Resistance to Erythromycin and Telithromycin in Streptococcus pyogenes Isolates Obtained between 1999 and 2002 from Greek Children with Tonsillopharyngitis: Phenotypic and Genotypic Analysis

ABSTRACT Since the late 1990s, the prevalence of erythromycin-resistant Streptococcus pyogenes has significantly increased in several European countries. Between January 1999 and December 2002, 1,577 isolates of S. pyogenes were recovered from children with tonsillopharyngitis living in various areas of Western Greece. Erythromycin resistance was observed in 379 (24%) of the 1,577 isolates. All erythromycin-resistant strains along with 153 randomly selected erythromycin-susceptible S. pyogenes isolates were tested for their antimicrobial susceptibility, resistance phenotypes, and genotypes. Representative isolates underwent emm gene sequence typing. Isolates with reduced susceptibility to telithromycin (MIC, ≥2 μg/ml) were studied for multilocus sequence type, L22, L4, and 23S rRNA mutations. Of the total 379 erythromycin-resistant isolates, 193 (50.9%) harbored the mef(A) gene, 163 (43%) erm(A), 1 (0.3%) mef(A) plus erm(A), and 22 (5.8%) the erm(B) gene. Among the erythromycin-susceptible isolates, emm 1 (25%), emm 2 (12.5%), and emm 77 (12.5%) predominated. Furthermore, among the erythromycin-resistant isolates, emm 4 (30.6%), emm 28 (22.2%), and emm 77 (12.5%) prevailed. Resistance to telithromycin was observed in 22 (5.8%) of the erythromycin-resistant isolates. Sixteen (72.7%) of the 22 isolates appeared to be clonally related, since all of them belonged to emm type 28 and multilocus sequence type 52. One of the well-known mutations (T2166C) in 23S rRNA, as well as a new one (T2136C), was detected in erythromycin- and telithromycin-resistant isolates. High incidence of macrolide resistance and clonal spread of telithromycin resistance were the characteristics of the Greek S. pyogenes isolates obtained from 1999 to 2002.

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Two Distinct Genetic Elements Are Responsible forerm(TR)-Mediated Erythromycin Resistance in Tetracycline-Susceptible and Tetracycline-Resistant Strains of Streptococcus pyogenes

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01378-10 ◽

2011 ◽

Vol 55 (5) ◽

pp. 2106-2112 ◽

Cited By ~ 22

Author(s):

Andrea Brenciani ◽

Erika Tiberi ◽

Alessandro Bacciaglia ◽

Dezemona Petrelli ◽

Pietro E. Varaldo ◽

...

Keyword(s):

Streptococcus Pyogenes ◽

Integration Site ◽

Hot Spot ◽

The Other ◽

23S Rrna ◽

Erythromycin Resistance ◽

High Identity ◽

Content Type ◽

Genetic Elements ◽

Resistant Strains

ABSTRACTInStreptococcus pyogenes, inducible erythromycin (ERY) resistance is due to posttranscriptional methylation of an adenine residue in 23S rRNA that can be encoded either by theerm(B) gene or by the more recently describederm(TR) gene. Twoerm(TR)-carrying genetic elements, showing extensive DNA identities, have thus far been sequenced: ICE10750-RD.2 (∼49 kb) and Tn1806(∼54 kb), from tetracycline (TET)-susceptible strains ofS. pyogenesandStreptococcus pneumoniae, respectively. However, TET resistance, commonly mediated by thetet(O) gene, is widespread inerm(TR)-positiveS. pyogenes. In this study, 23S. pyogenesclinical strains witherm(TR)-mediated ERY resistance—3 TET susceptible and 20 TET resistant—were investigated. Twoerm(TR)-carrying elements sharing only a short, high-identityerm(TR)-containing core sequence were comprehensively characterized: ICESp1108 (45,456 bp) from the TET-susceptible strain C1 and ICESp2905 (65,575 bp) from the TET-resistant strain iB21. While ICESp1108 exhibited extensive identities to ICE10750-RD.2 and Tn1806, ICESp2905 showed a previously unreported genetic organization resulting from the insertion of separateerm(TR)- andtet(O)-containing fragments in a scaffold of clostridial origin. Transferability by conjugation of theerm(TR) elements from the same strains used in this study had been demonstrated in earlier investigations. Unlike ICE10750-RD.2 and Tn1806, which are integrated into anhsdMchromosomal gene, both ICESp1108 and ICESp2905 shared the chromosomal integration site at the 3′ end of the conservedrumgene, which is an integration hot spot for several mobile streptococcal elements. By using PCR-mapping assays,erm(TR)-carrying elements closely resembling ICESp1108 and ICESp2905 were shown in the other TET-susceptible and TET-resistant test strains, respectively.

