Pros & Cons of Antibiotics

Pros & Cons of Antibiotics: Can antibiotics cure the coronavirus? No. What about from the regular flu? No. But antibiotics can save your life if you have an infection like strep throat, MRSA or a wound.  Antibiotics are used for STDs, whooping cough, acne and staph infections. Antibiotics are one of the most overused and inappropriately used drugs. Overprescribing of antibiotics is a serious problem worldwide as it leads to antibiotic resistance, when certain bacteria become immune to the effects of antibiotics. This can lead to infections that are very difficult for doctors to treat.

According to the CDC’s 2019 report on Antibiotic Resistance Threats in the United States, each year in the US more than 2.8 million people become infected with bacteria that are resistant to antibiotics (aka superbugs), more than 35,000 people will die as a result, and new alternatives are slow in coming. But what really troubles many medical experts is the fact that too many individuals — patients and physicians alike — aren’t taking the messages seriously.

Nearly one-third of prescribed antibiotics are not needed, according to a CDC study. The reason? Many common ailments that send people to their physician or a hospital emergency room, such as a hacking, painful cough or a upper respiratory infection, or any number of viral illnesses, won’t respond to antibiotics, which are effective on bacterial infections only. So if your doctor refuses to prescribe an antibiotic after diagnosing you with a cold or the flu, don’t blame the doctor. Instead, rest, drink fluids and avoid spreading your germs around.

“Antibiotic resistance is an epic problem,” says Belinda E. Ostrowsky, MD, field medical officer for the CDC, Division of Healthcare Quality Promotion in New York City.

Antibiotic Pros & Cons

Antibiotics are miracle drugs, for sure. When introduced in the 1940s, they dramatically reduced the numbers and severity of illness and death from bacterial infections such as pneumonia. There are more than 100 types of antibiotics — you’re likely most familiar with penicillins such as amoxicillin, ampicillin, dicloxacillin, and oxacillin. — and each has the ability to target certain types of infections. They either kill bacteria or keep them from reproducing. What antibiotics can’t do is fight viral infections (like colds, flu, upper respiratory infections), allergies, many earaches, and most sore throats (those not due to strep).

Antibiotics kill good bacteria along with the bad. They also carry the potential of setting off harmful adverse reactions (more on that below). In other words, antibiotics are serious medicine that shouldn’t be taken casually.

Yet many people “continue to cling to the notion of ‘why not take something if there’s even a chance that it will make me better?,’ when in reality there are big risks,” says Jason G. Newland, MD, medical director in charge of patient safety at Children’s Mercy Hospital in Kansas City, Missouri. “Risks that can land you in the hospital.”

Researchers say this mindset can lead to adverse reactions, such as antibiotic resistance and serious adverse events.  A study published in the journal Medical Decision Making, found that patients were more likely to expect their healthcare provider to write a prescription for an antibiotic for their ailment rather than remain sick. This influenced doctors to prescribe more antibiotics, even though they knew more about the potential side effects of the drugs. The researchers believe that patients and doctors are driven by the idea that they’re better off taking a risk with antibiotics than remaining sick, downplaying the side effects of antibiotics.

Side Effects of Antibiotics

The side effects associated with antibiotics aren’t trivial. They range from merely annoying (mild rashes, minor skin irritations, or a short bout of diarrhea) to potentially life-threatening reactions (anaphylactic shock, for example).

A host of serious reactions to antibiotics can lead to time missed from work or school; one or more trips to the doctor to treat the new symptoms and find a new way to treat the original infection; or worse, hospitalization and/or long-term debilitating complications.

These side effects include, but aren’t limited to:

• Bad rash
• Bad sore throat
• Respiratory difficulties
• Nausea and vomiting
• Diarrhea
• Stomach pain
• Swelling of joints
• Stevens-Johnson Syndrome (a rare skin disorder most associated with sulfonamides such as Bactrim)
• Retinal detachment
• Compromised kidney function, associated with fluoroquinolones such as Cipro, Levaquin (levofloxacin) and Avelox (moxifloxacin)
• Widespread pain (with symptoms similar to fibromyalgia)
• Tendinitis
• Heart palpitations
• Muscle spasms
• Compromised gut health (associated with repeated use of antibiotics prescribed for intestinal, urinary, and systemic infections).

This last side effect is of unique concern because of the important role gut bacteria play in one’s overall health. The facts aren’t entirely known, but a growing body of research links beneficial gut-dwelling bacteria to an active metabolism, improved heart health, better stress hormone levels, fewer allergies, and certain immune system responses.

