Relationships between the sensitivities in vitro of Neisseria gonorrhoeae to spiramycin, penicillin, streptomycin, tetracycline, and erythromycin.

In a clinical trial of spiramycin, Schmidt, Niordson, Reyn, and Bentzon (1965) observed a positive correlation between the susceptibility of gonococcal strains in vitro to spiramycin and sodium penicillin G, and that the gonococcal strains from thirteen patients not cured by spiramycin were less sensitive to penicillin. Positive correlation could also be demonstrated between the inhibitory values of spiramycin and tetracycline for strains that were both resistant to streptomycin and less sensitive to penicillin. Reyn and Bentzon (1968) confirmed that a comparatively high degree of resistance to spiramycin in vitro was correlated with an increased resistance to penicillin. The correlation was most evident for strains that were resistant to streptomycin. Another peculiar feature observed was that of the fourteen strains with moderately decreased susceptibility to penicillin; seven were highly sensitive to spiramycin but at the same time completely resistant to streptomycin. Strains with moderately decreased susceptibility to penicillin were rarely found in that material, and it was suggested that they might represent a group with special genetic qualities. In contrast to the Danish results reported Durel, Roiron, and Nicod (1967) did not observe any correlation between the susceptibility to penicillin and spiramycin in a study of 302 gonococcal strains. In the present study, the material was supplemented by selected groups of strains with a view to further analysis of the relationships between the sensitivities of gonococcal strains to spiramycin and penicillin. Material and Methods In addition to the 173 gonococcal strains examined in the preceding paper mentioned above, 338 strains isolated during the years 1960-1968 were examined with penicillin (penicillin 0, Leo), streptomycin (dihydrostreptomycinum ®, Leo), tetracycline (tetracyclin 0, Lepetit), and spiramycin (rovamycin ®, May and Baker). The sensitivity to erythromycin ® (Abbott) was examined for 93 of the 338 new strains. Care was taken in selecting the supplementary material to include strains with varying degrees of decreased sensitivity to penicillin simultaneous with sensitivity to streptomycin. The whole series comprised 411 gonococcal strains covering a 1,000-fold range of sensitivity to penicillin; 279 of these were sensitive and 132 resistant to streptomycin. Except in the examination with erythromycin, the plate-dilution method described by Reyn and co-workers was used (Reyn, Korner, and Bentzon, 1958; Reyn, Bentzon, and Ericsson, 1963). The results were given in pg./ml. of 50 per cent. inhibitory concentrations (IC50-values). Strains with IC5O-values . 0-045 ,ug. sodium penicillin G per ml. were considered as being "less sensitive". The sensitivity to erythromycin was determined by a diffusion method using 20 hours' prediffusion (Thomsen, 1962). Five strains artificially made more resistant to penicillin by subculture at increasing concentrations of penicillin were examined in a special experiment. These strains were already less sensitive to penicillin and tetracycline and were completely resistant to streptomycin. The IC.6-values of the original strains and two samples of each strain with different levels of increased resistance to penicillin were determined with penicillin, spiramycin, and erythromycin. Results The IC54-values obtained with penicillin and spiramycin for each of the 411 strains were plotted against each other in a coordinate system. It was