NEW ANTIBIOTIC ATTACK S DRUG RESISTANT MICROBES

The multitude of microbes scientists have found populating the human body have good, bad and mostly mysterious implications for our health. But when something goes wrong, we defend ourselves with the undiscriminating brute force of traditional antibiotics, which wipe out everything at once, regardless of the consequences.

Researchers at Rockefeller University and their collaborators are working on a smarter antibiotic. And in research to be published October 5 in Nature Biotechnology, the team describes a 'programmable' antibiotic technique that selectively targets the bad bugs, particularly those harboring antibiotic resistance genes, while leaving other, more innocent microbes alone.

"In experiments, we succeeded in instructing a bacterial enzyme, known as Cas9, to target a particular DNA sequence and cut it up," says lead researcher Luciano Marraffini, head of the Laboratory of Bacteriology. "This selective approach leaves the healthy microbial community intact, and our experiments suggest that by doing so you can keep resistance in check and so prevent certain types of secondary infections, eliminating two serious hazards associated with treatment by classical antibiotics."

The new approach could, for instance, reduce the risk of C. diff, a severe infection of the colon, caused by the Clostridium difficile bacterium, that is associated with prolonged courses of harsh antibiotics and is a growing public health concern.

The Cas9 enzyme is part of a defense system that bacteria use to protect themselves against viruses. The team coopted this bacterial version of an immune system, known as a CRISPR (clustered regularly interspaced short palindromic repeats) system and turned it against some of the microbes. CRISPR systems contain unique genetic sequences called spacers that correspond to sequences in viruses. CRISPR-associated enzymes, including Cas9, use these spacer sequences as guides to identify and destroy viral invaders.

The researchers were able to direct Cas9 at targets of their choosing by engineering spacer sequences to match bacterial genes then inserting these sequences into a cell along with the Cas9 gene. The cell's own machinery then turns on the system. Depending on the location of the target in a bacterial cell, Cas9 may kill the cell or it may eradicate the target gene. In some cases, a treatment may prevent a cell from acquiring resistance, they found.

"We previously showed that if Cas9 is programmed with a target from a bacterial genome, it will kill the bacteria. Building on that work, we selected guide sequences that enabled us to selectively kill a particular strain of microbe from within a mixed population," says first author David Bikard, a former Rockefeller postdoc who is now at the Pasteur Institute in Paris.

In initial experiments, Bikard and colleagues targeted a strain of the common skin and respiratory bacteria Staphylococcus aureus that is resistant to the antibiotic kanamycin. Treatment by Cas9 programmed to target a part of the resistance gene killed most of the resistant Staph, but left behind the kanamycin-susceptible Staph.

Targeted bacterial genocide is only one option. Bacteria share genes, including those conferring drug resistance, in the form of rings of DNA known as plasmids. In a second series of experiments, researchers turned Cas9 on tetracycline resistance-harboring plasmids in a strain of the potentially deadly multidrug resistant bacteriaStaphylococcus aureus (MRSA). Not only did the resistant cells become sensitive to tetracycline after Cas9 destroyed the plasmids, but the arrival of Cas9 in other Staphcells acted as an immunization, preventing them from taking on resistance-carrying plasmids.

And, in a final set of experiments, conducted in collaboration with Vincent Fischetti's Laboratory of Bacterial Pathogenesis and Immunology, adjunct faculty member Chad Euler confirmed their test tube results on living skin, by using Cas9 to selectively kill kanamycin-resistant Staph infecting the shaved backs of mice.

In spite of the promising results, the delivery system needs improvement. The researchers used bacteria-infecting viruses to inject the programmed Cas9 enzymes into the bacterial cells, but these viruses only attack specific types of cells. Scientists need to devise a less discriminating method of delivery, before the technology can be used to develop a new class of antibiotics, Marraffini says.

In addition to its potential as a much-needed new weapon against drug-resistant microbes, the new system could also be used to advance research on the complex populations of microbes in the body, about which very little is known. "There are enormous microbial communities in the human body," Marraffini says. "Programmable Cas9 enzymes may make it possible to analyze these populations by eliminating their members, one by one, and studying the effects."

