What is Antibiotic Resistance?

What if I told you there were trillions of tiny bacteria all around you? It's true. Microorganisms called bacteria were some of the first life forms to appear on Earth. Though they consist of only a single cell, their total biomass is greater than that of all plants and animals combined. And they live virtually everywhere: on the ground, in the water, on your kitchen table, on your skin, even inside you. Don't reach for the panic button just yet. Although you have 10 times more bacterial cells inside you than your body has human cells, many of these bacteria are harmless or even beneficial, helping digestion and immunity. 

But there are a few bad apples that can cause harmful infections, from minor inconveniences to deadly epidemics. Fortunately, there are amazing medicines designed to fight bacterial infections. Synthesized from chemicals or occurring naturally in things like mold, these antibiotics kill or neutralize bacteria by interrupting cell wall synthesis or interfering with vital processes like protein synthesis, all while leaving human cells unharmed. 

The deployment of antibiotics over the course of the 20th century has rendered many previously dangerous diseases easily treatable. But today, more and more of our antibiotics are becoming less effective. Did something go wrong to make them stop working? The problem is not with the antibiotics but the bacteria they were made to fight, and the reason lies in Darwin's theory of natural selection. Just like any other organisms, individual bacteria can undergo random mutations. Many of these mutations are harmful or useless, but every now and then, one comes along that gives its organism an edge in survival. 

And for a bacterium, a mutation making it resistant to a certain antibiotic gives quite the edge. As the non-resistant bacteria are killed off, which happens especially quickly in antibiotic-rich environments, like hospitals, there is more room and resources for the resistant ones to thrive, passing along only the mutated genes that help them do so. 

Reproduction isn't the only way to do this; some can release their DNA upon death to be picked up by other bacteria, while others use a method called conjugation, connecting through pili to share their genes. Over time, the resistant genes proliferate, creating entire strains of resistant super bacteria. So, how much time do we have before these superbugs take over? Well, in some bacteria, it's already happened. For instance, some strands of staphylococcus aureus, which causes everything from skin infections to pneumonia and sepsis, have developed into MRSA, becoming resistant to beta-lactam antibiotics, like penicillin, methicillin, and oxacillin. Thanks to a gene that replaces the protein beta-lactams normally target and bind to, MRSA can keep making its cell walls unimpeded. Other super bacteria, like salmonella, even sometimes produce enzymes like beta-lactams that break down antibiotic attackers before they can do any damage, and E. coli, a diverse group of bacteria that contains strains that cause diarrhea and kidney failure, can prevent the function of antibiotics, like quinolones, by actively booting any invaders that manage to enter the cell.

But there is good news. Scientists are working to stay one step ahead of the bacteria, and although development of new antibiotics has slowed in recent years, the World Health Organization has made it a priority to develop novel treatments. Other scientists are investigating alternate solutions, such as phage therapy or using vaccines to prevent infections. Most importantly, curbing the excessive and unnecessary use of antibiotics, such as for minor infections that can resolve on their own, as well as changing medical practice to prevent hospital infections, can have a major impact by keeping more non-resistant bacteria alive as competition for resistant strains. In the war against super bacteria, deescalation may sometimes work better than an evolutionary arms race. https://www.youtube.com/watch?v=znnp-Ivj2ek

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The Resistance Fighter

As a visiting research fellow at the Pasteur Institute in 1962, on leave from medical school, Stuart Levy met a Japanese scientist who introduced him to an exciting recent breakthrough by researchers from his country. “The Japanese had discovered that resistance to antibiotics could be transferred from one bacterium to another,” Levy says—even across species. “This was unheard of previously. It was the beginning of studies on transferrable drug-resistance genes and infectious drug resistance.” Inspired, Levy traveled to Tokyo’s Keio University in 1964 and spent several months in Tsutomu Watanabe’s laboratory, working on the so-called R (resistance) factors. Watanabe is credited with bringing the topic to a wide scientific audience with the publication of a 1963 review in English, highlighting the results of Japanese research on what he called the “infective heredity” of multidrug resistance.

