Perspectives of pharmacy employees on an inappropriate use of antimicrobials in Kathmandu, Nepal.

BACKGROUND: Unregulated antimicrobial use is common in both hospital and community settings of low- and middle-income countries (LMICs). However, discrete data regarding the use/misuse of antimicrobials at pharmacies in LMICs are limited. This study was conducted to understand knowledge, attitude, and practice of pharmacy employees on antimicrobial dispensing in Nepal. METHODS: We conducted a cross-sectional survey using a structured questionnaire on 801 pharmacy employees working in community and hospital pharmacies located in Lalitpur metropolitan city (LMC) of Kathmandu, Nepal between April 2017 and March 2019. RESULTS: A majority (92%) of respondents agreed that demand for non-prescription antimicrobials was common. Asking for prescription before dispensing was ranked as the first preference by majority (69%) of participants. Suspected respiratory tract infection was the most common reason demanding for non-prescription antimicrobials with the highest mean rank of 1.5. Azithromycin was the most commonly prescribed and sold antimicrobial, as reported by 46% and 48% of participants respectively. A majority (87%) of respondents agreed on antimicrobial resistance (AMR) to be a global public health threat; and misuse/overuse of antimicrobials was perceived as the most common cause of AMR with a mean rank of 1.93. CONCLUSION: Our study revealed that unfounded dispensing and use of antimicrobials is prevalent among pharmacies in Kathmandu, Nepal. This over reliance on antimicrobials, notably azithromycin, may escalate burden of AMR. We identified several drivers of inappropriate antimicrobial dispensing practice in pharmacies, which will aid public health authorities in addressing these issues. Further studies considering role of other stakeholders, such as doctors, veterinarians, general public, and policy makers are required to obtain a more holistic perspectives on practices of antimicrobial use so to curb the extant AMR crisis.

Epidemiology, etiology, and diagnosis of health care acquired pneumonia including ventilator-associated pneumonia in Nepal.

Epidemiologic data regarding health care acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP) from Nepal are negligible. We conducted a prospective observational cohort study in the intensive care unit (ICU) of a major tertiary hospital in Nepal between April 2016 and March 2018, to calculate the incidence of VAP, and to describe clinical variables, microbiological etiology, and outcomes. Four hundred and thirty-eight patients were enrolled in the study. Demographic data, medical history, antimicrobial administration record, chest X-ray, biochemical, microbiological and haematological results, acute physiology and chronic health evaluation II score and the sequential organ failure assessment scores were recorded. Categorical variables were expressed as count and percentage and analyzed using the Fisher's exact test. Continuous variables were expressed as median and interquartile range and analyzed using Kruskal-Wallis rank sum test and the pairwise Wilcoxon rank-sum test. 46.8% (205/438) of the patients required intubation. Pneumonia was common in both intubated (94.14%; 193/205) and non-intubated (52.36%; 122/233) patients. Pneumonia developed among intubated patients in the ICU had longer days of stay in the ICU (median of 10, IQR 5-15, P< 0.001) when compared to non-intubated patients with pneumonia (median of 4, IQR 3-6, P< 0.001). The incidence rate of VAP was 20% (41/205) and incidence density was 16.45 cases per 1,000ventilator days. Mortality was significantly higher in patients with pneumonia requiring intubation (44.6%, 86/193) than patients with pneumonia not requiring intubation (10.7%, 13/122, p<0.001, Fisher's exact test). Gram negative bacteria such as Klebsiella and Acinetobacter species were the dominant organisms from both VAP and non-VAP categories. Multi-drug resistance was highly prevalent in bacterial isolates associated with VAP (90%; 99/110) and non-VAP categories (81.5%; 106/130). HAP including VAP remains to be the most prevalent hospital-acquired infections (HAIs) at Patan hospital. A local study of etiological agents and outcomes of HAP and VAP are required for setting more appropriate guidelines for management of such diseases.

Risk factors for the development of neonatal sepsis in a neonatal intensive care unit of a tertiary care hospital of Nepal.