How The Antibiotic Ceftriaxone Can Reduce Chronic Pain

Today's short post from news-medical.net (see link below) looks at the potential for an antibiotic being used for analgesic purposes. Studies have shown that a dose of Ceftriaxone, an antibiotic used to kill microbes before surgery, has a significant effect on pain thresholds after the surgery. A small Italian study is mentioned here, involving 45 patients undergoing neuro surgery of one form or another. Those patients who had been injected with a single dose of the antibiotic prior to surgery could withstand post operative pain significantly better than those who did not. There are implications for the future treatment of neuropathic pain, if the process can be further refined and better targeted. This sort of study may mean little to the casual reader but it does illustrate the process of getting a new treatment into general practice. First, as is the case here, a success story has to be spotted and then others will take the idea or theory and try to apply it to other general situations. It may take years but at least you now know that an antibiotic can perform an analgesic function and may provide an alternative pain prevention tool in the future.

Study explores analgesic activity of ceftriaxone in humans

Published on June 26, 2013

A single dose of the antibiotic ceftriaxone given for antimicrobial prophylaxis prior to surgery enhanced patient pain thresholds after the procedure, according to a study published in The Journal of Pain, the peer review publication of the American Pain Society, www.americanpainsociety.org.

Previous studies have shown that drugs with a mode of action to enhance glutamate clearance might be effective in the treatment of chronic pain. In animals, repeated does of the antibiotic ceftriaxone have reduced both visceral and neuropathic pain. The drug induces activation of the GLT-1 gene. This is the first study to explore the analgesic activity of ceftriaxone in humans.

Researchers at University Sapienza in Rome analyzed whether a single dose of ceftriaxone given for antimicrobial prophylaxis prior to surgery could enhance patient pain thresholds after surgery. Forty-five patients undergoing surgery for carpal tunnel syndrome or ulner nerve compression disease participated in the study. They were randomized in three treatment groups: IV doses of saline, saline with ceftriaxone and saline with cefazolin. Injections were administered one hour prior to surgery, and mechanical pain thresholds were measured 10 minutes before the injections and 4 to 6 hours following surgery. No analgesic drugs were allowed in the first six hours after surgery.

Results in the human subjects showed that those treated with saline and cefazolin showed no change in mechanical pain thresholds six to seven hours after surgery, but pain thresholds in patients given a single preoperative does of ceftriaxone increased significantly.

This is the first study showing analgesia resulted from administration of an antibiotic in humans. The authors concluded that ceftriaxone should be the drug of choice for surgical prophylaxis in situations when pain does not rapidly resolve following surgery or when strong pain is expected to occur after surgery.

SOURCE American Pain Society

http://www.news-medical.net/news/20130626/Study-explores-analgesic-activity-of-ceftriaxone-in-humans.aspx

ANTIBIOTIC MIGHT RAISE HEART RISKS

Taking the widely used antibiotic clarithromycin may boost some patients’ odds of dying from heart-related causes, a new study suggests.

Because millions of people receive this antibiotic each year, the findings require urgent confirmation, said the Danish researchers behind the study. However, they emphasized that the actual risk is small and that guidelines for the use of the drug should not be changed until more information is available.

One heart expert wasn’t surprised by the finding, however.

“Some commonly used antibiotics should be taken with caution, especially for those people who are at risk for heart disease,” said Dr. Suzanne Steinbaum, a preventive cardiologist at Lenox Hill Hospital in New York City.

“As it has been shown before, not all antibiotics are created equal when it comes to increasing the risk of cardiovascular death,” she said. “If you have an underlying heart condition, be certain to discuss it with your doctor before taking an antibiotic prescription. There are definitely safer alternatives.”

Clarithromycin and another antibiotic called roxithromycin belong to a group of antibiotics called macrolides. It’s believed that macrolides increase the risk of potentially deadly heart rhythm problems, the Danish researchers explained.

