Who's the Beecham nowwww? Ampicillin

Ahhhhh, antibiotics. We all use it in our lives, professionally or personally, no one really makes it without these anti (from the greek "against") biotics (also from the greek "bios" = life) that populate our heads whenever some infection takes partial control of our systems. In molecular microbiology they are just the perfect selection markers that when linked to the genes of interest allow us to verify whether the insertion happened or not. Antibiotics have been generating dual emotion overloads in the scientific and common population. Some are against the agents that to which bacteria can begin to be overexposed and accustomed. Some think we are not developing and researching these substances enough. I have my own opinion about it, but it's way too soon to disclose it here. I prefer to just bring some evidence on the way these substances are, work and degrade, and even what to expect in case of accidental ingestion.

Antibiotics can act differently on bacteria, but in general they fall within two classes: the bactericidal (killing bacteria) and the the bacteriostatic (inhibiting their reproduction).

I am not an antibiotic connoisseur, but I have been working with some agents like Streptomycin, Tetracycline, Carbenicillin, Kanamycin, Spectinomycin and so forth. All applied in the molecular microbiological contexts of Escherichia coli and Pseudomonas aeruginosa, thus, for some of these antibiotics, resistances and stock concentrations can be quite different. But that is not the purpose of this post; as the main objective is to tell you a little more than what you might already know, something like "Let's learn by telling people". So, please, follow me in this simple discovery of a few antibiotics, this week starting by Ampicillin.

Ampicillin (usually sold as Ampicillin sodium) is a beta-lactam (figure 2) antibiotic, meaning that it contains a beta-lactam nucleus in its structure. Its chemical formula is C8H10NNaO5S and has a molecular weight of 371.39 [1]. Derived from the penicillin family, this aminopenicillin (amino group attached to the penicillin structure) shares some properties with the more famous Amoxicillin (a bacteriolytic substance commonly prescribed to children). Ampicillin has specific basic and acidic catalysed hydrolysis [2] and its rate of degradation increases quite substantially with increasing initial drug concentration due to dimerisation (roughly, a reaction that produces two bonded monomers). Calorimeric studies involving Ampicillin show that at a constant values of temperature, ionic strength, pH its degradation respects a pseudo-first order kynetics [for further information access here]. The mechanism of degradation of ampicillin is pH dependent [2] and it can be slightly noticed by a change of temperature produced by the cleavage of the beta-lactam ring (maybe not sensed without the appropriate tools since the heat produced by such cleavage remains constant between 25 celsius and 48 celsius) [2].

Ampicillin is a semi-synthetic white(ish)/yellow(ish) crystalline powder effective on many bacteria from Gram-positive to Gram-negative and it works like any other penicillin - by disrupting the peptidoglycan bonds in specific penicillin binding proteins present in the cellular wall of those bacteria holding no resistant machinery to avoid the consequent cell lysis. In addition, Ampicillin inhibits the last stage of the cell wall synthesis and is likely to have also an autolysin inhibitor action [1]. 

You shall not store it at room temperature if in aqueous form> Keep it in between 2 to 8 Celsius as this is the appropriate range of temperatures to avoid thermal degradation of the powder. Some labs accept storing Ampicillin below 30 Celsius [5]. Nevertheless, keep in the fridge at 4°C after reconstitution. 

There are a few side effects when exposed to toxic levels of ampicillin, yet they are believe to be minor. Inflammation and redness of the tongue, mild diarrhea, vomiting, nausea, irritated mouth, irritated throat. Severe immunologic responses might be the case when one observes rashes, difficulties in breathing, hives, swelling of the mouth, face, lips, tongue, stomach pain, stomach cramps and discharge are just a few of the most severe possible symptoms [4].

The usual adult prescribed upper limit dose is around 4g a day [5]. An over dosage knows no common antidote!!!!!!!!, just consider discontinuing treatment or simply not playing with your luck! Seek for immediate medical advice!!!

Ampicillin sodium can worth around $65 in the USA (10g) and £39 in the UK (10ml), and as a solution it needs to respect a few quality standards from which I stress two very important ones: a) sterile-filtered and, b) cell culture tested.

Ampicillin has been used in counteracting infections since the early 1960's after the pharmaceutical company The Beecham Group plc announced its discovery back in 1963 [3].

Next week: Carbenicillin.

1st image taken from Corning, [http://cellgro.com/ampicillin-sodium-salt-2.html], last viewed on the 10th of September 2012, last updated in 2012.

3rd image taken from {1].

[1] TOKU-E, [http://www.toku-e.com/Upload/Products/PDS/20120618002031.pdf], last viewd on the 10th of September 2012, last updated on the 12th of January 2010.

[2] Olyiai, R. and Liendenbaum, S. (1991). "Stability testing of pharmaceuticals by isothermal heat conductioncalorimetry: Ampicillin in aqueous solution". International Journal of Pharmaceutics, 73, pp. 33-36.

[3] ABPI, [http://www.abpi.org.uk/industry-info/achievements/timeline/Pages/1960s.aspx], last viewd on the 10th of September 2012, last updated in 2012.

[4] Drugs.com, Ampicillin side effects, [http://www.drugs.com/sfx/ampicillin-side-effects.html], last viewed on the 10th of September 2012, last updated on the 06th of August 2012.

[5] Medical Explorer - drugs and Medications, Ampicillin, [http://www.medical-explorer.com/drugs-a/ampicillin_1.html], last viewed on the 10th of September 2012, last update unknown.