And Penicillins

 Though antimicrobials have been around forever, we have only known about them since the late 1920’s.  A fungal contaminant on a bacterial culture inhibited the organism from growing. The contaminant was Penicillium notatum. This occurred in Dr. Alexander Flemings lab.  It was several years before this diffusible bacteriolytic substance could be sufficiently produced and used.

 Though penicillin got us through, WWII it was clear that it was not effective against all microbes.  Soil microbes such as streptomycin have been used to produce many more antibiotics. A culture of this organism smells like dirt. The best example is the smell under your house. This branched bacteria is between bacteria and fungus.  Organisms need to protect their ‘personal space’ and they do so by producing antimicrobials.

 Genes that help an organism become resistant to a particular antibiotic may be found on their chromosome or on plasmids.  Some whole groups of organisms are inherently resistant because of a chromosomal gene. It is so prevalent that the resistance pattern can be used to help identify the organism.  Resistance is many times acquired. Genes, especially on plasmids pass from organism to organism easily or are passed via viruses.  Promiscuity is rampant.

 All penems have the structure above. The square is called the beta lactam ring.  Penicillin is one of many in this beta lactam group and is produced by a fungus. Penicillin is generally active against gram positive organisms but is good against many more. Examples are syphilis and GC.

 Penicillium chrysogeum is the organism which produces penicillin today.  Given orally though not all is able to withstand the acid in the stomach.  Given IV also  Penicillins inhibit the peptidoglycan cross-linking step in the biosynthesis of the bacterial cell wall. The result of this cross-link inhibition is an unstable bacterial cell wall which can more easily break and compromise the bacterial cell.  Penicillin V  Procaine benzylpenicillin – IM (the procaine is to dull the pain of the shot)  Benzathine benzylpenicillin- IM

 lecguide/unit1/prostruct/penres.html lecguide/unit1/prostruct/penres.html  Go to this site to watch how drugs with beta lactam rings keep transpeptidases from crosslinking parts of the cell wall

Ampicillin is effective against gram positives but also gram negatives. It was introduced in the early 1960s and is still used today. The difference is the amino group seen above. That addition helps it penetrate the cells wall of gram negatives. Amoxicillin is an aminopenicillin like ampicillin and is adsorbed well, better than most penicillin. This is the most commonly prescribed drug for children. All of you have had this drug. You may know the drug Augmentin. Augmentin = Amoxicillin + Clavulanic Acid These are usually pink and taste good.

 Many organisms produce an enzyme called beta- lactamase. This enzyme cleaves the beta-lactam ring inactivating the drug.  New drugs resistant to the enzyme such as methicillin were produced.  Methicillin is not used today because it has been replaced with more stable drugs but the terminology remains. Nafcillin, oxacillin, (flucloxacillin and dicloxacillin) are used.  If an organism such as Staphylococcus aureus is resistant to this group of drugs, it is termed ‘methicillin resistant’. This is not a good thing because it means that there are only a few remaining antibiotics that may be used to treat the patient.

 Just another example to show that penicillins are not just for gram positives, this drug is used to treat Pseudomonas.  You may have heard the term ‘swimmers ear’. This is a general term but can mean an ear infection with a water bug called Pseudomonas aeruginosa. It grows out with a green pigment on media and even produces it at the site of infection.  This has to be given IV or IM and like Augmentin is given with a beta-lactamase inhibitor. (Clavulanic acid and tazobactam make the drug they are given with more resistant to the enzyme beta-lactamase)