUK for one month. Patient 3 was a younger sibling of patient 2. METHODS: Drug susceptibility of two consecutive Mycobacterium tuberculosis isolates from each patient was tested by the BACTEC 460 radiometric method. DNA fingerprinting was performed using spoligotyping and mycobacterial interspersed repetitive units of variable numbers of tandem repeats (MIRU-VNTR) analysis. All patients initially received the World Health Organization category I regimen. RESULTS: The isolates collected during the first TB episode were resistant to isoniazid, rifampin and ethambutol. After subsequent retreatment regimens with rifampin, isoniazid, streptomycin, pyrazinamide (8 months) and rifampin, isoniazid, streptomycin, pyrazinamide, ciprofloxacin (21 months), patients 1 and 2 developed additional resistance to streptomycin and quinolones. Patient 3 received only the category I regimen and consecutive isolates retained the initial drug susceptibility pattern. All isolates were genetically indistinguishable by spoligotyping and MIRU-VNTR, indicating the same origin. CONCLUSIONS: These observations highlight the risk of nosocomial transmission of multidrug-resistant (MDR) TB and the possible selection of secondary resistance to second-line drugs if a single new drug is added at the time of retreatment of MDR TB patients.     

五个月短程化疗及六个月全程间歇方案治疗菌阳肺结核的临床对照研究

目的考核利福喷丁（Ｌ）的疗效；缩短疗程或全程间歇以减少用药次数；观察全程应用吡嗪酰胺（Ｚ）对疗效及毒副反应的影响。方法以利福平（Ｒ）为对照，采用５个月疗程方案（Ⅰ组２ＳＨＲＺ／３Ｒ２Ｈ２Ｚ２，Ⅱ组２ＳＨＲＺ／３Ｌ１Ｈ２Ｚ２）、６个月全间歇方案（Ⅲ组２Ｓ３Ｈ３Ｒ３Ｚ３／４Ｌ１Ｈ２Ｚ２，Ⅳ组２Ｓ３Ｈ３Ｒ３Ｚ３／４Ｌ１Ｈ２Ｅ２），观察Ｚ的全程应用结果，巩固期以乙胺丁醇（Ｅ）为对照。３６６例初治菌阳肺结核随机分入以上４组。结果（１）３３９例完成疗程者中３２９例治疗成功，满疗程时痰菌阴转率Ⅰ～Ⅳ组分别为９７０％、９４１％、１０００％、９７２％。Ｘ线病灶有效率依序为９６０％、９７６％、１０００％和９４４％。５个月组与６个月组空洞关闭率分别为７７％及７６％。各组相互比较均无显著性差异（Ｐ＞０．０５），未见严重副作用。（２）３０５例完成３年随访，Ⅰ、Ⅱ、Ⅲ、Ⅳ组细菌学加Ｘ线复发分别为２、３、６和３例。结论本研究结果进一步证明Ｌ是长效、高效、安全、便于督导的新药；巩固期用Ｚ无必要；现有基本药物合理联用有可能缩短疗程为５个月，值得进一步研究。     

Comparison of a daily and three intermittent retreatment regimens for pulmonary tuberculosis administered under programme conditions

One daily and 3 thrice weekly retreatment regimens given for 12 months under programme conditions were compared. The daily regimen was rifampicin and ethambutol (RE7). The three intermittent regimens also contained rifampicin and ethambutol: one of them, rifampicin and ethambutol throughout (RE3); the next one supplemented with pyrazinamide for the first 3 months (REZ3); the last one supplemented with prothionamide for the first 3 months (REPt3). The pyrazinamide containing regimen was subdivided into ordinary and high dose groups. The subjects for retreatment were those who have had, at least, more than 6 months of initial triple chemotherapy of isoniazid, PAS and streptomycin at the health centres, and failed to convert to bacteriologically negative status. Among 419 patients who were available for sensitivity tests before commencing retreatment, 393 (94.3%) were resistant to isoniazid. Six hundred and seventy-four patients (674) were allocated randomly to the regimens: 64 patients were excluded due to various pretreatment reasons and 109 did not complete 12 months of chemotherapy. There remain 501 patients who completed their retreatment. As assessed at 12 months, a bacteriologically favourable response was achieved in 68% of 135 RE7 patients, 62% of 129 RE3 patients, 74% of 132 REZ3 patients, and in 79% of 108 REPt3 patients. Adverse reactions were uncommon: 4% in RE7, 5% in RE3 and 9% in REZ3, but 32% in REPt3. Relapse rates during 2 years after termination of chemotherapy were 15% in RE7, 14% in RE3 and REZ3, and 26% in REPt3, as calculated by life table analysis.     

