Previous Article | Next Article 
Antimicrobial Agents and Chemotherapy, March 2001, p. 789-793, Vol. 45, No. 3
Antimicrobial Research Laboratory, National
Public Health Institute, Turku,1 and
Department of Ophthalmology, University of
Turku,2 20520 Turku, Finland
Received 14 August 2000/Returned for modification 16 November
2000/Accepted 13 December 2000
The in vitro susceptibilities of 184 erythromycin-resistant
streptococci to a novel ketolide, telithromycin (HMR 3647),
were tested. These clinical isolates included 111 Streptococcus
pyogenes, 18 group C streptococcus, 18 group G streptococcus, and
37 Streptococcus pneumoniae strains. The MICs for all but
eight S. pyogenes strains were Ketolides represent a new generation
of macrolides, in which a 3-keto group replaces L-cladinose
in the lactone ring. Ketolides have shown to be more active in vitro
than other macrolides against various gram-positive bacteria such as
Enterococcus species (6, 24),
Staphylococcus aureus (6, 13), and
Streptococcus species, including erythromycin-resistant
Streptococcus pneumoniae and Streptococcus
pyogenes strains (6, 16, 18). On the other hand,
methicillin-resistant and some erythromycin-resistant S. aureus strains, as well as some Staphylococcus
epidermidis strains (1, 18), seem to be resistant to
ketolides (1, 6, 13).
In streptococci, there are two well-characterized macrolide resistance
mechanisms: target site modification and active drug efflux. Target
site modification is mediated by methylases encoded by the
erm (erythromycin ribosome methylation) genes (21,
26). Methylation of A2058 of the peptidyl transferase loop of
23S rRNA causes resistance to macrolides as well as to lincosamides and streptogramin B antibiotics (the MLSB resistance phenotype)
(26). The expression of the erm genes can be
either constitutive or inducible (27). In streptococci,
erm genes are carried on both the chromosome and plasmids
(2, 21) and are associated with conjugative transposons
(25). The active-efflux mechanism, encoded by the
mef (macrolide efflux) genes, is more specific and causes resistance only to 14- and 15-member-ring macrolides (the M resistance phenotype) (3, 22). Expression of mef genes is
constitutive (C. Arpin, M. H. Canron, P. Noury, and C. Quentin,
Letter, J. Antimicrob. Chemother. 44:133-134, 1999).
The mef genes are chromosomal (11, 17) and, at
least in the case of S. pyogenes, can be transferred by
conjugation (11).
The present work was carried out to study the activity of a novel
ketolide, telithromycin (HMR 3647), against
Streptococcus species with known macrolide resistance
determinants. In addition, its activity against nine S. pneumoniae strains with an unknown macrolide resistance mechanism
was tested.
Bacterial strains.
Altogether 184 erythromycin-resistant
streptococcal strains (MIC,
0066-4804/01/$04.00+0 DOI: 10.1128/AAC.45.3.789-793.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
In Vitro Activities of the Novel Ketolide Telithromycin (HMR
3647) against Erythromycin-Resistant Streptococcus
Species
ABSTRACT
Top
Abstract
Introduction
Materials and Methods
Results and Discussion
References
0.5 µg/ml, indicating
that telithromycin is active in vitro against
erythromycin-resistant Streptococcus strains. All strains for which MICs were 
1 µg/ml had an erm(B) resistance
gene and six strains for which MICs were 4 µg/ml had a constitutive
erm(B) gene (MIC range, 4 to 64 µg/ml). Interestingly,
for S. pneumoniae strains with a constitutive
erm(B) gene, MICs were 0.25 µg/ml (MIC range, 0.008
to 0.25 µg/ml). Our in vitro data show that for S. pyogenes strains which constitutively express the
erm(B) methylase gene, MICs are so high that the strains
might be clinically resistant to telithromycin.
