rifampin and quinupristin-dalfopristin

Bacterial meningitis caused by Streptococcus pneumoniae is an important cause of neurological morbidity and mortality in both children and adults. With increasing antibiotic resistance in pneumococci and documented microbiological failure in treatment of pneumococcal meningitis with cefotaxime and ceftriaxone, the need for alternative antibiotic therapy is critical. Of the currently available options, vancomycin has shown the most promise, particularly when used in combination with ceftriaxone or cefotaxime. Rifampin, also used in combination with either ceftriaxone or cefotaxime, has demonstrated encouraging preliminary results against antibiotic-resistant pneumococci as well. Chloramphenicol has unexpectedly yielded discouraging clinical results in children with infection caused by penicillin-resistant strains. Of the investigational antibiotics currently in clinical trials for the treatment of meningitis, meropenem, a carbapenem-class antibiotic, has demonstrated increased activity against penicillin-resistant pneumococci compared with that of other beta-lactam antibiotics, while having a safety profile similar to that of the cephalosporins.

Topics: Adult; Anti-Bacterial Agents; Anti-Infective Agents; Child; Child, Preschool; Chloramphenicol; Clindamycin; Female; Fluoroquinolones; Humans; Infant; Infant, Newborn; Lactams; Male; Meningitis, Bacterial; Naphthyridines; Penicillin Resistance; Rifampin; Streptococcal Infections; Streptococcus pneumoniae; Vancomycin; Virginiamycin

Topics: Anti-Bacterial Agents; Bacteremia; Bacterial Typing Techniques; Ceftaroline; Cephalosporins; Drug Resistance, Multiple, Bacterial; Electrophoresis, Gel, Pulsed-Field; Gene Expression; Genes, Bacterial; Humans; Linezolid; Methicillin; Methicillin Resistance; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Phylogeny; Rifampin; Staphylococcal Infections; Tetracycline; Turkey; Vancomycin; Vancomycin Resistance; Virginiamycin

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

The present study was carried out to assess the frequency of methicillin-resistant staphylococci (MRS) among racehorses (n=209) and veterinary personnel (n=13) as well as environmental surfaces (n=14) at an equine hospital in Adana, Turkey. In addition, species distribution, antimicrobial susceptibility, resistance genes, staphylococcal chromosomal cassette mec (SCCmec) type and clonality of these isolates were also investigated. MRS were identified by 16S rRNA sequencing, and typed by pulsed-field gel electrophoresis (PFGE). As a result, MRS was isolated in horses (48.3%), clinic staff (92.3%) and environmental samples (71.4%). Of the 123 MRS isolates, 118 isolates were identified as Staphylococcus lentus, and the remaining ones were found to be S. sciuri (n=3), S. intermedius (n=1) and S. fleuretti (n=1). All isolates were found to be susceptible against vancomycin, quinupristin-dalfopristin and rifampicin. Additionally, single or various combinations of resistance genes were detected among MRS isolates. SCCmec type II was identified in all isolates. Similar PFGE patterns were observed among MRS isolated from horses, humans, and environmental samples. Since MRS were concurrently isolated from horses and humans it is suggested that cross-transmission of MRS between horses and humans might occur. However, it cannot be ruled out that transmission is human to animal or animal to human.

Topics: Animal Technicians; Animals; Cross Infection; DNA Primers; Electrophoresis, Gel, Pulsed-Field; Genes, MDR; Horse Diseases; Horses; Humans; Methicillin Resistance; Polymerase Chain Reaction; Rifampin; Species Specificity; Staphylococcal Infections; Staphylococcus; Turkey; Vancomycin; Virginiamycin

We compared the in vitro activity of dalfopristin and quinupristin combined with five intravenous antibiotics in a 3-dimensional model. We tested six strains of Staphylococcus aureus selected with different patterns of resistance to methicillin and erythromycin. Dalfopristin and quinupristin displayed a very synergistic activity against all the strains with a mean 16- or 32-fold decrease of inhibitory concentrations in combination. That synergy was even better against erythromycin-resistant strains. In combination with tigecycline or fosfomycin, the antibacterial activity could be consistently enhanced with the same decrease of inhibitory concentrations. A synergy was also observed, less regularly and at a lower level, with rifampin, gentamicin or vancomycin. Combinations of dalfopristin and quinupristin with tigecycline or fosfomycin could be very interesting in clinical practice because the inhibitory effect could be achieved with very low concentrations of each component, even when erythromycin-resistant strains are concerned.

