The Centers for Disease Control and Prevention (CDC) has classified a number of bacteria as presenting urgent, serious, and concerning threats, many of which are already responsible for placing a substantial clinical and financial burden on the U.S. health care system, patients, and their families. Coordinated efforts to implement new policies, renew research efforts, and pursue steps to manage the crisis are greatly needed.



History of Antibiotics



The management of microbial infections in ancient Egypt, Greece, and China is well-documented. The modern era of antibiotics started with the discovery of penicillin by Sir Alexander Fleming in 1928. Since then, antibiotics have transformed modern medicine and tried helping out saving millions of lives. Antibiotics were first prescribed to treat serious infections in the 1940s. Penicillin was successful in controlling bacterial infections among World War II soldiers. However, shortly thereafter, penicillin resistance became a substantial clinical problem, so that, by the 1950s, many of the advances of the prior decade were threatened.7 In response, new beta-lactam antibiotics were discovered, developed, and deployed, restoring confidence. However, the first case of methicillin-resistant Staphylococcus aureus (MRSA) was identified during that same decade, in the United Kingdom in 1962 and in the United States in 1968.



Unfortunately, resistance has eventually been seen to nearly all antibiotics that have been developed ,Vancomycin was introduced into clinical practice in 1972 for the treatment of methicillin resistance in both S. aureus and coagulase-negative staphylococci. It had been so difficult to induce vancomycin resistance that it was believed unlikely to occur in a clinical setting. However, cases of vancomycin resistance were reported in coagulase-negative staphylococci in 1979 and 1983. From the late 1960s through the early 1980s, the pharmaceutical industry introduced many new antibiotics to solve the resistance problem, but after that the antibiotic pipeline began to dry up and fewer new drugs were introduced. As a result, in 2015, many decades after the first patients were treated with antibiotics, bacterial infections have again become a threat.



Benefits of Antibiotics



Antibiotics have not only saved patients’ lives, they have played a pivotal role in achieving major advances in medicine and surgery. They have successfully prevented or treated infections that can occur in patients who are receiving chemotherapy treatments; who have chronic diseases such as diabetes, end-stage renal disease, or rheumatoid arthritis; or who have had complex surgeries such as organ transplants, joint replacements, or cardiac surgery.



Antibiotics have also helped to extend expected life spans by changing the outcome of bacterial infections. In 1920, people in the U.S. were expected to live to be only 56.4 years old; now, however, the average U.S. life span is nearly 80 years. Antibiotics have had similar beneficial effects worldwide. In developing countries where sanitation is still poor, antibiotics decrease the morbidity and mortality caused by food-borne and other poverty-related infections.



CAUSES OF THE ANTIBIOTIC RESISTANCE CRISIS



Overuse



As early as 1945, Sir Alexander Fleming raised the alarm regarding antibiotic overuse when he warned that the “public will demand [the drug and] … then will begin an era … of abuses.” The overuse of antibiotics clearly drives the evolution of resistance. Epidemiological studies have demonstrated a direct relationship between antibiotic consumption and the emergence and dissemination of resistant bacteria strains. In bacteria, genes can be inherited from relatives or can be acquired from nonrelatives on mobile genetic elements such as plasmids. This horizontal gene transfer (HGT) can allow antibiotic resistance to be transferred among different species of bacteria. Resistance can also occur spontaneously through mutation. Antibiotics remove drug-sensitive competitors, leaving resistant bacteria behind to reproduce as a result of natural selection.Despite warnings regarding overuse, antibiotics are overprescribed worldwide.



In the U.S., the sheer number of antibiotics prescribed indicates that a lot of work must be done to reduce the use of these medications. An analysis of the IMS Health Midas database, which estimates antibiotic consumption based on the volume of antibiotics sold in retail and hospital pharmacies, indicated that in 2010, 22.0 standard units (a unit equaling one dose, i.e., one pill, capsule, or ampoule) of antibiotics were prescribed per person in the U.S. The number of antibiotic prescriptions varies by state, with the most written in states running from the Great Lakes down to the Gulf Coast, whereas the West Coast has the lowest use  In some states, the number of prescribed courses of treatment with antibiotics per year exceed the population, amounting to more than one treatment per person per year.



 



Antibiotic Prescriptions per 1,000 Persons Of All Ages According to State, 20105



The frequency with which doctors prescribe antibiotics varies greatly from state to state. The reasons for this variation are being studied and might suggest areas where improvements in antibiotic prescribing (fewer unnecessary prescriptions) would be most helpful.