Tuberculous meningitis: is a 6-month treatment regimen sufficient?

SETTING: The British Thoracic Society and the American Thoracic Society advise 12 months treatment for tuberculous meningitis, with at least isoniazid (H), rifampicin (R) and pyrazinamide (Z). OBJECTIVE: To establish whether a 6-month treatment regimen for tuberculous meningitis is equally as effective as longer treatment. METHOD: Medline search for papers published between 1978 and 1999. Inclusion criteria: study populations of patients with tuberculous meningitis in whom the diagnosis was confirmed with clinical, cerebrospinal fluid and epidemiological findings; a treatment regimen with at least HRZ and at least 12 months of follow-up after the completion of treatment. Outcome measure: the number of relapses. RESULTS: There were four 6-month treatment regimens (G6) and seven longer treatment regimens (G>6); 160/197 (81%) patients completed the 6-month treatment regimens, while 577/675 (85%) completed the longer-term regimens. The clinical stage of patients in the G6 group was poorer than in the G>6 group. Relapse occurred in two out of 131 (1.5%) G6 and in 0 out of 591 G>6 patients. CONCLUSION: Although no studies have compared 6-month treatment regimens with longer treatment, it can be concluded on the basis of this literature review that 6-month treatment is sufficient for tuberculous meningitis with fully susceptible mycobacteria.     

Chemotherapeutic treatment for spinal tuberculosis.

AIM: To evaluate whether 6 months of chemotherapy for patients with spinal tuberculosis prevents relapse as effectively as more than 6 months of chemotherapy. METHOD: Literature review. Medline search including references, from January 1978 to November 2000. Inclusion criteria for publications: diagnosis of spinal tuberculosis confirmed bacteriologically and/or histologically, or probable on the basis of clinical and radiological parameters; treatment regimen (whether or not in combination with surgery) included isoniazid (H), rifampicin (R) and pyrazinamide (Z); follow-up period after completion of treatment of 12 months or more. Exclusion criteria: patients with relapse who had previously been treated adequately for tuberculosis. OUTCOME PARAMETERS: Relapse rate. RESULTS: Four publications were found with HRZ regimens of 6 months' duration and 10 publications with HRZ regimens of >6 months' duration. A number of patients had received HRE (E = ethambutol) for > or = 9 months. In the results, no distinction was made between treatment groups. HRZ for 6 months led to a relapse rate of 0% (0/56, 95%CI 0.0-6.4); follow-up after surgical intervention ranged from 6 to 108 months. HRZ for > or = 9 months (> or = 119 patients) or HRE for > or = 9 months (< or = 71 patients) led to a relapse rate of 2% (4/218, 95%CI 0.6-5.0); follow-up after surgical intervention was 6-168 months. Despite the small number of studies, 6 months of therapy is probably sufficient for patients with spinal tuberculosis.     

