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 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.