Pattern of first- and second-line drug resistance among pulmonary tuberculosis retreatment cases in Pakistan.

BACKGROUND: Drug resistance in general, and multidrug-resistant tuberculosis (MDR-TB) in particular, threatens global tuberculosis (TB) control efforts. Population-based estimates of drug resistance are needed to develop strategies for controlling drug-resistant TB in Pakistan. OBJECTIVE: To obtain population-based data on Mycobacterium tuberculosis drug resistance in Pakistan. METHODS: To obtain drug resistance data, we conducted a population-based study of TB cases in all provinces of Pakistan. We performed culture and drug susceptibility testing on M. tuberculosis isolates from patients with a prior history of anti-tuberculosis treatment (retreatment cases) from all over the country. RESULTS: Of 544 isolates from previously treated cases, 289 (53.1%) were susceptible to all first-line drugs, 255 (46.9%) were resistant to at least one anti-tuberculosis drug and 132 (24.3%) were MDR-TB. Among MDR-TB isolates, 47.0% were ofloxacin (OFX) resistant. Extensively drug-resistant TB was found in two (0.4%) isolates. CONCLUSION: Prevalence of drug resistance in retreatment isolates was high. The alarmingly high prevalence of OFX resistance among MDR-TB isolates may threaten the success of efforts to control and treat MDR-TB.

Prevalence of primary multidrug resistance to anti-tuberculosis drugs in Pakistan.

SETTING: Pakistan ranks sixth in the world in terms of tuberculosis (TB) burden, with a World Health Organization estimated incidence of 181 per 100000, or 286000 new cases annually. Hospital-based data indicate a significant problem of multidrug-resistant TB (MDR-TB) in the country and highlight the need to assess its extent at community level. In this cross-sectional study, sputum samples from 742 untreated newly diagnosed pulmonary TB patients from all over the country were used. OBJECTIVE: To assess the prevalence of primary drug resistance in Pakistan. RESULTS: Of 672 culture-positive patients, 76 (11.3%) showed resistance to one or more drugs. Resistance to streptomycin (10 microg/ml) was found in 36 (5.4%) patients, isoniazid (INH) (1 microg/ml) in 51 (7.6%), rifampicin (RMP) (5 microg/ml) in 15 (2.2%), ethambutol (10 microg/ml) in 12 (1.8%) and pyrazinamide in 22 (3.3%) samples. Forty-six (6.8%) of the isolates tested were resistant to a single drug, 10 (1.5%) to two drugs, 12 (1.8%) to three drugs, and 6 (0.9%) to four drugs, while 2 (0.3%) isolates were resistant to all five first-line agents. Primary MDR-TB was 1.8% (n=12) (INH 1 microg/ml, RMP 5 microg/ml). CONCLUSION: The results of this study show a prevalence of primary MDR-TB in Pakistan of <2%, which needs to be addressed through an effective DOTS strategy.

Cefaclor AF vs Clarithromycin in acute exacerbation of chronic bronchitis (B3M-PK-AJBG).

OBJECTIVE: To compare the efficacy and safety of Cefaclor AF vs Clarithromycin in the treatment of acute exacerbation of chronic bronchitis in adult subjects. PATIENTS AND METHODS: This study was conducted on 300 patients suffering from acute exacerbation of chronic bronchitis, who attended the out patient clinics of ten different hospitals throughout Pakistan. Pneumonia, bronchiectasis and tuberculosis were excluded with the help of chest radiography and sputum smear examination. Pretherapy sputum culture and sensitivity (c/s) were tested and patients were randomized and supplied with either tablet Cefaclor 375 mg or tablet Clarithromycin 250 mg to be taken twice daily. Patients were evaluated at day 0 and then at day 3-5 and day 10-11. Post therapy sputum c/s was done on day 10-11. A fourth and final visit was planned on day 20-24 which was optional. At each visit, the severity of disease and the signs and symptoms were recorded on the clinical report forms according to the preset standards. RESULTS: Of 136 patients in the Cefaclor group and 142 patients in the Clarithromycin group, cure was achieved in 44 vs 35 subjects, improvement in 78 vs 91 subjects and failure in 16 vs 18 subjects among Cefaclor vs Clarithromycin groups respectively. The overall clinical efficacy (cure and improvement combined ) was 88.4% in the Cefaclor group and 87.5% in the Clarithromycin group. Nine patients in the Cefaclor group and patients in the Clarithromycin group had one adverse event whereas twelve patients in each group had two or more adverse events. CONCLUSIONS: The above results show that both Cefaclor AF and Clarithromycin are equally effective and safe in the treatment of acute exacerbation of chronic bronchitis in adult patients.