Antibiotics

Mary E. Wilson, M.D., is a renowed leader in global health and infectious diseases who holds academic appointments at the Harvard T.H. Chan School of Public Health and the University of California, San Francisco. She lectures frequently in US and abroad, is widely published, and serves on multiple national and international boards and advisory committees.

"Wilson's final two chapters are notable for suggesting methods to reduce the need for antibiotics and presenting newer approaches to diagnosing and treating bacterial infections." --Tony Miksanek, Booklist

• ACKNOWLEDGEMENTS PREFACE Why should you read this book? Why did I write this book? 1. ORIGIN AND FUNCTION What is an antibiotic? What is the difference between an antibiotic and antimicrobial? How do antibiotics work? What is the difference between broad and narrow-spectrum antibiotics? Why do we have so many different ones? Do antibiotics work against viruses? Why do people confuse bacteria and viruses? How were antibiotics discovered? Where do antibiotics come from? How are antibiotics made? Are new antibiotics created in the laboratory or discovered in nature? What happens when a compound with antibacterial activity is discovered? How does it come to be used to treat infections? Are the same antibiotics used all over the world? How common are substandard and falsified antibiotics? What is the WHO model list of essential medicines? 2. USE IN HUMANS How are antibiotics administered? What are the routes of administration besides by mouth and by injection? What determines how they should be given? Are pills as effective as injections? Where does the antibiotic go in the body? Does it reach all organs and tissues? What is its fate? Does any part of the antibiotic leave the body in urine or feces? What happens after an antibiotic leaves the body? Why are antibiotics that are not absorbed used? How does one decide which antibiotic to use? What information about each antibiotic is available to the pharmacist, the health provider, and the patient? TABLE Full prescribing information How long does it take for an antibiotic to work? Why are some antibiotics given as a single dose and others prescribed for weeks or longer? What determines the right dose of an antibiotic? Can one overdose on an antibiotic? Does an antibiotic have any effect other than against the bacteria being treated? How long does the effect of an antibiotic last? Why are some infections, such as tuberculosis, always treated with multiple different antibiotics taken simultaneously? Does one always have to take the entire course of prescribed antibiotics? Can one take leftover antibiotics for a new infection? Or give it to a family member or friend? What should one do with leftover antibiotics? Is it dangerous to take expired antibiotics? When are antibiotics used to prevent infections (in contrast to treating an established infection)? How are antibiotics used to prevent infections in surgery? In what other settings are antibiotics used to prevent infections? When are antibiotics used to treat an entire population in mass treatment campaigns? What are the consequences of mass treatment with antibiotics? How are antibiotics used in the human population? Who receives them? What are the main reasons that antibiotics are prescribed? Why is antibiotic use so common for respiratory infections? Does antibiotic use vary by region or by country? Is antibiotic use increasing or decreasing? How much is spent on antibiotics? 3. CONSEQUENCES OF USE: Adverse events associated with use of antibiotics in humans What is the difference between an allergic reaction and an adverse reaction? What are the signs and symptoms of an allergic reaction? How common are adverse reactions? How much antibiotic does it take to cause an adverse reaction? Do genetic factors influence drug reactions? What are drug-drug interactions? Does exposure to the sun make one more likely to have a reaction to an antibiotic? Why have side effects from ciprofloxacin (and other fluoroquinolones) gotten so much attention? What is Clostridium (Clostridioides) difficile or C. diff. and where did it come from? What is driving the increase in cases? What predisposes someone to Clostridium difficile infection and how does it spread? How is it treated? What is a fecal microbiota transplant? Can fecal microbiota transplantation be used to treat other conditions? Why do yeast infections occur during and after treatment with antibiotics? What is the microbiome and why is it so important? What is the Human Microbiome Project? What are the functions of the human microbiome? How do antibiotics affect the human microbiome? Does human use of antibiotics and other agents affect animal microbiota? Do other drugs besides antibiotics affect the microbiome? Can the gut microbiota be protected from the effect of antibiotics? 4. OTHER USES OF ANTIBIOTICS (NON HUMAN USE) What are the uses of antibiotics other than to treat infections in humans? What proportion of antibiotics produced in recent years had a non-human use? Why are antibiotics given to healthy animals? Which animals receive antibiotics? Which antibiotics are used? Are the same antibiotics used in people also use in animals? Are antibiotics used in food animals in other countries? How are antibiotics used in aquaculture? Is it OK for people to take antibiotics that were made for fish or other animals? What are the consequences of use of antibiotics in animals? Is any antibiotic still present in the meat, fish, eggs, or milk when they are sold for human consumption? Why are antibiotics used in bees? Do plants develop infections? Why and how often are antibiotics used in plants? Can humans pick up infections from plants? How can plant infections affect human health? Is food from plants contaminated with antibiotics? Does feeding animals antibiotics in large production facilities (such as industrial production of chickens, pigs, and cattle) have impact on the local environment? What are other sources of antibiotics in the environment? 