[Downloaded free from http://www.ijmm.org on Tuesday, December 11, 2012, IP: 125.16.60.178] || Click here to download free Android application for this journal Indian Journal of Medical Microbiology, (2012) 30(4): 381-3 1 Guest Editorial Development of antibiotic resistance and its audit in our country: How to develop an antibiotic policy Chand Wattal Persistent indiscriminate use and rising antibiotic resistance world over may result in “Post antibiotic era” in 7-10 years from now. This is an emergency situation for public health care and calls for immediate redress. Implementation of effective antibiotic policy can be one significant step in this direction. The basis of antibiotic policy rests in generating microbiological data and prescription auditing at any one geographical place. But there is a scarcity of quality literature on classified antibiogrammes from India, which is an impediment in formulating local, regional or national-level antibiotic policy. Why are we shy of measuring and sharing the data resulting in its scarcity. Anti-biogramme, prescription auditing and generation of drug resistance index (DRI) could take us a long way in looking at the control of resistance and rational use of antibiotics in our country. The concept of time and concentration-dependent class of antibiotics with understanding of their pharmacokinetics and pharmocodynamics are important factors for successful antibiotic therapy. I consider development of antibiotic resistance no less than global warming. Various issues involved in utilizing antibiotics intelligently and measuring its impact as well are discussed here. Overuse of antimicrobial agents has been described world over in both community[1,2] and hospital[3,4] settings. In addition to its effect on patients,[5] antibiotic misuse can provoke emergence of bacterial resistance[3] and increase healthcare cost.[6] It is evident that optimizing antibiotic use is a challenge that deserves to be undertaken. It has been observed that the infectious disease physician plays a crucial role in controlling antibiotic Corresponding author (email: <[email protected]>) Department of Clinical Microbiology and Immunology, Sir Ganga Ram Hospital, New Delhi, India Received: 31-08-2012 Accepted: 18-10-2012 Access this article online Quick Response Code: Website: www.ijmm.org PMID: *** DOI: 10.4103/0255-0857.103755 use in the hospital,[7] but a multidisciplinary team approach is known to do better.[6,8] Bantar et al.[9] published alarming rate of bacterial resistance in a surveillance study involving 27 Argentinean health-care centres and noted high rate of nosocomial infections, surgical prophylaxis errors leading to unnecessary cost increases in the hospital[10] and confirmation of misuse of antibiotics in the same hospital. These findings provide compelling evidence of the need for more rational use of anti-microbial agents. To our knowledge, a systematic strategy for control of antibiotic use in our country has not been undertaken or published, as a result of which it is difficult to compare consumption of antibiotics across hospitals in India. Inappropriate empiric antibiotic therapy is widespread and is associated with increased mortality in critically ill patients. Initial antibiotic selection must account for a variety of host, microbiologic and pharmacological factors. Institution-specific data, such as susceptibility patterns and local antibiotic use need be known. Tailoring antimicrobial therapy based upon culture and sensitivity results if available, will help reduce cost, decrease the incidence of super-infection and minimize the emergence of resistance. Therefore, it could be rewarding to invest in seeking microbiological answers in a patient whom we clinically believe has an infective aetiology (bacterial) before instituting antibiotics. The concept of antibiotic policy is not new and a lot of effort goes into this exercise wherever it is undertaken. It is its implementation in letter and spirit that requires serious thinking. Antibiotic Resistance Scenario and Prescription Auditing With the current anti-infective therapies, multidrug resistant (MDR) organisms have come to stay unless we change our practices. The matter is rendered more complicated due to the presence of Extended Spectrum β-lactamase (ESBL) and carbapenamaseproducing organisms as a result of the unbridled use of Cephalosporins[3,11] and carbapenems.[4] Though this is the scenario world over, particularly in intensive care units, in our country, we are more vulnerable due to the overwhelmingly indiscrete use and across-the-counter availability of antibiotics. [Downloaded free from http://www.ijmm.org on Tuesday, December 11, 2012, IP: 125.16.60.178] || Click here to download free Android application for this journal 382 Indian Journal of Medical Microbiology Illustrating this point is the high prevalence of Methicillin Resistant Staphylococcus aureus (35%43% in ICU) and VRE (10%-44%) prevalent in Indian hospitals.[12,13] In a study at our institute, we demonstrated a rise in consumption and resistance to broadspectrum anti-microbial agents and also established an association between consumption and resistance to these antibiotics.[4] There was a significant (P < 0.05) rise in ESBL producers in E. coli from 40 to 61 per cent over a period of 10 years.