INTRODUCTION
Top
Abstract
Introduction
Materials and Methods
Results and Discussion
References
MATERIALS AND METHODS
Top
Abstract
Introduction
Materials and Methods
Results and Discussion
References
1 µg/ml) selected by the erythromycin
resistance mechanism and 51 erythromycin-susceptible streptococcal
strains (MIC, 0.25 µg/ml) were analyzed. These strains included 131 S. pyogenes, 28 group C streptococcus (GCS), 29 group G
streptococcus (GGS), and 47 S. pneumoniae strains (Table
1).
Erythromycin-resistant S. pyogenes strains were collected
from the United States, Argentina, and various European countries
between 1986 and 1997. Erythromycin-susceptible S. pyogenes
strains were collected from Finland as described previously (9,
11). The GCS and GGS strains were collected in the North Karelian region in Finland between 1992 and 1995 (12).
S. pneumoniae strains were obtained from microbiological
laboratories situated all over Finland between 1994 and 1998. Each
laboratory identified the strains using their own standard microbiology
techniques and sent the strains to the Antimicrobial Research
Laboratory of the National Public Health Institute, Turku, Finland,
where the identification was further confirmed based on colony
morphology and hemolysis on Blood Agar Base (Oxoid Ltd., Basingstoke,
Hampshire, England) plates supplemented with 7.5% sheep blood. For
S. pyogenes, GCS, and GGS strains the Streptex test (Murex
Biotech Ltd., Kent, England) was also used, and for S. pneumoniae, the Optochin Disc (Oxoid Ltd.) or Slidex Pneumo-Kit
(bioMérieux SA, Marcy l'Etoile, France) was also used. Two
control strains, S. pyogenes ATCC 10389 and S. pneumoniae ATCC 49619, were tested together with the studied strains.
TABLE 1.
Streptococcus strains characterized according
to their macrolide resistance determinants and MICs
MIC testing. MIC testing was done using the agar dilution technique. The bacteria were cultured for 20 h in air at 35°C on Mueller-Hinton II (Becton Dickinson Microbiology Systems, Cockeysville, Md.) agar plates supplemented with 5% sheep blood. The antibiotics used were telithromycin (HMR3647), erythromycin, azithromycin, clarithromycin (Hoechst Marion Roussel [Aventis Pharma], Romainville Cedex, France), quinupristin-dalfopristin (30/70) (RP59500), spiramycin (Rhône-Poulenc Rorer, Vitrysur-Seine, France), and clindamycin (Sigma-Aldrich Chemie, Gmbh, Steinheim, Germany). If available, NCCLS MIC breakpoints were used (15); otherwise, interpretation of MIC results was done based on the distribution of MICs.
Phenotyping. The double-disk method with erythromycin (diffusible content, 78 µg) and clindamycin (diffusible content, 25 µg) (Neo-sensitabs; A/S Rosco, Taastrup, Denmark) disks was used for classification of macrolide resistance phenotypes. The disks were placed 15 to 20 mm apart on Mueller-Hinton II agar plates supplemented with 5% sheep blood. Bacteria were cultured for 20 h in 5% CO2 at 35°C. After incubation, blunting of the clindamycin zone of inhibition proximal to the erythromycin disk was considered to indicate inducible MLSB resistance (20). In addition to strains with well-characterized macrolide resistance types (the MLSB and M phenotypes), nine S. pneumoniae strains with a novel resistance phenotype were included in the analyses. In these nine strains no known macrolide resistance gene has been found by PCR. These strains are resistant to erythromycin, azithromycin, and clarithromycin, and the spiramycin and clindamycin MICs for these strains are elevated compared to those for strains with the M resistance phenotype, although MICs of clindamycin are not as high as for strains with a constitutive erm(B) resistance gene. Resistance to clindamycin is not inducible (unpublished observations). A similar phenotype for S. pneumoniae has been previously described for clinical isolates (8) and recently also for laboratory strains carrying mutations in 23S rRNA or ribosomal protein L4 (23).
