Ribosomal Mutations in Streptococcus pneumoniae Clinical Isolates

ABSTRACT Eleven clinical isolates of Streptococcus pneumoniae, isolated in Finland during 1996 to 2000, had an unusual macrolide resistance phenotype. They were resistant to macrolides and streptogramin B but susceptible, intermediate, or low-level resistant to lincosamides. No acquired macrolide resistance genes were detected from the strains. The isolates were found to have mutations in domain V of the 23S rRNA or ribosomal protein L4. Seven isolates had an A2059C mutation in two to four out of the four alleles encoding the 23S rRNA, two isolates had an A2059G mutation in two alleles, one isolate had a C2611G mutation in all four alleles, and one isolate had a 69GTG71-to-69TPS71 substitution in ribosomal protein L4.

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Ribosomal Mutations Conferring Resistance to Macrolides in Streptococcus pneumoniae Clinical Strains Isolated in Germany

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.47.7.2319-2322.2003 ◽

2003 ◽

Vol 47 (7) ◽

pp. 2319-2322 ◽

Cited By ~ 33

Author(s):

Ralf René Reinert ◽

Angela Wild ◽

Peter Appelbaum ◽

Rudolf Lütticken ◽

Murat Yücel Cil ◽

...

Keyword(s):

Streptococcus Pneumoniae ◽

Amino Acid ◽

Ribosomal Protein ◽

Macrolide Resistance ◽

23S Rrna ◽

Resistance Phenotype ◽

Clinical Strains ◽

Acid Alteration ◽

Amino Acid Alteration

ABSTRACT Among a collection of 4,281 pneumococcal isolates, 7 strains isolated in Germany had an unusual macrolide resistance phenotype. The isolates were found to have multiple mutations in the 23S rRNA and alterations in the L4 ribosomal protein. One strain had an amino acid alteration in the L22 ribosomal protein.

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Mutation in 23S rRNA Responsible for Resistance to 16-Membered Macrolides and Streptogramins in Streptococcus pneumoniae

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.45.1.319-323.2001 ◽

2001 ◽

Vol 45 (1) ◽

pp. 319-323 ◽

Cited By ~ 90

Author(s):

Florence Depardieu ◽

Patrice Courvalin

Keyword(s):

Escherichia Coli ◽

Streptococcus Pneumoniae ◽

Clinical Isolate ◽

23S Rrna ◽

Resistance Phenotype ◽

Domain V

ABSTRACT Streptococcus pneumoniae clinical isolate BM4455 was resistant to 16-membered macrolides and to streptogramins. This unusual resistance phenotype was due to an A2062C (Escherichia coli numbering) mutation in domain V of the four copies of 23S rRNA.

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Antistreptococcal Activity of Telithromycin Compared with Seven Other Drugs in Relation to Macrolide Resistance Mechanisms in Russia

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.46.9.2963-2968.2002 ◽

2002 ◽

Vol 46 (9) ◽

pp. 2963-2968 ◽

Cited By ~ 26

Author(s):

Roman S. Kozlov ◽

Tatiana M. Bogdanovitch ◽

Peter C. Appelbaum ◽

Lois Ednie ◽

Leonid S. Stratchounski ◽

...

Keyword(s):

