This document discusses antimicrobial resistance and provides an overview of several key topics:
1. It outlines various bacterial infections and classes of antibiotics used to treat them, as well as the history and classification of antibiotics.
2. It discusses the growing issue of antimicrobial resistance (AMR), costs and consequences associated with AMR, and examples of "superbugs" demonstrating resistance.
3. It covers interventions and strategies to address AMR, including improved stewardship, surveillance, research and development of new antibiotics, and prevention efforts.
2. Bacterial classes
Infectious diseases
History & Classes of antibiotics
Antimicrobial resistance (AMR)
Consequences/Costs of AMR
Superbugs & Super-resistance
Alerts on AMR
Interventions of AMR
Causes & Prevention of AMR
Concluding remarks
3. 1. A statement of an intention to inflict pain, injury,
damage, or other hostile action on someone in
retribution for something done or not
2. A person or thing likely to cause damage or
danger
Oxford
6. History of Antibiotics
www.nobelprize.org
• Alexander Fleming in 1928 accidentally
discovers PENICILLIN
• Penicillin quickly became a primary treatment for
pneumonia, diphtheria, syphilis, gonorrhea,
scarlet fever, and many other infections
7. Antibacterial antibiotics are commonly classified based on
◦ Mechanism of action
Those that target the bacterial cell wall
Cell membrane
interfere with essential bacterial enzymes
Those that target protein synthesis
◦ Chemical structure
Compounds isolated from living organisms
Semi synthetic
Synthetic
◦ Spectrum/Biological activity
Narrow-spectrum" antibacterial antibiotics target specific types of bacteria,
such as Gram negative or Gram positive bacteria
Whereas broad-spectrum antibiotics affect a wide range of bacteria
◦ Or use based on local application
First-line antibiotics
Second-line agents
Third-line antibiotics
9. There are about 209 marketed antibiotics for the
treatment of bacterial and fungal infections
Of these 209 marketed antibiotics, 87 (42%) are
classified as beta lactams (carbapenems,
cephalosporins, monobactams and penicillins).
Lack of innovation in the development of new antibiotic
molecules has increased greatly the challenge of
treating and eradicating certain infecting pathogens
Biopharm, 2012
10. Antimicrobial resistance occurs when bacteria
changes in ways that reduces/eliminates the
effectiveness of the drug designed to
cure/prevent the infection
Antibacteria resistance is currently recognised
as a major medical challenge
Resistance is also evident in other
microorganisms-namely;
Parasites
Fungi
And viruses
11. Hospital
MRSA
Glycopeptide-resistant
enterococci (GRE)
Enterobacteriaceae with
extended spectrum ß-
lactamases (ESBLs) or
carbapenemases
Pseudomonas aeruginosa
Stenotrophomonas maltophilia
Acinetobacter baumannii
Community
Mycobacterium
tuberculosis
Neisseria gonorrhoeae
Streptococcus
pneumoniae
Salmonella enterica
Group A streptococci
CA-MRSA
Boundary becoming increasingly blurred
Adapted from LJV Piddock, 2013
15. Drug resistance is so common and the term can
be described in so many ways;
◦ MDR
◦ XDR
◦ PDR
16. Mortality
◦ In Europe, 25,000 people die every year from drug-resistant
infections
Morbidity
◦ Prolonged illness
◦ 2.5 million extra in hospital days
◦ Greater chance of resistant organisms to spread to others
Cost
◦ 1.6 billion Euros extra cost
◦ 600 millions days of loss of productivity
Limited Options
◦ Few new drugs on the horizon
17. Rank Cause of death
Deaths
2002
(in millions)
Percentage
of all deaths
Deaths
1993
(in millions)
1993 Rank
N/A All infectious diseases 14.7 25.9% 16.4 32.2%
1
Lower respiratory
infections
3.9 6.9% 4.1 1
2 HIV/AIDS 2.8 4.9% 0.7 7
3 Diarrheal diseases 1.8 3.2% 3.0 2
4 Tuberculosis (TB) 1.6 2.7% 2.7 3
5 Malaria 1.3 2.2% 2.0 4
6 Measles 0.6 1.1% 1.1 5
7 Pertussis 0.29 0.5% 0.36 7
8 Tetanus 0.21 0.4% 0.15 12
9 Meningitis 0.17 0.3% 0.25 8
Worldwide Mortality due to Infectious Diseases
18. Predicted mortality for patients with and without antimicrobial-resistant infection (ARI)
Roberts et al., 2009 Clin Infect Dis.