BACKGROUND: Sepsis is an overwhelming and life-threatening response to bacteria in bloodstream and a major cause of neonatal morbidity and mortality. Understanding the etiology and potential risk factors for neonatal sepsis is urgently required, particularly in low-income countries where burden of infection is high and its epidemiology is poorly understood. METHODS: A prospective observational cohort study was conducted between April 2016 and October 2017 in a level three NICU at a tertiary care hospital in Nepal to determine the bacterial etiology and potential risk factors for neonatal sepsis. RESULTS: Among 142 NICU admitted neonates, 15% (21/142) and 32% (46/142) developed blood culture-positive and -negative neonatal sepsis respectively. Klebsiella pneumoniae (34%, 15/44) and Enterobacter spp. (25%, 11/44) were the most common isolates. The antimicrobial resistance of isolates to ampicillin (100%, 43/43), cefotaxime (74%, 31/42) and ampicillin-sulbactam (55%, 21/38) were the highest. BlaTEM (53%, 18/34) and blaKPC (46%, 13/28) were the commonest ESBL and carbapenemase genes respectively. In univariate logistic regression, the odds of sepsis increased with each additional day of use of invasive procedures such as mechanical ventilation (OR 1.086, 95% CI 1.008-1.170), umbilical artery catheter (OR 1.375, 95% CI 1.049-1.803), intravenous cannula (OR 1.140, 95% CI 1.062-1.225); blood transfusion events (OR 3.084, 95% CI 1.407-6.760); NICU stay (OR 1.109, 95% CI 1.040-1.182) and failure to breast feed (OR 1.130, 95% CI 1.060-1.205). Sepsis odds also increased with leukopenia (OR 1.790, 95% CI 1.04-3.082), increase in C-reactive protein (OR 1.028, 95% CI 1.016-1.040) and decrease in platelets count (OR 0.992, 95% CI 0.989-0.994). In multivariate analysis, increase in IV cannula insertion days (OR 1.147, 95% CI 1.039-1.267) and CRP level (OR 1.028, 95% CI 1.008-1.049) increased the odds of sepsis. CONCLUSIONS: Our study indicated various nosocomial risk factors and underscored the need to improve local infection control measures so as to reduce the existing burden of sepsis. We have highlighted certain sepsis associated laboratory parameters along with identification of antimicrobial resistance genes, which can guide for early and better therapeutic management of sepsis. These findings could be extrapolated to other low-income settings within the region.

Azithromycin and cefixime combination versus azithromycin alone for the out-patient treatment of clinically suspected or confirmed uncomplicated typhoid fever in South Asia: a randomised controlled trial protocol.

Background: Typhoid and paratyphoid fever (enteric fever) is a common cause of non-specific febrile infection in adults and children presenting to health care facilities in low resource settings such as the South Asia.  A 7-day course of a single oral antimicrobial such as ciprofloxacin, cefixime or azithromycin is commonly used for its treatment. Increasing antimicrobial resistance threatens the effectiveness of these treatment choices. We hypothesize that combined treatment with azithromycin (active mainly intracellularly) and cefixime (active mainly extracellularly) will be a better option for the treatment of typhoid fever in South Asia. Methods: This is a phase IV, international multi-centre, multi-country, comparative participant-and observer-blind, 1:1 randomised clinical trial. Patients with suspected uncomplicated typhoid fever will be randomised to one of the two interventions: Arm A: azithromycin 20mg/kg/day oral dose once daily (maximum 1gm/day) and cefixime 20mg/kg/day oral dose in two divided doses (maximum 400mg bd) for 7 days, Arm B: azithromycin 20mg/kg/day oral dose once daily (max 1gm/day) for 7 days AND cefixime-matched placebo for 7 days. We will recruit 1500 patients across sites in Bangladesh, India, Nepal and Pakistan. We will assess whether treatment outcomes are better with the combination after one week of treatment and at one- and three-months follow-up. Discussion: Combined treatment may limit the emergence of resistance if one of the components is active against resistant sub-populations not covered by the other antimicrobial's activity. If the combined treatment is better than the single antimicrobial treatment, this will be an important result for patients across South Asia and other typhoid endemic areas. Clinicaltrials.gov registration: NCT04349826 (16/04/2020).

