Antimicrobial resistance

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Volume 15, Number 1, 2011 Volume 15, Number 1, 2011

REGIONAL

HEALTH FORUM

REGIONAL

HEALTH FORUM

WHO South-East Asia Region

Special issue on

Antimicrobial Resistance in South-East Asia

Special issue on

Antimicrobial Resistance in South-East Asia

World Health Day 2011

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ISSN 1020 4237

Publications of the World Health Organization enjoy copyright protection in accordance with the provisions of Protocol 2 of the Universal Copyright Convention. For rights of reproduction or translation, in part or in toto, of publications issued by the WHO Regional Office for South-East Asia, application should be made to the Regional Office for South-East Asia, World Health House, Indraprastha Estate, New Delhi 110002, India.

The designations employed and the presentation of the material in this publication do not imply the expression of any opinion whatsoever on the part of the Secretariat of the World Health Organization concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries.

The views expressed in this publication are those of the author(s) and do not necessarily reflect the decisions or stated policy of the World Health Organization; however they focus on issues that have been recognized by the Organization and Member States as being of high priority.

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Editorial

The burgeoning challenge of antimicrobial resistance

Rajesh Bhatia*

The discovery of penicillin by Fleming1 revolutionized mankind’s fight against communicable diseases. By 1940s, this drug was available for clinical use. Since then penicillin and many other antimicrobial agents that were discovered subsequently have saved millions of lives all over the world. So huge was the initial impact of antimicrobial agents that many people erroneously started believing that “time has come to close the chapter of communicable diseases”. Unfortunately, they had not comprehended the versatility of microorganisms and the array of survival mechanisms developed by them over several millennia of their existence.

While the successful clinical use of penicillin2_{is widely known and lauded,} detection of resistance to penicillin in 1940 itself3_{was ignored by the global community.} Facilitated by the continuous and indiscriminate use of antimicrobials in health, veterinary and industrial sectors, the microorganisms slowly and steadily started developing resistance to several antimicrobial agents giving rise to multidrug resistant organisms. Antimicrobial resistance (AMR) is now proclaimed as the most important challenge being faced by humanity in its fight against infectious diseases. The emergence and spread of resistance in several microorganisms have rendered the management of many infectious diseases difficult. Failure to discover new antimicrobial agents has further hampered the war against infectious agents.

Antimicrobial resistance is now no longer a local problem. It has international ramifications. In the modern era of travel and trade, resistant organisms rapidly cross the man-made boundariesthrough humans or the food chain. The emerging threat of resistance in malaria, tuberculosis (TB) and the human immunodeficiency virus (HIV)/AIDS is a huge impediment to achievement of the Millennium Development Goals (MDGs) by 20154_.

This special issue of the Regional Health Forum provides ample evidence to demonstrate that AMR is a burgeoning and hugely neglected problem in the WHO South-East Asia (SEA) Region. The problem is assuming serious proportions in all Member States. The overview of the status of resistance in various microorganisms in Bangladesh5_, Nepal6_{and Sri Lanka}7_{indicates the extent of} the problem and its implications for care of patients and public health.

Bhatia et al.8_{have discussed the problem} of resistance to first-line antiTB drugs, which has become a concern for national TB control programmes. It is estimated that around 180 000 cases of multidrug-resistant (MDR)-TB occur annually in this Region with more than 80% of these being in Bangladesh, India, Indonesia, Myanmar and Thailand9_._{The drugs} needed to treat MDR-TB are over 100 times more expensive than the first-line drugs used to treat non-resistant forms9_.

The generic antiretroviral (ART) drugs available in the Region are contributing greatly towards improving the survival rate of patients worldwide and in rendering HIV a chronic but a manageable condition. A large number of *Department of Communicable Diseases,

WHO Regional Office for South-East Asia

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patients from India have been followed up by Balakrishna et al.10_{to elaborate the intricacies} of ART therapy. Although the response to ART drugs is excellent when these are delivered at health facilities, there also are reports of emergence of resistance, which are a serious cause of concern.

Resistant malaria has already become a major issue for the population of 400 million living in areas that expose them to the high risk of contracting it. Artemisinin-based combination therapies (ACT) have recently been introduced in virtually all countries in which malaria is endemic. However, surveillance data from the Thai Ministry of Public Health indicate that clinical failures of artemisinin-based therapies exist on the Thai-Cambodian border, whereas efficacy with artesunate-mefloquine along the western borders of Thailand remains high11, 12_.

There has been a substantial change in the antimicrobial susceptibility of Neisseria gonorrhoeae. Thirty years back, gonorrhoea used to respond effectively to penicillin. Now the resistance to penicillin, tetracyclines and fluoroquinolones is widespread across the Region13_.

Pentavalent antimonials have been successfully used for treatment of kala-azar since the last six decades. Since the 1970s, however, their conventional dosages have failed to achieve the desired results with 60% unresponsiveness being reported with the WHO regimen in Bihar, India. The newer oral drug, miltefosine is a potent antileishmanial drug with a longer half-life, but requires rational use in affected areas14_.

Typhoid and paratyphoid fever continue to be important causes of illness and death, particularly among children and adolescents in the SEA Region where this disease is associated with poor sanitation and unsafe food and water. Shortly after the emergence of MDR S. Typhi in this Region, case fatality rates approaching 10% (close to 12.8% recorded in pre-antibiotic era) were reported15_{. Rational}

use of some of the recommended drugs for typhoid fever can prolong the life of these drugs, especially chloramphenicol16_.

More than 50% isolates of Staphylococcus aureus in hospital settings are now methicillin resistant. The resistant strains are widely prevalent in developing as well as developed countries, and are creating major issues in the proper management of seriously ill patients in hospitals17_.

Multiresistant klebsiellae, Pseudomonas and Acinetobacter species have given a new dimension to the problem of hospital-associated infections. A. baumannii has become an important pathogen in intensive care units. In a study done in Thailand, the mortality rate for patients admitted due to imipenem-resistant A. baumannii was 52% as compared with 19% for those infected with the sensitive variant18_{. Kumthorn et al.}19_describe the growing problem of A. baumanii group in hospital settings in Thailand. It is likely that similar situations are prevalent in other countries too.

The presence of a drug-resistant gene,

bla_NDM-1_, in several members of the family

Enterbacteriaceae has given rise to organisms that are resistant to a large number of commonly used antimicrobial agents. A reality check on these organisms and their recent emergence has been articulated by Rodrigues20_.

