Ceftazidime-avibactam alone or in combination with Aztreonam versus Polymyxins in the management of carbapenem-Resistant Klebsiella pneumoniae nosocomial Infections (CAPRI study): a retrospective cohort study from South India.

INTRODUCTION: Carbapenem-resistant Klebsiella pneumoniae (CRKP) infections commonly cause hospital-acquired infections. The study aimed to compare the outcomes of CRKP infections between patients receiving ceftazidime avibactam +/- aztreonam and polymyxins in a hospital setting with a high prevalence of New Delhi Metallo Beta Lactamase production. METHODS: We conducted a retrospective cohort study from January 2020 to September 2022 in critically ill adult patients admitted to a non-COVID-19 medical intensive care unit with CRKP infection. The patients were followed up for a total of 30 days or death, whichever was later. RESULTS: Of a total of 106 patients included in the study, 65 patients received polymyxins and 41 patients received ceftazidime-avibactam +/- aztreonam. Higher 30-day mortality was noted in the polymyxin group (56.9% vs. 29.2%, P = 0.005). The mean time to event (mortality) in ceftazidime-avibactam +/- aztreonam was 23.9 + 1.5 days which was significantly higher compared to polymyxins (17.9 + 1.2 days, p = 0.006). On Cox regression analysis, after adjusting for the covariates, the hazard ratio for time to event with the use of polymyxin was 2.02 (95% CI: 1.03-3.9). CONCLUSION: Ceftazidime-avibactam + aztreonam is possibly associated with better clinical outcomes in patients infected with CRKP.

Successful Use of Cefepime-Zidebactam (WCK 5222) as a Salvage Therapy for the Treatment of Disseminated Extensively Drug-Resistant New Delhi Metallo-ß-Lactamase-Producing Pseudomonas aeruginosa Infection in an Adult Patient with Acute T-Cell Leukemia.

With limited and often toxic treatment options, carbapenem-resistant Gram-negative infections are associated with significant mortality. Cefepime-zidebactam is a promising antibiotic option undergoing a phase 3 trial that has activity against diverse antibiotic-resistant mechanisms in Gram-negative pathogens due to its ß-lactam enhancer mechanism, mediating multiple PBP binding. We report a case of disseminated infection caused by a New Delhi metallo-ß-lactamase-producing, extensively drug-resistant Pseudomonas aeruginosa isolate in a patient with acute T-cell leukemia, successfully managed with cefepime-zidebactam as a salvage therapy.

A Randomized, Double-blinded, Controlled, Multicentre Phase III Study to Evaluate the Efficacy and Safety of Telmisartan /Amlodipine/Hydrochlorothiazide Compared to Telmisartan/Hydrochlorothiazide in Patients with Essential Hypertension.

OBJECTIVE: Triple drug combination has shown to be effective in controlling blood pressure (BP) with low rates of drug-related side effects. The present study was conducted to compare the efficacy and safety of a triple pill of telmisartan/amlodipine/hydrochlorothiazide (HCTZ) with a dual combination of telmisartan/HCTZ in treating hypertensive patients who did not respond to monotherapies. METHODS: A total of 512 patients were randomized to receive either low-dose triple pill or the dual combination therapy. The primary endpoint was BP normalization after 8 weeks. The secondary endpoints were BP normalization at 4 weeks, changes in BP from baseline to Week 8, comparison of BP normalization between treatment groups, and difference in BP responder rates. The analysis was conducted on the intent-to-treat (ITT), modified intent-to-treat (mITT) and per protocol (PP) population. RESULTS: Statistically significant difference was noted between triple pill and telmi+HCTZ in the normalization of BP at Week 8 in the mITT (p=0.041) and PP (p=0. 038) populations. Also, a statistically significant improvement was observed in BP normalization in triple pill group compared with telmi+HCTZ group in ITT (p=0.022) and mITT (p=0.015) populations after 4 weeks. At Week 8, a significant reduction in BP was seen compared to the baseline in both the treatment groups. There was no statistically significant difference between the two treatment groups in BP normalization. Diastolic BP responder rates were significantly better for triple pill group in PP population (p=0.046). CONCLUSIONS: The triple pill was found to be effective in achieving early normalization of BP in hypertensive patients who did not respond to monotherapies.

