ru-66647 and quinupristin-dalfopristin

Periodic investigations into patterns of antimicrobial resistance can help to optimize the efficacy of treatment and limit the development of resistance.. The aim of this study was to update information on patterns of antimicrobial resistance in Staphylococcus aureus isolated from skin infections in South Korea.. We retrospectively analyzed clinical information and in vitro antimicrobial resistance data for 965 clinical S. aureus isolates obtained from skin infections during 2010-2013 in a university hospital in South Korea.. The rate of resistance to oxacillin (methicillin-resistant S. aureus [MRSA]) was 47.4%. Similar rates of resistance to erythromycin (45.6%), fusidic acid (44.0%), and clindamycin (42.3%) were noted. The rate of resistance to mupirocin was 8.4%. Overall, 4.9% of isolates were resistant to both fusidic acid and mupirocin. None of the isolates showed resistance to habekacin, synercid, teicoplanin, or vancomycin. Generally, antimicrobial resistance rates did not increase from 2010 to 2013 except with reference to a few agents such as mupirocin and rifampin. Isolates from surgical patients, inpatients, non-dermatology outpatients, and adult patients showed relatively high rates of resistance to multiple antimicrobials. Resistance to mupirocin was not only lower than that to fusidic acid but was consistent across clinical contexts.. The prevalence of MRSA in skin infections in South Korea did not increase during 2010-2013. Isolates from dermatology outpatients showed relatively lower rates of resistance to multiple antimicrobials than isolates from non-dermatology outpatients. Among topical antimicrobials, resistance to mupirocin was relatively low regardless of clinical condition.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Child; Child, Preschool; Ciprofloxacin; Clindamycin; Dibekacin; Drug Resistance, Multiple, Bacterial; Erythromycin; Female; Fusidic Acid; Gentamicins; Humans; Infant; Infant, Newborn; Ketolides; Male; Methicillin-Resistant Staphylococcus aureus; Middle Aged; Mupirocin; Oxacillin; Republic of Korea; Retrospective Studies; Rifampin; Staphylococcal Skin Infections; Staphylococcus aureus; Teicoplanin; Tetracycline; Vancomycin; Virginiamycin; Young Adult

Antibacterial agents are used in malaria therapy due to their effect on two prokaryote organelles, the mitochondrion and the apicoplast. We demonstrate here that the ribosome-blocking antibiotics telithromycin and quinupristin-dalfopristin, but not linezolid, inhibit the growth of Plasmodium falciparum. Both drugs induce delayed death in the parasite, suggesting that their effect involves the impairment of apicoplast translation processes.

Topics: Animals; Humans; Ketolides; Malaria, Falciparum; Parasitic Sensitivity Tests; Plasmodium falciparum; Protein Biosynthesis; Protein Synthesis Inhibitors; Time Factors; Virginiamycin

Topics: Anti-Bacterial Agents; beta-Lactams; Daptomycin; Ertapenem; Humans; Ketolides; Minocycline; Ofloxacin; Tigecycline; Virginiamycin

The antibacterial activities of clindamycin, synercid, telithromycin, linezolid and mupirocin were evaluated against erythromycin-resistant Gram-positive coccal clinical isolates collected in Korean hospitals. In Staphylococcus aureus, synercid, linezolid and mupirocin were the most active agents. Against coagulase-negative staphylococci (CNS), synercid, linezolid and mupirocin were also active. Telithromycin and synercid resistance was common against enterococci, only linezolid and mupirocin were active. The reason of low activity of telithromycin against staphylococci and enterococci is because most of the isolates were constitutively resistant to erythromycin. Synercid, telithromycin, linezolid and mupirocin were active against streptococci.

Topics: Acetamides; Anti-Bacterial Agents; Clindamycin; Drug Resistance, Bacterial; Erythromycin; Gram-Positive Bacterial Infections; Gram-Positive Cocci; Humans; Ketolides; Korea; Linezolid; Microbial Sensitivity Tests; Mupirocin; Oxazolidinones; Virginiamycin

