ANTIMICROBIAL. AGENTS AND CHEMOTHERAIY, Apr. 1978, p. 70i-702 0066-4804/78/0013-0701$02.00/0 Copyright © 1978 American Society for Microbiology
Vol. 13, No. 4 Printed in U.S.A.
Susceptibility of Skin and Throat Strains of Group A Streptococci to Rosamicin and Erythromycin GEORGE SAROGLOU AND ALAN L. BISNO* Department of Medicine, Division of Infectious Diseases, University of Tennessee Center for the Health Sciences, Memphis, Tennessee 38163 Received for publication 16 May 1977
The minimal inhibitory concentrations of rosamicin and erythromycin were compared for 210 strains of group A streptococcus isolated from a diverse spectrum of streptococcal diseases. Of these strains, 97.6% were inhibited by 0.1 to 0.2 jig of rosamicin per ml, whereas 90.9% were inhibited by 0.025 to 0.05 yg of erythromycin per ml. The minimal inhibitory concentration of rosamicin for 154 strains exceeded that of erythromycin by at least fourfold. Five group A strains of streptococcus that were highly resistant to erythromycin were even more resistant to rosamicin.
Rosamicin, a new macrolide antibiotic, has in vitro activity equivalent or superior to that of erythromycin against a variety of microorganisms, including aerobic and anaerobic gramnegative rods and certain gram-positive cocci (1, 7, 9; S. Shadomy, L. Paxton, and M. A. Tipple, Abstr. Annu. Meet. Am. Soc. Microbiol. 1976, A31, p. 6). Very limited data are available regarding the activity of rosamicin against group A streptococcus, and there has been no systematic survey of its activity against streptococcal strains isolated from clinical specimens. This study was undertaken to compare the in vitro activities of rosamicin and erythromycin against group A streptococci isolated from a diverse spectrum of streptococcal diseases, including sore throat, pyoderma, acute rheumatic fever, acute glomerulonephritis, and disseminated streptococcal infection. Serogrouping of beta-hemolytic streptococci was performed by the method of Swift et al. (8). M and T typing of group A strains was done by standard techniques (5, 8), using antisera provided by the U.S. Center for Disease Control, Atlanta, Ga. Rosamicin base (Schering Corp., Bloomfield, N.J.) and erythromycin base (Eli Lilly & Co., Indianapolis, Ind.) were obtained in pure form from the manufacturers. Agar dilution
susceptibility testing was performed on plates containing Mueller-Hinton agar (BBL) and 5% defibrinated sheep blood. The inoculum, consisting of a 1:1,000 dilution of an overnight growth of group A streptococci, was applied by means of an inoculum replicator apparatus (6). Over 90% of group A streptococci tested were inhibited by erythromycin in concentrations of 0.05 ,ug or less per ml in agar plate dilution
susceptibility tests (Table 1). This agrees with previous studies of this antibiotic (3, 4). In contrast, only 1.9% of group A streptococci were susceptible to rosamicin in concentrations as low as 0.05 ,ug/ml, and most strains required 0.2 ,ug/ml for growth inhibition (Table 1). Only 1 of the 210 strains tested had a minimal inhibitory concentration (MIC) of rosamicin that was lower than that of erythromycin; for 3 strains, the MIC for both antibiotics was the same. For 154 strains, the MIC of rosamicin exceeded that of erythromycin by at least fourfold. The MICs of both antibiotics for pharyngeal and pyoderma isolates were similar. Isolates from cases of acute glomerulonephritis, acute rheumatic fever, or disseminated infection were not unusually resistant, although the number of strains available for study in the latter two categories was small. Strains tested included representatives of 22 different M serotypes and a wide variety of T serotype patterns. There was no discernible relationship between M and T serotypes and susceptibility to rosamicin or
erythromycin. Effects of pH on MIC were studied with four strains using broth dilution tests. In these studies, pH of the broth was adjusted over a range of 6.3 to 8.3. As anticipated, both drugs were more active at alkaline pH. The superior inhibitory activity of erythromycin, on a microgram-formicrogram basis, was maintained throughout the pH range tested. Five strains of group A streptococci highly resistant to erythromycin (MICs, 3.125 to 6.25 ,ug/ml) and clindamycin (2) were kindly made available to us by A. W. Karchmer, Harvard
701
702
ANTIMICItOB. AGENTS CHEMOTHER.
