Single ascending dose safety, tolerability, and pharmacokinetic study of econazole in healthy volunteers.

INTRODUCTION: Econazole has been found efficacious as antitubercular in in vitro and in vivo animal studies. However, limited information is available for its safety and pharmacokinetics in humans. In our present study we have conducted single ascending dose, safety, and pharmacokinetic evaluation in healthy human volunteers with the purpose of enabling translation for tuberculosis. METHODS: This study was conducted as a single-center, ascending-dose, placebo-controlled, double blind design. Three ascending dose were chosen (250 , 500 , and 1000 mg) to be administered as a single oral dose. The volunteers were screened for potential eligibility. Participants were randomized to receive either Econazole or Placebo in a 6:2 design. Safety assessments and pharmacokinetic evaluations were carried out for each cohort. RESULTS: Econazole was found to be safe at all dose levels. No serious or severe adverse events occurred during the study. The AUC (0-∞) showed a response relationship with a value of 49 ± 3.47 h* µg/ml, 17. 86 ± 8.40 hr* µg/ml, 35.54 ± 13.94 hr* µg/ml for 250 mg, 500 mg, and 1000 mg, respectively. CONCLUSION: Based on the findings of our study, a dose of 500 mg Econazole, once a day orally was considered as appropriate for further evaluation.

A multicentre point prevalence survey (PPS) of antimicrobial use amongst admitted patients in tertiary care centres in India.

OBJECTIVES: Data from point prevalence surveys (PPSs) in India are scarce. Conducting PPSs is especially challenging in the absence of electronic medical records, a lack of dedicated resources and a high patient load in resource-poor settings. This multicentre survey was conducted to provide background data for planning and strengthening antimicrobial stewardship programmes across the country. METHODS: This inpatient PPS was conducted over 2 weeks in May 2019 simultaneously across five study centres in India. Data about patient characteristics, indications for antimicrobials use and details of each antimicrobial prescribed including supportive investigation reports were collected in predesigned forms. RESULTS: A total of 3473 admitted patients in wards and ICUs were covered across five study centres. Of these, 1747 (50.3%) patients were on antimicrobials, with 46.9% patients being on two or more antimicrobials. Out of the total antimicrobials prescribed, 40.2% of the antimicrobials were prescribed for community-acquired infection requiring hospitalization followed by surgical prophylaxis (32.6%). Third-generation cephalosporins and drugs from the 'Watch' category were prescribed most commonly. Only 22.8% of the antimicrobials were based on microbiology reports. CONCLUSIONS: The survey demonstrated a high use of antimicrobials in admitted patients with a considerable proportion of drugs from the 'Watch' category. The targets for interventions that emerged from the survey were: improving surgical prophylaxis, decreasing double anaerobic cover, initiating culture of sending cultures and de-escalation with targeted therapy.

Assessment of Appropriateness of Antimicrobial Therapy in Resource-Constrained Settings: Development and Piloting of a Novel Tool-AmRAT.

Inappropriate antimicrobial prescribing is considered to be the leading cause of high burden of antimicrobial resistance (AMR) in resource-constrained lower- and middle-income countries. Under its global action plan, the World Health Organization has envisaged tackling the AMR threat through promotion of rational antibiotic use among prescribers. Given the lack of consensus definitions and other associated challenges, we sought to devise and validate an Antimicrobial Rationality Assessment Tool-AmRAT-for standardizing the assessment of appropriateness of antimicrobial prescribing. A consensus algorithm was developed by a multidisciplinary team consisting of intensivists, internal medicine practitioners, clinical pharmacologists, and infectious disease experts. The tool was piloted by 10 raters belonging to three groups of antimicrobial stewardship (AMS) personnel: Master of Pharmacology (M.Sc.) (n = 3, group A), Doctor of Medicine (MD) residents (n = 3, group B), and DM residents in clinical pharmacology (n = 4, group C) using retrospective patient data from 30 audit and feedback forms collected as part of an existing AMS program. Percentage agreement and the kappa (κ) coefficients were used to measure inter-rater agreements amongst themselves and with expert opinion. Sensitivity and specificity estimates were analyzed comparing their assessments against the gold standard. For the overall assessment of rationality, the mean percent agreement with experts was 76.7% for group A, 68.9% for group B, and 77.5% for group C. The kappa values indicated moderate agreement for all raters in group A (κ 0.47-0.57), and fair to moderate in group B (κ 0.22-0.46) as well as group C (κ 0.37-0.60). Sensitivity and specificity for the same were 80% and 68.6%, respectively. Though evaluated by raters with diverse educational background and variable AMS experience in this pilot study, our tool demonstrated high percent agreement and good sensitivity and specificity, assuring confidence in its utility for assessing appropriateness of antimicrobial prescriptions in resource-constrained healthcare environments.

Impact of an antimicrobial stewardship and monitoring of infection control bundle in a surgical intensive care unit of a tertiary-care hospital in India.

OBJECTIVES: Antimicrobial stewardship (AMS) in resource-limited settings lacks models that can be readily adapted to their settings. Here we discuss the impact of a combined strategy of AMS and monitoring of infection control practices in a tertiary-care centre of a developing country. METHODS: This study was undertaken in the surgical unit of a tertiary-care hospital over an 8-month period. In the first 2 months (baseline phase), prospective audit and feedback alone was undertaken, while in the next 6 months (intervention phase) this was supplemented with strategies such as antimicrobial timeout, correction of doses and bundle approach for prevention of hospital-acquired infections. RESULTS: A total of 337 patients were included (94 in the baseline phase and 243 in the intervention phase). There was a decrease in days of therapy per 1000 patient-days (1000PD) (1112.3 days vs. 1048.6 days), length of therapy per 1000PD (956 days vs. 936.3 days) and defined daily doses (DDD) per 1000PD for most antimicrobials. A decrease in double cover for Gram-negative infections (9.6% vs. 2.9%) but an increase in double anaerobic cover (4.2% vs. 7.4%) was observed. There was a decrease in the incidence of ventilator-associated pneumonia per 1000 ventilator-days in the intervention phase (46.4 vs. 35.4), whereas central line-associated bloodstream infections per 1000 central line-days remained the same (14.7 vs. 14.8). CONCLUSION: This study shows that implementation of routine AMS activities with monitoring of infection control practices can help decrease overall antimicrobial use. With furtherance of measures to control infection, antimicrobial use may be further curtailed.

