IMA Policy on Antimicrobial/Antibiotic Resistance

IMA Policy on Antimicrobial/Antibiotic Resistance

Ensuring universal health coverage and achievement of Sustainable Development Goals

Issuing Authority: Indian Medical Association (IMA)

Scope: The policy covers use of antibiotics in human healthcare and applies to all IMA members.

Contact Person: Dr KK Aggarwal, President, Indian Medical Association

Definitions

·         Antimicrobial resistance for doctors

·         Antibiotic resistance for public

Preamble

Growing antibiotic resistance has made it difficult to treat many bacterial infections such as gonnorhea, typhoid and urinary tract infections. Within antimicrobial resistance (AMR), antibacterial resistance or antibiotic resistance as it is much better understood, is the main focus of global efforts for its containment.

The Ministry of Health & Family Welfare (MoHFW) has identified AMR as one of the top 10 priorities for its collaborative work with WHO. India’s National Action Plan on Antimicrobial Resistance (NAP-AMR)[1], was launched at the ‘Inter-Ministerial Consultation on Antimicrobial Resistance (AMR) containment’ on April 19, 2017. The Delhi Declaration on Antimicrobial Resistance[2]– an inter-ministerial consensus, was also released at the end of the Inter-Ministerial Consultation with a pledge to adopt a collaborative One Health approach towards prevention and containment of AMR in India.

The NAP-AMR identifies six strategic priorities:

1.     Improving awareness and understanding of AMR through effective communication, education and training

2.     Strengthening knowledge and evidence through surveillance

3.     Reducing the incidence of infection through effective infection prevention and control

4.     Optimizing the use of antimicrobial agents in health, animals and food

5.     Promoting investments for AMR activities, research and innovations

6.     Strengthening India’s leadership on AMR

Policy point 1

Etiology-based treatment of infections to be adopted instead of syndromic management; with focus on strengthening and utilizing microbiology laboratory services, especially culture sensitivity.

Policy point 2

Antibiotic information may also be included as a part of the informed consent process for medicolegal safety. 

Policy point 3

Any antibiotic prescribed to put in a box, in patient prescriptions for ease of identification

Policy point 4

Total number of antibiotic tablets/capsules to be specified along with treatment duration

Policy point 5

Antibiotics not to be prescribed for fever with rash; cough or cold; suspected or confirmed dengue, malaria, chikungunya, viral hepatitis or any viral syndrome, unless clinically warranted

Policy point 6

Appropriate antibiotics to be prescribed at the earliest to manage suspected sepsis, meningitis, pneumonia or positive cases of tuberculosis

Policy point 7

All prescriptions to be accompanied with a rider stating ‘no refill without doctor’s prescription’ (could be printed on the prescription pad as footer)

Policy point 8

Every medical establishment to draw its own antibiotic policy (IV to oral antibiotic switch, antibiotic preference based on local antibiogram, infection prevention and control, reuse of medical devices and safe syringe practices)

Policy point 9

MDR TB and XDR TB to be notified to health authorities and surveillance teams (IDSP)

Policy point 10

Ensure root cause analysis for any outbreak of MDR infection in hospital/healthcare facility

Policy point 11

Recommend shifting Schedule H antibiotics to H1, and H1 antibiotics to Schedule X

Policy point 12

All food products must be labeled  with “Antibiotic status”

Policy point 13

Antibiotic waste disposal policy to be developed to prevent contamination of the environment; preventing discharge of untreated waste into soil and rivers

Remember

·         Costlier and newer antibiotics do not necessarily mean they are more effective.

·         Just as you do not start treatment in TB, HIV, HCV unless proven by laboratory based diagnosis, wherever possible, preferably initiate antibiotic therapy with a positive laboratory-based diagnosis for bacterial infection(s).

·         Adhere to recommended immunization schedules and hygiene practices (hand hygiene, infection prevention and control practices, sanitation) in health care settings as well as in the community.

·         Follow cough etiquettes and respiratory hygiene, as well as inform your patients about the same.

·         Earlier shift from broad-spectrum to narrow spectrum targeted antibiotics based on culture and sensitivity reports. 

·         Educate patients about the principles of food hygiene “heat it, boil it, cook it, peel it or forget it”.

·         Before prescribing an antibiotic, always ask yourself 5 questions:

1.     Is it necessary?

2.     What is the most effective antibiotic?

3.     What is the most affordable antibiotic?

4.     What is the most effective dose?

5.     What is the most effective duration for prescribing the antibiotic?

Clinical tips

1.     It is the ‘bacteria’ that develop resistance to antibiotics and not the human body.

2.     Organisms sensitive to first and second generation cephalosporins, will always be sensitive to higher generation cephalosporins.

3.     Any organism sensitive to penicillin, ampicillin, amoxicillin, would invariably be sensitive to amoxicillin-clavulanic acid, piperacillin-tazobactam, carbapenems and cephalosporins.

