Pill Pushing©

The Best of Pill Pushing - Cipro - The most dangerous antibiotic on the planet? - (6/26/2017)

By Dr. Ron Gasbarro


The drug in question – Cipro (ciprofloxacin). 
 

The culture at the time – The world’s conscience will never forget: On the morning of September 11, 2001, Al-Qaeda-affiliated hijackers flew two Boeing 767 jets into New York’s World Trade Center, beginning with the North Tower at 8:46 AM then the South Tower at 9:03 AM, in a coordinated act of terrorism. After burning for 56 minutes, the South Tower collapsed at 9:59 AM. 29 minutes later, the North Tower collapsed. The attacks on the World Trade Center, as well as those on the Pentagon and the plane that went down near Shanksville, Pennsylvania, resulted in 2,977 deaths, including 343 firefighters and 72 police and other law enforcement officers [Congress, 2002]. People were terrified. Would other terrorists implode our country and render us powerless? As it turns out, Bacillus anthracis, the bacterium that causes the disease anthrax, was the next scare tactic shortly after the 9/11 attacks. 


Concentrated anthrax spores were used for bioterrorism in the 2001 Anthrax Attacks in the United States, delivered by mailing postal letters containing the spores [Cole, 2009]. The letters were sent to several news media offices and two Democratic senators: Tom Daschle of South Dakota and Patrick Leahy of Vermont. As a result, 22 were infected and five died [Pimental, 2004]. In addition to the anthrax vaccine, which was mostly used for those in the military, there was one oral drug that was approved by the FDA for protection following exposure to the airborne bug – ciprofloxacin. 


Ciprofloxacin is a broad-spectrum fluoroquinolone (quinolone) antibiotic used for bacterial infections that came into clinical use around 1990 [Goosens, 2007]. As bacteria were becoming resistant to the penicillins, the fluoroquinolones quickly became an important drug class. The novel drug family, which also includes Levaquin™ (levofloxacin) and Avelox™ (moxifloxacin), was so well-liked by clinicians that its use between 1990 and 1993 doubled [Livermore, 2002]. Their spectrum of activity includes most strains of bacterial pathogens responsible for respiratory, urinary tract, gastrointestinal, and abdominal infections. Ciprofloxacin and other fluoroquinolones are valued for their broad spectrum of activity, excellent tissue penetration, and for their availability in both oral and intravenous formulations. 


The good, the bad, and/or the ugly – Other drug classes were eventually approved for the prevention of anthrax:  the cyclines (e.g., doxycycline) and the penicillins (e.g., amoxicillin). The fact that ciprofloxacin, at the time, was the only approved antibiotic for anthrax prevention, added a new word to the medical lexicon: stockpiling. Both the government and individual patients can stockpile antibiotics. The American government stockpiles antibiotics to care for its citizens, and to be ready to respond to an actual bioterrorist event. Conversely, individuals can hoard antibiotics “just in case” of a bioterrorist attack. Compared to the last quarter of 2000, prescriptions for ciprofloxacin rose 42% [Shaffer, 2003]. A survey of prescribers in Wisconsin and Minnesota revealed that 1 out of every 3 patients asked for ciprofloxacin after the anthrax scare was publicized [Belongia, 2005]. 


Disadvantages to stockpiling a broad-spectrum antibiotic like ciprofloxacin are worth noting. The hoarder will store the drug without specific instructions. Could he tell you what are the unique symptoms of anthrax and which ones could be the symptoms of some other disease? Without precise directions, the average Joe, is likely to panic and take the drug for a common illness, cold, or cough, thinking it may be anthrax when it is not which is not anthrax. Thus, stockpiling ciprofloxacin could lead to widespread misuse of this important antibiotic prior to any bioterrorist event. This can create the perfect storm for the emergence of bacterial resistance to the drug in dangerous bacteria such as B. anthracis, which cause pneumonia, urinary tract infections, peritonitis, septicemias, sexually transmitted diseases, and so on, which would normally be treated using ciprofloxacin.


The impact of drug on culture – Even though ciprofloxacin has been on the market for a quarter century, dangerous side effects are continuously emerging.


It can wreck your legs: Tendonitis and tendon rupture 

A tendon is the fibrous tissue that attaches muscle to bone in the human body. Ciprofloxacin, as with all the fluoroquinolones, is associated with an increased risk of tendinitis and tendon rupture, regardless of age [Ciprofloxacin 2014]. In fact, there is a black box warning on the package insert alerting the patient to watch for this adverse event. (A black box warning is the sternest warning by the FDA that a medication can carry and still remain on the market in the United States.) This risk of tendon damage is heightened in older patients usually over 60 years of age, in patients taking corticosteroid drugs (e.g., prednisone, methylprednisolone), and in patients with kidney, heart or lung transplants. This side effect most frequently involves the Achilles tendon, and rupture of that tendon may require surgical repair. Tendinitis and tendon rupture in the rotator cuff (the shoulder), the hand, the biceps, the thumb, and other tendon sites have also been reported. Factors, in addition to age and corticosteroid use, that may independently increase the risk of tendon rupture include strenuous physical activity, renal failure, and previous tendon disorders such as rheumatoid arthritis. Tendinitis and tendon rupture have also occurred in patients taking fluoroquinolones who do not have the above risk factors. Inflammation and tendon rupture can occur, sometimes bilaterally, even within the first 48 hours, during or after completion of therapy; cases occurring up to several months after completion of therapy have been reported. If your Achilles tendon ruptures, you might feel a pop or snap, followed by an immediate sharp pain in the back of your ankle and lower leg that is likely to affect your ability to walk properly. Ciprofloxacin should be discontinued if you experience pain, swelling, inflammation or rupture of a tendon. You should rest at the first sign of tendinitis or tendon rupture, and to contact your healthcare provider regarding changing to an antibiotic that is not within the fluoroquinolone class. 


