Pharmacophoric screening of newly synthesized isoniazid derivatives and their antimycobacterial activity

Mycobacterium tuberculosis is clinically recognized as a causative agent of Tuberculosis. Keeping in view, this study was endeavored to screen our previously synthesized seventeen INH analogues for their antimycobacterial potential using proportion method. During this process, INH and all the seventeen compounds were examined at different concentrations of 0.05, 0.1 and 0.2microg/mL which were prepared using Lowenstein-Jensen [LJ] base. For drug susceptibility test, three Mycobacterial strains ATCC H37Rv, known INH-sensitive and INH-resistant strains were selected, sub-cultured on LJ Medium and serial diluted to achieve 1: 10, 1: 100, 1: 1000 and 1: 10000 from calibrated bacterial suspension Mcfarland No. 1. Dilutions of 1: 100 and 1: 10000 were added to drug free medium and 1: 100 bacterial suspension was added to each of the test concentrations and finally incubated for 4-6 weeks at 37 degree C. It was observed that only compounds II and XI were active against MTb. Compounds III, IX and X also showed activity but were less potent. Ligand Scout 3.02[il_10] was used to perform pharmacophore-based screening where important pharmacophoric features were identified in the structures of these compounds which could be related to their observed antimycobacterial activity

ratio of smear-negative tuberculosis in Sindh: an insight using fluorescence microscopy

Background: Sputum smear microscopy is the most useful tool used for the screening of presumptive tuberculosis cases. Conventionally Ziehl-Neelsen [ZN] based staining is used to microscopically screen sputum from the presumptive Tuberculosis Cases. However, Fluorescent microscopy [FM] is now gradually replacing the conventional ZN microscopy because of its higher efficiency and efficacy in detecting Mycobacterium tuberculosis. In patients, who do not produce sufficiently high number of bacilli, and are known as Smear-negative, efficacy of both types of microscopy remains questionable as no Mycobacteria are detected in the sputum of these patients and they are falsely labelled as smear-negative

Objective: This retrospective study was conducted on the patient samples received from different parts of Sindh to study the proportions of false-negative tuberculosis using fluorescent microscopy

Materials and Methods: A retrospective cross-sectional study was conducted from June 2014 to June 2016 at the Tuberculosis Laboratories of Dow University of Health Sciences. Data analyzed for 1439 samples received during 24-month period, which had subsequently been confirmed by culture. All laboratory work was performed as per guidelines of the National Program. Statistical analysis was performed on MedCalc[registered sign] and Open Epi[registered sign]

Results: During 24-month period, among the 1439 cases, 832[57.81%] were from males and 499 [34.67%] were smear negative. Culture showed that 72 [14.42%] were false-negative among all-negatives. Overall sensitivity observed was 92.21% [95%CI 90.29%-93.85%] and specificity 82.91% [95%CI 79.38%- 86.06%]. The proportion of false negativity among all negatives in females [16.11%] was significantly higher [p=0.002] as compared to males [13.47%]

Conclusions: Even with the introduction of Fluorescent Microscopy, smear microscopy cannot be solely relied upon for the diagnosis of tuberculosis, as considerable number of patients producing insufficient number of bacilli to be detected by microscopy

Multi-drug resistant Pseudomonas aeruginosa: a threat of nosocomial infections in tertiary care hospitals

To determine the resistance patterns of Pseudomonas aeruginosa to currently available anti-pseudomonal drugs and frequency of nosocomial infections caused by multi drug resistant Pseudomonas aeruginosa in hospitals. Clinical isolates of Pseudomonas aeruginosa were collected from patients admitted in different hospitals of Karachi between July 2012 and June 2013. The isolates were identified by conventional and Analytical Profile Index 20NE kit methods while the antibiograms of these isolates were determined by Kirby- Bauer disc diffusion method. Of the 204 isolates, 79[39%] were obtained from intensive care units. Overall, 135[66%] isolates belonged to men, and 35[17.2%] belonged to 10-15 year age group. The overall antibiogram pattern showed high resistance to commonly used antibiotics like Ofloxacin 125[61.3%], Cefepime 117[57.3%], Ceftazidime 110[53.9%], Amikacin 108[53%]. Of all the isolates, 129[63.2%] were considered multidrug resistant. The most effective antibiotics were Colistin, Polymyxin B and Meropenem. Increasing multidrug resistance among nosocomial pathogens is an alarming situation in a hospital setting and requires prompt management of these cases