Antimicrobial resistance in viruses and fungi is making management of diseases caused by these microorganisms difficult. The recently detected resistance in influenza viruses21_{and fungi of medical importance}22 should draw researchers’ special attention to this menace, which is now threatening the hitherto neglected organisms.

Antimicrobial resistance has several severe consequences. The patient remains sick for a longer period thus requiring prolonged treatment usually with expensive and at times toxic drugs. Not only there is greater morbidity and mortality but the burden on health system

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also increases. The impact of modern technological and complex surgeries gets negated when the patient after successful intervention gets infected with resistant microorganisms. From the public health perspective, the patient acts as a reservoir of infection for a longer period thus putting at risk more members of the community and health-care workers. All these factors have a substantial effect on the economy, at both individual and societal levels. In fact, it is difficult to imagine effective newer surgical procedures, transplantations and prolonged chemotherapy for various cancers, care of the critically ill young and the old, or prolonged treatment of HIV-infected persons in the absence of measures aimed at effective containment of AMR4_.

The need for new antibiotics to address the emerging resistance in microorganisms cannot be overstated. There has been a near-empty antibiotic pipeline23_{. However, there is} some light at the end of the tunnel with a few significant new global initiatives that are under way. Some antimicrobial agents are being developed and are awaiting approval of the Food and Drug Administration of the United States of America24_{. The European} Commission recently sought proposals for new antibiotic research and development for multidrug-resistant Gram negative pathogens.

This quickly led to the establishment of a joint EU-US Transatlantic Taskforce on Antimicrobial Resistance. The call by the Infectious Diseases Society of America for a 10x20 initiative viz., development of 10 new antibiotics by 202025_{, should trigger new} research and development by the pharma companies.

We need to recognize that the problem of resistance is complex and encompasses biological, behavioural, technical, economic, regulatory and educational dimensions that require a comprehensive response. It requires ownership and active participation by several stakeholders, and a strategic approach with objectives that include establishment of a national alliance for prevention and control of antimicrobial resistance. The WHO Regional Office for South-East Asia has recently developed one such strategy26_{. It addresses} four areas that need attention of national authorities; governance; regulatory mechanisms; building national capacity; and mobilizing active participation of communities.

Recognizing the emerging importance of this subject and to enhance its visibility for an early action, “antimicrobial resistance” is the theme of the World Health Day 2011. Far too long, antimicrobial resistance has been an unrecognized and neglected problem. The time to act is now.

References and bibliography

(1) Fleming A. On the antibacterial action of cultures of a

Penicillium with special reference to their use in the isolation of B.influenzae. British J Experimental Pathology 1929, 10; 226-236.

(2) Chain E, Florey HW, Gardner AD et al,. Penicillin as a chemotherapeutic agent. Lancet 1940 ii; 226-228. (3) Abraham EP and Chain E. An enzyme from bacteria

able to destroy penicillin. Nature 1940. 146; 837.Nature 1940.

(4) Bhatia R and Narain JP. The growing challenge of antimicrobial resistance in the South-East Asia Region - Are we losing the battle? Indian J Med Res 132, November 2010, pp 482-486.

(5) Faiz MA and Basher A. Antimicrobial resistance: Bangladesh experience. Regional Health Forum 2011,15:1-8.

(6) Kafle KK and Pokhrel BM. Antimicrobial resistance at different levels in Nepal. Regional Health Forum 2011, 15:9-17.

(7) Patabendige CGUA, Chandrasiri NS, Karunanayake LI et al: Antimicrobial resistance in resource-poor settings – Sri Lanka experience. Regional Health Forum 2011, 15:18-26.

(8) Bhatia V, Hyder MKA and Nair N. Drug resistance in TB in SEA Region. Regional Health Forum 2011, 15:44-51.

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(9) Nair N, Wares F and Sahu S. Tuberculosis in the WHO South-east Asia Region. Bulletin of WHO2010; 88:164.

(10)Balakrishnan P, Saravanan S, Madhavan V et al. HIV-1 drug resistance among drug-naïve and HAART treated patients in India: Current status. Regional Health Forum 2011, 15:27-43.

(11)Rahman MM, Ortega L, Rastogi RM et al. Antimalarial drug resistance. Regional Health Forum 2011; 15:52-56.

(12)Delacollete C, Bustos MD, Thimasarn K et al.. Antimalarial and artimesinin resistance in Mekong subregion. Regional Health Forum 2011; 15:131-133.

(13)Bala M. Antimicrobial resistance in Neisseria gonorrhoeae in SEA. Regional Health Forum 2011; 15:63-73.

(14)Sinha PK and Bhattacharjee S. Antimicrobial resistance in Leishmania donovani. Regional Health Forum 2011; 15:134.

(15)Gupta A. Multidrug-resistant typhoid fever in children: 22. epidemiology and therapeutic approach. Pediatr Infect Dis J 1994; 13 : 134-40.

(16)Harish BN and Menezes GA. Preserving efficacy of chloramphenicol against typhoid fever in a tertiary care hospital, India. Regional Health Forum 2011; 15:92-96.

(17)Ray P, Gautam V and Singh R. Methicillin resistant Staphylococcus aureus in developing and developed countries: implications and solutions. Regional Health Forum 2011; 15:74-82.

(18)Jamulitrat S, Arunpan P, Phainuphong P. Attributable mortality of imipenem-resistant nosocomial

Acinetobacter baumannii blood stream infection. J Med Assoc Thailand 2009; 92 : 413-9.

(19)Malathum K, Dejsirilert S and Thongmali O. Growing problem of multidrug resistant Acinetobacter baumanni in Thailand. Regional Health Forum 2011; 15:87-91.

(20)Rodrigues C . Carbapenem resistant

enterobacteriaceae- a reality check. Regional Health Forum 2011; 15:83-86.

(21)Chittaganpitch M, Waicharoen S, De silva JW et al. Oseltamivir resistant influenza viruses in Thailand 2008-2010. Regional Health Forum 2011; 15:57-62.

(22)Chakrabarty A. Drug resistance in fungi - an emerging problem. Regional Health Forum 2011; 15:97-103. (23)European Medicine Agency .European Centre for

Disease Prevention and Control Joint Technical Report:the bacterial challenge- time to react, 2009. Available at: http://www.ema.

europa.eu/docs/en_GB/document_library/Report/20 09/11/WC500008770.pdf

(24)Arias CA. Murray BE. Antibiotic resistant bugs in the 21st_{century - A clinical super-challenge. N Engl J Med}

2009: 360 : 439-42.

