FARRELL DJ, MORRISSEY I, BAKKER S, BUCKRIDGE S, BORGER J, FELMINGHAM D; Interscience Conference on Antimicrobial Agents and Chemotherapy (43rd: 2003: Chicago, Ill.).

Abstr Intersci Conf Antimicrob Agents Chemother Intersci Conf Antimicrob Agents Chemother. 2003 Sep 14-17; 43: abstract no. C2-69.

GR Micro Limited, London, United Kingdom.

BACKGROUND: Target modifications by ribosomal mutation of key sites in 23S rRNA and the riboproteins L4 and L22 are known to cause MAC[R] in SPN. The aim of this study was to investigate the global prevalence of such mutations and their in vitro effect on antimicrobials targeting the bacterial ribosome. METHODS: Isolates of SPN were collected worldwide as part of the PROTEKT studies (Global 1999-2002 and US 2000-2001). MICs were determined using NCCLS methodology. 23S rRNA, L4 and L22 riboprotein genes were amplified and sequenced in MAC[R] isolates negative for methylase and efflux genes. RESULTS: From 23,543 isolates of SPN collected, 86 (0.37%) MAC[R] isolates were negative for methylase and efflux mechanisms. 61/86 isolates had the following mutations that have been previously described in either in vitro selected or clinical isolates (Mutation [n]); A2059G (41), A2058G (13), A2059C (2), C2611A (1), C2611G (1), L4 G95D (3). 16/86 isolates had previously undescribed mutations; A2058U + L4 I78V (2), A2059C + L4 G71R (1), A2059G + G2057A (1), L22 [109]RTAHIT[114]tandem repeat (2), L4 K86S + [69]GTGR[72]deletion (1), L4 [68]KG[69] to [68]KEG[69] (1), L4 [64]PPWRQ[67] to [64]P__Q[67] (1), L4 [69]GT[70] to [69]VP[70] (2), L4 [69]GTG[71] to [69]TPS[71] + V88I (1), L4 E30K + [69]GTG[71] to [69]TPS[71] + V88I (2), L4 K68Q (1). 9 isolates had no mutations in 23SrRNA, L4 or L22. 4 isolates were resistant to Q/D (MIC = 4 mg/L, mutations in bold). 2 isolates demonstrated reduced activity to linezolid (MIC = 4 mg/L, in italics). Telithromycin demonstrated good activity against all isolates (range = 0.004 - 1, MIC[50] = 0.06 mg/L). CONCLUSIONS: The prevalence of MAC[R] by ribosomal mutation was low. Q/D resistance due to L4 K86S + [69]GTGR[72] deletion has not been reported previously. Furthermore, this is the first report of non-susceptibility to linezolid in SPN and this was associated with 2 distinct mutations. Telithromycin was active against all isolates.

Publication Types:

• Meeting Abstracts

Keywords:

• Acetamides
• Anti-Bacterial Agents
• Disease Susceptibility
• In Vitro
• Ketolides
• Methyltransferases
• Microbial Sensitivity Tests
• Mutation
• Oxazolidinones
• RNA, Ribosomal
• Ribosomes
• Virginiamycin
• dalfopristin
• genetics
• linezolid
• quinupristin
• telithromycin

Other ID:

• GWAIDS0026606

UI: 102266230

From Meeting Abstracts