Evaluation of cut-off values of interferon-gamma-based assays in the diagnosis of M. tuberculosis infection.

SETTING: A chest disease centre in Istanbul, Turkey. OBJECTIVE: The diagnostic accuracy of interferon-gamma-based assays for Mycobacterium tuberculosis infection may be improved by using lower cut-off values for the tuberculin skin testing (TST), QuantiFERON-TB Gold (QFT) and T-SPOT.TB (T-SPOT) assays. DESIGN: Three assays, TST, QFT and T-SPOT, were evaluated for their diagnostic performance with respect to different cut-off values. This evaluation was carried out in a comparative study involving 100 patients with untreated culture-confirmed cavitary pulmonary tuberculosis (TB) and 47 healthy subjects. RESULTS: The sensitivities of the assays were: TST 70%, QFT 78% and T-SPOT 83.5%, while their specificities were TST 35%, QFT 89.4% and T-SPOT 84.8%. Both QFT and T-SPOT were significantly more specific than TST (both P < 0.001), but were similiar to each other (P = 0.5). Receiver operating characteristic analysis revealed that a cut-off value of 0.818 IU/ml for QFT maximises specificity without significant loss of test sensitivity. Using lower cut-off values for T-SPOT and TST, however, also increased the sensitivity of the assay but resulted in a significant decrease in specificity. CONCLUSION: Lower cut-off values for TST, QFT and T-SPOT increased the sensitivity of each assay, but only with a lower cut-off value for QFT could specificity be maintained.

The role of surgery and fluoroquinolones in the treatment of multidrug-resistant tuberculosis.

SETTING: Although modern tuberculosis treatment relies on chemotherapy, surgery is accepted as adjuvant treatment for multidrug-resistant tuberculosis (MDR-TB). OBJECTIVE: To evaluate the effect of resectional surgery and fluoroquinolones on long-term treatment success and survival in a large group of MDR-TB cases. DESIGN: A total of 252 patients with MDR-TB were included in this retrospective cohort study. Multiple logistic regression was used to determine independent predictive factors for long-term treatment success, and survival analyses were done based on different treatment approaches with or without surgery. RESULTS: The mean age of the study cohort was 37.9 +/- 12.5 years; 204 (80%) were males. Long-term treatment success was associated with resistance to fewer drugs, female sex, younger age and limited disease. Sixty-six patients (26.2%) had undergone resectional surgery after 2-16 months of treatment. The highest long-term treatment success and survival rates were achieved in patients who both received fluoroquinolones and underwent surgery (P = 0.001 vs. other groups). CONCLUSION: Although the treatment success rate was higher in patients treated with surgery and fluoroquinolones compared to other groups, an additional significant benefit from surgery could not be demonstrated. Larger scale studies are needed to clarify this issue.

Side effects associated with the treatment of multidrug-resistant tuberculosis.

SETTING: Süreyyapasa Centre for Chest Diseases and Thoracic Surgery, Istanbul, Turkey. OBJECTIVE: To report the frequency of treatment side effects in cases of multidrug-resistant (MDR-TB) tuberculosis. DESIGN: A retrospective review of the medical records of 263 patients who received individualised treatment for MDR-TB between April 1992 and June 2004. RESULTS: One or more side effects developed in 182 cases (69.2%). These effects led the clinicians to withdraw one or more drugs from the treatment regimen in 146 cases (55.5%). Side effects observed most frequently included: ototoxicity (41.8%), psychiatric disorders (21.3%), gastrointestinal disturbance (14.0%), arthralgia (11.4%), epileptic seizures (9.9%), hepatitis (4.5%), and dermatological effects (4.5%). At the time of analysis, treatment was successful in 204 (77.6%) cases. Fifty-nine patients (22.4%) had poor outcomes. CONCLUSION: Timely and aggressive management of drug side effects means that high side effect rates in MDR-TB treatment need not compromise success rates.

Treatment outcome of relapse and defaulter pulmonary tuberculosis patients.

