Study after study, and such influential researchers as Dr. Martin Blaser (at New York University) have warned about antibiotics having a negative effect on the human microbiome - that they kill off gut microbes. And all conclude that therefore antibiotics should be used carefully - only when needed. But there are other reasons to be cautious about antibiotics as a recent article warned. Some people who take the class of antibiotics called fluoroquinolones develop a syndrome called fluoroquinolone-associated disability (FQAD) which causes crippling side-effects, including irreversible nerve damage. People who have fallen ill after taking fluoroquinolones call it being "floxed".
The FDA currently has "black box" warnings about fluoroquinolones - that they can cause tendon rupture or a risk of irreversible nerve damage in those taking the antibiotics. Black box warnings are placed inside a black box on drug labels and call attention to serious or life-threatening risks. Millions have taken these drugs, but some (the FDA considers it a rare event) develop the serious side-effects.
Many people (myself included) have taken fluoroquinolones, such as Levaquin, over the years for sinusitis treatment. Some have taken them multiple times. Most have not reported side-effects (including myself), but those who developed serious side-effects (floxed) are desperate for sinusitis treatments that don't involve taking antibiotics. Which is where alternative treatments using probiotics such as Lactobacillus sakei come in (yes, it works for sinusitis!). Excerpts from Nature (the international journal of science):
In 2014, Miriam van Staveren went on holiday to the Canary Islands and caught an infection. Her ear and sinuses throbbed, so she went to see the resort doctor, who prescribed a six-day course of the popular antibiotic levofloxacin. Three weeks later, after she had returned home to Amsterdam, her Achilles tendons started to hurt, then her knees and shoulders. She developed shooting pains in her legs and feet, as well as fatigue and depression. “I got sicker and sicker,” she says. “I was in pain all day.” Previously an active tennis player and hiker, the 61-year-old physician could barely walk, and had to climb the stairs on all fours. Since then, she has seen a variety of medical specialists. Some dismissed her symptoms as psychosomatic. Others suggested diagnoses of fibromyalgia or chronic fatigue syndrome. Van Staveren is in no doubt, however. She’s convinced that the antibiotic poisoned her.
She’s not alone. Levofloxacin is one of a class of drugs called fluoroquinolones, some of the world’s most commonly prescribed antibiotics. In the United States in 2015, doctors doled out 32 million prescriptions for the drugs, making them the country’s fourth-most popular class of antibiotic. But for a small percentage of people, fluoroquinolones have developed a bad reputation. On websites and Facebook groups with names such as Floxie Hope and My Quin Story,thousands of people who have fallen ill after fluoroquinolone treatment gather to share experiences. Many of them describe a devastating and progressive condition, encompassing symptoms ranging from psychiatric and sensory disturbances to problems with muscles, tendons and nerves that continue after people have stopped taking the drugs. They call it being ‘floxed’.
For decades, regulatory agencies and the medical profession were sceptical that a brief course of antibiotics could have such a devastating, long-term impact. But after persistent campaigning by patient groups, attitudes began to change in 2008, when the US Food and Drug Administration (FDA) announced the first of what would be a series of strong alerts about the side effects of fluoroquinolone drugs, including tendon rupture and irreversible nerve damage. In 2016, the agency accepted the existence of a potentially permanent syndrome that it calls fluoroquinolone-associated disability (FQAD), and recommended that the drugs be reserved for serious infections. That move has triggered other regulatory agencies to reassess the antibiotics: Health Canada warned doctors of rare cases of persistent or disabling side effects in January 2017, and the European Medicines Agency (EMA) is expected to publish the results of a safety review this year, after a public hearing planned for June.
Fluoroquinolones are valuable antibiotics, and safe for most people. Yet they are so widely prescribed that their side effects might have harmed hundreds of thousands of people in the United States alone, say scientists who are working with patients to unpick FQAD’s causes. Fluoroquinolone toxicity, they say, provides a compelling example of an emerging understanding that antibiotics don’t just harm microbes — they can severely damage human cells, too. Until recently, investigations into the side effects of antibiotics have focused on how the drugs disrupt the human microbiome, says James Collins, a medical engineer at the Massachusetts Institute of Technology in Cambridge. “Antibiotics are also disrupting our cells, and in pretty hefty ways,” he says.
Quinolone antibiotics, first developed in the 1960s, kill bacteria by blocking enzymes called class II topoisomerases, which normally untangle DNA during cell replication. These enzymes usually cut DNA’s double helix, pass another part of the strand through the gap, and then mend the cut. But quinolones bind to the enzymes, preventing them from mending their cuts. In the 1980s, researchers added fluorine atoms to the quinolones’ structures. This allowed the antibiotics to penetrate tissues throughout the body, including the central nervous system, and boosted their effectiveness against a broad range of bacterial infections.
