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H. K. Geiss - One of the best experts on this subject based on the ideXlab platform.

  • Molecular analysis of Linezolid resistance in clinical Enterococcus faecium isolates by polymerase chain reaction and pyrosequencing
    European Journal of Clinical Microbiology & Infectious Diseases, 2011
    Co-Authors: P. Schnitzler, K. Schulz, C. Lampson, M. Geiss, H. K. Geiss
    Abstract:

    Resistance to Linezolid has been associated with a G2576T mutation in the 23 S rRNA gene. Clinical isolates of Linezolid-sensitive and Linezolid-resistant vancomycin-resistant Enterococcus faecium of a liver transplant patient have been analysed for the G2576T mutation by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP), conventional sequencing and pyrosequencing. A clear association between the number of mutated 23 S rRNA genes and the level of Linezolid resistance has been demonstrated. Linezolid susceptibility re-emerged after cessation of Linezolid therapy; however, the re-initiation of Linezolid therapy resulted in the re-emergence of Linezolid-resistant strains. Pyrosequencing rapidly detected the number of mutated alleles and is superior to conventional PCR-RFLP for the detection of heterozygous mutations.

  • Varying Linezolid susceptibility of vancomycin-resistant Enterococcus faecium isolates during therapy: a case report
    The Journal of antimicrobial chemotherapy, 2005
    Co-Authors: Stefanie Swoboda, Stefan Fritz, M. E. Martignoni, Rita Feldhues, Torsten Hoppe-tichy, Markus W. Büchler, H. K. Geiss
    Abstract:

    Objectives: Linezolid is an oxazolidinone antibiotic used in the treatment of infections caused by vancomycin-resistant enterococci. Resistance to Linezolid has been associated with a G2576U mutation in domain V of the 23S rRNA. Patient and methods: We present clinical details and susceptibility data from multiple Enterococcus faecium strains isolated from a liver transplant patient over 13 months. MICs of Linezolid, vancomycin and quinupristin/dalfopristin were determined using Etest. Molecular typing was performed by pulsedfield gel electrophoresis. Domain V of the 23S rRNA gene in the vancomycin-resistant Enterococcus faecium was amplified. Linezolid concentrations were analysed by HPLC. Results: We report the emergence of resistance to Linezolid in a vancomycin-resistant Enterococcus faecium during Linezolid treatment. After discontinuation of the Linezolid therapy, the isolate reverted to susceptibility. However, after re-administration of Linezolid the vancomycin-resistant Enterococcus faecium became resistant to Linezolid again. The isolates that were resistant to Linezolid had a G2576T mutation in their 23S rDNA. Conclusion: We describe a clinical case that shows the shift of a vancomycin-resistant Enterococcus faecium from Linezolid resistance to susceptibility and then back to resistance again related to Linezolid therapy.

Jon B Bruss - One of the best experts on this subject based on the ideXlab platform.

  • Safety and tolerability of Linezolid in children.
    The Pediatric infectious disease journal, 2003
    Co-Authors: Lisa Saiman, Johhanna Goldfarb, Sheldon A Kaplan, Kenneth Wible, Barbara Edge-padbury, Sharon Naberhuis-stehouwer, Jon B Bruss
    Abstract:

    Linezolid, an oxazolidinone, is effective in the treatment of adults and children with community-acquired and nosocomial pneumonia and uncomplicated and complicated skin and skin structure infections (SSSIs), including infections caused by Gram-positive resistant pathogens. Because of the increasing use of Linezolid, it is important to review the common adverse events (AEs) associated with its use in children with the use of data from clinical trials. The safety and tolerability of Linezolid in pediatric patients with Gram-positive infections were determined in four pediatric clinical studies. Study I included pediatric patients with community-acquired pneumonia; Study II included otitis media; Study III included SSSIs; and Study IV included complicated SSSIs, nosocomial pneumonia and bacteremia. Studies I and II had no comparator arm. Study III was randomized and compared Linezolid with cefadroxil. Study IV also was randomized and compared Linezolid with vancomycin. Patients <12 years of age received Linezolid 10 mg/kg; patients age 12 years and older received 600 mg (intravenous/oral). Dosing frequency (two to three times daily) varied depending on age and clinical diagnosis. The primary safety endpoints were AEs, drug-related AEs, serious AEs and selected laboratory tests. In the 4 studies 958 patients were included in the intent-to-treat analysis. In the Linezolid vs. cefadroxil study (Study III), the most common AEs in patients treated with Linezolid were diarrhea (7.8%), headache (6.5%) and upper respiratory tract infection (3.7%). In the Linezolid vs. vancomycin study (Study IV), the most common AEs in the Linezolid group were fever (14.1%), diarrhea (10.8%) and vomiting (9.4%). The most common drug-related AEs for Linezolid in all 4 studies were diarrhea, vomiting, loose stools and nausea. None of these common AEs or drug-related AEs occurred more frequently in patients treated with Linezolid than in those in the comparator group. Linezolid was safe and well-tolerated in pediatric patients with community-acquired pneumonia, otitis media, SSSIs and infections caused by Gram-positive resistant pathogens.

