When Catherine Slater started taking the antibiotics that her doctor prescribed for a small infected cyst on her shoulder, she felt the worst heartburn and indigestion she’d ever had in her life.
The retired schoolteacher from Aberdeenshire, Scotland, was not about to let a little “discomfort” dissuade her from following her doctor’s orders, however. “I just drank lots of water, gritted my teeth and carried on. After all, it was only for a week.”
Two weeks later, however, the gray and orange pills were gone, but Catherine’s vague gut symptoms continued off and on. She ignored the nausea and stomach pain one morning and set out with her husband to have lunch with friends, but as the day went on, she felt worse. She couldn’t finish her meal, and later she was alarmed to discover that her urine was very dark brown. She dug out the flucloxacillin package insert she had kept because of her earlier symptoms and found a statement about the “rare” side-effect of liver damage that could be fatal in people over 50.
Handed a sample of her urine the next day, her doctor dismissed Catherine’s suggestion that she had liver damage; he was certain she only had a urinary tract infection. She insisted he test her liver, however, and when the results came back, she was called to the hospital for an ultrasound to assess the damage, and blood testing began that would continue for months.
She began reading how to heal your liver with diet and lifestyle changes. Excess bile fluid spilled from her stressed liver into her bloodstream, so her skin yellowed like a fake suntan. The whites of her eyes yellowed, too. Her urine remained dark brown and her bowel movements were pale gray.
“My skin became dreadfully itchy. I would wake through the night tearing at my skin, so I had to sleep wearing silk glove liners. Some people have committed suicide because of the itching.”
Some 10 percent of those with drug-induced jaundice die or require a liver transplant. Another 20 percent of them have chronic liver damage more than six months after stopping the drugs.1
Fortunately, Catherine recovered within a few months. But why wasn’t she warned? And why didn’t her doctor recognize her symptoms immediately?
Dozens of studies in the medical literature describe delayed-onset drug-induced liver injury (DILI) as a possible side-effect of antibiotics at least as far back as 1985 – more than a quarter-century before Catherine was given them. Nearly a decade earlier, one UK study had recommended that all patients be warned of the risk of liver injury from flucloxacillin and that alternatives be used first.2
Catherine’s case reveals a system full of gaps that leave patients vulnerable to known injuries – not just from flucloxacillin but from antibiotics in general.
They are among the most-prescribed drugs on the planet. In the US, doctors write 270 million antibiotic prescriptions – equivalent to 84 antibiotic prescriptions per 100 people – every year. And countries like Mongolia, Turkey and Greece consume far higher amounts per capita.3
How ‘rare’ is rare?
There have been thousands of peer-reviewed studies on antibiotic side-effects and case reports of people suffering a wide range of symptoms, including a Clostridium difficile ‘superbug’ infection causing gut pain and life-threatening diarrhea, skin rashes progressing to potentially fatal blistering burns all over the body, brain inflammation and sudden heart attacks.4
One 2017 study by CDC researchers examining the medical records of 1,488 adult patients admitted to Johns Hopkins Hospital in Baltimore who’d been on systemic antibiotics for at least 24 hours found that 20 percent of them experienced an adverse event their doctor attributed to the drugs.5
Given the hundreds of millions of antibiotic prescriptions being written, this translates into tens of millions of adverse effects and millions of deaths globally each year.
‘Floxed’ patients
One class of antibiotics called fluoroquinolones, with names like ciprofloxacin (trade name Cipro), moxifloxacin (Avelox) and levofloxacin (Levaquin), have come to public attention with waves of complaints from people describing a particularly frightening laundry list of debilitating side-effects.
Thousands of previously healthy people who were prescribed the drugs for garden-variety sinus infections, urinary tract infections and coughs developed progressive conditions that included symptoms ranging from wracking fatigue, mood and sensory disturbances to problems with muscles, tendons and nerves that continued long after they quit the drugs. Some patients refer to it as being “floxed.”
Under public pressure, the US Food and Drug Administration (FDA) recognized the condition in 2015, dubbing it fluoroquinolone-associated disability, or FQAD. At special committee hearings on the drugs, the agency described how out of 1,122 such cases, 178 people, or 16 percent, had conditions affecting at least two different body systems, including the heart and central nervous system, that persisted as long as nine years.6
Terry Aston, a patient advocate who testified at the hearings, said she developed FQAD following several floxacillin prescriptions, and her life was destroyed by devastating fatigue and nerve pain. “I lost my job. I lost my life as I knew it and the way I loved it. And I’m not the only one. There are thousands of others just like me. Some of them are children.”