Streptococcus Pneumoniae ◽

Ribosomal Protein ◽

Streptococcus Pyogenes ◽

Prevalence Rate ◽

Resistance Mechanism ◽

Resistance Mechanisms ◽

Macrolide Resistance ◽

Penicillin G ◽

23S Rrna

ABSTRACT The susceptibilities of 468 recent Russian clinical Streptococcus pneumoniae isolates and 600 Streptococcus pyogenes isolates, from 14 centers in Russia, to telithromycin, erythromycin, azithromycin, clarithromycin, clindamycin, levofloxacin, quinupristin-dalfopristin, and penicillin G were tested. Penicillin-nonsusceptible S. pneumoniae strains were rare except in Siberia, where their prevalence rate was 13.5%: most were penicillin intermediate, but for three strains (two from Smolensk and one from Novosibirsk) the MICs of penicillin G were 4 or 8 μg/ml. Overall, 2.5% of S. pneumoniae isolates were resistant to erythromycin. Efflux was the prevalent resistance mechanism (five strains; 41.7%), followed by ribosomal methylation encoded by constitutive erm(B), which was found in four isolates. Ribosomal mutation was the mechanism of macrolide resistance in three isolates; one erythromycin-resistant S. pneumoniae isolate had an A2059G mutation in 23S rRNA, and two isolates had substitution of GTG by TPS at positions 69 to 71 in ribosomal protein L4. All S. pyogenes isolates were susceptible to penicillin, and 11% were erythromycin resistant. Ribosomal methylation was the most common resistance mechanism for S. pyogenes (89.4%). These methylases were encoded by erm(A) [subclass erm(TR)] genes, and their expression was inducible in 96.6% of isolates. The rest of the erythromycin-resistant Russian S. pyogenes isolates (7.6%) had an efflux resistance mechanism. Telithromycin was active against 100% of pneumococci and 99.2% of S. pyogenes, and levofloxacin and quinupristin-dalfopristin were active against all isolates of both species.

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Mechanisms of Macrolide Resistance in Clinical Pneumococcal Isolates in France

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.45.2.636-638.2001 ◽

2001 ◽

Vol 45 (2) ◽

pp. 636-638 ◽

Cited By ~ 27

Author(s):

Frederic Fitoussi ◽

Catherine Doit ◽

Pierre Geslin ◽

Naima Brahimi ◽

Edouard Bingen

Keyword(s):

Streptococcus Pneumoniae ◽

Genetic Basis ◽

Macrolide Resistance ◽

Clinical Isolates ◽

Resistance Phenotype

ABSTRACT The genetic basis of macrolide resistance was investigated in a collection of 48 genotypically unrelated clinical isolates ofStreptococcus pneumoniae obtained between 1987 and 1997 in France. All strains were resistant to erythromycin, clindamycin, and streptogramin B, exhibiting a macrolide-lincosamide-streptogramin B resistance phenotype, and harbored the erm(B) gene. None of the strains carried the mef(A) or erm(A) subclass erm(TR) gene.

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In Vitro Activity of Telithromycin against SpanishStreptococcus pneumoniae Isolates with Characterized Macrolide Resistance Mechanisms

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.45.9.2427-2431.2001 ◽

2001 ◽

Vol 45 (9) ◽

pp. 2427-2431 ◽

Cited By ~ 32

Author(s):

Marı́a-Isabel Morosini ◽

Rafael Cantón ◽

Elena Loza ◽

Marı́a-Cristina Negri ◽

Juan-Carlos Galán ◽

...

Keyword(s):

Streptococcus Pneumoniae ◽

Resistance Genes ◽

Resistance Mechanisms ◽

Macrolide Resistance ◽

Vitro Activity ◽

Penicillin G ◽

In Vitro Activity ◽

Resistance Phenotype ◽

Erythromycin A

ABSTRACT The susceptibilities to telithromycin of 203 Streptococcus pneumoniae isolates prospectively collected during 1999 and 2000 from 14 different geographical areas in Spain were tested and compared with those to erythromycin A, clindamycin, quinupristin-dalfopristin, penicillin G, cefotaxime, and levofloxacin. Telithromycin was active against 98.9% of isolates (MICs, ≤0.5 μg/ml), with MICs at which 90% of isolates are inhibited being 0.06 μg/ml, irrespective of the resistance genotype. The corresponding values for erythromycin were 61.0% (MICs, ≤0.25 μg/ml) and >64 μg/ml. The erm(B) gene (macrolide-lincosamide-streptogramin B resistance phenotype) was detected in 36.4% (n = 74) of the isolates, which corresponded to 93.6% of erythromycin-intermediate and -resistant isolates, whereas the mef(A) gene (M phenotype [resistance to erythromycin and susceptibility to clindamycin and spiramycin without blunting]) was present in only 2.4% (n = 5) of the isolates. One of the latter isolates also carried erm(B). Interestingly, in one isolate for which the erythromycin MIC was 2 μg/ml, none of these resistance genes could be detected. Erythromycin MICs forS. pneumoniae erm(B)-positive isolates were higher (range, 0.5 to >64 μg/ml) than those for erm(B)- andmef(A)-negative isolates (range, 0.008 to 2 μg/ml). The corresponding values for telithromycin were lower for both groups, with ranges of 0.004 to 1 and 0.002 to 0.06 μg/ml, respectively. The erythromycin MIC was high for a large number oferm(B)-positive isolates, but the telithromycin MIC was low for these isolates. These results indicate the potential usefulness of telithromycin for the treatment of infections caused by erythromycin-susceptible and -resistant S. pneumoniaeisolates when macrolides are indicated.

