Do Cipro and Levaquin Cause Abdominal Aortic Aneurysms?

Melina Kibbe, MD, of the University of North Carolina Medical Center at Chapel Hill published an article in JAMA Surgery reviewing any possible relationship between taking fluoroquinolones antibiotics such as Cipro or Levaquin and the subsequent development of an abdominal aortic aneurysm.  An aneurysm is a weakening in the wall of a blood vessel that balloons out like the defect on a damaged tire or basketball and has the potential to rupture causing exsanguination and sudden death. Dr Kibbe is also the editor of JAMA Surgery.

The study looked at health insurance company data on antibiotics and aneurysm diagnosis and repair.  They found that 7.5 aneurysms formed per 10,000 fluoroquinolone prescriptions filled at 90 days. This was significantly higher than the 4.6. per 10,000 aneurysms formed after patients took non-fluroquinolone antibiotics.  Patients filling fluroquinolone prescriptions were more likely to undergo repair of aneurysms than those who took other types.

The study used data from IBM MarketScan health insurance claims from 2005 to 2017 in adults aged 18-64.  The study included data on 27,827,254 individuals. The data did not include smoking or hypertensive history or family history of vascular disease. The authors were hoping the FDA would require a warning or caution to high-risk individuals for developing an aneurysm.

We already see an increase in ruptured tendons in patients taking fluroquinolones – especially women who have taken corticosteroids. They are also associated with C difficile colitis, nerve damage, emotional health issues and low blood sugar events. 

Despite these known draw backs to these medications, patients continually demand to have Cipro or Levaquin on hand in case they develop a urine infection or upper respiratory infection or are travelling and concerned about traveler’s diarrhea. 

More research is needed to determine the exact risk of prescribing these medications. Should we be doing scans on patients with hypertension and or smoking history who frequently use these drugs to screen for an abdominal aortic aneurysm?  This is a question that will be addressed by a study soon.  While the research is in process, we need to make sure that our prescribing of these antibiotics is the safest choice for our patients.

Who Is Addressing the Availability, Safety & Efficacy of our Medications?

I watched all three presidential debates this summer with health care being a time-consuming topic for all. Universal health care and Medicare-for-All, with or without an option for private insurance, were debated and discussed at length.

At the same time NBC Nightly News presented a story documenting that all our antibiotics come from production in China. With globalization policies, which promote moving production to lower cost overseas factories, there is no longer any production of antibiotics in the USA. A former member of the Joint Chief of Staffs, citing the current trade conflicts and China’s aggressive military stance in the Pacific, considers this a security issue. I have heard not one question or comment on this topic in the debates?

This week, once again, the blood pressure medicines losartan and valsartan were recalled because they contained potential carcinogens. These generics were produced in India, Asia and Israel. These same drugs have been recalled multiple times in the last few years for similar problems.

Due to reduction in funding for FDA inspections, many of these foreign plants have not been inspected for years. We can add recalls of generics to drug shortages. We suffered a shortage of intravenous fluids for hydration because the primary production site in Puerto Rico was destroyed in a hurricane. We had shortages of morphine and its derivatives for treatment of orthopedic trauma and post-surgical pain. They substituted foreign-produced short acting fentanyl. I saw pediatric ER physicians unable to administer the most effective treatments for sickle cell crisis in children because it required the use of a narcotic drip to offset the dramatic pain the treatments induce as they stop the crisis.

Then there are the psychiatric patients on antidepressant generics who are paying hundreds of dollars per month for products that wear off in 16 hours rather than 24 as the brand product did. Their symptoms creep back in allowing them to tell time based on the reduced efficacy of these products. By law, generics are required to provide 80% of the “bioavailability” of the brand product but what does that mean and who is testing?

This all began when the Reagan Administration closed the FDA research lab. Prior to that, all new products were sent to that lab for approval prior to being released in America. On their watch, a pharmaceutical product never had to be recalled. Big Pharma complained they took too long as did some consumer groups. This resulted in the defunding and closing of the lab. Products are now outsourced to private reference labs and their reports are sent to the FDA for review. The frequent drug recalls contrast to the success of promoting safety when the FDA did it themselves.

