Activity of ceftobiprole against Streptococcus pneumoniae isolates exhibiting high-level resistance to ceftriaxone

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• 作者：Todd A. Daviesp> ; p>p>tdavies1@its.jnj.comp> ; Robert K. Flammp>1p> ; A. Simon Lynch
• 关键词：Penicillin-binding proteins ; murM ; ¦Â-Lactams ; Cephalosporins ; Serotypes
• 刊名：International Journal of Antimicrobial Agents
• 出版年：2012
• 出版时间：June, 2012
• 年：2012
• 卷：39
• 期：6
• 页码：534-538
• 全文大小：381 K

文摘

Tracking Resistance in the US Today (TRUST) 2008 surveillance data showed that 6 % of Streptococcus pneumoniae were non-susceptible to ceftriaxone [minimum inhibitory concentration (MIC) ? ¦Ìg/mL] and that 8 % of the ceftriaxone-non-susceptible isolates exhibited high-level resistance (MIC ?#xA0;8 ¦Ìg/mL). Here we describe the activity of ceftobiprole against ceftriaxone-resistant isolates and characterise the genotypic traits associated with resistance. Thirty isolates with ceftriaxone MICs ?#xA0;8 ¦Ìg/mL were analysed by sequencing of penicillin-binding protein (PBP) and murM genes. Sequencing of pbp1a, pbp2b and pbp2x showed nine PBP patterns, with the most common (n = 17) being: PBP1a T371S (STMK motif), P432T (SRNVP motif); PBP2b T446A (SSNT motif), A619G (KTGTA motif); and PBP2x T338A and M339F (STMK motif), L364F, I371T, R384G, M400T, L546V (LKSGT motif); six isolates had the same pattern without the PBP2b A619G change. For these 23 isolates, MICs were 8 ¦Ìg/mL for ceftriaxone, 4-8 ¦Ìg/mL for penicillin and 0.5-2 ¦Ìg/mL for ceftobiprole. The remaining seven isolates with higher MICs (ceftriaxone 8-32 ¦Ìg/mL, penicillin 4-32 ¦Ìg/mL and ceftobiprole 2-4 ¦Ìg/mL) had fewer PBP active-site motif substitutions. The majority of isolates (17/30) had murM alleles similar to the wild-type, whilst the rest had alleles reflecting a mosaic structure. No murM alleles were associated with higher MICs. Against these 30 isolates, ceftobiprole was 4-16-fold more active than ceftriaxone. Widely described PBP and MurM substitutions probably account for the high ceftriaxone MICs (8 ¦Ìg/mL) in the majority of isolates. However, seven isolates with ceftriaxone MICs of 8-32 ¦Ìg/mL had fewer PBP substitutions in active-site motifs, suggesting either that there is another resistance mechanism or that unique PBP mutations may contribute to high-level ¦Â-lactam resistance.