Topics: Anti-Bacterial Agents; Drug Therapy, Combination; Fosfomycin; Gentamicins; In Vitro Techniques; Microbial Sensitivity Tests; Minocycline; Rifampin; Staphylococcus aureus; Tigecycline; Vancomycin; Virginiamycin

We compared the efficacy of quinupristin/dalfopristin versus vancomycin, alone or in combination with rifampicin, in a rabbit model of methicillin-resistant Staphylococcus aureus-induced arthritis. Vancomycin, alone or in combination with rifampicin, and quinupristin/dalfopristin+rifampicin were significantly more effective than quinupristin/dalfopristin alone.

Topics: Animals; Anti-Bacterial Agents; Arthritis, Infectious; Disease Models, Animal; Drug Therapy, Combination; Methicillin Resistance; Microbial Sensitivity Tests; Rabbits; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Vancomycin; 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

There are marked differences in the amount of immunoreactive components such as lipoteichoic acid (LTA) released from Gram-positive bacteria following exposure to different antibiotics. Little is known about the kinetics and amount of release of such components in relation to bacterial killing.. Bacterial killing and LTA release from Streptococcus pneumoniae type 3 during exposure to ceftriaxone, meropenem, rifampicin, rifabutin, quinupristin/dalfopristin, and trovafloxacin in tryptic soy broth were quantified microbiologically and by ELISA, respectively. We applied a mathematical model to characterize quantitatively the amount of lipoteichoic acid released and the statistical moments of this release.. The model approach revealed that (i) the lag time to release of LTA was very similar for individually killed bacterial cells (approximately 120 min), whatever the killing mechanism effected by the antibiotic, and (ii) the amount of LTA released per killed bacterial cell, a value that we regard as an indicator of the relation between antibacterial efficacy and possible adverse immunostimulatory effects due to release of cell wall components, differs markedly between antibiotics, even at antibiotic concentrations inducing equal killing. Rifamycins were most effective in killing S. pneumoniae while causing the least LTA release per killed bacterial cell; the amount released was about one-half that by quinupristin-dalfopristin and trovafloxacin, and one-quarter that by ceftriaxone and meropenem.. In the evaluation of antibacterial drugs, the present model provides useful information on the whole process of bacterial killing and release of immunoreactive components from the bacterial cell wall.

Topics: Anti-Bacterial Agents; Ceftriaxone; Lipopolysaccharides; Meropenem; Rifabutin; Rifampin; Streptococcus pneumoniae; Teichoic Acids; Thienamycins; Virginiamycin

The aim of this study was to investigate in vitro the post-antibiotic effect (PAE) of 19 antibacterial agents against two strains of Bacillus anthracis (ST-1 and Sterne strains).. PAE was determined by calculating the time required for the viable counts of antibiotic-exposed bacteria (at concentrations of 10x MIC and exposure for 2 h) at 37 degrees C to increase by 1 log10 above the counts observed immediately after antibiotic removal compared with the corresponding time for controls not exposed to antibiotics.. The PAEs of the fluoroquinolones (ciprofloxacin, ofloxacin, levofloxacin, moxifloxacin and garenoxacin) were 2-5 h. The macrolide (erythromycin, clarithromycin and telithromycin) PAEs were 1-4 h, and that of clindamycin was 2 h. The PAEs induced by tetracycline and minocycline were 1-3 h. The PAEs induced by the beta-lactams (penicillin G, amoxicillin and ceftriaxone), vancomycin, linezolid and chloramphenicol were 1-2 h. The PAE induced by rifampicin was 4-5 h. Quinupristin/dalfopristin had the longest PAE, lasting for 7-8 h.. Our results indicate that the PAE is unrelated to the MIC but may be related to the rapidity of bacterial kill. These observations may bear importance on treatment regimens of human anthrax.

Topics: Acetamides; Anti-Bacterial Agents; Bacillus anthracis; beta-Lactams; Chloramphenicol; Clindamycin; Fluoroquinolones; Linezolid; Macrolides; Microbial Sensitivity Tests; Oxazolidinones; Rifampin; Tetracyclines; Vancomycin; Virginiamycin

Staphylococcus aureus strains resistant to a variety of antimicrobial agents are often found in the hospital environment and are responsible for many life-threatening infections. The activity of quinupristin/dalfopristin against 84 Staphylococcus aureus bloodstream isolates (both methicillin resistant and methicillin sensitive) was compared to the activity of vancomycin, teicoplanin, erythromycin, oxacillin, clindamycin, gentamicin, rifampicin. The Minimum Inhibitory Concentrations of these agents was evaluated with the Epsilometer Test. Quinupristin/dalfopristin inhibited all methicillin-sensitive strains at 1mg/L, and 75% of methicillin-resistant strains at 1.5mg/L. According to these results, quinupristin-dalfopristin shows promising in-vitro activity and may be a welcome alternative treatment for methicillin-resistant staphylococcal infections, resulting in reduced use of glycopeptides.