Lower Vitamin D Metabolites Levels Were Associated With Increased Coronary Artery Diseases in Type 2 Diabetes Patients in India.

The purpose of the present study was to measure six vitamin D metabolites and to find the association between vitamin D deficiency and coronary artery diseases in diabetes (T2DM_CAD). Four groups [control (n = 50), type 2 diabetes (T2DM, n = 71), coronary artery diseases (CAD, n = 28), T2DM_CAD (n = 38)] of total 187 subjects were included in the study. Six vitamin D metabolites (D2, D3, 25(OH)D2, 25(OH)D3, 1,25(OH)2D2, 1,25(OH)2D3), total 25(OH)D and total 1,25(OH)2D were measured by UPLC/APCI/HRMS method in these subjects. Although all the vitamin D metabolites were significantly decreased in T2DM_CAD as compared to both control and T2DM subjects (p < 0.05), only two metabolites i.e., 25(OH)D3 and total 25(OH)D were significantly (p < 0.05) decreased in the T2DM subjects as compared with the control subjects (p < 0.05). Vitamin D3, 1,25(OH)2D2, 25(OH)D, and 1,25(OH)2D levels were significantly decreased in T2DM_CAD subjects as compared with CAD subjects (p < 0.05). Further, multiple logistic regression analysis revealed that total 25(OH)D and total 1,25(OH)2D can be used to predict T2DM (OR 0.82.95% CI 0.68-0.99; p = 0.0208) and T2DM with CAD (OR 0.460, 95% CI 0.242-0.874; p = 0.0177), respectively. Our data concludes that lower concentration of 1,25(OH)2D is associated with type 2 diabetes coexisting with coronary artery diseases in South Indian subjects.

Hyperglycaemia enhances nitric oxide production in diabetes: a study from South Indian patients.

BACKGROUND: We have previously reported that increased glucose levels were associated with higher serum nitric oxide (NO) levels in fructose-fed insulin resistant rats. However, the relationship between hyperglycemia and serum NO level was not clear. Therefore, the present study was designed to find the association between hyperglycemia and serum NO levels in Type 2 diabetic (T2DM) patients and T2DM with cardiovascular complication. METHODS: Endothelial cells (HUVEC) were treated with of D-glucose (10-100mM), and NO levels and NOS gene expression was measured. Hyperglycaemia was induced in Sprague-Dawley rats, and serum NO levels were measured after 8 weeks. For clinical evaluation, five groups of patients were recruited: Control (CT, n=48), Type 2 diabetes (T2DM, n=26), T2DM with hypertension (DMHT, n=46), Coronary artery diseases (CAD, n=29) and T2DM with coronary artery diseases (DMCD, n=38). NO (nitrite + nitrate) levels were measured from human serum. RESULTS: We found a significant (p<0.05) and dose-dependent increase in NO levels in HUVEC cells after 4 hours of high glucose exposure. eNOS and iNOS gene expression was increased in HUVEC cells after different concentrations and time periods of glucose treatment. We also observed significant (149.1 ± 25 µM, p<0.01) increase in serum NO levels in hyperglycaemic rats compared to control (76.6 ± 13.2 µM). Serum NO level was significantly higher in T2DM (111.8 µM (81.7-122.4), p<0.001) and DMCD patients ((129.4 µM (121.2-143.5), p <0.001) but not in CAD patients (76.4 µM (70.5-87)), as compared to control (68.2 µM (56.4-82.3)). We found significantly lower NO levels (83.5 µM (60.5-122.9)) in subjects suffering from diabetes since more than 5 years, compared to subjects (115.3 µM (75.2-127.1), p<0.001) with less than 5 years. CONCLUSION: In conclusion, high NO levels were observed in South Indian diabetic patients. Higher glucose levels in serum might be responsible for activation of endothelial cells to enhance NO levels.