Antibiotics and Antibiotic Resistance Carl Heneghan Professor of EBM Nuffield Dept of Primary Care Health Sciences, University of Oxford

Warm up quiz…..

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Antibiotics are powerful medicines that fight bacterial infection Literal translation anti – against biotic – living things

How antibiotics work Antibiotics can be either Broad Spectrum Kill a wide range of bacteria e.g. Penicillin Narrow Spectrum Kill a specific type or group of bacteria e.g. Isoniazid Antibiotics work in one of two ways Bactericidal Kills the bacteria Bacteriostatic Prevents the bacteria from dividing

The history of antibiotics “When I woke up just after dawn on September 28, 1928, I certainly didn't plan to revolutionise all medicine by discovering the world's first antibiotic, or bacteria killer. But I suppose that was exactly what I did.” 1928, Sir Alexander Fleming

The history of antibiotics Penicillin production in the beginning: glass flasks and milk churns used for making early forms of penicillin The US to produce 2.3 million doses in time for the invasion of Normandy in the spring of 1944.

Antibiotic prescribing across Europe 20.6 per 1000 10.8 per 1000

Antiobitic resistance Selective toxicity - greater harm to microbes than host, done by interfering with essential biological processes common in bacteria but not human cells. LD50 vs. MIC - Therapeutic index (the lowest dose toxic to the patient divided by the dose typically used for therapy). High TI are less toxic to the patient. Bactericidal vs. bacteriostatic Static rely on normal host defenses to kill or eliminate the pathogen after its growth has been inhibited. (UTIs) CIDAL given when host defenses cannot be relied on to remove or destroy pathogen. Favorable pharmacokinetics - drug interxns, how drug is distributed, metabolized and excreted in body (unstable in acid, can it cross the Blood-brain barrier, etc) Spectrum of activity broad spectrum - wide Narrow spectrum - narrow range (pathogen must be ID’d) Lack of “side effects” allergic, toxic side effects, suppress normal flora Little resistance development

Cuases of Antibiotic Resistance Overuse Antibiotics used to treat infections when they are not needed or not effective i.e. for viral infections e.g., influenza Misuse Not completing a prescribed course Using antibiotics not prescribed for you

Causes of Antibiotic Resistance Widespread antibiotic use has caused more bacteria to become resistant, a process called evolutionary pressure. Increasing global availability since the 1950s Uncontrolled sale resulting in antibiotics being used when not indicated.  Use of broad-spectrum antibiotics when not indicated Antibiotic use in livestock feed at low doses for growth promotion Releasing large quantities into the environment during pharmaceutical manufacturing.

Clinical deployment of new antibiotics (blue bars) has quickly been followed by the evolution of bacteria able to resist their effects (red).

Discovery of teixobactin = a new class of antibiotics, first to be described in many years. Teixobactin was able to kill bacteria that cause wound infections from cuts and scratches such as Staphylococcus aureus including MRSA, those that cause pneumonia (Streptococcus pneumoniae) and Mycobacterium tuberculosis (TB). .

Preventing Infections

Respiratory virus spread can be prevented by hygienic measures, such as handwashing, especially around young children.

Antimicrobial Stewardship “…. the microbes are educated to resist penicillin and a host of penicillin-fast organisms is bred out… In such cases the thoughtless person playing with penicillin is morally responsible for the death of the man who finally succumbs to infection with the penicillin-resistant organism. I hope this evil can be averted.” - Sir Alexander Fleming, June 1945 Lynfield, The Continued Assault of Antibiotic-Resistance; IDSA Congressional briefing. Accessed 7.27.14 at http://www.idsociety.org/WHDbriefing/

Thank You @carlheneghan