Topics: Anti-Bacterial Agents; Bacteremia; Clindamycin; Cross Infection; Erythromycin; Gentamicins; Humans; Methicillin Resistance; Microbial Sensitivity Tests; Oxacillin; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Teicoplanin; Vancomycin; Virginiamycin

We evaluated the activities of quinupristin-dalfopristin (Q-D), alone or in combination with rifampin, against three strains of Staphylococcus aureus susceptible to rifampin (MIC, 0.06 microg/ml) and to Q-D (MICs, 0.5 to 1 microg/ml) but displaying various phenotypes of resistance to macrolide-lincosamide-streptogramin antibiotics: S. aureus HM1054 was susceptible to quinupristin and dalfopristin (MICs of 8 and 4 microg/ml, respectively); for S. aureus RP13, the MIC of dalfopristin was high (MICs of quinupristin and dalfopristin for strain RP13, 8 and 32 microg/ml, respectively); and S. aureus HM1054R was obtained after conjugative transfer of macrolide-lincosamide-streptogramin B constitutive resistance to HM1054, and the MIC of quinupristin for this strain was high (MICs of quinupristin and dalfopristin, 64 and 4 microg/ml, respectively). In vitro time-kill curve studies showed an additive effect [corrected] between Q-D and rifampin, at a concentration of four times the MIC, against the three strains. Rabbits with aortic endocarditis were treated 4 days with Q-D, rifampin, or their combination. In vivo, the combination was highly bactericidal and synergistic against strains susceptible to quinupristin (HM1054 and RP13) and sterilized 94% of the animals. In contrast, the combination was neither synergistic nor bactericidal against the quinupristin-resistant strain (HM1054R) and did not prevent the emergence of mutants resistant to rifampin. We conclude that the in vivo synergistic and bactericidal activity of the combination of Q-D and rifampin against S. aureus is predicted by the absence of resistance to quinupristin but not by in vitro combination studies.

Topics: Animals; Anti-Bacterial Agents; Drug Resistance, Microbial; Drug Synergism; Drug Therapy, Combination; Endocarditis, Bacterial; Female; Kinetics; Lincosamides; Macrolides; Microbial Sensitivity Tests; Mutation; Phenotype; Rabbits; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Virginiamycin

This in vitro study evaluated the activities of vancomycin, LY333328, and teicoplanin alone and in combination with gentamicin, rifampin, and RP59500 against Staphylococcus aureus isolates with intermediate susceptibilities to vancomycin. Ampicillin-sulbactam and trovafloxacin were also evaluated. LY333328 and ampicillin-sulbactam resulted in bactericidal activity against all isolates. The combination of gentamicin with glycopeptides showed synergistic activity, while rifampin had no added benefit.

Topics: Ampicillin; Anti-Bacterial Agents; Antibiotics, Antitubercular; Drug Therapy, Combination; Fluoroquinolones; Gentamicins; Glycopeptides; Lipoglycopeptides; Microbial Sensitivity Tests; Naphthyridines; Rifampin; Staphylococcus aureus; Sulbactam; Teicoplanin; Time Factors; Vancomycin; Virginiamycin

Quinupristin/dalfopristin (RP59500) is a novel streptogramin and a semisynthetic derivative of pristinamycins IA and IIB. The following properties of RP59500 were investigated: (i) its in-vitro activity against 164 hospital isolates of Staphylococcus aureus, 101 of which were methicillin-resistant (MRSA); (ii) its killing effect against 24 MRSA and seven methicillin-susceptible (MSSA) isolates; (iii) its interactions with rifampicin and ciprofloxacin against 18 MRSA isolates, six susceptible to both rifampicin and ciprofloxacin and 12 resistant to both, at 1 x MIC, 2 x MIC and 4 x MIC. Rifampicin and ciprofloxacin were applied at a concentration equal to their mean serum levels in order to establish the clinical relevance of the results. The MIC50, MIC90, MBC50 and MBC90 of quinupristin/dalfopristin were, respectively, < or = 0.015, 2, 0.12 and 2 mg/L for MRSA isolates and < or = 0.015, 0.06, < or = 0.015 and 0.25 mg/L for MSSA isolates. All isolates were inhibited by quinupristin/dalfopristin. Its killing effect varied with concentration and time, being optimal at 4 x MIC and after 24 h growth. Strains surviving 24 h exposure to this agent had much higher MICs than the parent strain, but only a limited number of them became resistant. Quinupristin/dalfopristin at 2 x MIC and 4 x MIC showed in-vitro synergy with rifampicin against highly resistant isolates mainly at 6 h and 24 h of growth involving 50-83% of MRSA isolates, and showed synergy with ciprofloxacin at 24 h involving 42-75% of isolates. The MIC increase in colonies surviving at 24 h was restricted by the presence of rifampicin or ciprofloxacin. In contrast, the above combinations acted synergically over the total number of MRSA strains susceptible to both rifampicin and ciprofloxacin. The above findings show that quinupristin/dalfopristin is a very potent antistaphylococcal agent, and that its activity against MRSA isolates is enhanced when it is combined with rifampicin or ciprofloxacin.

