Microbial Antibiotic Resistance - Micro 462 Lecture Notes PDF

Microbial antibiotic resistance - Micro 462 Prepared by Dr/ Essam KOTB Associate Professor of Microbiology, IAU University [email protected]...

Microbial antibiotic resistance - Micro 462 Prepared by Dr/ Essam KOTB Associate Professor of Microbiology, IAU University [email protected] +2/01121343400 +966/0563533550 1  Course specification 2  Reference books – Carlos F. Amábile-Cuevas (2016) Antibiotics and Antibiotic Resistance in the Environment. CRC Press, Taylor & Francis Group, London, UK – Anthony R.M. Coates (2012) Antibiotic Resistance. Springer Heidelberg New York – Antibiotic Resistance, 2010, Institute of Medicine Forum on Microbial Threat. 978-0-309-15611, National Academic Press, Washington. – Antimicrobial Resistance in the Environment, Patricia L Keen and Mark HMM Montforts. ISBN: 978-0-470-90542-5 Schedule of assessments during the semester Assessm ent Percentage of timing Total No Assessment Activities * Assessment (in week Score no) 1 Quiz 1 4 10% 2 Midterm 8 20% 3 Quiz 2 13 10% Team projects and 10-14 20% 4 presentations/H.W 5 Final Exam 15 40%  Course objectives After completing this course, you will be able to: 1. Understand what antibiotics are and how they work. 2. Understand how bacteria become resistant to antibiotics. 3. Appreciate the issues surrounding antibiotic resistance. 4. Know the challenges in developing new antibiotics. 5. Know about alternative approaches to tackle infectious diseases. Lesson 1: General overview of the history of infectious diseases and antibiotics Prepared by Dr/ Essam KOTB Associate Professor of Applied Microbiology, IAU [email protected] +2/01121343400 +966/0563533550  Objectives By the end of this lesson, you should be able to: 1. Define the term antibiotic and give examples. 2. Describe the importance of antibiotics in health care. 3. Analyse antibiotic data and make simple deductions about antibiotic use and resistance patterns. 4. Discuss the consequences of a future without antibiotics. 5. Build up your own opinion about this dilemma. Infectious diseases and antibiotics Most infectious diseases are caused by bacteria because they are the most numerous organisms and living in all habitats. The secret of their success in all habitats is their simplicity which allow them to adapt quickly to changes in their surroundings thus reproduce quickly and efficiently. Each adaptive characteristic passes rapidly to the next generation and a new strain evolves.  It should be emphasized that, most bacteria found in or on the human body are harmless M.Os called commensals (microbiota) living on the body without having any detrimental effect. However, a tiny proportion (about 500 species) are pathogenic – capable of causing diseases. – These pathogenic bacteria evade the body’s normal defenses to colonize body tissues or produce harmful toxins. Some bacteria are opportunistic pathogens – these don’t harm the normal hosts as they are not real pathogens but attack weak hosts due to weak immune system.  Until the mid-twentieth century, bacterial infections were difficult to treat and were a leading cause of mortality worldwide. In the 1940s, the antibiotics were introduced, and the outcomes of bacterial infections were improved dramatically. Antibiotics are organic chemical compounds which kill or inhibit bacteria. – Antibiotics which kill bacteria are called bactericidal antibiotics. – Antibiotics which inhibit bacterial growth are called bacteriostatic antibiotics.  They are produced naturally by M.Os especially those living in soil in order to stop bacteria competing for shelter, nutrients and other resources. Antibiotics specifically target bacteria – a characteristic that humans have exploited for their own advantage to avoid the side effects produced by traditional medications. Narrow-spectrum antibiotics - only affect a few bacterial types. Broad-spectrum antibiotics - affect a wider range of bacteria.  Most antibiotics are specifically effective against bacteria during the exponential phase of growth; why? Because during the exponential phase the bacterial cells are at their most activity, continually growing, dividing and forming new cells. The metabolic processes which underpin this period of growth such as the synthesis of DNA, RNA, proteins and cell wall are good targets for the antibiotics to disrupt it therefore kill or inhibit cells. For this, the bacterial spores are resistant to antibiotics because the metabolic processes are nearly dormant.  Classification of antibiotics (BG AMTO FRT) There are numerous antibiotics, some of which are naturally occurring while others are semi- or fully synthetic. Antibiotics are usually classified according to the chemical structure because structurally similar antibiotics have the same antibacterial activity (see below). Antibiotic class Example Cellular process Effect on targeted bacteria* ß-Lactams ampicillin bacterial cell wall Bactericidal (penicillins) synthesis ß-Lactams cephazolin bacterial cell wall Bactericidal (cephalosporins synthesis ) ß-Lactams imipenem bacterial cell wall Bactericidal (carbapenems) * Common synthesis effect but depends on the concentration at which the antibiotic is used. Antibiotic class Example Cellular process Effect on targeted bacteria* Aminoglycosides streptomycin Protein synthesis Bactericidal Macrolides azithromycin Protein synthesis Bacteriostatic Tetracyclines tetracycline Protein synthesis Bacteriostatic Oxazolidinones linezolid Protein synthesis Bacteriostatic Fluoroquinolone ciprofloxacin DNA synthesis Bactericidal s Rifamycins rifampicin RNA synthesis Bactericidal Not applicable Trimethopri Antimetabolite (e.g Bactericidal m folic acid) The pre-antibiotic era Before the discovery of antibiotics, the treatment options for bacterial infections were limited (video 3). People were not only vulnerable to potentially deadly infections like TB (tuberculosis) and meningitis, but also simple wound infections by bacteria led to sepsis and death in many cases. Common infections such as sore throats, which considered ‘non-serious’ today, were killers in the pre- antibiotic era. Routine procedures such as childbirth were also deadly.  