Efficacy and safety of bedaquiline containing regimens in patients of drug-resistant tuberculosis: An updated systematic review and meta-analysis.

Background: Tuberculosis is an infectious disease caused by Mycobacterium tuberculosis and leads to serious complications if left untreated. Some strains of Mycobacterium tuberculosis are multi-drug resistant and require treatment with newer drugs. Bedaquiline based treatment regimens have been used in patients who are diagnosed with drug resistant tuberculosis. The aim of this study is to assess the efficacy and safety profile of bedaquiline-based treatment regimens using a systematic review of existing literature and meta-analysis. Methods: In this study, an electronic search was carried out on PubMed, ScienceDirect, and Cochrane library to find relevant literature from March 2021 onwards. Random-effects model was used to assess pooled treatment success rate and 95 % CIs. p-value of <0.05 was suggestive of publication bias. The review is registered with PROSPERO: CRD42023432748. Results: A total of 543 articles were retrieved by database searching, out of which 12 new studies met the inclusion criteria. The total number of articles included in the review was 41 including 36 observational studies (having a total of 9,934 patients) and 5 experimental studies (having a total of 468 patients). The pooled treatment success rate was 76.9 % (95 % CI, 72.9-80.4) in the observational studies and 81.7 % (95 % CI, 67.2-90.7) in the experimental studies. Further subgroup analysis was done on the basis of treatment regimens containing bedaquiline only and treatment regimens containing bedaquiline and delamanid. The pooled treatment success rate in the studies consisting of patients who were treated with regimens containing bedaquiline only was 78.4 % (95 % CI, 74.2-82.1) and 73.6 % (95 % CI, 64.6-81.0) in studies consisting of patients who were treated with regimens containing bedaquiline and delamanid. There was no evidence of publication bias. Conclusions: In patients of drug resistant tuberculosis having highly resistant strains of Mycobacterium tuberculosis undergoing treatment with bedaquiline-based regimen demonstrate high rates of culture conversion and treatment success. Moreover, the safety profile of bedaquiline-based regimens is well-established in all studies.

Diagnostic Accuracy Of Rapid Fosfomycin Np Test For Detection Of Fosfomycin Resistance In Escherichia Coli In A Tertiary Care Hospital In Pakistan.

BACKGROUND: Emergence of resistance among Escherichia coli (E.coli) isolates against therapeutic options for UTIs (Urinary tract infections) has led to renewed interest in older antibiotics like Fosfomycin. In this study we evaluated diagnostic accuracy of Rapid Fosfomycin NP test based on glucose metabolism for rapid Fosfomycin susceptibility testing among urinary E.coli isolates. METHODS: In a cross-sectional validation study conducted in the Microbiology Department, Armed Forces Institute of Pathology, Rawalpindi, Pakistan from 15th March to 15th September 2020, 149 consecutive urine specimens were included as per selection criteria. Rapid Fosfomycin NP test was performed as per protocol of Nordmann P et al on urinary E.coli isolates for detection of Fosfomycin resistance and results were compared with reference modified Kirby-Bauer disk diffusion method. RESULTS: Out of total 149 E.coli isolates from 149 urine specimens, 80 were classified as Fosfomycin susceptible and 69 as Fosfomycin resistant by reference disk diffusion method. Sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy of rapid Fosfomycin NP test was found to be 94.2%, 98.75%, 98.48%, 95.2% and 96.64%, respectively. In our study reliable results were achieved after 2.5 hours of incubation. CONCLUSIONS: The rapid Fosfomycin NP test is valid and user-friendly technique which can be performed with minimal technical expertise. It is less time consuming than disk diffusion and Etest strips and easy to perform as compared to agar dilution method. It can be useful as alternative to agar dilution in urinary E.coli isolates which would help in selecting appropriate therapeutic option for UTIs.

Clinical and virological course of SARS-CoV 2 infected patients in a tertiary care hospital in Pakistan.

BACKGROUND: Acute respiratory illness caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) involved the whole globe within no time. Various studies published globally have shown variable severity of disease and mortality. The objective of our study was to describe clinical and epidemiological characteristics of the disease in our setup. METHODS: in this descriptive case series, individuals with signs and symptoms of Coronavirus disease-19 (COVID-19) and asymptomatic patients with history of close contact to confirmed COVID-19 patients were considered for SARS-CoV-2 Polymerase chain reaction (PCR) assay. Epidemiological and clinical features of only PCR positive cases were recorded. Data regarding hospitalization status, exposure to known COVID-19 patients, clinical feature and clinical outcome of patients was collected and interpreted. RESULTS: A total of 266 patients were found to be SARS-CoV 2 PCR positive which were included in the study. Mean age of patients was 39.45±31.9 years and majority of the patients in our study were male, i.e., 238 (89.5%). Most common clinical features among COVID-19 symptomatic patients were fever and dry cough followed by myalgias and sore throat. Eighteen (7%) out of 266 died in our setup. Time duration of viral shedding after initial positive PCR varied between 11 days to up to more than 55 days. CONCLUSION: Coronavirus disease-19 (COVID-19) can present with wide range of clinical spectrum and disease can be life threatening. Severity of disease, requirement of ICU care and mortality were directly related to age of the patient and underlying comorbidities. Rigorous precautionary measures are of utmost importance particularly in this high-risk population.

New Delhi Metallo-Beta-Lactamase Producing Carbapenem-Resistant Gram-Negative Bacilli: Microbiological And Genotypic Analyses At A Tertiary Care Hospital In Pakistan.

BACKGROUND: Metallo-beta-lactamases (MBL) catalyze the hydrolysis of beta-lactam antibiotics including carbapenems. A novel MBL subtype, New Delhi MBL (NDM), poses a serious public health problem. The aims of this study were to determine the frequency of NDM producers among the Carbapenem-resistant gram-negative bacilli (GNB) in hospitalized patients and carrying out the molecular analysis of the NDM genes as reliable data on this is not available in Pakistan. METHODS: We carried out a cross-sectional study on prospectively collected clinical samples from 113 patients hospitalised at Shaikh Zayed Hospital Lahore, Pakistan. All the samples that were carbapenem-resistant on routine sensitivity testing were selected for this study. Various microbiological and genotypic analyses of the samples were performed. RESULTS: The mean age of the patients was 47.8±20.8 years. About a quarter (25.7%) of the samples was from the urology ward and 43% were urine samples. Around two-third of the samples (n=74, 65.5%) tested positive for Non-Enterobacteriaceae GNB. Pseudomonas spp was the most common isolate among the Non-Enterobacteriaceae and E-coli amongst the Enterobacteriaceae. NDM gene was detected in 22 patients (19.5%). We did not find any association of the NDM gene with the demographic and clinical characteristics.. CONCLUSION: NDMpositive GNB are present in our hospitalized patients, which is worrisome as these bacteria can disseminate globally and lead to an extensive and uncontrollable spread of pandemic clones for which efficient antibiotic therapy is currently not available. Systemic surveillance network and infection control strategies should be established to curtail dissemination of NDM-producing GNB in Pakistan.