A brief history of antibiotics- or what do bread mold, arsenic, and soil all have in common?

Throughout history populations used plants, soils and foods to treat infections. Many of our modern-day antibiotics originated from these. Only recently- the past 100 years or so has the active compounds been isolated and purified for commercial use, saving millions of lives globally. We know antibiotics work, but how do they do their job? 

 In this 4-part series we will explore:

Part 1

• A brief history of antibiotics
• How antibiotics work- what mechanisms are at play when we take them

Part 2

• The role of biofilms in bacteria and why these present a challenge to our modern-day arsenal of antibiotics
• Antibiotic resistance challenges

Part 3

• When antibiotics are needed and when they aren’t appropriate
• Distinguish between an allergic reaction to an antibiotic and the symptoms the infection is treating

Part 4

• A review of each of the antibiotics found in the Jase Case and their use.

A brief history of antibiotics

• As far back as 350 A.D., tetracycline, a widely used antibiotic were found in bone fragments in ancient Sudanese Nubia. It is believed that stored contaminated grains back then helped cultivate a strain of tetracycline from Streptomycetes. By the late 40s tetracycline was purified and marketed commercially. This antibiotic covers a wide variety of infections, from acne to certain types of pneumonia, and some infections spread by mice and ticks.
• In ancient Egypt, China, Serbia, Greece and Rome moldy bread was used topically to treat infections. This was documented by John Parkison in his book “Theatrum Botanicum” which was published in 1640.
• Heavy metals, such as arsenic, bismuth and mercury were used to treat syphilis and gonorrhea with some success.  Salvarsan, an arsenic based chemical was discovered in 1909 by Paul Ehrlich. who is considered the father of microbial therapy. 
• In 1928 Alexander Fleming discovered mold growing on a petri dish that had staphylococcus bacteria in it. The mold prohibited the growth of the staph. He described the mold as a type of self-defense chemical that killed bacteria. He named it penicillin. It wasn’t until 1940 that penicillin was first used- to treat streptococcal meningitis. 
• Early 1930s- sulfa based drugs were discovered and produced by the Massengill Company in pill and tablet form. However, the company decided to mass produce an elixir without animal testing made from diethylene glycol (known today as antifreeze) which resulted in what was called the Sulfanilamide Disaster of 1937. More than 100 people died after ingesting this poison. This led to the Food Drug and Cosmetic Act in 1938 and the Drugs and Cosmetics Act of India, where controls are now in place on the manufacture and sale of drugs. 
• In the mid-1950s synthetic antibiotics were introduced (such as quinolones)

Before we dive into how antibiotics work it must be stated that they do not work on viruses such as colds, flu, covid, viral pneumonia, RSV, measles, etc. Sometimes there is confusion when an antibiotic is given when the patient has a virus. The virus can lower the bodys immune defenses, in turn making it susceptible to opportunistic bacteria. At that point an antibiotic may be indicated. 

• Inhibition of Cell Wall Synthesis 

Many antibiotics work by attacking the cell wall of bacteria. Specifically, the drugs prevent the bacteria from synthesizing a molecule in the cell wall called peptidoglycan, which provides the wall with the strength it needs to survive in the human body,

Examples are penicillin, Ceftin,vancomycin

• Inhibition of Protein Synthesis (Translation) 

Protein synthesis is a multistep process where DNA is first transcribed into a molecule of single-stranded messenger RNA (mRNA). Then, ribosomes translate it with the help of transfer RNA (tRNA) into long strings of amino acids, which become proteins. Protein synthesis inhibitors prevent proteins from being made by acting as inhibitors of translation or transcription. By blocking either of these processes, many types of antibiotics kill or impair the growth of bacteria by preventing them from making proteins.

Examples: tetracycline, erythromycin, streptomycin, gentamycin

• Alteration of Cell Membranes

Antimicrobial drugs that can target the microbial cell membrane to alter its functionality. Membrane lysis, or rupture, is a cell death pathway in bacteria frequently caused by cell wall-targeting antibiotics.

Examples are polymyxin and gramicidin

• Inhibition of Nucleic Acid Synthesis

• Antibiotics that interfere with the development of DNA or break DNA strands through enzyme inhibitors 

Examples: rifamycins and fluoroquinolones, metronidazole

• Antimetabolite Function

Antimetabolites are medications that interfere with the synthesis of DNA. Some antimetabolites are used in chemotherapy to kill cancer cells, while others are used as antibiotics since they inhibit bacterial folate synthesis. 

