Danielle Pavliv, Nydera Booker Pharm. D., MPH, and Sophia Lee, National Center for Health Research
Antibiotics treat and prevent diseases caused by bacteria, and they are among the most widely used prescription medications. It might surprise you to know that the Centers for Disease Control and Prevention (CDC) estimates that approximately half of the 100 million antibiotic prescriptions written each year in the United States are unnecessary. They are not effective treatments for the common cold, flu or other viral infections, and taking them when they are not needed can be harmful in two ways. #1: All medicines come with risks. Antibiotics also kill the good bacteria in your body that promote health-so taking them for the wrong illness means you get all the harm with none of the benefit. #2: The more an antibiotic is used, the more opportunities the bacteria have to learn to recognize and defend against this cure (antibiotic resistance). Antibiotics can save your life, but taking antibiotics when they are not truly needed increases the risk that these treatments will no longer be effective when people really do need them. So every instance of misuse ends up threatening the health of everyone.
Antibiotic resistance is a major public health issue and can result in longer hospital stays and an increase in the number of patients who die because their disease becomes more difficult to treat. There is also a significant cost to caring for these patients. It costs more than $5 billion annually to treat patients with antibiotic resistant infections.1 According to the CDC, antibiotic resistance costs our country four times that in excess health care costs, with people spending 8 million more days in the hospital than they otherwise would.2
Some antibiotics can cause serious adverse reactions that may be life-threatening (for an example, read our article on a new antibiotic). Antibiotics are the second most common cause of anaphylaxis, a severe allergic reaction with rapid onset that affects the entire body (food allergies are the most common). Liver damage is another possible serious consequence. Antibiotics can even be deadly; for example, the Z-Pak is a very popular antibiotic that can cause fatal side effects, especially for the elderly and people with heart problems. Less serious and more common reactions include nausea, vomiting, diarrhea, and skin rash.
In 2021, a Scottish study looked at over 8,000 patients who received a diagnosis of colorectal cancer between 1999 and 2011. The researchers found that antibiotic use increased the risk of being diagnosed with colon cancer at all ages. It was already known that antibiotics could alter the bacterial environment in the gut, leading to colorectal cancer in older adults. However, the study also showed that antibiotic use was associated with an increased risk of a particular type of colon cancer called proximal colon cancer in patients under 50. The study reported that two specific classes of antibiotics, quinolones (such as Cipro and Levaquin) and sulfonamides/trimethoprim (Bactrim), were associated with proximal colon cancer in the group of early onset patients. Quinolones will be discussed at length later in this article, but this study confirms the need to be more cautious when selecting antibiotics.3
There are many different classes of antibiotics, grouped by their pharmacological properties and chemical compounds. While all of the approved antibiotics should be capable of treating bacterial infections, different types are often used to treat different types of infections. This article is focused on the risks and benefits of quinolones.
Cipro, Levaquin, and other Quinolones
Quinolones are a type of antibiotic that has much more serious side effects than was known when they were first approved by the FDA. The most popular quinolones are fluoroquinolones, which include ciprofloxacin (Cipro), lomefloxacin (Maxaquin), norfloxacin (Noroxin), ofloxacin (Floxin), moxifloxacin (Avelox) and levofloxacin (Levaquin). All can be taken in pill form, and the last two can be injected or implanted. The different fluoroquinolonesvary slightly in ways that make them better or worse for some patients. For instance, not all are equally effective when taken in pill form. Some stay in the body longer than others so the patient doesn’t have to take them as often, some have a lower risk of side effects, while others have substantial risks whether taken alone or in combination with other drugs.4
Quinolones are broad spectrum antibiotics, which means they are effective against a wide range of diseases caused by bacteria. They were approved by the FDA to treat conditions including lower respiratory tract infections, skin infections and urinary tract infections. In addition, some types of fluoroquinolone can also treat inflammation of the prostate, sinusitis, and gonorrhea.
