Antimicrobial resistance at different levels of health-care services in Nepal K K Kafle* and BM Pokhrel** Abstract Infectious diseases are major health problems in Nepal. Antimicrobial resistance (AMR) amongst various pathogens have made it difficult to cure these diseases using economical and safe antimicrobial agents. AMR has been seen at various levels of health care delivery in Nepal. This paper briefly articulates the observations made by Alliance for Prudent Use of Antibiotics (APUA) Nepal. Introduction In Nepal, the types of institutions under the Department of Health Services comprise eight Central Hospitals, three Regional Hospitals, two Sub-regional Hospitals, 10 zonal hospitals and 65 district hospitals. The regional, subregional and zonal hospitals provide blood, urine and pus culture/sensitivity services. The district hospitals provide only Gram's and AFB staining services and culture/sensitivity services are not available there 1. Alliance for the Prudent Use of Antibiotics (APUA) is a non-profit organization with its headquarters in Boston (USA). Its mission is to improve infectious disease treatment and control worldwide through promoting appropriate antibiotic access and use and by reducing antibiotics resistance. APUA has affiliated chapters in 63 countries, and Nepal has a country chapter. APUA Nepal publishes its newsletter annually, which includes reports on sensitivity patterns of common isolates in *Prof. and Head of Clinical Pharmacology, Institute of Medicine, T.U. Teaching Hospital, and President, APUA- Nepal. **Prof. and Head of Microbiology, Institute of Medicine, T.U. Teaching Hospital, and General Secretary, APUA- Nepal. urine, blood and pus samples from different levels of hospitals in Nepal 2-8. This article compiles and evaluates the available data published in the APUA Nepal Newsletter from 2004 to 2010 on the resistance problem in selected common pathogens. Material and methods The data published in the APUA Nepal Newsletter on sensitivity patterns of common isolates in urine, blood and pus samples have been used for compilation and comparison. Data in the newsletter were obtained from hospital sources. Table 1 shows the list of health facilities included for data collection and their testing dates. It included three zonal and one regional hospital and three medical colleges. The common pathogens isolated in urine, blood and pus samples are shown in Table 2. The sensitivity patterns of common pathogens from the samples are presented in the Results section. The first two issues (2004 and 2005) of the APUA Nepal Newsletter published the sensitivity of pathogens Regional Health Forum Volume 15, Number 1, 2011 9
Table 1: Name of sampled health facilities and testing dates Name of health facility Testing dates Institute of Medicine (T.U. Teaching Hospital), Kathmandu 2004, 2006, 2007, 2009 Kathmandu Medical College, Kathmandu 2004 National Medical College, Birgunj 2005 Western Regional Hospital, Pokhara 2007 2008 Lumbini Zonal Hospital, Butwal 2005 Bheri Zonal Hospital, Nepalgunj 2005 Mechi Zonal Hospital, Jhapa 2010 Table 2: Health facility and common pathogens in urine, blood and pus samples Health facility Urine Blood Pus Testing date Zonal hospitals Regional Hospital Medical colleges E. coli, S. aureus, K. pneumoniae, P. mirabilis, P. vulgaris, P. aeruginosa E. coli, S. aureus, K. pneumoniae, Citrobacter E. coli, S. aureus, K. pneumoniae, Enterococcus spp., Pseudomonas spp, Proteus spp., E. faecalis S. typhi, S. paratyphi S. aureus, E. coli, P. mirabilis S. typhi E. coli, S. aureus, Pseudomonas S. aureus, S. typhi, S. paratyphi A, Enterobacter E. coli, S. aureus, K. pneumoniae, Streptococcus spp., Pseudomonas spp., Acinobacter 2005, 2010 2007 2008 2004, 2005, 2006, 2007, 2009 mentioning more than 50% rather than giving the actual percentage. The results show the range of sensitivity of each pathogen to individual antibiotic at each level of health facility. However, the results do not compare the status of sensitivity between 2004 and 2010. Results