1 1 24 CHEMOTHERAPY OF BACTERIAL DISEASES 



sodium oleate in 0.5-1 per cent solution is destructive for pneumococci, and that 

 weaker solutions, as o.i-o.ooi per cent, lessen the virulence of pneumococci and in- 

 crease their susceptibility to the destructive action of antipneumococcus serum, boric 

 acid overcoming the inhibitory influence of the protein constituents. Mixtures of this 

 kind yielded better results than optochin or antipneumococcus serum alone. 



Since these experiments on pneumococcus meningitis have indicated that it may 

 be possible to inject enough ethylhydrocuprein into closed sacs to raise the pneumo- 

 coccidal activity of the exudates without danger of irritation of the serous membranes 

 or the absorption of toxic amounts, Sands and myself have conducted similar experi- 

 ments on acute suppurative pneumococcus pleuritis induced in guinea pigs and dogs, 

 as having a possible value in the treatment of pneumococcus pleuritis with empy- 

 ema developing during croupous pneumonia. 



The experimental lesions in guinea pigs were very severe, consisting of acute sup- 

 purative pleuritis which involved both pleurae and the external portions of the peri- 

 cardium. The intrapleural administration of ethylhydrocuprein in a dose correspond- 

 ing to about 2 cc, of a 1 : 500 dilution per kilo of weight in each cavity, a total of 0,008 

 gm. of drug, had a marked curative influence in the majority of instances unless treat- 

 ment was delayed longer than twenty-four hours. Such a delay permitted the de- 

 velopment of severe bilateral pleuritis, pericarditis, and pneumococcus bacteremia. 

 Multiple injections of i cc. of a i : 500 solution per kilo into each pleural cavity had 

 an even more pronounced effect upon less severe infections. These results indicate the 

 possibility of chemical disinfection of infected serous cavities with drugs showing a 

 marked and selective bactericidal activity for the infecting bacterium in the presence 

 of pus, as optochin or ethylhydrocuprein hydrochlorid for the pneumococcus, even 

 though sufficient amounts of the drug cannot be administered by mouth, intra- 

 muscularly, or intravenously to influence a localized inflammatory process; further- 

 more, it is highly probable that some of the drug injected into the cavity is absorbed 

 into the blood, where it exerts some restraining influence upon the multipHcation of 

 bacteria, 



"Vucin" or isocytylhydrocuprein, prepared by Morgenroth, has been found highly 

 bactericidal for staphylococci and streptococci and has been successfully employed in 

 1 : 2,000 solution for the treatment of gas-bacillus infection of wounds. Stronger solu- 

 tions, however, are necrotizing. Solutions as high as 1:12,000 in doses of i cc. per 

 20 gm. have been found curative for mice inoculated subcutaneously with virulent 

 streptococci by Morgenroth 's method, and similar results have been observed in 

 staphylococcus infections. 



CINCHONA DERIVATIVES IN THE CHEMOTHERAPY OF BACTERL\L DISEASES OF MAN 



Ethylhydrocuprein (optochin) and other cinchonics have been reported by many 

 competent clinicians as possessing some practical therapeutic value in the treatment 

 of pneumococeus bacteremia and pneumonia of human beings. It is true that early 

 expectations have not been realized and that a therapie magna sterilisans has not been 

 secured, but unquestionably it is possible by proper administration to raise the 

 pneumococcidal activity of the blood, as well as probably increasing phagocytosis, and 

 these results are doubtless worth while. 



