WHAT CAN WE DO TO CONTROL ANTIBIOTIC RESISTANCE?

WHAT CAN WE DO TO CONTROL ANTIBIOTIC RESISTANCE?

Draft for ‘Indian Medical Association (IMA) Policy on Use of Antibiotics’ to be discussed at the Antimicrobial Resistance Conference supported by the World Health Organization (WHO) on November 11, 2017

Following are the issues to be discussed today to finalize and formulate IMA Policy with regard to use of antibiotics in order to control antibiotic resistance.

  • Antibiotic consent:Patients often demand antibiotics even when the doctor thinks it is unnecessary. ‘Antibiotic consent’ should be a part of the informed consent process, so that the patient is aware of the benefits and risks of antibiotics.
  • If you have prescribed antibiotics, put the name of the antibiotic in a box/underline it, so that patient can identify the antibiotic in his/her prescription
  • Write the total number of antibiotic tablets/capsules to be taken for the prescribed duration in the prescription and not just the dose administration schedule
  • Consider shifting Schedule H and H1 drugs to Schedule X
  • Antibiotic tax like sugar tax to prevent their overuse and also the money earned via tax on antibiotics can fund research into antibiotic resistance and/or development of new antibiotics
  • All food products should be labeled “Antibiotic free”.Antibiotic resistance is also a concern with regard to food safety. The bacteria that contaminate food can be resistant because of the use of antibiotics in people and for growth promotion or disease prevention in healthy food-producing animals. 
  • Antibiotic waste disposal policy to prevent contamination of the environment; discharge of untreated waste into soil and rivers is leading to spread of antibiotic resistance
  • Before prescribing antibiotic, always ask yourself

o    Is it necessary?

o    What is the most effective antibiotic?

o    What is the most affordable antibiotic?

o    What is the most effective dose?

o    What is the most effective duration for which the antibiotic should be administered?

Other Strategies to combat Antibiotic Resistance

  • Practice rational use of drugs (antibiotics)

o    Use when needed and according to guidelines

o    Avoid broad spectrum antibiotics without appropriate diagnosis

  • Prevent infections with the use of vaccination and by improving basic hygiene, including hand hygiene and infection control techniques and sanitation in health care settings as well as in the community
  • Farmers and food industry must stop using antibiotics routinely to promote growth and prevent disease in healthy animals to prevent the spread of antibiotic resistance. New “WHO guidelines on use of medically important antimicrobials in food-producing animals” released November 7, 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 it has been diagnosed in other animals in 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.”
  • One health approach, which recognizes that the health of people is connected to the health of animals and the environment. The goal is to achieve the best health for people, animals, and our environment through collaborative efforts of multiple stakeholders
  • India’s‘National Action Plan on Antimicrobial Resistance (NAP-AMR) 2017 – 2021’, was launched at the ‘Inter-Ministerial Consultation on antimicrobial resistance (AMR)containment in April 2017. The Ministry of Health & Family Welfare has identified AMR as one of the top 10 priorities for the ministry’s collaborative work with WHO.

A ‘Delhi Declaration’ (http://cseindia.org/userfiles/delhi_declaration_20170420.pdf), an inter-ministerial consensus released at the conclusion of this meeting pledged to adopt a holistic and collaborative approach towards prevention and containment of AMR in India.

Six strategic priorities have been identified under the NAP-AMR

  1.         improving awareness and understanding of AMR through effective communication, education and training;
  2.         strengthening knowledge and evidence through surveillance;

iii.        reducing the incidence of infection through effective infection prevention and control;

  1.         optimizing the use of antimicrobial agents in health, animals and food;
  2.         promoting investments for AMR activities, research and innovations; and
  3.         strengthening India’s leadership on AMR
  • Changing over to etiology based treatment of infections rather than a syndromic management.

Data from 77 countries show that antibiotic resistance is making gonorrhoea – a common sexually-transmitted infection – much harder, and sometimes impossible, to treat. The WHO Global Gonococcal Antimicrobial Surveillance Programme (WHO GASP) data from 2009 to 2014 find widespread resistance to ciprofloxacin (97% of countries that reported data in that period found drug-resistant strains), increasing resistance to azithromycin (81%), and the emergence of resistance to the current last-resort treatment: the extended-spectrum cephalosporins (ESCs) oral cefixime or injectable ceftriaxone (66%) (WHO News Release, July 7, 2017).

  • Ensure universal health coverage
  • New guidelines to be formulated taking into consideration the existing local, regional and national resistance and susceptibility data in the country
  • Hospital antibiotic policy should be formulated based on local susceptibility patterns
  • Reporting of antibiotic-resistant infections to surveillance groups to strengthen knowledge through surveillance and research
  • Educating the patients and the general public about the dangers of misuse or noncompliance to antibiotic

Background: About Antibiotic Resistance

 

The prevalence of antibiotic resistance is escalating worldwide at an alarming pace, with not enough resources available to control it. The WHO has recognized antibiotic resistance as a significant public health problem in its first global report “Antimicrobial resistance: Global report on surveillance” released in 2014.

