Threat of antibiotic resistant bacteria to humans
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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.

Threat of antibiotic resistant bacteria to humans Threat of antibiotic resistant bacteria to humans Presentation Transcript

  • David O. Ogbolu olusogadave@yahoo.com; d.o.ogbolu@bham.ac.uk
  •  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
  •  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
  • Bacterial cells and arrangements
  •  Tuberculosis  Urinary tract infection  Gastrointestinal tract infection  Sepsis  Surgical wound infection  Pneumonia  Skin and soft tissue infection
  • 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
  •  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
  •  Penicillin and cephalosporins  Carbapenems  Polymixins  Quinolones and Fluoroquinolones  Sulphonamide  Macrolides  Tetracyclines  Aminoglycosides  Lipopeptides  Glycylcyclines  Oxazolidinones
  •  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
  •  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
  • 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
  • ‘’the war against diseases has been won’’
  • Antimicrobial Resistance Progression
  • Davies and Davies, 2010; MMBR
  •  Drug resistance is so common and the term can be described in so many ways; ◦ MDR ◦ XDR ◦ PDR
  •  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
  • 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
  • Predicted mortality for patients with and without antimicrobial-resistant infection (ARI) Roberts et al., 2009 Clin Infect Dis. APACHE score
  •  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
  •  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
  • 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
  •  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
  •  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
  • 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
  •  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
  •  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
  •  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
  •  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
  •  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
  • (Lewis, 2012 Antibiotic Pipeline
  • New threat from superbugs equipped with NDM-! Lancet Infect Dis
  • J Assoc Physicians India
  •  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
  •  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
  •  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
  •  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)
  • APUA Field Report: Nigeria. 2013 31(2)
  • 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
  •  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
  • Drugs already in market  Daptomycin  Linezolid  Alvimopan  Fidaxomicin  Tigecycline Drugs at different stages of clinical trial  Ceftolozane/tazobactam  Surotomycin  Bevenopran  AYX1
  •  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
  •  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
  • Who is wining the war!!!
  • Antibiotic Action – www.antibiotic-action.com
  • Antimicrobials Research Group LAUTECH
  • Thank you!