Treatment during that era includes: 1. Herbal remedies. 2. Pastes from insects. 3. Chemicals such as mercury for syphilis. 4. Bloodletting. 5. Draining of pus from wounds. 6. Fresh air used for TB. Those approaches relieved the symptoms and did little against the underlying cause therefore, the outcomes were largely ineffective.  For example, George Washington the funding of USA suffered a sore throat and died from such simple infection. The Black Death of the 14th century killed a quarter of Europe. The plague bacterium causes your flesh dies and rots while you're still alive. Thence there's tuberculosis, a slow and deadly killer, the cause of lung abscesses. Gangrene and tetanus caused by soil bacteria residing in every dirty bullet, scalpel, wood and glass pieces. The old physicians would laugh in your face if you told them that microscopic life is killing people. They were still clung to theories passed down from the ancient Greek who claimed that, the cause of diseases were devils' or fairies' punishments, and that healing was a gift from God.  Now we know that infectious diseases are caused by microorganisms. This discovery, was known as the germ theory of diseases, which was a pivotal moment in medicine. This theory was established and proved by Louis Pasteur and Robert Koch (back to micro307 course).  By the early twentieth century, efforts to tackle infectious diseases were focused on finding drugs that can kill the bacterial pathogen without harming the patient – so-called ‘magic bullets’. Salvarsan and Sulfonamides were the first magic bullets of chemical origin. Alexander Fleming’s chance discovery in 1928 of the first natural antibiotic – penicillin – paved the way for research into other ‘magic bullets’ to cure bacterial infections. This was the start of the antibiotic era. Since their introduction in the 1940s, antibiotics have saved millions of lives (Figure 3). Thence deadly diseases such as pneumonia, and TB were treatable, in addition, everyday infections and minor injuries become no longer life-threatening.  (a) Childbirth- (b) All infectious related infection diseases. (puerperal fever) Figure 3 Effect of antibiotics on death rates in UK between 1931 and 1957 from (a) childbirth-related infection (puerperal fever) and (b) all infectious diseases. The arrows indicate when specific antibiotics were introduced.  For this, antibiotics were extensively used in medicine for: 1. Treatment of patients and improvement of the survival rates during childbirths and surgical operations. 2. Prophylaxis - that is they are taken before routine surgical procedures to prevent infection by internal sterilization. Unfortunately, recently antibiotics are no longer looked as the ‘magic bullets’, why?? 3. Because of our over-reliance (over-use) on them to prevent and treat human infections. 4. Their use in nonmedical purposes (mis-use), such as in veterinary medicine, agriculture, canning, food preservation which has led to lose most of their power and resistance against them has appeared.  Antibiotic resistance can be natural resistance. However, the overuse and misuse of antibiotics exerts a selective pressure on bacteria to adapt and survive thus, acquired resistance appeared. There is a coincidence between the antibiotic use and the rise of antibiotic resistance. For example, between 2000 and 2010, total global antibiotic consumption increased by over 30%, also antibiotic resistance increased dramatically. By analysing country-specific data for the period 2000 to 2010, we can build up a picture of antibiotic use and resistance worldwide. Figure 4 Percentage change in antibiotic consumption per capita 2000–2010. Percentage decrease is indicated in blue while percentage increase is indicated in red. Lower percentage changes are indicated by lighter colours. Superbugs There is a constant race between antibiotics and bacteria. A superbug is a bacterium that got resistance to ignore the impact of multiple antibiotics (Video 4, Article 2 Bacteria that resist ‘last antibiotic’ found in UK). What is the warning? – All bacteria become superbugs resisting all antibiotics. How big could the impact be? – At the moment, some antibiotics still used to treat infections. – In the near future, we will have infections that can no longer be treated. In addition, things like surgery may be fatal to do because bacterial contamination will not be resolved. For this, in 2017, WHO published a list of 5 superbugs for which alternative treatments are urgently required (K. Pneumoniae, E. coli, Staph. aureus, N. gonorrhoeae, Str. Bacterium Antibiotic resistance Priority rating K. pneumoniae Multi-drug Critical E. coli Multi-drug Staph. aureus Methicillin, Vancomycin High N. gonorrhoeae Cephalosporins, Fluoroquinolones Str. pneumoniae Penicillins Medium Case study (The link between antibiotic use and antibiotic resistance e.g Cephalosporins). Study figure 4a and b which compare cephalosporin use from 2000 to 2015 in the UK and South Africa then answer the following questions. Figure 4a Figure 4b Activity 1: Try to answer the following questions from charts. How did cephalosporin use change over time in each country? Which country had the lowest consumption in 2015? What reason accounts for the decrease in cephalosporin consumption in the UK since 2007? Which country is more vulnerable to develop resistant bacteria to cephalosporin?  Activity 2: Try to answer those questions from charts. Now study figure 4c and d which compare cephalosporin resistance among K. pneumoniae and E. coli clinical isolates in the UK and South Africa then answer the following question. Figure 4c What was the resistance pattern for each organism in each country? Figure 4d  Next lesson you will find out: 1. How different antibiotics work and how they target bacteria in the body leaving the body cells unharmed. 2. Why some antibiotics are active against a wide range of bacteria, but others are not. Thanks for your attention Questions?