Isn’t it time for the health care debate, especially the presidential debates, to discuss the safety, efficacy, supply and cost of pharmaceutical products? I am all for bringing production home to the USA, restoring the FDA funding for the reopening of their lab as an impartial test site and putting the cost of repeatedly testing the generics for efficacy even after approval and release on the backs of Big Pharma. Let’s see these topics introduced to the health care debate too.

Antibiotic Use – Independent of Physician Prescribing

A recent article in the Annals of Internal Medicine looked at individuals who took antibiotics without them being prescribed by physicians at a visit.  The authors looked at 31 published studies between January 2000 and March 2019.  The medications came from family and friends, online distribution sites, drugs prescribed for their animals by their veterinary doctors and those stored after a previous indicated use.   When asked about it, and the reasons why these patients took these medications, the main factors cited were lack of health insurance or lack of healthcare access, cost of physician visits or medications, long waiting times in clinics, embarrassment for needing antibiotics, lack of transportation and/or easy availability of antibiotics  from other sources.

We are currently going through an antibiotic resistance crisis in the world.  Most of the fault lays with agricultural industry feeding livestock tons of antibiotics to fatten them up. Patterns of resistance develop on the farms and are passed species to species.

To remedy this, the US agriculture industry, especially in chicken production, has cut back drastically on this process.  At the same time, we are requesting physicians to work with infectious disease doctors in stewardship programs to reduce their use of ineffective antibiotics and to prescribe with precision when these medications are needed.  It works. Studies are beginning to show the benefits of these programs.

Despite this, the pressure from patients to be given something when they pay for, and invest in, a medical evaluation for an infection is overwhelming. In the setting of telemedicine, as well as walk-in and urgent care centers, reviews and patient satisfaction survey results are tied to whether the patient was given an antibiotic whether it was indicated or not.

As bacteria become resistant to common and inexpensive antibiotics, pharmaceutical manufacturers are not being incentivized to produce newer more efficacious medications.  At the same time, older useful antibiotics which do not generate much of a profit are not even being ordered and stored by chain pharmacies that lose money each time the older generics are prescribed.

To begin solving this problem, an improvement of our health literacy is required. Education in schools and in public health announcements, both in print and social media, need to realistically address the issue. This education will not replace the need for access to health care and health, but it is a beginning to make individuals understand how, when and why these “miraculous” medications can and should be used.

Antibiotic Associated Colitis Increases Risk

At least a half dozen times per week patient’s call with symptoms of a viral upper respiratory tract infection or present to the office for a visit with symptoms and signs of a cold.  These illnesses are caused by small viral particles which do not respond to antibiotic treatment.   Your body’s defense system attacks these viral particles and over a period of hours to days defeats them.   Despite years of ongoing public health announcements and handouts by doctors and nurses and attempts at patient education you find yourself negotiating with strong willed patients who want a “Z Pack” or some other antibiotic which they do not need.  “I know my body,” they argue.  “My northern or previous physician knew to always give me an antibiotic, why won’t you?”

The answer is quite simple. They do not work to shorten the course, intensity or duration of your illness. They do in fact put you at risk of developing complications of antibiotic use. When your infection requires the use of antibiotics to restore health, it is worth taking these risks. When you do not need the medication it definitely is not. This was confirmed by an article and research presented by E Erik Dubberke, MD of Washington University School of Medicine in Saint Louis, Missouri commenting on Medicare Data about the death rate associated with antibiotic related colitis infections due to Clostridia Difficile.  Bacteria normally reside in our large intestine and promote health and digestion.  When we prescribe an antibiotic it kills off the healthy and beneficial bacteria as well as the infection related bacteria. This destruction of healthy bacteria creates an environment conducive to “opportunistic “bacteria normally suppressed by the normal flora to invade and take over your gut. The resulting fever, cramping, diarrhea with blood occurs as the intestine become inflamed with colitis. One of the common opportunistic pathogens is Clostridia Difficile.

Dr. Dubberke looked at Medicare data and compared 175,000 patients older than 65 years of age and diagnosed with Clostridia difficile infection and compared them to 1.45 million control patients. He found that those with clostridia difficile infection had a 44% increased risk of death. When comparing admissions to nursing homes for treatment there was an 89% increased risk due to antibiotic related colitis care.