(25)IDSA. Infectious Diseases Society of America. The 10x20 Initiative: Pursuing a Global Commitment to develop 10 new antibacterial drugs by 2020. Clin Infect Dis 2010; 50 : 1081-3.

(26)WHO. Regional Strategy on Prevention and Containment of Antimicrobial Resistance 2010-2015. Available at:

http://www.searo.who.int/LinkFiles/BCT_hlm-407.pdf, accessed on Jan 7, 2011.

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Antimicrobial resistance: Bangladesh experience

Md. Abul Faiz* and Ariful Basher**

Abstract

Infectious diseases are major health problems in Bangladesh requiring frequent use of antimicrobials. Diagnosis and treatment of most of the bacterial diseases are empirical. Microbial sensitivity patterns of common infections like respiratory tract infection, urinary tract infection, enteric fever, wound infection are not routinely available for decision making in drug selection. Many infectious diseases do not respond to conventional antimicrobial agents. Standard treatment guidelines of different microbes are not sufficient for the purpose, moreover the community awareness programme is imperfect. There is no routine antimicrobial surveillance or quality assurance in place. Multidrug resistant (MDR) TB in primary infection is ~3%, and MDR enteric fever is an emerging threat in Bangladesh. Due to drug resistant falciparum

malaria, artemisinin-based combination therapy is used; visceral leishmaniasis is treated with oral miltefosine although sodium stibugluconate is still sensitive but found to be at times toxic and difficult to deliver. Available evidence does not support the optimal diagnosis and treatment of bacterial infections in Bangladesh.

Antibiotics are available as non-prescription drugs in medicine shops and irrational use is not uncommon. Adherence to treatment protocol and compliance with treatment course of antimicrobials need to be emphasized at different levels.

Measures for prevention and containment of antimicrobial resistance are necessary in Bangladesh. It should be taken as a national priority and the establishment of a national alliance or regulation governing the use of antimicrobials should be considered.

Introduction

Antimicrobial resistance is a worldwide problem. The selection and spread of resistant organisms in developing countries that can often be traced to complex socioeconomic and behavioural antecedents contribute to the escalating problem of antibiotic resistance. Factors such as unregulated dispensing and manufacture of antimicrobials, truncated antimicrobial therapy, inadequate access to effective drugs and sometimes drugs of questionable quality and overall poverty are

likely to be contributing to antimicrobial resistance.1

Antimicrobials are the most commonly prescribed group of drugs in general practice and in hospitals. Despite the improved trend of health care in Bangladesh, infectious diseases remain priority public health problem, where widespread use of different antimicrobials against bacterial, fungal, viral and parasitic infections is required. Most antimicrobials are prescribed, with the decision to apply based on best-guess empiric therapy. A majority of the prescribers in Bangladesh diagnose infection by clinical assessment and suspect a microbial aetiology.2 _{The important factors} associated with resistant bacteria are poor hospital hygiene, overcrowding, lack of *Professor of Medicine, (Post Retirement Leave),

Sir Salimullah Medical College, Mitford, Dhaka-1100, Bangladesh.

**Medical Officer, KHFP Center, B. Baria, Bangladesh.

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resources for infection control and lack of personnel trained in controlling infection in hospital.

Methodology

This article is based on a review of related literature, newspaper articles and online searches using Pubmed, Google and Banglajol. Combinations of key words related to each of the subject areas were used. Websites of relevant institutions, government and nongovernmental organizations were also searched. The literature thus obtained was categorized and reviewed carefully.

Drug resistance pattern of common

infectious diseases

Systematic drug sensitivity reports against microorganisms from countries like Bangladesh are sparse. Many studies and interventions have focused on surveillance in hospitals and on the education of physicians. So far very limited data are available on the use of antibiotics. Indeed, Bangladesh is facing dual problems. On the one hand it failed to eradicate age-old infectious diseases due to indiscriminate and irrational use of antimicrobials. On the other hand also it is facing ICU-related drug-resistant micro-organisms like those in developed countries.

Antibiotics are most frequently prescribed for acute respiratory tract infections, acute watery diarrhoea, acute trauma and gastro-intestinal symptoms.4_{The most frequently} prescribed antibiotics are ceftriaxone (30.19%) followed by cefixime (18.87%), and amoxycillin (16.98%).3_{It was observed that} cephalosporins accounted for more than 55% of the total antibiotics used, where the highest uses were by ceftriaxone, cefixime, and cefuroxime.3_{This probably explains why} ceftriaxone and cefixime have abnormally high resistance.

A study suggested that Pseudomonas aeruginosa responsible for wound, urine, ear, throat and other infections were more than 50% resistant to commonly-used antibiotics in Bangladesh, including ciprofloxacin, genta-micin, ceftriaxone, cefixime and azithromycin.4 Azithromycin was 100% ineffective in wound and urine infections, while ceftriaxone and cefixime was 100% ineffective in tracheal in-fections.5_{Another study also reports that}

Escherichia coli was resistant in 40% of cases to commonly used antibiotics ceftriaxone, levofloxacin, ciprofloxacin, amoxicillin and ampicillin and 95% resistant to azithromycin.5

Klebsiella pneumoniae also showed similar patterns.6_{It was observed that 43.2% and} 39.5% of isolated E. coli and K. pneumoniae respectively had ESBL phenotypes.7 _{This rate is} higher than in countries of the Western Pacific Region,8_{North America or Europe and some} South American nations.9

Cholera germs have acquired resistance to a number of antimicrobials including tetracycline.10 _{Over the year, shigellosis have} shown great propensity to develop resistance to antibiotics. In 1996, reports from Matlab and Dhaka showed that more then 95% Shigella dysenteriae isolated were resistant to ampicillin, cotrimoxazole and nalidixic acid and 14%-40% were resistant to methicillin.11 _In 1973, S. flexneri isolates were universally susceptible to ampicillin; however, by 1979 susceptibility decreased to 79% in urban Bangladesh. Similarly, the susceptibility of S. flexneri to tetracycline dropped from 79% in 1973 to 15% in 1979.12_{In a recent study, at} least 25% of S.flexneri were resistant to three commonly used antibiotics such as ampicillin, co-trimoxazole and nalidixic acid.13

