Molecular surveillance of macrolide, tetracycline and quinolone resistance mechanisms in 1191 clinical European Streptococcus pneumoniae isolates

Schmitz, Franz‐Josef; Perdikouli, Mirella; Beeck, Andreas; Verhoef, J.; Fluit, Ad C.

doi:10.1016/s0924-8579(01)00427-7

Cited by 50 publications

(34 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…As regards M-type isolates, recent Italian rates ranging between one-third (in the present study) and one-fifth (6,13,20,23) of erythromycin-resistant isolates contrast with the complete absence of M-type pneumococci in recent surveys carried out in a country as close as France (1,10). Rates of M-type isolates similar to those found in Italy have been reported in Greece (35), in a multinational European study (30), in Georgia (United States) (11), and in Taiwan (17); lower rates have been reported in Spain (32), Belgium (8), Central and Eastern European countries (24), and South Africa (22); higher rates have been reported in Germany (27), Japan (26), Canada (16), and in a nationwide study in the United States (9). mef(A) and mef(E) genes in M-type pneumococci.…”

supporting

confidence: 68%

Phenotypes and Genotypes of Erythromycin-Resistant Pneumococci in Italy

et al. 2003

View full text Add to dashboard Cite

Of 120 erythromycin-resistant pneumococci isolated in Italian hospitals, 39 (32.5%) were M-type isolates, carrying the mef gene alone. The mef gene was also detected, together with erm(AM), in one constitutively resistant isolate and in five isolates of the partially inducible phenotype. Among the 45 mef-positive isolates, 25 (55.6%) carried mef(A) and 20 (44.4%) carried mef(E) as observed from PCR-restriction fragment length polymorphism analysis of a 1,743-bp amplicon. The same result was obtained by a similar method applied to a more common 348-bp amplicon.Macrolide resistance in Streptococcus pneumoniae is due to either target site modification-generally depending on a posttranscriptional modification of 23S rRNA mediated by ermclass methylases (39) or less often on mutations in 23S rRNA or ribosomal proteins (7, 37, 38)-or active efflux. In this study, 120 erythromycin-resistant pneumococci were investigated for macrolide resistance phenotypes and genotypes, with emphasis on the discrimination between mef(A) and mef(E).Efflux-mediated resistance. The efflux mechanism, which reduces the intracellular antibiotic concentration to subtoxic levels (40), is associated with a resistance pattern (M phenotype) characterized by resistance, among macrolides-lincosamidesstreptogramin B (MLS), only to 14-and 15-membered macrolides, usually at a low level (34). M-type resistance is mediated by the mef gene, two variants of which are conventionally described: one, mef(A), originally discovered in Streptococcus pyogenes (5), and the other, mef(E), originally discovered in S. pneumoniae (36). Considering that the mef genes are detected mostly by a PCR method unable to distinguish between the two variants (33) and that mef(A) and mef(E) have 90% identity (36), they are regarded as a single gene class, designated mef(A) (28). However, mef(A) and mef(E) have recently been shown to be carried by different genetic elements in S. pneumoniae, which are inserted at different sites in the chromosome. Both elements carry, adjacent to mef, an open reading frame showing homology to the msr(A) gene associated with macrolide efflux in Staphylococcus aureus (6,12,29). Due to a number of important differences in the properties of mef(A)-and mef(E)-carrying pneumococci, it has been recommended that the distinction between the two genes be maintained (6).Bacterial strains and typing. The 120 erythromycin-resistant pneumococci studied (for which the MIC of erythromycin was Ն1 g/ml) were independent isolates, collected from several laboratories throughout Italy between 1999 and 2002. All were clinical strains, isolated from a variety of clinical specimens (upper respiratory tract material, sputum, blood, cerebrospinal fluid). Multiple isolates from the same patient were excluded.Strain identification was confirmed in our laboratory by conventional tests such as susceptibility to optochin and solubility in bile and by employing the API system (BioMérieux, Marcyl'Etoile, France). Serotyping, done by the capsular swelling test using specific anti...

show abstract

supporting

confidence: 68%

Phenotypes and Genotypes of Erythromycin-Resistant Pneumococci in Italy

et al. 2003

View full text Add to dashboard Cite

show abstract

“…To our knowledge, in Europe only the tet(M) gene has been detected so far in pneumococci (15,45). The analysis of the tet(M)-carrying mobile elements revealed their remarkable diversity in the population studied.…”

Section: Discussionmentioning

confidence: 89%

Clonal Diversity and Resistance Mechanisms in Tetracycline-Nonsusceptible Streptococcus pneumoniae Isolates in Poland