“I think it’s natural for people to tend to underestimate the downside of things,” says Dr. Ostrowsky. “That includes taking antibiotics until something like a C. difficile infection (a potentially deadly infection that causes severe diarrhea) strikes you hard and quickly travels.”

“The thing to be aware of with side effects is that you don’t know if or how your body will react until it’s too late,” adds Dr. Newland. “I’m not suggesting that antibiotics aren’t necessary or aren’t important, but they need to be prescribed and taken wisely.”

Case in point: Epidemiological researchers have tied cases of C. difficile to antibiotics prescribed by dentists. The study was presented at an infectious disease conference called IDWeek 2017.

Over a 6-year period, the Minnesota Department of Health (MDH) examined 1,626 people with community-associated C. difficile. Out of that demographic, 136 people reported that they were prescribed antibiotics for dental procedures.

Researchers found that older patients were prescribed antibiotics more often for dental procedures and were more likely to receive clindamycin — the antibiotic that is linked with C. difficile infection. The results showed that 34% of those who received antibiotics for dental procedures had no mention of antibiotics in their medical charts.

Additionally, MDH also led another survey that found 36% of dentists prescribed antibiotics in situations that are generally not recommended by the American Dental Association (ADA). Dentists prescribe antibiotics for infections such as abscesses, but in some conditions prescribe antibiotics before procedures to prevent infection. The ADA no longer recommends that practice in most cases.

Researchers have also tied cases of colon cancer to antibiotic use. A 2019 study in the journal GUT showed that the greater the dose or the longer time antibiotics were taken, the higher the risk of colon cancer. Penicillin, particularly ampicillin/amoxicillin, showed an increased colon cancer risk. Tetracycline antibiotics appeared to reduce the risk of rectal cancer.

Fluoroquinolones

The Food and Drug Administration (FDA) put a black-box warning (the most serious alert) on fluoroquinolones because an agency safety review found that both oral and injectable fluoroquinolones are associated with disabling side effects involving tendons, muscles, joints, nerves and the central nervous system.

Side effects of fluoroquinolones can happen hours to weeks after the drug is taken. Common fluoroquinolones include Levaquin, Cipro, Avelox, Floxin (ofloxacin) and Factive (gemifloxacin). FDA labeling limits fluoroquinolones to patients who are unable to take other antibiotics for acute bacterial sinusitis, acute bacterial exacerbation of chronic bronchitis and uncomplicated urinary tract infections.

More than 60,000 reports have been sent to the FDA of patients detailing side effects associated with fluoroquinolone antibiotics, including more than 6,500 deaths. According to an article published in the journal Nature, side effects associated with these antibiotics are rarely reviewed or studied, and analysts don’t know why the drugs cause “rare but disabling” side effects. The piece also suggests that drug manufacturers have very little interest in researching medications that have been on the market for decades, which is partly due to the fact that there are no incentives offered for researching profitable drugs. Also, some researchers have avoided publishing studies that critically evaluate and go against drug companies because they fear that the well-funded pharmaceutical companies may retaliate. (See MedShadow’s Floxed? The Painful, Life-Lasting Effects of Some Antibiotics)

Some types of fluoroquinolones were even pulled from the market by the FDA because of “unjustifiable risks of adverse effects.” Janssen Pharmaceuticals discontinued both the oral and IV versions of Levaquin. The company claimed the reason for the discontinuation was due to the availability of other treatment options as well as their aim to develop medicines for unmet needs. Levaquin may still be available in pharmacies through 2020, however, and generic versions of levofloxacin will still be made.

Hypoglycemia (glucose deficiency in bloodstream) : Additional labeling changes for fluoroquinolones were mandated after an FDA review found instances of hypoglycemic coma in cases where patients — particularly older ones — on fluoroquinolones experienced hypoglycemia. As a result, a subsection of fluoroquinolone labeling will now have to indicate the potential risk of coma with hypoglycemia.

Mental health: Among all fluoroquinolones, a range of mental health side effects is already described in the warnings and precautions section of the drug label, though they differ by individual drug. The new label changes will make these side effects — including disturbances in attention, disorientation, agitation, nervousness, memory impairment and delirium — consistent across the entire class.