Ciprofloxacin has been extensively used in Bangladesh for the treatment of suspected gonorrhoea as it is relatively cheap and effective, and only a single oral dose is required. But as a consequence of the long-time, versatile and large-scale use of this group of antimicrobial agents in areas where over-the-counter availability of drugs without

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prescription is common, a substantial increase in resistant strains occurred. Data from one study seem to reflect the consequence of the long standing usage of ciprofloxacin for the treatment of suspected gonorrhoea using syndromic management at sexually transmitted infections (STI) clinics in Bangladesh. The most striking finding of the study is the emergence of isolates resistant to three or more antimicrobial agents. More than half of the isolates are resistant to three drugs, including ciprofloxacin. Of the multidrug-resistant isolates, more than half were both PPNG (penicillinase-producing Neisseria gonorrheae) and TRNG (tetracycline resistant Neisseria gonorrheae).14

“Wonder drugs” for treating typhoid have now become a challenge to the physicians. A study conducted in an urban hospital of Bangladesh noted that 75% of Salmonella typhi were resistant to nalidixic acid vis-a-vis ciprofloxacin. 15_{In another study conducted in} one referral centre in 2005 a total of 57% of S. Typhi strains isolated were MDR (multidrug-resistant) and NAR (nalidaxic acid (multidrug-resistant).16

A study report from Dhaka Shishu Hospital revealed that the principal organisms for neonatal sepsis are Klebsiella, Acinatobactor, E coli, coagulase negative staphylococci and Staphylococcus aureus. Maximum sensitive drugs are imipenem, ciprofloxacin, gentamycin and cotrimoxazole.17 Imipenem is costly and ciprofloxacin has inadequate safety data. Bacterial isolates are becoming resistant to a different generation of cephalosporin.17

Infections caused by opportunistic organisms are difficult to control due to multidrug resistance, which limits therapeutic options in critically ill and debilitated patients, especially from the intensive care units (ICU), where prevalence of the organism is the most noted. Acinetobacter baumannii is now recognized to be the species commonly found.18

The prevalence of MDR-TB was 3% among new and 15.4% in previously treated patients in Bangladesh.4_._{In a published report,} 42 isolates of sputum samples from different areas of Bangladesh were studied in a supranational reference laboratory (SRL) in Antwerp, Belgium. Among 42 strains, 35 (83%) were found resistant to both isoniazid and rifampicin (MDR). Among these MDR strains, 40% were found resistant to any one of the second-line drugs (kanamycin, ofloxacin, ethionamide, and para-amino salicylic acid). However, none of the strains were found to be extensively drug resistant (XDR).19_Another study found drug resistance of Mycobacterium tuberculosis to at least one drug in 53.68 % cases which is highly alarming. The highest resistance (40%) was found against isoniazid, which is the most popular drug, followed by rifampicin (32.63 %). Resistance to streptomycin was found in 13.68 % cases, to ethambutol in 11.58 % and to pyrazinamide in 10.53% cases.20_{Experts identified} inappropriate and irregular treatment beyond programmatic control, lack of diagnostic facility and treatment of existing MDR cases as the contributing factors to the rising number of MDR and XDR-TB patients.21

Multi-drug resistance of Plasmodium falciparum parasites developed in Asia earlier than in other malarious areas around the world. As early as 1957, chloroquine (CQ) resistance appeared, whilst sulfadoxine— pyrimethamine (SP) resistance first emerged in 1967, both at the Thai-Cambodia border. Since then, it has been described in all Asian countries. In Bangladesh, the restrictions, together with clear case definitions and treatment guidelines for malaria, have not been able to block the spread of resistance to the country’s malaria treatment and the current situation of antimalarial drug resistance. Drug resistance to chloroquine and sulphadoxine-pyrimethamine is reported from areas of Chittagong Hill Tract Districts.22_Antimalarial drug efficacy trials documented that chloroquine had been found to be resistant for treatment of Plasmodium falciparum malaria

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to the extent ranging from 40% to 70% in the highly endemic malaria areas.23,24

The Ministry of Health therefore revised the guidelines for malaria treatment with the introduction of artemisinin-based combination therapy (ACT) for the treatment of uncomplicated falciparum malaria.

The adequacy of methods used to conduct studies on treatment of visceral leishmaniasis and reports on them varied. Unresponsiveness to antimony has developed steadily in the past to such an extent that antimony is now being replaced, despite attempts to stop its progression by increasing the dose and duration of therapy. The classic second-line treatments are unsuited — pentamidine is toxic and its efficacy has also declined, and amphotericin B deoxycholate is effective but requires hospitalization for long periods and toxicity is common. Liposomal amphotericin B is very effective and safe but currently unaffordable because of its high price.25 _{Miltefosine — the first oral drug for} visceral leishmaniasis — is now registered but its efficacy is controversial. At present, a combination drug trial is going on in Bangladesh to find out the optimal management and to prevent resistance. Meanwhile, the WHO Expert Committee has published a report on the control of leishmaniasis emphasizing the advantages of combination treatment including cost, toxic effects and reducing the probability of selection of drug-resistant parasites.26_In several phase 3 studies in India, three separate combinations showed 98%-99% cure rates.

There are a wide range of prescribers in the private and public sectors. The private health sector is rapidly expanding and is not well supervised and regulation of antibiotics is virtually non-existent. There is no central organization entrusted to oversee the use and investigations related to antibiotic use. Many patients use out-of-pocket expenditure for treatment and investigations even in public sector facilities. There is no national antimicrobial policy and few institutes have

antimicrobial guidelines which are also not in practice.27_{There is no uniformity among the} prescribers in commonly prevalent infections although national guidelines are prepared for certain important prevalent infections, for example malaria, kala-azar and tuberculosis. Completion of the course of the prescribed antibiotic is not supervised and is likely to be poor in compliance for various reasons. All these factors facilitate antimicrobial resistance.

Societal issues outside the medical sphere

Many developing countries including Bangladesh allow the dispensation of antibiotics without a prescription; this can lead to self-medication and dispensation of drugs by untrained people. In one survey from the Rajbari district, 100 000 doses of antibiotics had been dispensed without a prescription in one month.28_{In another study, 92%} medications dispensed by pharmacies were without a prescription.29_{Poverty-stricken} patients may forgo the cost of a physician consultation and self-medicate. They demand antibiotic treatment even when not indicated.