Levy published several papers with Watanabe, including a description of episomal resistance factors of Enterobacteriaceae and an investigation of methods for inhibiting their transfer. “We didn’t know at the time about the mechanism, but we knew it was an exciting moment in the history of antibiotics and resistance,” says Levy. “Later, transfer was linked to small pieces of DNA—plasmids—that bore different resistances to antibiotics.”

Here, Levy talks about the prank he and his twin brother (Jay Levy, who was among the first to discover the HIV virus) executed that earned them a brief spot in the limelight; how science allowed him to travel the world—and befriend Samuel Beckett; and an urgent call to a castle in Prague about chicken eggs.

Levy Learns

Sunday mornings. As young kids growing up in Wilmington, Delaware, Levy and his identical twin brother Jay used to accompany their father, a physician, on Sunday house calls. “House calls were not that common then, but not as rare as they are now,” says Levy. His father, who came from a poor immigrant family, would visit patients, many of whom could only pay him with food grown in their gardens or with services. “He would see the Italian gardener who would exchange Dad’s expertise for his fruit. He was brought up under that kind of understanding, and the patients respected and loved him. He would sometimes discuss with us patients he was seeing; that is probably how my interest in medicine began.”

“That low-dose antibiotics given as growth promotion will lead to high levels of resistance [in humans] was a surprise. No one has tried to replicate that study to this day.”

All in the family. “My twin brother, sister, and I were all interested in biology. We lived in the country near a farm and spent a lot of time outdoors with the animals. All three of us went to medical school, but, unlike my father, we stayed in academic circles rather than going into private practice. My brother, Jay Levy, and my sister, Ellen Koenig, both do HIV research.”

Foray into football. Both Levy and his twin brother wanted to play high school football, but their parents refused, fearing injury. So the head coach took on both boys as coaches. “We got to be near the team and did things like measurements and statistics of the plays. My parents didn’t know then what we know now about concussions, because no one talked about that, but they knew it was a potentially dangerous sport,” says Levy.

Playing both sides. At Williams College, Levy majored in English. “My brother knew by sophomore year that he wanted to go to medical school; I only made the decision my junior year. But I had lots of interests, namely literature and arts. I loved the fact that I could keep these interests and still go to medical school. When I could do something and not give up another I loved, I was happy,” Levy says.

Mistaken identity. After exchanging identities for a day in high school, the Levy brothers took the prank even further in college. As sophomores, the twins swapped identities for an entire week and each wrote an essay about the experience. Stuart lived life as Jay at Wesleyan University and Jay as Stuart at Williams. “This was our first taste of being in the limelight.” The brothers had received permission from the presidents of their respective colleges to switch spots, but then played a prank on those authorities—telling them the wrong week for the intended swap. “We wanted to see if we could even fool the presidents and had a few friends help us play along. When classmates suspected a change, we answered by stating our wish to be considered individuals and not a single entity.”

Levy Launches

Medical school travels. Stuart Levy started medical school at the University of Pennsylvania in 1960. His brother, in medical school at Columbia University, received a Fulbright scholarship and studied at the Sorbonne Institute in Paris. “Our relationship was such that we wanted the other to have what we had, so when my brother was successful in getting a position in Paris at the Sorbonne, he told me, ‘You have to do this, it’s fantastic to be here on your own! There is never anyone directing you,’ ” says Levy. The following year, he followed Jay to Europe, first as a research scholar in Milan and then at the Pasteur Institute in Paris. There Levy worked on a model of viral resistance in a mammalian cell line in Raymond Latarjet’s laboratory. “To tell you the truth, I didn’t care what I was doing, I just wanted to have a new experience, and Latarjet was a wonderful mentor. He loved golf, which is what I was raised on. We had wonderful times golfing together at dusk,” Levy recalls.

For the love of literature. “When my brother was first in Paris, he met Samuel Beckett. Jay had written his thesis at Wesleyan on Beckett and sent it to Sam’s address, which everyone said you could not get through to. Beckett liked what [Jay] had written. Beckett was not a snob, he was shy. So Jay introduced me to Beckett when I was in Paris and every four to six weeks we would have lunch together in the Latin Quarter. I’d tell him what we were doing in the laboratory, and he would share with me accounts about the production of his new play. It was such a unique opportunity.”