[3] We also observed a predominant burden, particularly in intensive care unit (ICU)’ s, of MDR Acinetobacter spp. and CRE Klebsiella spp.[3,4] Surprisingly , amongst the enterobacteriaceae, Klebsiella spp. has become the most notorious bug having acquired New Delhi Metallobeta lactamase -1 genes, as compared to other enterobacteriaceae.[14] Resistance to even the [13] newly introduced drug, tigecycline, has risen to 37%. The creeping resistance to colistin in MDR bacteria[13] is probably the “last straw” in this pandemonium. This grim scenario warrants a directed effort towards continued surveillance and antibiotic stewardship to minimize selection pressure and spread. The high resistance coupled with high anti-microbial consumption of approx. 201.2-226.5 Defined Daily Dose per 100 bed days in tertiary-care hospitals needs some serious introspection by all stake holders.[3] Unfortunately, data on anti-microbial consumption too, are scarce in India. In our community, during the surveillance of antimicrobial prescription by physicians in Delhi, we found high and irrational use of antibiotics in the community, due to peer pressure to prescribe high-end antibiotics and/ or inability to diagnose infections, as the main reasons for abuse of antibiotics.[15,16] More importantly, communicating data of anti-microbial prescription to policymakers for actionable plan remains a challenge. Development of a new index[17] called DRI is an effort in this direction. DRI is comparable to the composite economic indices that measure consumer prices and a stock market value. It is an aggregate resistance to various drugs across specified period of time. Annual change in the DRI helps in assessing the rate of depletion of antibiotic effectiveness and also identify difficult to treat organisms e.g., Klebsiella spp., and Acinetobacter spp. DRI can also help measure outcomes of any policy being implemented, e.g., antibiotic policy. The advantages of DRI are: • It is comparable across time and location • Calculable with minimal data • Simple enough for policymakers and non-infectious disease medical practitioners to comprehend gaps in drug effectiveness, affordability and accessibility. Several strategies for regulating anti-microbial vol. 30, No. 4 prescribing practices have been proposed, such as formulary replacement or restriction,[18] introduction of order forms,[19] health care provider education, feedback activities[20] and required approval from an infectious diseases physician for drug prescription.[7] Although most of these interventions have been assessed separately, data from prospective studies evaluating the impact of these different strategies in the same hospital setting remain scarce. In addition, results of a coordinated approach by a multidisciplinary team composed of infectious disease physicians, clinical microbiologists and pharmacists have rarely been reported.[8] We have shown a significant reduction in antibiotic use when Hospital Infection Control (HIC) committee performed feedback activities. For feedback activities and effective antibiotic policy it requires regular yearly data on anti-biogramme and antibiotic consumption. It is needless to emphasise that this data are expected to be quality-controlled. Lack of this could either be due to inadequate resources for compilation of such data or shying away from disclosing it in public domains for fear of backlash. The recent episode of NDM1 as one of the novel mechanism of resistance acquired by bacteria did see us in the eye of the storm. Thereafter, an urgent need has been felt to create a reliable data base across the country regarding the prevalence of antibiotic resistance in the community and hospitals. The Ministry of Health and Family Welfare Govt. of India is ceased with the burning issue of drug resistance, prescription auditing and HIC in the country, and has started an initiative in this direction. Extensive guidelines have been made by the experts from all the fields of medicine, veterinary and agriculture and horticulture sciences involving Central Scientific and Industrial Research Organization (CSIR) as well. A schedule H1 has been created for top-end antibiotics, and drugs like cephalosporins, amikacin, carbapenems, glycopeptides and tigecycline to be made available only at tertiary-care health facilities. While restrictions in the use of antibiotics in resource-constrained settings is recommended, it cannot be viewed without balancing treatment access to poor patients in rural India, an issue put at the forefront by our Union Health Minister. For the first time in the 15th fiveyear plan, the planning commission has allocated funds adequately to lay down the firm foundation of a network across the country to make the base-line data of antibiotic resistance available. Three central govt.