SETTING: Tuberculosis clinic in a referral hospital. OBJECTIVE: To evaluate the effect of risk factors on the outcome of retreatment in relapse and defaulter pulmonary tuberculosis patients. DESIGN: A total of 57 retreatment tuberculosis patients treated and monitored in our centre between January 1997 and June 1999 were evaluated with respect to treatment outcome. Factors which have on effect on treatment outcome were investigated. RESULTS: Of 57 patients, 37 (64.9%) were classified as relapse cases and 20 (35.1%) as defaulters. The treatment success rate was 71.9% (68.4% cure rate and 3.5% completion rate). Failure was encountered in 22.8%. Twenty-six patients (45.6%) exhibited resistance to at least one drug, namely rifampicin. The multidrug-resistance (MDR) rate was 18.5%. Treatment success rates were 100% and 50%, respectively, in patients in whom susceptibility to all drugs and resistance to at least one drug were detected. Successful outcome was possible in 68.8% of patients with any rifampicin resistance and in 20% of patients with MDR tuberculosis. Retreatment resulted in failure in 80% and 100%, respectively, of patients whose sputum cultures remained positive at the end of the second and third months. CONCLUSION: Drug resistance proved the most important factor affecting treatment outcome. Success rates in retreatment of patients with any rifampicin resistance or MDR tuberculosis are low. Conversion to negative sputum results at the end of the second and third months of retreatment seems to be a significant parameter for a successful outcome.

Treatment adherence of 717 patients with tuberculosis in a social security system hospital in Istanbul, Turkey.

SETTING: Tuberculosis clinic in a teaching hospital run by the social security system, Istanbul, Turkey. OBJECTIVE: To determine risk factors associated with treatment adherence. DESIGN: Seven hundred and seventeen patients who commenced treatment for tuberculosis in our clinic from May 1991 to May 1997 were evaluated retrospectively with respect to treatment adherence. Factors with an effect on treatment adherence were investigated. RESULTS: Sputum conversion was achieved in 88.9% of the cases within the first 2 months of treatment. Seven patients died during treatment; of the 710 patients remaining, 106 (14.9%) were non-adherent. This rate decreased from 34.4% in 1991 to 2.0% in 1997. In multi-variate logistic regression analysis, only previous treatment history for tuberculosis was related to non-adherence; treatment adherence rate in new cases was 88.9%, while it was 66.7% in previously treated cases (P < 0.001). CONCLUSION: In new cases, a treatment adherence rate of 88.9% can be considered satisfactory. However, in previously treated cases, an adherence rate of 66.4% must be considered unsatisfactory. Previously treated cases in particular should therefore receive directly observed treatment.

The treatment of multidrug-resistant tuberculosis in Turkey.

BACKGROUND: We evaluated the results of treatment in 158 consecutive patients with multidrug-resistant tuberculosis who were treated at our center in Istanbul. METHODS: A total of 21 female patients and 137 male patients (age range, 15 to 68 years) received treatment for multidrug-resistant tuberculosis between March 1992 and October 1999. The patients had previously received a mean of 5.7 antituberculosis drugs and were infected with organisms that were resistant to a mean of 4.4 drugs. All patients were infected with organisms that were resistant to both isoniazid and rifampicin. The regimens we used were selected on the basis of previous treatment protocols and the results of susceptibility tests. All patients received at least three drugs thought to be active; the treatment was continued for at least 18 months after the conversion to a negative culture and for at least 24 months in the absence of first-line drugs. RESULTS: The mean number of drugs given during the study was 5.5 (range, 3 to 9). Surgical resection was performed in 36 patients. Adverse effects led to discontinuation of one or more drugs in 62 patients (39 percent). Cultures became negative in 150 patients (95 percent) after a mean of 1.9 months (range, 1 to 9). The overall success rate of treatment was 77 percent, with cures in 78 patients (49 percent) and probable cures in 43 (27 percent). Treatment failed in 13 patients (8 percent). Seven patients died (4 percent). Seventeen patients (11 percent) did not complete the treatment regimen. The patients with unsuccessful outcomes were older than those with successful outcomes (mean age, 42 years vs. 36 years; P=0.008), had received a larger number of drugs previously (median, six vs. five; P=0.048), were more likely to have been treated previously with ofloxacin (57 percent vs. 30 percent, P=0.004), and were less likely to have received ofloxacin as part of the study protocol (65 percent vs. 84 percent, P=0.018). Thirty-eight percent of the patients with unsuccessful outcomes were infected with organisms that were resistant to more than five drugs. In a step-down logistic-regression analysis, a successful outcome was independently associated with a younger age (P=0.013) and the absence of previous treatment with ofloxacin (P=0.005). CONCLUSIONS: Most patients with multidrug-resistant tuberculosis can be cured with the use of appropriate, intensive treatment regimens.

