Activity of Telithromycin Against Multi-Drug ResistantStreptococcus pneumoniaeand Molecular Characterization of Macrolide and Tetracycline Resistance Determinants

Abstract

The antistreptococcal activity of telithromycin and 11 different comparators was evaluated in 26 multi-drug resistant (MDR) Streptococcus pneumoniae strains collected during 2002-2003 as part of the ongoing PROTEKT (Prospective Resistant Organism Tracking and Epidemiology for the Ketolide Telithromycin) Italian Surveillance Program. The strains were characterized for their susceptibility to antibiotics both at the phenotypic and genotypic levels; furthermore, the association of erm(B), mef(A) class and tet(M) genes, as well as the mobile elements carrying them were determined. The strains in this study were resistant to penicillin (MIC > or = 2 mg/l) in 23.1% of cases, resistant to tetracycline in 88.4%, to cotrimoxazole in 34.6% and cefuroxime in 26.9% while only telithromycin and levofloxacin retained 100% activity against all microorganisms. Co-existence of different resistance determinants was found in 19.2% of all isolates collected in our laboratory, coming from southern Italy. Twenty-three isolates showing the MLSB phenotype of resistance possessing the erm(B) gene (88.5%), associated with tet(M), were carried on the same Tn1545-like element, while two isolates showing the M phenotype possessing the mef(A) gene alone, were carried on Tn1207.1. In only one strain were mef(E) and tet(M) together carried on Tn2009.

A Novel Ketolide, RBx 14255, with Activity against Multidrug-Resistant Streptococcus pneumoniae

“…Ketolides are active against pneumococci that have a macrolide efflux pump (9). Telithromycin is active against macrolide-resistant pneumococci that contain either the methylase or the efflux mechanism of resistance (8,9). However, the greater frequency of liver damage with telithromycin than with other macrolides resulted in its withdrawal of approval for two of three indications after postmarketing reports (11,28).…”

“…Antibacterial resistance, and macrolide resistance in S. pneumoniae in particular, is increasing worldwide, and this presents treatment challenges to physicians (8,27). Ketolides are active against pneumococci that have a macrolide efflux pump (9).…”

“…Telithromycin, the first member of the ketolide family, was developed to overcome macrolide resistance, and in vitro data showed activity against erythromycin-resistant strains (8)(9)(10). Telithromycin demonstrated high efficacy against S. pneumoniae isolates that cause community-acquired respiratory tract infection.…”

Conjugal mobilization of the mega element carryingmef(E) fromStreptococcus salivariustoStreptococcus pneumoniae

“…The entire element carrying mef (E) was amplified by long PCR using MS146/MS147 primers designed on the nucleotide sequence of mega ends (Cascone et al , 2005). Sequence analysis demonstrated that mega of strain 3C30 is 5388 bp long and is 100% identical to the mega element described previously in S. salivarius (GenBank accession no. )…”

Evaluation of the in vitro activity of tigecycline against multiresistant Gram-positive cocci containing tetracycline resistance determinants

“…Genomic DNA was extracted from all bacterial cultures as previously described [8] and used as a template for amplification. PCR experiments were carried out by established procedures following the reported conditions for the use of individual primer pairs and following procedures previously published [9]. PCR products were analysed by electrophoresis on 1% agarose gels (Sigma-Aldrich, St Louis, MO).…”