-controlled hospitals, Lady Hardinge Medical College, Safdarjang Hospital and Ram Manohar Lohia Hospital have taken the lead in establishing a work module for the rest of the country to emulate, in framing an antibiotic policy and HIC guidelines based on their own anti-biogrammes. A model work sheet has been developed by the expert group committee on rational antibiotic use and framing of antibiotic policy which has been web cast on the official web site of the National Centre for Diseases Control (NCDC) earlier called as National Institute of Communicable Diseases (NICD) www.ijmm.org [Downloaded free from http://www.ijmm.org on Tuesday, December 11, 2012, IP: 125.16.60.178] || Click here to download free Android application for this journal October-December 2012 Wattal: AMR and developing antibiotic policy (http://www.scribd.com/doc/54122265/Indian-NationalPolicy-for-Containment-of-Antimicrobial-Resiatance-2011). Networking of laboratories across the country as has been realized is essential for a consensus guideline and to understand the requirement of vaccines for our country. It is also required to understand the researchable areas relevant for our country. It is hard to understand as to why do we fear sharing our data. As a result, the national data base does not exist. Or if any sparse data are available, is it qualitycontrolled? Why are we shying away from this activity? Should we all answer? 10. 11. 12. 13. References 1. Ganguly NK, Arora NK, Chandy SJ, Fairoze MN, Gill JP, Gupta U, et al. Rationalizing antibiotic use to limit antibiotic resistance in India. Indian J Med Res 2011;134:281-94. 2. Gonzales R, Steiner JF, Sande MA. Antibiotic prescribing for adults with colds, upper respiratory tract infections, and bronchitis by ambulatory care physicians. JAMA 1997;278:901-4. 3. Datta S, Wattal C, Goel N, Oberoi JK, Raveendran R, Prasad KJ. A ten year analysis of multi-drug resistant blood stream infections caused by Escherichia coli & Klebsiella pneumoniae in a tertiary care hospital. Indian J Med Res 2012;135:907-12. 4. Goel N, Wattal C, Oberoi JK, Raveendran R, Datta S, Prasad KJ. Trend analysis of antimicrobial consumption and development of resistance in non-fermenters in a tertiary care hospital in Delhi, India. J Antimicrob Chemother 2011;66:1625-30. 5. Beilby J, Marley J, Walker D, Chamberlain N, Burke M; FIESTA Study Group. Effect of changes in antibiotic prescribing on patient outcomes in a community settings: A natural experiment in Australia. Clin Infect Dis 2002;34:55-64. 6. Barenfanger J, Short MA, Groesch AA. Improved antimicrobial interventions have benefits. J Clin Microbiol 2001;39:2823-8. 7. John JF Jr, Fishman NO. Programmatic role of the infectious diseases physician in controlling antimicrobial costs in the hospital. Clin Infect Dis 1997;24:471-85. 8. Gums JG, Yancey RW Jr, Hamilton CA, Kubilis PS. A randomized, prospective study measuring outcomes after antibiotic therapy intervention by a multidisciplinary consult team. Pharmacotherapy 1999;19:1369-77. 9. Bantar C, Famiglietti A, Goldberg M. Three-year surveillance study of nosocomial bacterial resistance in Argentina. The 14. 15. 16. 17. 18. 19. 20. 383 Antimicrobial Committee; and the National Surveillance Program (SIR) Participants Group. Int J Infect Dis 2000;4:85-90. Bustos JL, Vesco E, Tosello C, Almará A, Boleas M, Magnin E, et al. Alarming baseline rates of nosocomial infection and surgical prophylaxis errors in a small teaching hospital in Argentina. Infect Control Hosp Epidemiol 2001;22:264-5. Cunha BA. Antibiotic resistance. Med Clin North Am 2000;84:1407-29. Wattal C, Goel N, Oberoi JK, Raveendran R, Datta S, Prasad KJ. Surveillance of multidrug resistant organisms in tertiary care hospital in Delhi, India. J Assoc Physicians India 2010;58:32-6. Sir Ganga Ram Hospital. Microbiology newsletter, 2012. Available from: http://sgrh.com/newsletters/mb%20apr%20 2012.pdf. [Last accessed 2012 Aug 25]. Snitkin ES, Zelazny AM, Thomas PJ, Stock F, Henderson DK, Palmore TN; NISC Comparative Sequencing Program Group et al. Tracking a hospital outbreak of carbapenem-resistant Klebsiella pneumoniae with whole-genome sequencing. Sci Transl Med 2012;4:148ra116. Wattal C, Raveendran R, Kotwani A, Sharma A, Bhandari SK, Sorensen TL, et al. “Establishing a new methodology for monitoring of antimicrobial resistance and use in the community in a resource poor setting”. J Appl Ther Res 2009;7:16-24. Kotwani A, Wattal C, Katewa S, Joshi PC, Holloway K. Factors influencing primary care physicians to prescribe antibiotics in Delhi India. Fam Pract 2010;27:684-90. Laxminarayan R, Klugman KP. Communicating trends in resistance using a drug resistance index. BMJ Open 2011;1:e000135. Lee J, Carlson JA, Chamberlain MA. A team approach to hospital formulary replacement. Diagn Microbiol Infect Dis 1995;22:239-42. Gyssens IC, Blok WL, van den Broek PJ, Hekster YA, van der Meer JW. Implementation of an educational program and an antibiotic order form to optimize quality of antimicrobial drug use in a department of internal medicine. Eur J Clin Microbiol Infect Dis 1997;16:904-12. De Santis G, Harvey KJ, Howard D, Mashford ML, Moulds RF. Improving the quality of antibiotic prescription patterns in general practice. The role of educational intervention. Med J Aust 1994;160:502-5. How to cite this article: Wattal C. Development of antibiotic resistance and its audit in our country: How to develop an antibiotic policy. Indian J Med Microbiol 2012;30:381-3. Source of Support: Nil, Conflict of Interest: None declared. Announcement “Quick Response Code” link for full text articles The journal issue has a unique new feature for reaching to the journal’s website without typing a single letter. Each article on its first page has a “Quick Response Code”. 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