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Molecular Basis of Macrolide Resistance inCampylobacterStrains Isolated from Poultry in South Korea

BioMed Research International ◽

10.1155/2018/4526576 ◽

2018 ◽

Vol 2018 ◽

pp. 1-9 ◽

Cited By ~ 3

Author(s):

Bai Wei ◽

Min Kang

Keyword(s):

Molecular Mechanisms ◽

Macrolide Resistance ◽

23S Rrna ◽

Rrna Gene ◽

Campylobacter Coli ◽

Erythromycin Resistance ◽

23S Rrna Gene ◽

Ribosomal Protein L22 ◽

Resistant Strains ◽

Azithromycin Resistance

We investigated the molecular mechanisms underlying macrolide resistance in 38 strains ofCampylobacterisolated from poultry. Twenty-seven strains were resistant to azithromycin and erythromycin, five showed intermediate azithromycin resistance and erythromycin susceptibility, and six showed azithromycin resistance and erythromycin susceptibility. FourCampylobacter jejuniand sixCampylobacter colistrains had azithromycin MICs which were 8–16 and 2–8-fold greater than those of erythromycin, respectively. The A2075G mutation in the 23S rRNA gene was detected in 11 resistant strains with MICs ranging from 64 to ≥ 512μg/mL. Mutations including V137A, V137S, and a six-amino acid insertion (114-VAKKAP-115) in ribosomal protein L22 were detected in theC. jejunistrains. Erythromycin ribosome methylase B-erm(B) was not detected in any strain. All strains except three showed increased susceptibility to erythromycin with twofold to 256-fold MIC change in the presence of phenylalanine arginine ß-naphthylamide (PAßN); the effects of PAßN on azithromycin MICs were limited in comparison to those on erythromycin MICs, and 13 strains showed no azithromycin MIC change in the presence of PAßN. Differences between azithromycin and erythromycin resistance and macrolide resistance phenotypes and genotypes were observed even in highly resistant strains. Further studies are required to better understand macrolide resistance inCampylobacter.

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In Vitro Activity of CEM-101 against Streptococcus pneumoniae and Streptococcus pyogenes with Defined Macrolide Resistance Mechanisms

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01123-09 ◽

2009 ◽

Vol 54 (1) ◽

pp. 230-238 ◽

Cited By ~ 46

Author(s):

Pamela McGhee ◽

Catherine Clark ◽

Klaudia M. Kosowska-Shick ◽

Kensuke Nagai ◽

Bonifacio Dewasse ◽

...