A high prevalence of multi-drug resistant Gram-negative bacilli in a Nepali tertiary care hospital and associated widespread distribution of Extended-Spectrum Beta-Lactamase (ESBL) and carbapenemase-encoding genes.

BACKGROUND: Multi-drug resistance (MDR) and extensive-drug resistance (XDR) associated with extended-spectrum beta-lactamases (ESBLs) and carbapenemases in Gram-negative bacteria are global public health concerns. Data on circulating antimicrobial resistance (AMR) genes in Gram-negative bacteria and their correlation with MDR and ESBL phenotypes from Nepal is scarce. METHODS: A retrospective study was performed investigating the distribution of ESBL and carbapenemase genes and their potential association with ESBL and MDR phenotypes in E. coli, Klebsiella spp., Enterobacter spp. and Acinetobacter spp. isolated in a major tertiary hospital in Kathmandu, Nepal, between 2012 and 2018. RESULTS: During this period, the hospital isolated 719 E. coli, 532 Klebsiella spp., 520 Enterobacter spp. and 382 Acinetobacter spp.; 1955/2153 (90.1%) of isolates were MDR and half (1080/2153) were ESBL producers. Upon PCR amplification, blaTEM (1281/1771; 72%), blaCTXM-1 (930/1771; 53%) and blaCTXM-8 (419/1771; 24%) were the most prevalent ESBL genes in the enteric bacilli. BlaOXA and blaOXA-51 were the most common blaOXA family genes in the enteric bacilli (918/1771; 25%) and Acinetobacter spp. (218/382; 57%) respectively. Sixteen percent (342/2153) of all isolates and 20% (357/1771) of enteric bacilli harboured blaNDM-1 and blaKPC carbapenemase genes respectively. Of enteric bacilli, Enterobacter spp. was the most frequently positive for blaKPC gene (201/337; 60%). The presence of each blaCTX-M and blaOXA were significantly associated with non-susceptibility to third generation cephalosporins (OR 14.7, p < 0.001 and OR 2.3, p < 0.05, respectively).The presence of each blaTEM, blaCTXM and blaOXA family genes were significantly associated with ESBL positivity (OR 2.96, p < 0.001; OR 14.2, p < 0.001 and OR 1.3, p < 0.05 respectively) and being MDR (OR 1.96, p < 0.001; OR 5.9, p < 0.001 and OR 2.3, p < 0.001 respectively). CONCLUSIONS: This study documents an alarming level of AMR with high prevalence of MDR ESBL- and carbapenemase-positive ESKAPE microorganisms in our clinical setting. These data suggest a scenario where the clinical management of infected patients is increasingly difficult and requires the use of last-resort antimicrobials, which in turn is likely to intensify the magnitude of global AMR crisis.

Causes of visual impairment and blindness in children in three ecological regions of Nepal: Nepal Pediatric Ocular Diseases Study.

PURPOSE: To study the causes of blindness and visual impairment in children in three ecologically diverse regions of Nepal. MATERIALS AND METHODS: This is a baseline survey report of a 3-year longitudinal population-based study. One district each from the three ecological regions - Terai, Hills, and Mountains - was selected for the study. Village Development Committees from each district were selected by random sampling. Three community health workers were given training on vision screening and identification of abnormal ocular conditions in children. Health workers who examined children and collected data using pretested questionnaire performed house-to-house surveys. Children with abnormal vision or ocular conditions were referred to and examined by pediatric ophthalmologists. RESULTS: A total of 10,950 children aged 0-10 years, 5,403 from Terai, 3,204 from Hills, and 2,343 from Mountains, were enrolled in the study. Of them, 681 (6.2%) were nonresponders. The ratio of boys to girls was 1.03:1. Prevalence of blindness was 0.068% (95% confidence interval [CI] 0.02%-0.12%) and visual impairment was 0.097% (95% CI 0.04%-0.15%). Blindness was relatively more prevalent in Terai region (0.08%, 95% CI 0.02%-0.13%). The most common cause of blindness was amblyopia (42.9%) followed by congenital cataract. Corneal opacity (39%) was the most common cause of unilateral blindness. CONCLUSION: More than two-thirds of the causes that lead to blindness and visual impairment were potentially preventable. Further, nutritional and genetic studies are needed to determine the factors associated with ocular morbidity and blindness in these regions.