It can blow out your nervous system: Peripheral neuropathy

Fluoroquinolones, like ciprofloxacin, are quinolones with fluoride molecules attached. The fluoride penetrates your blood-brain barrier. This ability to penetrate sensitive tissues is what makes fluoride such a potent neurotoxin, able to get into your brain and damage the nerves in your central nervous system. Ciprofloxacin can cause sudden, serious, and potentially permanent nerve damage called peripheral neuropathy. Peripheral neuropathy is damage to the nerves that send information to and from the brain and spinal cord and the rest of the body. Damage interrupts this connection, and the symptoms depend on which nerves are affected. In general, the symptoms are in the arms and legs and include numbness, tingling, burning, or shooting pain. The package insert for ciprofloxacin states that peripheral neuropathy has been listed as a “rare” side effect [Ciprofloxacin, 2014]. However, there have been reports of long-lasting nerve damage and disability in patients taking this type of medication. One study showed that nervous system symptoms occurred in 91% of patients taking fluoroquinolones which included pain, tingling and numbness, dizziness, malaise, weakness, headaches, anxiety and panic, loss of memory, psychosis [Cohen, 2001].


Another, more recent study demonstrated that peripheral neuropathy and another nervous system disorder Guillain-Barré syndrome are associated with ciprofloxacin use. States the author of that article, “This study re-emphasizes the link between fluoroquinolones and peripheral neuropathy and shows the potential association with more severe forms of nerve damage, for example, Guillain-Barré syndrome. Unless the benefit of fluoroquinolone therapy (e.g., overwhelming infection or development of bacterial resistance) outweighs peripheral neuropathy risk, treatment with alternative antibacterial agents is recommended” [Ali, 2014] 


Indeed the latest package insert quietly hints that “damage to the nerves in arms, hands, legs, or feet can happen in people who take fluoroquinolones, including ciprofloxacin. Talk with your healthcare provider right away if you get any of the following symptoms of peripheral neuropathy in your arms, hands, legs, or feet: pain, burning, tingling, numbness, weakness. Ciprofloxacin may need to be stopped to prevent permanent nerve damage” [Ciprofloxacin package insert, 2014].


 

Where the drug is today

Despite its dangerous and insidious side effects, ciprofloxacin remains a frequently prescribed drug for all types of infections. According to the journal Drug Topics, over 20 million outpatient prescriptions were written for ciprofloxacin in 2010, making it the 35th most commonly prescribed drug, and the 5th most commonly prescribed antibacterial, in the US. Again, unless your infection is life-threatening or antimicrobial resistance to other antibiotic classes makes using ciprofloxacin and the other quinolones clinically necessary, request a non-quinolone antibiotic for your condition. 

 

Ron Gasbarro, PharmD is a registered pharmacist, medical writer, and principal at Rx-Press.com. Write him with any ideas or comments at ron@rx-press.com 


References


Ali AK. Peripheral neuropathy and Guillain-Barré syndrome risks associated with exposure to systemic fluoroquinolones: a pharmacovigilance analysis. Ann Epidemiol. 2014;24:279-85.


Belongia EA, Kieke B, Lynfield R, Davis JP, Besser RE. Demand for prophylaxis after bioterrorism-related anthrax cases, 2001. Emerg Infect Dis. 2005;11:42-8.


Cole LA. The Anthrax Letters: A Bioterrorism Expert Investigates the Attacks that Shocked America. New York: Skyhorse Publishing; 2009.


Congress. Congressional Record, Vol. 148, Pt. 7, 23 May 2002 – 12 June 2002; Government Printing Office; p. 9909.


Goossens H, Ferech M, Coenen S, Stephens P; European Surveillance of Antimicrobial Consumption Project Group. Comparison of outpatient systemic antibacterial use in 2004 in the United States and 27 European countries. Clin Infect Dis. 2007;44:1091-5. 


Livermore DM, James D, Reacher M, et al. Trends in fluoroquinolone (ciprofloxacin) resistance in Enterobacteriaceae from bacteremias, England and Wales, 1990–1999. Emerg Infect Dis. [serial on the Internet]. 2002 May. Available at http://wwwnc.cdc.gov/eid/article/8/5/01-0204  


Petri WA Jr. The quinolones.  Sulfonamides, trimethoprim-sulfamethoxazole, quinolones, and agents for urinary tract infections. In: Brunton LL, Chabner BA, Knollman BC, eds. Goodman & Gilman’s The Pharmacological Basis of Therapeutics. 12th ed. New York: McGraw-Hill; 2011:1463-76. 


Pimental RA, Christensen KA, Krantz BA, Collier RJ. Anthrax toxin complexes: heptameric protective antigen can bind lethal factor and edema factor simultaneously. Biochem Biophys Res Commun. 2004;322:258-62.


Shaffer D, Armstrong G, Higgins K, et al. Increased US prescription trends associated with the CDC Bacillus anthracis antimicrobial postexposure prophylaxis campaign. Pharmacoepidemiol Drug Saf. 2003;12:177–8.

 


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