Common pathogens in urine and their resistance The common pathogens in urine included E. coli, S. aureus and K. pneumoniae. E. coli is highly resistant to ampicillin and cotrimoxazole and their sensitivity is poor with cefotaxime as well. The other gram-ve bacilli K. pneumoniae is mostly resistant to cephalexin and nalidixic acid. Similarly, S. aureus is mostly resistant to ampicillin and cephalexin (Table 3-5). Common pathogens in blood and their resistance The common pathogens include S. typhi and S. paratyphi and they are mostly sensitive to antibiotics that were tested (Table 6). Common pathogens in pus and their resistance E. coli and S. aureus are the commonest pathogens in pus. E. coli is highly resistant to ampicillin and is mostly resistant to cotrimoxazole. Similarly, S. aureus is also highly resistant to ampicillin (Table 7-8). 10 Regional Health Forum Volume 15, Number 1, 2011
Table 3: Antibiotic sensitivity in E. coli from urinary tract pathogens* Amoxycillin Cefotaxime Ceftazidime Chloramphenicol Nalidixic Acid Norfloxacin Health facility level Zonal hospitals 83.3 NR 20.8 NR NR NR NR NR NR NR 41.7 62.5 68.8 70.8 Regional Hospital 80.0 NR 29.2 76.2 58.9 NR NR 56.5 8.3 38.5 22.2 87.5 36.4 57.1 Medical colleges 89.4 21.3-65.3 13.3 NR NR 45.6 98.0 83.3 5.2- NR 48.0-63.7 40.6-95.6 29.5-44.7-91.0 44.7-64.7 Testing dates ranged from 2004 2010 * = first two issues (2004 and 2005) of APUA-Nepal Newsletter published sensitivity patterns of pathogens which were 50% or more sensitive without giving actual percentage. Regional Health Forum Volume 15, Number 1, 2011 11
Table 4: Antibiotic sensitivity in S. aureus from urinary tract pathogens* Cloxacillin Erythromycin Norfloxacin Health facility level Zonal hospital 0.0 NR NR 0.0 NR NR 50.0 NR NR NR Regional Hospital NR 50.0 NR NR NR NR NR NR 50.0 50.0 NR Medical colleges 67.3 16.5-60.1 NR 36.3-64.4 85.2 92.2 44.2-80.3 57.7-84.0 42.6-62.8 95.6-98.6 50.0- Testing dates ranged from 2004 2010, * = first two issues (2004 and 2005) of APUA-Nepal Newsletter published sensitivity patterns of pathogens which were 50% or more sensitive without giving actual percentage. 12 Regional Health Forum Volume 15, Number 1, 2011
Table 5: Antibiotic sensitivity in K. pneumoniae from urinary tract pathogens* Amoxycillin Ceftazidime Nalidixic Acid Norfloxacin Tetracycline Health facility level Zonal hospital NR 0.0 NR NR NR NR 0.0 NR 33.3 NR NR NR NR 83.3 NR Regional Hospital NR NR 25.0 33.3 NR NR 50.0 NR NR 16.7 75.0 75.0 83.3 NR Medical colleges 64.7 4.6- NR NR NR 93.1 88.0 7.6-58.4 82.0 40.5-73.2 93.1 35.7-45.9-93.2 46.0-88.3 Testing dates ranged from 2004 2010. * = first two issues (2004 and 2005) of APUA-Nepal Newsletter published sensitivity patterns of pathogens which were 50% or more sensitive without giving actual percentage. Regional Health Forum Volume 15, Number 1, 2011 13
Table 6: Antibiotic sensitivity in S. enterica typhi and Para-typhi A from blood pathogens* Amoxycillin Cefotaxime Ceftazidime Chloramphenicol Imipenem Health facility level Zonal hospital NR 50.0 NR NR NR NR NR NR NR 50.0 Regional Hospital NR 43.5 NR NR 94.5 NR 61.1 NR 95.8 Medical colleges NR 91.8 NR 42.0- NR 42.0- Testing data ranged from 2004 2010. * = first two issues (2004 and 2005) of APUA-Nepal Newsletter published sensitivity patterns of pathogens which were 50% or more sensitive without giving actual percentage. 14 Regional Health Forum Volume 15, Number 1, 2011
Table 7: Antibiotic sensitivity in S. aureus from pus pathogens* Chloramphenicol Cloxacillin Erythromycin Procaine Penicillin Health facility level Zonal hospital 87.5 25.0 NR NR NR 12.5 NR NR 75.0 37.5 NR NR 75.0 NR NR Regional Hospital 50.0 66.7 70.0 71.4 NR 57.1 57.1 NR 57.9 NR 63.1 Medical colleges 79.4 22.7-37.0 NR NR 31.6-83.6 NR 75.3 57.1-88.6 45.6-70.9 53.2-79.3 74.2 NR NR Testing dates ranged from 2005 2010. * = first two issues (2004 and 2005) of APUA-Nepal Newsletter published sensitivity patterns of pathogens which were 50% or more sensitive without giving actual percentage. Regional Health Forum Volume 15, Number 1, 2011 15