Factors associated with childhood ocular morbidity and blindness in three ecological regions of Nepal: Nepal pediatric ocular disease study.

BACKGROUND: Nepal Pediatric Ocular Diseases Study is a three year longitudinal population based study. Here we present the baseline survey report which aims to investigate various risk factors associated with childhood ocular morbidity and blindness in three ecological regions of Nepal. METHOD: This baseline survey is a population based cross sectional study. The investigation was conducted in a district from each of the following regions: Terai, Hill and Mountain. The Village Development Committees (VDCs) from each district were selected by random sampling. Three Community health workers were given training on vision screening and identification of abnormal ocular signs in children. They conducted a house to house survey in their respected districts examining the children and gathering a standardized set of data variables. Children with abnormal vision or ocular signs were then further examined by pediatric ophthalmologists. RESULTS: A total of 10950 children aged 0-10 years (5403 from Terai, 3204 from the hills, 2343 from the mountains) were enrolled in the study. However 681 (6.2%) were non responders. The male to female ratio was 1.03. The overall prevalence of ocular morbidity was 3.7% (95% CI of 3.4%-4%) and blindness was 0.07% (95% CI of 0.02%-0.12%). Ocular morbidity was more prevalent in the mountain region whereas blindness was more prevalent in the Terai region.Children from the Terai region were more likely to suffer from congenital ocular anomalies compared to the other regions. Children whose mother smoked, drank alcohol, or was illiterate were significantly afflicted with ocular diseases (p < 0.05). In addition,a higher prevalence of ocular disease was related to children with past medical history of systemic illnesses, abnormal postnatal period or missing childhood vaccinations. Blindness was more prevalent in children who suffered from a systemic illness. Females and under-nourished children were more likely to have ocular morbidity and blindness. CONCLUSION: It was found that childhood blindness was more prevalent in the Terai region, the undernourished, females and in those with co-morbid systemic illnesses. This study strongly suggests that prevention of childhood blindness requires additional resources to address these disparity.

Health literacy of common ocular diseases in Nepal.

BACKGROUND: Poor health literacy is often a key cause of lack of or delayed uptake of health care services. The aim of this study was to assess the health literacy of common ocular diseases, namely cataract, glaucoma, night blindness, trachoma and diabetic retinopathy in Nepal. METHODS: A cross sectional study of 1741 participants randomly selected from non-triaged attendants in the outpatient queue at Tilganga Institute of Ophthalmology, a semi urban general population of Bhaktapur district of Kathmandu Valley and patients attending rural outreach clinics. Participants responded to trained enumerators using verbally administered, semi structured questionnaires on their awareness and knowledge of cataract, glaucoma, diabetic retinopathy, night blindness, and trachoma. RESULTS: The awareness of cataract across the entire sample was 49.6%, night blindness was 48.3%, diabetic retinopathy was 29%, glaucoma was 21.3% and trachoma was 6.1%. Patients presenting to rural outreach clinics had poorer awareness of cataract, glaucoma, diabetic retinopathy, night blindness and trachoma compared to those from a semi-urban community and an urban eye hospital (p<0.05), Old age was directly associated with poorer awareness of cataract, glaucoma, night blindness, trachoma and diabetic retinopathy (p<0.05). Female gender was associated with lower awareness of cataract, glaucoma, night blindness and trachoma (p<0.05). Literacy was associated with greater awareness of cataract, glaucoma, diabetic retinopathy, night blindness and trachoma (p<0.05). Higher education was significantly associated with greater awareness of cataract, night blindness and trachoma (p<0.05). Multivariate analysis found that the awareness of common ocular diseases was significantly associated with level of education (p<0.05). Similarly, awareness of cataract, glaucoma, trachoma and night blindness was associated with female gender (p<0.05) whereas awareness of cataract, night blindness, trachoma and diabetic retinopathy was associated with age (p<0.05) but the awareness glaucoma and diabetic retinopathy was associated with camps. CONCLUSIONS: Low awareness of common ocular conditions is associated with factors such as female gender, old age, lower levels of education and rural habitation. A would be successful health promotion programs should specifically target health determinants to promote health literacy and to ensure timely utilization of eye care services.