She brought 6,480 purple Mardi Gras beads to the hearings, one for each person damaged by fluoroquinolone antibiotics on some Facebook support groups – groups that now have more than 10,000 members.
‘You’ll be fine’
A number of patients testified to the FDA committee how their doctors had dismissed them. Chris Jones, a former firefighter in southern California, told the hearings that he was incorrectly prescribed Cipro for what turned out to be a minor injury, not an infection.
“After two weeks I was sent to a urologist, and I told him about the pain in my legs and the thousands of stories I’ve read on the internet of people being harmed by this drug,” Jones told the hearing. “He scolded me and told me to stay off the internet, that I was young and healthy, and to keep taking the antibiotic. I’ll be just fine.” But Chris wasn’t fine. “I went from playing soccer in the Firefighter Olympics, working a physically demanding job, to not being able to walk to my
own mailbox.”
For decades, most doctors and regulatory agencies were unwilling to believe that a brief course of antibiotics could have such devastating lifelong impact. But it is clear now that antibiotics can wreak wide-ranging havoc.
Microbiome mayhem
Antibiotics are very effective killers, but they are not very discriminating. They are like napalm to our microbiome. Researchers recently identified 1,952 new bacterial species in the human gut.7 The quest to figure out the role of each of these in maintaining or disturbing our health has barely begun.
We know that the ecology of these microbes is critical to our wellbeing, and they comprise 70 to 80 percent of our immune system. We don’t know what critical microbes we may be wiping out with each antibiotic dose, but generally, the greater diversity of bugs we have, the better our odds of good health.
It may be missing microbes that explain why, for example, antibiotic use has been shown for years to elevate the risk of inflammatory bowel disease.8 And why a 2017 study found that children who are treated with antibiotics in the first three years of life have double the odds of developing asthma.9
Most people still assume that antibiotics can’t harm our cells, but that may be wishful thinking. It turns out that the mitochondria – the tiny engines structured just like simple bacteria that power every human cell – may be antibiotics’ accidental victim.
A 2010 study by Pfizer pharmaceutical researchers found that some antibiotics affected mitochondria. In particular, every fluoroquinolone drug they tested damaged mitochondria in human liver cells.
“Antibiotics are also disrupting our cells, and in pretty hefty ways,” James Collins, a medical engineer at the Massachusetts Institute of Technology in Cambridge, MA, told the journal Nature in 2018. In 2013, his team reported that several classes of antibiotics inhibited mitochondrial function in a range of mammalian cells.
“We were surprised at how strong the effect was and how common the effect was across the different classes . . . The largest effects were seen in the quinolones.”10
Bizarre effects
Many antibiotic symptoms like FQAD fit the mitochondrial toxicity picture, but others are hard to explain, such as “benign” thick black hair growth on the tongue with the use of minocycline.11 So is the “rare” life-threatening blistering disease Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), which is estimated to affect two to seven million people worldwide every year.12
One 38-year-old father from Holly, Colorado, was given an antibiotic prescription for a staph infection in his jaw. Two weeks later, Josh Dennis began experiencing intense itching, and blistering burns rapidly covered 90 percent of his body, causing him to go blind for weeks.
His skin sloughed off, and the membranes of the mouth blistered so he looked “like a zombie.” Placental tissue was surgically implanted over his eyes to save them. His condition gradually improved, but he was lucky to survive.
Rachel Brummert was 36 years old when her doctor prescribed her the fluoroquinolone Levaquin for a suspected sinus infection. Two weeks later, she was walking in a parking lot when, “I heard and felt it pop. I thought someone kicked me.”
She dropped from the pain, which she says was “worse than kidney stones, which I’ve had.” Her Achilles tendon had ruptured. “I could see in the ambulance that it had balled up into a baseball-sized swelling in my calf.”
A tendon in her big toe was removed to repair the Achilles, but that was just the first of 30 tendon ruptures that Rachel has had in the 13 years since she took Levaquin.
She has had 24 separate surgeries and doesn’t know if or when it will strike again. Memory issues, brain fog and seizures that she experienced early on have subsided. “I thought it would go away too, but I’m 40 now. I’m still rupturing.” Rachel told WDDTY. “It puts you out. You can’t work. It’s expensive and dehumanizing.”
