Trs Bedi

Open label comparative trial of mono versus dual antibiotic therapy for Typhoid Fever in adults

Background Emerging resistance to antibiotics renders therapy of Typhoid Fever (TF) increasingly challenging. The current single-drug regimens exhibit prolonged fever clearance time (FCT), imposing a great burden on both patients and health systems, and potentially contributing to the development of antibiotic resistance and the chronic carriage of the pathogens. The aim of our study was to assess the efficacy of combining third-generation cephalosporin therapy with azithromycin on the outcomes of TF in patients living in an endemic region. Methods An open-label, comparative trial was conducted at Dhulikhel Hospital, Nepal, between October 2012 and October 2014. Only culture-confirmed TF cases were eligible. Patients were alternately allocated to one of four study arms: hospitalized patients received either intravenous ceftriaxone or a combination of ceftriaxone and oral azithromycin, while outpatients received either oral azithromycin or a combination of oral azithromycin and cefexime. The primary outcome evaluated was FCT and the secondary outcomes included duration of bacteremia. Results 105 blood culture-confirmed patients, of whom 51 were treated as outpatients, were eligible for the study. Of the 88 patients who met the inclusion criteria for FCT analysis 41 patients received a single-agent regimen, while 47 patients received a combined regimen. Results showed that FCT was significantly shorter for the latter (95 versus 88 hours, respectively, p = 0·004), and this effect was exhibited in both the hospitalized and the outpatient sub-groups. Repeat blood cultures, drawn on day 3, were positive for 8/47 (17%) patients after monotherapy, versus 2/51 (4%) after combination therapy (p = 0·045). No severe complications or fatalities occurred in any of the groups. Conclusions Combined therapy of third-generation cephalosporins and azithromycin for TF may surpass monotherapy in terms of FCT and time to elimination of bacteremia. Trial registration Trial registration number: NCT02224040.

The epidemiology of typhoid fever in the Dhulikhel area, Nepal: A prospective cohort study

Introduction Typhoid fever (TF) continues to cause considerable morbidity and mortality in Nepal, but only limited epidemiologic data is available about TF outside Kathmandu. Methods As part of an interventional trial, we performed a prospective cohort study of bacteremic TF patients in Dhulikhel Hospital between October 2012 and October 2014. Demographic, epidemiological, clinical, and microbiologic data were recorded. Results 116 bacteremic typhoid patients were included in the study. Most were young, healthy, adults (mean age 27.9±12 years), 41.4% of whom were female. More than 70% of patients were employed in non-manual services or were university students. Salmonella Typhi accounted for 64/115 (55.7%) of all isolates, while Salmonella Paratyphi accounted for 51/115 (44.3%), of which 42 were Paratyphi A and 9 Paratyphi B. A significant proportion of TF cases occurred also during the dry season (48/116, 41.6%). The clinical presentation of Salmonella Typhi and Paratyphi infections was similar, except for a greater proportion of arthralgia in patients with Salmonella Typhi. Most Salmonella Typhi and Paratyphi isolates were resistant to nalidixic acid and susceptible to older antibiotics. One Salmonella Paratyphi isolate was resistant to ceftriaxone. Conclusions TF remains common in the Dhulikhel area, even among those with a high level of education. Public health measures aimed at reducing the incidence of TF in the Dhulikhel area are warranted. The relative burden of TF caused by Salmonella Paratyphi is rising; a vaccine with activity against Salmonella Paratyphi is needed. Since Salmonella Paratyphi B was more prevalent in this cohort than in large cohorts of patients from Kathmandu, it is likely that there are significant regional variations in the epidemiology of TF outside Kathmandu.

Role of tiotropium in chronic obstructive pulmonary disease exacerbation

Introduction : Chronic obstructive pulmonary disease (COPD) remains a major public health problem. Many patients suffering from chronic obstructive lungs diseases are of poor economic status, mostly illiterate, therefore has a direct bearing on patient compliance. Tiotropium is a new anticholinergic therapy for chronic obstructive pulmonary disease that differs from ipratropium by its functional relative selectively for musarinic receptor subtypes and which allows single dosing a day. This study presents a cost-effectiveness, efficacy, and side-effects of Ipratropium bromide and Tiotropium in COPD. Methods : Prospective study was conducted In Kathmandu University Teaching Hospital, between the year 2008 and 2009 in terms of cost-effectiveness, efficacy, and side-effects of Tiotropium and Ipratropium amongst COPD patients. Results : Tiotropium and Ipratropium were prescribed in total of 57 patients (30 in ipratropium bromide and 27 in tiotropium bromide) for the management of COPD among outpatients. There were no significant differences in age, height, weight and baseline lung function parameters (FEV1 and PEF) between the two drugs i.e. ipratropium bromide and tiotropium bromide. Significant improvement in lung function parameters were found in each respective group of drugs after bronchodilator therapy. Tiotropium results in significant reduction of Chronic Obstructive Pulmonary disease exacerbations and significant improvement in quality of life, lung function, and dyspnoea compared to ipratropium. The additional cost to achieve these favorable outcomes was cheaper than Ipratropium bromide. (Nepalese Rs. 7.03 per day for tiotropium as compared to Rs. 9.06 for Ipratropium) Conclusions : Tiotropium results in significant reduction of chronic obstructive pulmonary disease exacerbations and significant improvement in quality of life, lung function and dyspnoea compared to Ipratropium. Keywords: Chronic obstructive pulmonary disease; ipratropium; tiotropium DOI: http://dx.doi.org/10.3126/joim.v32i2.4937 Journal of Institute of Medicine , August, 2010; 32: 5-10