However, potentially dangerous side effects include:5,6
- Arrhythmia (heart rate rhythm is too fast, too slow or irregular)
- Tendon ruptures (more likely in those also taking corticosteroids)
- Changes in blood sugar levels (which can be dangerous for patients with diabetes who take oral medication for hypoglycemia, which is low blood sugar)
- Neuropathy (a kind of nerve damage which can cause pain and numbness, and can also affect internal organs in some cases)
- Central nervous system problems (such as insomnia, seizures, anxiety, paranoia, nervousness or agitation)
Fluoroquinolone cause more than 20,000 ER visits per year.7 A CDC study found that even the safer fluoroquinolones resulted in high rates of hospitalization due to psychiatric and neurologic adverse events. In addition to the adverse reactions bulleted above, patients have developed hallucinations and suicidal thoughts shortly after taking these antibiotic,8,9 or severe liver and kidney problems.10,11 As mentioned above, quinolones were also associated with early onset of proximal colon cancer.3
That is why fluoroquinolones should be taken only when needed and for the appropriate amount of time.Unfortunately, the improper use of fluoroquinolones is widespread, with 1 in 3 patients being given them unnecessarily. This includes patients being given the drug for longer than necessary, for conditions not caused by bacteria, or for conditions where the use of another drug was more appropriate.12 The result was longer hospital stays and more medication-related complications.
Some of the major reasons for the overuse of fluoroquinolones and other antibiotics include pressure from patients and the willingness of health care providers to prescribe antibiotics for common ailments that would clear up on their own. Advertisements and marketing also add to overuse, as does a lack of clear clinical guidance on the appropriate use of antibiotics.13,14 And although antibiotics are not effective against colds, flu and other viral infections, yet they continue to be given to patients who “need” to take a prescription medication for these conditions.15
While many antibiotics can be obtained at low cost, fluoroquinolones are more expensive, especially when used to treat common ailments. One study comparing the cost of several antibiotics for treating an uncomplicated urinary tract infection (UTI) found that fluoroquinolones were among the most expensive. It cost $30.45 to treat a UTI patient with Ciprofloxacin (100mg twice daily) for three days as compared to only $11.64 with TMP-SMX (160/800mg twice daily) for three days.16
Black Box Warnings and Patient Response
In 2008, the FDA announced that fluoroquinolones needed a black box warning because of serious tendon damage – the agency’s most urgent warning about a drug’s risks and side effects. The FDA states that risk of tendon rupture is even more likely “in people older than 60, in those taking corticosteroid drugs, and in kidney, heart, and lung transplant recipients.”17 In March 2011, the FDA added a second black box warning concerning the risk that these drugs would “exacerbate muscle weakness in persons with myasthenia gravis,” a kind of neuromuscular disorder.18
Black box warnings often reduce the number of prescriptions, so companies try to convince the FDA that the warnings are unnecessary and delay them for as long as possible. On October 30, 2012, Johnson and Johnson settled more than 800 lawsuits for failure to adequately warn patients prior to the FDA mandate of the risk of tendon ruptures associated with Levaquin, and the company faces thousands more such lawsuits.19 This highlights how even with FDA review, the risk of severe side effects from a “safe” drug may not be fully realized or made public until it has been on the market for several years.
Information about the serious health problems caused by these drugs has increased in recent years. In May 2016, the FDA encouraged physicians and other healthcare providers to avoid prescribing quinolones for uncomplicated urinary tract infections, sinus infections, and chronic obstructive pulmonary disease (COPD) unless other antibiotics had been tried and were unsuccessful.20 Research has found that FDA’s advice resulted in fewer prescriptions for quinolones for these conditions. For example, in 2015, before the announcement, quinolones were prescribed for 42% cases of urinary tract infections treated with antibiotics. By late 2018, two years after the announcement, they were prescribed for only 19% of urinary tract infections treated with antibiotics.20
On December 20 2018, the FDA released a report on the impact of fluoroquinolones on ruptures of the aorta, the main artery in the body.21 Tearing or rupture of the aorta, called aortic dissection or aneurysm, causes internal bleeding, often resulting in death. The report was based on reports that patients and physicians made to the FDA, which found an increased risk of aortic dissection/aneurysm in patients using fluoroquinolones.
