ru-66647 and Staphylococcal-Infections

This study aims to explore the antibacterial activity of cethromycin against Staphylococcus aureus (S. aureus), and its relationship with multilocus sequence typing (MLST), erythromycin ribosomal methylase (erm) genes and macrolide-lincosamide-streptogramin B (MLSB) phenotypes of S. aureus.. The minimum inhibitory concentrations (MICs) of cethromycin against 245 S. aureus clinical isolates ranged from 0.03125 to ≥ 8 mg/L, with the resistance of 38.8% in 121 methicillin-resistant S. aureus (MRSA). This study also found that cethromycin had strong antibacterial activity against S. aureus, with the MIC ≤ 0.5 mg/L in 55.4% of MRSA and 60.5% of methicillin-sensitive S. aureus (MSSA), respectively. The main MLSTs of 121 MRSA were ST239 and ST59, and the resistance of ST239 isolates to cethromycin was higher than that in ST59 isolates (P = 0.034). The top five MLSTs of 124 MSSA were ST7, ST59, ST398, ST88 and ST120, but there was no difference in the resistance of MSSA to cethromycin between these STs. The resistance of ermA isolates to cethromycin was higher than that of ermB or ermC isolates in MRSA (P = 0.016 and 0.041, respectively), but the resistance of ermB or ermC isolates to cethromycin was higher than that of ermA isolates in MSSA (P = 0.019 and 0.026, respectively). The resistance of constitutive MLSB (cMLSB) phenotype isolates to cethromycin was higher than that of inducible MLSB (iMLSB) phenotype isolates in MRSA (P < 0.001) or MSSA (P = 0.036). The ermA, ermB and ermC genes was mainly found in ST239, ST59 and ST1 isolates in MRSA, respectively. Among the MSSA, the ermC gene was more detected in ST7, ST88 and ST120 isolates, but more ermB genes were detected in ST59 and ST398 isolates. The cMLSB phenotype was more common in ST239 and ST59 isolates of MRSA, and was more frequently detected in ST59, ST398, and ST120 isolates of MSSA.. Cethromycin had strong antibacterial activity against S. aureus. The resistance of MRSA to cethromycin may had some clonal aggregation in ST239. The resistance of S. aureus carrying various erm genes or MLSB phenotypes to cethromycin was different.

Topics: Anti-Bacterial Agents; Drug Resistance, Multiple, Bacterial; Erythromycin; Humans; Ketolides; Lincosamides; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Multilocus Sequence Typing; Staphylococcal Infections; Staphylococcus aureus; Streptogramin B

Staphylococcus aureus isolates, collected from various clinical samples, were analysed to evaluate the contribution of the genetic background of both erythromycin-resistant (ERSA) and -susceptible (ESSA) S. aureus strains to biofilm formation.. A total of 66 ESSA and 43 ERSA clinical isolates were studied for adhesiveness and biofilm formation under different atmospheres. All isolates were evaluated for phenotypic and genotypic macrolide resistance, and for clonal relatedness by pulsed-field gel electrophoresis (PFGE), and by spa typing on representative isolates.. A high genetic heterogeneity was encountered, although 10 major PFGE types accounted for 86 % with a few small spatially and temporally related clusters. Overall, biofilm formation under anoxia was significantly lower than under oxic and micro-aerophilic atmospheres. Biofilm formation by ESSA was significantly higher compared to ERSA under oxic and micro-aerophilic conditions. Adhesiveness to plastic was significantly higher among respiratory tract infection isolates under micro-aerophilic conditions, while surgical site infection isolates formed significantly higher biomass of biofilm under oxic and micro-aerophilic atmospheres compared to anoxia. Pulsotype 2 and 4 strains formed significantly higher biofilm biomass than pulsotype 1, with strains belonging to CC8 forming significantly more compared to those belonging to CC5, under both oxic and micro-aerophilic atmospheres.. S. aureus biofilm formation appears to be more efficient in ESSA than ERSA, associated with specific S. aureus lineages, mainly CC8 and CC15, and affected by atmosphere. Further studies investigating the relationship between antibiotic resistance and biofilm formation could prove useful in the development of new strategies for the management of S. aureus infections.

