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Vance G Fowler - One of the best experts on this subject based on the ideXlab platform.

  • presence of genes encoding the panton valentine leukocidin exotoxin is not the primary determinant of outcome in patients with complicated skin and skin structure infections due to methicillin resistant staphylococcus aureus results of a multinationa
    Journal of Clinical Microbiology, 2009
    Co-Authors: Ingyu Bae, Martin E Stryjewski, Tom H Rude, Giang T Tonthat, Lindsay F Reilly, Steven L Barriere, Fredric C Genter, G R Corey, Vance G Fowler
    Abstract:

    The role of Panton-Valentine leukocidin (PVL) in determining the severity and outcome of complicated skin and skin structure infections (cSSSI) caused by methicillin (Meticillin)-resistant Staphylococcus aureus (MRSA) is controversial. We evaluated potential associations between clinical outcome and PVL status by using MRSA isolates from patients enrolled in two large, multinational phase three clinical trials assessing telavancin for the treatment of cSSSI (the ATLAS program). MRSA isolates from microbiologically evaluable patients were genotyped by pulsed-field gel electrophoresis (PFGE) and PCR for pvl and 31 other putative virulence determinants. A single baseline pathogen of MRSA was isolated from 522 microbiologically evaluable patients (25.1%) among 2,079 randomized patients. Of these MRSA isolates, 83.2% (432/519) exhibited the USA300 PFGE genotype and 89.1% (465/522) were pvl positive. Patients with pvl-positive MRSA were more likely than those with pvl-negative MRSA to be young, to be North American, and to present with major abscesses (P < 0.001 for each). Patients were significantly more likely to be cured if they were infected with pvl-positive MRSA than if they were infected with pvl-negative MRSA (91.6% versus 80.7%; P = 0.015). This observation remained statistically significant after adjustment for presence of abscess, fever, or leukocytosis; infection size; diabetes; patient age; and study medication received. The fnbA, cna, sdrC, map-eap, sed, seg, sei, sej, SCCmec type IV, and agr group II genes were also associated with clinical response (P < 0.05). This contemporary, international study demonstrates that pvl was not the primary determinant of outcome in patients with MRSA cSSSI.

  • presence of genes encoding the panton valentine leukocidin exotoxin is not the primary determinant of outcome in patients with complicated skin and skin structure infections due to methicillin resistant staphylococcus aureus results of a multinationa
    Journal of Clinical Microbiology, 2009
    Co-Authors: Giang T Tonthat, Martin E Stryjewski, Tom H Rude, Ralph G Corey, Lindsay F Reilly, Steven L Barriere, Fredric C Genter, Vance G Fowler
    Abstract:

    The role of Panton-Valentine leukocidin (PVL) in determining the severity and outcome of complicated skin and skin structure infections (cSSSI) caused by methicillin (Meticillin)-resistant Staphylococcus aureus (MRSA) is controversial. We evaluated potential associations between clinical outcome and PVL status by using MRSA isolates from patients enrolled in two large, multinational phase three clinical trials assessing telavancin for the treatment of cSSSI (the ATLAS program). MRSA isolates from microbiologically evaluable patients were genotyped by pulsed-field gel electrophoresis (PFGE) and PCR for pvl and 31 other putative virulence determinants. A single baseline pathogen of MRSA was isolated from 522 microbiologically evaluable patients (25.1%) among 2,079 randomized patients. Of these MRSA isolates, 83.2% (432/519) exhibited the USA300 PFGE genotype and 89.1% (465/522) were pvl positive. Patients with pvl-positive MRSA were more likely than those with pvl-negative MRSA to be young, to be North American, and to present with major abscesses (P < 0.001 for each). Patients were significantly more likely to be cured if they were infected with pvl-positive MRSA than if they were infected with pvl-negative MRSA (91.6% versus 80.7%; P = 0.015). This observation remained statistically significant after adjustment for presence of abscess, fever, or leukocytosis; infection size; diabetes; patient age; and study medication received. The fnbA, cna, sdrC, map-eap, sed, seg, sei, sej, SCCmec type IV, and agr group II genes were also associated with clinical response (P < 0.05). This contemporary, international study demonstrates that pvl was not the primary determinant of outcome in patients with MRSA cSSSI.