We determined the activities of new antibiotics telithromycin (ketolide) and quinupristin/dalfopristin (streptogramins) against 88 macrolide and/or lincosamide resistant coagulase-negative staphylococci (CoNS) isolates with defined resistance gene status. Telithromycin susceptibility was determined only in erythromycin-sensitive isolates (15) indicating the same mechanisms of resistance. In contrast, all erythromycin-resistant isolates (73) were either constitutively resistant to telithromycin (13 isolates with constitutive erm genes) or demonstrated telithromycin D-shaped zone (60 isolates with inducible msr(A) and/or erm). However, the level of inducible resistance conferred by msr(A) (35 isolates) was borderline even after induction by erythromycin. No quinupristin/dalfopristin resistant isolate was observed if tested by disk-diffusion method (DDM) but 18 isolates were intermediate (MIC = 1-3 mg/L) and two isolates resistant (MIC = 8 mg/L) if tested by E-test. All these isolates were resistant to streptogramin A and harbored vga(A) gene (1 isolate) or vga(A)LC gene (19 isolates). MICs for quinupristin/dalfopristin were higher for isolates with combination of streptogramin A resistance and constitutive MLSB resistance (MIC = 3-8 mg/L in 4 isolates) than for streptogramin A-resistant isolates susceptible to streptogramin B (MIC = 0.5-2 mg/L in 16 isolates). In addition to S. haemolyticus, vga(A)LC was newly identified in S. epidermidis and S. warnerii indicating its widespread occurrence in CoNS. Misidentification of low-level resistant isolates by DDM may contribute to dissemination of streptogramin A resistance.

Topics: Anti-Bacterial Agents; Clindamycin; Coagulase; Drug Resistance, Bacterial; Erythromycin; Ketolides; Macrolides; Methicillin Resistance; Microbial Sensitivity Tests; Staphylococcus; Streptogramin A; Streptogramin B; Virginiamycin

Microbial resistance to antibiotics currently spans all known classes of natural and synthetic compounds. It has not only hindered our treatment of infections but also dramatically reshaped drug discovery, yet its origins have not been systematically studied. Soil-dwelling bacteria produce and encounter a myriad of antibiotics, evolving corresponding sensing and evading strategies. They are a reservoir of resistance determinants that can be mobilized into the microbial community. Study of this reservoir could provide an early warning system for future clinically relevant antibiotic resistance mechanisms.

Topics: Amino Acid Substitution; Anti-Bacterial Agents; Ciprofloxacin; Daptomycin; Drug Resistance, Multiple, Bacterial; Erythromycin; Genes, Bacterial; Ketolides; Macrolides; Microbial Sensitivity Tests; Molecular Sequence Data; Mutation; Rifampin; Soil Microbiology; Streptomyces; Trimethoprim Resistance; Vancomycin Resistance; Virginiamycin

One hundred and sixty viridans group streptococci (VGS) and 26 Gemella spp. resistant to erythromycin were studied to detect macrolide lincosamide and streptogramin B (MLS(B)) phenotypes and to investigate resistance rates to other antibiotics. The M phenotype was most prevalent in both bacterial groups (59.6% in VGS, 69.2% in gemellae) and the iMLS(B) phenotype was found least often (9.3 and 13.9%, respectively). All isolates with M phenotype had the mef(A/E) gene, being prevalent the mef(E) subclass. cMLS(B) and iMLS(B) strains contained the erm(B) gene, alone or in combination with the mef(A/E) gene. Thirteen isolates were intermediately resistant to quinupristin/dalfopristin and 11 strains showed low susceptibility to telithromycin. Linezolid was active against all the isolates tested and tetracycline resistance was the major one in VGS (41.6%) and Gemella spp. (46.2%).

Topics: Acetamides; Anti-Bacterial Agents; Bacterial Proteins; Drug Resistance; Erythromycin; Genes, Bacterial; Humans; Ketolides; Lincosamides; Linezolid; Macrolides; Membrane Proteins; Methyltransferases; Microbial Sensitivity Tests; Oxazolidinones; Staphylococcaceae; Streptogramin B; Tetracycline Resistance; Virginiamycin; Viridans Streptococci

To date, 86 of 7,746 macrolide-resistant Streptococcus pneumoniae isolates from 1999 to 2002 PROTEKT (Prospective Resistant Organism Tracking and Epidemiology for the Ketolide Telithromycin) surveillance studies were negative for methylase and efflux mechanisms. Mutations in 23S rRNA or the genes encoding riboprotein L4 or L22 were found in 77 of 86 isolates. Six isolates were resistant to quinupristin-dalfopristin and two were resistant to linezolid, while telithromycin demonstrated good activities against all isolates.