Table 8: Antibiotic sensitivity in E. coli from pus pathogens* Amoxycillin Cefotaxime Norfloxacin Polymyxin B Health facility level Zonal hospital 87.5 NR 25.0 NR NR NR NR 12.5 37.5 NR NR Regional Hospital 70.0 NR 42.8 61.5 44.4 NR 25.0 60.0 33.3 50.0 NR NR 61.5 NR Medical colleges 85.8 69.2 6.6 NR NR 55.0-89.3 42.8-88.4 8.9-70.2 38.0-67.3 41.7-62.3 78.2 NR NR Testing dates ranged from 2005 2010. * = first two issues (2004 and 2005) of APUA-Nepal Newsletter published sensitivity patterns of pathogens that were 50% or more sensitive without giving the actual percentage. 16 Regional Health Forum Volume 15, Number 1, 2011
Discussion Infectious disease is a common ailment in Nepal. In Nepal, antimicrobial resistance is a major problem, contributing to increased treatment costs, hospital stay, morbidity and mortality. The resistance is more common among Gram-negative than Gram-positive organisms, the precise extent of the problem is not known since the majority of the published reports derive from individual units or hospitals 9. Resistance to commonly available and affordable antimicrobials poses a major concern in the management of bacterial infection. Imprudent practices in the use of antimicrobial agents in human medicine and for prophylaxis in animal husbandry may contribute significantly to the emergence of multidrug-resistant (MDR) strains 10. Transmission of highly resistant bacteria from patient to patient within the hospital environment (nosocomial transmission) References and bibliography (1) Annual report 2008 09. Department of Health Services, Government of Nepal. http://practicalaction.org/docs/region_nepal/np_ann ualreport08-09.pdf - accessed 9 March 2011. (2) APUA-Nepal. Sensitivity patterns of common isolates from major hospitals of Kathmandu valley. APUA- Nepal Newsletter. 2004; 1(1). (3) APUA-Nepal. Sensitivity profiles of common isolates from three hospitals outside valley. APUA-Nepal Newsletter. 2005; 2(1). (4) APUA-Nepal. Comparative study of sensitivity patterns of common isolates in Tribhuvan University, Teaching Hospital (TUTH). APUA-Nepal Newsletter. 2006; 3(1). (5) APUA-Nepal. Comparative study of sensitivity patterns of common isolates in Tribhuvan University Teaching Hospital (TUTH). APUA-Nepal Newsletter. 2007; 4(1). amplifies the problem of antimicrobial resistance and may result in the infection of patients who are not receiving antimicrobials. Despite its proven efficacy in containing and preventing additional infection and curbing the associated antibiotics use, infection control is among the slowest disciplines to gain widespread implementation. Failure to carry out simple infection control practices such as changing gloves and washing hands is both dangerous and all too common. It often stems from the failure to recognize its importance, understaffing, and/or forgetfulness. Controlling the spread and emergence of drug resistance in the hospital is best administered by an active, coordinated infection control programme, which may include targeted cohorting of infected patients, enhanced surveillance, isolation or rigorous barrier precautions, early discharge, and alterations in antimicrobial usage 11. (6) APUA-Nepal. Comparative study of sensitivity patterns of common isolates in Western Regional Hospital (WRH). APUA-Nepal Newsletter. 2008; 5(1). (7) APUA-Nepal. Comparative study of sensitivity patterns of common isolates in Tribhuvan University Teaching Hospital (TUTH). APUA-Nepal Newsletter. 2009; 6(1). (8) APUA-Nepal. Comparative study of sensitivity patterns of common isolates in Mechi Zonal Hospital. APUA- Nepal Newsletter. 2010; 7(1). (9) APUA. Antimicrobial resistance in India: current scenario. APUA Newsletter. 2008; 26,(!). (10) APUA. Multidrug-resistant escherichia coli from apparently healthy children in Kenya. APUA Newsletter. 2007; 25(1). (11) APUA. Infection control: a potent antimicrobial resistance containment strategy. APUA Newsletter. 2008; 26(2& 3). Regional Health Forum Volume 15, Number 1, 2011 17