  • Hematologic effects of Linezolid in young children.
    Pediatric Infectious Disease Journal, 2003
    Co-Authors: H. Cody Meissner, Barbara Edge-padbury, Sharon Naberhuis-stehouwer, Timothy R. Townsend, Wanda Wenman, Sheldon L. Kaplan, María Morfin, Jon B Bruss
    Abstract:

    Background Linezolid is an effective and well-tolerated antibiotic for the treatment of Gram-positive infections, including hospital and community-acquired pneumonia and complicated and uncomplicated skin and skin structure infections. In adults Linezolid treatment for >/=2 weeks has been associated with reversible hematopoietic suppression, primarily thrombocytopenia. Objective To evaluate the occurrence of hematologic effects in children with Gram-positive infections in an open label study of Linezolid vs. vancomycin. Methods Detailed analyses of hematologic data, including reported hematologic adverse events, complete blood counts, reticulocyte index (RI) and iron studies (serum iron and transferrin saturation), were conducted in both groups at baseline and during and after treatment with the use of an intent-to-treat analysis. Results Three hundred sixteen patients (median age, 1.65 yr) randomized 2:1 to Linezolid (n = 215) or vancomycin (n = 101) were treated. Total treatment durations were similar in the vancomycin group (12.2 +/- 6.4 days; median, 11.0 days) and the Linezolid group (11.3 +/- 5.0 days; median, 11.0 days) (P = 0.20). No significant differences were noted in drug-related hematologic events, such as thrombocytopenia (Linezolid, 1.9% vs. vancomycin, 0%; P = 0.170), anemia (Linezolid, 1.4% vs. vancomycin, 1.0%; P = 0.771) or neutropenia (Linezolid, 0% vs. vancomycin, 0%). Hemoglobin values also were similar between treatment groups when assessed by shifts from baseline to lowest recorded value. Frequency of occurrence of any substantially abnormal value for hemoglobin (15.7% vs. 12.4%), platelets (12.9% vs. 13.4%) and neutrophils (5.9% vs. 4.3%) were similar in the Linezolid and vancomycin groups. No clinically relevant changes in RI or iron studies were noted between treatment groups, and parallel increases in RI occurred with both Linezolid and vancomycin. Conclusions No significant differences in hematologic profiles between Linezolid and vancomycin occurred in this pediatric population.

  • Hematologic effects of Linezolid in young children.
    The Pediatric infectious disease journal, 2003
    Co-Authors: H. Cody Meissner, Barbara Edge-padbury, Sharon Naberhuis-stehouwer, Wanda Wenman, Sheldon L. Kaplan, María Morfin, Timothy Townsend, Jon B Bruss
    Abstract:

    Linezolid is an effective and well-tolerated antibiotic for the treatment of Gram-positive infections, including hospital and community-acquired pneumonia and complicated and uncomplicated skin and skin structure infections. In adults Linezolid treatment for >/=2 weeks has been associated with reversible hematopoietic suppression, primarily thrombocytopenia. To evaluate the occurrence of hematologic effects in children with Gram-positive infections in an open label study of Linezolid vs. vancomycin. Detailed analyses of hematologic data, including reported hematologic adverse events, complete blood counts, reticulocyte index (RI) and iron studies (serum iron and transferrin saturation), were conducted in both groups at baseline and during and after treatment with the use of an intent-to-treat analysis. Three hundred sixteen patients (median age, 1.65 yr) randomized 2:1 to Linezolid (n = 215) or vancomycin (n = 101) were treated. Total treatment durations were similar in the vancomycin group (12.2 +/- 6.4 days; median, 11.0 days) and the Linezolid group (11.3 +/- 5.0 days; median, 11.0 days) (P = 0.20). No significant differences were noted in drug-related hematologic events, such as thrombocytopenia (Linezolid, 1.9% vs. vancomycin, 0%; P = 0.170), anemia (Linezolid, 1.4% vs. vancomycin, 1.0%; P = 0.771) or neutropenia (Linezolid, 0% vs. vancomycin, 0%). Hemoglobin values also were similar between treatment groups when assessed by shifts from baseline to lowest recorded value. Frequency of occurrence of any substantially abnormal value for hemoglobin (15.7% vs. 12.4%), platelets (12.9% vs. 13.4%) and neutrophils (5.9% vs. 4.3%) were similar in the Linezolid and vancomycin groups. No clinically relevant changes in RI or iron studies were noted between treatment groups, and parallel increases in RI occurred with both Linezolid and vancomycin. No significant differences in hematologic profiles between Linezolid and vancomycin occurred in this pediatric population.

