Macrolide Resistance Phenotypes and Genotypes in French Clinical Isolates of Streptococcus pneumoniae

Angot, P.; Vergnaud, M.; Auzou, Michel; Leclercq, Roland

doi:10.1007/pl00011229

Cited by 48 publications

(22 citation statements)

References 18 publications

(18 reference statements)

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“…The predominance among erythromycin-resistant pneumococci of the isolates carrying the erm(AM) gene over those carrying the mef(E) gene observed in this study (76.5 versus 23.5%) is consistent with the results of other recent studies from European countries (2,3,13,16,25), South Africa (11), and Japan (15). It is worth noting that in some European reports the rate of isolates carrying the mef(E) gene was particularly low (Ͻ10%) (2, 3, 13, 16).…”

Section: Discussionsupporting

confidence: 93%

Differentiation of Resistance Phenotypes among Erythromycin-Resistant Pneumococci

et al. 2001

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Laboratory differentiation of erythromycin resistance phenotypes is poorly standardized for pneumococci. In this study, 85 clinical isolates of erythromycin-resistant (MIC > 1 g/ml) Streptococcus pneumoniae were tested for the resistance phenotype by the erythromycin-clindamycin double-disk test (previously used to determine the macrolide resistance phenotype in Streptococcus pyogenes strains) and by MIC induction tests, i.e., by determining the MICs of macrolide antibiotics without and with pre-exposure to 0.05 g of erythromycin per ml. By the double-disk test, 65 strains, all carrying the erm(AM) determinant, were assigned to the constitutive macrolide, lincosamide, and streptogramin B resistance (cMLS) phenotype, and the remaining 20, all carrying the mef(E) gene, were assigned to the recently described M phenotype; an inducible MLS resistance (iMLS) phenotype was not found. The lack of inducible resistance to clindamycin was confirmed by determining clindamycin MICs without and with pre-exposure to subinhibitory concentrations of erythromycin. In macrolide MIC and MIC-induction tests, whereas homogeneous susceptibility patterns were observed among the 20 strains assigned to the M phenotype by the double-disk test, two distinct patterns were recognized among the 65 strains assigned to the cMLS phenotype by the same test; one pattern (n ‫؍‬ 10; probably that of the true cMLS isolates) was characterized by resistance to rokitamycin also without induction, and the other pattern (n ‫؍‬ 55; designated the iMcLS phenotype) was characterized by full or intermediate susceptibility to rokitamycin without induction turning to resistance after induction, with an MIC increase by more than three dilutions. A triple-disk test, set up by adding a rokitamycin disk to the erythromycin and clindamycin disks of the double-disk test, allowed the easy differentiation not only of pneumococci with the M phenotype from those with MLS resistance but also, among the latter, of those of the true cMLS phenotype from those of the iMcLS phenotype. While distinguishing MLS from M resistance in pneumococci is easily and reliably achieved, the differentiation of constitutive from inducible MLS resistance is far more uncertain and is strongly affected by the antibiotic used to test inducibility.Ribosomal target site modification due to methylases encoded by erm class genes is the most common and extensively investigated mechanism of erythromycin resistance in streptococci (28). It has long been known that ribosome methylation causes reduced binding of and coresistance to macrolide, lincosamide, and streptogramin B (MLS) antibiotics and that in streptococci MLS resistance can be expressed either constitutively (cMLS phenotype) or inducibly (iMLS phenotype) (9,12,27). Only recently has a macrolide efflux mechanism been described for streptococci (24), in which it is associated with a new resistance pattern (M phenotype) characterized by resistance to 14-and 15-membered macrolides and susceptibility to 16-membered macrolides, lincosamides, and s...

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Section: Discussionsupporting

confidence: 93%

Differentiation of Resistance Phenotypes among Erythromycin-Resistant Pneumococci

et al. 2001

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“…The distribution of phenotypes and genotypes of erythromycin-resistant pneumococci may vary considerably from area to area. 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).…”

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confidence: 67%

Phenotypes and Genotypes of Erythromycin-Resistant Pneumococci in Italy

et al. 2003

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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...