Examples: levofloxacin, norfloxacin, and ciprofloxacin

Dementia is a general term for loss of memory, language, problem-solving and other thinking abilities that are severe enough to interfere with daily life. Alzheimer’s is the most common type of dementia. It takes a toll on families and especially caregivers. Holidays and get togethers can be challenging for both families and the patient.

Some symptoms of early onset of dementia are:

• Confusion
• Loss of coordination-tripping, unable to hold items
• Memory loss especially short term
• Inability to reason complex situations
• Emotional lability- anger, sadness, depression.

As dementia progresses symptoms become more pronounced, and leads to physical inability to take care of self independently

Risk factors for dementia

• Genetics
• Age- older adults are more at risk for a dementia diagnosis
• Alcohol abuse
• Smoking
• Social isolation

Types of dementia

Alzheimer’s dementia

• Twice as many women as men are diagnosed with Alzheimer’s dementia
• Most are over 65 years.

Alzheimer’s disease leads to nerve cell death and tissue loss throughout the brain. Over time, the brain shrinks dramatically, affecting nearly all its functions.

Symptoms are mild to start and progress over time. Early symptoms are forgetfulness- of names or items such as keys are, unable to recall family or friends names along with forgetting special dates or appointments

As disease progresses changes in mood, depth perception and inability to organize thoughts and cognition are apparent. In later stages of Alzheimer’s the person experiences hallucinations, delusions and is physically incapable of performing basic hygiene.

Frontotemporal

Frontotemporal dementia (FTD), also called Picks disease is one of the less common types of dementia. It covers a range of different conditions that can affect personality, behavior, and language. FTD is mostly diagnosed in people under 65. Average onset is between 40 and 60 years, however it can occur as early as 20 years old.

Dementia with Lewy bodies

Dementia with Lewy bodies (DLB) is caused by Lewy body disease. In this disease, tiny

clumps of proteins – known as Lewy bodies – appear in the nerve cells of the brain, and progresses to decline in reasoning, independent function. and cognition. It can be hard to diagnose because it presents similar to many psychiatric symptoms

Vascular Dementia

 This type of dementia- which is sometimes called “Post Stroke Dementia” is different from Alzheimer’s or Lewy Body Dementia. Vascular Dementia is brain damage caused by bleeding or harm in the brain-such as a stroke. Symptoms that identify Vascular Dementia are observed immediately following a stroke and can include:

• Changes in personality,
• Depending on the area of the brain that has been affected- thinking short attention span
• Difficulty reasoning organizing and analyzing thoughts

Correct diagnosis of dementia can be challenging

Many medical conditions, physical and emotional factors, along with medications can mimic dementia.

Medical conditions that can present as dementia like symptoms:

• Liver and kidney disease– accumulation of toxic metabolic waste products in the blood can cause confusion and inability to form cohesive thoughts.
• Infections– notably urinary tract infections can cause confusion and personality changes.This is more common in older population, symptoms of urinary tract infection sometimes present with different symptoms than younger population. Other infections should also be ruled out, such as syphilis or Lyme disease.
• Cancer-especially brain cancer- by tumor pressing on the brain- or an immune response in which antibodies against the brain are formed, producing a “paraneoplastic syndrome”.
• Endocrine dysregulation– such as thyroid gland (hypo or hyperthyroid) or diabetes- both of these conditions can alter mood, ability to coordinate and concentrate.
• Head trauma– concussion
• Depression– which can alter and slow thought processes and cause inability to make decisions along with irritability and mood changes.

Physical conditions that can present as dementia like symptoms

• Poor vision– resulting in tripping, falling and bumping into furniture, walls, stairs, etc
• Hearing loss– A Lancet Commission report on hearing loss showed a link between hearing loss and cognitive decline, leading to a diagnosis of dementia.
• Lack of sleep– inability to concentrate or pay attention can mimic dementia, however research points to altered sleep patterns , even one nights sleep disruption has been shown to increase the beta amyloid plaque – the protein that causes dementia in the brain.

Medications that can mimic dementia

Some medications can take a long time before symptoms set in, so if you notice any cognitive changes even without a change in medication- either over the counter or prescription review with your care provider your concerns.