Antibiotics are wonderful when appropriate. They will always carry a risk of a side effect, adverse reaction or complication which is a risk worth taking in the correct setting.  It is clearly not worth the risk when your doctor tells you that it will not work.

CDC and ACP: Stop Prescribing Antibiotics for Common Respiratory Infections

The Affordable Health Care Act has created patient satisfaction surveys which can affect a physician’s reimbursement for services rendered plus their actual employment by large insurers and health care systems. This has created a fear of not giving patients something or something they want at visits for colds, sore throats and other viral illnesses. Aaron M Harris, MD, MPH, an internist and epidemiologist with the CDC noted that antibiotics are prescribed at 100 million ambulatory visits annually and 41% of these prescriptions are for respiratory conditions. The unnecessary use of antibiotics has resulted in an increasing number of bacteria developing resistance to common antibiotics and to a surge in Emergency Department visits for adverse effects of these medications plus the development of antibiotic related colitis. To address the issue of overuse of antibiotics, Dr Harris and associates conducted a literature review of evidence based data on the use of antibiotics and its effects and presented guidelines for antibiotic use endorsed by the American College of Physicians and the Center for Disease Control.

  1. Physicians should not prescribe antibiotics for patients with uncomplicated bronchitis unless they suspect pneumonia are present”. Acute bronchitis is among the e most common adult outpatient diagnoses, with about 100 million ambulatory care visits in the US per year, more than 70% of which result in a prescription for antibiotics.” The authors suggested using cough suppressants, expectorants, first generation antihistamines, and decongestants for symptom relief.
  2. Patients who have a sore throat (pharyngitis) should only receive an antibiotic if they have confirmed group A streptococcal pharyngitis. Harris group estimates that antibiotics for adult sore throats are needed less than 2% of the time but are prescribed at most outpatient visits for pharyngitis. Physicians say it is quicker and easier to write a prescription than it is to explain to the patient why they do not need an antibiotic.
  3. Sinusitis and the common cold result in overprescribing and unnecessary use of antibiotics often. Over four million adults are diagnosed with sinusitis annually and more than 80% of their ambulatory visits result in the prescribing of an antibiotic unnecessarily. “ Treatment with antibiotics should be reserved for patients with acute rhinosinusitis who have persistent symptoms for more than ten days, nasal discharge or facial pain that lasts more than 3 consecutive days and signs of high fever with onset of severe symptoms. They also suggest patients who had a simple sinusitis or cold that lasted five days and suddenly gets worse (double sickening) qualified for an antibiotic

Last year two patients in the practice who were treated with antibiotics prescribed elsewhere for situations outside the current guidelines developed severe antibiotic related colitis. They presented with fever, severe abdominal pain and persistent watery bloody diarrhea. Usual treatment with oral vancomycin and cholestyramine did not cure the illness. One patient lost thirty pounds, the other sixty pounds. Fecal transplants were required to quell the disease. At the same time community based urine infections now require a change in antibiotic selection because so many of the organisms are now resistant to the less toxic, less expensive , less complicated antibiotics that traditionally worked.

“My doctor always gives me an antibiotic and I know my body and what it needs,” can no longer be the criteria for antibiotic use.

Viagra, Cialis and Levitra Use and Malignant Melanoma

Risk v1Jiali Han, Ph.D of the Indiana University School of Public Health in Indianapolis reported in JAMA that use of Viagra or sildenafil was associated with an 84% greater risk of malignant melanoma. Their preliminary data obtained from the Health Professionals Follow-up Study (HPFS) looked at 51,529 men aged 40 – 75 years old and all health professionals. Beginning in 1986 these individuals filled out a detailed health questionnaire every other year. The researchers reached their conclusions after reviewing the 2,000 HPFS survey and excluding all participants with a history of melanoma, squamous cell cancer or basal cell skin cancer prior to calendar year 2000. They were left with 25,848 men who had a mean baseline age of 64.8 years. 5.3 % of these men (1370) reported use of sildenafil (Viagra). From 2000 until 2010 142 melanomas were reported in that group.