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“…The MLS B phenotype was most common among noninvasive isolates. These observations are consistent with the results of studies in other European countries, where MLS B -and M-type isolates predominate among noninvasive and invasive strains, respectively (3,8,24,35). This distribution of different resistance phenotypes may be a clonal phenomenon, as observed in this study.…”

Section: Discussionsupporting

confidence: 93%

Molecular Epidemiology of Macrolide-Resistant Isolates of Streptococcus pneumoniae Collected from Blood and Respiratory Specimens in Norway

et al. 2005

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Norway has a low prevalence of antimicrobial resistance, including macrolide-resistant Streptococcus pneumoniae (MRSP). In a nationwide surveillance program, a total of 2,200 S. pneumoniae isolates were collected from blood cultures and respiratory tract specimens. Macrolide resistance was detected in 2.7%. M-type macrolide resistance was found in 60% of resistant isolates, and these were mainly mef(A)-positive, serotype-14 invasive isolates. The erm(B)-encoded macrolide-lincosamide-streptogramin B (MLS B ) type dominated among the noninvasive isolates. One strain had an A2058G mutation in the 23S rRNA gene. Coresistance to other antibiotics was seen in 96% of the MLS B -type isolates, whereas 92% of the M-type isolates were susceptible to other commonly used antimicrobial agents. Serotypes 14, 6B, and 19F accounted for 84% of the macrolideresistant isolates, with serotype 14 alone accounting for 67% of the invasive isolates. A total of 29 different sequence types (STs) were detected by multilocus sequence typing. Twelve STs were previously reported international resistant clones, and 75% of the macrolide-resistant isolates had STs identical or closely related to these clones. Eleven isolates displayed 10 novel STs, and 7/11 of these "Norwegian strains" coexpressed MLS B and tetracycline resistance, indicating the presence of Tn1545. The invasive serotype-14 isolates were all classified as ST9 or single-locus variants of this clone. ST9 is a mef-positive M-type clone, commonly known as England 14 -9, reported from several European countries. These observations suggest that the import of major international MRSP clones and the local spread of Tn1545 are the major mechanisms involved in the evolution and dissemination of MRSP in Norway.Antimicrobial resistance is an increasing problem worldwide, and several countries have implemented surveillance systems in recent years. The Norwegian surveillance program for antimicrobial resistance (NORM) was established in 1999 and has reported yearly on the epidemiology of antimicrobial resistance and the usage of antimicrobial agents. Antimicrobial susceptibility data on common pathogens such as Escherichia coli, Klebsiella spp., Haemophilus influenzae, Staphylococcus aureus, Streptococcus pneumoniae, and Streptococcus pyogenes confirm that antimicrobial resistance is still a limited problem in Norway (28). The prevalence of macrolide-resistant S. pneumoniae (MRSP) has increased dramatically in several European countries (16) but is still relatively low in Northern Europe (31, 34). In Norway, macrolide resistance in S. pneumoniae blood culture isolates has increased from 2.4% in 2000 to 4.8% in 2002 and 6.0% in 2003 (28). Macrolides are used as second-line alternatives in the treatment of respiratory tract infections, because the prevalence of non-penicillin-susceptible S. pneumoniae is below 3% in Norway. They are recommended only for patients who are allergic to penicillin or are suspected of having atypical pneumonia. Thus, the increase in MRSP is of clinical concern as we...

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Macrolide Resistance Phenotypes and Genotypes in French Clinical Isolates of Streptococcus pneumoniae

Cited by 48 publications

References 18 publications

Differentiation of Resistance Phenotypes among Erythromycin-Resistant Pneumococci

Differentiation of Resistance Phenotypes among Erythromycin-Resistant Pneumococci

Phenotypes and Genotypes of Erythromycin-Resistant Pneumococci in Italy

Molecular Epidemiology of Macrolide-Resistant Isolates of Streptococcus pneumoniae Collected from Blood and Respiratory Specimens in Norway

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