The management of anti-tuberculosis drug-induced hepatotoxicity.

SETTING: A tuberculosis ward in a chest disease teaching hospital. OBJECTIVE: To compare the efficacy of two different retreatment protocols on hepatotoxicity recurrence in tuberculosis treatment. DESIGN: In a prospective, randomised study, 45 patients with new tuberculosis developed hepatotoxicity after anti-tuberculosis treatment. Patients in Group I (n = 20) were retreated with a drug regimen consisting of isoniazid, rifampicin, ethambutol and streptomycin administered by gradually increasing the number and dosage of the drugs. Patients in Group II (n = 25) were retreated with the same regimen (isoniazid, rifampicin, pyrazinamide and ethambutol) in the same dosages throughout. RESULTS: Hepatotoxicity recurred in respectively zero and six (24%) patients in Groups I and II (P = 0.021). Of the six patients with recurrence of hepatitis, one could not be followed up. The other five received the same retreatment protocol as Group I. By the end of retreatment, all patients were cured. CONCLUSION: The recurrence rate of hepatotoxicity in the retreatment of tuberculosis is higher in the reintroduction of a full-dose regimen including pyrazinamide, which causes more hepatotoxicity than gradual reintroduction of a regimen without pyrazinamide.

Role of surgery in multi-drug-resistant tuberculosis: results of 27 cases.

OBJECTIVE: To evaluate the results of resectional surgery as an adjuvant therapy in multi-drug resistant tuberculosis. METHODS: A total of 27 human immunodeficiency virus (HIV)-negative patients with multi-drug resistant tuberculosis underwent resectional surgery between 1993 and 1996. The lesions were bilateral in 16 cases, with a preponderance of cavities on one side. Out of 27 cases, 5 patients had unilaterally destroyed lung; 20 patients underwent pneumonectomy (15 left, 5 right). Lobectomy operations included bilobectomy superior (n = 1), right lower lobectomy (n = 2), right upper lobectomy (n = 3), and left upper lobectomy with superior segmentectomy (n = 1). RESULTS: Because of haemorrhage, 2 cases who underwent a right and left pneumonectomy, respectively, required revision on the first day . Bronchopleural fistula was found in 2 cases with left pneumonectomy. Apical residual space was left in one of the 3 patients who underwent right upper lobectomy. Retreatment protocols resulted in negative cultures and smears in all patients with an average duration of 4 months (1-6 months). A total of 4 patients (16%) completed a retreatment period of 18-24 months with negative cultures. Only 1 patient (3.7%) developed relapse in the 17th month of retreatment. Patients with negative cultures numbered 22 and continued receiving retreatment. CONCLUSIONS: Our results indicate that surgical management of multi-drug resistant tuberculosis, combined with chemotherapy, provides a more favourable outcome than that obtained with medical therapy alone.

Alarming drug-resistance rates for tuberculosis in Süreyyapasa Hospital, Turkey.