Intravitreal bevacizumab in macular edema secondary to branch retinal vein occlusion: 12-month results.

PURPOSE: The purpose of this study was to evaluate the long-term safety, anatomical, and visual outcomes following intravitreal bevacizumab (Avastin; Genentech) on macular edema (ME) secondary to branch retinal vein occlusion (BRVO). METHODS: A prospective, interventional case series study was conducted among patients with ME due to BRVO, from June 2008 to October 2011. Intravitreal bevacizumab (1.25 mg/0.05 mL) was given at 4-6 weekly intervals until the ME subsided, and cases were followed up for a year. Complete ophthalmic evaluations and measurement of central retinal thickness (CRT) by optical coherence tomography were performed at baseline and follow-up visits. RESULTS: Sixty-three eyes of 63 patients were included in the study. The mean age was 58.22 years (standard deviation [SD], 12.3). The CRT at baseline was 515.3 ± 189.4 µm, and it significantly improved at each follow-up, with a CRT of 233.6 ± 101.5 µm at 12 months. The best-corrected visual acuity (BCVA) at baseline was 0.82 ± 0.54, and it significantly improved at each follow-up, with a BCVA of 0.40 ± 0.25 at 12 months (P < 0.001). The BCVA was better in 76% of the patients with a more than three-line increase in 55.5% of the eyes. The average number of intravitreal bevacizumab injections was 3.1 (range, 1-6 injections). Recurrent ME occurred in 30.2% of cases. There were no major ocular or systemic adverse events. CONCLUSION: Intravitreal bevacizumab appears to be a safe and effective drug for reducing ME and improving visual acuity secondary to BRVO at 12-month follow-up at a tertiary referral eye hospital in Nepal.

Is laser photocoagulation still effective in diabetic macular edema? Assessment with optical coherence tomography in Nepal.

AIM: To find out the outcome of laser photocoagulation in clinically significant macular edema (CSME) by optical coherence tomography (OCT) METHODS: It was a prospective, non-controlled, case series study enrolling 81 eyes of 64 patients with CSME between August 2008 and January 2010. All patients received modified grid photocoagulation with frequency doubled Nd: YAG laser. Each patient was evaluated in terms of best-corrected visual acuity (BCVA) and regression or progression of maculopathy after laser therapy at 1, 3 and 6 months. Spearman's correlation test was used to show the correlation between BCVA and total macular volume (TMV). Analysis of variance (ANOVA) was used to compare among groups and independent t-test was used to compare in each group. RESULTS: There is high correlation between BCVA and TMV (P≤0.001). BCVA improved in 50.6 %, remained static in 39.5% and deteriorated in 9.9% patients after 6 month of treatment. The Baseline TMV (mean and SD) were 9.26±1.83, 10.4±2.38), 11.5±3.05), 8.89±0.75 and 9.47±1.98mm(3) for different OCT patterns, ST (sponge like thickening), CMO (cystoid macular edema), SFD (subfoveal detachment), VMIA (Vitreo macular interface abnormality) and average TMV respectively (P=0.04). After 6 months of laser treatment, the mean TMV decreased from 9.47±1.98mm(3) to 8.77±1.31mm(3) (P=0.01). In ST there was significant decrease in TMV, P=0.01, Further within these groups at 6 months, they were significantly different, P=0.01. CONCLUSION: OCT showed the different morphological variant of CSME while the response of treatment is different. TMV decreased the most and hence showed the improvement in vision after 6 months of laser treatment. In the era of Anti vascular endothelial growth factors (VEGFs), efficacy of laser seems to be in shadow but it is still first line of treatment in developing nation like Nepal where antiVEGFs may not be easily available and affordable.