Tangents. Levy did his residency in medicine at Mount Sinai Hospital in New York City. While there, he spent much of his free time working in the laboratory of Charlotte Friend, a microbiologist who had discovered a virus that caused a leukemia-like disorder in mice. “She took me under her wing—I was always looking for something else to do other than look at pathology slides. Jay did the same. We weren’t interested in the status quo. We did what was needed to get the degree, but also pursued our own interests,” says Levy. Although his clinical focus was officially hematology, Levy continued to pursue his interest in antibiotic resistance. “I was so interested in infectious diseases that I used to go on the rounds with the infectious-diseases group in addition to my regular clinical duties.”

A system to call his own. Levy became a staff scientist at the National Institutes of Health (NIH) in 1967, working for two years in Loretta Leive’s lab on synthesis of the lipopolysaccharide that populates the outer membrane of E. coli. As an independent researcher on R plasmids and chromosomeless minicells, Levy developed a way to purify large amounts of these E. coli minicells, which form from an aberrant cell division site and possess no bacterial chromosome—what he calls the plasmid-in-minicell system. “The NIH brought me together with senior scientists in the field, but no one was interested in tetracycline resistance. They wanted to understand enzymatic resistance,” says Levy. In 1970, Levy demonstrated that the tetracycline resistance gene is found on plasmids that are transferred to minicells.

Mechanism of resistance. In 1971, Levy moved to the Tufts University School of Medicine as an assistant professor of medicine and of molecular biology and microbiology; he has remained ever since. There, his lab went on to show that an R plasmid encoded a protein associated with tetracycline resistance and that no other positive regulation was required for the bacterium to synthesize this protein. “There could be several hundred genes on the plasmid, and in the 1970s, we were not that sophisticated yet to identify the specific gene,” says Levy. In 1978, his lab determined that the plasmid-derived resistance to tetracycline involved a novel transport system for tetracyclines. Levy’s lab then discovered the first active efflux mechanism, showing that E. coli resistant to tetracycline actively pumped the drug out of the cell and that this mechanism of resistance was encoded by a single R-plasmid gene. Levy also showed that a nonefflux mechanism was present as well. Others subsequently demonstrated that this second mechanism for tetracycline resistance involved a ribosome protection protein. “The use of minicells and the discovery of the mechanism of tetracycline resistance is what really put me on a clear path to a successful career,” says Levy.

Levy Leads

Ahead of his time. The Animal Health Institute of New York asked Levy to study growth-promoting antibiotics in farm animals. “They were looking for scientists who had not spoken negatively about this use of antibiotics,” says Levy. Still a young investigator, Levy fit the bill. His lab found a farm outside of Boston that was willing to have scientists come in and raise chickens. Levy’s students raised 150 control and 150 experimental chickens fed regular and tetracycline-spiked feed, respectively. “There is a funny story about me at a castle in Prague and not remembering that I had placed an order for 300 eggs, one-half male and one-half female. Someone was looking for me all over the castle so that I would confirm [over the phone] that we should order the eggs anyway. There is no way to identify if eggs are male or female!” The study, published in 1976 in the New England Journal of Medicine, showed the ecological effects of feeding farm animals low-dose antibiotics: not only did the antibiotic-resistant bacteria replace the microbiota in the animals’ intestines, they also altered the gut microbiome of the humans who lived and worked on the farm. Through contact with the chickens and their tetracycline-laced feed, resistance was in turn transferred to the microbiome of the animal handlers. Levy’s lab also demonstrated that animals can transfer antibiotic-resistance plasmids to humans and other animals. “That low-dose antibiotics given as growth promotion will lead to high levels of resistance was a surprise,” says Levy. “No one has tried to replicate that study to this day.”

Multidrug-resistance find. Levy’s laboratory also identified a chromosomal operon found in different bacterial species that results in drug resistance to different classes of antibiotics, including tetracyclines, penicillins, and fluoroquinolones. “[The discovery] was serendipitous. I was trying to get a chromosomal mutant to tetracycline, and when the bacteria grew, they were multidrug resistant from the start, which meant there was a single locus that controlled multidrug resistance and that emerged with selection from a single drug exposure,” says Levy.