Antimicrobials are available over the counter and any antimicrobials can be prescribed by any health care provider. Most of the drugs are prescribed or sold in Bangladesh by non-qualified or relatively less qualified health workers.30_{In the national} disease control programmes antibiotics are allowed to be given by health workers in certain cases like ARI. Antibiotics are also prescribed unnecessarily for example in viral fevers, and clean post-operative cases.31_Due to the unresponsiveness of the health system with respect to basic amenities, inappropriate client–provider interaction and staff attitudes, patients especially the poor prefer to seek health care from informal providers. These informal providers are deeply embedded in the local community and culture, easily accessible and provide inexpensive services to the villagers with occasional deferred payments and payment in kind instead of cash.

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The providers include traditional practitioners and unqualified allopathic practitioners having varying duration of training in diagnosing and treating common ailments mostly from unregulated private institutions of dubious quality. These categories of providers, of greatest importance to the poor and disadvantaged population in rural areas, have largely been ignored by the public sector/government till now, as well as by NGOs.

The widespread and inappropriate use of antibiotics has resulted in the development of a progressively antibiotic-resistant microbial ecosystem in Bangladesh. A study among children from a rural community showed that 50% children had enteric flora resistant to ampicillin, cotrimoxazole and streptomycin throughout the year.32

No information is available from resource-poor settings on the extent of environmental antibiotic usage and its relationship to the prevalence of antibiotic resistant bacteria in animals. Most surprising was the widespread use of animal antibiotics and the anecdotal reports of “resistant” animal infections.33

Overview of the prevailing drugs market

Unethical drug promotion and marketing of substandard and unnecessary drugs in Bangladesh is not uncommon. A medical practioner can prescribe any drug used for the common cold to cancer. Moreover, polypharmacy is very common among the rural medical practitioners with antibiotics and vitamins prescribed widely.31 _{The prescription} procedure of antibiotics in Bangladesh is less than ideal as prior identification of the pathogens and its sensitivity to the drug is rarely determined before the drug is prescribed.34_{Currently, drug companies are} the only organizations in Bangladesh to provide information to health personnel and it is often not appropriate information.33

The excessive and inappropriate use of antibiotics adds an unnecessary economic burden to healthcare system and coincides with an increase in drug-resistant organisms, which has resulted in the use of more expensive and toxic drugs. The quality and efficacy of locally manufactured antimicrobial drugs are also largely unregulated. Often multiple brands of the same agent are available, and potency equivalents of the active antibiotic may be a fraction of the appropriate dose. A recent assay involving 15 brands of ciproloxacin showed that 47% of samples contained less than the specified amounts of the active ingredient 35_Counterfeit drugs like other counterfeit materials are likely to compete favorably in the markets of a developing country like Bangladesh.

Prescription patterns of antimicrobials

Some sporadic studies reported disturbing self-medication behaviours among the general population in Bangladesh.29_{Children are} mostly affected by inappropriate prescribing of antibiotics. In a study it was shown that 26% of purchased drugs were antibiotics for children aged 0-4 year(s) and 48% of antibiotics were purchased in quantities of less than a single day's dose.36 _{Pneumonia and diarrhoea are} the two most common infectious diseases among children in Bangladesh with annual deaths of about 230 000 children due to diarrhoea.37_{But the percentages of} appropriate antimicrobial treatment of pneumonia and diarrhoea were 57.1% and 67.8% respectively as shown in one study.38 Misuse of drugs in the treatment of acute diarrhoea among under-five children is highly prevalent and WHO-recommended treatments were seen in only 26.7% of cases and metronidazole was prescribed in all 38.6% cases.39

Multiple and inappropriate antimicrobial drugs is the most common treatment error in dysentery.36 _{About 50% to 80% of Bangladeshi} patients infected with shigellae have a history

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6 Regional Health Forum – Volume 15, Number 1, 2011 of taking at least one antibiotic in the 15 days

before a hospital visit.40

Some examples of obsolete treatment used for a long time are: thiacetazone-based antitubercular regimen; use of ineffective chloroquine; S-P or short course quinine Q3F for treatment of falciparum malaria on clinical criteria; over-reliance on sodium antimony gluconate for treatment of kala-azar; over-the-counter purchase of unnecessary antibiotics for viral syndrome; and provision of incomplete course of antibiotic in public hospitals and private practice.

One study in a medical college hospital revealed that the total number of patients who received antimicrobials (69.0%) were prescribed antibiotics for suspected or proven infection and 31.0% and 42.1% of all antimicrobials prescribed were considered inappropriate for prophylaxis. Lack of hospital restrictions on antibiotic use and inappropriate usage for prophylaxis are the main reasons for inappropriate therapy.41

Conclusion

A good, representative database on the current status of antibiotic resistance among common and important pathogens is essential for the proper treatment of infectious diseases in the country. Energetic measures to slow down the emergence and spread of antimicrobial resistance should include programmes on surveillance, education and research on antimicrobial resistance, and regulation of use of antimicrobials in hospitals and in the community.

It is indeed urgently needed to determine antimicrobial practices in the low-income population, determine the duration of compliance to therapy, reasons for non-compliance, sources of medications and prevalence of use of antimicrobials so that we can better apply the regional recommend-dations for containment of antimicrobial resistance.

References and bibliography

(1) World Health Organization. Overcoming antimicrobial resistance. Geneva: WHO, 2000. (2) Faiz MA, Rahman MR. Rational antimicrobial use.

Journal of Chittagong Medical College Teacher Association. 2004; 15(1&2): 1-3.

(3) Fahad BM, Matin A, M.C. Shill, Asish K D. Antibiotic usage at a primary health care unit in Bangladesh. Australian Medical Journal. 2010; 3(7): 414 – 421. (4) Rashid A, Chowdhury A, Rahman S HZ, Begum S A, Muazzam N. Infections by Pseudomonas aeruginosa and Antibiotic Resistance Pattern of the Isolates from Dhaka Medical College Hospital. Bangladesh Journal of Medical Microbiology. 2007; 01(02): 48-51. (5) Lina TT, Rahman SR, Gomes DJ. Multiple-antibiotic

resistance mediated by plasmids and integrons in uropathogenic escherichia coli and klebsiella pneumoniae – Bangladesh. Journal of Microbiology. 2007; 24(1): 19 - 23.

(6) Rahman M M, Haq J A, Hossain M A, Sultana R, Islam F, Islam A.H.M.S. Prevalence of extended-spectrum-lactamase-producing Escherichia coli and Klebsiella pneumoniae in an urban hospital in Dhaka, Bangladesh. International Journal of Antimicrobial Agents. 2004; 24: 508 – 510.