4.     Restrict and minimize use of colistin/ polymyxin/fosfomycin/ linezolid in practice.

5.     Avoid prescribing quinolones (ciprofloxacin/levofloxacin/moxifloxacin) in routine practice. Quinolones are reserved as anti-TB drugs.

6.     Gram positive organisms – Staphylococci, Streptococci and Enterococci – are inherently resistant to colistin/polymyxin.

7.     Gram negative organisms – E. coli, Klebsiella, Pseudomonas, Acinetobacter, Proteus, Salmonella, Shigella – are inherently resistant to vancomycin and teicoplanin.

8.     Pseudomonas is invariably resistant to tigecycline, doxycycline, nitrofurantoin, cefixime, cefotaxime, ceftriaxone, trimethoprim-sulfamethoxazole.

9.     Proteus, Serratia, Providencia, Morganella are resistant to tigecycline, nitrofurantoin, colistin.

10.  MRSA is always resistant to penicillin, ampicillin, amoxicillin, cephalosporins, piperacillin-tazobactam, amoxicillin-clavulanic acid, carbapenems and generally sensitive to vancomycin, teicoplanin, linezolid, daptomycin, mupirocin.

Annexure

Background to the development of IMA policy on AMR/antibiotic resistance

Antibiotic resistance is a significant public health problem and has made it difficult to treat many infections such as TB, typhoid, pneumonia, gonorrhea. Antibiotic resistance increases duration of hospitalization, probability of adverse drug reactions as well as risk of therapeutic failure and associated mortality. No age group is exempt from antibiotic resistance. Second- or third-line drugs are expensive and result in increased costs of treatment. ² These drugs may also be less effective and have more side effects.

We are on the verge of a post-antibiotic era because many antibiotics that were previously effective against bacteria, are no more so. As a result, many common infections can become life threatening and may bring us back to the pre-antibiotic era. WHO’s list of antibiotic-resistant "priority pathogens", which included 12 classes of bacteria (Box 1) that pose the greatest threat to human health, aims to prioritize research against gram negative organisms especially those causing infections in the community. These pathogens are increasingly becoming resistant to existing antibiotics and in urgent need of newer treatments.

Box 1: Global priority list of antibiotic-resistant bacteria to guide research, discovery, and development of new antibiotics[3] Priority 1: Critical ·         Acinetobacter baumannii, carbapenem-resistant ·         Pseudomonas aeruginosa, carbapenem-resistant ·         Enterobacteriaceae, carbapenem-resistant, ESBL-producing Priority 2: High ·         Enterococcus faecium, vancomycin-resistant ·         Staphylococcus aureus, methicillin-resistant, vancomycin-intermediate and resistant ·         Helicobacter pylori, clarithromycin-resistant ·         Campylobacter spp., fluoroquinolone-resistant ·         Salmonellae, fluoroquinolone-resistant ·         Neisseria gonorrhoeae, cephalosporin-resistant, fluoroquinolone-resistant Priority 3: Medium ·         Streptococcus pneumoniae, penicillin-non-susceptible ·         Haemophilus influenzae, ampicillin-resistant ·         Shigella spp., fluoroquinolone-resistant

Key factors contributing to development of antibiotic resistance

Human health

o    Prescribing antibiotics for viral infections like the common cold, flu, diarrhea

o    Administering broad-spectrum antibiotics without a definitive diagnosis or indication for antimicrobial treatment

§  Prescribing antibiotics for fungal infections (invasive candidiasis, chronic pulmonary aspergillosis in patients with smear-negative pulmonary tuberculosis, fungal asthma, life-threatening invasive aspergillosis in patients with chronic obstructive pulmonary disease) on account of incorrect diagnosis

§  Overtreatment and undertreatment of Pneumocystis pneumonia in HIV-positive patients.

o    Overprescribing antibiotics (patient pressure and peer pressure)

o    Inappropriate antibiotic use: wrong drug, wrong doses (including subtherapeutic doses), or antibiotic not required

o    Relying on syndromic approach to manage infections instead of evidence-based prescribing.⁴

o    Noncompliance to prescribed antibiotics (not completing the entire antibiotic course; missing doses- accidently or deliberately)

o    Antibiotic misuse due to ease of access (over the counter availability, unregulated supply chains leading to over-medication, and self-medication by patients)

o    Lack of compliance to infection prevention and control measures including poor hygiene have contributed to the propagation and spread of resistant bacteria strains. ⁶

Animal health and agriculture

o    Overuse of antibiotics as growth supplements in livestock and aquaculture

o    Antibiotic additives in agricultural farms

The resistant bacteria in animals can spread to humans through the consumption of food or through direct contact with food-producing animals or through environmental spread (e.g. human sewage and runoff water from agricultural sites).⁴

Environment

o    The role of environment in the spread of antibiotic resistance is also being recognized.²