5. ANTIBIOTIC RESISTANCE What is antibiotic resistance? Where did antibiotic resistance come from? What are the mechanisms bacteria use to evade antibiotics? How do bacteria destroy or disable the antibiotic? How can bacteria change an antibiotic in order to resist it? How can bacteria prevent antibiotics from getting through the cell wall of the bacteria? How do bacteria manage to pump antibiotics out of the bacterial cell? How can bacteria alter the target of antibiotic action in the bacteria? How can bacteria bypass key functions to survive despite the presence of antibiotics? What else can bacteria do to prevent being killed? How does one test bacteria for resistance to antibiotics? See FIGURE1 also cited in USE section How does antibiotic resistance spread among bacteria? See Figure 2 (also cited earlier in this chapter) Where does this transfer of resistance genes among bacteria take place? How do resistant bacteria and resistance genes spread globally? What is the role of travel in the movement of resistant bacteria and resistance genes globally? How do travelers pick up multiply-resistant bacteria? Where are the resistant bacteria found? How often do travelers pick up resistant bacteria? Do they spread them to others? What is medical tourism? Are travelers who receive care abroad at risk for infections with resistant bacteria? Are mass gatherings an important source of infections and spread of infections or resistance? What is wastewater epidemiology? How does resistance in spread in health care facilities? Are there ways that resistant bacteria spread that do not involve movement of humans? Do pets carry antibiotic resistant bacteria? What are other routes of spread of bacteria from animals to humans? Does antibiotic resistance ever disappear? Which bacteria have developed resistance? Why does tuberculosis (TB) remain such a serious global problem? Why is gonorrhea so hard to treat? Are resistant bacteria found in all countries? Is the level of resistance influenced by the amount of antibiotic used in a region or country? What can be done to slow or stop antibiotic resistance? 6. CONSEQUENCES OF ANTIBIOTIC RESISTANCE What are the most important consequences of having infections caused by antibiotic resistant bacteria? Are infections caused by antibiotic-resistant bacteria less severe? More severe? The same? Are outcomes worse for antibiotic-resistant infections? What would be the consequences if antibiotics stopped working? What do people mean by the "post-antibiotic era"? What medical procedures today rely on the availability of highly effective preventive antibiotics? Do we have antibiotics to use when bacteria become resistant to first-line drugs? Are these other antibiotics as safe and effective as the first-line drugs? Are they available and affordable? Can antibiotics still be used for prevention when bacteria become resistant? Are people dying today because of antibiotic resistant infections? Why are antibiotics sometimes called "societal/social drugs"? How does my taking an antibiotic affect my neighbors and the community? 7. INTERVENTIONS TO REDUCE THE NEED FOR ANTIBIOTICS and ALTERNATIVES TO ANTIBIOTICS Are there ways we can reduce risks of infections so that we do not need antibiotics? How do clean water and improved sanitation reduce use of antibiotics? How can processing and handling of food affect antibiotic use? How can using vaccines reduce need for antibiotics? Are vaccines used to prevent infections in animals? Can they prevent infections that could affect humans? How can controlling vectors like mosquitoes and ticks reduce antibiotic use? Are healthcare-associated infections a common reason for antibiotic treatment? Do antiseptics and alcohol-based hand sanitizers work against all microbes? How can copper be used to decrease infections? Are there approaches to treating infections that do not involve antibiotics - treatment approaches that do not drive development of resistance the way the use of antibiotics does? What other approaches to treating infections are being tried that do not involve antibiotics? What is bacteriophage therapy? Does it work? Is it being used today? How are phage and bacteriocins used today? 8. PRESERVING ANTIBIOTICS and DEVELOPING NEW ANTIBACTERIAL TREATMENTS How common is inappropriate prescribing of antibiotics? What approaches have been effective in increasing the appropriate use of antibiotics and decreasing inappropriate prescribing by clinicians? What can individuals do to reduce the inappropriate use of antibiotics? What are antibiotic stewardship programs? Do antibiotic stewardship programs work? Why do stewardship programs focus on reported allergies to antibiotics? What is the role of better diagnostic testing in reducing use of antibiotics? What is procalcitonin and can it help guide antibiotic treatment? Are procalcitonin levels useful in diagnosis of infection in infants? Why did use of rapid diagnostic tests lead to increased use of antibiotics in some settings. Are there approaches that use urine, saliva, breath, or other specimens to diagnose infections? What is the role of national and international agencies in reducing inappropriate use of antibiotics? Why aren't pharmaceutical companies developing more new antibiotics? Why don't we have more antibiotics in the pipeline? Which bacteria are highest priority for development of new antibiotics? Which antibiotics or antibacterial products are currently in the pipeline? Whose responsibility is it to develop new antibiotics? Who pays for their development? What incentives or other approaches might increase the development of new antibiotics? What are priority areas in looking for ways to treat bacterial infections? GLOSSARY