  • inoculum effect with cefazolin among clinical isolates of methicillin susceptible staphylococcus aureus frequency and possible cause of cefazolin treatment failure
    Antimicrobial Agents and Chemotherapy, 2009
    Co-Authors: Esteban C Nannini, Martin E Stryjewski, Agathe Bourgogne, Tom H Rude, Ralph G Corey, Vance G Fowler, Kavindra V Singh, Barbara E. Murray
    Abstract:

    Methicillin (Meticillin)-susceptible Staphylococcus aureus (MSSA) strains producing large amounts of type A β-lactamase (Bla) have been associated with cefazolin failures, but the frequency and impact of these strains have not been well studied. Here we examined 98 MSSA clinical isolates and found that 26% produced type A Bla, 15% type B, 46% type C, and none type D and that 13% lacked blaZ. The cefazolin MIC90 was 2 μg/ml for a standard inoculum and 32 μg/ml for a high inoculum, with 19% of isolates displaying a pronounced inoculum effect (MICs of ≥16 μg/ml with 107 CFU/ml) (9 type A and 10 type C Bla producers). At the high inoculum, type A producers displayed higher cefazolin MICs than type B or C producers, while type B and C producers displayed higher cefamandole MICs. Among isolates from hemodialysis patients with MSSA bacteremia, three from the six patients who experienced cefazolin failure showed a cefazolin inoculum effect, while none from the six patients successfully treated with cefazolin showed an inoculum effect, suggesting an association between these strains and cefazolin failure (P = 0.09 by Fisher's exact test). In summary, 19% of MSSA clinical isolates showed a pronounced inoculum effect with cefazolin, a phenomenon that could explain the cases of cefazolin failure previously reported for hemodialysis patients with MSSA bacteremia. These results suggest that for serious MSSA infections, the presence of a significant inoculum effect with cefazolin could be associated with clinical failure in patients treated with this cephalosporin, particularly when it is used at low doses.

Dietrich Mack - One of the best experts on this subject based on the ideXlab platform.

  • rapid differentiation of staphylococcus aureus staphylococcus epidermidis and other coagulase negative staphylococci and Meticillin susceptibility testing directly from growth positive blood cultures by multiplex real time pcr
    Journal of Medical Microbiology, 2010
    Co-Authors: Leanne Jukes, Jane Mikhail, Naledi Bomemannathoko, Stephen J Hadfield, Llinos G Harris, Khalid Elbouri, Angharad P Davies, Dietrich Mack
    Abstract:

    This study evaluated a multiplex real-time PCR method specific for the mecA, femA-SA and femA-SE genes for rapid identification of Staphylococcus aureus, Staphylococcus epidermidis and non-S. epidermidis coagulase-negative staphylococci (CoNS), and Meticillin susceptibility testing directly in positive blood cultures that grew Gram-positive cocci in clusters. A total of 100 positive blood cultures produced: 39 S. aureus [12 Meticillin-resistant S. aureus (MRSA), 31 % of all the S. aureus]; 30 S. epidermidis (56.6 % of the CoNS), 8 Staphylococcus capitis (15.1 %), 3 Staphylococcus saprophyticus (5.7 %), 4 Staphylococcus hominis (7.5 %), 3 Staphylococcus haemolyticus (5.7 %), 2 Staphylococcus warneri (3.8 %), 1 Staphylococcus cohnii (1.9 %) and 2 unidentified Staphylococcus spp. (3.8 %); and 1 Micrococcus luteus in pure culture. Two blood cultures had no growth on subculture and five blood cultures grew mixed CoNS. For the 95 blood cultures with pure growth or no growth on subculture, there was very good agreement between real-time PCR and the BD Phoenix identification system for staphylococcal species categorization in S. aureus, S. epidermidis and non-S. epidermidis CoNS and Meticillin-resistance determination (Cohen's unweighted kappa coefficient κ=0.882). All MRSA and Meticillin-susceptible S. aureus were correctly identified by mecA amplification. PCR amplification of mecA was more sensitive for direct detection of Meticillin-resistant CoNS in positive blood cultures than testing with the BD Phoenix system. There were no major errors when identifying staphylococcal isolates and their Meticillin susceptibility within 2.5 h. Further studies are needed to evaluate the clinical benefit of using such a rapid test on the consumption of glycopeptide antibiotics and the alteration of empiric therapy in the situation of positive blood cultures growing staphylococci, and the respective clinical outcomes.