Antibiotics and politics. Levy has testified many times before Congress on the subject of antibiotic resistance. “Our study from 1976 was [and still is] the only prospective U.S. study on this, and industry didn’t want more studies. They were upset that our data showed them to be wrong. This was highly political.” Levy says he is now more optimistic about prudent antibiotic use, as this issue has garnered more and more attention, especially since this past March when the White House announced a national action plan, allocating $1.2 billion to combat antibiotic-resistant bacteria. “I think the moment has come for new antibiotics and better use of antibiotics so that people are not as subject to resistance emerging through animal use of other drugs. We won’t see real change until there is a genuine commitment to improve antibiotic use, and I think it’s coming.”

Banding together. In 1981, Levy founded the Alliance for the Prudent Use of Antibiotics (APUA), an international nonprofit with chapters in 65 countries. The idea started at a meeting in the Dominican Republic in the early 1980s because of concern about rising antibiotic resistance in the developing world. The organization provides funding for countries in the developing world to study antibiotic resistance. “I’ve learned a lot from being part of the APUA. The science is one thing, but you need to package the science with good politics to get what you want,” says Levy.

Up to the challenge. “We did the first study that took a patient-by-patient analysis of resistance in a [single] Chicago hospital and what the cost was,” says Levy. The analysis showed a cost of about $21,000 per antimicrobial-resistant infection patient, producing a cost to the hospital of about $4 million and a total societal cost of as high as $15 million including the loss of productivity. “[The study] came from a challenge that Ted Kennedy gave me. He said that if you are not going to save money you won’t get much interest in [antibiotic resistance], and we took him up on the challenge.”

Dream experiment. If money were no object, Levy says, he would design an experiment that would definitively and quantitatively demonstrate the link between subtherapeutic use in animals and the emergence of antibiotic-resistant infections in people.

Influential mentor. “I think the biggest training I received was with Watanabe, and that was just for a summer! He was patient, methodical, and a master.”

Greatest Hits

- Discovered the first active efflux pump involved in tetracycline resistance in Enterobacteriaceae

- Identified the mar operon, a bacterial regulatory locus that results in multidrug resistance to different antibiotics as well as to disinfectants

- Provided some of the first evidence that feeding animals low doses of antibiotics leads to high levels of resistant bacterial strains that can spread to other animals, people, and the environment

- Established the international Alliance for the Prudent Use of Antibiotics

- In 1993, published The Antibiotic Paradox: How Miracle Drugs Are Destroying the Miracle

- Served as an advisor on antibiotic resistance to multiple organizations, including the National Institutes of Health, the World Health Organization, the FDA, and the Environmental Protection Agency

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Antibiotic Resistance Can Boost Bacterial Fitness

Certain mutations that seem to confer antibiotic resistance in three different pathogenic bacterial species also provide a growth advantage and increased virulence during an infection, according to a study published in Science Translational Medicine today (July 22). While there are many well-known examples of antibiotic-resistance mutations that reduce bacterial fitness, scientists at the Brigham and Women’s Hospital and Harvard Medical School and their colleagues have found that some antibiotic-resistant pathogenic bacteria outgrow their antibiotic-sensitive counterparts, even in the absence of antibiotic selection.

“This study calls into question the concept that antibiotic resistance leads to less virulence,” said Stuart Levy, a microbiologist who studies antibiotic resistance at the Tufts University School of Medicine and was not involved in the study. However, he noted, this study is not the first to report evidence of mutations that both provide resistance and boost the fitness of certain pathogenic microorganisms.

Many microbiologists have assumed that because antibiotic-resistant strains of bacteria are typically at a disadvantage when it comes to growth, halting the use of antibiotics could weed out such resistance, mitigating concerns tied to the rising numbers of drug-resistant infections. “[This study] leads to the question of whether that strategy would work,” said Amy Anderson, who studies anti-infective resistance at the University of Connecticut, but was not involved in the study. “If true, that has far-reaching implications.”

