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Ronald N. Jones - One of the best experts on this subject based on the ideXlab platform.

  • Ceftaroline activity tested against viridans group streptococci from US hospitals
    Diagnostic Microbiology and Infectious Disease, 2015
    Co-Authors: Helio S Sader, Mariana Castanheira, David J Farrell, Rodrigo E Mendes, Robert K Flamm, Paul R. Rhomberg, Ronald N. Jones
    Abstract:

    A total of 840 clinically relevant viridans group streptococci (VGS) isolates (1/patient episode) were collected from 71 US medical centers in 2013-2014. These organisms were tested for susceptibility by reference broth microdilution methods against ceftaroline and selected comparator agents. All isolates were speciated by matrix-assisted laser desorption ionization-time-of-flight (MALDI-TOF) mass spectrometry and were primarily from skin/soft tissue (32.6%) and bloodstream (32.3%) infections. Ceftaroline was highly active against all VGS species/groups with MIC50 and MIC90 values ranging from ≤0.015 to 0.03μg/mL and ≤0.015 to 0.06μg/mL, respectively. The highest ceftaroline MIC value was only 0.5μg/mL (0.5% of strains) and ceftaroline (MIC50/90, 0.03/0.06μg/mL) was 8-fold more active than ceftriaxone (MIC50/90, 0.25/0.5μg/mL). The VGS groups most susceptible to ceftaroline were Streptococcus mutans and Streptococcus bovis (MIC90, ≤0.015μg/mL), whereas the highest ceftaroline MIC values were observed among Streptococcus mitis and Streptococcus sanguinis groups. In summary, ceftaroline exhibited potent in vitro activity against VGS, including many uncommonly isolated species/groups for which very limited susceptibility information is currently available to guide therapy.

  • telavancin in vitro activity against a collection of methicillin resistant staphylococcus aureus isolates including resistant subsets from the united states
    Antimicrobial Agents and Chemotherapy, 2015
    Co-Authors: Rodrigo E Mendes, Helio S Sader, David J Farrell, Robert K Flamm, Ronald N. Jones
    Abstract:

    Telavancin had MIC50, MIC90, and MIC100 values of 0.03, 0.06, and 0.12 μg/ml, respectively, against methicillin-susceptible Staphylococcus aureus, methicillin-resistant S. aureus (MRSA), and non-multidrug-resistant (non-MDR) and MDR subsets. MRSA with elevated MIC values for vancomycin (2 to 4 μg/ml) or daptomycin (1 to 2 μg/ml) had telavancin MIC50 (0.06 μg/ml) values 2-fold higher than those of isolates with lower MIC results (MIC50, 0.03 μg/ml). However, telavancin had MIC90 and MIC100 results of 0.06 and 0.12 μg/ml (100% susceptible), respectively, regardless of the MRSA subset.

  • baseline activity of telavancin against gram positive clinical isolates responsible for documented infections in u s hospitals 2011 2012 as determined by the revised susceptibility testing method
    Antimicrobial Agents and Chemotherapy, 2015
    Co-Authors: Rodrigo E Mendes, Helio S Sader, David J Farrell, Robert K Flamm, Ronald N. Jones
    Abstract:

    Telavancin had MIC50 and MIC90 values of 0.03 and 0.06 μg/ml (100.0% susceptible), respectively, against methicillin-resistant and -susceptible Staphylococcus aureus. Telavancin was active against vancomycin-susceptible Enterococcus faecalis (MIC50/90, 0.12/0.12 μg/ml; 100% susceptible) and Enterococcus faecium (MIC50/90, 0.03/0.06 μg/ml), while higher MIC values were obtained against vancomycin-resistant E. faecium (MIC50/90, 1/2 μg/ml) and E. faecalis (MIC50/90, >2/>2 μg/ml). Streptococci showed telavancin modal MIC results of ≤ 0.015 μg/ml, except against Streptococcus agalactiae (i.e., 0.03 μg/ml). This study reestablishes the telavancin spectrum of activity against isolates recovered from the United States (2011-2012) using the revised broth microdilution method.

  • ceftobiprole activity against over 60 000 clinical bacterial pathogens isolated in europe turkey and israel from 2005 to 2010
    Antimicrobial Agents and Chemotherapy, 2014
    Co-Authors: David J Farrell, Helio S Sader, Robert K Flamm, Ronald N. Jones
    Abstract:

