Straight from the Heart: IMA-IAP-NNF Policy on viability in India

Straight from the Heart: IMA-IAP-NNF Policy on viability in India

As per the ILCOR / AAP / AHA 2015 Neonatal Resuscitation Guidelines Subsection on Withholding Resuscitation we quote:

“There is a no evidence to support the use of any particular delivery room prognostic score presently available over gestational age assessment alone, in preterm infants at less than 25 weeks gestation”.

As per the NRP Guidelines 3rd Edition (India) “Neonatal Resuscitation: India

“Questions about initiation of Resuscitation for extremely premature babies is a grey area. Babies born between 24+ to 28 weeks has been increasing in the developed countries, it may still not be true for most parts of our country. Non initiation of Resuscitation may be considered appropriate in confirmed gestation below 25 weeks (20 weeks to 24 completed weeks), anencephaly, and confirmed lethal genetic malformation disorder”.

The most read textbook of community medicine in India ‘Park’s Textbook of Preventive and Social Medicine’ states that “viability is a stage when foetus becomes capable of living independently, this has been fixed administratively at 28 weeks, when the foetus weighs approximately 1000 g”.[1]

IMA-IAP-NNF Policy

Viability is defined as >28 weeks and more than 1000 grams. Anything less than that level of treatment has to be decided on case to case basis based on chances of intact survival, informed consent taking into consideration social determinants of health. Basic care should not be compromised.

Reference

1.      Park K. Demography and Family Planning. In: Park K, editor. Park’s Textbook of Preventive and Social Medicine. 24th ed. Jabalpur: Bhanot; 2017.p.539.

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/

IMA Policy on Antibiotics

IMA Policy on Antibiotics

At the Antimicrobial Resistance Conference, held in New Delhi yesterday, to discuss the IMA Antibiotic Policy, the following decisions were taken.

• Doctors should write the antibiotic in a box to differentiate it from other drugs in the prescription.
• The role of antibiotics should be discussed in an informed consent.
• When prescribing antibiotics, clear instructions should be given to the patient about no refill of antibiotic prescription without signature of the doctor.
• No antibiotic cover or prophylactic antibiotic should be given without a high degree of clinical suspicion.
• No antibiotics should be prescribed in following conditions:

o    Small bowel diarrhea

o    Fever with cough and cold

o    Dengue

o    Chikungunya

o    Malaria

o    Fever with rash

• Early initiation of antibiotics is the rule in suspected sepsis, bacterial pneumonia, meningitis and confirmed TB.
• Food Safety and Standards Authority of India (FSSAI) should make it mandatory for food companies to label all poultry and agriculture products as “Antibiotic-free”.
• IMA will be writing to the Health Ministry to formulate clear guidelines about safer disposal of left over antibiotics.

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

                     i.        improving awareness and understanding of AMR through effective communication, education and training;

                    ii.        strengthening knowledge and evidence through surveillance;

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

                   iv.        optimizing the use of antimicrobial agents in health, animals and food;

                    v.        promoting investments for AMR activities, research and innovations; and

                   vi.        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.

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).