Martin E Stryjewski - One of the best experts on this subject based on the ideXlab platform.

  • presence of genes encoding the panton valentine leukocidin exotoxin is not the primary determinant of outcome in patients with complicated skin and skin structure infections due to methicillin resistant staphylococcus aureus results of a multinationa
    Journal of Clinical Microbiology, 2009
    Co-Authors: Ingyu Bae, Martin E Stryjewski, Tom H Rude, Giang T Tonthat, Lindsay F Reilly, Steven L Barriere, Fredric C Genter, G R Corey, Vance G Fowler
    Abstract:

    The role of Panton-Valentine leukocidin (PVL) in determining the severity and outcome of complicated skin and skin structure infections (cSSSI) caused by methicillin (Meticillin)-resistant Staphylococcus aureus (MRSA) is controversial. We evaluated potential associations between clinical outcome and PVL status by using MRSA isolates from patients enrolled in two large, multinational phase three clinical trials assessing telavancin for the treatment of cSSSI (the ATLAS program). MRSA isolates from microbiologically evaluable patients were genotyped by pulsed-field gel electrophoresis (PFGE) and PCR for pvl and 31 other putative virulence determinants. A single baseline pathogen of MRSA was isolated from 522 microbiologically evaluable patients (25.1%) among 2,079 randomized patients. Of these MRSA isolates, 83.2% (432/519) exhibited the USA300 PFGE genotype and 89.1% (465/522) were pvl positive. Patients with pvl-positive MRSA were more likely than those with pvl-negative MRSA to be young, to be North American, and to present with major abscesses (P < 0.001 for each). Patients were significantly more likely to be cured if they were infected with pvl-positive MRSA than if they were infected with pvl-negative MRSA (91.6% versus 80.7%; P = 0.015). This observation remained statistically significant after adjustment for presence of abscess, fever, or leukocytosis; infection size; diabetes; patient age; and study medication received. The fnbA, cna, sdrC, map-eap, sed, seg, sei, sej, SCCmec type IV, and agr group II genes were also associated with clinical response (P < 0.05). This contemporary, international study demonstrates that pvl was not the primary determinant of outcome in patients with MRSA cSSSI.

  • presence of genes encoding the panton valentine leukocidin exotoxin is not the primary determinant of outcome in patients with complicated skin and skin structure infections due to methicillin resistant staphylococcus aureus results of a multinationa
    Journal of Clinical Microbiology, 2009
    Co-Authors: Giang T Tonthat, Martin E Stryjewski, Tom H Rude, Ralph G Corey, Lindsay F Reilly, Steven L Barriere, Fredric C Genter, Vance G Fowler
    Abstract:

    The role of Panton-Valentine leukocidin (PVL) in determining the severity and outcome of complicated skin and skin structure infections (cSSSI) caused by methicillin (Meticillin)-resistant Staphylococcus aureus (MRSA) is controversial. We evaluated potential associations between clinical outcome and PVL status by using MRSA isolates from patients enrolled in two large, multinational phase three clinical trials assessing telavancin for the treatment of cSSSI (the ATLAS program). MRSA isolates from microbiologically evaluable patients were genotyped by pulsed-field gel electrophoresis (PFGE) and PCR for pvl and 31 other putative virulence determinants. A single baseline pathogen of MRSA was isolated from 522 microbiologically evaluable patients (25.1%) among 2,079 randomized patients. Of these MRSA isolates, 83.2% (432/519) exhibited the USA300 PFGE genotype and 89.1% (465/522) were pvl positive. Patients with pvl-positive MRSA were more likely than those with pvl-negative MRSA to be young, to be North American, and to present with major abscesses (P < 0.001 for each). Patients were significantly more likely to be cured if they were infected with pvl-positive MRSA than if they were infected with pvl-negative MRSA (91.6% versus 80.7%; P = 0.015). This observation remained statistically significant after adjustment for presence of abscess, fever, or leukocytosis; infection size; diabetes; patient age; and study medication received. The fnbA, cna, sdrC, map-eap, sed, seg, sei, sej, SCCmec type IV, and agr group II genes were also associated with clinical response (P < 0.05). This contemporary, international study demonstrates that pvl was not the primary determinant of outcome in patients with MRSA cSSSI.