In the study, they analyzed more than 5 million courses of antibiotic treatment with clarithromycin, roxithromycin, or penicillin V given to Danish adults, aged 40 to 74, between 1997 and 2011.

During this period, 285 cardiac deaths occurred — 18 during the use of clarithromycin and 32 during the use of roxithromycin. After adjusting for other factors, the researchers concluded that ongoing use of clarithromycin was associated with a 76 percent higher risk of cardiac death, compared with the use of penicillin V.

The absolute risk difference was 37 cardiac deaths per 1 million courses with clarithromycin. The authors noted that there was no heightened risk of cardiac death after treatment with clarithromycin stopped.

Ongoing or past use of roxithromycin was not associated with increased risk of cardiac death, according to the study published online Aug. 19 in BMJ.

The study is “the first large-scale population-based observational study to show significantly increased cardiac risk with clarithromycin and the relative cardiac safety of roxithromycin,” wrote a team led by Henrik Svanstrom of the Statens Serum Institut in Copenhagen.

Because the study was observational in nature (looking over past data), it could not prove a cause-and-effect relationship. However, an expert familiar with antibiotics said the findings are worthy of concern.

Although the risk to any one patient remains very small, “it should still be considered by physicians before prescribing this antibiotic,” said Dr. Ambreen Khalil, an infectious disease specialist at Staten Island University Hospital in New York City. “Patients with underlying heart conditions who are taking medications that affect the heart rhythm may be particularly vulnerable,” she said.

Fluoroquinolone Antibiotic Neuropathy A Personal Story

Today's post from hormonesmatter.com (see link below) is an alarming personal story of how taking fluoroquinolone antibiotics changed one woman's life for ever. It cannot be over-stressed how important it is to talk over the side effects of certain antibiotics with your doctor. Fluoroquinolones have long been known to possibly bring on nerve damage and if you have neuropathy already, make it considerably worse. This article is a cautionary tale. Always get advice.

Fluoroquinolone Neuropathy Feels Like Acid Burning and Electrocution  
Wednesday, February 5th, 2014 / Janet Murray
 

My name is Janet Murray, I am 57 years old. I do not even know how to put my health story into words so that the human mind can understand the pain I have lived with. I lived in Canada and had been given many courses of Cipro for various illnesses over the last 30 years. Sometime ago, I began developing a lot of strange problems that no one could diagnose. I had GI difficulties, body pain, migraines every week, severe interstitial cystitis – so severe they wanted to remove my bladder. Thankfully, they did not. I was given many diagnoses too, including Chronic Fatigue Syndrome (CFS) and fibromyalgia. My cognitive abilities became so impaired. I loose words and my memory is shot. I had to leave my job with the Federal Government and work at home, at my own hours. I have been extremely fatigued for the last 25 years, but I never connected the dots between my health issues and the fluoroquinolone antibiotics like Cipro, Levaquin, Avelox and others until I blew out my forearm tendon, a classic post fluoroquinolone adverse reaction. It was only then that I began to learn more about the chronic symptoms that fluoroquinolone antibiotics evoke. I had them all and more. These symptoms didn’t appear all at once, and so it was difficult to identify at first, but over time, my illnesses became readily apparent and progressive to the point that it was no longer a question of if I was poisoned by a fluoroquinolone, but how badly.

Let me back up a little though and give you some more details. For years, I was fatigued and suffering from post fluoroquinolone reactions, but I didn’t know it. During that time, I had a long distance relationship with the love of my life in NJ. He waited and visited me back and forth for 10 years and I visited when I was well enough. When I was finally was well enough to immigrate to the US, I he asked me to marry him and so I stayed and had two wonderful years. We are jewelry designers and did the large shows. I functioned, at very low level and had to rest always, but I was living my dream. Even functioning at such a low level, I was happy after many years of hell.

One year, I kept getting bronchial issues and went to a walk in clinic. I was given Levaquin with Prednisone with NSAIDS and was on small dose of a benzodiazepine. Fluoroquinolones should never be used with steroids and NSAIDS, something I did not know at the time and apparently neither did the doctors. I took this combination again and again and again across that year.

