<i>Streptococcus pneumoniae</i>
            Isolates Resistant to Telithromycin

Rantala, Merja; Haanperä-Heikkinen, Marjo; Lindgren, Marianne; Seppälä, Helena; Huovinen, Pentti; Jalava, Jari

doi:10.1128/aac.50.5.1855-1858.2006

Cited by 17 publications

(7 citation statements)

References 23 publications

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“…However, safety issues have limited the clinical utility of this drug. Additionally, when the free area under the curve (AUC)/MIC ratio of telithromycin against macrolide-resistant pneumococci was examined carefully, even with low MICs, it could be seen that the number was not significantly above 25; thus, resistance was predicted, and this has indeed been the case, as evidenced by recent publications (25).…”

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confidence: 87%

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

McGhee

Clark

Kosowska-Shick

et al. 2010

Antimicrob Agents Chemother

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CEM-101 had MIC ranges of 0.002 to 0.016 g/ml against macrolide-susceptible pneumococci and 0.004 to 1 g/ml against macrolide-resistant phenotypes. Only 3 strains with erm(B), with or without mef(A), had CEM-101 MICs of 1 g/ml, and 218/221 strains had CEM-101 MICs of <0.5 g/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 g/ml against macrolide-susceptible strains and from 0.015 to 1 g/ml against macrolide-resistant strains. Against erm(B) strains, erythromycin, azithromycin, and clarithromycin MICs were 32 to >64 g/ml, while 17/19 strains had telithromycin MICs of 4 to 16 g/ml; CEM-101 MICs were 0.015 to 1 g/ml. By comparison, erm(A) and mef(A) strains had CEM-101 MICs of 0.015 to 0.5 g/ml, clindamycin and telithromycin MICs of <1 g/ml, and erythromycin, azithromycin, and clarithromycin MICs of 0.5 to >64 g/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 g/ml (parental strains) to 0.06 to 0.5 g/ml (resistant clones); for only one erm(B) mef(A) strain with a parental MIC of 1 g/ml was there a resistant clone with a MIC of 32 g/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 g/ml, and only for the one strain with erm(B) did CEM-101 MICs rise from 1 to 8 g/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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confidence: 87%

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

McGhee

Clark

Kosowska-Shick

et al. 2010

Antimicrob Agents Chemother

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“…In our previous study, we described the presence of heterogeneous telithromycin resistance that was associated with the erm(B) gene in a Finnish pneumococcal collection in 2002 (47). That type of telithromycin resistance was also observed in nine erm(B) isolates in this study.…”

Section: Discussionmentioning

confidence: 90%

“…According to an international longitudinal study, started in 1999, globally less than 1% of pneumococci are nonsusceptible to this agent, and no increasing trend was detected by 2005 (23). However, that study used the CLSI broth microdilution method, which, in our experience, does not favor the detection of this resistance type (47). The significance of this type of resistance is not clear, but it can offer an advantage in the presence of antimicrobial pressure favoring the selection of telithromycin-resistant pneumococci.…”

Section: Discussionmentioning

confidence: 93%

Temporal Trends of Antimicrobial Resistance and Clonality of Invasive Streptococcus pneumoniae Isolates in Finland, 2002 to 2006

Siira

Rantala

Jalava

et al. 2009

Antimicrob Agents Chemother

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The antimicrobial resistance of Streptococcus pneumoniae, or pneumococcus, is a growing global problem. In our study, 3,571 invasive pneumococcal isolates, recovered from blood and cerebrospinal fluid samples from patients in Finland between the years 2002 and 2006, showed an increase in erythromycin nonsusceptibility from 16% to 28% (P < 0.0001) over the 5-year study period, as well as a doubling of penicillin nonsusceptibility from 8% to 16% (P < 0.0001). Erythromycin nonsusceptibility increased especially in isolates derived from 0-to 2-year-old children and was 46% for this age group in 2006. Although multiresistance, defined as nonsusceptibility to penicillin, erythromycin, and tetracycline, was fairly rare (5.1% in 2006), 38% of the erythromycin-nonsusceptible isolates were also penicillin nonsusceptible, while 74% of the penicillin-nonsusceptible isolates were nonsusceptible to erythromycin. In contrast to the situation in continental Europe, but mirroring that in North America, the most frequent macrolide resistance determinant carried by 56% of the tested macrolide-resistant pneumococci was the mef gene. Serotypes 14, 9V, 19A, 6B, and 19F were most frequently nonsusceptible to erythromycin or penicillin. The penicillin-resistant invasive isolates (n ‫؍‬ 88) were genotyped by multilocus sequence typing, which revealed the presence of 25 sequence types, 9 of which were novel. The majority of the isolates were related to one of several globally disseminated penicillin-or multiresistant clones, most importantly the rlrA adhesion pilus carrying clones Spain 9V ST156 and Taiwan 19F ST236. The penicillin-resistant pneumococcal population in Finland is therefore a combination of internationally recognized genotypes as well as novel ones.

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“…Our results indicate that pneumococci with heterogeneous TEL resistance can be found in other countries, because many of our strains belonged to global clones. However, this resistance type is difficult to detect using the dilution method (8). We recommend that routine testing of TEL susceptibility of pneumococci be done with the disc diffusion method in a 5%-CO 2 atmosphere, especially in areas where erm(B) is a common resistance mechanism.…”

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confidence: 99%

“…In this resistance type, separate colonies grew inside the inhibition zone around the TEL disk in a disk diffusion test (8). In this study we investigated the molecular epidemiology of these 26 isolates and compared them to erm(B)-positive but TEL-susceptible (Tel s ) pneumococci (n ϭ 66) (9).…”

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confidence: 99%