  • inoculum effect with cefazolin among clinical isolates of methicillin susceptible staphylococcus aureus frequency and possible cause of cefazolin treatment failure
    Antimicrobial Agents and Chemotherapy, 2009
    Co-Authors: Esteban C Nannini, Martin E Stryjewski, Agathe Bourgogne, Tom H Rude, Ralph G Corey, Vance G Fowler, Kavindra V Singh, Barbara E. Murray
    Abstract:

    Methicillin (Meticillin)-susceptible Staphylococcus aureus (MSSA) strains producing large amounts of type A β-lactamase (Bla) have been associated with cefazolin failures, but the frequency and impact of these strains have not been well studied. Here we examined 98 MSSA clinical isolates and found that 26% produced type A Bla, 15% type B, 46% type C, and none type D and that 13% lacked blaZ. The cefazolin MIC90 was 2 μg/ml for a standard inoculum and 32 μg/ml for a high inoculum, with 19% of isolates displaying a pronounced inoculum effect (MICs of ≥16 μg/ml with 107 CFU/ml) (9 type A and 10 type C Bla producers). At the high inoculum, type A producers displayed higher cefazolin MICs than type B or C producers, while type B and C producers displayed higher cefamandole MICs. Among isolates from hemodialysis patients with MSSA bacteremia, three from the six patients who experienced cefazolin failure showed a cefazolin inoculum effect, while none from the six patients successfully treated with cefazolin showed an inoculum effect, suggesting an association between these strains and cefazolin failure (P = 0.09 by Fisher's exact test). In summary, 19% of MSSA clinical isolates showed a pronounced inoculum effect with cefazolin, a phenomenon that could explain the cases of cefazolin failure previously reported for hemodialysis patients with MSSA bacteremia. These results suggest that for serious MSSA infections, the presence of a significant inoculum effect with cefazolin could be associated with clinical failure in patients treated with this cephalosporin, particularly when it is used at low doses.

Tom H Rude - One of the best experts on this subject based on the ideXlab platform.

  • presence of genes encoding the panton valentine leukocidin exotoxin is not the primary determinant of outcome in patients with complicated skin and skin structure infections due to methicillin resistant staphylococcus aureus results of a multinationa
    Journal of Clinical Microbiology, 2009
    Co-Authors: Ingyu Bae, Martin E Stryjewski, Tom H Rude, Giang T Tonthat, Lindsay F Reilly, Steven L Barriere, Fredric C Genter, G R Corey, Vance G Fowler
    Abstract:

    The role of Panton-Valentine leukocidin (PVL) in determining the severity and outcome of complicated skin and skin structure infections (cSSSI) caused by methicillin (Meticillin)-resistant Staphylococcus aureus (MRSA) is controversial. We evaluated potential associations between clinical outcome and PVL status by using MRSA isolates from patients enrolled in two large, multinational phase three clinical trials assessing telavancin for the treatment of cSSSI (the ATLAS program). MRSA isolates from microbiologically evaluable patients were genotyped by pulsed-field gel electrophoresis (PFGE) and PCR for pvl and 31 other putative virulence determinants. A single baseline pathogen of MRSA was isolated from 522 microbiologically evaluable patients (25.1%) among 2,079 randomized patients. Of these MRSA isolates, 83.2% (432/519) exhibited the USA300 PFGE genotype and 89.1% (465/522) were pvl positive. Patients with pvl-positive MRSA were more likely than those with pvl-negative MRSA to be young, to be North American, and to present with major abscesses (P < 0.001 for each). Patients were significantly more likely to be cured if they were infected with pvl-positive MRSA than if they were infected with pvl-negative MRSA (91.6% versus 80.7%; P = 0.015). This observation remained statistically significant after adjustment for presence of abscess, fever, or leukocytosis; infection size; diabetes; patient age; and study medication received. The fnbA, cna, sdrC, map-eap, sed, seg, sei, sej, SCCmec type IV, and agr group II genes were also associated with clinical response (P < 0.05). This contemporary, international study demonstrates that pvl was not the primary determinant of outcome in patients with MRSA cSSSI.