• Anticholinergic medications-such as tolterodine or oxybutynin, often used to treat urinary incontinence, Benadryl used for allergies and for sleep,
• Tricyclic antidepressants such as amitriptyline for example
• Antipsychotics such as Seroquil
• Benzodiazepines such as Valium, Xanax, and Librium
• Sleep aids such as Sonata and Ambien
• Corticosteroids such as Prednisone
• Narcotic pain relievers- such as morphine
• Anti-Parkinson drugs such as trihexyphenidyl (Artrane)

It is important to make sure all other causes of confusion, memory loss, poor coordination, mood changes and other dementia mimicking signs have been considered before a diagnosis of dementia is made. Many medical conditions, physical conditions and drugs mimic the symptoms of dementia, take the time to review them and discuss with your care provider.

If a definite diagnosis of dementia has been made there are many resources available. One is the Alzheimers.org online support group and help with finding local resources to help with caring for your loved one.

What is a pulse oximeter and how does it work?

Pulse oximeters come as either a small unit with a built-in finger/toe clip, or as a small handheld device that has a wire probe with adhesive pads that can be applied to your finger, toe or earlobe.

“The pulse oximeter uses a cold light source that shines a light through the fingertip, making the tip appear to be red. By analyzing the light from the light source that passes through the finger, the device is able to determine the percentage of oxygen in the red blood cell.” Excerpt from the American Lung Association.

There are two categories of pulse oximeters: prescription use and over the counter (OTC).

According to the FDA “Prescription oximeters are reviewed by the FDA, receive 510(k) clearance, and are available only with a prescription. The FDA requires that these pulse oximeters undergo clinical testing to confirm their accuracy. They are most often used in hospitals and doctors’ offices, although they may sometimes be prescribed for home use.

Over-the-counter (OTC) oximeters are sold directly to consumers in stores or online and include smart phone apps developed for the purpose of estimating oxygen saturation. Use of OTC oximeters has increased as a result of the COVID-19 pandemic. These products are sold as either general wellness or sporting/aviation products that are not intended for medical purposes, so they do not undergo FDA review. OTC oximeters are not cleared by the FDA and should not be used for medical purposes.”

Limitations of OTC pulse oximeters

• A study done in November 2021 comparing white, black and Hispanic patients revealed the limitations of over the counter (OTC) pulse oximeters. Skin pigmentation plays a role in how accurate the pulse oximeters are. These devices work by absorbing light in hemoglobin, where oxygen is carried. However, darker pigmented individuals repeatedly had false high oxygen levels (3 times more than white individuals) because the light source from the oximeter can’t tell the difference between the hemoglobin and skin pigmentation. The darker the skin, the less accurate the reading. This prompted the FDA to review and issue a warning to the public on the use of these OTC devices.
• A program launched March 2020 by Penn University called “Covid Watch” to remotely monitor patients with COVID-19 who were well enough to stay home to recover found that questioning the patients on symptoms, such as shortness of breath or use of pulse oximeters did not change outcomes of patients’ recovery from Covid 19.
• Smokers read artificially high levels of oxygen -Instead of carrying oxygen on the red blood cells, which the pulse oximeter reads, carbon monoxide- from smoking, cooking over a grill or other forms of smoke- may be attached to the red blood cell receptors. The pulse oximeter cannot tell the difference between oxygen and carbon monoxide. This can produce a false high reading.
• Other factors can affect accuracy of OTC pulse oximeter such as poor circulation, nail polish on the finger being tested and even skin thickness.

The FDA advises the following:

• Do not rely only on a pulse oximeter to assess your health condition or oxygen level.
• If monitoring oxygen levels at home, pay attention to other signs or symptoms of low oxygen levels, such as:
• Bluish coloring in the face, lips, or nails;
• Shortness of breath, difficulty breathing, or a cough that gets worse;
• Restlessness and discomfort.
• Chest pain or tightness; and
• Fast or racing pulse rate.
• Be aware that some patients with low oxygen levels may not show any or all of these symptoms. Only a health care provider can diagnose a medical condition such as hypoxia (low oxygen levels).

Sometimes we rely too heavily on technology to assess and make healthcare decisions. This may be one of those cases. Use these OTC devices only under the supervision and care of your primary care provider. As stated above, physical assessment can tell just as much if not more than the popular OTC pulse oximeters. If you need to use one of these devices, ask for a prescription level device and receive proper instruction in its use.