Myasthenia gravis: Previously the FDA added a boxed warning about the risk of worsening symptoms for those with myasthenia gravis (a condition characterized by weakening of muscles under voluntary control). (See MedShadow’s FDA Warnings about Fluoroquinolone Antibiotics)

Aortic aneurysm and dissection: A study in the Journal of the American College of Cardiology found that taking fluoroquinolones can increase the risk of developing an aortic aneurysm and dissection (enlargement of and tears in the aorta, the heart’s main artery), and that risk increases the longer a person takes the medication. The two conditions are normally slow to develop, but researchers noted fluoroquinolones may speed up that process. Researchers analyzed records of around 1,200 patients that were hospitalized for aortic aneurysm and dissection and compared them to 1,200 control subjects. An editorial accompanying the study said that doctors should be careful in prescribing fluoroquinolones in those that have risk factors for aortic aneurysm, such as older age, smoking and hypertension.

Children at a higher risk

Children are at high risk for the side effects of antibiotics. About 70,000 emergency room visits each year by children are the result of side effects from antibiotics. In a study in the Journal of the Pediatric Infectious Diseases Society, researchers analyzed estimates of antibiotic prescriptions as well as data from a representative sample of hospitals for ER visits due to antibiotic use by children 19 and younger. About 86% of the visits were because of an allergic reaction, such as a rash, itching or angioedema, which is severe swelling beneath the skin.

The study also showed that children 2 and younger had the highest risk of experiencing an adverse event – 41% of ER visits were in this age group. In children 9 and younger, amoxicillin was the most common antibiotic that led to an adverse event. In children between the ages of 10 and 19, the drug was Bactrim (sulfamethoxazole/trimethoprim).

Researchers noted that prior research has found that about one-third of pediatric antibiotic prescriptions are unnecessary. They added that many more children likely experience side effects from antibiotics since the study only included adverse events that resulted in a visit to the ER.

“In the pediatric community alone we have recent data showing an excess of 11 million prescriptions a year for antibiotics that are likely unnecessary,” says Dr. Newland, who is also chair for the Pediatric Committee on Antimicrobial Stewardship within the Pediatric Infectious Diseases Society.

Psychiatric disorders with children  Researchers in Denmark have discovered another reason why antibiotics should be avoided in the pediatric community unless necessary. A study published in JAMA Psychiatry suggests that children who have infections and are treated with antibiotics are at an increased risk for developing psychiatric disorders.

The researchers examined the medical records of about 1 million children born in the country between 1992 and 2012 and followed their mental history for an average of 10 years. Children who developed a severe infection that required hospitalization had an 84% higher risk of developing a mental illness before turning 18, and a 42% increased risk of filling a prescription for a psychotropic medication, according to the study results.

The use of an antibiotic to treat an infection was associated with around a 40% increased risk for a future mental disorder and a 22% increased risk for being prescribed a psychiatric medication. The mental illnesses with the highest risk following infection were schizophrenia, obsessive-compulsive disorder, personality disorders, mental retardation, autism and ADHD (attention-deficit/hyperactivity disorder).

The researchers suggested several reasons for the association between infections, antibiotics and mental illnesses. The first is that an infection may impact the brain, increasing the risk for a mental disorder. Another theory is that antibiotics can negatively impact the “good” bacteria in the gut, which can subsequently alter the brain and increase the risk for mental disorders. Also, some people have a genetically higher risk of getting more infections and mental illnesses.

Side effects on seniors

Researchers at Tulane University analyzed whether long-term antibiotic use could lead to negative effects in a healthy person. Over the course of eight years, researchers followed and examined 37,510 women, aged 60 years and older, who reported their antibiotic use and were free of heart disease and cancer at the start of the study.

The results, presented at the American Heart Association’s Epidemiology and Prevention | Lifestyle and Cardiometabolic Health Scientific Sessions 2018, indicated that women in late adulthood who took antibiotics for two months or longer were 27% more likely to die from all causes during the study period than women who did not take antibiotics. Additionally, antibiotic use for two months or longer was associated with a 58% higher risk of cardiovascular death, compared to no antibiotic use.

Although a strong association between long-term antibiotic use and the risk of death was identified, the study’s lead author, Lu Qi, MD, PhD, noted, “It isn’t yet clear whether long-term antibiotic use is the specific cause of the association.”

“We now have good evidence that people who take antibiotics for long periods during adulthood may be a high-risk group to target for risk-factor modification to prevent heart disease and death,” said Qi.

Antibiotics and pregnancy

Some research suggests that certain antibiotics may be associated with a higher risk of miscarriage in early pregnancy. Researchers at the University of Montreal looked at data on about 96,000 pregnancies that ended in miscarriage. Of that number, about 8,700 women took an antibiotic during pregnancies.