John K Gibson - One of the best experts on this subject based on the ideXlab platform.

  • efficacy of Linezolid plus rifampin in an experimental model of methicillin susceptible staphylococcus aureus endocarditis
    Antimicrobial Agents and Chemotherapy, 2003
    Co-Authors: Charlene F Dailey, Paul J Pagano, Lewis V Buchanan, Jennifer A Paquette, Joseph V Haas, John K Gibson
    Abstract:

    The efficacy of Linezolid, alone or in combination with rifampin, against methicillin-susceptible Staphylococcus aureus in rabbits with experimental endocarditis was investigated. Linezolid (50 or 75 mg/kg of body weight), rifampin, and Linezolid (25, 50, or 75 mg/kg) plus rifampin produced statistically significant reductions in bacterial counts compared with those in untreated controls. Plasma or valvular vegetation levels of Linezolid in the groups treated with the Linezolid-rifampin combination were similar to those in the respective Linezolid-only treatment groups. At therapeutic levels of Linezolid, rifampin resistance was not observed. The results from this experimental model of endocarditis suggest that while rifampin did not provide synergy to the Linezolid dosing, it did not antagonize the efficacy of Linezolid.

  • efficacy of Linezolid in treatment of experimental endocarditis caused by methicillin resistant staphylococcus aureus
    Antimicrobial Agents and Chemotherapy, 2001
    Co-Authors: Charlene F Dailey, Donald H Batts, Lewis V Buchanan, Christine L Diletofang, Martha P Oramasshirey, Charles W Ford, John K Gibson
    Abstract:

    The efficacies of orally (p.o.) dosed Linezolid and intravenously (i.v.) dosed vancomycin against methicillin-resistant Staphylococcus aureus (MRSA) in rabbits with experimental aortic-valve endocarditis were investigated. After endocarditis was established with a recent clinical MRSA isolate, rabbits were dosed for 5 days with Linezolid (p.o., three times a day) at either 25, 50, or 75 mg/kg of body weight or vancomycin (i.v., twice a day) at 25 mg/kg. The 25-mg/kg Linezolid group had a high mortality rate and bacterial counts in the valve vegetations that were not different from those of the controls. Linezolid dosed p.o. at 50 and 75 mg/kg and i.v. vancomycin produced statistically significant reductions in bacterial counts compared to those of the untreated controls. The reduced bacterial counts and culture-negative valve rates for the animals treated with Linezolid at 75 mg/kg were similar to those for the vancomycin-treated animals. Concentrations of Linezolid in plasma were determined at several points in the dosing regimen. These results suggest that the efficacy of Linezolid in this infection model is related to trough levels in plasma that remain above the MIC for this microorganism. At the ineffective dose of Linezolid (25 mg/kg) the concentration at sacrifice was 0.045 times the MIC, whereas the concentrations of Linezolid in plasma in the 50- and 75-mg/kg groups were 2 and 5 times the MIC at sacrifice, respectively. The results from this experimental model suggest that the oxazolidinone Linezolid may be effective for the treatment of serious staphylococcal infections when resistance to other antimicrobials is present.

Marc H Scheetz - One of the best experts on this subject based on the ideXlab platform.

Stefanie Swoboda - One of the best experts on this subject based on the ideXlab platform.

  • Varying Linezolid susceptibility of vancomycin-resistant Enterococcus faecium isolates during therapy: a case report
    The Journal of antimicrobial chemotherapy, 2005
    Co-Authors: Stefanie Swoboda, Stefan Fritz, M. E. Martignoni, Rita Feldhues, Torsten Hoppe-tichy, Markus W. Büchler, H. K. Geiss
    Abstract:

    Objectives: Linezolid is an oxazolidinone antibiotic used in the treatment of infections caused by vancomycin-resistant enterococci. Resistance to Linezolid has been associated with a G2576U mutation in domain V of the 23S rRNA. Patient and methods: We present clinical details and susceptibility data from multiple Enterococcus faecium strains isolated from a liver transplant patient over 13 months. MICs of Linezolid, vancomycin and quinupristin/dalfopristin were determined using Etest. Molecular typing was performed by pulsedfield gel electrophoresis. Domain V of the 23S rRNA gene in the vancomycin-resistant Enterococcus faecium was amplified. Linezolid concentrations were analysed by HPLC. Results: We report the emergence of resistance to Linezolid in a vancomycin-resistant Enterococcus faecium during Linezolid treatment. After discontinuation of the Linezolid therapy, the isolate reverted to susceptibility. However, after re-administration of Linezolid the vancomycin-resistant Enterococcus faecium became resistant to Linezolid again. The isolates that were resistant to Linezolid had a G2576T mutation in their 23S rDNA. Conclusion: We describe a clinical case that shows the shift of a vancomycin-resistant Enterococcus faecium from Linezolid resistance to susceptibility and then back to resistance again related to Linezolid therapy.