Phenotypic low-level isoniazid resistance as a marker to predict ethionamide resistance in mycobacterium tuberculosis

Background: Tuberculosis is one of the most prevalent diseases in Pakistan. Pakistan has the highest burden of MDR-TB in the Eastern Mediterranean region. Ethionamide is an anti-tuberculous drug frequently used to treat MDR-TB. Its drug susceptibility testing is not easily available in resource limited settings. Since it acts on the same target protein as isoniazid (inhA protein encoded by inhA gene), we sought to find out if phenotypic isoniazid resistance can be a marker of ethionamide resistance.Materials and Methods: This was a retrospective observational study conducted at the Aga Khan University hospital section of microbiology. Data was retrieved between 2011 to 2014 for all culture positive MTB strains. All culture positive MTB isolates with susceptibilities to isoniazid and ethionamide recorded were included in the study. Isoniazid and ethionamide susceptibilities were performed using agar proportion method on Middlebrook 7H10 agar. Rate of Ethionamide resistance between low-level isoniazid resistant, high level isoniazid resistant and isoniazid sensitive MTB was compared.Results: A total of 11,274 isolates were included in the study. A statistically significant association (P \u3c 0.001) was found between Ethionamide resistance and low-level isoniazid resistance (26.6%) as compared to high-level isoniazid resistance (8.85%) and isoniazid sensitivity (0.71%) in MTB strains. However this association was not seen in XDR-TB strains.Conclusion: Low level isoniazid resistance may be used as marker for phenotypic ethionamide resistance and hence guide clinicians\u27 choice of antituberculous agent for MDR-TB in Pakistan. Further studies involving detection of genotypic association of isoniazid and ethionamide susceptibilities are needed before a final conclusion can be derived

Frequency of colistin and fosfomycin resistance in carbapenem-resistant Enterobacteriaceae from a tertiary care hospital in Karachi

Introduction: Management of infections with carbapenem-resistant Enterobacteriaceae (CRE) is challenging. In recent times, agents such as colistin and fosfomycin have been used in combination with other antibiotics to treat such infections. In this study, we aim to seek frequency of colistin and fosfomycin resistance in CRE from Pakistan. Methods: This study was conducted at clinical laboratories, Aga Khan University Hospital. In total, 251 CRE were included in the study. Colistin minimum inhibitory concentrations (MICs) were performed using broth microdilution (BMD) method and VITEK 2 system, whereas fosfomycin susceptibility was performed using Kirby-Bauer method. MIC50 and MIC90 were calculated for colistin and agreement between VITEK and BMD was also calculated. Results: Out of 251 strains colistin MIC of ≥4 g/mL was seen in 40 (15.9%). Of these strains 20 (50%) were Klebsiella pneumoniae. Colistin MIC50 and MIC90 were found to be 0.5 and 16 g/mL, respectively. BMD and VITEK 2 showed 100% categorical agreement. Essential agreement was 88.5% with kappa score 0.733 indicating strong agreement between VITEK and BMD. 31 out of 251 (12.3%) CREs were resistant to fosfomycin. Conculsion: Study shows frequency of colistin and fosfomycin resistance to be 15.9% and 12.3%, respectively. In countries where rate of CREs is high, emerging resistance against these last resort antibiotics is alarming as it leaves clinicians with almost no options to manage such multidrug resistant and extensively drug resistant infections

Bomb blast injuries: an exploration of patient characteristics and outcome using Pakistan National Emergency Departments Surveillance (Pak-NEDS) data.

BACKGROUND: Bomb blast injuries result in premature deaths and burdening of healthcare systems. The objective of this study was to explore the characteristics and outcome of patients presenting to the emergency departments in Pakistan with bomb blast injuries. METHODS: Active surveillance was conducted in seven major emergency departments of Pakistan from November 2010-March 2011. All the sites are tertiary care urban centers. All the patients who presented to the hospital\u27s emergency department (ED) following a bomb blast injury as per self-report or the ambulance personnel were included in the study. Frequency of demographics, injury pattern, and outcomes were calculated. RESULTS: A total of 103 patients with bomb blast injuries presented to the selected emergency departments. The median age of patients was 30 years. Around three-fourth of the patients were males (n = 74, 74.7%). Most of the bomb blast patients were seen in Peshawar (n = 41, 39.8%) and Karachi city (n = 31, 30.1%) and the most common mode of arrival was non-ambulance transport (n = 71, 76.3%). Upper limb injuries (n = 12, 40%) were common in the under 18 age group and lower limb injuries (n = 31, 39.2%) in the 18 years and above group. There were a total of 8 (7.7%) deaths reported out of these 103 patients. CONCLUSION: Bomb blast injuries in Pakistan generally affect young males. Non-ambulance transport is the most common way to access emergency departments (ED). Overall ED mortality is high and capturing data during a disaster in an emergency department is challenging