(7) Islam KMS. ESBL-a therapeutic challenge. Bangladesh Journal of Medical Microbiology. 2009; 03(01): 1 – 3.

(8) Darouiche RO. Treatment of infections associated with surgical implants. New England Journal of Medicine. 2004; 350: 1422 – 9.

(9) Iannini PB. Hospital–acquired Urinary Tract Infections: Implications for Treatment and Prevention. Current Opinion in Infectious Diseases. 2002; 4: 15 – 20. (10)World Health Organization, Regional Office for

South-East Asia.. Prevention and containment of antimicrobial resistance: report of a regional meeting, Chiang Mai, Thailand, 8 June – 11 June 2010. New Delhi: WHO-SEARO, 2010, Document No. SEA-HLM-408.

(11)Hossain MA, Rahman M, Ahmed QS, Malek MA, Sack RB, Albert MJ, Increasing frequency of

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(12)Khan MU, Shahidullah M. Contrasting epidemiology of Shigellae dysenteriae and Shigellae flexneri, Dacca. Transactions of the Royal Society of Tropical Medicine and Hygiene. 1980; 74: 528–533.

(13)Khan A.I., Huq S, Malek M A, Hossain M I, Talukder K.A., Sack D. A, Faruque S. G., Salam M A. Shigella serotypes among hospitalized patients in urban Bangladesh and their antimicrobial resistance. Epidemiology and infection. 2004; 132: 773 – 777. (14)Ahmed M U, Chawdhury F A H, Hossain M, Sultan S Z, Alam M, Salahuddin G, Alam A, Nessa K, Nahar S, Waris S A. Monitoring Antimicrobial Susceptibility of Neisseriagonorrhoeae Isolated from Bangladesh during 1997-2006 Emergence and Pattern of Drug-resistant Isolates. Journal of Health, Population and Nutrition. 2010; 28 (5): 443–449.

(15)Rahman MM, Haq JA, Morshed MAHG and Rahman MA. Salmonella typhi with decreased susceptibility to ciprofloxacin- An emerging problem in Bangladesh. International Journal of Antimicrobial Agents. 2005; 25: 345–346.

(16)Ahmed D, D’ Costa LT, Alam K, Nair GB, Hossain MA. Multidrug-resistant Salmonella enterica serover Typhi isolates with high-level resistance to ciprofloxacin in Dhaka, Bangladesh. Antimicrobial Agents and Chemotherapy. 2006; 50: 3516–7.

(17)Rasul C H, Hassan M A, Habibullah M. Neonatal sepsis and use of antibiotic, Pakistan. Journal of Medical Sciences. 2007; 23 (1).

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(19)Kamal SM, Hossain MS, Islam ABMT, Begum V, Bleumink MB, Deun AV, et al. Anti-TB drug resistance patterns among category 2 failure patients in Bangladesh. 1st International Conference on Lung Health, February 2008, Dhaka, Bangladesh. Dhaka: 2008.

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Microbiology. 2009; 03(01): 13-17.

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(24)World Health Organization. World malaria report http://rbm.who.int/wmr2005/profiles/bangladesh.pdf. Accessed 14 July 2005.

(25)Olliaro PL, Guerin PJ, Gerstl S, Haaskjold AA, Rottingen JA, Sundar S. Treatment options for visceral leishmaniasis: a systematic review of clinical studies done in India, 1980–2004. Lancet Infect Dis. 2005 Dec; 5(12): 673-74.

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leishmaniases report of the WHO expert committee on the control of leishmaniases. Geneva: WHO, 2010. (27)Bangabandhu Sheikh Mujib Medical University.

Antibiotic guidelines. Dhaka, 2005.

(28)Roy J. Health status, treatment and drug use in rural Bangladesh: a case study of a village. Australian Journal of Rural Health. 1997; 5(2): 70 – 5. (29)Ahmed SM, Hossain MA. Knowledge and practice of

unqualified and semi-qualified allopathic providers in rural Bangladesh: Implications for the HRH problem. Health Policy. 2007; 84: 332–343.

(30)Akter FU, Heller D, Smith A, Rahman MM, Milly AF. Antimicrobial use in paediatric wards of teaching hospitals in Bangladesh. Mymensingh Medical Journal. 2004; 13(1): 63 – 6.

(31)Chowdhury FR, Rahman MM, Huq MF, Begum S. Rationality of drug uses: its Bangladeshi perspectives. Mymensingh Medical Journal. 2006; 15(2): 215-9. (32)Mamun KZ. Prevalence and genetics of resistance to

commonly used antimicrobial agents in faecal enterobacteriaceae from children in Bangladesh. [PhD thesis]. University of Liverpool, 1991.

(33)Islam MS. A review on the policy and practices of therapeutic drug uses in Bangladesh. Calicut Medical Journal. 2006; 4(4): e2.

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(38)Akter FU, Heller D, Smith A, Rahman MM, Milly AF. Antimicrobial use in paediatric wards of teaching hospitals in Bangladesh. Mymensingh Medical Journal. 2004; 13(1): 63 – 6.

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accessed 6 January 2011). ₍₃₉₎_{Alam MB, Ahmed FU, Rahman ME. Misuse of drugs in} acute diarrhoea in under-five children. Bangladesh Medical Research Council Bulletin. 1998; 24 (2): 27-31.

(36)Baqui AH, Black RE, Arifeen SE, Yunus M, Zaman K, Begum N et al. Zinc Therapy for Diarrhoea Increased the Use of Oral Rehydration Therapy and Reduced the Use of Antibiotics in Bangladeshi Children. Journal of Health, Population and Nutrition. 2004; 22(4): 440 – 442.

(40)Editorials. Inappropriate treatment for dysentery. British Medical Journal. 1996; 313: 181-182.

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ARI in rural areas Bangladesh. Southeast Asian Journal of Tropical Medicine and Public Health. 2003; 34(2): 337 – 42.

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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 there1_.

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

urine, blood and pus samples from different levels of hospitals in Nepal2-8_.

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 *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.