Topics: A549 Cells; Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacterial Adhesion; Bacterial Proteins; Biofilms; Clindamycin; Drug Resistance, Bacterial; Electrophoresis, Gel, Pulsed-Field; Erythromycin; Female; Genotype; Humans; Ketolides; Macrolides; Male; Methicillin-Resistant Staphylococcus aureus; Middle Aged; Multilocus Sequence Typing; Penicillin-Binding Proteins; Phenotype; Staphylococcal Infections; Staphylococcus aureus; Young Adult

Staphylococci are one of the most common pathogens isolated from nosocomial and community acquired infections. Antibiotics such as clindamycin and erythromycin have been useful options for treating skin and soft-tissue infections caused by staphylococci. However, expression of macrolide-lincosamide-streptogramin B resistance (MLSB) can limit the effectiveness of these drugs. The aims of this study were to investigate the prevalence and phenotypes of MLSB resistance in staphylococcus strains isolated from clinical samples and to determine the telithromycin activity against these isolates. A total of 218 strains [92 Staphylococcus aureus and 126 coagulase-negative staphylococci (CNS)] isolated from different clinical samples (wound, abscess, blood, sterile body fluids, catheter, upper respiratory tract samples) between February 2011 to December 2012 were included in the study. The isolates were identified by using conventional methods and automated bacterial identification system (BD Phoenix 100™ System, Becton Dickinson, USA). Methicillin resistance of the isolates was determined with the use of cefoxitin (30 µg) disk and telithromycin (15 µg) activity was detected by Kirby-Bauer disk diffusion method. MLSB resistance phenotypes were investigated by the D-test method using erythromycin (15 µg) and clindamycin (2 µg) disks. Of 92 S.aureus isolates, 23 were methicillin-resistant (MRSA) and 69 were methicillin-susceptible (MSSA), whereas 78 of 126 CNS isolates were methicillin-resistant (MRCNS) and 48 were methicillin-susceptible (MSCNS). Hundred and seventy-two (79%) isolates were found as erythromycin-resistant, and the rates of erythromycin resistance in MRSA, MSSA, MRCNS and MSCNS strains were 83%, 71%, 95% and 63%, respectively. Inducible type of MLSB resistance (iMLSB type) was observed in 26%, 6%, 51% and 33%; chromosomal resistance (cMLSB type) in 32%, 27%, 27% and 17% and efflux pump connected resistance (MSB type) in 42%, 67%, 22% and 50% of the MRSA, MSSA, MRCNS and MSCNS, respectively. Forty-four (20%) strains were found susceptible to both clindamycin and erythromycin (S type resistance). Resistance due to enzymatic inactivation (L type) was observed only in two of the CNS strains (0.9%), one was methicillin-resistant and the other was susceptible. Total telithromycin resistance was detected as 26.6% (n= 58), while the resistance rates in MRSA, MSSA, MRCNS and MSKNS isolates were 35%, 35%, 28% and 8%, respectively. Telithromycin resistance rate w

Topics: Anti-Bacterial Agents; Drug Resistance, Multiple, Bacterial; Humans; Ketolides; Lincosamides; Macrolides; Phenotype; Staphylococcal Infections; Staphylococcus; Streptogramin B

Topics: Anti-Bacterial Agents; Drug Resistance, Bacterial; Erythromycin; Genes, Bacterial; Humans; In Vitro Techniques; Ketolides; Macrolides; Mutation; Selection, Genetic; Staphylococcal Infections; Staphylococcus aureus

To evaluate the uptake of HMR 3647 into human neutrophils (PMNs), human peritoneal macrophages (PMOs) and tissue-cultured cells (epithelial cells and fibroblasts), and to assess the intracellular activity of this drug.. Cell uptake of HMR 3647 was measured by radiometric assay, as described by Klemper and Styrt. Intracellular activity was determined by incubation for 3 h of PMNs containing bacteria in the presence of HMR 3647.. The intracellular concentrations were 130 and 71 times higher than extracellular concentrations in PMNs and PMOs, respectively (extracellular concentrations: 2-25 mg/L). The cellular-to-extracellular concentration ratios (C/E) for tissue-cultured cells were lower than those obtained in phagocytic cells but still greater than 5. The uptake of HMR 3647 was rapid and non-saturable in all cells. HMR 3647 was released slowly from phagocytic cells. HMR 3647 (extracellular concentration: 0.5-10 mg/L) did not significantly reduce the intracellular survival rate of Staphylococcus aureus ATCC 25923 in PMNs.. HMR 3647 reaches intracellular concentrations several times higher than extracellular concentrations within phagocytic and non-phagocytic cells. The slow efflux of this drug from phagocytic cells suggests that these cells may be a vehicle for it, delivering it to sites of infection.

Topics: Anti-Bacterial Agents; Cells, Cultured; Epithelial Cells; Fibroblasts; Humans; Ketolides; Macrolides; Macrophages, Peritoneal; Neutrophils; Phagocytes; Staphylococcal Infections; Staphylococcus aureus