David Skurnik and Gerald Pier of the Brigham and Harvard and their colleagues sought to test whether any strains among a library of 300,000 transposon insertion mutants of Pseudomonas aeruginosa—a common cause of lung and other infections in hospital patients—resulted in a growth advantage in vivo. The team used its entire library of loss-of-function mutants to infect the lungs of mice, and then sampled the bacterial populations from the animals’ organs throughout the resulting infections.

Using DNA sequencing, the researchers found that insertion mutations in 116 genes were particularly abundant after at least 24 hours of growth in the murine models.  One of the mutations isolated affected the oprD gene, which were previously linked to antibiotic resistance in P. aeruginosa-infected patients. Another, in the glpT gene is known to confer resistance to antibiotics in Escherichia coli. Both genes serve similar functions: oprD encodes a channel that allows carbapenem antibiotics to enter bacterial cells, while glpT permits a different antibiotic, fosfomycin, to get into cells.

These transposon mutants—as well as two strains isolated from patients with P. aeruginosa—were more virulent compared to antibiotic-sensitive strains in the mouse lung infection models. The glpT mutant could even kill macrophages in vitro, the researchers found, suggesting that the antibiotic resistance may be linked to the ability of P. aeruginosa to evade attack by the host immune system. Moreover, transposon mutants in genes that normally provide intrinsic drug resistance had a growth disadvantage in the mouse models of lung infection.

The researchers demonstrated similar results in both Acinetobacter baumannii and Vibrio cholera. “The new picture emerging from this work is that antibiotic resistance is not [necessarily] associated with a fitness cost, and is even associated with an increased fitness and an increased virulence,” Skurnik told The Scientist.

The team’s results do not suggest that antibiotic resistance is always linked with increased virulence or fitness in these three, or other species of pathogenic bacteria. And they only pertain to the loss-of-function mutations examined. Whether gain-of-function mutations or plasmid-borne antibiotic-resistance genes have similar effects on bacterial fitness and virulence has yet to be seen.

“The results are interesting, but I don’t think the findings challenge the idea that most [antibiotic-resistance mutations] confer reductions in fitness when measured in vitro or in vivo,” Dan Andersson, who studies bacterial evolution at Uppsala University in Sweden and was not involved in the study, wrote in an e-mail to The Scientist. Whether the newly identified mutations are bona fide resistance genes also remains to be seen, he added.

Levy noted that there may be inherent differences in fitness and virulence of engineered transposon strains versus drug-resistant strains isolated by selection on antibiotics.

Still, even if the growth advantage is only for certain classes of drug-resistant strains, the work raises questions on how to maximize efforts toward the prudent use of antibiotics, said Pier. “The assumption that if we just stop using antibiotics, bacterial strains around now would disappear—because they are less able to cause infection—may be very simplistic and naive.”

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What's Causes Antibiotic Resistance?

What are the possible consequences of antibiotic resistance?

Many of the available treatment options for common bacterial infections are becoming more and more ineffective. As a consequence, there are situations where infected patients cannot be treated adequately by any of the available antibiotics. This resistance may delay and hinder treatment, resulting in complications or even death. Moreover, a patient may need more care, as well as the use of alternative and more expensive antibiotics, which may have more severe side effects, or may need more invasive treatments, such as intravenous injection, to be given in hospitals.

A recent WHO report made a clear case that resistance of common bacteria to antibiotics has reached alarming levels in many parts of the world. In Europe, for example, there is an increase of the resistance to major antibiotics of common bacteria such as Escherichia coliwhich causes, among others, urinary tract infections, and also Staphylococcus aureus (the MRSA or methicillin-resistant Staphylococcus aureus), Klebsiella pneumoniae, and Pseudomonas aeruginosa.

For WHO, the consequence is that progress in modern medicine, which relies on the availability of effective antibacterial drugs, is now at risk. For instance:

Common infections such as pneumonia that can run in health care settings, may not respond to available or recommended drugs like penicillin, putting the lives of patients at risk;

Cystitis, one of the most common of all bacterial infections in women, may become untreatable or need to be treated by injected drugs, imposing also additional costs to the patients and to the health system in general;

Antibacterial drugs used to prevent infections after surgeries or to treat common infections in neonatal and intensive care may become less effective or ineffective.