Soil is a reservoir of antibiotic resistance genes. Since most antibiotics are derived from soil microorganisms, they are intrinsically resistant to many antibiotics. Soil also receives a large portion of excreted antibiotics through application of manure and sewage sludge as fertilizers.⁶

o    Antibiotic-resistant organisms can also spread via drinking water derived from surface water sources. ⁶ Large amounts of antibiotics are released into municipal wastewater due to incomplete metabolism in human beings or due to disposal of unused antibiotics.² Evidence suggests that conventional wastewater treatment process is inadequate in removing resistant bacteria from municipal wastewater.⁶

o    Exposure to dairy manure alters soil microbial communities and ecosystem function and leads to greater antibiotic resistance. ⁸

Research and development

o    The antibiotics R&D pipeline is dry, with very little new research being done on antibiotics.

o    A report released by WHO in September 2017, “Antibacterial agents in clinical development – an analysis of the antibacterial clinical development pipeline, including tuberculosis” shows a serious lack of new antibiotics under development to combat the growing threat of antimicrobial resistance. Most of the drugs currently in the clinical pipeline are modifications of existing classes of antibiotics and are only short-term solutions.

o    Teixobactin, the first in a new class of antibiotics produced by soil microorganism (provisionally named Eleftheria terrae) has been reported. It is the first antibiotic to be discovered in three decades and is still at an early stage of development.  Teixobactin has activity against Gram-positive (but not Gram-negative) organisms and mycobacteria and has a novel mode of action as it inhibits peptidoglycan biosynthesis. ⁷

AMR in India: Facts & Figures

o    Typhoid: 5-10% resistance to chloramphenicol, ampicillin, trimethoprim-sulfamethoxazole, 20% to quinolones and 60% to nalidixic acid

o    Meningococcal infection: 50% resistance to ciprofloxacin, tetracycline & trimethoprim-sulfamethoxazole

o    Gonococcal infections: 50-80% penicillin, 20-80% ciprofloxacin, 2-10% ceftriaxone

o    MDR TB: 3-5% new cases, 10-15% in treated cases

o    XDR TB: 4-7% of MDR cases

o    MRSA: 15-25%

o    Klebsiella ESBL: 30-50%

o    Community E. coli ESBL production 15%, carbapenem resistance 6-10%, NDM1 3.2-4.5%

o    Sewage E. coli ESBL 20-60%, carbapenem resistance 12-20% and NDM1 5-7.2%

o    E. coli in sewage: 25% resistant in domestic waste/70% resistant in domestic and hospital waste, 95% resistant to cephalosporins in hospital waste

Recommendations for cross-sectoral involvement 

One health approach recognizes that the health of people is connected to the health of animals and the environment and aims to achieve the best health for people, animals, and our environment through collaborative efforts of multiple stakeholders. The approach must be adopted to contain the growing problem of antibiotic resistance. New “WHO guidelines on use of medically important antimicrobials in food-producing animals” (November 2017) aim to help preserve the effectiveness of antibiotics that are important for human medicine by reducing their unnecessary use in animals.

Healthy animals should only receive antibiotics to prevent disease if disease is diagnosed in other animals of the same flock, herd, or fish population. Where possible, sick animals should be tested to determine the most effective and prudent antibiotic to treat their specific infection. Educating the patients and the general public about the dangers of misuse or noncompliance to antibiotics, is also an important role to play.

References

1.     Meropol SB, Haupt AA, Debanne SM. Incidence and outcomes of infections caused by multidrug-resistant Enterobacteriaceae in children, 2007-2015. J Pediatric Infect Dis Soc. 2017 Feb 22.

2.     Prestinaci F, Pezzotti P, Pantosti A. Antimicrobial resistance: a global multifaceted phenomenon. Pathog Glob Health. 2015;109(7):309-18.

3.     Saleh N, Awada S, Awwad R, et al. Evaluation of antibiotic prescription in the Lebanese community: a pilot study. Infect Ecol Epidemiol. 2015;5:27094.

4.     Ayukekbong JA, Ntemgwa M, Atabe AN.  The threat of antimicrobial resistance in developing countries: causes and control strategies. Antimicrob Resist Infect Control. 2017;6:47.

5.     Denning DW, Perlin DS, Muldoon EG, et al. Delivering on antimicrobial resistance agenda not possible without improving fungal diagnostic capabilities. Emerg Infect Dis. 2017;23(2):177-83.

6.     Fletcher S. Understanding the contribution of environmental factors in the spread of antimicrobial resistance. Environ Health Prev Med. 2015;20(4):243-52.

7.     Piddock LJ. Teixobactin, the first of a new class of antibiotics discovered by iChip technology? J Antimicrob Chemother. 2015;70(10):2679-80.

8.     Wepking C, Avera B, Badgley B, et al. Exposure to dairy manure leads to greater antibiotic resistance and increased mass-specific respiration in soil microbial communities. Proc Biol Sci. 2017;284(1851).

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[1] Accessible at http://www.searo.who.int/entity/india/topics/antimicrobial_resistance/nap_amr.pdf?ua=1

[2]Accessible at http://www.searo.who.int/entity/india/topics/antimicrobial_resistance/delhi_dec_amr.pdf?ua=1

[3]Accessible at http://www.who.int/medicines/publications/global-priority-list-antibiotic-resistant-bacteria/en/