Inferior conjunctival autografting for pterygium surgery: an alternative way of preserving the glaucoma filtration site in far western Nepal.

BACKGROUND: The purpose of this study was to evaluate the outcome of pterygium excision with inferior conjunctival autografting for primary pterygium. METHODS: This was a prospective noncomparative interventional case series study enrolling 50 eyes of 50 patients with primary pterygium between November 1, 2010 and October 30, 2011. All patients underwent the standard surgical technique for pterygium excision with inferior conjunctival autografting. The sampling method was purposive. The study variables were complications of surgery and recurrence rates during a follow-up period of 6 months. RESULTS: The mean age of the patients was 43 ± 7.97 (range 26-64) years. Grade 1 pterygium comprised 64% while grade 2 pterygium comprised 36% of cases. The mean size of pterygium was 3.2 ± 0.60 mm. Minor complications did occur, but only 4% required resuturing. Recurrence occurred in two eyes (4%) which we detected 3 months after surgery in both cases. We observed conjunctival scarring at the donor site in four eyes (8%); however, there was no symblepharon formation or restriction of upgaze. CONCLUSION: Inferior conjunctival autografting is an effective technique with a low recurrence rate. This is a useful technique when it is not possible or desirable to use the superior conjunctiva as a donor source. It is an especially good option for preserving the glaucoma filtration site for the future.

Prevalence of visual impairment, cataract surgery and awareness of cataract and glaucoma in Bhaktapur district of Nepal: the Bhaktapur Glaucoma Study.

BACKGROUND: Cataract and glaucoma are the major causes of blindness in Nepal. Bhaktapur is one of the three districts of Kathmandu valley which represents a metropolitan city with a predominantly agrarian rural periphery. This study was undertaken to determine the prevalence of visual impairment, cataract surgery and awareness of cataract and glaucoma among subjects residing in this district of Nepal. METHODS: Subjects aged 40 years and above was selected using a cluster sampling methodology and a door to door enumeration was conducted for a population based cross sectional study. During the community field work, 11499 subjects underwent a structured interview regarding awareness (heard of) and knowledge (understanding of the disease) of cataract and glaucoma. At the base hospital 4003 out of 4800 (83.39%) subjects underwent a detailed ocular examination including log MAR visual acuity, refraction, applanation tonometry, cataract grading (LOCSΙΙ), retinal examination and SITA standard perimetry when indicated. RESULTS: The age-sex adjusted prevalence of blindness (best corrected <3/60) and low vision (best corrected <6/18 ≥ 3/60) was 0.43% (95%C.I. 0.25 - 0.68) and 3.97% (95% C.I. 3.40 - 4.60) respectively. Cataract (53.3%) was the principal cause of blindness. The leading causes of low vision were cataract (60.8%) followed by refractive error (12%). The cataract surgical coverage was 90.36% and was higher in the younger age group, females and illiterate subjects. Pseudophakia was seen in 94%. Awareness of cataract (6.7%) and glaucoma (2.4%) was very low. Among subjects who were aware, 70.4% had knowledge of cataract and 45.5% of glaucoma. Cataract was commonly known to be a 'pearl like dot' white opacity in the eye while glaucoma was known to cause blindness. Awareness remained unchanged in different age groups for cataract while for glaucoma there was an increase in awareness with age. Women were significantly less aware (odds ratio (OR): 0.63; 95%, confidence interval (CI): 0.54 - 0.74) for cataract and (OR: 0.64; 95% CI: 0.50 - 0.81) for glaucoma. Literacy was also correlated with awareness. CONCLUSION: The low prevalence of visual impairment and the high cataract surgical coverage suggests that cataract intervention programs have been successful in Bhaktapur. Awareness and knowledge of cataract and glaucoma was very poor among this population. Eye care programs needs to be directed towards preventing visual impairment from refractive errors, screening for incurable chronic eye diseases and promoting health education in order to raise awareness on cataract and glaucoma among this population.