P-Aminobenzenesulfonamide and Antipneumococcai Serum Therapy in Type I Pneumococcal Infections of Rats

Abstract

Although Hörlein claimed that Prontosil was effective against Type III pneumococcal infections, experimental proof for this assertion was lacking until Rosenthal and Cooper, Gross, and Mellon independently investigated this problem. They demonstrated that P-aminobenzenesulfonamide gave mice a certain degree of protection against lethal doses of the particular strains of Type III pneumococcus employed. Buttle, Parish, Mc-Leod, and Stephenson, however, were unable to demonstrate any significant protection in mice infected with Types I and II pneumo-cocci, whereas Rosenthal obtained protection against all 3 fixed types. The lack of parallelism between pneumococcal septicemia in mice and pneumonia in man led to the choice of the experimental pneumococcal pneumonia in the rat, as a closer approximation to human pneumonia. The encouraging results obtained by treating such experimental Type III pneumonia with p-aminobenzenesulfonamide, have been duplicated in the treatment of human Type III pneumo-coccal pneumonia as reported by Heintzelman, Hadley and Mellon. The relative therapeutic efficacy of p-aminobenzenesulfonamide and of potent specific antipneumococcal serum was investigated in rats infected intrabronchially with the Type I (Neufeld) strain. The inoculum, 0.1 cc. of which was injected, consisted of an 18-hour broth culture diluted 1000 times with broth, and sufficient mucin (Armour) added to give a viscous solution. Fifty-six rats, infected in this manner, were divided into 4 groups of 14 each: Group A—Untreated controls. Group B—Given 250 units of Type I antipneumococcal serum intraabdominally 6 hours after infection, followed by 2 similar daily doses. Group C—Given 125 mg. of p-aminobenzenesulfonamide by mouth 6 hours after infection, followed by 10 daily similar doses. Group D—Treated 6 hours after infection by a combination of the treatments used in Groups B and C. Animals surviving to the 15th day were killed with ether. All animals of each group were necropsied and smears from the blood (femoral vein), peritoneum, and pleura, were stained by Gram's method. Sections were made from all lobes of the lungs of each rat. The effect of the various types of treatment on the survival-time and rate is shown graphically in Fig. 1. The gross and microscopic anatomic changes in the lungs, as well as the bacteriologic findings, are tabulated in Table I. A summary of the findings is given in Table II. Contrary to the results reported by Gunn and Nungester and by us,, a lobar type of pneumonia developed in only a few rats. Curiously enough, the most extensive and fully developed lobar type was seen in the non-survivors of the treated groups. Inflammatory changes were found in the lungs of every animal. Grossly, the changes were often minimal and not recognized. Bilateral empyema was frequently the outstanding postmortem finding. The most constant change was the interstitial pneumonia, more severe in the survivors than in the rats which died early. These interstitial changes represented, no doubt, the residues of subsiding pneumonias. The reduction in the mortality-rate from 93% in the control group to 21% in the groups treated with serum or the drug, and to 14% in the group treated with both, clearly indicates that p-aminoben-zenesulfonamide may have a definite place in the treatment of human Type I pneumococcal pneumonia in conjunction with specific anti-serum; and particularly where antiserum is not available for economic or other reasons. Concomitant with the drop in mortality-rate there was a reduction in bacteremia, peritonitis (determined by the smears), and empyema (Table II). The deaths in the drug-treated Group C occurred later than those of the serum-treated Group B, although they were numerically equal. Also, in the drug-treated group, 64% of the rats had no broncho- or lobar pneumonia, whereas only 50% of the rats in the serum-treated group were so spared. A rough approximation of the degree of microscopic involvement indicates less impairment in the group treated with p-aminobenzenesulfonamide than in the group treated with serum.