Izdebski

Sadowy

Fiett

et al. 2007

Antimicrob Agents Chemother

View full text Add to dashboard Cite

The frequency of tetracycline resistance in Streptococcus pneumoniae isolates in Poland is one of the highest in Europe. The aim of this study was to analyze the clonal diversity and resistance determinants of tetracyclinenonsusceptible S. pneumoniae isolates identified in Poland and to investigate the effect of tetracycline resistance on their susceptibilities to tigecycline, doxycycline, and minocycline. We have analyzed 866 pneumococcal isolates collected from 1998 to 2003 from patients with respiratory tract diseases, and 242 of these (27.9%) were found to be resistant to tetracycline. All of the resistant isolates were characterized by testing of their susceptibilities to other antimicrobials, serotyping, pulsed-field gel electrophoresis (PFGE), and identification of tetracycline resistance genes and transposons. Selected isolates representing the main PFGE types were analyzed by multilocus sequence typing. Among the isolates investigated, 27 serotypes and 146 various PFGE patterns, grouped into 90 types, were discerned. The most common PFGE type, corresponding to serotype 19F and sequence type 423, was represented by 22.3% of all of the tetracycline-resistant isolates. The tet(M) gene was the sole resistance gene in the group of isolates studied, and in over 96% of the isolates, the Tn916 family of tet(M)-containing conjugative transposons was detected. Several isolates contained specific variants of the transposons, the Tn1545-like, Tn3872-like, or Tn2009-like element. The correlation between the MICs of tetracycline, doxycycline, and minocycline was revealed, whereas no cross-resistance to tetracycline and tigecycline was observed.

show abstract

“…There was evidence of the clonal spread of these mechanisms, but only within the same center and not between centers in the same country or between countries. Although the 1.5% incidence of these mechanisms is relatively low, they were completely absent from isolates analyzed in a comparable study conducted 3 years ago (18). Testing of macrolide-resistant S. pneumoniae isolates remains in progress to monitor whether there is an increase in the prevalence and spread of this form of macrolide resistance.…”

Section: Discussionmentioning

confidence: 98%

“…This would suggest that acquisition of resistance caused by mutation is a relatively recent event, perhaps due to the selective pressure of increased levels of exposure to macrolides in recent years. In a large European surveillance study conducted from 1997 to 1999 (with 1,191 erythromycin A-resistant S. pneumoniae isolates), no isolates with ribosomal mutations were found (18). It will be interesting to monitor the prevalence of these mutations in future years of the PROTEKT study.…”

Section: Discussionmentioning

confidence: 99%

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

Farrell

Douthwaite

Morrissey

et al. 2003

Antimicrob Agents Chemother

103

View full text Add to dashboard Cite

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 g/ml).Macrolide, lincosamide, and streptogramin B (MLS B ) resistance in Streptococcus pneumoniae occurs either by modification of the drug-binding site or by active efflux of the drug. Target modification is usually the result of dimethylation of the adenine residue at position 2058 on the 23S rRNA by a methylase enzyme (30). In S. pneumoniae, Erm(B) [encoded by the erm(B) gene] is the enzyme mostly responsible (7, 30), although, more rarely, a methylase encoded by the erm(A) subclass erm(TR) gene is implicated (7,23).In vitro studies have demonstrated that target modification can also be achieved via mutations in domains II and V of 23S rRNA and in the genes encoding riboproteins L4 and L22 and can confer macrolide, lincosamide, streptogramin, and ketolide resistance (2, 24). Although previous reports are rare, such mutations have been found in MLS B -resistant clinical isolates (3,14,25). However, until now there have been no studies on the prevalence and epidemiology of these types of mutations in clinical isolates on a worldwide scale.PROTEKT (Prospective Resistant Organism Tracking and Epidemiology for the Ketolide Telithromycin) is a longitudinal, global, multicenter surveillance study of respiratory tract pathogens. We screened all macrolide-resistant S. pneumoniae isolat...

show abstract

Molecular surveillance of macrolide, tetracycline and quinolone resistance mechanisms in 1191 clinical European Streptococcus pneumoniae isolates

Cited by 50 publications

References 15 publications

Phenotypes and Genotypes of Erythromycin-Resistant Pneumococci in Italy

Phenotypes and Genotypes of Erythromycin-Resistant Pneumococci in Italy

Clonal Diversity and Resistance Mechanisms in Tetracycline-Nonsusceptible Streptococcus pneumoniae Isolates in Poland

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

Contact Info

Product

Resources

About