NOTES
TABLE 1. Susceptibility of 210 strains ofgroup A streptococci to rosamicin and erythromycin Clinical illness
Antibiotic
Rosamicin
Erythromycin
Site of isolation
Pharyngitis Pyoderma AGNa AGN ARFb Disseminated infectione Total
Throat Skin lesion Throat Skin lesion Throat
Pharyngitis Pyoderma AGN AGN ARF Disseminated infection Total
Throat Skin lesion Throat Skin lesion Throat
No. of strains tested 0.013
% Strains with MIC 0.025
106 50 17 27 6 4
0.05
0.1
0.2
0.9 2
32.1 18 35.3 48.1
66 80 64.7 48.1
3.8
210
1
0.5
1.9
29.5 6.6 6 23.6 3.7 16.7
0.9
25
77.3 78 58.8 74 83.3 75
15.2
75.7
7.6
0.5
210 0.9 2
0.4 > 0.8 0.9
100 75
25
106 50 17 27 6 4
(,tg/ml) of:
14.1 14 17.6 22.3
68.1
AGN, Acute post-streptococcal glomerulonephritis. ARF, Acute rheumatic fever. c Blood, 2 strains; cerebrospinal fluid, 1; liver abscess, 1. a
b
University. These isolates were even more resistant to rosamicin (MICs, 25 to 50 ,ug/ml). Published studies (1, 9) concerning the activity of rosamicin against beta-hemolytic streptococci provide information on only 32 strains. Waitz et al. (9) previously reported rosamicin to be more active than erythromycin against a small number of streptococcal strains which were relatively resistant to erythromycin. Only 1 of our 210 strains was resistant to erythromycin (MIC, 0.8 ,tg/ml), and this strain was susceptible to rosamicin in a concentration of 0.2 ,ug/ml. On the other hand, the five Harvard strains, which were highly resistant to erythromycin, were even more resistant to rosamicin. In the present study, the MIC of rosamicin exceeded that of erythromycin for nearly all strains tested. This study
was
supported by
a
grant from the Schering
Corp. We gratefully acknowledge the expert technical assistance of Carol Todd.
LITERATURE CIMD 1. Crowe, C. C., and W. E. Sanders, Jr. 1974. Rosamicin: evaluation in vitro and comparison with erythromycin
and lincomycin. Antimicrob. Agents Chemother.
5:272-275. 2. Drapkin, M. S., A. W. Karchmer, and R. C. Moellering, Jr. 1976. Bacteremic infections due to clindamycinresistant streptococci. J. Am. Med. Assoc. 236:263-265. 3. Eichkoff, T. C., M. Finland, and C. Wilcox. 1965. In vitro susceptibility of group A beta hemolytic streptococci to 18 antibiotics. Am. J. Med. Sci. 49:261-268. 4. Jones, W. F., H. A. Feldman, and M. Finland. 1975. Susceptibility of hemolytic streptococci, other than those of group D, to eleven antibiotics in vitro. Am. J. Clin. Pathol. 27:159-169. 5. Moody, M. D., J. Padula, D. Lizara, and C. T. Hall. 1965. Epidemiologic characterization of group A streptococci by T-agglutination and M-precipitation tests in the public health laboratory. Health Lab. Sci. 2:149-162. 6. Steers, E., E. L. Foltz, and B. S. Graves. 1959. Inocula replicating apparatus for routine testing of bacterial susceptibility to antibiotics. Antibiot. Chemother. 9:307-311. 7. Sutter, V. L., and S. M. Finegold. 1976. Rosamicin: in vitro activity against anaerobes and comparison with erythromycin. Antimicrob. Agents Chemother.
9:350-351. 8. Swift, H. F., A. T. Wilson, and R. C. Lancefield. 1943. Typing group A hemolytic streptococci by M precipitin reaction in capillary pipettes. J. Exp. Med. 78:127-133. 9. Waitz, J. A., C. G. Drube, E. L. Moss, and M. J. Weinstein. 1972. Biological studies with rosamicin, a new micromonospora-produced macrolide antibiotic. J. Antibiot. 25:647-652.
