Pooja Pandey

Carbapenems and Rifampin Exhibit Synergy against Mycobacterium tuberculosis and Mycobacterium abscessus.

ABSTRACT An effective regimen for treatment of tuberculosis (TB) is comprised of multiple drugs that inhibit a range of essential cellular activities in Mycobacterium tuberculosis. The effectiveness of a regimen is further enhanced if constituent drugs act with synergy. Here, we report that faropenem (a penem) or biapenem, doripenem, or meropenem (carbapenems), which belong to the β-lactam class of antibiotics, and rifampin, one of the drugs that forms the backbone of TB treatment, act with synergy when combined. One of the reasons (carba)penems are seldom used for treatment of TB is the high dosage levels required, often at the therapeutic limits. The synergistic combination of rifampin and these (carba)penems indicates that (carba)penems can be administered at dosages that are therapeutically relevant. The combination of faropenem and rifampin also limits the frequency of resistant mutants, as we were unable to obtain spontaneous mutants in the presence of these two drugs. The combinations of rifampin and (carba)penems were effective not only against drug-sensitive Mycobacterium tuberculosis but also against drug-resistant clinical isolates that are otherwise resistant to rifampin. A combination of doripenem or biapenem and rifampin also exhibited synergistic activity against Mycobacterium abscessus. Although the MICs of these three drugs alone against M. abscessus are too high to be of clinical relevance, their concentrations in combinations are therapeutically relevant; therefore, they warrant further evaluation for clinical utility to treat Mycobacterium abscessus infection, especially in cystic fibrosis patients.

Prospective multicentre evaluation of the direct nitrate reductase assay for the rapid detection of extensively drug-resistant tuberculosis

OBJECTIVES To perform a multicentre study evaluating the performance of the direct nitrate reductase assay (NRA) for the detection of multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis in sputum samples. METHODS The study was conducted in six laboratories performing tuberculosis diagnosis that were located in six different countries. The NRA was performed directly on sputum samples in parallel with the reference method used at each site. Detection of resistance was performed for rifampicin, isoniazid, ofloxacin and kanamycin. RESULTS Excellent agreement was obtained for all drugs tested at the majority of sites. The accuracy was 93.7%-100% for rifampicin, 88.2%-100% for isoniazid, 94.6%-100% for ofloxacin and 100% for kanamycin. The majority of NRA results were available at day 21 for sites 1, 2 and 5. Site 3 had a turnaround time of 13.9 days, at site 4 it was 18.4 days and at site 6 it was 16.2 days. The contamination rate ranged between 2.5% and 12%. CONCLUSIONS Rapid detection of drug resistance by the direct NRA on sputum smear-positive samples was accurate and easy to implement in clinical diagnostic laboratories, making it a good alternative for rapid screening for MDR and XDR tuberculosis.

Genotypic, Phenotypic and Clinical Validation of GeneXpert in Extra-Pulmonary and Pulmonary Tuberculosis in India

Background Newer molecular diagnostics have brought paradigm shift in early diagnosis of tuberculosis [TB]. WHO recommended use of GeneXpert MTB/RIF [Xpert] for Extra-pulmonary [EP] TB; critics have since questioned its efficiency. Methods The present study was designed to assess the performance of GeneXpert in 761 extra-pulmonary and 384 pulmonary specimens from patients clinically suspected of TB and compare with Phenotypic, Genotypic and Composite reference standards [CRS]. Results Comparison of GeneXpert results to CRS, demonstrated sensitivity of 100% and 90.68%, specificity of 100% and 99.62% for pulmonary and extra-pulmonary samples. On comparison with culture, sensitivity for Rifampicin [Rif] resistance detection was 87.5% and 81.82% respectively, while specificity was 100% for both pulmonary and extra-pulmonary TB. On comparison to sequencing of rpoB gene [Rif resistance determining region, RRDR], sensitivity was respectively 93.33% and 90% while specificity was 100% in both pulmonary and extra-pulmonary TB. GeneXpert assay missed 533CCG mutation in one sputum and dual mutation [517 & 519] in one pus sample, detected by sequencing. Sequencing picked dual mutation [529, 530] in a sputum sample sensitive to Rif, demonstrating, not all RRDR mutations lead to resistance. Conclusions Current study reports observations in a patient care setting in a high burden region, from a large collection of pulmonary and extra-pulmonary samples and puts to rest questions regarding sensitivity, specificity, detection of infrequent mutations and mutations responsible for low-level Rif resistance by GeneXpert. Improvements in the assay could offer further improvement in sensitivity of detection in different patient samples; nevertheless it may be difficult to improve sensitivity of Rif resistance detection if only one gene is targeted. Assay specificity was high both for TB detection and Rif resistance detection. Despite a few misses, the assay offers major boost to early diagnosis of TB and MDR-TB, in difficult to diagnose pauci-bacillary TB.