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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 E. coli, S. aureus, K. pneumoniae, P. mirabilis, P. vulgaris, P. aeruginosa

S. typhi, S. paratyphi

S. aureus, E. coli, P. mirabilis

2005, 2010

Regional Hospital E. coli, S. aureus, K. pneumoniae, Citrobacter

S. typhi E. coli, S. aureus, Pseudomonas

2007–2008

Medical colleges E. coli, S. aureus, K. pneumoniae, Enterococcus spp., Pseudomonas spp, Proteus spp., E. faecalis

S. aureus, S. typhi, S. paratyphi A, Enterobacter

E. coli, S. aureus, K. pneumoniae, Streptococcus spp., Pseudomonas spp., Acinobacter

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).

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1

Table 3: Antibiotic sensitivity in E. coli from urinary tract pathogens*

Health facility

level _Amikacin

Amoxycilli

n

Ampicilli

n

Azithromycin Cefix

ime

Cefot

ax

ime

Ceftazidime Ceftr

iax

one

Cephalexin

Chloramphe

nicol

Ciproflox

acin

Cotrimoxazole Gen

tamyci

n

Nalidi

xic

Acid

Nitrofurantoin Norfloxacin Ofloxaci

n

Zonal hospitals >50.0-83.3

NR 20.8 NR NR NR NR NR NR NR >50.0 41.7 >50.0 62.5 68.8 >50.0 70.8

Regional Hospital 80.0 NR 29.2 76.2 58.9 NR NR 100.0 100.0 100.0 56.5 8.3 38.5 22.2 87.5 36.4 57.1

Medical colleges >50.0-89.4

21.3-65.3

13.3 NR NR 45.6

>50.0-98.0

>50.0-83.3 5.2->50.0

NR

48.0-63.7 40.6->50.0

>50.0-95.6

29.5->50.0

44.7-91.0

44.7-64.7

>50.0

NR: Not reported, not all sites reported all drugs. Testing dates ranged from 2004–2010

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Table 4: Antibiotic sensitivity in S. aureus from urinary tract pathogens*

Health facility level

Amikac

in

Ampic

illin

Azithromyc

in

Ceftriaxone Ceph

alexin

Ciprofloxacin Cloxac

illin

Cotrimoxazole Erythromycin Gentamycin Nitrofura

ntoin

Norfloxacin Oflo

xacin

Zonal hospital 100.0 0.0 NR NR 0.0 NR NR 50.0 NR NR 100.0 NR 100.0

Regional Hospital NR 50.0 100.0 NR NR 100.0 NR NR NR NR 50.0 50.0 NR

Medical colleges >50.0-_67.3 16.5-_60.1 NR >50.0-_100.0 36.3-_64.4 >50.0-_85.2 >50.0-_92.2 44.2-_80.3 57.7-_84.0 42.6-_62.8 95.6-_98.6 _100.050.0- >50.0

NR: Not reported, not all sites reported all drugs. Testing dates ranged from 2004–2010,

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Table 5: Antibiotic sensitivity in K. pneumoniae from urinary tract pathogens*

Amikac

in

Am

oxyc

ill

in

Ampic

illin

Azithromyc

in

Cefixime

Ceftazidime Ceftriaxone Ceph

alexin

Ciprofloxacin _{Cotrimoxazole} Gentamycin Nalidixic

Ac

id

Nitrofura

ntoin

Norfloxacin Oflo

xacin

Tetracyc

line

Zonal

hospital 100.0 NR 0.0 NR NR NR NR 0.0 NR 33.3 NR NR NR NR 83.3 NR

Regional

Hospital NR NR 100.0 25.0 33.3 NR 100.0 NR 50.0 NR NR 16.7 75.0 75.0 83.3 NR

Medical colleges

>50.0-64.7

4.6->50.0 NR NR NR

>50.0-93.1

>50.0-88.0

7.6-58.4

>50.0-82.0

40.5-73.2

>50.0-93.1

35.7->50.0

45.9-93.2

46.0-88.3 >50.0 >50.0

NR: Not reported, not all sites reported all drugs. Testing dates ranged from 2004–2010.

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Table 6: Antibiotic sensitivity in S. enterica typhi and Para-typhi A from blood pathogens*

Amikac

in

Am

oxyc

ill

in

Ampic

illin

Azithromyc

in

Cefixime _Cefotaxime

Ceftazidime Ceftriaxone Ceph

alexin

Chloramphenicol Ciprofloxacin Cotrimoxazole

Gentamycin Imipenem Oflo

xacin

Zonal

hospital >50.0 NR 50.0 NR NR NR NR 100.0 NR >50.0 >50.0 >50.0 NR NR 50.0

Regional

Hospital 100.0 NR 43.5 100.0 100.0 NR NR 94.5 NR 100.0 100.0 61.1 100.0 NR 95.8

Medical

colleges NR 100.0

>50.0-91.8 100.0 NR 100.0

>50.0-100.0

42.0-100.0

>50.0-100.0 NR 100.0

42.0-100.0

NR: Not reported, not all sites reported all drugs. Testing data ranged from 2004–2010.

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Table 7: Antibiotic sensitivity in S. aureus from pus pathogens*

Amikac

in

Ampic

illin

Azithromyc

in

Cefixime

Ceftriaxone Ceph

alexin

Chloramphenicol Ciprofloxacin

Cloxac

illin

Cotrimoxazole Erythromycin Gentamycin Nitrofura

ntoin

Oflo

xacin

Pro

caine

Penicillin

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 100.0 50.0 66.7 70.0 71.4 NR 100.0 57.1 57.1 100.0 NR 57.9 NR 63.1 100.0

Medical colleges

>50.0-79.4

22.7-37.0 NR NR >50.0

31.6-83.6 NR

>50.0-75.3

57.1-88.6

45.6-70.9

53.2-79.3

>50.0-74.2 NR >50.0 NR

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Table 8: Antibiotic sensitivity in E. coli from pus pathogens*

Amikac

in

Am

oxyc

ill

in

Ampic

illin

Azithromyc

in

Cefixime _Cefotaxime

Ceftriaxone Ceph

alexin

Ciprofloxacin _{Cotrimoxazole} Gentamycin Nitrofura

ntoin

Norfloxacin Oflo

xacin

Polymyxin

B

Zonal hospital

>50.0-87.5 NR 25.0 NR NR NR NR 12.5 >50.0 37.5 NR >50.0 >50.0 >50.0 NR

Regional

Hospital 70.0 NR 42.8 61.5 44.4 NR 25.0 100.0 60.0 33.3 50.0 NR NR 61.5 NR

Medical colleges

>50.0-85.8 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

>50.0-78.2 NR NR >50.0 >50.0

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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 hospitals9_{. 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) strains10_.