Some classes of antibiotics, such as fluoroquinolones, macrolides and tetracyclines were associated with an increased risk of miscarriage before the 20th week of pregnancy, the researcher reported in the Canadian Medical Association Journal.

The antibiotics on the list – such as Zithromax and Cipro (ciprofloxacin) — are used to treat a wide range of infections, such as urinary tract infections and respiratory infections.

“Our study found that penicillins and cephalosporins are not associated with risk of spontaneous abortion,” lead study author Anick Bérard, PhD, told ABC News. “Similarly, we found no risk with erythromycin and nitrofurantoin. These are some of the most-used drugs used to treat UTIs, so our study shows that they are real treatment options.”

Using Less Won’t Harm You

If doctors prescribe fewer antibiotics for colds, coughs and ear infections, it will not put people at risk for more serious infections, and may actually help people by minimizing the side effects often seen with the class of drugs. That’s the conclusion of a study led by researchers at King’s College London (KCL), UK. They analyzed patient records from 610 general practices in the UK from 2005 to 2014. Medical offices that prescribed fewer antibiotics for respiratory tract infections did not have higher rates of serious bacterial complications, the researchers reported. “Reducing the proportion of [respiratory tract infection] consultations with antibiotics prescribed by 10% is expected to be accompanied by some 2,000 fewer antibiotic prescriptions for each practice over 10 years,” the researchers, led by Martin Gulliford, PhD, a professor of public health at KCL, wrote. However, results showed that clinics prescribing fewer antibiotics had slightly higher rates of pneumonia and quinsy (throat inflammation that is a complication of tonsillitis), though they could both easily be treated with antibiotics once identified. But this only accounted for once case a year for every 7,000 patients. “Even a substantial reduction in antibiotic prescribing was predicted to be associated with only a small increase in numbers of cases observed, and this would be expected to reduce the risks of antibiotic resistance, the side effects of antibiotics, and the medicalization of largely self-limiting illnesses,” the researchers noted.

Doctors under pressure

Doctors are on the front line of the problem of antibiotic resistance, working with hospitals and colleagues to reinforce or even re-write prescribing guidelines. In particular, there’s a strong movement to reduce the use of antibiotics in urgent care centers and emergency rooms, where physicians are often rushed, may be uncertain of a diagnosis, or don’t feel confident that patients will follow up on their own if they’re not given an antibiotic. A study in the journal Academic Emergency Medicine notes the rising demand for urgent and emergency care services. The researchers report that people tend to go to emergency rooms or urgent care centers in part because they perceive that their condition is urgent, the facility is more convenient, or they don’t have confidence in their primary care provider.

A study in JAMA Internal Medicine found that among patients with viral respiratory illnesses, for which antibiotics don’t work, about 46% who went to urgent care centers and 25% who went to emergency rooms were given antibiotics. And according to a study in BMJ, as many as 43% of antibiotic prescriptions given to patients in doctors’ office visits could be inappropriate. The researchers used official diagnostic codes to identify whether each antibiotic prescription was accompanied by appropriate, inappropriate, or no documented indication. According to their criteria, 57%, or around 74 million, prescriptions were deemed appropriate, while 25%, or about 32 million, were considered inappropriate, and 18%, or around 24 million, lacked either an appropriate or inappropriate documented indication.

New antibiotics

There’s promising, albeit slow-moving, work among chemists to create new antibiotics. (More research funding would greatly help speed up the process, but the economics involved mean there’s less incentive for pharmaceutical companies to bump antibiotic development up on the priority list.) The FDA has developed a program to help push new antibiotics through the approval process on a fast track. Under this program, new antibiotics designed specifically to fight infections resistant to existing antibiotics would receive a qualified infectious disease product (QIDP) designation — skipping tests usually required until after the drugs are already being used.

One example is the November 2019 approval of Fetroja (cefiderocol), which is indicated for complicated urinary tract infections (cUTIs), including kidney infections, in patients who have limited or no alternative treatment options. Fetroja, which is administered by injection, was developed under the FDA’s QIDP designation and is meant to treat only antimicrobial-resistant infections. In a study of 448 patients with cUTIs, infections disappeared in about 73% of those treated with Fetroja seven days after completing treatment compared to about 55% of those treated with a different antibiotic. Common adverse reactions in those injected with Fetroja included diarrhea, nausea, vomiting, elevated liver tests, rash and others. Labeling includes a warning about higher all-cause mortality in critically ill patients with multi-drug resistant infections.