Resistance gene determinations and clonality studies. Macrolide resistance genes were determined using PCR as described previously (11). The clonality of six S. pyogenes strains was studied using serotyping (14), Vir typing (5), and random amplified polymorphic DNA analysis (19).
| |
RESULTS AND DISCUSSION |
|---|
|
Top
Abstract
Introduction
Materials and Methods
Results and Discussion
References
|
|---|
In this study, the in vitro activities of
telithromycin and six other antibiotics against 184 erythromycin-resistant and 51 erythromycin-susceptible
Streptococcus strains were studied (Table 1 and Fig.
1). In general, telithromycin
was more active than 14- and 15-member-ring macrolides
(erythromycin, azithromycin, and clarithromycin) against
erythromycin-resistant Streptococcus strains. MICs of
telithromycin were 0.5 µg/ml for all but eight S. pyogenes strains (see below). Quinupristin-dalfopristin, a mixture
of streptogramin A and B antibiotics, showed activity similar to that
of telithromycin, although MICs were somewhat higher (MIC
at which 90% of the isolates are inhibited [MIC90], 0.5 to 4 µg/ml). Clindamycin (a lincosamide) was active against strains with an inducible erm methylase gene
(MIC90, 0.063 to 0,5 µg/ml) and was even more
active than telithromycin against strains with a
mef gene (MIC90, 0.063 to 0.125 µg/ml).
The clindamycin MICs for strains with a constitutive erm
methylase gene were high (MIC90, >64 µg/ml). Also,
S. pneumoniae strains with the novel resistance
phenotype were intermediate or resistant to clindamycin (MIC90, 4 µg/ml). Spiramycin (a 16-member-ring macrolide)
showed activity similar to that of telithromycin against
strains with a mef resistance gene. However, the spiramycin
MICs for all strains with an erm methylase gene (inducible
or constitutive) and for S. pneumoniae strains with the
novel resistance phenotype were elevated (MIC90, 4 to >64
µg/ml).
|
The eight S. pyogenes strains for which the telithromycin MICs were elevated included one strain with an inducible erm(B) gene (MIC, 1 µg/ml), one strain with two resistance genes [an inducible erm(B) gene and a mef(A) gene; MIC, 4 µg/ml], and, most importantly, six strains with a constitutive erm(B) gene (MIC90, 64 µg/ml). These six S. pyogenes strains belonged to six different serotypes (T12M22 opacity factor positive, T12M12 opacity factor negative, T1M1 opacity factor negative, T12M66 opacity factor positive, T6M6 opacity factor negative, and T28R28 opacity factor positive), six different Vir types, and six different random amplified polymorphic DNA types, indicating that the strains were not of the same clonal origin. In contrast to the case for S. pyogenes strains, telithromycin MICs for gene S. pneumoniae strains with the constitutive erm(B) were low (MIC90, 0.25 µg/ml). This finding is concordant with a previous study where telithromycin MICs for S. pneumoniae strains with the constitutive MLSB phenotype of erythromycin resistance were low (MIC90, 0.25 µg/ml) (16). Similar to the case for S. pyogenes, telithromycin MICs for constitutively erythromycin-resistant S. aureus strains have been shown to be elevated (6). Telithromycin MICs for S. pyogenes and GGS strains which had an inducible erm(TR) gene were low (MIC90, 0.063 µg/ml). In contrast to the case for the constitutive erm(B) gene, constitutive expression of the erm(TR) gene in one S. pyogenes strain did not increase the telithromycin MIC.