Vol. 13, No. 4 Printed in U.S.A.
Susceptibility of Skin and Throat Strains of Group A Streptococci to Rosamicin and Erythromycin GEORGE SAROGLOU AND ALAN L. BISNO* Department of Medicine, Division of Infectious Diseases, University of Tennessee Center for the Health Sciences, Memphis, Tennessee 38163 Received for publication 16 May 1977
The minimal inhibitory concentrations of rosamicin and erythromycin were compared for 210 strains of group A streptococcus isolated from a diverse spectrum of streptococcal diseases. Of these strains, 97.6% were inhibited by 0.1 to 0.2 jig of rosamicin per ml, whereas 90.9% were inhibited by 0.025 to 0.05 yg of erythromycin per ml. The minimal inhibitory concentration of rosamicin for 154 strains exceeded that of erythromycin by at least fourfold. Five group A strains of streptococcus that were highly resistant to erythromycin were even more resistant to rosamicin.
Rosamicin, a new macrolide antibiotic, has in vitro activity equivalent or superior to that of erythromycin against a variety of microorganisms, including aerobic and anaerobic gramnegative rods and certain gram-positive cocci (1, 7, 9; S. Shadomy, L. Paxton, and M. A. Tipple, Abstr. Annu. Meet. Am. Soc. Microbiol. 1976, A31, p. 6). Very limited data are available regarding the activity of rosamicin against group A streptococcus, and there has been no systematic survey of its activity against streptococcal strains isolated from clinical specimens. This study was undertaken to compare the in vitro activities of rosamicin and erythromycin against group A streptococci isolated from a diverse spectrum of streptococcal diseases, including sore throat, pyoderma, acute rheumatic fever, acute glomerulonephritis, and disseminated streptococcal infection. Serogrouping of beta-hemolytic streptococci was performed by the method of Swift et al. (8). M and T typing of group A strains was done by standard techniques (5, 8), using antisera provided by the U.S. Center for Disease Control, Atlanta, Ga. Rosamicin base (Schering Corp., Bloomfield, N.J.) and erythromycin base (Eli Lilly & Co., Indianapolis, Ind.) were obtained in pure form from the manufacturers. Agar dilution
susceptibility testing was performed on plates containing Mueller-Hinton agar (BBL) and 5% defibrinated sheep blood. The inoculum, consisting of a 1:1,000 dilution of an overnight growth of group A streptococci, was applied by means of an inoculum replicator apparatus (6). Over 90% of group A streptococci tested were inhibited by erythromycin in concentrations of 0.05 ,ug or less per ml in agar plate dilution
susceptibility tests (Table 1). This agrees with previous studies of this antibiotic (3, 4). In contrast, only 1.9% of group A streptococci were susceptible to rosamicin in concentrations as low as 0.05 ,ug/ml, and most strains required 0.2 ,ug/ml for growth inhibition (Table 1). Only 1 of the 210 strains tested had a minimal inhibitory concentration (MIC) of rosamicin that was lower than that of erythromycin; for 3 strains, the MIC for both antibiotics was the same. For 154 strains, the MIC of rosamicin exceeded that of erythromycin by at least fourfold. The MICs of both antibiotics for pharyngeal and pyoderma isolates were similar. Isolates from cases of acute glomerulonephritis, acute rheumatic fever, or disseminated infection were not unusually resistant, although the number of strains available for study in the latter two categories was small. Strains tested included representatives of 22 different M serotypes and a wide variety of T serotype patterns. There was no discernible relationship between M and T serotypes and susceptibility to rosamicin or
erythromycin. Effects of pH on MIC were studied with four strains using broth dilution tests. In these studies, pH of the broth was adjusted over a range of 6.3 to 8.3. As anticipated, both drugs were more active at alkaline pH. The superior inhibitory activity of erythromycin, on a microgram-formicrogram basis, was maintained throughout the pH range tested. Five strains of group A streptococci highly resistant to erythromycin (MICs, 3.125 to 6.25 ,ug/ml) and clindamycin (2) were kindly made available to us by A. W. Karchmer, Harvard
701
702
ANTIMICItOB. AGENTS CHEMOTHER.