  • presence of genes encoding the panton valentine leukocidin exotoxin is not the primary determinant of outcome in patients with complicated skin and skin structure infections due to methicillin resistant staphylococcus aureus results of a multinationa
    Journal of Clinical Microbiology, 2009
    Co-Authors: Giang T Tonthat, Martin E Stryjewski, Tom H Rude, Ralph G Corey, Lindsay F Reilly, Steven L Barriere, Fredric C Genter, Vance G Fowler
    Abstract:

    The role of Panton-Valentine leukocidin (PVL) in determining the severity and outcome of complicated skin and skin structure infections (cSSSI) caused by methicillin (Meticillin)-resistant Staphylococcus aureus (MRSA) is controversial. We evaluated potential associations between clinical outcome and PVL status by using MRSA isolates from patients enrolled in two large, multinational phase three clinical trials assessing telavancin for the treatment of cSSSI (the ATLAS program). MRSA isolates from microbiologically evaluable patients were genotyped by pulsed-field gel electrophoresis (PFGE) and PCR for pvl and 31 other putative virulence determinants. A single baseline pathogen of MRSA was isolated from 522 microbiologically evaluable patients (25.1%) among 2,079 randomized patients. Of these MRSA isolates, 83.2% (432/519) exhibited the USA300 PFGE genotype and 89.1% (465/522) were pvl positive. Patients with pvl-positive MRSA were more likely than those with pvl-negative MRSA to be young, to be North American, and to present with major abscesses (P < 0.001 for each). Patients were significantly more likely to be cured if they were infected with pvl-positive MRSA than if they were infected with pvl-negative MRSA (91.6% versus 80.7%; P = 0.015). This observation remained statistically significant after adjustment for presence of abscess, fever, or leukocytosis; infection size; diabetes; patient age; and study medication received. The fnbA, cna, sdrC, map-eap, sed, seg, sei, sej, SCCmec type IV, and agr group II genes were also associated with clinical response (P < 0.05). This contemporary, international study demonstrates that pvl was not the primary determinant of outcome in patients with MRSA cSSSI.

  • inoculum effect with cefazolin among clinical isolates of methicillin susceptible staphylococcus aureus frequency and possible cause of cefazolin treatment failure
    Antimicrobial Agents and Chemotherapy, 2009
    Co-Authors: Esteban C Nannini, Martin E Stryjewski, Agathe Bourgogne, Tom H Rude, Ralph G Corey, Vance G Fowler, Kavindra V Singh, Barbara E. Murray
    Abstract:

    Methicillin (Meticillin)-susceptible Staphylococcus aureus (MSSA) strains producing large amounts of type A β-lactamase (Bla) have been associated with cefazolin failures, but the frequency and impact of these strains have not been well studied. Here we examined 98 MSSA clinical isolates and found that 26% produced type A Bla, 15% type B, 46% type C, and none type D and that 13% lacked blaZ. The cefazolin MIC90 was 2 μg/ml for a standard inoculum and 32 μg/ml for a high inoculum, with 19% of isolates displaying a pronounced inoculum effect (MICs of ≥16 μg/ml with 107 CFU/ml) (9 type A and 10 type C Bla producers). At the high inoculum, type A producers displayed higher cefazolin MICs than type B or C producers, while type B and C producers displayed higher cefamandole MICs. Among isolates from hemodialysis patients with MSSA bacteremia, three from the six patients who experienced cefazolin failure showed a cefazolin inoculum effect, while none from the six patients successfully treated with cefazolin showed an inoculum effect, suggesting an association between these strains and cefazolin failure (P = 0.09 by Fisher's exact test). In summary, 19% of MSSA clinical isolates showed a pronounced inoculum effect with cefazolin, a phenomenon that could explain the cases of cefazolin failure previously reported for hemodialysis patients with MSSA bacteremia. These results suggest that for serious MSSA infections, the presence of a significant inoculum effect with cefazolin could be associated with clinical failure in patients treated with this cephalosporin, particularly when it is used at low doses.