One issue stated in the WHO report is that there are very few antibiotics discovered and developed since 1985 to replace those becoming ineffective.

One issue stated in the WHO report is that there are very few antibiotics discovered and developed since 1985 to replace those becoming ineffective.

Which are the main infections becoming resistant to antibiotics ?

Bacteria causing a wide range of common infections may become resistant to one or many antibiotics: urinary tract infection, pneumonia, skin infection, diarrhea, bloodstream infection. The high proportions of resistance to third generation cephalosporins reported for E. coli and K. pneumonia, for example, means that treatment of severe infections caused by these bacteria must now rely mainly on another antibiotic family that is more expensive and may not be available in resource-constrained settings. In addition, this can only last as long as these bacteria do not become resistant to this other alternative.

Patients in hospitals are at special risk for infections by resistant and very pathogenic bacteria that can be present in hospitals and clinics, the so-called nosocomial infections, and which are unrelated to their reason for admission.

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Solutions for Antibiotic Resistance

1. Collect Data

The European Union has detailed, 15-year data on antibiotic use by drug, and resistance data by microbe, covering 26 countries. They know what and where the problems are. For example, Greece has the highest per capita use of antibiotics, and The Netherlands has among the lowest. The proportion of Klebsiella isolates that are carbapenemase-producing in Greece is 38%, and in The Netherlands it is 0.2%. The proportion of S aureus isolates that are methicillin-resistant is 58% in Greece and 1.6% in The Netherlands. These data are strong testimony supporting the acknowledged association between antibiotic abuse and resistance, and they identify areas of great need for corrective intervention. In the United States, we have no comparable data.

2. Stop Antibiotic Use on the Farm

A full 80% of antibiotic use in the United States is for growth promotion and disease prevention in farm animals. Resistant bacteria and resistance genes can be traced from the chickens to the chicken meat in grocery stores and, finally, to blood cultures in patients (The "farm to fork” phenomenon). The practice of antibiotics for growth promotion on the farm was stopped in Denmark many years ago, with no apparent economic or animal health consequences.

3. Practice Antibiotic Stewardship

Antibiotic stewardship has many elements:

• Use a procalcitonin level as a biomarker for infection to avoid unnecessary antibiotic use, as has been shown to be successful in nearly every well-controlled trial.

• Short courses of antibiotics are virtually always effective in well-controlled trials.

• Switch antibiotics from intravenous (IV) to oral formulations to hasten discharge and reduce risks associated with IV catheters. This switch is easily done with many antibiotics (linezolid, metronidazole, fluoroquinolones, some cephalosporins, fluconazole, etc).

• Use colistin carefully. Colistin, available since 1961, is increasingly needed but is saddled with dosing errors because the recommendations in the package insert are wrong

• Avoid antibiotic redundancy, as illustrated by the report that 23% of 782,821 patients were given metronidazole on top of another agent for anaerobic bacteria.

4. Reduce Inappropriate Antibiotic Use in Outpatients

The abuse of antibiotics is well known and in large part reflects consumer demand because the patient expects to walk out of the clinic with a prescription for that viral respiratory tract infection. A Cochrane review of all methods to reduce antibiotic abuse in the clinic concluded that the "3-day prescription" was the only method with documented success.This means telling the patients with "sinusitis" that they probably have a viral infection that is likely to get better within 3 days, and providing a prescription that is dated 3 days later for use if the patient is not better or is getting worse at that time.

Public campaigns can work but they are costly. France conducted a national campaign to convince patients and providers to do better, with a target of a 25% reduction in antibiotic prescriptions in the entire country. They achieved a 26% reduction! We also need to communicate better via modern technologies such as Twitter. For example, a tweet that proclaimed "Finally over my cold, thank God for Z-pack" had 850,375 followers. We need to do better in social networking arenas to reach that audience.