Transmission of highly resistant bacteria from patient to patient within the hospital environment (nosocomial transmission)

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 usage11_.

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).

(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).

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Antimicrobial resistance in resource-poor settings –

Sri Lankan experience

C.G.U.A Patabendige*, N.S. Chandrasiri**, L. I. Karunanayake***, G.K.D. Karunaratne+_{, P. Somaratne***, J.P Elwitigala}++_{and P. Chandrasiri}+++_,

Abstract

An increasing trend in antimicrobial resistance in healthcare settings has been observed and demonstrated in Sri Lanka with the improvement of microbiological services in the country. Some good studies have been carried out in different localities, giving the level of resistance. There is an observation made by health professionals about upward trend in development of antimicrobial resistance in pathogenic microorganisms in the community but data to demonstrate it is scarce.

Though there is no national antimicrobial policy, local policies are in operation in some hospitals. Data from the ongoing antimicrobial resistance surveillance will be used for the formulation of the national antimicrobial policy in the future. The Sri Lanka College of Microbiologists, the Sri Lanka Medical Association and the Task Force in Microbiology are some of the professional organizations who are working hard on this subject. The increasing trend in antimicrobial resistance is likely to be due to multiple reasons. Strengthening rational use, legal provisions for prescribing, registration policies, infection control activities, training of health-care workers and the community, further strengthening of microbiology laboratories by providing continuous supply of consumables and necessary equipment to perform standardized methodology would help in combating this problem. Furthermore, a situational analysis of irrational use of antimicrobials in agriculture and fishery and quick action to minimize it and assuring continuous supply of good quality antibiotics to be used according to the antimicrobial policies are essential in controlling this menace. Otherwise an uncontrollable situation will emerge causing morbidity and mortality due to infections with resistant micro-organisms with no antimicrobials effective for their management.

Introduction

Sri Lanka is a developing country with a state-sponsored free health system with co-existing

private health care. The country has achieved good life expectancy as well as low maternal and neonatal mortality rates compared to most other Asian countries during the past few decades. Currently, the country faces a problem of an increasing trend in antimicrobial resistance in microorganisms in both health care and community settings probably due to multiple reasons. Some of these organisms are extended spectrum ß lactamase (ESBL) producing coliforms, multidrug-resistant Pseudomonas and Acinetobacter spp, methicillin resistant Staphylococcus aureus (MRSA), penicillin resistant Streptococcus pneumoniae and quinolone resistant Salmonella typhi and *Consultant Microbiologist, National Cancer Institute,

Maharagama, Sri Lanka

**Consultant Microbiologist, Colombo South Teaching Hospital, Kalubowila, Sri Lanka

***Consultant Micorbiologist, Medical Research Institute, Colombo 08, Sri Lanka

+_{Consultant Microbiologist, Lady Ridgeway Hospital,} Colombo 08, Sri Lanka

***Consultant Microbiologist, Medical Research Institute,Colombo 08, Sri Lanka

++_{Consultant Microbiologist, National Tuberculosis (TB)} Reference Laboratory, Welisara, Sri Lanka

+++_{Consultant Micorbiologist, National Hospital of Sri} Lanka, Colombo, Sri Lanka

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Salmonella paratyphi A. Appropriate and timely action needs to be taken by the authorities in order to minimize the morbidity and mortality due to antimicrobial resistant infections and also to preserve the effectiveness of antimicrobial agents which are used in management of microbial infections.

Situation in health-care settings

For the detection of antimicrobial resistance in different microorganisms which are of medical importance and observing its trends, it is extremely important to identify the microorganisms accurately and carry out antimicrobial sensitivity according to standardized methodology. Till the turn of century, microbiology facilities were not widespread in the country. Currently almost all teaching hospitals and some general hospitals in different provinces are served by consultant microbiologists. With the appointment of these consultants, microbiology services improved countrywide thus helping to implement stan-dardized, universally accepted methodology for antimicrobial sensitivity testing and also proper identification of the infectious agents to the species level. In addition to the onsite consultant microbiologists, they serve as offsite consultants to the hospitals where onsite consultants have not been appointed yet, by giving advice on antimicrobial prescribing and microbiological testing needs. Qualified medical laboratory technologists and laboratory assistants actively work in all microbiology laboratories in the government sector.

At present, there is an ongoing antimicrobial resistance surveillance project in the country involving 10 surveillance centres namely six from the Western and one each from the Sabaragamuwa, Southern, Central and Uva provinces for monitoring of Gram negative micro organisms. The project will be extended for the identification of the gram positive organisms 2011. Data obtained from the surveillance centres during the past year will be analysed early next year and data will

be used for the formulation of the national antibiotic policy. The surveillance data will be published in the near future. The Task Force in Microbiology which has been set up under the chairmanship of the Director General of Health Services and with the participation of consultant microbiologists from different healthcare settings in different provinces has recognized the monitoring of antimicrobial resistance as a national priority.

Though there is no national antimicrobial policy, the consultant microbiologists who are working in the hospital settings have prepared local policies for their institutions taking into account the prevalence rates of the microbial pathogens and their sensitivity pattern. But compliance is variable from satisfactory to poor in different settings.

Though limited training programmes have been held locally at hospital settings, training imparted to doctors on rational use of antimicrobials is not satisfactory. Public awareness about rational use of antimicrobials is poor. Drug review committees and drug therapeutic committees have been set up in hospitals as a requirement of the Ministry of Health but their active operation to reach the goals in prevention and control of antimicrobial resistance is questionable at present.

Though there are no regulations directly related to antimicrobial use at present, there are indirect controls such as at the time of registration, it is granted as schedule 11 – B drug for all antimicrobials, leaving them to be prescribed by a registered medical practitioner but prescribing by unqualified personnel is occurring indicating the need for strengthening the legal provisions for prescribing of antimicrobials. Use of substandard antimicrobials is a problem together with the lack of continuous supply of standard antimicrobials. Remedial actions are being taken by the relevant authorities to address this issue. The level of irrational use of antimicrobials in agriculture and fishery in the country is unknown. Through personal

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communications, we have been made aware that some of the antibiotics are being used as growth promoters in agriculture and fishery in the country.

In resource-poor settings, implementation of good infection control practices to prevent cross-infections due to multidrug-resistant organisms is questionable. Though health-care workers are aware about the practices, adequate resources are not available for effective implementation.