1 1 22 CHEMOTHERAPY OF BACTERIAL DISEASES 



of lobar pneumonia, and toxic effects were sometimes produced. These have generally 

 been transient and have usually disappeared when the drug was discontinued. The 

 principal ones that occur are referable to the eye and the ear. In some cases vomiting 

 has been reported; this may be due in some instances to the bitter taste of the drug, 

 which rivals quinin in that respect. 



The symptoms referable to the ear comprise ringing and roaring noises and 

 partial deafness; they are transient and disappear shortly after the drug is discon- 

 tinued. Those referable to the eyes are more serious. The pupils may be fixed and 

 dilated and may not react to light; ophthalmoscopic examination may show tortuos- 

 ity of the retinal vessels with some narrowing of the arteries. The amblyopia is usually 

 temporary, but in a few very severe cases atrophy of the optic nerves has resulted. 



There is some ground for believing that the visual disturbances which have oc- 

 curred in about 4-5 per cent of cases of pneumonia may depend to a certain extent on 

 idiosyncrasy indicated by the fact that some patients develop amblyopia after they 

 have had only 2 gm. or less of optochin (numoquin) whereas others do not acquire it 

 even after they have received as much as from 10 to 16 gm. 



CINCHONA DERIVATIVES IN THE CHEMOTHERAPY OF EXPERIMENTAL INFECTIONS 



Morgenroth and Levy originally employed mice infected with pneumococci and 

 treated them with subcutaneous injections of optochin (base) suspended in oil. With 

 this method 80-100 per cent of mice were protected against fatal infections, and the 

 specific action of ethylhydrocuprein on the pneumococcus was found to be greater 

 than that of any other compound of the series examined, namely, quinin, hydro- 

 quinin (methylhydrocuprein), isopropylhydrocuprein, isobutylhydrocuprein, and 

 isoamylhydrocuprein. 



Moore has also confirmed the curative effects of optochin base in pneumococcus 

 infections of mice. Working with 2 per cent suspensions in sterile olive oil and inject- 

 ing 0.5 cc. per 20 gm. subcutaneously immediately after infection followed by an 

 equal dose on the second day and 0.4 cc. on the third day, he observed a well-marked 

 protective action against many multiples of the minimal lethal dose of all four groups 

 of pneumococci. Cohen, Heist, and myself, however, working with the soluble ethyl- 

 hydrocuprein hydrochlorid, were not able to elicit as good results as reported by these 

 investigators. Our work was conducted with mice and rabbits infected with ten to 

 one thousand times the minimal lethal dose of types I, II, and III pneumococci by 

 intraperitoneal injection about two hours after the drugs had been administered; in 

 addition to ethylhydrocuprein we also employed quinin and urea hydrochlorid and 

 other cinchonics. Our percentage of "cures" with ethylhydrocuprein hydrochlorid 

 given intravenously within two hours after inoculation with 50 M.L.D. of culture was 

 less than 10 per cent. Doses ranging from o.oi to 0.03 gm. per kilo of body weight 

 usually prolonged life beyond that of the controls from one to four days, but ulti- 

 mately the majority of the mice and rabbits succumbed. 



Hydroquinin hydrochlorid in amounts as high as 0.04 gm. per kilo of body weight 

 given from one to four hours after infection with 50 M.L.D. of culture did not ap- 

 preciably prolong life except in a few instances when the animals lived from one to 

 three days longer than the controls. 