Some FDA-approved fluoroquinolones were swiftly withdrawn from the market after severe adverse reactions and several deaths — trovafloxacin, withdrawn in 1999, damaged livers, for instance. But others became the drug of choice both for serious infections and for routine complaints, despite rare side effects. “These are heavily used drugs because they are very effective,” says Joe Deweese, a biochemist who studies topoisomerases at Lipscomb University College of Pharmacy in Nashville, Tennessee. ....
But by that point, some people had already flagged potential problems. In 1998, US journalist Stephen Fried (now at Columbia Journalism School in New York) published a book called Bitter Pills about his wife’s severe and long-lasting neurological reaction to ofloxacin. It helped to trigger a wave of reports on websites such as the Quinolone Antibiotics Adverse Reaction Forum, which by 2001 hosted more than 5,000 posts. The late Jay Cohen, then a psychiatrist and medical researcher at the University of California, San Diego, contacted patients through the sites and published 45 case studies1. Cohen warned that after taking fluoroquinolones, some people had developed serious problems in multiple organs. These effects came on rapidly and lasted for months or years.
Cohen’s work was largely dismissed at the time because of his reliance on online forums. But complaints and patient petitions continued. From the 1980s to the end of 2015, the FDA received reports from more than 60,000 patients detailing hundreds of thousands of ‘serious adverse events’ associated with the 5 fluoroquinolones still on the market (most commonly tendon rupture, as well as neurological and psychiatric symptoms), including 6,575 reports of deaths. The FDA says that the reports of adverse events it receives — sent in by drug manufacturers, by doctors and directly by consumers — cannot be used to reach conclusions about the severity of problems associated with drugs. Still, the fluoroquinolones have attracted more complaints than other more widely used antibiotics.
In 2008, the FDA announced ‘black box’ warnings of tendon rupture among those given the antibiotics; in 2013, it added a risk of irreversible nerve damage. (Such warnings are placed inside a black box on drug labels, and call attention to serious or life-threatening risks.) As alerts mounted, patients launched lawsuits against manufacturers of the drugs, claiming they had not been adequately informed of risks. These cases have been variously won, lost or settled for undisclosed sums, and many are still in progress; manufacturers argue that they handled risks appropriately, and work with the FDA to update safety labels.
In November 2015, the FDA voted to recognize FQAD as a syndrome on the basis of 178 cases that the agency regarded as clear-cut: otherwise healthy people who took fluoroquinolones for minor ailments and then developed disabling and potentially irreversible conditions2. The FDA also noted a disturbing pattern: fluoroquinolones had a much higher percentage of disabilities among their serious-adverse-event reports than did other antibiotics.
Beatrice Golomb at the University of California, San Diego, has been working for a decade with people affected by fluoroquinolones, beginning with David Melvin, a police officer and keen cyclist who had to use a wheelchair after he was given levofloxacin for suspected epididymitis in 2007. Accumulating evidence, Golomb says, suggests that fluoroquinolones are damaging mitochondria, the power packs inside human cells that evolved from symbiotic, bacteria-like cells billions of years ago. This kind of harm can affect every cell in the body, explaining why a wide range of symptoms can appear and get worse over time.
Isolated studies from the 1980s onwards have suggested that fluoroquinolones impair mitochondrial function, but a 2013 study4 by Collins and his colleagues is the most convincing, researchers say. They reported that antibiotics in several classes triggered oxidative stress — a build-up of reactive, oxygen-containing molecules — in mitochondria, inhibiting their function across a range of mammalian cells, as well as in mice. “We were surprised at how strong the effect was and how common the effect was across the different classes,” Collins says. But “the largest effects were seen in the quinolones”.
At a conference last September, Bennett reported preliminary data that might hint at why only some people develop serious side effects from fluoroquinolones. He took saliva samples from 24 people who reported neuropsychiatric side effects — such as memory loss, panic attacks and depression — and found that 13 of them (57%) shared a gene variant usually seen in only 9% of the population. Bennett is not revealing the gene’s identity because he has a patent application in process, but he says that it seems to be a site related to poor metabolism of the quinolones. Such a mutation might cause dangerously high levels of the drug to accumulate in cells, including in the brain.
.... Manufacturers don’t have an incentive to fund post-market safety studies, particularly for off-patent drugs such as cipro and levofloxacin, where the vast majority of sales are from generics firms. “So there is really nobody to champion this work,” says Bennett. Another factor is scientists’ reluctance to publish results that drug companies might find unfavourable. “There’s a long history of adverse action against people who expose drug and chemical harms,” says Golomb.