The susceptibility patterns to 'classic' tuberculous pleuritis can reflect the circulating strains in a society. The records of patients with 'classic' tuberculous pleuritis were reviewed retrospectively. Eighty-six patients were selected who were hospitalized between January 1990 and April 1994. Pleural fluid and tissue samples of patients were cultured in Lowenstein-Jensen medium. The isolated strains were subjected to drug susceptibility testing based on the absolute concentration method. We obtained 40 positive cultures in 86 patients with 'classic' tuberculous pleuritis. The resistance rate was 75% to one or more drugs, 27.5% to two drugs, 15% to three drugs, and 10% to four drugs. The resistance rates to isoniazid, rifampicin, streptomycin, and ethambutol were 32.5, 55,42.5 and 32.5%, respectively. The resistance to isoniazid + rifampicin was 7.5%. Our findings indicate that the resistance rates for 'classic' tuberculous pleuritis are considerably high, reflecting the currently circulating resistance patterns in our region. The best regimen for new tuberculous cases and the appropriate regimens for drug-resistant cases should be designed and conducted by a nationwide institution.

Intrathoracic tuberculous lymphadenopathy: clinical and bronchoscopic features in 17 adults without parenchymal lesions.

BACKGROUND: Whilst intrathoracic lymphadenitis is a characteristic sign of primary tuberculosis in children, its presence without parenchymal lesions in adults is unusual and makes the diagnosis using noninvasive techniques difficult. The diagnostic role of bronchoscopy in adults with intrathoracic tuberculous lymphadenitis is reported. METHODS: Seventeen patients with intrathoracic lymphadenopathy seen during 1993 who had all undergone bronchoscopy and had been found to have tuberculosis in the absence of any parenchymal lung lesions were evaluated retrospectively. RESULTS: Right paratracheal lymphadenopathy was observed on the plain chest radiograph in all the patients. Fifteen of the 17 patients had an endobronchial abnormality and samples taken at bronchoscopy gave a definitive diagnosis in nine (53%) of the 17. Four patients had ulcerating endobronchial granuloma and all had biopsy samples positive for tuberculosis. Transbronchial or transcarinal needle aspiration samples were diagnostic in five of 11 patients (45%) subjected to the procedure. Peripheral lymph node biopsy diagnosed tuberculosis in two cases and in the remaining six patients the diagnosis wa achieved by mediastinoscopy or thoracotomy. CONCLUSIONS: Bronchoscopy has an important role in the diagnosis of intrathoracic tuberculous lymphadenopathy in adults and should be considered before other invasive procedures.

High initial and acquired drug resistance in pulmonary tuberculosis in Turkey.

SETTING: Süreyyapasa Center for Chest Diseases and Thoracic Surgery, Istanbul, Turkey between January 1992 and December 1992. OBJECTIVE: To evaluate the prevalances of initial and acquired resistance to antituberculosis drugs in our center. DESIGN: 785 patients with pulmonary tuberculosis (both old = 525/785 and new = 260/785 cases) referred to our center were evaluated with respect to their drug resistance patterns. RESULTS: The overall resistance rate (1 or more drugs) was 35.5%, with initial resistance 26.6% (140 of 525) and acquired resistance 53.4% (139 of 260). Initial resistance to streptomycin was the most frequent (20.6%), followed by rifampicin (10.8%), isoniazid (5.1%) and ethambutol; (4.2%). Initial resistance was noted as 16.4% to 1 drug, 7.7% to 2 drugs, 1.2% to 3 drugs and 1.3% to 4 drugs. Acquired resistance to rifampicin was the most frequent (36.2%) followed by streptomycin 31.9%, and isoniazid 30%. Acquired resistance was found as 18.7% to 1 drug, 19.3% to 2 drugs, 9.6% to 3 drugs and 5.8% to 4 drugs. CONCLUSION: High initial drug resistance in Turkey may well threaten the success rates of antituberculosis treatment and it is therefore mandatory to begin antituberculosis treatment in routine practice in our country with at least 4 first-line drugs, replacing streptomycin with ethambutol due to high resistance to streptomycin. In conclusion there is an urgent need for a nationwide tuberculosis control programme in Turkey, where the treatment of old cases is still challenging, in order to combat the grave situation of high initial and acquired drug resistance.