NOTES
TABLE 1. Susceptibility of 210 strains ofgroup A streptococci to rosamicin and erythromycin Clinical illness
Antibiotic
Rosamicin
Erythromycin
Site of isolation
Pharyngitis Pyoderma AGNa AGN ARFb Disseminated infectione Total
Throat Skin lesion Throat Skin lesion Throat
Pharyngitis Pyoderma AGN AGN ARF Disseminated infection Total
Throat Skin lesion Throat Skin lesion Throat
No. of strains tested 0.013
% Strains with MIC 0.025
106 50 17 27 6 4
0.05
0.1
0.2
0.9 2
32.1 18 35.3 48.1
66 80 64.7 48.1
3.8
210
1
0.5
1.9
29.5 6.6 6 23.6 3.7 16.7
0.9
25
77.3 78 58.8 74 83.3 75
15.2
75.7
7.6
0.5
210 0.9 2
0.4 > 0.8 0.9
100 75
25
106 50 17 27 6 4
(,tg/ml) of:
14.1 14 17.6 22.3
68.1
AGN, Acute post-streptococcal glomerulonephritis. ARF, Acute rheumatic fever. c Blood, 2 strains; cerebrospinal fluid, 1; liver abscess, 1. a
b
University. These isolates were even more resistant to rosamicin (MICs, 25 to 50 ,ug/ml). Published studies (1, 9) concerning the activity of rosamicin against beta-hemolytic streptococci provide information on only 32 strains. Waitz et al. (9) previously reported rosamicin to be more active than erythromycin against a small number of streptococcal strains which were relatively resistant to erythromycin. Only 1 of our 210 strains was resistant to erythromycin (MIC, 0.8 ,tg/ml), and this strain was susceptible to rosamicin in a concentration of 0.2 ,ug/ml. On the other hand, the five Harvard strains, which were highly resistant to erythromycin, were even more resistant to rosamicin. In the present study, the MIC of rosamicin exceeded that of erythromycin for nearly all strains tested. This study
was
supported by
a
grant from the Schering
Corp. We gratefully acknowledge the expert technical assistance of Carol Todd.
LITERATURE CIMD 1. Crowe, C. C., and W. E. Sanders, Jr. 1974. Rosamicin: evaluation in vitro and comparison with erythromycin
and lincomycin. Antimicrob. Agents Chemother.
5:272-275. 2. Drapkin, M. S., A. W. Karchmer, and R. C. Moellering, Jr. 1976. Bacteremic infections due to clindamycinresistant streptococci. J. Am. Med. Assoc. 236:263-265. 3. Eichkoff, T. C., M. Finland, and C. Wilcox. 1965. In vitro susceptibility of group A beta hemolytic streptococci to 18 antibiotics. Am. J. Med. Sci. 49:261-268. 4. Jones, W. F., H. A. Feldman, and M. Finland. 1975. Susceptibility of hemolytic streptococci, other than those of group D, to eleven antibiotics in vitro. Am. J. Clin. Pathol. 27:159-169. 5. Moody, M. D., J. Padula, D. Lizara, and C. T. Hall. 1965. Epidemiologic characterization of group A streptococci by T-agglutination and M-precipitation tests in the public health laboratory. Health Lab. Sci. 2:149-162. 6. Steers, E., E. L. Foltz, and B. S. Graves. 1959. Inocula replicating apparatus for routine testing of bacterial susceptibility to antibiotics. Antibiot. Chemother. 9:307-311. 7. Sutter, V. L., and S. M. Finegold. 1976. Rosamicin: in vitro activity against anaerobes and comparison with erythromycin. Antimicrob. Agents Chemother.
9:350-351. 8. Swift, H. F., A. T. Wilson, and R. C. Lancefield. 1943. Typing group A hemolytic streptococci by M precipitin reaction in capillary pipettes. J. Exp. Med. 78:127-133. 9. Waitz, J. A., C. G. Drube, E. L. Moss, and M. J. Weinstein. 1972. Biological studies with rosamicin, a new micromonospora-produced macrolide antibiotic. J. Antibiot. 25:647-652.