A study by Lee et al revealed a doubling of the rate of aortic aneurysms in patients who took fluoroquinolones compared to patients who were not on that medication. The risk was especially high in patients over the age of 70. Another study (Pasternak et al) found a 60% increased risk in patients who took fluoroquinolones versus those who took amoxicillin. Daneman et al, looking exclusively at older patients over the age of 65, noted that patients on fluoroquinolones were twice as likely to have an aortic aneurysm within 30 days of taking the drug.
The FDA advises patients considering quinolones to speak with their doctor about any previous history of connective tissue disease illness, hypertension, atherosclerosis or genetic diseases that may put them at higher risk fromfluoroquinolones.
Antibiotics can save lives and improve health, but their safe use requires “substantial evidence of effectiveness to justify any potential harm.”22 The number of people harmed by these drugs would be reduced if several precautions were taken. First and foremost, antibiotics should not be prescribed or taken for infections caused by a virus. Even when there is a bacterial infection, antibiotics should be chosen with care to ensure that patients receive the antibiotic that is most effective for their specific condition and comes with the fewest risks. Just as penicillins are best for syphilis and macrolides for tonsillitis, quinolones are only preferred for treating certain types of bacterial infections, such as pneumonia, urinary tract infections, and some skin infections. For patients over 60 with any of these conditions, other antibiotics may be a safer option.
To reduce the spread of resistance for these antibiotics or other types, clinicians should choose a drug that is effective in the disease treatment or prevention, but does not disturb the body’s good bacteria.
Health care providers and pharmacists should explain potential side effects and any risk factors for any antibiotic, and also consider safer alternatives when possible The American College of Physicians has the following warnings for consumers:23,24
- Don’t insist on antibiotics for yourself or your children.
- Ask your doctor, “Is this antibiotic really necessary?”
- Take only with a doctor’s instructions-don’t take antibiotics left over from old prescriptions, those given to you by friends or family, or purchased abroad without a prescription.
- Prevent infections by washing hands thoroughly. Wash fruits and vegetables thoroughly. Avoid raw eggs and undercooked meats-especially ground meats.
- Keep immunizations up-to-date, especially for influenza and pneumonia if you are a senior citizen or have a chronic illness.
- Finish each antibiotic prescription-even if you feel better. If you don’t finish the prescription some resistant bacteria may stay with you and multiply, requiring a different and most likely stronger antibiotic when the infection returns weeks later.
All articles are reviewed and approved by Dr. Diana Zuckerman and other senior staff.
The National Center for Health Research is a nonprofit, nonpartisan research, education and advocacy organization that analyzes and explains the latest medical research and speaks out on policies and programs. We do not accept funding from pharmaceutical companies or medical device manufacturers. Find out how you can support us here.
When new drugs are harmful: Telavancin (VIBATIV) for skin infections
Choosing wisely: medication and treatments you probably DON’T need
Antibiotic uses and challenges — our comprehensive review published on Medscape
- Goff DA. Antimicrobial stewardship: bridging the gap between quality care and cost. Curr Opin Infect Dis. 2011;24(suppl 1):S11-20.
- Antimicrobial (Drug) Resistance; Quick facts. National Institute of Allergy and Infectious Diseases. http://www.niaid.nih.gov/topics/antimicrobialresistance/understanding/Pages/quickFacts.aspx
- Bassett M. Are antibiotics linked to early-onset colorectal cancer? MedPage Today. https://www.medpagetoday.com/meetingcoverage/additionalmeetings/93412. July 3, 2021.
- Centers for Disease Control and Prevention. Quinolones and the Clinical Laboratory. December 2010. Retrieved at: http://www.cdc.gov/HAI/settings/lab/Quinolones-Clinical-Laboratory.html.
- Roberts, JR. Adverse reactions to fluoroquinolones. Emergency Medicine News. Oct 2008;30(10):16-18.
- Powers JH, Phoenix JA, Zuckerman DM. Antibiotic uses and challenges-A comprehensive review from NRCWF. Medscape Family Medicine. June 2010. Retrieved from: http://www.medscape.com/viewarticle/723457.
- Shehab N, Patel PR, Srinivasan A, Budnitz DS. Emergency department visits for antibiotic-associated adverse events. Clin Infect Dis. Centers for Disease Control and Prevention. 2008;47(6):735-743.