Modulation of metabolic alterations of obese diabetic rats upon treatment with Salacca zalacca fruits extract using H NMR-based metabolomics

Fruit of salak (Salacca zalacca) is tradition ally used and commercialized as an an tidiabetic agent. How ever, the scientific evidence to prove this traditional use is lack ing. This re search was aimed to evaluate the metabolic changes of obese-diabetic (OBDC) rats treated with S. zalacca fruit using proton-nuclear magnetic resonance ( H NMR)-based metabolomics approach. This re search presents the first report on the in vitro antidiabetic effect of S. zalacca fruits ex tract us ing this approach. The obtained results in dicated that the administration of 400 mg/ kg bw of 60% ethanolic S. zalacca extract for 6 weeks significantly de creased the blood glucose level and normalized the blood lipid pro file of the OBDC rats. The potential biomarkers in urine were 2-oxoglutarate, alanine, leucine, succinate 3-hydroxy butyrate, taurine, betaine, allantoin, acetate, dimethylamine, creatine, creatinine, glucose, phenyl-acetyl glycine, and hippurate. Based on the data obtained, the metabolite pro files of the urine of treated rats by the 60% ethanolic extract could not be fully improved the metabolic complications of diabetic rats. The ex tract of S. zalacca fruit was able to de crease the ketones bodies as 3-hydroxy butyrate and acetoacetate. It has also improved energy metabolism, involving glucose, acetate, lactate, 2-hydroxy butyrate, 2-oxoglutarate, citrate, and succinate. More over, it decreased metabolites from gut microflora, including choline. This extract had significant effect on amino acid metabolism, metabolites from gut microflora, bile acid metabolism and creatine. The result can further support the traditional claims of S. zalacca fruits in management of diabetes. This finding might bevaluable in understanding the molecular mechanism and pharmacological properties of this medicinal plant for managing diabetes mellitus

Adolopment of adult diabetes mellitus management guidelines for a Pakistani context: Methodology and challenges

IntroductionPakistan has the highest national prevalence of type 2 diabetes mellitus (T2DM) in the world. Most high-quality T2DM clinical practice guidelines (CPGs) used internationally originate from high-income countries in the West. Local T2DM CPGs in Pakistan are not backed by transparent methodologies. We aimed to produce comprehensive, high-quality CPGs for the management of adult DM in Pakistan.MethodsWe employed the GRADE-ADOLOPMENT approach utilizing the T2DM CPG of the American Diabetes Association (ADA) Standards of Medical Care in Diabetes – 2021 as the source CPG. Recommendations from the source guideline were either adopted as is, excluded, or adapted according to our local context.ResultsThe source document contained 243 recommendations, 219 of which were adopted without change, 5 with minor changes, and 18 of which were excluded in the newly created Pakistani guidelines. One recommendation was adapted: the recommended age to begin screening all individuals for T2DM/pre-diabetes was lowered from 45 to 30 years, due to the higher prevalence of T2DM in younger Pakistanis. Exclusion of recommendations were primarily due to differences in the healthcare systems of Pakistan and the US, or the unavailability of certain drugs in Pakistan.ConclusionA CPG for the management of T2DM in Pakistan was created. Our newly developed guideline recommends earlier screening for T2DM in Pakistan, primarily due to the higher prevalence of T2DM amongst younger individuals in Pakistan. Moreover, the systematic methodology used is a significant improvement on pre-existing T2DM CPGs in Pakistan. Once these evidence based CGPs are officially published, their nationwide uptake should be top priority. Our findings also highlight the need for rigorous expanded research exploring the effectiveness of earlier screening for T2DM in Pakistan

A case report on isolation of linezolid- and vancomycin-resistant enterococcus faecium species from cerebrospinal fluid of a patient suffering from ventriculoperitoneal shunt-associated meningitis