The authors theorize that Viagra and the other drugs promote tumor growth by inadvertently inhibiting our immune system’s ability to suppress tumor growth messages at the genetic and molecular level. They emphasize that this is a preliminary study that does not prove cause and effect but does generate enough concern to warrant the creation of a study to answer the question” Our data provide epidemiological evidence on possible skin adverse effects of PDE5A inhibitors and support continued investigation of this relationship.” There was no mention of frequency of use or dosage and development of melanoma.

The authors were clear that if the relationship does in fact hold true, it extends to all the drugs in this class. Considering the billions of dollars in pharmaceutical profit involved it is hard to imagine that the question will not be addressed in a well-planned and funded study.

Is that Z Pack for the Cough Safe? Do Antibiotics Trigger Arrhythmias?

Azithromycin“Hello Dr Reznick, this is JP, I have a runny nose, a cough productive of yellowish green phlegm, a scratchy throat and I ache all over. My northern doctor always gives me a Z Pack or levaquin or Cipro when I get this. I know my body well and I need an antibiotic. Saul and I are scheduled to go see the children and grandchildren next week and I want to knock this out of my system. Can you just call in a Z-Pack? I don’t have time to come in for a visit.”

This is a common phone call at my internal medicine practice. Despite the Center for Disease Control and the American Academy of Infectious Disease Physicians running an education al campaign on the correct use of antibiotics, patients still want what they want , when they want it. The Annals of Family Medicine , March/April issue contained a study by G. Rao, M.D., PhD of the University of South Carolina in Columbia which examined whether a Z Pack (azithromycin) or a fluroquinolone (levaquin) can cause arrhythmias and an increased risk of death. Their study was a result of a 2012 study in the New England Journal of Medicine that proved that macrolide antibiotics were associated with a higher cardiovascular death risk and rate than penicillin type antibiotics such as amoxicillin. To examine this issue closely, Rao and associates examined data from U.S. veterans who received outpatient treatment with amoxicillin (979,380 patients), azithromycin (Z Pack 594,792 patients) and levofloxacin (levaquin 201,798 patients). These were patients in the VA health system between 1999 and April 2012. Their average age was 56.5 years.

The patients were prescribed the antibiotics for upper respiratory illnesses (11 %), chronic obstructive pulmonary disease (14 %) and ear- nose and throat infections (29.3 %). The azithromycin was administered as a Z Pack and the risk of an arrhythmia or cardiovascular death was increased for the 5 days the patient took the medication. For every million doses of azithromycin administered there were 228 deaths at five days and 422 at 10 days. For levaquin there were 384 deaths at five days and 714 deaths at 10 days per million prescriptions administered. Ampicillin showed far lower numbers with 154 deaths at 5 days and 324 deaths at 10 days per million prescriptions.

The overall risk of arrhythmia and cardiovascular death was quite low with all the medications but clearly levaquin carried a higher risk than azithromycin or amoxicillin. The risk of arrhythmia with levaquin was about the same with azithromycin.

This study points out another danger of taking antibiotics inappropriately or indiscriminately. We usually point out the dangers of antibiotic resistance and antibiotic related colitis when explaining to a patient why we do not want to prescribe an antibiotic when none is warranted. We can now add arrhythmias and sudden cardiac death to the list. This doesn’t mean we shouldn’t take an antibiotic when appropriate. It does mean we may want to avoid certain antibiotics in patients who have cardiovascular risk factors.

Computerized Prescribing and Pain Medications

As part of the government initiative to modernize health information recording and exchange , doctors and health care providers are encouraged (with financial incentives) to prescribe medications using the computer.  This “e-RX” system allows you to send prescriptions to the patients’ designated pharmacy right from your computer screen with a few clicks and turns of your computer mouse controls. The only medications you are not permitted to prescribe are narcotics, controlled substances and pain medications with narcotic contents.

At the same time this initiative is occurring, there is a massive crackdown in the State of Florida on prescribing medications for pain. Sloppy legislation in Tallahassee by the State Legislature led to the opening and growth of “pill mills.”   Drug addicts and suppliers from all over the country routinely travelled to Florida to obtain massive quantities of prescription medications from these fraudulent facilities staffed by criminal physicians. The medications ended up on the streets causing numerous drug and alcohol related deaths around the country.