Topics: Acetamides; Anti-Bacterial Agents; Dose-Response Relationship, Drug; Drug Resistance, Bacterial; Humans; Ketolides; Linezolid; Macrolides; Mutation; Oxazolidinones; Pneumococcal Infections; Ribosomes; RNA, Ribosomal, 23S; Streptococcus pneumoniae; Virginiamycin

The in vitro activity of levofloxacin, moxifloxacin, gatifloxacin, erythromycin, telithromycin, linezolid, synercid and vancomycin was measured against 36 genetically defined, gyrA/grlA double mutant MRSA clinical strains with an MIC to ciprofloxacin > or = 8 mg/l. The three newer fluoroquinolones tested were more active than ciprofloxacin. Resistance rates for levofloxacin and gatifloxacin were high (44.5 and 36.1%, respectively). All the strains were moxifloxacin-susceptible, though most of them had MICs close to the break point. All the strains were intermediate or resistant to erythromycin and most were also resistant to telithromycin. No strains were resistant to linezolid, synercid or vancomycin (MIC(90): 2, 1 and 2 mg/l, respectively).

Topics: Acetamides; Anti-Bacterial Agents; Drug Resistance, Bacterial; Drug Resistance, Multiple; In Vitro Techniques; Ketolides; Linezolid; Macrolides; Methicillin Resistance; Microbial Sensitivity Tests; Oxazolidinones; Staphylococcus aureus; Vancomycin; Virginiamycin

Non-typeable Haemophilus influenzae, which is a cause of disease in the upper and lower respiratory tract, can survive intracellularly in human epithelial cells and macrophages. We studied the in vitro activity of five antibiotics against intracellular non-typeable H. influenzae in human type II alveolar epithelial cells. The eukaryotic cells were loaded with bacteria, and extracellular bacteria were killed by gentamicin. After the cells were washed, antibiotics were added at concentrations of 0.12-64 mg/L for 18 h before the numbers of viable intracellular bacteria were determined. Of the antibiotics tested, ciprofloxacin and quinupristin/dalfopristin were the most potent agents, followed by clarithromycin and telithromycin. Ampicillin was not active against intracellularly localized, non-typeable H. influenzae.

Topics: Ampicillin; Anti-Bacterial Agents; Bacterial Typing Techniques; Ciprofloxacin; Clarithromycin; Haemophilus influenzae; Humans; Intracellular Fluid; Ketolides; Macrolides; Microbial Sensitivity Tests; Tumor Cells, Cultured; Virginiamycin

To determine in vitro susceptibilities of a large series of speciated coagulase-negative staphylococci (CNS) against three new antibiotics, linezolid, quinupristin/dalfopristin and telithromycin.. Susceptibilities to three new antibiotics and oxacillin, vancomycin, clindamycin and erythromycin were determined by the agar dilution method, as described by the NCCLS.. Resistance to linezolid was not observed in any isolates, although MIC90 values varied between species. Fifteen of 658 (2.3%) isolates were resistant to quinupristin/dalfopristin, but < 1% of the clinically most important isolates of Staphylococcus epidermidis, Staphylococcus haemolyticus and Staphylococcus hominis demonstrated resistance to this agent. Susceptibility to clindamycin correlated with susceptibility to quinupristin/dalfopristin; however, resistance to clindamycin did not predict quinupristin/dalfopristin resistance. Telithromycin was the least active of the new agents tested, showing activity similar to that of clindamycin. Susceptibility and resistance to clindamycin were predictive of susceptibility and resistance to telithromycin.. Clindamycin susceptibility can be used as a surrogate marker for susceptibility to quinupristin/dalfopristin and telithromycin. Quinupristin/dalfopristin and linezolid show good activity against both mecA-positive and -negative CNS.

Topics: Acetamides; Anti-Bacterial Agents; Coagulase; Drug Resistance, Multiple, Bacterial; Humans; Ketolides; Linezolid; Macrolides; Microbial Sensitivity Tests; Oxazolidinones; Staphylococcus; Virginiamycin