An interesting question is why the Erm(B) methylase does not protect S. pneumoniae as well as it protects S. pyogenes against telithromycin. The Erm(B) methylases of S. pneumoniae and S. pyogenes are nearly identical (99% similarity at the amino acid level [21]), so it is unlikely that the differences in the erm(B) genes can explain differences in susceptibility to telithromycin. Structural differences in the 23S rRNA molecules or other ribosomal components are more likely explanations. Ketolides as well as other macrolides interact with the peptidyl transferase loop in the V domain of the 23S rRNA. For example, both telithromycin and erythromycin protect positions A2058, A2059, and G2505 of the 23S rRNA against chemical modification (7, 28). It has also been shown that hairpin 35 in domain II of the 23S rRNA constitutes a part of the binding site of macrolides and ketolides (7, 28). Telithromycin protects against chemical modification, and erythromycin enhances chemical modification, of residue A752 in hairpin 35 (7). Actually, using different ketolide derivatives it has been shown that interaction with hairpin 35 is essential for the antimicrobial activity of ketolides (4). Methylation of A2058 of the peptidyl transferase loop in the V domain confers resistance to MLSB antibiotics by inhibiting the binding of the antibiotics to the ribosomes. However, as we have shown here with S. pneumoniae and as has been shown with several other bacteria (6, 18), this methylation does not protect against telithromycin. It has been proposed that although methylation of A2058 weakens the binding of macrolides and ketolides to the ribosomes by interfering with the interaction between the antibiotic and the residues on the peptidyl transferase loop, it does not prevent the strong interaction of ketolides with hairpin 35. This interaction therefore is probably enough to bind the antibiotic to the ribosome and to prevent protein synthesis (28). The same is true with mutations in the peptidyl transferase loop, which can inhibit binding of macrolides but not ketolides to the ribosomes if ketolides have alkyl-aryl 11/12 lactone ring extensions, which can make contact with hairpin 35 and the drug (4). It might be that in S. pyogenes the interaction of telithromycin with hairpin 35 is weaker than that in S. pneumoniae and because of that, telithromycin can not bind to the ribosomes of S. pyogenes if A2058 is methylated. Structural differences in the ribosomes of the two bacteria may thus explain the differences in the interactions between telithromycin and hairpin 35.
Quite recently, Tait-Kamradt et al. (23) demonstrated that in S. pneumoniae mutations in the 23S rRNA or ribosomal protein L4 can cause resistance to macrolides. Mutations in the pepdityl transferase loop of the 23S rRNA caused phenotypes that were similar but not identical to those described in this work for S. pneumoniae strains without any known macrolide resistance genes. The type, number, and positions of mutations in the peptidyl transferase loop affect the phenotype, so it is possible that the strains we describe here also carry resistance-causing mutations in 23S rRNA molecules.
Telithromycin is a novel ketolide that belongs to the macrolide family of antibiotics. Our work in addition to several other studies, indicates that the new ketolides are active in vitro against various gram-positive bacteria, including strains that are resistant to other macrolides (6, 16). Telithromycin MICs were high only for S. pyogenes strains with the constitutive erm(B) resistance gene. In recent years these strains have comprised about 10% of all erythromycin-resistant S. pyogenes strains in Finland (11) and several other countries (10). Although the presence of a constitutive erm(B) gene in S. pyogenes varies in different countries (10), it seems that telithromycin has good in vitro activity against most S. pyogenes strains.
| |
ACKNOWLEDGMENTS |
|---|
We thank Tuula Randell and Anna-Liisa Lumiaho for their excellent technical assistance. We are grateful to the Finnish Study Group for Antimicrobial Resistance and to Androulla Efstratiou, Emilio Pérez-Trallero, Antoaneta Detcheva, Michael Jacobs. Horacio Lopardo, J. P. Garrahan, Dianella Savoia, Claes Schalén. Eva Tzelepi, and Pietro Varaldo for the bacterial strains used in this study. We also thank André Bryskier (Aventis Pharma Inc.) for supplying telithromycin.
This work was supported by a grant from Aventis Pharma Inc.
| |
FOOTNOTES |
|---|
* Corresponding author. Mailing address: National Public Health Institute, Turku, Kiinamyllynkatu 13, 20520 Turku, Finland. Phone: 358-2-2519255. Fax: 358-2-2519254. E-mail: jari.jalava{at}utu.fi.
| |
REFERENCES |
|---|
|
Top
Abstract
Introduction
Materials and Methods
Results and Discussion
References
|
|---|
| 1. |
Boswell, F. J.
