cross contamination. This new methodology involves using Lactobacillus species and shows a clear zone of inhibition as well as allowing for a determination of minimum inhibitory concentration. Industrial production techniques Fermentation Industrial microbiology can be used to produce antibiotics via the process of fermentation, where the source microorganism is grown in large containers (100,000–150,000 liters or more) containing a liquid growth medium. Oxygen concentration, temperature, pH and nutrient are closely controlled. As antibiotics are secondary metabolites, the population size must be controlled very carefully to ensure that maximum yield is obtained before the cells die. Once the process is complete, the antibiotic must be extracted and purified to a crystalline product. This is easier to achieve if the antibiotic is soluble in organic solvent. Otherwise it must first be removed by ion exchange, adsorption or chemical precipitation. Semi-synthetic A common form of antibiotic production in modern times is semi-synthetic. Semi-synthetic production of antibiotics is a combination of natural fermentation and laboratory work to maximize the antibiotic. Maximization can occur through efficacy of the drug itself, amount of antibiotics produced, and potency of the antibiotic being produced. Depending on the drug being produced and the ultimate usage of said antibiotic determines what one is attempting to produce. An example of semi-synthetic production involves the drug ampicillin. A beta lactam antibiotic just like penicillin, ampicillin was developed by adding an addition amino group (NH2) to the R group of penicillin. This additional amino group gives ampicillin a broader spectrum of use than penicillin. Methicillin is another derivative of penicillin and was discovered in the late 1950s, the key difference between penicillin and methicillin being the addition of two methoxy groups to the phenyl group. These methoxy groups allow methicillin to be used against penicillinase producing bacteria that would otherwise be resistant to penicillin. Synthetic Not all antibiotics are produced by bacteria; some are made completely synthetically in the lab. These include the quinolone class, of which nalidixic acid is often credited as the first to be discovered. Like other antibiotics before it the discovery of nalidixic acid has been chalked up to an accident, discovered when George Lesher was attempting to synthesize chloroquine. However a recent investigation into the origin of quinolones have discovered that a description for quinolones happened in 1949 and that patents were filed concerning quinolones some 5 years before Lesher's discovery. Strains used for the production In the