PENlClLLIlN S87 



pressive host of investigators has studied the clinical use of this drug. 

 The Oxford or Florey unit has been generally adopted as the 

 standard of denoting the antibacterial potency of penicillin. It has 

 been defined as "that amount of penicillin which when dissolved in 

 50 ml. of meat extract broth just inhibits completely the growth of 

 test strain of Staphylococcus aureus."^ Because the serial dilution 

 method used by Fleming was not altogether satisfactory, an agar cup 

 plate method of assay similar to that which had been used by Red- 

 dish "■" and Ruehle ^» was employed by the Oxford workers. An agar 

 plate which has been inoculated with the test organism is first pre- 

 pared. Small glass or porcelain tubes are set on the agar. The 

 sample to be tested is then placed in these cylinders and the plate is 

 incubated. The drug diffuses out into the medium and the develop- 

 ment of the test organism is inhibited, clear zones being produced 

 around the tubes. In general, there is a correlation between the 

 potency of the sample and the size of the clear zones, within certain 

 limits. The Oxford group have defined the unit of antibacterial 

 activity as that amount of penicillin which when dissolved in 1 cc. 

 of water gives the same inhibition as the original standard. They 

 found experimentally that an inhibition zone 24 mm. in diameter 

 was thus obtained. The very fact that so many modifications of the 

 original serial dilution and the agar cup methods have been proposed 

 indicates that an absolutely satisfactory method of assay has yet 

 to be devised. Until a chemical method of assay is developed, there 

 w^ill no doubt be many more modifications suggested. Foster and 

 Woodruff 1° have discussed the merits and faults of the various assay 

 methods. 



A number of organisms have been found capable of producing 

 penicillin. In general, they belong to the P. notatum-chrysogenum 

 group although organisms of the Aspergillus genus have been re- 

 ported to form antibiotic substances with properties very similar to 

 if not identical with those of penicillin. The organism used for the 

 commercial production of this chemotherapeutic agent depends on 

 the method of production. 



Four methods of producing penicillin have been proposed. The 

 earlier preparations of penicillin were produced by surface cultures. 

 P. notatuni NRRL 1249.B21 strain has been most generally used for 

 the production of the antibiotic by this method. Spores of the mold 

 are used to inoculate a layer of culture medium, usually 1.5 to 2 cm. 

 in depth. The mold can be grown in flasks or bottles which are incu- 

 bated at 22° to 25° C. A thin pellicle begins to appear some twenty- 

 four hours after inoculation; a definite white growth is present by the 