APACHE score
19. The term “superbugs” refers to microbes with
enhanced morbidity and mortality
In some cases, super-resistant strains have also
acquired increased virulence and enhanced
transmissibility
Realistically, antibiotic resistance can be
considered a virulence factor
Gram-negative bacteria are highly efficient in
developing mechanisms of antimicrobial
resistance
20. Klebsiella pneumoniae, which causes many types of
healthcare-associated infections, including pneumonia,
urinary tract infections, and bloodstream infections
E. coli, which causes the majority of urinary tract
infections
Pseudomonas aeruginosa has evolved from being a
burn wound infection into a major nosocomial threat
Acinetobacter baumannii is a more recent Gram-
negative pathogen and is also primarily nosocomial are
sometimes resistant to all antibiotics
Neisseria gonorrhoeae, which causes the sexually
transmitted infection gonorrhea, the second most
commonly reported infectious disease in the United
States
21. Rise in the proportions of E. coli from bacteraemias in England, Wales and Northern Ireland
resistant to fluoroquinolones (white), oxyimino-cephalosporins (grey) and both (black)
Livermore, 2009 JAC
22. Gram-positive organism Staphylococcus aureus
enjoyed extensive press coverage over the years
S. aureus has a close association with humankind:
it is carried as a nasal commensal in 30% of the
population
Its presence has long been linked to common skin
infections such as boils
Although, it does not have the historical reputation
of M. tuberculosis, but in recent years, this
multidrug-resistant pathogen has emerged as one
of the major nosocomial infections
23. The landmark discovery and introduction of
methicillin in 1959 were thought to be a sure
defense against the penicillinases
The appearance of methicillin-resistant S. aureus
(MRSA) within just 3 years led inexorably to other
multiantibiotic-resistant variants
MRSA has moved outside the hospital and
become a major community-acquired (CA)
pathogen, with enhanced virulence and
transmission characteristics
In 2004, 40-60% S. aureus strains are MRSA and
usually MDR with low level resistance to
vancomycin
Treatment failures lead to more death with MRSA
and use of more reserved drugs
DeLeo et al., 2009; J Clin Invest
24. Numbers of MRSA bacteraemias in England by 6 month periods from 2001 to 2008 (bars, left axis) and
rates of bacteraemia per 10000 bed days (line, right axis)
Livermore, 2009, JAC
25. A long-recognized hospital denizen, the toxin-
producing anaerobe Clostridium difficile, is
increasingly found as the cause of severe intestinal
infections
Hypervirulent toxin-producing strains have been
recognized
Being a Gram-positive spore former, it is a hardy
organism and is readily transmitted by hospital
personnel, on equipment, and as aerosols
Its renewed prominence is considered the result of
extensive hospital use of antibiotics such as
expanded-spectrum cephalosporins, the newer
penicillins, and fluoroquinolones
In other words, these infections are the direct result
of antibiotic use
26. Tuberculosis is a leading cause of death 8 million people
develop active TB yearly with 1.7 million dying
TB was considered conquered in Europe due to the
ground-breaking discoveries of streptomycin and isoniazid
Resistance development was rapid and TB re-emerged as
a major public health problem
However for a variety of reasons multidrug resistance
continues to compromise TB therapy throughout the world
M. tuberculosis strains resistant to four or more of the front-
line treatments- XDR strains) have appeared and spread
rapidly in the last decade
And now there are TDR strains, which are totally drug
resistant!