1998.
The in-vitro activity of HMR 3647, a new ketolide antimicrobial agent.
J. Antimicrob. Chemother.
42:703-709 |
| 2. | Ceglowski, P., and J. C. Alonso. 1994. Gene organization of the Streptococcus pyogenes plasmid pDB101: sequence analysis of the orf eta-copS region. Gene 145:33-39[CrossRef][Medline]. |
| 3. | Clancy, J., J. Petitpas, F. Dib-Hajj, W. Yuan, M. Cronan, A. V. Kamath, et al. 1996. Molecular cloning and functional analysis of a novel macrolide-resistance determinant, mefA, from Streptococcus pyogenes. Mol. Microbiol. 22:867-879[CrossRef][Medline]. |
| 4. | Douthwaite, S., L. H. Hansen, and P. Mauvais. 2000. Macrolide-ketolide inhibition of MLS-resistant ribosomes is improved by alternative drug interaction with domain II of 23S rRNA. Mol. Microbiol. 36:183-193[CrossRef][Medline]. |
| 5. | Gardiner, D., J. Hartas, B. Currie, J. D. Mathews, D. J. Kemp, and K. S. Sriprakash. 1995. Vir typing: a long-PCR typing method for group A streptococci. PCR Methods Appl. 4:288-293[Medline]. |
| 6. |
Hamilton-Miller, J. M. T., and S. Shah.
1998.
Comparative in-vitro activity of ketolide HMR 3647 and four macrolides against gram-positive cocci of known erythromycin susceptibility status.
J. Antimicrob. Chemother.
41:649-653 |
| 7. | Hansen, L. H., P. Mauvais, and S. Douthwaite. 1999. The macrolide-ketolide antibiotic binding site is formed by structures in domains II and V of 23S ribosomal RNA. Mol. Microbiol. 31:623-631[CrossRef][Medline]. |
| 8. |
Johnston, N. J.,
J. C. de Azavedo,
J. D. Kellner, and D. E. Low.
1998.
Prevalence and characterization of the mechanisms of macrolide, lincosamide, and streptogramin resistance in isolates of Streptococcus pneumoniae.
Antimicrob. Agents Chemother.
42:2425-2426 |
| 9. | Kataja, J., P. Huovinen, A. Muotiala, J. Vuopio-Varkila, A. Efstratiou, G. Hallas, et al. 1998. Clonal spread of group A streptococcus with the new type of erythromycin resistance. J. Infect. Dis. 177:786-789[Medline]. |
| 10. |
Kataja, J.,
P. Huovinen, and H. Seppala.
2000.
Erythromycin resistance genes in group A streptococci of different geographical origins.
J. Antimicrob. Chemother.
46:789-792 |
| 11. |
Kataja, J.,
P. Huovinen,
M. Skurnik, and H. Seppälä.
1999.
Erythromycin resistance genes in group A streptococci in Finland.
Antimicrob. Agents Chemother.
43:48-52 |
| 12. |
Kataja, J.,
H. Seppälä,
M. Skurnik,
H. Sarkkinen, and P. Huovinen.
1998.
Different erythromycin resistance mechanisms in group C and group G streptococci.
Antimicrob. Agents Chemother.
42:1493-1494 |
| 13. |
Malathum, K.,
T. M. Coque,
K. S. Singh, and B. E. Murray.
1999.
In vitro activities of two ketolides, HMR 3647 and HMR 3004, against gram-positive bacteria.
Antimicrob. Agents Chemother.
