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Objective: Organophosphorus poisoning (OPP) is a major concern for developing countries. There are no guidelines for the prophylactic use of antibiotics in the management of OPP which in such critical cases might add to the economic burden of the patients as well as antibiotic resistance. We compared the health and economic outcomes in patients prescribed with prophylactic antibiotics with respect to the patients not prescribed with any antibiotics. Methods: A retrospective observational study was carried out for two years for patients admitted to ICU with OPP. Patients were graded for severity of OPP, and divided into two groups based on prophylactic prescription and no prescription of antibiotics. The length of stay (LOS), hospitalization cost and outcomes were measured and compared between the two groups using statistical tests. Results: Out of the 254 patients observed, 108 were prescribed with prophylactic antibiotics and 94 were not prescribed with any antibiotic. There was a significant difference between LOS, cost of treatment and outcomes in the two groups ( p < 0.001). When antibiotics were not prescribed, the odds of improvement was 1.854 times higher compared to those who received prophylactic antibiotics although after adjusting for severity of poisoning, significance was lost. On an average, 2–3 antibiotics were prescribed to every patient in the first group. Conclusion: OPP is an important health concern where issues of antibiotic misuse and overuse are practiced. Our study suggested that systemic antibiotic prophylaxis did not offer any advantage over non-use of any antibiotics in patients with OPP. [ABSTRACT FROM AUTHOR]

Introduction: The increased use of organophosphate (OP) insecticides and the ever increasing possibility of terror groups using nerve agents underscore the need to develop effective and safe antidotes against OP poisoning. While intramuscular administration of nerve gas antidotes like atropine sulphate has certain lacunae, intravenous route is neither practical nor feasible in the field conditions for mass casualties. The objective was to develop a novel atropine sulphate nasal drop formulation, evaluate and characterize it using scintigraphy and to carry out safety–efficacy study in human volunteers with a view to obtain early pharmacological effects in comparison to the existing options, particularly the conventional intramuscular route. Methods: Permeability studies were done using atropine sulphate solution containing variable amount of chitosan. Radiometric method was developed for scintigraphy studies while standard spectroscopy was used for the quantification of atropine sulphate in fluids. Concentration of atropine sulphate in nasal drops to produce therapeutic concentration in blood was calculated. Six volunteers (age range 18–53 years) were administered the formulation delivering 6mg of atropine sulphate each. Bioavailability and atropinization were noted serially. Results: Based on the results of in vitro, human scintigraphy and analytical data, 1% atropine sulphate–0.5% chitosan was chosen as the final nasal formulation. Human bioavailability curve was created which showed that the therapeutic concentration of the drug in blood was reached within 5min with nasal drops suggesting that drug delivery through the nasal route is significantly better than the intramuscular route. Unpaired t-test between the means of baseline value of heart rate and that of each time interval showed that increase in heart rate of all the volunteers became significant at 15min (P <0.01) and extremely significant at 30min (P <0.001). Correlation was evident from 5min (c >0.7). Pupil diameter showed maximal increase at 30min (P <0.01). Conclusions: This novel product, 1% atropine sulphate–0.5% chitosan nasal drops might be a safe and efficacious emergency treatment of organophosphorous poisoning with several advantages over the present management, including early atropinization and capability of mass treatment in least amount of time. [Copyright &y& Elsevier]

Abstract: The aim of the work was to develop, characterize, and carry out a clinical trial with nano–atropine sulfate (nano-AS) dry powder inhaler (DPI), because this route may offer several advantages over the conventional intramuscular route as an emergency treatment, including ease of administration and more rapid bioavailability. Different batches of nanoparticles of AS were produced using variants of nanoprecipitation method. The influence of the process parameters, such as the types and quantity of solvent and nonsolvent, the stirring speed, the solvent-to-nonsolvent volume ratio, and the drug concentration, was investigated. The methodology resulted in optimally sized particles. Bulk properties of the particles made by the chosen methodology were evaluated. A clinical trial was conducted in six healthy individuals using a single DPI capsule containing 6 mg nano-AS DPI in lactose. Early blood bioavailability and atropinization pattern confirmed its value as a potential replacement to parenteral atropine in field conditions. The formulation seems to have the advantage of early therapeutic drug concentration in blood due to absorption through the lungs as well as sustained action due to absorption from the gut of the remaining portion of the drug. [Copyright &y& Elsevier]