Role of yoga and meditation on serum DHEAS level in first year medical students

Background: Dehydroepiandrosterone sulfate (DHEAS), secreted by adrenal cortex, acts in the human body as a neurosteroid, cardio-protective, anti-diabetic, anti-obesity and immune-enhancing agent. It is also reported as a youth hormone. But due to various stimulators of stress, and also as an antagonist of cortisol, DHEAS level decreases. Yoga and meditation regulates the level of hormones and neurotransmitters that affect physiological function. Methods: This study was performed on 1st yr. medical students whose DHEAS level was low due to acute stress. 55 medical students were selected as participants through counseling and were divided into Yoga group (n= 27) and control group (n=28). Their morning serum DHEAS level was assessed and yoga group were instructed to practice Yoga (1hr/day for 12 weeks) under supervision of Yoga instructor. No such instruction was given to control group. Results: As a marker of youth and immunity, increase in DHEAS level decreases susceptibility to infections, reduces aging process as well as improves other functions. Yoga and meditation is documented to increase DHEAS level in regular practitioners. Statistical analysis has shown an increase in morning S. DHEAS level in yoga practitioners. Prestudy and post study values were 3.5±2.48 and 3.61±1.73 respectively in yoga group (overall 3.1% increase, P Value = 0.025, significant at 0.05) whereas 3.36±1.98 and 2.58±1.49 respectively in control group (23.2% decrease, P Value =0.84, not significant). Conclusions: This study concludes that practicing Yoga has significantly raised S. DHEAS level in medical students and improved their immunological status as well as enhances mood and behavior.

Effect of antihistaminics on amplitude of rabbit gut

Background: The small intestine, like the rest of the gastrointestinal tract, is an intelligent organ. It generates a wide variety of motor patterns to meet motility requirements in different situations. Its basic motor function after a meal is to mix the chyme with exocrine and intestinal secretions, agitate its contents too. Methods: In vitro study is done to explore the effect of 1st generation antihistaminic (chlorpheniramine maleate) and second generation antihistaminic (Fexofenadine) on amplitude of gut motility by isolated rabbit gut preparation on Dale’s Organ bath, part of terminal ileum is used for study. Eight rabbits weighing 2 to 4.5 kg were used for study. The effect of antihistaminic observed that both drugs reduce amplitude. Results: The effect of Chlorpheniramine malete and Fexofenadine on amplitude observed and it found that both decrease the amplitude significantly. Conclusions: This study establishes a correlation between amplitude of gut and effect of antihistaminic suggests that antihistaminic drug both first generation and second generation decreases the amplitude of gut motility with a significant response.

De Novo Histoid Leprosy.

Histoid leprosy is an uncommon entity with specific clinical, histopathological and bacteriological features. Histoid lepromas are sudden eruption of dome shaped lesions usually associated with dapsone resistance, as a variant of lepromatous leprosy or rarely arising de novo. We report a case who presented for the first time with histoid features with no history of taking dapsone/antileprosy treatment earlier in an elderly male with small to large lesions over normal skin in the post-leprosy elimination era.