 

No age group is exempt from antibiotic resistance. A retrospective study published in the March 2017 issue of the Journal of the Pediatric Infectious Diseases Society observed 700% increase in multidrug-resistant Gram-negative enteric Enterobacteriaceae infections between January 1, 2007, and March 31, 2015.1

 

Its impact on patients and communities are well-known. Antibiotic resistance has made it difficult to treat many infections such as TB, typhoid, pneumonia, gonorrhea. Antibiotic resistance also increases hospitalization duration, adverse drug reactions, therapeutic failure and associated mortality. When infections become resistant to first-line antibiotics, then second- or third-line drugs, which are costly resulting 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 where many of the antibiotics to which bacteria have developed resistance may become obsolete and there may no longer be any cure for many common infections, which once again may take their toll on human life like in the pre-penicillin era.

 

In its global report, the WHO has also cautioned about the likelihood of post-antibiotic era stating, “A post-antibiotic era—in which common infections and minor injuries can kill—far from being an apocalyptic fantasy, is instead a very real possibility for the 21st century”.

 

This year, WHO published its first ever list of antibiotic-resistant “priority pathogens”, which included 12 classes of bacteria (as below) in addition to multidrug-resistant tuberculosis that pose the greatest threat to human health. These pathogens are increasingly becoming resistant to existing antibiotics and urgently in need of new treatments. (WHO News Release, February 2, 2017)

WHO list of antibiotic-resistant priority pathogens

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

 

 Factors contributing to antibiotic resistance 

The major factor determining antibiotic resistance is use of antibiotics. But, there are several other factors, which also influence the emergence of antibiotic resistance.

  • Overprescribing of antibiotics

o    Patient pressure

o    Peer pressure

  • Inappropriate prescribing of antibiotics: Wrong drug, wrong doses, or antibiotic not required

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

o    Prescribing subtherapeutic doses of antibiotics: In a pilot cross-sectional study Saleh et al, the prescribed dose and the duration of the treatment were inaccurate in 52% and 64% of the cases, respectively. 3

o    Administering broad-spectrum antibiotics without a definitive diagnosis and indication for antimicrobial treatment. 4

o    Prescribing antibiotics in fungal infection due to incorrect diagnosis: A study published February 2017 issue of CDC’s journal Emerging Infectious Diseases concluded that “the lack of availability and underuse of nonculture fungal diagnostics results in overprescribing, prescription of unduly long courses of antibacterial agents, and excess empirical use of antifungal agents and leaves many millions of patients with undiagnosed fungal infections”. 5 

This study also cited four common clinical situations, where lack of routine diagnostic testing for fungal diseases often worsens the problem.

  • Inaccurate diagnosis of fungal sepsis in hospitals and intensive care units, resulting in inappropriate use of broad-spectrum antibacterial drugs in patients with invasive candidiasis.
  • Failure to diagnose chronic pulmonary aspergillosis in patients with smear-negative pulmonary tuberculosis.
  • Misdiagnosis of fungal asthma, resulting in unnecessary treatment with antibacterial drugs instead of antifungal drugs and missed diagnoses of life-threatening invasive aspergillosis in patients with chronic obstructive pulmonary disease.
  • Overtreatment and undertreatment of Pneumocystis pneumonia in HIV-positive patients.
  • Relying on syndromic approach to manage infections instead of evidence-based prescribing.4
  • Noncompliance and self-medication by patients
  • Patients not completing the entire antibiotic course; missing doses, either by accident or deliberate
  • Antibiotic misuse due to their availability over the counter, without prescription and through unregulated supply chains 
  • Poor hygiene and lack of compliance with infection prevention and control measures have contributed to the propagation and spread of resistant bacteria strains. 6
  • Overuse of antibiotics as additives in agriculture and as growth supplements in livestock and in aquaculture. 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
  • Availability of very few new antibiotics is another factor that has contributed to antibiotic resistance. A report released in September 2017 by WHO “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.

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 in at an early stage of development.  Teixobactin has activity against Gram-positive (but not Gram-negative) organisms and mycobacteria and a novel mode of action inhibiting peptidoglycan biosynthesis. 7

  • The role of environment in the spread of antibiotic resistance is now being recognized. 2

o    Soil is a reservoir of antibiotic resistance genes, since most antibiotics are derived from soil microorganisms that are intrinsically resistant to the antibiotics produced. 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. 6Large 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 the conventional wastewater treatment process is inadequate in removing resistant bacteria from municipal wastewater. 6Exposure to dairy manure alters soil microbial communities and ecosystem function and leads to greater antibiotic resistance. 8

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.
  1. Prestinaci F, Pezzotti P, Pantosti A. Antimicrobial resistance: a global multifaceted phenomenon. Pathog Glob Health. 2015;109(7):309-18.
  1. 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.
  1. 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.
  1. 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.
  1. Fletcher S. Understanding the contribution of environmental factors in the spread of antimicrobial resistance. Environ Health Prev Med. 2015;20(4):243-52.
  2. Piddock LJ. Teixobactin, the first of a new class of antibiotics discovered by iChip technology? J Antimicrob Chemother. 2015;70(10):2679-80.
  1. 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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