My reaction to these drugs was delayed and so it did not occur to me to link the Levaquin or my past Cipro use to my strange symptoms. I have since learned that delayed adverse reactions are common post fluoroquinolones. After my first script that year I was more tired, could not walk far and something was not right. I didn’t know what though. During the second year I woke up with acid pain in the shoulder and could not lift it. I was told I had frozen shoulder. It was really a tendon rupture, common post fluoroquinolone.

The pain in my forearm and shoulder was horrific. It took 8 months before I could move my arm again. Then I woke up one morning and the same thing was happening on my buttock tendons. I had the same horrific, acid-like pain. Those tendons ruptured. I crawled for 4 months and tried to stand when I could. I could no longer walk, the pain was unbearable.

One morning I woke up and my entire body felt like it was beaten with a baseball bat. I had a shot-like feeling in the base of my neck. I sat up, vomited and shook. The next day my entire body started to shake. I felt like I had been electrocuted. I had sharp pains of electricity though my entire body. My skin felt ripped off of the bones with electric jabs and jolts. I had large jolts of electricity cursing through my body. I sat for 5 months frozen, feeling like I was living in a body of large, angry hornets, stinging me all over 24 hours a day, 7 days a week. The electrocutions were never ending.

My stomach almost shut down almost. Every joint in my body popped and cracked when I moved. My legs would not hold me. I lost the vision in my right eye due to a macular tear. I lost four teeth due severe periodontal damage. Other symptoms include:
Up to 40 mouth sores at a time. The doctors say they look like burns or lesions. I wonder if it’s not a form of Steven-Johnson Syndrome.
Swaying, if walking, dizzy, feeling of being “stoned” in the head.
Sensory chills so severe with stinging that it takes 4 hot water bottles and wearing then down top as well.
Arms and hands go dead and numb
Constant feelings of being electrocuted
Severe bowel constipation
Intolerance to most foods
Body hair stopped growing
My skin has become very thin and transparent with enlarged veins.
Pin prick sores on my legs and what looks like burns all over my body.

On the right, the burn-like lesions all over my body. On the left, the pin-prick sores on my legs.
I experience severe changes in body temperature.
Feelings of terror and anxiety, not related to any surrounding, that come out of the blue
Severe depression
Hyperthyroid

And the strange symptoms go on and on. No one seemed to understand. I was almost dead. I dropped 40 pounds in three months. My heart pounds non-stop. Terrors and jolts surge through me. I was hysterical and crying.

The doctors keep saying I have fibromyalgia. FIBRO, I am being electrocuted..!! It couldn’t have fibro. I sat and thought this is NO normal illness but nothing showed up much on my tests. I have seen 50 doctors and no one can find anything. I feel like I have been poisoned. I soon learned, I was not alone. It was the Levaquin, a fluoroquinolone antibiotic that I have since learned, causes severe peripheral neurophathies, mitochondrial damage, and all of the seemingly unrelated symptoms that I have experienced over the last couple of years.

Right now, I am in so much pain, I cry daily. I wake up with night terrors, heart pounding. My feet feel frozen, as if they are dying due to extreme hypothermia – the kind mountain climbers face when their fingers and toes turn black. That’s what my feet feel like. My tongue burns like a hornet’s nest, day in, day out. It has been a year now, living with all over the body hornet stings and large tree like branch zapping about 40 at a time. I had the EMG and nerve biopsy that shows axonal swelling. I had an MRI showing two white matter lesions in the frontal lobe, the doctors say are consistent with MS or Lyme disease.

I should mention, I also tested positive for the MTHFR mutation that makes methylating vitamin B’s difficult. Even with the axonal damage, no one knows what to do. They tried to give me painkillers but I cannot tolerate them and vomit them back up. I have been on Paxil for years, more because I cannot seem to withdraw from it than anything else. Gabapentin, even at a high dose, does nothing and so I suffer. I cannot take this much longer. I cannot live with the nerve pain. Please help.