Giang T Tonthat - One of the best experts on this subject based on the ideXlab platform.

  • presence of genes encoding the panton valentine leukocidin exotoxin is not the primary determinant of outcome in patients with complicated skin and skin structure infections due to methicillin resistant staphylococcus aureus results of a multinationa
    Journal of Clinical Microbiology, 2009
    Co-Authors: Giang T Tonthat, Martin E Stryjewski, Tom H Rude, Ralph G Corey, Lindsay F Reilly, Steven L Barriere, Fredric C Genter, Vance G Fowler
    Abstract:

    The role of Panton-Valentine leukocidin (PVL) in determining the severity and outcome of complicated skin and skin structure infections (cSSSI) caused by methicillin (Meticillin)-resistant Staphylococcus aureus (MRSA) is controversial. We evaluated potential associations between clinical outcome and PVL status by using MRSA isolates from patients enrolled in two large, multinational phase three clinical trials assessing telavancin for the treatment of cSSSI (the ATLAS program). MRSA isolates from microbiologically evaluable patients were genotyped by pulsed-field gel electrophoresis (PFGE) and PCR for pvl and 31 other putative virulence determinants. A single baseline pathogen of MRSA was isolated from 522 microbiologically evaluable patients (25.1%) among 2,079 randomized patients. Of these MRSA isolates, 83.2% (432/519) exhibited the USA300 PFGE genotype and 89.1% (465/522) were pvl positive. Patients with pvl-positive MRSA were more likely than those with pvl-negative MRSA to be young, to be North American, and to present with major abscesses (P < 0.001 for each). Patients were significantly more likely to be cured if they were infected with pvl-positive MRSA than if they were infected with pvl-negative MRSA (91.6% versus 80.7%; P = 0.015). This observation remained statistically significant after adjustment for presence of abscess, fever, or leukocytosis; infection size; diabetes; patient age; and study medication received. The fnbA, cna, sdrC, map-eap, sed, seg, sei, sej, SCCmec type IV, and agr group II genes were also associated with clinical response (P < 0.05). This contemporary, international study demonstrates that pvl was not the primary determinant of outcome in patients with MRSA cSSSI.

  • presence of genes encoding the panton valentine leukocidin exotoxin is not the primary determinant of outcome in patients with complicated skin and skin structure infections due to methicillin resistant staphylococcus aureus results of a multinationa
    Journal of Clinical Microbiology, 2009
    Co-Authors: Ingyu Bae, Martin E Stryjewski, Tom H Rude, Giang T Tonthat, Lindsay F Reilly, Steven L Barriere, Fredric C Genter, G R Corey, Vance G Fowler
    Abstract:

    The role of Panton-Valentine leukocidin (PVL) in determining the severity and outcome of complicated skin and skin structure infections (cSSSI) caused by methicillin (Meticillin)-resistant Staphylococcus aureus (MRSA) is controversial. We evaluated potential associations between clinical outcome and PVL status by using MRSA isolates from patients enrolled in two large, multinational phase three clinical trials assessing telavancin for the treatment of cSSSI (the ATLAS program). MRSA isolates from microbiologically evaluable patients were genotyped by pulsed-field gel electrophoresis (PFGE) and PCR for pvl and 31 other putative virulence determinants. A single baseline pathogen of MRSA was isolated from 522 microbiologically evaluable patients (25.1%) among 2,079 randomized patients. Of these MRSA isolates, 83.2% (432/519) exhibited the USA300 PFGE genotype and 89.1% (465/522) were pvl positive. Patients with pvl-positive MRSA were more likely than those with pvl-negative MRSA to be young, to be North American, and to present with major abscesses (P < 0.001 for each). Patients were significantly more likely to be cured if they were infected with pvl-positive MRSA than if they were infected with pvl-negative MRSA (91.6% versus 80.7%; P = 0.015). This observation remained statistically significant after adjustment for presence of abscess, fever, or leukocytosis; infection size; diabetes; patient age; and study medication received. The fnbA, cna, sdrC, map-eap, sed, seg, sei, sej, SCCmec type IV, and agr group II genes were also associated with clinical response (P < 0.05). This contemporary, international study demonstrates that pvl was not the primary determinant of outcome in patients with MRSA cSSSI.