Tendinitis and tendon rupture were recognized side-effects of fluoroquinolones before the drugs were ever marketed. A black box warning, the most stringent warning possible, was added in 2008 (see timeline, page 30), two years after Rachel was prescribed it.
One of her surgeons connected the dots to Levaquin, but it was too late for a lawsuit because by then she had missed New Jersey’s two-year statute of limitations. To add insult to her injury, “It turns out I never had an infection. Had I just kind of left it, I think I would have felt better in a few days.”
Full disclosure
Rachel’s horrific experience led her to become a consumer advocate/patient representative at FDA hearings. It’s clear she understands antibiotic issues better than most doctors or health regulators.
For starters, she says, the FDA’s MedWatch drug adverse event reporting system is voluntary, and the agency knows that less than 10 percent of doctors report adverse events.
Furthermore, health agencies are not ensuring that doctors ‘get the memo’ or using their authority to put a full-stop to dangerous prescribing practices such as the use of fluoroquinolone for uncomplicated sinusitis, Rachel adds.
Part of the reason is their funding. For example, “The FDA gets 50 percent its funding from Pharma,” she says. Since 1992 when drug authorization fees were introduced, drug companies have become the FDA’s ‘clientele,’ giving directives rather than being directed. It’s a bit like the FDA getting half its funding from tobacco companies.
Too little, too late
“The antibiotics issue really parallels the opioid crisis,” says Alan Cassels, a drug policy researcher at the University of Victoria in Canada and author of three books including Selling Sickness: How the World’s Biggest Pharmaceutical Companies Are Turning Us All Into Patients (Nation Books, 2006). “Even though there have been the black box warnings by government, most of the time, they are just too little, too late.”
“For their part, pharmaceutical companies are simply criminal recidivists which break the law, pay the fine and then break the law again,” he says. “The media are not as critical as they need to be,” and doctors are not the “gatekeepers they should be for the drugs they prescribe.”
Patients with antibiotic experiences like Rachel Brummert and Catherine Slater advise patients to be their own gatekeepers.
“I keep away from doctors as much as I possibly can,” Catherine says now. “If I have to consult them, I make it clear that they can advise, but I will make the decisions and refuse most prescribed medicines.”
“Do your homework” before you take any drug, advises Rachel. “If you don’t have all the information, you can’t give informed consent. Read the package insert. Go online. I know doctors don’t like Google, but I tell people, ‘Google it.'”
And read What Doctors Don’t Tell You.
A toxic history
When your doctor prescribes you an antibiotic, you may assume it has been rigorously tested and that you will be told of any dangerous side-effects to watch out for. Not true. Most antibiotic side-effects turn up during “post-marketing surveillance,” years after they are approved, as this chronology of the commonly prescribed class of antibiotics called fluoroquinolones reveals.
Late 1980s to 1990s:
Fluoroquinolone antibiotics (levofloxacin, ciprofloxacin and trovafloxacin) are released on the market, and by 1993 ciprofloxacin (Cipro) becomes the most frequently used antibiotic in the world.1
1992:
Temafloxacin is recalled from the market within months of its release due to numerous reports of serious adverse events including three deaths.2
July 1999:
Trovafloxacin (Trovan) use is severely restricted by the US Food and Drug Administration (FDA) after it’s shown to induce serious, sometimes fatal, liver damage.3
October 1999:
Grepafloxacin (trade name Raxar) is withdrawn due to its risk of “severe cardiovascular events” including sudden death.4
2001:
Sparfloxacin is withdrawn from US markets due to phototoxicity5 and a link to toxic epidermal necrolysis, a severe skin condition involving a purplish rash and blisters.6
2008:
The FDA attaches a black box warning to all fluoroquinolones advising of their increased risk of severe tendinitis and tendon rupture, and notes other serious adverse effects including convulsions, hallucinations, depression, serious cardiovascular events and potentially fatal diarrhea caused by the superbug Clostridium difficile. It instructs doctors to use the drugs only for bacterial infe
ctions.
Public Citizen, a consumer rights organization, asks the FDA to issue doctors a warning letter along with the black box, but the FDA refuses.7
2011:
The FDA attaches a second black box warning advising of the risk of worsening muscle weakness for individuals with the autoimmune disorder myasthenia gravis.