Effect of drugs modulating serotonergic system on the analgesic action of paracetamol in mice.

OBJECTIVE: The underlying mechanisms for the analgesic action of paracetamol (PCT) are still under considerable debate. It has been recently proposed that PCT may act by modulating the Serotonin system. This study was conducted to verify the influence of Serotonin modulating drugs (buspirone, ondansetron, and fluoxetine) on the analgesic effect of PCT. MATERIALS AND METHODS: Thirty adult albino mice were assigned to five groups: Normal saline, PCT, fluoxetine selective serotonin reuptake inhibitor (SSRI) + PCT, buspirone (5-HT1A Agonist) + PCT, and ondansetron (5HT3 antagonist) + PCT. Hot-plate and formalin test were used to determine pain threshold, tests being conducted 60 min after the last treatment. Statistical analysis was done using analysis of variance followed by Dunnet's test. RESULTS: Coadministration of buspirone with PCT attenuated the antinociceptive activity of PCT (P < 0.001), whereas fluoxetine + PCT increased pain threshold in the hot-plate and formalin test (P = 0.0046). Analgesic effect of PCT was not affected by ondansetron in formalin models. It attenuated analgesic action of PCT in hot-plate test (P = 0.0137). CONCLUSION: The results suggest that 5-HT1 receptors could also be responsible for the analgesic effect of PCT. Also, higher analgesia is produced by co-administration of SSRI (fluoxetine) + PCT.

Antibiotic Prescribing Pattern in a Tertiary Level Neonatal Intensive Care Unit.

INTRODUCTION: Neonatal sepsis is a major cause of morbidity and mortality worldwide especially in developing countries, which justifies early diagnosis and prompt treatment with antibiotics. Antibiotics are the most frequently used medicines in Neonatal Intensive care units. Data regarding rational antibiotic use in neonates is very limited. Hence, it is essential that the antibiotic prescribing patterns be evaluated periodically for its rational use. Therefore, the present study been carried out to identify the prescribing patterns of antibiotics in neonatal intensive care unit of a tertiary care hospital, Western Maharashtra, India. MATERIALS AND METHODS: A prospective observational study was carried out for 6 months between April to September 2014. The data regarding patient demographics and antibiotic use was collected daily in a structured proforma. Collected data was subjected to statistical analysis. RESULTS: Out of total 528 neonates with male preponderance (62%), 370 received antibiotics. Mean gestational age and birth weight were 35±3.2 weeks and 2±0.7 kg respectively. Mean length of hospital stay was 14.26±15.36 days (range 1 to 136 days). A total of 1123 antibiotics were prescribed to 370 neonates. The majority of neonates (55.9%) received between 1-2 antibiotics, 37.3% had 3 to 5 antibiotics prescribed, while 6.7% neonates were prescribed more than 5 antibiotics. Number of antibiotics used had statistically significant inverse relationship with gestational age. Among antibiotics; Amikacin, Cefotaxime and Levofloxacin were the drugs most often prescribed. Amikacin and Cefotaxime were given more to term infants whereas other antibiotics like Levofloxacin, Pipercillin- tazobactam and Meropenem were prescribed more to preterm and outborn neonates. CONCLUSION: The use of a high number of antibiotics is a common practice. Although the indications for use of most antibiotics could be justified, the increased frequency of anbiotics use in some neonates was of concern. Guidelines for the use of antibiotics in neonates are required and larger studies are needed on this issue.

Effect of previous scorpion bite(s) on the action of intrathecal bupivacaine: A case control study.

BACKGROUND: During the routine practice in the institution, it was observed that there were persistent incidents of inadequate/failed spinal anaesthesia in patients with a history of single or multiple scorpion bite/s. To test any possible correlation between scorpion bite and the altered response to spinal anaesthesia, a case control study was conducted involving patients with a history of scorpion bite/s and without such a history. METHODS: Randomly selected 70 (n=70) patients of either sex and age range of 18-80 years, were divided into two equal groups, giving past history of one or multiple scorpion bites and giving no such a history. The anaesthetic management was identical inclusive of subarachnoid block with 3.5 ml. 0.5% bupivacaine heavy. The onsets of sensory, motor and peaks of sensory and motor blocks were observed with the pin-prick method and Bromage scale. After waiting for 20 min, if the block was inadequate, then balanced general anaesthesia was administered. The analysis of the data and application of various statistical tests was carried out using Chi-square test, percentages, independent sample t-test and paired t-test. RESULTS: Demographically both groups were comparable. In scorpion bite group, the time of onsets of both sensory and motor blocks and time for the peak of sensory and motor blocks were significantly prolonged, 4 patients had failed/inadequate sensory block and 5 patients had failed/inadequate motor block while all the patients in non-bite group had adequate intra-operative block. CONCLUSION: We conclude that there appears to be a direct correlation between the histories of old, single or multiple scorpion bites and development of resistance to effect of local anaesthetics administered intra-thecally.