Topics: Anti-Bacterial Agents; Ciprofloxacin; Cross Infection; Dose-Response Relationship, Drug; Drug Interactions; Humans; Methicillin Resistance; Microbial Sensitivity Tests; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Time Factors; Virginiamycin

Topics: Aged; Doxycycline; Drug Resistance, Microbial; Drug Synergism; Drug Therapy, Combination; Endocarditis, Bacterial; Enterococcus faecium; Gram-Positive Bacterial Infections; Humans; Male; Rifampin; Vancomycin; Virginiamycin

A total of 68 viridans group streptococci, including 31 Streptococcus sanguis, 12 S. mitis, 3 S. salivarius, and 8 S. milleri from blood, and an additional 14 S. milleri from abscesses and normally sterile sites, were tested against penicillin, amoxicillin, cefazolin, ceftriaxone, meropenem, clindamycin, quinupristin/dalfopristin, rifampin, levofloxacin, ofloxacin, vancomycin, and gentamicin with the microdilution method. The susceptibility rates for S. sanguis were: penicillin, 74%; amoxicillin, 84%; ceftriaxone, 94%; clindamycin, 87%, and vancomycin, 100%. The susceptibility rates for S. mitis were: penicillin, 42%; amoxicillin, 67%; ceftriaxone, 58%; clindamycin, 100%; and vancomycin, 100%. The susceptibility rates for S. milleri were: penicillin, 100%, amoxicillin. 100%; ceftriaxone, 100%, clindamycin, 100%; and vancomycin, 100%. Two of the three isolates of S. salivarius were susceptible to penicillin, amoxicillin, and ceftriaxone; all were susceptible to clindamycin and vancomycin. Levofloxacin, quinupristin/dalfopristin, and rifampin were highly active against all isolates.

Topics: Amoxicillin; Anti-Bacterial Agents; Cefazolin; Ceftriaxone; Clindamycin; Drug Resistance, Microbial; Gentamicins; Humans; Levofloxacin; Meropenem; Microbial Sensitivity Tests; Ofloxacin; Penicillins; Rifampin; Streptococcal Infections; Streptococcus; Thienamycins; Vancomycin; Virginiamycin

Topics: Anti-Bacterial Agents; Clindamycin; Drug Resistance, Microbial; Drug Synergism; Erythromycin; Microbial Sensitivity Tests; Penicillin Resistance; Penicillins; Rifampin; Streptococcus pneumoniae; Sulfamethoxazole; Trimethoprim; Virginiamycin

The susceptibility of clinical isolates of methicillin-susceptible and -resistant staphylococci from cancer patients with central venous catheter bacteremia to quinupristin/dalfopristin, a semisynthetic streptogramin, was determined in vitro. Susceptibility of these isolates to nine other antistaphylococcal antibiotics was also determined for comparison. A total of 197 staphylococcal strains were tested from 1983 to 1992. Quinupristin/dalfopristin was bactericidal against all isolates, independent of their resistance to methicillin. Its activity was similar to that of vancomycin but superior to that of teicoplanin. Quinupristin/dalfopristin may prove to be an important addition to our armamentarium against catheter-related staphylococcal infections.

Topics: Anti-Bacterial Agents; Anti-Infective Agents; Antibiotics, Antitubercular; Bacteremia; Catheterization, Central Venous; Cefamandole; Cephalosporins; Ciprofloxacin; Clindamycin; Daptomycin; Humans; Methicillin; Methicillin Resistance; Microbial Sensitivity Tests; Neoplasms; Novobiocin; Oxacillin; Penicillins; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Staphylococcus epidermidis; Teicoplanin; Vancomycin; Virginiamycin

The in-vitro activity of RP 59500, a new semisynthetic injectable streptogramin, was compared with that of erythromycin, rifampicin and ciprofloxacin against 189 Legionella spp. Rifampicin was the most active agent tested. RP 59500 was found to be more active than erythromycin against most strains, but less active than ciprofloxacin. Legionella pneumophila serogroups 1, 3, 4, 5 and 6 were more susceptible to RP 59500 than were L. pneumophila serogroups 2, 7, and 8. Legionella micdadei was the least susceptible species to RP 59500 and erythromycin. RP 59500 was similar in activity against isolates obtained from both patients and environmental sources. This activity was generally better than that of erythromycin.

Topics: Ciprofloxacin; Cross Infection; Drug Resistance, Microbial; Erythromycin; Humans; In Vitro Techniques; Legionella; Microbial Sensitivity Tests; Respiratory Tract Infections; Rifampin; Virginiamycin