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Distribution of macrolide resistance genes erm(B) and mef(A) among 160 penicillin-intermediate clinical isolates of Streptococcus pneumoniae isolated in Southern France

Pathologie Biologie ◽

10.1016/s0369-8114(01)00212-7 ◽

2001 ◽

Vol 49 (7) ◽

pp. 522-527 ◽

Cited By ~ 9

Author(s):

H Marchandin ◽

H Jean-Pierre ◽

E Jumas-Bilak ◽

L Isson ◽

B Drouillard ◽

...

Keyword(s):

Streptococcus Pneumoniae ◽

Resistance Genes ◽

Macrolide Resistance ◽

Clinical Isolates ◽

Southern France

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Macrolide Resistance by Ribosomal Mutation in Clinical Isolates of Streptococcus pneumoniae from the PROTEKT 1999-2000 Study

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.47.6.1777-1783.2003 ◽

2003 ◽

Vol 47 (6) ◽

pp. 1777-1783 ◽

Cited By ~ 71

Author(s):

D. J. Farrell ◽

S. Douthwaite ◽

I. Morrissey ◽

S. Bakker ◽

J. Poehlsgaard ◽

...

Keyword(s):

United States ◽

Streptococcus Pneumoniae ◽

The United States ◽

Resistance Mechanisms ◽

Macrolide Resistance ◽

Primer Extension ◽

Clinical Isolates ◽

23S Rrna ◽

Resistant Organism ◽

Rrna Methylation

ABSTRACT Sixteen (1.5%) of the 1,043 clinical macrolide-resistant Streptococcus pneumoniae isolates collected and analyzed in the 1999-2000 PROTEKT (Prospective Resistant Organism Tracking and Epidemiology for the Ketolide Telithromycin) study have resistance mechanisms other than rRNA methylation or efflux. We have determined the macrolide resistance mechanisms in all 16 isolates by sequencing the L4 and L22 riboprotein genes, plus relevant segments of the four genes for 23S rRNA, and the expression of mutant rRNAs was analyzed by primer extension. Isolates from Canada (n = 4), Japan (n = 3), and Australia (n = 1) were found to have an A2059G mutation in all four 23S rRNA alleles. The Japanese isolates additionally had a G95D mutation in riboprotein L22; all of these originated from the same collection center and were clonal. Three of the Canadian isolates were also clonal; the rest were not genetically related. Four German isolates had A2059G in one, two, and three 23S rRNA alleles and A2058G in two 23S rRNA alleles, respectively. An isolate from the United States had C2611G in three 23S rRNA alleles, one isolate from Poland had A2058G in three 23S rRNA alleles, one isolate from Turkey had A2058G in four 23S rRNA alleles, and one isolate from Canada had A2059G in two 23S rRNA alleles. Erythromycin and clindamycin resistance gradually increased with the number of A2059G alleles, whereas going from one to two mutant alleles caused sharp rises in the azithromycin, roxithromycin, and rokitamycin MICs. Comparisons of mutation dosage with rRNA expression indicates that not all alleles are equally expressed. Despite their high levels of macrolide resistance, all 16 isolates remained susceptible to the ketolide telithromycin (MICs, 0.015 to 0.25 μg/ml).

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