Keyword(s):

Streptococcus Pyogenes ◽

Bacterial Species ◽

Resistance Mechanisms ◽

Macrolide Resistance ◽

23S Rrna ◽

Resistant Strains ◽

Resistant Mutants ◽

The One ◽

Selection Of

ABSTRACT CEM-101 had MIC ranges of 0.002 to 0.016 μg/ml against macrolide-susceptible pneumococci and 0.004 to 1 μg/ml against macrolide-resistant phenotypes. Only 3 strains with erm(B), with or without mef(A), had CEM-101 MICs of 1 μg/ml, and 218/221 strains had CEM-101 MICs of ≤0.5 μg/ml. CEM-101 MICs were as much as 4-fold lower than telithromycin MICs against all strains. For Streptococcus pyogenes, CEM-101 MICs ranged from 0.008 to 0.03 μg/ml against macrolide-susceptible strains and from 0.015 to 1 μg/ml against macrolide-resistant strains. Against erm(B) strains, erythromycin, azithromycin, and clarithromycin MICs were 32 to >64 μg/ml, while 17/19 strains had telithromycin MICs of 4 to 16 μg/ml; CEM-101 MICs were 0.015 to 1 μg/ml. By comparison, erm(A) and mef(A) strains had CEM-101 MICs of 0.015 to 0.5 μg/ml, clindamycin and telithromycin MICs of ≤1 μg/ml, and erythromycin, azithromycin, and clarithromycin MICs of 0.5 to >64 μg/ml. Pneumococcal multistep resistance studies showed that although CEM-101 yielded clones with higher MICs for all eight strains tested, seven of eight strains had clones with CEM-101 MICs that rose from 0.004 to 0.03 μg/ml (parental strains) to 0.06 to 0.5 μg/ml (resistant clones); for only one erm(B) mef(A) strain with a parental MIC of 1 μg/ml was there a resistant clone with a MIC of 32 μg/ml, with no detectable mutations in the L4, L22, or 23S rRNA sequence. Among two of five S. pyogenes strains tested, CEM-101 MICs rose from 0.03 to 0.25 μg/ml, and only for the one strain with erm(B) did CEM-101 MICs rise from 1 to 8 μg/ml, with no changes occurring in any macrolide resistance determinant. CEM-101 had low MICs as well as low potential for the selection of resistant mutants, independent of bacterial species or resistance phenotypes in pneumococci and S. pyogenes.

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Phenotypes and Genotypes of Erythromycin-ResistantStreptococcus pyogenes Strains in Italy and Heterogeneity of Inducibly Resistant Strains

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.43.8.1935 ◽

1999 ◽

Vol 43 (8) ◽

pp. 1935-1940 ◽

Cited By ~ 129

Author(s):

Eleonora Giovanetti ◽

Maria Pia Montanari ◽

Marina Mingoia ◽

Pietro Emanuele Varaldo

Keyword(s):

