Adverse effects of multidrug-resistant tuberculosis treatment with a standardized regimen: a report from Iran.

Compared with the treatment of drug-sensitive tuberculosis, the treatment of multidrug-resistant tuberculosis (MDR-TB) is more difficult. This study was conducted at the national referral center of tuberculosis in Tehran, Iran, to evaluate adverse drug reactions of treatment of MDR-TB. From 2006 to 2009, all patients admitted into Masih Daneshvari Hospital in Tehran, Iran, for MDR-TB were considered for this study. The standard treatment for MDR-TB consisted of amikacin, prothionamide, ofloxacin, and cycloserine. Ethambutol and pyrazinamide were added to treatment if mycobacterium was sensitive to them. All adverse effects observed in patients were recorded in our registry. Eighty patients were considered in the study; of this cohort, 44 were male and 36 were female. The mean age of patients was 40.64 ± 17.53 years (range, 14-81 years). All patients received standardized therapy for MDR-TB. The major adverse effects included neurologic side effects (depression, convulsions, consciousness, psychosis, suicide; 7.5%), hepatitis (5%), rash (1.3%), renal toxicity (3.8%), and auditory toxicity (14.5%). Those with neurologic side effects had less favorable outcome (P value = 0.038) and risk of death was increased among them (odds ratio, 13.8; 95% confidence interval, 2.2-86.77). Other adverse effects did not show statistical significance in our analysis. A major adverse effect such as neurologic side effects (depression, convulsions, consciousness, and psychosis) can result in an increased chance of death among patients with MDR-TB.

Incidence, clinical and epidemiological risk factors, and outcome of drug-induced hepatitis due to antituberculous agents in new tuberculosis cases.

Drug-induced hepatitis (DIH) is an important issue in tuberculosis (TB) treatment. We intend to assess the incidence, risk factors, and outcome of hepatitis due to anti-TB drugs. The study is carried out at the national TB referral center 2006-2008 including all documented new cases of TB. All patients received standard anti-TB treatment. If DIH occurred, all drugs were discontinued and reinitiated after liver function tests (LFT) normalization in a stepwise way. Of total 761 patients, 99 (13.0%) patients developed DIH during anti-TB treatment. There was no difference in sex, nationality, smoking, or opium use history between the hepatitis group and the control group (P > 0.05). DIH was significantly higher in patients older than 65 years (P = 0.019). The mean duration of DIH from the beginning of treatment was 17.53 +/- 19.42 days (median = 12; 1-125 days). Also, the mean of the time elapsed from DIH till the (LFT) normalization was 10.26 +/- 5.95 (median = 9; 0-32 days). Anorexia, nausea, vomiting, abdominal pain, jaundice, diarrhea, decreased level of consciousness, and fever were significantly higher in patients with DIH. In DIH group, 13 patients (13.4%) died, whereas in the control group, death occurred just in 21 cases (3.2%) (P < 0.001, 95% confidence interval = 2.26-9.70, odds ratio = 4.7). After adjusting with logistic regression, all the anticipated factors retained the statistical significance. Our study indicated that DIH most often occurs during the first 2 weeks of anti-TB treatment. DIH development is associated with old age, certain clinical manifestations, and higher death rates.

Extensively drug-resistant tuberculosis: 2 years of surveillance in Iran.

BACKGROUND: Extensively drug-resistant (XDR) tuberculosis (TB) is a cause of concern, because it renders patients untreatable with available drugs. In this study, we documented the existence and transmission of XDR TB among patients with multidrug-resistant TB. These patients were referred to the National Research Institute of Tuberculosis and Lung Diseases (Tehran, Iran) for treatment and diagnosis from 2003 to 2005. METHODS: The sputum specimens from a total of 2030 patients with TB were digested, examined microscopically for acid-fast bacilli, and inoculated into Lowenstein-Jensen slants by standard procedures. Testing of susceptibility to first-line drugs was performed for 1284 Mycobacterium tuberculosis isolates. Subsequently, the strains that were identified as multidrug-resistant M. tuberculosis (113 isolates) were subjected to susceptibility testing for second-line drugs. Spoligotyping and restriction fragment-length polymorphism were performed for strains that were identified as XDR M. tuberculosis. RESULTS: A total of 12 (10.9%) of 113 multidrug-resistant M. tuberculosis strains were resistant to all 8 second-line drugs tested and, therefore, were denoted as XDR M. tuberculosis. Retrospective analysis of the cases of XDR TB showed that all of them belonged to 1 of 2 epidemiological clusters, either a single-family cluster (4 cases) or a cluster of close contacts (8 cases). The strains were identified as belonging to the M. tuberculosis superfamilies Haarlem 1 and East African Indian 3. CONCLUSIONS: The emergence of XDR TB cases in Iran highlights the need to reinforce the Iranian TB policy with regard to control and detection strategies.

Treatment of multiple drug-resistant tuberculosis (MDR-TB) in Iran.

SETTING: Masih Daneshvari Hospital, Tehran, Iran, 2000-2002. OBJECTIVE: To evaluate the effectiveness of multiple drug-resistant tuberculosis (MDR-TB) treatment for the first time in Iran. DESIGN: All cases of MDR-TB with complete follow-up data were recruited and results of their treatments were evaluated. RESULTS: MDR-TB treatment was initiated with 5.23 drugs, on average. Isoniazid, amikacin, and ofloxacin were present in the drug regimen of all patients. Average duration of the treatment was 18.5 months (range, 7-36). Over 76% of the patients responded to the treatment (negative smear and culture). Cure and probable cure were documented in seven (41.2%) and four (23.5%) of the patients, respectively. No failure in the treatment occurred when cycloserine was present in the treatment regimen. CONCLUSION: A majority of the MDR-TB patients in Iran can be cured with the use of appropriate treatment regimens. An even greater success could be achieved by providing more second-line drugs.