Vancomycin-resistant enterococci (VRE) are one of the most common nosocomial infections. Linezolid has been used to treat such infections extensively. Over time there have been reports where linezolid resistance in enterococci has been documented. This is the first report from Pakistan where linezolid- and vancomycin-resistant Enterococcus faecium was isolated from cerebrospinal fluid (CSF) sample from infected ventriculoperitoneal (VP) shunt

Utility of Line Probe Assay for diagnosis of extrapulmonary tuberculosis

Introduction: In 2008, the World Health Organization (WHO) approved a rapid molecular test known as Line Probe Assay (LiPA) for the diagnosis of multidrug-resistant tuberculosis (MDR-TB) in pulmonary specimens. Due to lack of available data, its use in extra-pulmonary tuberculosis (EPTB) specimens has not been determined yet. Recommendations for the use of Xpert MTB/RIF in EPTB have been issued, but alternative rapid molecular tests for EPTB diagnosis need to be evaluated. Method: LiPA (GenoType® MTBDRplus 2.0 Hain Lifescience) was performed on 97 specimens of extrapulmonary origin at the clinical laboratory at Aga Khan University (Dec 2012–Jan 2014). The results were compared with TB cultures in solid and liquid medium. Results: 97 specimens were tested simultaneously for culture and LiPA, including pleural fluid (35), CSF (22), pus (17), tissue (10) and urine (3). Concentrated smear was positive for 7 while 14 were culture positive for MTB. All 7/7 smear-positive specimens were LiPA positive, while 6/7 were culture positive. Amongst the smear-negative specimens, 8/90 were culture positive and 9/90 were LiPA positive. The overall sensitivity and specificity of LiPA for the detection of MTB in the EPTB specimens was 71.4% (95% CI 41.9–91.4) and 92.8% (95% CI 84.9–97.3), respectively. The highest sensitivity (100%) was seen in urine as 2 of 3 which were culture positive were also LiPA positive. Pus samples showed sensitivity of 85.7% and specificity of 70%. Conclusion: The study shows that LiPA has good overall sensitivity and specificity compared with culture. Although the number of samples was very small, the applicability appears to be most useful in urine and pus specimens and should be explored further as a diagnostic tool in these cases

A new and simple method for the synthesis of highly functionalised pyrrolizidines, indolizidines and pyrroloazepines

The reaction of 5-, 6- and 7-membered cyclic thioimidates with cyclopropenones gives access to highly functionalised pyrrolizidines, indolizidines and pyrroloazepines via a formal [3+2] cycloaddition proces

Salacca zalacca: A short review of the palm botany, pharmacological uses and phytochemistry

Salacca zalacca (Gaertn.) Voss (family Arecaceae) is the snake fruit commonly known in Malay language as salak in Malaysia. This exotic fruit has diverse and potential pharmacological properties due to its high antioxidant content. It is often consumed due to its sweet taste. The abundant natural sugar and fibre along with minerals and vitamin makes it a nutritious fruit. Phytochemical investigation on this fruit has revealed the presence of flavonoids, phenolics, glycosides as well as some volatile and aromatic compounds, including gallic acid, quercetin, chlorogenic acid, epicatechin, proanthocyanidins, lycopene and β-carotene. Pharmacological studies on the fruit flesh and peel have shown some tremendous antioxidant, anti-inflammatory, anticancer and antidiabetic potential. This review provides the botanical information of Salacca zalacca as well as its scientific investigations involving the distinct pharmacological and phytochemical benefits. This could help in highlighting the lacking data and research gaps on this plant

Salacca zalacca: a short review of the palm botany, pharmacological uses and phytochemistry

Salacca zalacca (Gaertn.) Voss (family Arecaceae) is the snake fruit commonly known in Malay language as salak in Malaysia. This exotic fruit has diverse and potential pharmacological properties due to its high antioxidant content. It is often consumed due to its sweet taste. The abundant natural sugar and fibre along with minerals and vitamin makes it a nutritious fruit. Phytochemical investigation on this fruit has revealed the presence of flavonoids, phenolics, glycosides as well as some volatile and aromatic compounds, including gallic acid, quercetin, chlorogenic acid, epicatechin, proanthocyanidins, lycopene and β-carotene. Pharmacological studies on the fruit flesh and peel have shown some tremendous antioxidant, anti-inflammatory, anticancer and antidiabetic potential. This review provides the botanical information of Salacca zalacca as well as its scientific investigations involving the distinct pharmacological and phytochemical benefits. This could help in highlighting the lacking data and research gaps on this plan