The drug sensitivity to 10 antibiotics of the 1, 353 strains of hemolytic streptococci consisting of 843 patient strains and 510 healthy-carrier strains (1, 176 strains of which were from Group A) ...which were collected in 1972-74 at 26 institutions scattersring throughout the country were subjected to the study. All the strains were found sensitive to PC, AB-PC, and CEX in contrast to Macrolide antibiotics such as EM, JM, OL and MDM together with LCM to which they were either sensitive or partly (33-38%) highly resistant and thus two peaks of the MIC distribution curve for each of Macrolides were depicted. The MIC of TC distributed widely ranging from sensitive area to highly resistant area (53% belonged to 100 μg) whereas in case of CP the distribution was within a relatively narrow range and 58% fell into 25-50μg. Though the strain number was small, the sensitivity of the Groups B, C, and G to Macrolides was still retained. Among these three Groups Group B was least sensitive Regarding the resistance pattern, 11 patterns appeared, of which sevenfold resistance such as TC/CP/EM/OL/JM/MDM/LCM occupied the first rank (427 strains), followed by TC single-resistance (278 strains), TC/CP double-resistance (243 strains), CP single-resistance (19 strains) and other minors in this order. The total number of strains up to the third rank from the first one occupied 96% of the whole number of resistant strains examined. The 422 strains showing sevenfold-resistant pattern, with the exception of 5 untypable strains, fell into type 12. This was a marked contrast to the other patterns such as TC, CP, or TC/CP which covered a variety of types. Type 4 was siso outstanding in such context that all the 84 strains, with exception of 6 strains, were TC single-resistant. Further, type 3 was apparently differed from type 4 and showed TC/CP double resistance suggesting liability to the acquisition of CP-resistance. Since type 3 is an newly appeared epidemic type, any decisive conclusion can hardly be drawn about its resistance character, but type 4 has a long history of epidemic and therefore it can be mentioned that this type bears some barriers to the resistance acquisition to CP and Macrolides. Thus it was made clear for thefirst time that there exist some differences or orders among types in the liability of resistance acquisition to each of the antibiotics, i.e., the resistance pattern may differ according to type. A similar finding relevant to resistance acquisition of type 12 was obtained between our epidemiological data and the experimental results on resistance transduction by bacteriophage performed by Ubukata, Konno, and Fujii (J. Antibiotics. 28, 681, 1975). Our data, as shown in Table 5, suggested that the sevenfold resistance was initially accomplished by three-step acquisition of type-12 strains through TC-single and then TC/CP-double resistance. Furthermore a difference in rapidity of the resistance acquisition between the three steps was noted which was reflected by the time-lag between the year intervals, as can be postulated from those on the abscissa in Fig. 1, in whidh the steap upheaval of the percentage resistance started. This relative time-lag of the second-step resistance acquisition to the third one might be explained by the results of transduction experiment performed by them in which the transduction of TC-single resistance was, without exception, brought about independently and separately from other antibiotic resistance, whereas CP- and Macrolide resistance were transduced concomitantly. The causative factor of the alteration of the “epidemic wave” from type 4 to type 12 occurring in the past has not been made clear up to now, however it may also be explained by the marked difference in resistance acquisition of these two types to CP and Macrolides.
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