July 2014:
The FDA requires fluoroquinolone labels to warn of possibly irreversible nerve damage.8
August 2014:
An FDA review states that levofloxacin (Levaquin) is only advised for children who have inhaled anthrax or been exposed to plague (about 17 cases per year), yet reports 68,664 pediatric prescriptions between 2011 and 2014.9
2016:
The FDA requires drug makers to “enhance” their pamphlet warnings about the association of fluoroquinolones with potentially permanent, disabling side-effects involving tendons, muscles, joints, nerves and the central nervous system that can occur together.
Mental health side-effects include memory impairment and agitation. It states that fluoroquinolones should not be used in patients with uncomplicated infections like bronchitis unless there are no other treatment options.10
December 2017:
Janssen Pharmaceuticals, a subsidiary of Johnson & Johnson, halts manufacturing of Levaquin, but says leftovers of the drugs will be available until 2020. Generic versions of the drug fill the market.
July 2018:
The FDA strengthens its warnings in the prescribing information stating fluoroquinolones may cause low blood sugar levels that can result in serious problems, including coma.
New label changes require adding new mental health side-effects: disturbances in attention, disorientation, agitation, nervousness, memory impairment and serious delirium, even after just one dose.11
December 2018:
The FDA’s latest warning: fluoroquinolone antibiotics can increase ruptures in the aorta, the main artery of the body, which can lead to dangerous bleeding and death.12
2019:
At least 78,040 fluoroquinolone serious adverse events and 6,816 deaths have been reported to the FDA to date, including 2,840 cases this year. 13
Safer alternatives
Antibiotics for run-of-the-mill infections have been compared to using elephant guns to kill an ant. Here are some safer options to try first.
Ozone
Many municipal drinking water systems use ozone gas for purification instead of chlorine. It is 100 times more effective at destroying bacteria and other microbes than bleach without leaving behind dangerous compounds or causing antimicrobial resistance.
Research shows that ozone gas stimulates the immune system to promote healing, improves circulation and reduces pain and inflammation, and it’s increasingly being used in dentistry and medicine.
In one case report, a 56-year-old man with a rash rapidly spreading on his upper leg where he had been bitten by a tick a few days earlier received hyperbaric ozone therapy, where a portion of the blood is removed, ozonated and then replaced.
Photographs showed the rash had disappeared two days later.1
If intravenous ozone therapy is not an option, try ozonated oil topically. In one study, ozonated oil and water applied topically to Staphylococcus aureus and MRSA eradicated the bugs in minutes.2
Ozonated olive oil has also proven to be very effective for combating aggressive bacteria in gum disease and promoting wound healing.3
Which products to choose? Look for ozonated olive oil sold in a dark glass container, and check to see that the ozonated oil is whitish or clear like water, not yellow or greenish, which indicates incomplete ozonation. It should be thick or gel-like at room temperature and should have a distinct, almost antiseptic, scent.4
Vitamin C
Nobel Prize winner Linus Pauling’s claims about vitamin C to overcome infections are being validated by a growing body of scientific evidence, including a 2017 study showing that vitamin C given intravenously (1.5 grams every 6 hours) in a cocktail with thiamine and hydrocortisone reduced one hospital’s death rate from sepsis, a life-threatening blood infection, from 40.4 percent to 8.5 percent.5
A 2017 review of the literature found 148 published animal studies demonstrating the ability of vitamin C to prevent or limit infections caused by bacteria, viruses and protozoa.
Among human studies, five different clinical trials have shown that taking vitamin C can halve the number of colds in physically active people, and three have shown it to prevent pneumonia. One controlled trial has also reported benefits for tetanus patients.6
How to take it: To shorten colds, take at least 6 to 8 grams per day in divided dosages. For more serious infections, 1 gram per hour until bowel tolerance is reached.
Garlic
Used by the ancient Greeks, Romans and Egyptians, garlic has long been a weapon of choice against infection; British researchers were recently “astonished” when they reproduced a ninth-century recipe of garlic, onion and cow bile for eye infections and found that it destroys MRSA.7
The active ingredient in garlic, allicin, has been shown to powerfully combat infection-causing bacteria, fungi and viruses.8
How to take it: Swallow one clove daily to prevent infection. Remove the thin skin around a clove of garlic, crush beforehand, swallow the entire clove and chase with a drink.