43:930-936 |
| 14. | Muotiala, A., H. Seppälä, P. Huovinen, and J. Vuopio-Varkila. 1997. Molecular comparison of group A streptococci of T1M1 serotype from invasive and noninvasive infections in Finland. J. Infect. Dis. 175:392-399[Medline]. |
| 15. | NCCLS. 1999. Performance standards for antimicrobial susceptibility testing; ninth informational supplement, M100-S9, vol. 19. NCCLS, Wayne, Pa. |
| 16. |
Reinert, R. R.,
A. Bryskier, and R. Lütticken.
1998.
In vitro activities of the new ketolide antibiotics HMR 3004 and HMR 3647 against Streptococcus pneumoniae in Germany.
Antimicrob. Agents Chemother.
42:1509-1511 |
| 17. |
Santagati, M.,
F. Iannelli,
M. R. Oggioni,
S. Stefani, and G. Pozzi.
2000.
Characterization of a genetic element carrying the macrolide efflux gene mef(A) in Streptococcus pneumoniae.
Antimicrob. Agents Chemother.
44:2585-2587 |
| 18. |
Schülin, T.,
C. B. Wennersten,
R. C. Moellering, Jr., and G. M. Eliopoulos.
1998.
In-vitro activity of the new ketolide antibiotic HMR 3647 against gram-positive bacteria.
J. Antimicrob. Chemother.
42:297-301 |
| 19. |
Seppälä, H.,
Q. He,
M. österblad, and P. Huovinen.
1994.
Typing of group A streptococci by random amplified polymorphic DNA analysis.
J. Clin. Microbiol.
32:1945-1948 |
| 20. |
Seppälä, H.,
A. Nissinen,
Q. Yu, and P. Huovinen.
1993.
Three different phenotypes of erythromycin-resistant Streptococcus pyogenes in Finland.
J. Antimicrob. Chemother.
32:885-891 |
| 21. |
Seppälä, H.,
M. Skurnik,
H. Soini,
M. C. Roberts, and P. Huovinen.
1998.
A novel erythromycin resistance methylase gene (ermTR) in Streptococcus pyogenes.
Antimicrob. Agents Chemother.
42:257-262 |
| 22. | Sutcliffe, J., A. Tait-Kamradt, and L. Wondrack. 1996. Streptococcus pneumoniae and Streptococcus pyogenes resistant to macrolides but sensitive to clindamycin: a common resistance pattern mediated by an efflux system. Antimicrob. Agents Chemother. 40:1817-1824[Abstract]. |
| 23. |
Tait-Kamradt, A.,
T. Davies,
M. Cronan,
M. R. Jacobs,
P. C. Appelbaum, and J. Sutcliffe.
2000.
Mutations in 23S rRNA and ribosomal protein L4 account for resistance in pneumococcal strains selected in vitro by macrolide passage.
Antimicrob. Agents Chemother.
44:2118-2125 |
| 24. |
Torres, C.,
M. Zarazaga,
C. Tenorio,
A. Portillo,
Y. Saenz,
F. Ruiz, et al.
1998.
In vitro activity of the new ketolide HMR3647 in comparison with those of macrolides and pristinamycins against Enterococcus spp.
Antimicrob. Agents Chemother.
42:3279-3281 |
| 25. |
Trieu-Cuot, P.,
C. Poyart-Salmeron,
C. Carlier, and P. Courvalin.
1990.
Nucleotide sequence of the erythromycin resistance gene of the conjugative transposon Tn1545.
Nucleic Acids Res.
18:3660 |
| 26. | Weisblum, B. 1995. Erythromycin resistance by ribosome modification. Antimicrob. Agents Chemother. 39:577-585[Medline]. |
| 27. | Weisblum, B. 1995. Insights into erythromycin action from studies of its activity as inducer of resistance. Antimicrob. Agents Chemother. 39:797-805[Medline]. |
| 28. | Xiong, L., S. Shah, P. Mauvais, and A. S. Mankin. 1999. A ketolide resistance mutation in domain II of 23S rRNA reveals the proximity of hairpin 35 to the peptidyl transferase centre. Mol. Microbiol. 31:633-639[CrossRef][Medline]. |
Antimicrobial Agents and Chemotherapy, March 2001, p. 789-793, Vol. 45, No. 3
0066-4804/01/$04.00+0 DOI: 10.1128/AAC.45.3.789-793.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
This article has been cited by other articles:
-
Richter, S. S., Heilmann, K. P., Dohrn, C. L., Beekmann, S. E., Riahi, F., Garcia-de-Lomas, J., Ferech, M., Goossens, H., Doern, G. V.
