PHARMACOLOGY OF ANTIBIOTICS — WELCH 401 



The final picture in those animals which survived revealed gross and 

 microscopical thickening of the leptomeninges with or without hydro- 

 cephalus. One animal was observed to have a fully developed hydro- 

 cephalus involving all ventricles. 



The observations in patients, together with the reproduction of the 

 pathological processes in animals, indicate that tyrothricin solutions 

 should not be used for the irrigation of sinus cavities in close proxim- 

 ity to the subarachnoid spaces and emphasize again the inherent 

 toxicity of this drug. 



PENICILLIN 



Penicillin is by far the most widely employed of the antibiotics now 

 available to the general practitioner and in many of the bacterial 

 infections it remains the drug of choice. The toxicity of pencillin was 

 shown early to be extremely low and, in general, the impressions 

 gained at that time have been borne out in the extensive use of this 

 drug. The original studies showed that even with relatively crude 

 preparations there was little to indicate contraindication to its use 

 in man. Further studies substantially confirmed the fact that crude 

 amorphous penicillin had little, if any, true toxicity, although an 

 occasional sensitization occurred with this material. As early as 

 1944, at which time only amorphous material was available, it was 

 demonstrated that insofar as the calcium and sodium salts of penicillin 

 were concerned, its acute toxicity appeared to be associated with the 

 cation rather than with penicillin per se. Later studies of the sodium, 

 lithium, ammonium, strontium, calcium, magnesium, and potassium 

 salts showed conclusively that the toxicity of these penicillin salts was 

 primarily associated with the cation. These studies were carried out 

 with penicillin salts that were not pure although their potencies were 

 on the order of 1,000 units per mg. The apparent toxicity of peni- 

 cillin decreased as the purity of commercial preparations improved. 

 Therefore it is important in discussing the pharmacology of penicillin 

 to give consideration to the fact that all the reports concerning toxicity 

 made prior to the advent of crystalline penicillin G were based on 

 amorphous penicillin containing impurities, which may have been 

 responsible for certain of the toxic effects ascribed to penicillin itself. 

 It should be emphasized that the penicillin commercially available 

 today is largely crystalline penicillin G. Amorphous penicillin is no 

 longer produced. The presently manufactured penicillin approaches 

 the theoretical potency — 1,667 units of activity per mg. (60 mg. per 

 100,000 units) . 



One of the toxic effects observed with amorphous penicillin, an 

 abrupt rise in temperature following injection, was due, without 

 doubt, to pyrogenic impurities. The presence of these pyrogenic 