High Mortality Associated with Retreatment of Tuberculosis in a Clinic in Kampala,Uganda: A Retrospective Study

The World Health Organization recommends for tuberculosis retreatment a regimen of isoniazid (H), rifampicin (R), ethambutol (E), pyrazinamide (Z), and streptomycin (S) for 2 months, followed by H, R, E, and Z for 1 month and H, R, and E for 5 months. Using data from the National Tuberculosis and Leprosy Program registry, this study determined the long-term outcome under programmatic conditions of patients who were prescribed the retreatment regimen in Kampala, Uganda, between 1997 and 2003. Patients were traced to determine their vital status; 62% (234/377) patients were found dead. Having ≤ 2 treatment courses and not completing retreatment were associated with mortality in adjusted analyses.     

Controlled clinical trial of a regimen of two durations for the treatment of isoniazid resistant pulmonary tuberculosis

Patients with pulmonary tuberculosis who were failures of primary chemotherapy with strains resistant to isoniazid or to isoniazid and streptomycin were allocated at random to receive a regimen of rifampicin and ethambutol for 6 (4RE) or 9 months (7RE), supplemented in both treatment series by streptomycin plus pyrazinamide for the first 2 months. The patients were treated in hospital for the first 2 months and thereafter treatment was supervised on a daily basis in the nearest health institution by an appointed member of staff or at home by responsible members of the community. A total of 306 patients was admitted and 226 patients remained for analysis at the end of chemotherapy, 179 with a strain resistant to isoniazid alone and 47 with a strain resistant to isoniazid and streptomycin. There were only two failures at the end of chemotherapy, one in the 6-month series who had resistance to both isoniazid and streptomycin pretreatment, and one in the 9-month series who had resistance to isoniazid alone. For the 144 patients with initial resistance to isoniazid alone assessed up to 30 months, the relapse rates were low in both series: 4% for the 72 patients in the 6-month series and 3% for the 72 patients in the 9-month series. However, for the 34 patients with resistance to both drugs, three of the 14 in the 6-month but none of 20 in the 9-month series relapsed.     

The prevalence of Mycobacterium tuberculosis drug resistance in New Caledonia, 1995-1996.

SETTING: Study of the susceptibility to anti-tuberculosis drugs of Mycobacterium tuberculosis strains isolated in New Caledonia, a French South Pacific Territory, where tuberculosis continues to be a public health problem. OBJECTIVE: To assess the stability of this susceptibility in order to justify both non-systematic susceptibility testing and the implementation of simplified chemotherapy regimens. METHODS: Over a period of nearly 2 years (1995-1996), every new case of tuberculosis confirmed by the laboratory was included in the study. A total of 105 strains were tested against five anti-tuberculosis drugs: isoniazid, rifampicin, ethambutol, pyrazinamide and streptomycin. RESULTS: No primary drug resistance was detected for the main drugs. One strain with acquired resistance to isoniazid and streptomycin was isolated from one of the 12 patients suffering a relapse of the disease. CONCLUSIONS: The results of this exhaustive study justify the non-systematic approach to susceptibility testing for new patients. However, for strains isolated from patients suffering from relapse or therapeutic failure, or who belong to a high risk population, drug susceptibility testing should be performed. This kind of management will aid in the detection of possible isoniazid and streptomycin resistance, thus avoiding the selection and possible emergence of strains resistant to rifampicin. The results of the study argue for the use of a fixed dose regimen using triple combination tablets of isoniazid, rifampicin and pyrazinamide (HRZ) for 2 months, followed by dual drug therapy (HR) for 4 months.     

Controlled clinical trial of three short-course regimens of chemotherapy for pulmonary tuberculosis in Nigeria--a preliminary report

A controlled clinical trial of daily short course (6-month) chemotherapy in newly diagnosed cases of pulmonary tuberculosis in Nigerians was carried out. The three regimens used contained streptomycin, isoniazid, rifampicin and pyrazinamide in the initial phase; and isoniazid plus rifampicin or isoniazid plus rifampicin and/or pyrazinamide in the continuation phase. Sputum culture conversion was satisfactory after 2 and 6 months of treatment and no positive cultures were found one year after treatment had been completed. Side effects were few and consisted mainly of arthralgia, possibly associated with pyrazinamide.