The FDA also announced the approval of Xenleta (lefamulin) in 2019. Xenleta was also given QIDP designation and is indicated for community-acquired bacterial pneumonia (CABP). Xenleta showed success in two clinical trials with a total of 1,289 patients, working as well as another antibiotic used to treat CABP

Taken intravenously or orally, common side effects of Xenleta include changes in heart rhythm, diarrhea, nausea, vomiting and liver enzyme elevation. Animal studies showed fetal harm with Xenleta, so it should not be taken by pregnant women.

Also in 2019, the FDA approved Pretomanid Tablets in combination with bedaquiline and linezolid for the treatment of a specific type of highly treatment-resistant tuberculosis (TB) of the lungs, which is a serious public health threat. Pretomanid was approved under an FDA program called Limited Population Pathway for Antibacterial and Antifungal Drugs (LPAD). These drugs are intended to treat only certain people with serious or life-threatening infections and no available alternative treatments. Pretomanid was only the second drug approved under this program, which was created in 2016. The first, Arikayce (amikacin liposome inhalation suspension), was approved in 2018 for the treatment of lung disease caused by a group of bacteria, Mycobacterium avium complex (MAC).

Common side effects of Pretomanid in combination with bedaquiline and linezolid included damage to the nerves, anemia, nausea, vomiting, headache, increased liver enzymes, indigestion, rash, increased pancreatic enzymes, visual impairment, low blood sugar and diarrhea. Common side effects of Arikayce include dysphonia (difficulty speaking), cough, hearing damage, upper airway irritation, musculoskeletal pain, fatigue, diarrhea and nausea.

Some critics of the fast track plan worry that drug companies might have little incentive to broadly test such an antibiotic once it’s been approved for use in a small group. Unless safeguards are put in place, it might eventually be used in millions of people without full knowledge of side effects and long-term effects.

Antibiotics in food-producing animals

Efforts are also being made to reduce the use of antibiotics in food-producing animals. In December 2019 the FDA reported that sales and distribution of antimicrobials for use in animals decreased by 21% since 2009, the first year of reporting, and by 38% since 2015, the year of the highest sales and distribution of the drugs for animal use. Looking at 2018 data, the FDA noted that this overall trend indicates that ongoing efforts to support antimicrobial stewardship are having an impact.

Your Role in Combating Antibiotic Resistance

Clearly this is a jigsaw puzzle that requires a group effort to solve. Patients — including you — have a part to play, and evidence is mounting that many people do understand the issue and want to reverse it. “I’m optimistic and enthused that the public is taking notice of antibiotic resistance,” says Dr. Ostrowsky. “It gives me hope.”

Echoing that optimism is Dr. Newland. While top-level changes among hospitals, physicians, researchers and pharmaceutical companies are necessary, there’s a lot consumers can do to help reverse the trend, he says.

Take the following points as your new “Do I need antibiotics?” gospel:

1. Remember: Sniffle, sneeze, no antibiotics, please. If you have a viral illness, such as the common cold or the flu, accept that there isn’t a drug that will cure it.
2. Be mindful of how you discuss your symptoms with your doctor. Physician surveys find that doctors are more likely to prescribe antibiotics when patients use diagnostic language (“I think my son has an ear infection,” “I think I have strep throat”) compared to when they describe their symptoms (“My son’s been grabbing his ears and seems miserable,” “It really hurts when I swallow”). Even if you’re not expecting or hinting around for an antibiotic prescription, your busy doctor may misread your intent and give you one anyway — all in the name of patient satisfaction.
3. Be aware that doctors are more likely to prescribe an antibiotic if they believe you’re expecting it, even if your doctor doesn’t believe you have a bacterial infection. A study conducted among 400 doctors in the United Kingdom presented different situations where physicians had to decide if they would prescribe antibiotics. Physicians were more likely to prescribe one if patients had high expectations of receiving it.
4. Ask about alternatives. If your doctor says “Let’s take a wait and see approach,” ask about alternative remedies to try while waiting (nasal lavage? Humidifier? Acupuncture and be open to trying them.
5. Don’t go on a hunt for a willing accomplice. If your doctor sends you home with a recipe for chicken soup instead of a Z-pack, yes, you’ll likely find it fairly easy to find another doctor willing to write that script. But resist that urge for a quick fix — see tip number one.
6. Ask questions. If you are handed an antibiotic prescription, don’t leave without having a discussion about: what criteria your symptoms meet to warrant the antibiotic; the possible and common side effects; what you should do if you experience a reaction. Be sure you completely understand the doctor’s dosing instructions.

“We need everyone on board with these efforts,” says Dr. Newland. “Without families realizing the importance of the situation we won’t solve the problem.”