(2008). Increasing telithromycin resistance among Streptococcus pyogenes in Europe. J Antimicrob Chemother
61: 603-611
[Abstract] [Full Text] -
Wolter, N., Smith, A. M., Farrell, D. J., Northwood, J. B., Douthwaite, S., Klugman, K. P.
(2008). Telithromycin Resistance in Streptococcus pneumoniae Is Conferred by a Deletion in the Leader Sequence of erm(B) That Increases rRNA Methylation. Antimicrob. Agents Chemother.
52: 435-440
[Abstract] [Full Text] -
Wolter, N., Smith, A. M., Low, D. E., Klugman, K. P.
(2007). High-Level Telithromycin Resistance in a Clinical Isolate of Streptococcus pneumoniae. Antimicrob. Agents Chemother.
51: 1092-1095
[Abstract] [Full Text] -
Rantala, M., Haanpera-Heikkinen, M., Lindgren, M., Seppala, H., Huovinen, P., Jalava, J., the Finnish Study Group for Antimicrobial Resistan,
(2006). Streptococcus pneumoniae Isolates Resistant to Telithromycin.. Antimicrob. Agents Chemother.
50: 1855-1858
[Abstract] [Full Text] -
Rantala, M., Huikko, S., Huovinen, P., Jalava, J., the Finnish Study Group for Antimicrobial Resistan,
(2005). Prevalence and Molecular Genetics of Macrolide Resistance among Streptococcus pneumoniae Isolates Collected in Finland in 2002. Antimicrob. Agents Chemother.
49: 4180-4184
[Abstract] [Full Text] -
Green, M., Allen, C., Bradley, J., Dashefsky, B., Gilsdorf, J. R., Marcon, M. J., Schutze, G. E., Smith, C., Walter, E., Martin, J. M., Edwards, K. A., Barbadora, K. A., Rumbaugh, R. M., Wald, E. R.
(2005). In Vitro Activity of Telithromycin against Macrolide-Susceptible and Macrolide-Resistant Pharyngeal Isolates of Group A Streptococci in the United States. Antimicrob. Agents Chemother.
49: 2487-2489
[Abstract] [Full Text] -
Novotny, G. W., Jakobsen, L., Andersen, N. M., Poehlsgaard, J., Douthwaite, S.
(2004). Ketolide Antimicrobial Activity Persists after Disruption of Interactions with Domain II of 23S rRNA. Antimicrob. Agents Chemother.
48: 3677-3683
[Abstract] [Full Text] -
Shi, J., Montay, G., Chapel, S., Hardy, P., Barrett, J. S., Sack, M., Marbury, T., Swan, S. K., Vargas, R., Leclerc, V., Leroy, B., Bhargava, V. O.
(2004). Pharmacokinetics and Safety of the Ketolide Telithromycin in Patients with Renal Impairment. J Clin Pharmacol
44: 234-244
[Abstract] [Full Text] -
Kaieda, S., Okitsu, N., Yano, H., Hosaka, Y., Nakano, R., Okamoto, R., Takahashi, H., Inoue, M.
(2003). Induction of telithromycin resistance in Streptococcus pneumoniae. J Antimicrob Chemother
52: 736-737
[Full Text] -
Seppala, H., Haanpera, M., Al-Juhaish, M., Jarvinen, H., Jalava, J., Huovinen, P.