A few other clues that might be helpful for understanding this mess. When I tried acupuncture to relieve the nerve pain, it made it worse. The hornet’s nest sting lit up. Ditto for niacin. When I was given niacin, my body reacted very strongly. If there are doctors, researchers, patients, or anyone out there that can help reduce the pain I experience, who can help heal, reverse, or even just slow what seems to be a progression of increasing pain, please leave your comments here.

http://www.hormonesmatter.com/fluoroquinolone-neuropathy-acid-burning-electrocution/

Antibiotic Side Effects Include Neuropathy Vid

Today's post from click2houston.com (see link below) is a video with transcript of a news report on fluoroquinolone antibiotics such as Cipro and Levaquin (amongst others). The warning is clear and has been highlighted several times on this blog, yet these antibiotics are still routinely issued in their millions every day across the world. Be warned; if you're susceptible to, or already have neuropathic symptoms, it may be best to stay well clear of these antibiotics. At the very least, a serious discussion with your doctor may be necessary - there are always alternatives.

Thousands of adverse reactions reported from common antibiotics
Patients claim they were not properly warned of side effects from Levaquin, Ciprofloxacin
Author: Haley Hernandez, Reporter Published On: Apr 13 2015





HOUSTON - Less than a year ago, David Crain, a healthy and vibrant 33-year-old musician and personal trainer, was in the prime of his life. “I was running 6 miles in the August heat with my shirt off, screaming, yelling, listening to music effortlessly,” he said. Now, he can barely play his guitar.

Just about all I can do. It's hurting. If I do it now, I'll pay for it later,” Crain said.

Last June Crain went to the emergency room for what doctors believed was colitis. He was prescribed the antibiotic Ciprofloxacin, a generic form of Bayer’s Cipro, and began taking the recommended dosage.

“I think around about day seven or day eight, I just noticed like every time I would stand up I’d just be super-fatigued,” Crain said. “My ears rang all the time, I had trouble walking in the second month. My shoulders hurt, my tendons hurt.”

Tammy Renzi was prescribed the antibiotic Levaquin for a sinus infection. Six days into her 10-day dosage, she said she knew something wasn't right.

“I had a heaviness in my thighs. I had pressure in my lower spine. My vertebrae felt like they were rubbing on each other and I could hear the snapping in them,” Renzi said.

Both Crain and Renzi are not alone. From November 1997 to May 2011, more than 85,000 adverse reactions to Levaquin were reported to the Food and Drug Administration, including 1,174 deaths.

More than 67,000 adverse reactions to Cipro were also reported, including 1,257 deaths.

Dr. Charles Bennett, state chair of Medication Safety at the University of South Carolina, has been tracking the issue. He said Crain and Renzi's reactions may be caused by a mysterious genetic predisposition.

“Research should be done to identify those genetic factors,” Bennett said. “You certainly wouldn't want to take a drug if you knew you had a genetic predisposition to its side effects.”

Until that research is done, Bennett has petitioned the FDA, requesting stronger warnings.

“The current insert has a black box warning for tendon rupture and neurologic damage. It needs to be beyond the package insert,” he said.

Channel 2 Investigates reached out to both drug manufacturers.

According to Bayer Corporation, the FDA issued a drug safety communication requiring that "the drug labels and medication guides for all fluoroquinolone antibacterial drugs be updated to better describe the serious side effect of peripheral neuropathy."

Johnson & Johnson, Levaquin’s parent company, wrote, “Since 2004, the Levaquin label has informed physicians and patients about possible side effects related to peripheral neuropathy.”

Crain and Renzi said they want everyone to know the risks so that they don't end up with the same fate.

“I wouldn't take it again if my life depended on it,” Renzi said.

“My biggest fear is that I’m, you know, my son is never going to know who I was,” Crain said.

Renzi and Crain are not currently considering legal action, but in 2012 Johnson & Johnson settled lawsuits with 845 plaintiffs who claimed they were not properly warned about the risks.

http://www.click2houston.com/news/more-than-2000-adverse-reactions-reported-from-common-prescription-medications/32350128