Information from the microbiome could be particularly important. This is in very early development, but initial studies show that antibiotics such as ciprofloxacin, commonly prescribed for 1 week, have a profound and sometimes lasting effect on the colonic microbiome. Furthermore, excessive antibiotics in childhood have been associated strongly with subsequent obesity and inflammatory bowel disease.

Despite these concerns, we need to be careful with an anti-antibiotic campaign that goes too far, because antibiotics are great drugs when indicated.

5. Adopt Rapid Diagnostic Tests

Molecular methods are coming fast. We now have a polymerase chain reaction test for the detection of MRSA, vancomycin-resistant Enterococcus, Neisseria gonorrhoeae, Chlamydia trachomatis, group B Streptococcus, tuberculosis, Candida albicans, and many others. Coming soon are tests that will detect practically every bacterium as well as other pathogens, making an etiologic diagnosis to facilitate antibiotic decision-making within 1-2 hours of collecting the culture. Interpretation will be tricky, however, because many specimens will need quantitation and there will be a predictable need for substantial stewardship.

6. Develop New Drugs

"Big pharma" previously developed new antibiotics in response to the continuing development of resistance. They no longer do this because they cannot regain their investment as a result of idiosyncrasies of short-term use, low price standards, and the antiquated model of the US Food and Drug Administration (FDA). Does anyone think that it would be possible to conduct a 2000-patient study with, for example, pneumonia caused by multidrug-resistant bacteria?

We need a novel method to deal with antibiotic development and its related costs. Possibilities include:

• A public-private partnership such as the combined resources of the Bill & Melinda Gates Foundation, Janssen Pharmaceuticals, and the TB Alliance, which has now produced bedaquiline, the first new FDA-approved drug for tuberculosis in the past 40 years;

• Federal support for this effort, such as use of Biomedical Advanced Research and Development Authority (BARDA) funds that originally targeted only bioterrorism; and

• The need for a novel system for testing drugs and diagnostics, such as the new National Institutes of Health-funded Antibiotic Resistance Network.

7. Integrate Antibiotic Resistance Initiatives Into Healthcare Reform

We need convincing evidence of the benefit of infection-prevention initiatives in the context of healthcare reform, with the goal of saving both lives and money. An example of success with this strategy is the "5-step plan to prevent central line bacteremia." The plan was logical, but it needed verification. It was tested in 103 intensive care units in Michigan, with the anticipated impressive results. Subsequently the plan was introduced in the CDC network, with the study authors' conclusion that "If every hospital did this, it would annually save 27,000 lives and $1.8 billion."

Healthcare reform priorities are ripe for similar prevention methods, including MRSA bacteremia, Clostridium difficile infection, surgical-site infection, and catheter-associated urinary tract infections. Caution must be used to prevent "gaming the system," however, as illustrated by the experience with central line bacteremia. When financial penalties were instituted, national rates of central line bacteremia declined by 25% within 1 week!

8. Create a Plan for the United States

We need a comprehensive plan for the United States that includes some or all of the points listed above. The European Union has a plan with identified priorities to address antibiotic resistance, supported by funding of $220 million per year. It is humbling that although we recognize the crisis of antibiotic resistance and our role in producing it, the United States has no comparable plan in place for resolving it

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Antibiotic Resistance and MRSA

Staphylococcus aureus is a bacterium that can be found on the skin and in the throat. It cause range of illnesses from minor skin infections to life-threatening disease such as meningitis and septicemia.

Some strains of Staphylococcus aureus have evolved become resistant to one or more of the commonly used antibiotics including methicillin. These are termed methicillin-resistant Staphylococcus aureus (MRSA). MRSA is especially prevalent in hospitals:

- Here patients tend to be more vulnerable to the infection

i.e. older, sicker and weaker.

- People live together and are examined by doctors and nurses that have just touched other patients.

- Many antibiotics strains are used, any resistant strains therefore have an advantage,

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Antibiotic Resistance and TB

TB is a bacterial disease of the lungs. Antibiotics can be used to treat TB but they need to be taken for 6 - 9 months and this is where the problem lies. 