The susceptibilities to telithromycin of 203 Streptococcus pneumoniae isolates prospectively collected during 1999 and 2000 from 14 different geographical areas in Spain were tested and compared with those to erythromycin A, clindamycin, quinupristin-dalfopristin, penicillin G, cefotaxime, and levofloxacin. Telithromycin was active against 98.9% of isolates (MICs, < or =0.5 microg/ml), with MICs at which 90% of isolates are inhibited being 0.06 microg/ml, irrespective of the resistance genotype. The corresponding values for erythromycin were 61.0% (MICs, < or =0.25 microg/ml) and >64 microg/ml. The erm(B) gene (macrolide-lincosamide-streptogramin B resistance phenotype) was detected in 36.4% (n = 74) of the isolates, which corresponded to 93.6% of erythromycin-intermediate and -resistant isolates, whereas the mef(A) gene (M phenotype [resistance to erythromycin and susceptibility to clindamycin and spiramycin without blunting]) was present in only 2.4% (n = 5) of the isolates. One of the latter isolates also carried erm(B). Interestingly, in one isolate for which the erythromycin MIC was 2 microg/ml, none of these resistance genes could be detected. Erythromycin MICs for S. pneumoniae erm(B)-positive isolates were higher (range, 0.5 to >64 microg/ml) than those for erm(B)- and mef(A)-negative isolates (range, 0.008 to 2 microg/ml). The corresponding values for telithromycin were lower for both groups, with ranges of 0.004 to 1 and 0.002 to 0.06 microg/ml, respectively. The erythromycin MIC was high for a large number of erm(B)-positive isolates, but the telithromycin MIC was low for these isolates. These results indicate the potential usefulness of telithromycin for the treatment of infections caused by erythromycin-susceptible and -resistant S. pneumoniae isolates when macrolides are indicated.

Topics: Anti-Bacterial Agents; Clindamycin; Drug Resistance, Microbial; Erythromycin; Humans; Ketolides; Macrolides; Microbial Sensitivity Tests; Spain; Streptococcus pneumoniae; Virginiamycin

The susceptibilities of Mycoplasma hominis, Mycoplasma pneumoniae, and Ureaplasma urealyticum to eight new antimicrobial agents were determined by agar dilution. M. pneumoniae was susceptible to the new glycylcycline GAR-936 at 0.12 microg/ml and evernimicin at 4 microg/ml, but it was resistant to linezolid. It was most susceptible to dirithromycin, quinupristin-dalfopristin, telithromycin, reference macrolides, and josamycin. M. hominis was susceptible to linezolid, evernimicin, and GAR-936. It was resistant to macrolides and the ketolide telithromycin but susceptible to quinupristin-dalfopristin and josamycin. U. urealyticum was susceptible to evernimicin (8 to 16 microg/ml) and resistant to linezolid. It was less susceptible to GAR-936 (4.0 microg/ml) than to tetracycline (0.5 microg/ml). Telithromycin and quinupristin-dalfopristin were the most active agents against ureaplasmas (0.06 microg/ml). The new quinolone gatifloxacin was active against M. pneumoniae and M. hominis at 0.12 to 0.25 microg/ml and active against ureaplasmas at 1.0 microg/ml. The MICs of macrolides were markedly affected by pH, with an 8- to 32-fold increase in the susceptibility of M. pneumoniae as the pH increased from 6.9 to 7.8. A similar increase in susceptibility with increasing pH was also observed with ureaplasmas. Tetracyclines showed a fourfold increase of activity as the pH decreased 1 U, whereas GAR-936 showed a fourfold decrease in activity with a decrease in pH.

Topics: 4-Quinolones; Acetamides; Aminoglycosides; Anti-Bacterial Agents; Aza Compounds; Erythromycin; Fluoroquinolones; Gatifloxacin; Humans; Hydrogen-Ion Concentration; Ketolides; Linezolid; Macrolides; Microbial Sensitivity Tests; Minocycline; Moxifloxacin; Mycoplasma hominis; Mycoplasma pneumoniae; Oxazolidinones; Quinolines; Tetracyclines; Tigecycline; Ureaplasma urealyticum; Virginiamycin

Four different compounds belonging to the macrolide-lincosamide-streptogramin B (MLSb) class of antimicrobial agents were tested against 611 Streptococcus pneumoniae strains. The ketolide (HMR 3647, previously RU66647) and the streptogramin (quinupristin-dalfopristin) were both active against pneumococci with high-level MLSb resistance (clindamycin-resistant strains) as well as those with low-level macrolide resistance (clindamycin-susceptible strains).

Topics: Anti-Bacterial Agents; Clindamycin; Erythromycin; Humans; Ketolides; Macrolides; Penicillin Resistance; Phenotype; Pneumococcal Infections; Streptococcus pneumoniae; Virginiamycin