Penicillin: How Does Penicillin Work?

medicalnewstoday.com

Penicillin: How Does PenicillinWork?

By Tim Newman8-10 minutes

Penicillins are a group of antibiotics used to treat a largerange of bacterial infections. They are derivedfrom Penicillium fungi and can be taken orally or viainjection.

Penicillin has saved millions of lives since its initial discovery. In2010, more than 7.3 billion standard units of penicillin (pill,capsule, or ampoule) were consumed, worldwide.

The penicillins were the first antibacterial drugs used by doctors,and they attack a wide range of bacteria. Penicillin's discoveryand consequent manufacture have changed the face ofmedicine.

Fast facts on penicillinHere are some key points about penicillin. More detail andsupporting information is in the main article.

Penicillin was the first antibiotic to be used medically

There are a number of penicillin strains used for differentmedical applications

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Alexander Fleming is credited with penicillin's discovery

Penicillin works by interfering with bacteria cell walls

Less than 1 percent of people are dangerously allergic topenicillin

Penicillin: A short history

The discovery of a mold growing in an uncovered Petri dish ledto the use of penicillin to treat bacterial infections.The discovery of penicillin's antibiotic powers is attributed toAlexander Fleming. The story goes that he returned to hislaboratory one day in September 1928 to find a Petri dishcontaining Staphylococcus bacteria with its lid removed.

The dish had become contaminated by blue-green mold. Henoted that there was a clear ring surrounding the mold wherethe bacteria had been inhibited from growing.


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This discovery of the mold - Penicillium notatum - and hisrecognition of its special powers set the wheels in motion tocreate one of the most used drugs in medical history.

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In March 1942, Anne Miller became the first civilian to be treatedsuccessfully with penicillin having almost died from a hugeinfection following a miscarriage.

Although Fleming often gets the accolade for having inventedthe first antibiotic, there was a lot of work to do before penicillincould become as commonly used and useful as it is today.

The bulk of the work was eventually carried out by scientistswho had a much better-stocked laboratory and a deeperunderstanding of chemistry than Fleming. Dr. Howard Florey, Dr.Norman Heatley, and Dr. Ernst Chain carried out the first in-depth and focused studies.

Interestingly, and with impressive foresight, Fleming's NobelPrize acceptance speech warned that the overuse of penicillinmight, one day, lead to bacterial resistance.


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How penicillin works

Penicillin works by indirectly bursting bacterial cell walls. It doesthis by acting directly on peptidoglycans, an important part ofbacteria's structure.

The peptidoglycan in bacteria's cell walls increases theirstrength and keeps external fluids and particles from enteringthem.

Peptidoglycans form a mesh-like structure around the bacteria'splasma membrane.

When a bacterium multiplies, small holes open up in their cellwalls as the cells divide. These holes are then backfilled withnewly produced peptidoglycans, and the wall is reconstructed.That is unless penicillin is in the vicinity.

Penicillins inhibit the protein struts that link the peptidoglycanstogether in the wall. This inhibition prevents the bacterium fromclosing the hole in its wall.

Because of the difference in pressure between the inside of thebacterium and the surrounding fluid, water rushes into the holeand the bacterium bursts.

How do bacteria become resistant to penicillin?

Contrary to popular opinion, it is not the patient who developsresistance to penicillin but the bacteria itself.

Bacteria have been around for billions of years. During this time,they have suffered extreme environments and, as such, have a


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great deal of experience in adapting. Additionally, theyregenerate very rapidly, making any genetic changes across apopulation relatively swift.

There are three common ways in which bacteria can develop animmunity to penicillin:

Penicillinase - sometimes bacteria produce penicillinases (e.g.beta-lactamase), enzymes that degrade penicillin. This ability isthen transmitted throughout the bacterial group via a plasmid (asmall ring of DNA) in a process called conjugation - the bacterialequivalent of sexual reproduction, where new geneticinformation is shared between individuals.

Altered bacterial structure - some bacteria subtly change theformat of their peptidoglycan wall or the penicillin-bindingproteins so that the penicillin can no longer bind to it.

Penicillin removal - other bacteria develop systems to exportpenicillin. Bacteria have efflux pumps that are used to transportsubstances out of the cell. Some of these pumps can berepurposed to dispose of penicillin.

Penicillin side effects

Below are some of the side effects that have been noted duringpenicillin usage:

Common side effects


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Headaches are a common side effect of penicillin use.Vaginal itching and discharge - due to either a yeast infection orbacterial vaginosis

Sore mouth and tongue, sometimes with white patches

Diarrhea

Headache

Less common side effects

Shortness of breath or irregular breathing

Joint pain

Sudden lightheadedness and fainting

Puffiness and redness of the face

Rashes and hives

Scaly, red skin


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Rare side effects

Anxiety, fear, or confusion

Sense of impending death

Anxiety and hallucinations

Yellowing of the eyes and skin

Sore throat

Unusual bleeding

Diarrhea and reduced urination

Convulsions

Abdominal cramps, spasms, tenderness, or pain

Nausea and vomiting

Potential problems with penicillin use

Although penicillins are widely used, as with any drug, there canbe some issues or contraindications that occur:

Breast-feeding - breast-feeding mothers may pass smallamounts of penicillin to their babies. This can result in allergicreactions, diarrhea, fungal infections, and skin rash.

Interactions - some drugs can interact with penicillin. It isimportant to check with a doctor before taking multiplemedications.

Bleeding problems - some penicillins (carbenicillin, piperacillin,and ticarcillin) can make pre-existing bleeding problems worse.


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Oral contraceptives - penicillins can impede the effectivenessof oral contraceptives, raising the chances of pregnancy.

Cystic fibrosis - patients with cystic fibrosis are more prone togetting fever and skin rash when taking piperacillin.

Kidney disease - patients with kidney disease have anincreased risk of side effects.

Methotrexate - methotrexate interferes with cell growth and isused to treat a number of conditions including leukemia andsome autoimmune problems. Penicillin prevents the body fromdisposing of the drug, potentially leading to seriouscomplications.

Phenylketonuria - some stronger, chewable amoxicillin tabletshave high levels of aspartame that the body converts tophenylalanine. This is dangerous for anyone withphenylketonuria.

Gastrointestinal problems - patients with a history of stomachulcers or other intestinal diseases might be more likely todevelop colitis when taking penicillin.

Penicillin allergy

Some people exhibit allergies to penicillin. Allergic reactionsnormally include hives, wheezing, and swelling, particularly ofthe face. Around 10 percent of people report an allergy topenicillin but the true figure is closer to 1 percent, and only 0.03percent exhibit life-threatening allergic effects.

Alcohol and penicillin


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Although alcohol does not interact with penicillin, it may alterhow effective it is. For this reason, it is not advised that peopledrink alcohol with penicillin.

Alcohol and penicillin also share side effects in some people -dizziness and nausea, for instance - so in combination, the sideeffects could be worsened.

It is also worth noting that certain antibiotics do have seriousreactions with alcohol, for instance, metronidazole andtinidazole.

Penicillin has saved countless lives throughout its impressivemedical career. Modern clinicians, however, worry about theonward march of antibiotic resistance. Only time will tell how theantibiotics of the future will jump this worrying hurdle.

With medical advances moving as swiftly as they currently are,anything could be around the corner. In the words of Fleming:"one sometimes finds what one is not looking for."


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Penicillin: How Does Penicillin Work?