In many other countries, antibiotics are unregulated and available over the counter without a prescription. This lack of regulation results in antibiotics that are easily accessible, plentiful, and cheap, which promotes overuse.The ability to purchase such products online has also made them accessible in countries where antibiotics are regulated.



Inappropriate Prescribing



Incorrectly prescribed antibiotics also contribute to the promotion of resistant bacteria. Studies have shown that treatment indication, choice of agent, or duration of antibiotic therapy is incorrect in 30% to 50% of cases. One U.S. study reported that a pathogen was defined in only 7.6% of 17,435 patients hospitalized with community-acquired pneumonia (CAP). In comparison, investigators at the Karolinska Institute in Sweden were able to identify the probable pathogen in 89% of patients with CAP through use of molecular diagnostic techniques (polymerase chain reaction [PCR] and semiquantitative PCR). In addition, 30% to 60% of the antibiotics prescribed in intensive care units (ICUs) have been found to be unnecessary, inappropriate, or suboptimal.



Incorrectly prescribed antibiotics have questionable therapeutic benefit and expose patients to potential complications of antibiotic therapy. Subinhibitory and subtherapeutic antibiotic concentrations can promote the development of antibiotic resistance by supporting genetic alterations, such as changes in gene expression, HGT, and mutagenesis. Changes in antibiotic-induced gene expression can increase virulence, while increased mutagenesis and HGT promote antibiotic resistance and spread.Low levels of antibiotics have been shown to contribute to strain diversification in organisms such as Pseudomonas aeruginosa. Subinhibitory concentrations of piperacillin and/or tazobactam have also been shown to induce broad proteomic alterations in Bacteroides fragilis.8



Extensive Agricultural Use



In both the developed and developing world, antibiotics are widely used as growth supplements in livestock. An estimated 80% of antibiotics sold in the U.S. are used in animals, primarily to promote growth and to prevent infection Treating livestock with antimicrobials is said to improve the overall health of the animals, producing larger yields and a higher-quality product.



The antibiotics used in livestock are ingested by humans when they consume food The transfer of resistant bacteria to humans by farm animals was first noted more than 35 years ago, when high rates of antibiotic resistance were found in the intestinal flora of both farm animals and farmers. More recently, molecular detection methods have demonstrated that resistant bacteria in farm animals reach consumers through meat products.This occurs through the following sequence of events: 1) antibiotic use in food-producing animals kills or suppresses susceptible bacteria, allowing antibiotic-resistant bacteria to thrive; 2) resistant bacteria are transmitted to humans through the food supply; 3) these bacteria can cause infections in humans that may lead to adverse health consequences.



The agricultural use of antibiotics also affects the environmental microbiome Up to 90% of the antibiotics given to livestock are excreted in urine and stool, then widely dispersed through fertilizer, groundwater, and surface runoff. In addition, tetracyclines and streptomycin are sprayed on fruit trees to act as pesticides in the western and southern U.S.While this application accounts for a much smaller proportion of overall antibiotic use, the resultant geographical spread can be considerable.1 This practice also contributes to the exposure of microorganisms in the environment to growth-inhibiting agents, altering the environmental ecology by increasing the proportion of resistant versus susceptible microorganisms.



Antibacterial products sold for hygienic or cleaning purposes may also contribute to this problem, since they may limit the development of immunities to environmental antigens in both children and adults. Consequently, immune-system versatility may be compromised, possibly increasing morbidity and mortality due to infections that wouldn’t normally be virulent.



Availability of Few New Antibiotics



The development of new antibiotics by the pharmaceutical industry, a strategy that had been effective at combating resistant bacteria in the past, had essentially stalled due to economic and regulatory obstacles  Of the 18 largest pharmaceutical companies, 15 abandoned the antibiotic field. Mergers between pharmaceutical companies have also substantially reduced the number and diversity of research teams. Antibiotic research conducted in academia has been scaled back as a result of funding cuts due to the economic crisis.



in the covid era ,we has extensively used higher antibiotics ,and various other drugs combination in trying to treat corona infection  with combination and higher groups that should not have been used for treating a viral infection 



hence antimicrobial resistance has developed and now the doctors are having a tough time treating previously simple infection as they are resistant to mostly all the perviously used antibiotics like azithromycin ,cefexime,cefpodoxime,cefuroxime,amoxicillin but now the sensitivity has gone for feropenem,linezolid,cilastin,imepenem.



If we dont regulate the use of antibiotics urgently ,the day is not far when the world would land into a crisis of bacteria which is resistant to every man made antibiotic !!



Safe Gastro and Surgery Center ,Agra



DR KARAN R RAWAT 



GASTRO / ADVANCED LAPROSCOPIC / LASER  SURGEON