The “sloppy” Florida State Legislature then attempted to rectify the problem by passing new rules and regulations that closed the “pill mills” with the help of the police and drug enforcement authorities but has frightened the legitimate physician population into not being willing to prescribe for legitimate chronic pain. Their actions included updating physicians’ online profile with the state licensing agency to declare whether you write narcotic scripts for chronic pain or not.  If you reply “yes” you are apparently placed on a list of “chronic pain” prescribing doctors that the public can access as well as the criminal elements looking for doctors to write scripts for cash.

At the same time legislation now requires doctors to take specific courses to prescribe some of the newer pain delivery products necessitating the physician to leave their practice to train on the use of the new medications. The result is that legitimate neurologists and anesthesiologists are shying away from seeing chronic pain patients less than 65 years of age even if they have been referred and have legitimate needs for pain medications.

This brings me back to computerized prescription ordering. If you are trying to track narcotic prescriptions, why prevent the doctors from using the computer to prescribe controlled substances?   What is easier to track and trace, a computerized order or a hand written prescription?   It would seem that computerized record keeping through electronic order entry would be the preferred method of tracking narcotic prescriptions.

Antibiotic Use in Sinusitis

In the Journal of the American Medical Association researchers reported that treatment with antibiotics did not improve the speed of recovery or perceived symptoms in patients who took antibiotics.   One hundred sixty-six (166) adults were either given a course of amoxicillin or a placebo three times a day for acute rhino sinusitis. There was no difference in symptomatology at day three or day 10 between the two groups.

If a physician documented severe nasal obstruction the use of antibiotics did produce some perceived improvement in symptoms. There were no differences in the groups for any secondary outcomes, including days missed from work or school, additional health care consultation or recurrence of symptoms .   All the patients were allowed to take medications other than antibiotics for symptom relief during the study.  The conclusion is that antibiotics are not necessary for the treatment of acute rhino sinusitis.

Pradaxa: More Concerns. More Myocardial Infarctions?

Pradaxa is part of a new group of anticoagulants (thrombin X inhibitors) that eventually will allow anticoagulation by the pill route without requiring patients to alter their food and medication intake and avoid foods and medications that interfere with the anticoagulant as patients must do with Warfarin. Pradaxa additionally eliminates the need to take blood tests (INR/ PT) to monitor the dosage as one has to do with Warfarin (Coumadin).

There is a large commercial advertising campaign underway on TV and print media to encourage patients with atrial fibrillation to ask their doctors to switch them from Coumadin to Pradaxa (Dabigatrin).  The campaign bases its claims on the RE-LY trial of 18,000 patients at 80 medical centers throughout the world who took the 150 mg dosage and had significantly fewer strokes than patients taking Warfarin.  The original study was criticized because many of the patients in the Warfarin (Coumadin) group were not on enough Warfarin or at a therapeutic PT/INR to prevent embolic strokes so the comparison with Pradaxa may not be valid. Another criticism involved the fact that Pradaxa can cause major bleeding and there is no antidote to stop the bleeding. Patients on Pradaxa who are bleeding are advised to undergo hemodialysis to remove the drug from their system because there are no medications or treatments available to stop Pradaxa related bleeding.

One wonders how the Food and Drug Administration approved this product for general use under these circumstances without conducting further testing?  The issue becomes even more confusing with the addition of data presented by Ken Uchino, MD, and Adrian Hernandez MD, PhD of the Cleveland Clinic in the online version of the Archives of Internal Medicine. They claim that by reviewing the RE-LY data there is a 38% relative increase in the risk of a myocardial infarction (MI) or heart attack in the Pradaxa group. In an accompanying editorial in the same journal, clinicians at the Hadassah- Hebrew University Medical Center in Jerusalem wrote, “The robust finding that Dabigatran is associated with increased rates of MI (heart attack) is alarming and emphasizes the need for continued critical appraisal of new drugs after phase III trials.”

In my practice I generally will not switch to a new or controversial medication until it has been on the US market for at least one year. I make exceptions for orphan drugs, products to treat incurable diseases with no other choices available. The 12 months gives the medical and scientific community a chance to see how the medication performs and what unexpected adverse effects may be associated with it.

Thrombin X inhibitors are the wave of the future. With no way to stop the bleeding, and data on their safety and efficacy still accumulating, they are just not ready for prime time yet.