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PREVENTION OF GONORRHEA WITH PENICILLIN TABLETS FREE

HARRY EAGLE, M.D.LIEUTENANT (jg) ; A. V. GUDE; G. E. BECKMANN, M.D.; G. MAST, M.D.CAPTAIN ; J. J. SAPERO; J. B. SHINDLEDECKER
[+] Author Affiliations

Opinions or conclusions contained in this report are those of the authors and are not to be construed as necessarily reflecting the views or the endorsement of the Navy Department.

Abbott Laboratories, Commercial Solvents Corporation, Lederle Laboratories, Inc., Eli Lilly and Company, Chas. F. Pfizer, Schenley Laboratories and The Upjohn Company supplied the penicillin tablets for this study and Sharpe & Dohme, Inc., the placebo.

Mr. Jerome Cornfield and Mr. Nathan Mantel of the Office of the Statistical Coordinator, Division of Public Health Methods, assisted in calculating rates and determining the significance of the observed differences.


JAMA. 1949;140(11):940-943. doi:10.1001/jama.1949.02900460010004
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It has been shown in a number of experimental infections1 that the amount of penicillin necessary for cure increases with the number of organisms inoculated. Thus, in white mice infected with pneumococci, the single curative dose of aqueous penicillin G increased in one experiment from 5 to 260 mg. per kilogram of body weight as the inoculum was increased from 15 to 200,000 organisms.1c

Corollary to these observations, it was found that the longer the interval between inoculation and treatment, the more drug was required for cure. Presumably because of the interim multiplication of organisms, effectively bactericidal levels had to be provided for longer and longer aggregate periods in order to kill enough of the bacteria to effect cure. In syphilitic rabbits, the 50 per cent curative dose of penicillin (in oil and wax) 4 hours after intratesticular inoculation with 2,000 organisms was 1,420 units per kilogram of

REFERENCES

Eagle, H., and others:  Prevention of Gonorrhea with Penicillin Tablets , Pub. Health Rep. 63: 1411-1415 ( (Oct. 29) ) 1948;.
Eagle, H.; Magnuson, H. J., and Fleischman, R.:  Relation of the Size of the Inoculum and the Age of the Infection to the Curative Dose of Penicillin in Experimental Syphilis, with Particular Reference to the Feasibility of Its Prophylactic Use , J. Exper. Med. 85:423-440 ( (April) ) 1947;.
Eagle, H.; Musselman, A. D., and Fleischman, R.: The Effect of Size of the Inoculum and the Age of the Infection on the Curative Dose of Penicillin in Experimental Infections, to be published.
It is estimated that in the particular study group there was sexual exposure in more than SO per cent of all liberties.
Pelouze, P. S.: Gonorrhea in the Male and Female , ed. 3, Philadelphia, W. B. Saunders Company, 1939;.
Midway in this period, the total number of subjects in the station, and available for the study, was suddenly reduced from 361 to 224.
A total of 43 infections were observed after 3,616 liberties in the control group, and 5 infections after 3,011 liberties in the experimental group (corrected as indicated in fourth [§] footnote of table 1 for those who failed to take prophylaxis). If the rate per thousand liberties was the same among the controls and the experimental group, the expected number of infections would have been 26 among the controls and 22 among the experimental subjects instead of 43 and 5, respectively. The chi square test indicates that a difference of this magnitude or greater between the expected and actual number of infections could have occurred by chance less than one time in a million. Even if the infections where prophylaxis is known not to have been taken are included as failures in the experimental group, the difference between the experimental and control groups is still highly significant. So computed, there were 14 infections in 3,787 liberties in the experimental group, and 43 infections in 3,616 control liberties. Were there no difference in the rates in the two groups, the expected values would have been 28 and 29, respectively. A difference between the actual and expected values of this magnitude or greater could have occurred by chance alone about once in thirty thousand times.
Assuming that the number of liberties per man remained at the level of 3 per week, the average of the preceding 40 weeks of the study.
Campbell, V. W. H.; Dougherty, W. J., and Curtis, C. E.:  Delayed Administration of Oral Penicillin as Prophylaxis for Gonorrhea , read before the Annual Scientific Session of American Venereal Disease Association, Washington, D. C., April 8, 1949 .
Romansky, M. J.: Personal communication to the authors
Eisenberg, H.; Plotke, F.; Laughlin, M. E., and Baker, A. H.:  Penicillin in the Prophylactic Treatment of Syphilis , read before the Annual Scientific Session of American Venereal Disease Association, Washington, D. C., April 8, 1949 .

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Eagle, H., and others:  Prevention of Gonorrhea with Penicillin Tablets , Pub. Health Rep. 63: 1411-1415 ( (Oct. 29) ) 1948;.
Eagle, H.; Magnuson, H. J., and Fleischman, R.:  Relation of the Size of the Inoculum and the Age of the Infection to the Curative Dose of Penicillin in Experimental Syphilis, with Particular Reference to the Feasibility of Its Prophylactic Use , J. Exper. Med. 85:423-440 ( (April) ) 1947;.
Eagle, H.; Musselman, A. D., and Fleischman, R.: The Effect of Size of the Inoculum and the Age of the Infection on the Curative Dose of Penicillin in Experimental Infections, to be published.
It is estimated that in the particular study group there was sexual exposure in more than SO per cent of all liberties.
Pelouze, P. S.: Gonorrhea in the Male and Female , ed. 3, Philadelphia, W. B. Saunders Company, 1939;.
Midway in this period, the total number of subjects in the station, and available for the study, was suddenly reduced from 361 to 224.
A total of 43 infections were observed after 3,616 liberties in the control group, and 5 infections after 3,011 liberties in the experimental group (corrected as indicated in fourth [§] footnote of table 1 for those who failed to take prophylaxis). If the rate per thousand liberties was the same among the controls and the experimental group, the expected number of infections would have been 26 among the controls and 22 among the experimental subjects instead of 43 and 5, respectively. The chi square test indicates that a difference of this magnitude or greater between the expected and actual number of infections could have occurred by chance less than one time in a million. Even if the infections where prophylaxis is known not to have been taken are included as failures in the experimental group, the difference between the experimental and control groups is still highly significant. So computed, there were 14 infections in 3,787 liberties in the experimental group, and 43 infections in 3,616 control liberties. Were there no difference in the rates in the two groups, the expected values would have been 28 and 29, respectively. A difference between the actual and expected values of this magnitude or greater could have occurred by chance alone about once in thirty thousand times.
Assuming that the number of liberties per man remained at the level of 3 per week, the average of the preceding 40 weeks of the study.
Campbell, V. W. H.; Dougherty, W. J., and Curtis, C. E.:  Delayed Administration of Oral Penicillin as Prophylaxis for Gonorrhea , read before the Annual Scientific Session of American Venereal Disease Association, Washington, D. C., April 8, 1949 .
Romansky, M. J.: Personal communication to the authors
Eisenberg, H.; Plotke, F.; Laughlin, M. E., and Baker, A. H.:  Penicillin in the Prophylactic Treatment of Syphilis , read before the Annual Scientific Session of American Venereal Disease Association, Washington, D. C., April 8, 1949 .
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