Streptococcus Pyogenes ◽

Tetracycline Resistance ◽

Erythromycin Resistance ◽

Testing Conditions ◽

Resistant Strains ◽

Methylase Gene ◽

Set Up ◽

Susceptibility Patterns ◽

Disk Test ◽

Level Resistance

ABSTRACT A total of 387 clinical strains of erythromycin-resistant (MIC, ≥1 μg/ml) Streptococcus pyogenes, all isolated in Italian laboratories from 1995 to 1998, were examined. By the erythromycin-clindamycin double-disk test, 203 (52.5%) strains were assigned to the recently described M phenotype, 120 (31.0%) were assigned to the inducible macrolide, lincosamide, and streptogramin B resistance (iMLS) phenotype, and 64 (16.5%) were assigned to the constitutive MLS resistance (cMLS) phenotype. The inducible character of the resistance of the iMLS strains was confirmed by comparing the clindamycin MICs determined under normal testing conditions and those determined after induction by pregrowth in 0.05 μg of erythromycin per ml. The MICs of erythromycin, clarithromycin, azithromycin, josamycin, spiramycin, and the ketolide HMR3004 were then determined and compared. Homogeneous susceptibility patterns were observed for the isolates of the cMLS phenotype (for all but one of the strains, HMR3004 MICs were 0.5 to 8 μg/ml and the MICs of the other drugs were >128 μg/ml) and those of the M phenotype (resistance only to the 14- and 15-membered macrolides was recorded, with MICs of 2 to 32 μg/ml). Conversely, heterogeneous susceptibility patterns were observed in the isolates of the iMLS phenotype, which were subdivided into three distinct subtypes designated iMLS-A, iMLS-B, and iMLS-C. The iMLS-A strains (n = 84) were highly resistant to the 14-, 15-, and 16-membered macrolides and demonstrated reduced susceptibility to low-level resistance to HMR3004. The iMLS-B strains (n = 12) were highly resistant to the 14- and 15-membered macrolides, susceptible to the 16-membered macrolides (but highly resistant to josamycin after induction), and susceptible to HMR3004 (but intermediate or resistant after induction). The iMLS-C strains (n = 24) had lower levels of resistance to the 14- and 15-membered macrolides (with erythromycin MICs increasing two to four times after induction), were susceptible to the 16-membered macrolides (but resistant to josamycin after induction), and remained susceptible to HMR3004, also after induction. The erythromycin resistance genes in 100 isolates of the different groups were investigated by PCR. All cMLS and iMLS-A isolates tested had theermAM (ermB) gene, whereas all iMLS-B and iMLS-C isolates had the ermTR gene (neither methylase gene was found in isolates of other groups). The M isolates had only the macrolide efflux (mefA) gene, which was also found in variable proportions of cMLS, iMLS-A, iMLS-B, and iMLS-C isolates. The three iMLS subtypes were easily differentiated by a triple-disk test set up by adding a josamycin disk to the erythromycin and clindamycin disks of the conventional double-disk test. Tetracycline resistance was not detected in any isolate of the iMLS-A subtype, whereas it was observed in over 90% of both iMLS-B and iMLS-C isolates.

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Molecular epidemiology of macrolide resistant Group A streptococci from Puducherry, India

The Journal of Infection in Developing Countries ◽

10.3855/jidc.9132 ◽

2017 ◽

Vol 11 (09) ◽

pp. 679-683 ◽

Cited By ~ 1

Author(s):

Tintu Abraham ◽

Sujatha Sistla

Keyword(s):

Streptococcus Pyogenes ◽

Macrolide Resistance ◽

Streptococcal Infections ◽

Genetic Determinants ◽

Erythromycin Resistance ◽

Group A ◽

Macrolide Resistance Gene ◽

Resistant Group ◽

Resistant Strains ◽

Resistance Rates

Introduction: In penicillin allergic patients, macrolides are the most commonly used antibiotics for treating streptococcal infections, irrespective of the higher resistance rates. The objective of this study was to evaluate the comparative prevalence, phenotypes, and genetic determinants of macrolide resistance and associated emm types among different clinical isolates of Streptococcus pyogenes. Methodology: A total of 173 Streptococcus pyogenes isolates were examined for macrolide resistance phenotype by double-disc test, resistance determinants by multiplex PCR and emm genotyping. Results: Erythromycin resistance was found in 51.4% of isolates, with MIC90 ≥ 256 µg/mL Inducible phenotype was commonly found (iMLS, 67.4%) followed by the M phenotype (32.5%). Among these isolates, 65.1% harboured ermB and 32.5% mefA as sole macrolide resistance gene, whereas presence of both, ermB plus mefA was observed in 2.2% cases. The most common types among resistant strains were emm63 (11.2%), emm44 (6.7%), emm42 (5.6%), and emm75.3, emm82, emm85, emm92, emm111.1 (4.4% each). Statistically significant association was observed between emm63, emm44 and erythromycin resistance (p ≤ 0.05). Association of these emm types and macrolide resistance have not been reported earlier. Conclusion: Higher macrolide resistance in this study can be attributed to overuse and misuse of this antibiotic. These findings indicate that macrolides should not be empirically used for treating severe streptococcal infections.

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The global prevalence ptxP3 lineage of Bordetella pertussis was rare in young Children with the Co-purified aPV vaccination: a 5 years retrospective study

10.21203/rs.2.23947/v1 ◽

2020 ◽

Author(s):

Zengguo Wang ◽

Yang Luan ◽

Quanli Du ◽

Chang Shu ◽

Xiaokang Peng ◽

...

