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Threat of antibiotic resistant bacteria to humans

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  • 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.
  • Transcript

    • 1. David O. Ogbolu olusogadave@yahoo.com; d.o.ogbolu@bham.ac.uk
    • 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
    • 4. Bacterial cells and arrangements
    • 5.  Tuberculosis  Urinary tract infection  Gastrointestinal tract infection  Sepsis  Surgical wound infection  Pneumonia  Skin and soft tissue infection
    • 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
    • 8.  Penicillin and cephalosporins  Carbapenems  Polymixins  Quinolones and Fluoroquinolones  Sulphonamide  Macrolides  Tetracyclines  Aminoglycosides  Lipopeptides  Glycylcyclines  Oxazolidinones
    • 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
    • 12. ‘’the war against diseases has been won’’
    • 13. Antimicrobial Resistance Progression
    • 14. Davies and Davies, 2010; MMBR
    • 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
    • 28.  Other serious infections include nosocomial (hospital-linked) infections with; ◦ Burkholderia cepacia, Campylobacter jejuni, Citrobacter freundii, Enterobacter spp., Enterococcus faecium, Enterococcus faecalis, Haemophilus influenzae, Proteus mirabilis, Serratia spp., Staphylococcus epidermidis, Stenotrophomonas maltophilia, and Streptococcus pneumoniae
    • 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
    • 30. (Lewis, 2012 Antibiotic Pipeline
    • 31. New threat from superbugs equipped with NDM-! Lancet Infect Dis
    • 32. J Assoc Physicians India
    • 33.  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
    • 34.  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
    • 35.  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
    • 36.  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)
    • 37. APUA Field Report: Nigeria. 2013 31(2)
    • 38. MICs of recipient strains after transfer of VIM, NDM or unknown carbapenemases Strain Gene(s)a Minimum Inhibitory Concentrations, MIC (mg/L) IPM MPM ETP CAZ CIP AZT NAL COL AK CHL GEN TIG Donor U36 VIM >64 32 >64 >64 32 8 >64 32 >64 >64 >64 32 U37 VIM/NDM 16 16 64 >64 >64 >64 >64 1 >64 >64 >64 2 U28 unknown 16 16 >64 >64 >64 16 >64 4 32 >64 >64 2 Representative transconjugates/transformants T-U36 VIM 1 4 16 >64 0.25 >64 >64 ND >64 32 >64 0.5 T-U37 NDM 2 4 4 >64 8 >64 >64 ND 1 2 8 0.25 T-U28 unknown 8 16 >64 2 2 32 16 ND 1 16 8 0.25 Control strain NCTC 10418 0.12 <0.03 <0.03 <0.03 <0.03 0.03 1 0.12 1 2 0.5 0.06
    • 39.  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
    • 40. Drugs already in market  Daptomycin  Linezolid  Alvimopan  Fidaxomicin  Tigecycline Drugs at different stages of clinical trial  Ceftolozane/tazobactam  Surotomycin  Bevenopran  AYX1
    • 41.  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
    • 42.  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
    • 43. Who is wining the war!!!
    • 44. Antibiotic Action – www.antibiotic-action.com
    • 45. Antimicrobials Research Group LAUTECH
    • 46. Thank you!