- TB that is resistant to the 2 most commonly used antibiotics (isoniazid and rifampin) is called multidrug resistant (MDR) TB.

- MDR TB requires treatment for 18-24 months with "second-line drugs" (there are currenly only six second-line drugs) that are much less effective, poorly tolerated by the patient, and far more costly. 

- Extensively drug-resistant TB (XDR TB) is a subset of MDR TB caused by strains of bacteria that are resistant to the most effective first- and second- line drugs.

Why have these resistance strains increased?

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Prevent Antibiotic Resistance Now!!

They are some important steps should be taken by every human to prevent and stop antibiotic resistance.

Doctors, nurses, veterinarians and other health workers

Don’t prescribe or dispense antibiotics unless they are truly necessary and you have made all efforts to test and confirm which antibiotic your human patient or the animal you are treating should have. Today, it is estimated that in half of all cases, antibiotics are prescribed for conditions caused by viruses, where they do no good. You can also do more to prevent infections in the first place by ensuring your hands, instruments and environment are clean, and employing vaccines where appropriate.

People using healthcare

* Talk with your healthcare provider about antibiotic resistance:

 - Ask whether an antibiotic is likely to be beneficial for your illness

 - Ask what else you can do to feel better sooner

* Do not take an antibiotic for a viral infection like a cold or the flu.

* Do not save some of your antibiotic for the next time you get sick. Discard any leftover medication once you have completed your prescribed course of treatment.

* Take antibiotics only when prescribed by a certified health professional, but also don’t be timid about asking if you feel you really need them. If you take an antibiotic, always complete the full prescription, even if you feel better, because stopping treatment early promotes the growth of drug-resistant bacteria.

* Do not take antibiotics prescribed for someone else. The antibiotic may not be appropriate for your illness. Taking the wrong medicine may delay correct treatment and allow bacteria to multiply.

* If your healthcare provider determines that you do not have a bacterial infection, ask about ways to help relieve your symptoms. Do not pressure your provider to prescribe an antibiotic.

Farmers and others in the agriculture sector

Ensure that antibiotics given to animals are used only to control or treat infectious diseases and under veterinary supervision. Misuse of antibiotics in livestock, aquaculture and crops is a key factor contributing to antibiotic resistance and its spread into the environment, food chain and humans. Clean and uncrowded conditions and vaccination of animals can reduce the need to use antibiotics.

Governments

We need robust national action plans to tackle antibiotic resistance. Critical steps are improved surveillance of antibiotic-resistant infections, regulation of the appropriate use of quality medicines, and education about the dangers of overuse.

Development organisations

Compared with populations in industrialised nations, people in low-income countries are not getting fair access to antibiotics. Countries seeking donor help to strengthen their health systems need guidance to ensure essential antibiotics are affordable, reach the people who really need them, and are used responsibly.

Industry

Industry needs to move faster and more aggressively to research and develop new antibiotics, but we also have to implement new ways of stimulating research and development. Many talk of an antibiotic “discovery void” since the late 1980s. We are currently in a race between drug development and bacterial evolution. Incentives for developing new antibiotics can help. There are some encouraging trends.

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What the Industry do from Antibiotics?

In our life when we hear about antibitics, we always relate antibiotics with humans. But the truth is not only humans are taking antibiotics.

More than 80% of antibiotics are given for animals for the rapid growth and to prevent from sicks caught from not clean environments. It's maybe sounds great but they are not.

Over the years there has been a significant increase in the amount of antibiotic resistance super-bugs and if you were to get ill, it could be very hard, even impossible to find a cure to recover.

When consumer reports tested chicken, it showed that two thirds of the chicken samples contained harmful bacteria, to make matters worse, more than half the bugs were resistant to antibiotics! Furthermore, some meat labels are not approved by the government and are even misleading, making the customer feel as though the product is perfectly healthy.

The good news is, some labels are honest and sell healthy produce, particularly labels which are organic. From this it could be concluded that some parts of the meat industry are willing to put aside the public’s health in order to make more money, whether this comes as a shock or not, is irrelevant, it is important to make sure you check labels before purchasing meat.

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