Keyword(s):

Cohort Study ◽

Retrospective Study ◽

Vaccination Status ◽

23S Rrna ◽

Erythromycin Resistance ◽

Antibiotic Susceptibility Test ◽

Significant Difference ◽

Resistant Strains ◽

The Difference ◽

Additional Antigen

Abstract Background: The global prevalent ptxP3 strains varies from about 10% to about 50% of circulating B. pertussis population in different areas of China. Methods To investigate the difference of vaccination status between different genotypes in the circulating B. pertussis after 10 years of acellular pertussis vaccine (aPV) used in China. The nasopharyngeal swabs and isolates of B. pertussis from these patients were used to perform genotyping of antigen genes. We use antibiotic susceptibility test against erythromycin and sequencing methods for site 2047 of 23S rRNA to determine the resistance status. Results The ptxP1 allele with erythromycin resistant strains infection (total of 449 samples) consisted of 84.70% to 96.70% from 2012 to 2016. Only 2 of the 21 ptxP3 strains infected in children vaccinated with co-purified aPV, that showed a significant difference between the ptxP1 strains does (χ 2 =6.87, P=0.032). Conclusions The ptxP1 allele with erythromycin resistant B. pertussis was steadily increased in Xi’an, China from 2012 to 2016, where co-purified aPV was prevalence used . We assumed that the co-purified aPV might protect against ptxP3 strains more efficient, which generated a rare chance for ptxP3 strains to be under the antibiotic pressure and further developed to be erythromycin resistance. A further cohort study and the mechanisms of the additional antigen proteins of co-purified aPV protected against B. pertussis should be consideration.

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Antimicrobial Resistance Profiles and Macrolide Resistance Mechanisms of Campylobacter coli Isolated from Pigs and Chickens

Microorganisms ◽

10.3390/microorganisms9051077 ◽

2021 ◽

Vol 9 (5) ◽

pp. 1077

Author(s):

Ji-Hyun Choi ◽

Dong Chan Moon ◽

Abraham Fikru Mechesso ◽

Hee Young Kang ◽

Su-Jeong Kim ◽

...

Keyword(s):

Nalidixic Acid ◽

Ribosomal Proteins ◽

Resistance Mechanisms ◽

23S Rrna ◽

Considerable Proportion ◽

Rrna Gene ◽

Campylobacter Coli ◽

Erythromycin Resistance ◽

Public Health Hazards ◽

Resistance Rates

We identified 1218 Campylobacter coli isolates from fecal and carcass samples of pigs (n = 643) and chickens (n = 575) between 2010 and 2018. About 99% of the isolates were resistant to at least one antimicrobial agent. The isolates exhibited high resistance rates (>75%) to ciprofloxacin, nalidixic acid, and tetracycline. Azithromycin and erythromycin resistance rates were the highest in isolates from pigs (39.7% and 39.2%, respectively) compared to those of chickens (15.8% and 16.3%, respectively). Additionally, a low-to-moderate proportion of the isolates were resistant to florfenicol, gentamicin, clindamycin, and telithromycin. Multidrug resistance (MDR) was found in 83.1% of the isolates, and profiles of MDR usually included ciprofloxacin, nalidixic acid, and tetracycline. We found point mutation (A2075G) in domain V of the 23S rRNA gene in the majority of erythromycin-resistant isolates. Multilocus sequence typing of 137 erythromycin-resistant C. coli isolates revealed 37 previously reported sequence types (STs) and 8 novel STs. M192I, A103VI, and G74A substitutions were frequently noted in the ribosomal proteins L4 or L22. Further, we identified a considerable proportion (>90%) of erythromycin-resistant isolates carrying virulence factor genes: flaA, cadF, ceuE, and VirB. The prudent use of antimicrobials and regular microbiological investigation in food animals will be vital in limiting the public health hazards of C. coli in Korea.

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