    Ceftobiprole medocaril is a newly approved drug in Europe for the treatment of hospital-acquired pneumonia (HAP) (excluding patients with ventilator-associated pneumonia but including ventilated HAP patients) and community-acquired pneumonia in adults. The aim of this study was to evaluate the in vitro antimicrobial activity of ceftobiprole against prevalent Gram-positive and -negative pathogens isolated in Europe, Turkey, and Israel during 2005 through 2010. A total of 60,084 consecutive, nonduplicate isolates from a wide variety of infections were collected from 33 medical centers. Species identification was confirmed, and all isolates were susceptibility tested using reference broth microdilution methods. Ceftobiprole had high activity against methicillin-susceptible Staphylococcus aureus (MSSA) (100.0% susceptible), methicillin-susceptible coagulase-negative staphylococci (CoNS), beta-hemolytic streptococci, and Streptococcus pneumoniae (99.3% susceptible), with MIC90 values of 0.25, 0.12, ≤0.06, and 0.5 μg/ml, respectively. Ceftobiprole was active against methicillin-resistant S. aureus (MRSA) (98.3% susceptible) and methicillin-resistant CoNS, having a MIC90 of 2 μg/ml. Ceftobiprole was active against Enterococcus faecalis (MIC50/90, 0.5/4 μg/ml) but not against most Enterococcus faecium isolates. Ceftobiprole was very potent against the majority of Enterobacteriaceae (87.3% susceptible), with >80% inhibited at ≤0.12 μg/ml. The potency of ceftobiprole against Pseudomonas aeruginosa (MIC50/90, 2/>8 μg/ml; 64.6% at MIC values of ≤4 μg/ml) was similar to that of ceftazidime (MIC50/90, 2/>16 μg/ml; 75.4% susceptible), but limited activity was observed against Acinetobacter spp. and Stenotrophomonas maltophilia. High activity was also observed against all Haemophilus influenzae (MIC90, ≤0.06 μg/ml) and Moraxella catarrhalis (MIC50/90, ≤0.06/0.25 μg/ml) isolates. Ceftobiprole demonstrated a wide spectrum of antimicrobial activity against this very large longitudinal sample of contemporary pathogens.

  • antimicrobial activity of ceftaroline tested against drug resistant subsets of streptococcus pneumoniae from u s medical centers
    Antimicrobial Agents and Chemotherapy, 2014
    Co-Authors: Robert K Flamm, Helio S Sader, David J Farrell, Ronald N. Jones
    Abstract:

    Streptococcus pneumoniae isolates (6,958) were collected from patients at 163 U.S. medical centers during 2009 through 2012. Isolates were evaluated for multidrug resistance (MDR) to penicillin, ceftriaxone, erythromycin, tetracycline, trimethoprim-sulfamethoxazole, and levofloxacin. Ceftaroline was 16-fold more potent than ceftriaxone (MIC50/MIC90, ≤0.25/2 μg/ml) against all isolates. For MDR isolates (35.2% of tested strains), ceftaroline (MIC50/MIC90, 0.06/0.25 μg/ml; 100.0% susceptible) was the most active agent tested, being 8-fold more potent than ceftriaxone (MIC50/MIC90, 0.5/2 μg/ml) and 16-fold more potent than penicillin (MIC50/MIC90, 1/4 μg/ml).

Robert K Flamm - One of the best experts on this subject based on the ideXlab platform.

  • in vitro activity of apx001a manogepix and comparator agents against 1 706 fungal isolates collected during an international surveillance program in 2017
    Antimicrobial Agents and Chemotherapy, 2019
    Co-Authors: M A Pfaller, Robert K Flamm, Michael D Huband, Paul Bien, M Castanheira
    Abstract:

    Current antifungal agents cover a majority of opportunistic fungal pathogens; however, breakthrough invasive fungal infections continue to occur and increasingly involve relatively uncommon yeasts and molds, which often exhibit decreased susceptibility. APX001A (manogepix) is a first-in-class small-molecule inhibitor of the conserved fungal Gwt1 protein. This enzyme is required for acylation of inositol during glycosylphosphatidylinositol anchor biosynthesis. APX001A is active against the major fungal pathogens, i.e., Candida (except Candida krusei), Aspergillus, and hard-to-treat molds, including Fusarium and Scedosporium In this study, we tested APX001A and comparators against 1,706 contemporary clinical fungal isolates collected in 2017 from 68 medical centers in North America (37.3%), Europe (43.4%), the Asia-Pacific region (12.7%), or Latin America (6.6%). Among the isolates tested, 78.5% were Candida spp., 3.9% were non-Candida yeasts, including 30 (1.8%) Cryptococcus neoformans var. grubii isolates, 14.7% were Aspergillus spp., and 2.9% were other molds. All isolates were tested by CLSI reference broth microdilution. APX001A (MIC50, 0.008 μg/ml; MIC90, 0.06 μg/ml) was the most active agent tested against Candida sp. isolates; corresponding anidulafungin, micafungin, and fluconazole MIC90 values were 16- to 64-fold higher. Similarly, APX001A (MIC50, 0.25 μg/ml; MIC90, 0.5 μg/ml) was ≥8-fold more active than anidulafungin, micafungin, and fluconazole against C. neoformans var. grubii Against Aspergillus spp., AXP001A (50% minimal effective concentration [MEC50], 0.015 μg/ml; MEC90, 0.03 μg/ml) was comparable in activity to anidulafungin and micafungin. Aspergillus isolates (>98%) exhibited a wild-type phenotype for the mold-active triazoles (itraconazole, posaconazole, and voriconazole). APX001A was highly active against uncommon species of Candida, non-Candida yeasts, and rare molds, including 11 isolates of Scedosporium spp. (MEC values, 0.015 to 0.06 μg/ml). APX001A demonstrated potent in vitro activity against recent fungal isolates, including echinocandin- and fluconazole-resistant strains. The extended spectrum of APX001A was also notable for its potency against many less common but antifungal-resistant strains. Further studies are in progress to evaluate the clinical utility of the methyl phosphate prodrug, APX001, in difficult-to-treat resistant fungal infections.