(2003). Antimicrobial susceptibility patterns and macrolide resistance genes of viridans group streptococci from normal flora. J Antimicrob Chemother
52: 636-644
[Abstract] [Full Text] -
Hsueh, P.-R., Teng, L.-J., Wu, T.-L., Yang, D., Huang, W.-K., Shyr, J.-M., Chuang, Y.-C., Wan, J.-H., Yan, J.-J., Lu, J.-J., Wu, J.-J., Ko, W.-C., Chang, F.-Y., Yang, Y.-C., Lau, Y.-J., Liu, Y.-C., Lee, C.-M., Leu, H.-S., Liu, C.-Y., Luh, K.-T.
(2003). Telithromycin- and Fluoroquinolone-Resistant Streptococcus pneumoniae in Taiwan with High Prevalence of Resistance to Macrolides and {beta}-Lactams: SMART Program 2001 Data. Antimicrob. Agents Chemother.
47: 2145-2151
[Abstract] [Full Text] -
Hsueh, P.-R., Teng, L.-J., Lee, C.-M., Huang, W.-K., Wu, T.-L., Wan, J.-H., Yang, D., Shyr, J.-M., Chuang, Y.-C., Yan, J.-J., Lu, J.-J., Wu, J.-J., Ko, W.-C., Chang, F.-Y., Yang, Y.-C., Lau, Y.-J., Liu, Y.-C., Leu, H.-S., Liu, C.-Y., Luh, K.-T.
(2003). Telithromycin and Quinupristin-Dalfopristin Resistance in Clinical Isolates of Streptococcus pyogenes: SMART Program 2001 Data. Antimicrob. Agents Chemother.
47: 2152-2157
[Abstract] [Full Text] -
Morosini, M.-I., Canton, R., Loza, E., del Campo, R., Almaraz, F., Baquero, F.
(2003). Streptococcus pyogenes isolates with characterized macrolide resistance mechanisms in Spain: in vitro activities of telithromycin and cethromycin. J Antimicrob Chemother
52: 50-55
[Abstract] [Full Text] -
Pihlajamaki, M., Jalava, J., Huovinen, P., Kotilainen, P.
(2003). Antimicrobial Resistance of Invasive Pneumococci in Finland in 1999-2000. Antimicrob. Agents Chemother.
47: 1832-1835
[Abstract] [Full Text] -
Betriu, C., Culebras, E., Gomez, M., Rodriguez-Avial, I., Sanchez, B. A., Agreda, M. C., Picazo, J. J.
(2003). Erythromycin and Clindamycin Resistance and Telithromycin Susceptibility in Streptococcus agalactiae. Antimicrob. Agents Chemother.
47: 1112-1114
[Abstract] [Full Text] -
Reinert, R. R., Lutticken, R., Bryskier, A., Al-Lahham, A.
(2003). Macrolide-Resistant Streptococcus pneumoniae and Streptococcus pyogenes in the Pediatric Population in Germany during 2000-2001. Antimicrob. Agents Chemother.
47: 489-493
[Abstract] [Full Text] -
Betriu, C., Culebras, E., Redondo, M., Rodriguez-Avial, I., Gomez, M., Boloix, A., Picazo, J. J.
(2002). Prevalence of macrolide and tetracycline resistance mechanisms in Streptococcus pyogenes isolates and in vitro susceptibility to telithromycin. J Antimicrob Chemother
50: 436-438
[Full Text] -
Liu, M., Douthwaite, S.
(2002). Activity of the Ketolide Telithromycin Is Refractory to Erm Monomethylation of Bacterial rRNA. Antimicrob. Agents Chemother.
46: 1629-1633
[Abstract] [Full Text] -
Pihlajamaki, M., Kataja, J., Seppala, H., Elliot, J., Leinonen, M., Huovinen, P., Jalava, J.
(2002). Ribosomal Mutations in Streptococcus pneumoniae Clinical Isolates. Antimicrob. Agents Chemother.
46: 654-658
[Abstract] [Full Text]
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Copyright © 2009 by the American Society for Microbiology. For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»