Some Antibiotics Are Riskier Than Others: What You Should Know About Quinolones

By Danielle Pavliv and Nyedra Booker, PharmD, MPH
March 2013

 

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.

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

 

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 administered via injection, implant or infusion. The different fluoroquinolones have slightly different characteristics 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.[3]

Quinolones are broad spectrum antibiotics (meaning they are effective against a wide range of diseases caused by bacteria), 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.  Potentially dangerous side effects include: [4],[5]

  • 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)

In 2001, levofloxacin (Levaquin) was described as the fluoroquinolone with the lowest rate of adverse drug reactions, but that does not mean it is safe, or even as safe as other types of antibiotics.[6],[7] In fact, according to a 2008 CDC study, almost one out of every 1,000 fluoroquinolone prescriptions caused adverse events leading to an emergency room visit. This represented more than 20,000 ER visits per year.[8]

While many doctors prescribe fluoroquinolones because they are supposed to have a better safety profile than some other antibiotics, the CDC study found that even the newer fluoroquinolones that are assumed to be safer resulted in high rates of hospitalization due to psychiatric and neurologic adverse events. In addition to the adverse reactions bulleted above,  numerous case studies have reported patients developing hallucinations and suicidal thoughts shortly after taking these antibiotics,[9],[10] or severe liver and kidney problems.[11],[12]

Given the potential risks of taking fluoroquinolones, they should be taken only when needed and for the appropriate amount of time. Several studies have shown that improper use of fluoroquinolones is widespread, with 1 in 3 patients being given fluoroquinolones unnecessarily. This included 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.[13] 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, the relatively low cost, advertisements and marketing,  and a lack of clear clinical guidance on the appropriate use of antibiotics.[14], [15] Also as previously discussed, 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.[16]

While many antibiotics can be obtained at low cost, fluoroquinolones are expensive, especially when used to treat common ailments. One study comparing the cost of several antibiotics including trimethoprim-sulfamethoxazole (TMP-SMX/Bactrim), fluoroquinolones (Ciprofloxacin and Gatifloxacin), and cephalosporins (Cephalexin) 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.[17]

 

Black Box Warnings and Patient Response

 

­In 2008, the FDA announced that a black box warning – the agency’s most urgent warning about a drug’s risks and side effects — was warranted for fluoroquinolones because of the risk of damage to tendons. The FDA states that risk “is further increased in people older than 60, in those taking corticosteroid drugs, and in kidney, heart, and lung transplant recipients.”[18] 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.[19]

Black box warnings often reduce the number of prescriptions, so companies repeatedly 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.[20] 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.

Bottom Line

Antibiotics can save lives and improve health, but their safe use requires “substantial evidence of effectiveness to justify any potential harm.”[21] 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 not caused by bacteria. 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. Even 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:[22],[23]

  • 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.

References


[1] Goff DA. Antimicrobial stewardship: bridging the gap between quality care and cost. Curr Opin Infect Dis. 2011;24(suppl 1):S11-20.

[2] Antimicrobial (Drug) Resistance; Quick facts. National Institute of Allergy and Infectious Diseases. http://www.niaid.nih.gov/topics/antimicrobialresistance/understanding/Pages/quickFacts.aspx

[3] 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.

[4] Roberts, JR. Adverse reactions to fluoroquinolones. Emergency Medicine News. Oct 2008;30(10):16-18.

[5] 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.

[6] Rubinstein E. History of quinolones and their side effects. Chemotherapy. 2001;47(S2):3-8.

[7] Carbon C. Comparison of side effects of levofloxacin versus other fluoroquinolones. Chemotherapy. 2001;47(S2):9-14.

[8] 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.

[9] LaSalvia EA, Domek GJ, Gitlin DF, et al. Fluoroquinolone-induced suicidal ideation. Gen Hosp Psychiatry. 2010;32:108-10.

[10] Labay-Kamara U, Manning S, McMahon T. Fluoroquinolone-induced suicidal ideation and suicidality. Psychosomatics. 2012 Jan-Feb;53:1.

[11] 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.

[12] 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.

[13] Werner NL, Hecker MT, Sethi AK, et al. Unnecessary use of fluoroquinolone antibiotics in hospitalized patients. BMC Infectious Diseases. 2011;11:187.

[14] Karabay O, Ozdemir D, Guclu E, et al. Attitudes and behaviors of family physicians regarding use of antibiotics. JMID. 2011;1(2):53-57.

[15] 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.

[16] The spread of superbugs: What can be done about the rising risk of antibiotic resistance? The Economist. Mar 2011.

[17] Mehnert-Kay SA. Diagnosis and management of uncomplicated urinary tract infections. Am Fam Physician. 2005;72:451-6.

[18] 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.

[19] 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.

[20] 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

[21] Powers JH. Risk perception and inappropriate antimicrobial use: Yes, it can hurt. Clin Infect Dis. 2009;48:1350-3.

[22] 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/.

[23] American College of Physicians. Antibiotics: Do you really need them? Retrieved at: http://www.acponline.org/patients_families/pdfs/health/antibiotics.pdf.