- LaSalvia EA, Domek GJ, Gitlin DF, et al. Fluoroquinolone-induced suicidal ideation. Gen Hosp Psychiatry. 2010;32:108-10.
- Labay-Kamara U, Manning S, McMahon T. Fluoroquinolone-induced suicidal ideation and suicidality. Psychosomatics. 2012 Jan-Feb;53:1.
- Qian Qi, Nasr SH, Akogyeram CO, et al. Myoglobin-associated acute kidney injury in the setting of ciprofloxacin administration. Am J Kidney Dis. 2012;59(3):462-66.
- Figueira-Coelho J, Pereira O, Picado B, et al. Acute hepatitis associated with the use of levofloxacin. Clin Ther. 2010 Sep;32(10):1733-7.
- Werner NL, Hecker MT, Sethi AK, et al. Unnecessary use of fluoroquinolone antibiotics in hospitalized patients. BMC Infectious Diseases. 2011;11:187.
- Karabay O, Ozdemir D, Guclu E, et al. Attitudes and behaviors of family physicians regarding use of antibiotics. JMID. 2011;1(2):53-57.
- White AR (BSAC Working Party on the Urgent Need: Regenerating Antibacterial Drug Discovery and Development). Effective antibacterials: at what cost? The economics of antibacterial resistance and its control. 2011;66:1948-53.
- The spread of superbugs: What can be done about the rising risk of antibiotic resistance? The Economist. Mar 2011.
- Mehnert-Kay SA. Diagnosis and management of uncomplicated urinary tract infections. Am Fam Physician. 2005;72:451-6.
- U.S. Food and Drug Administration. Information for Healthcare Professionals: Fluoroquinolone Antimicrobial Drugs [ciprofloxacin (marketed as Cipro and generic ciprofloxacin), ciprofloxacin extended-release (marketed as Cipro XR and Proquin XR), gemifloxacin (marketed as Factive), levofloxacin (marketed as Levaquin), moxifloxacin (marketed as Avelox), norfloxacin (marketed as Noroxin), and ofloxacin (marketed as Floxin)]. May 2009. Retrieved at: http://www.fda.gov/drugs/drugsafety/postmarketdrugsafetyinformationforpatientsandproviders/ucm126085.htm.
- U.S. Food and Drug Administration. Risk of fluoroquinolone-associated Myasthenia Gravis Exacerbation February 2011 label changes for fluoroquinolones. March 2011. Retrieved at: http://www.fda.gov/Safety/MedWatch/SafetyInformation/ucm247115.htm.
- Fisk, MC, Hawkins, B. Johnson & Johnson settles 845 Levaquin lawsuits. Bloomberg Businessweek. Nov 2011. Retrieved from: http://www.businessweek.com/news/2012-11-01/johnson-and-johnson-reaches-settlement-in-845-levaquin-cases
- Tran PT, Antonelli PJ, Hincapie-Castillo JM, Winterstein AG. Association of US Food and Drug Administration Removal of Indications for Use of Oral Quinolones With Prescribing Trends. JAMA Internal Medicine. Published online April 19, 2021. doi:10.1001/jamainternmed.2021.1154
FDA warns about increased risk of ruptures or tears in the aorta blood vessel with fluoroquinolone antibiotics in certain patients. https://www.fda.gov/Drugs/
DrugSafety/ucm628753.htm?utm_ campaign=New%20FDA%20Drug% 20Safety%20Communication%20on% 20oral%20and%20injectable% 20fluoroquinolone&utm_medium= email&utm_source=Eloqua
- Powers JH. Risk perception and inappropriate antimicrobial use: Yes, it can hurt. Clin Infect Dis. 2009;48:1350-3.
- Flynn R, Eckel E, Zuckerman D. National Research Center for Women and Families. The facts about medication for colds and the flu. May 2011. Retrieved at: http://www.center4research.org/2010/03/the-facts-about-medication-for-colds-and-the-flu/.
- American College of Physicians. Antibiotics: Do you really need them? Retrieved at: http://www.acponline.org/patients_families/pdfs/health/antibiotics.pdf.