To safely treat childhood ear infection: Crush a clove of garlic into one tablespoon of oil. Let stand for 30 minutes to release the active ingredient, allicin, strain, gently warm the oil in a cup set in hot water and apply inside the affected ear every hour until the worst symptoms have improved.
Honey
Used since Biblical times for wounds and as a salve to draw out infection, honey can promote wound healing. When compared against conventional methods, a honey-saturated surgical dressing was found to significantly reduce surgical scarring.9
Manuka honey, which is produced by bees that forage on the tea tree native to New Zealand and known to have particularly potent antimicrobial properties, has been shown to kill 60 different bacteria including antibiotic methicillin-resistant Staphylococcus aureus (MRSA),10 and to combat Pseudomonas aeruginosa, a bacteria that causes difficult-to-treat lung infections, especially in people with cystic fibrosis. When tested against three top antibiotics in a laboratory model of such an infection, manuka honey inhibited the bacteria where super-high concentrations of the antibiotics could not.11
How to take it: Make sure you buy manuka honey with a high Unique Manuka Factor (UMF), which measures chemical properties of the honey including its level of glyoxal, a naturally occurring antimicrobial.
Oregano
Oil from the herb oregano, which contains the potent antimicrobial compounds carvacrol and thymol, has been shown to have inhibitory effects against a host of bacteria.12
How to take it: To relieve nasal congestion and combat sinus infections, colds and allergies, add a few drops of oregano oil to a small pot of boiling water. Being careful not to get burned in the steam, place your head under a towel over the pot and breathe deeply. Don’t use if you’re allergic to other herbs in the same plant family such as lavender, sage, marjoram and basil.
References – main text
1 Scand J Gastroenterol, 2017; 52: 617-23
2 Eur
J Gastroenterol Hepatol, 2007; 19: 15-20
3 World Health Organization, WHO Report on Surveillance of Antibiotic Consumption, 2018.
4 J AOAC Int, 2018; 101: 1119-26; Orphanet J Rare Dis, 2010; 5: 39; Arch Intern Med, 1999; 159: 1185-94; Expert Opin Drug Saf, 2015; 14: 295-303
5 JAMA Intern Med, 2017; 177: 1308-15
6 US Food and Drug Administration, Joint Meeting of the Antimicrobial Drugs Advisory Committee and the Drug Safety and Risk Management Advisory Committee, November 5, 2015.
7 Nature, 2019; 568: 499-504
8 Am J Gastroenterol, 2011; 106: 2133-42
9 Pediatr Allergy Immunol, 2017; 28: 430-7
10 Nature, 2018; 555: 431-3; Sci Transl Med, 2013; 5: 192ra85
11 N Engl J Med, 2018; 379: e16
12 StatPearls, Stevens Johnson Syndrome (Toxic Epidermal Necrolysis), 2018
References – time line
1 Drugs, 1993; 45(suppl 3): 59-64
2 FDA Press Release June 5, 1992
3 JAMA, 1999; 282: 19
4 WHO Drug Information, 1999; 13(4)
5 Arch Dermatol Res, 1996; 288: 45-50
6 Indian J Dermatol Venereol Leprol, 2003; 69: 235-6
7 BMJ, 2008; 337: 135
8 FDA News Release, July 26, 2016
9 FDA Research Office of Surveillance and Epidemiology, Pediatric Postmarketing Pharmacovigilance and Drug Utilization Review, August 14, 2014
10 FDA Safety Announcement, May 12, 2016
11 FDA Safety Announcement, July 10, 2018
12 FDA Safety Communication, December 20, 2018
13 FDA Serious Adverse Events Reporting System, Public Dashboard
References – SAFER ALTERNATIVes
1 Med Gas Res, 2018; 8: 121-4
2 Mol Med Rep, 2018; 17: 2449-55
3 J Indian Soc Periodontol, 2016; 20: 32-5; Biosci Rep, 2017; 37: BSR20170658
4 J Intercult Ethnopharmacol, 2014; 3: 49-50
5 Chest, 2017; 151: 1229-38
6 Nutrients, 2017; 9: 339
7 BBC News, March 30, 2015
8 Appl Microbiol Biotechnol, 2001; 57: 282-6
9 Forsch Komplementmed 2016; 23: 12-5
10 Asian Pac J Trop Biomed, 2011; 1: 154-60
11 Front Microbiol, 2019; 10: 869
12 J Sci Food Agric, 2013; 93: 2707-14; Int J Mol Sci, 2017; 18: 1283
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