Fears et al., 2010
27. M. tuberculosis strains resistant to four or more
of the front-line treatments (i.e., extremely drug-
resistant [XDR] strains) have appeared and
spread rapidly in the last decade or so
And now there are TDR strains, which are totally
drug resistant!
No effective treatment or prevention after 2
decades of WHO declaration of TB as a global
emergency
29. 109 candidate antibiotics in the clinical pipeline
Approximately 70% of which are in early
development (Preclinical and Phase 1)
In contrast, there are just 9 candidates at Phase
3, while there are 31 at Phase 2
These pipeline developments are being
progressed by 66 companies
Nine (14%) are major international corporations
and 57 (86%) are Small/Medium Sized
Enterprises (SMEs)
Biopharm, 2012
36. WHO 2009: “Antibiotic resistance - one of the
three greatest threats to human health”
WHO World Health Day. 7 April 2011:
Antimicrobial resistance: no action today, no cure
tomorrow
Margaret Chan, Director General, WHO,
September 2012 “If health fails, all else fails”
Adapted from LJV Piddock, 2013
37. The range of topics discussed was broad and
included; urbanisation, pollution, climate
change, biodiversity, ageing population, etc
The need to combat antimicrobial drug
resistance was given a high profile despite
considerable attention AMR has received in the
UK
Importance of international agreements and
complementary policies were reiterated
Working with existing agencies such as the
WHO for emergence of effective tools
The Biologist, 2013
38. Improve how we prevent and manage infections in people
and in animals
Improve education and training around the prescribing of
antibiotics to reduce inappropriate
Collect better data on the resistance of bugs so we can track
them more effectively
Provide funding of up to £4million to set up a new National
Institute of Health Research (NIHR) Health Protection
Research Unit which will focus on AMR and healthcare
associated infections
Explore ways to encourage the development of new
antibiotics, rapid diagnostics, etc
Department of Health, Sep. 2013
39. Antibiotic Resistance Monitoring & Reference
Laboratory (ARMRL)
The Stop TB Partnership
The Center for Diseases Dynamics, Economics &
Policy
European Antimicrobial Resistance Surveillance
Network (EARS-Net)
National Institute of Allergy and Infectious Diseases
(NIAID)
International Network for the Study and Prevention
of Emerging Antimicrobial Resistance (INSPEAR)
42. Use of antibiotics
Inadequate infection control practices
Lack of interest by pharmaceutical companies in
research and development of new drugs
Use of antibiotics in food animals and agriculture
Intrinsic nature of some bacteria
Uncontrolled release of antibacterial compounds
into the environment
International travel, trade, adoption all facilitate the
globalization of antimicrobial resistance
The AIDS epidemics and other types of
immunocompromise diseases
43.
44. Drugs already in market
Daptomycin
Linezolid
Alvimopan
Fidaxomicin
Tigecycline
Drugs at different stages of clinical trial
Ceftolozane/tazobactam
Surotomycin
Bevenopran
AYX1
45. Novel antimicrobial agents
Use of natural products
Combinational therapy
Vaccines
Immunomodulatory agents
Probiotics
Bacteriophage therapy
Control of all antibiotic treatments
Effective surveillance systems for early detection of AMR
Improvement of heathcare provider and public education
Robust research to guide the previously mentioned action
46. Resistance is inevitable- The problem of
resistance accompanies the use of NEW drugs
The simple UNPOPULAR thorough washing of
hands
View antibiotic resistance as a global crisis akin to
AIDS
Predicted mortality for patients with and without antimicrobial-resistant infection (ARI). APACHE, Acute Physiology and Chronic Health Evaluation.
Rise in the proportions of E. coli from bacteraemias in England, Wales and Northern Ireland resistant to fluoroquinolones (white), oxyimino-cephalosporins (grey) and both (black). Based on laboratories' reports to the HPA.
Numbers of MRSA bacteraemias in England by 6 month periods from 2001 to 2008 (bars, left axis) and rates of bacteraemia per 10 000 bed days (line, right axis). Based on mandatory reporting to the HPA.