  • Antimicrobial Susceptibility of Pseudomonas aeruginosa to Ceftazidime-Avibactam, Ceftolozane-Tazobactam, Piperacillin-Tazobactam, and Meropenem Stratified by U.S. Census Divisions: Results from the 2017 INFORM Program.
    Antimicrobial agents and chemotherapy, 2018
    Co-Authors: Helio S Sader, Robert K Flamm, Cecilia G Carvalhaes, Mariana Castanheira
    Abstract:

    Pseudomonas aeruginosa isolates (n = 1,909) were collected from 70 U.S. medical centers, and their susceptibilities were tested using the broth microdilution method. Ceftazidime-avibactam (MIC50/MIC90, 2/8 mg/liter) and ceftolozane-tazobactam (MIC50/MIC90, 0.5/2 mg/liter) were the most active (i.e., had the highest susceptibility rates) compounds after colistin, with national susceptibility rates of 96.9% and 97.5%, respectively. Overall, piperacillin-tazobactam (MIC50/MIC90, 4/128 mg/liter) and meropenem (MIC50/MIC90, 0.5/16 mg/liter) were active against 77.5% and 76.0% of the isolates, respectively. Susceptibility variations across census divisions were documented for many antimicrobials.

  • in vitro activity of plazomicin against gram negative and gram positive isolates collected from u s hospitals and comparative activities of aminoglycosides against carbapenem resistant enterobacteriaceae and isolates carrying carbapenemase genes
    Antimicrobial Agents and Chemotherapy, 2018
    Co-Authors: Mariana Castanheira, Rodrigo E Mendes, Andrew P Davis, Alisa W Serio, Kevin M Krause, Robert K Flamm
    Abstract:

    Plazomicin and comparator agents were tested by using the CLSI reference broth microdilution method against 4,825 clinical isolates collected during 2014 and 2015 in 70 U.S. hospitals as part of the ALERT (Antimicrobial Longitudinal Evaluation and Resistance Trends) program. Plazomicin (MIC50/MIC90, 0.5/2 μg/ml) inhibited 99.2% of 4,362 Enterobacteriaceae at ≤4 μg/ml. Amikacin, gentamicin, and tobramycin inhibited 98.9%, 90.3%, and 90.3% of these isolates, respectively, by applying CLSI breakpoints. The activities of plazomicin were similar among Enterobacteriaceae species, with MIC50 values ranging from 0.25 to 1 μg/ml, with the exception of Proteus mirabilis and indole-positive Proteeae that displayed MIC50 values of 2 μg/ml. For 97 carbapenem-resistant Enterobacteriaceae (CRE), which included 87 isolates carrying blaKPC, plazomicin inhibited all but 1 isolate at ≤2 μg/ml (99.0% and 98.9%, respectively). Amikacin and gentamicin inhibited 64.9% and 56.7% of the CRE isolates at the respective CLSI breakpoints. Plazomicin inhibited 96.5 and 95.5% of the gentamicin-resistant isolates, 96.9 and 96.5% of the tobramycin-resistant isolates, and 64.3 and 90.0% of the amikacin-resistant isolates according to CLSI and EUCAST breakpoints, respectively. The activities of plazomicin against Pseudomonas aeruginosa (MIC50/MIC90, 4/16 μg/ml) and Acinetobacter species (MIC50/MIC90, 2/16 μg/ml) isolates were similar. Plazomicin was active against coagulase-negative staphylococci (MIC50/MIC90, 0.12/0.5 μg/ml) and Staphylococcus aureus (MIC50/MIC90, 0.5/0.5 μg/ml) but had limited activity against Enterococcus spp. (MIC50/MIC90, 16/64 μg/ml) and Streptococcus pneumoniae (MIC50/MIC90, 32/64 μg/ml). Plazomicin activity against the Enterobacteriaceae tested, including CRE and isolates carrying blaKPC from U.S. hospitals, supports the development plan for plazomicin to treat serious infections caused by resistant Enterobacteriaceae in patients with limited treatment options.

  • antimicrobial activity of oritavancin and comparator agents when tested against gram positive bacterial isolates causing infections in cancer patients 2014 16
    Journal of Antimicrobial Chemotherapy, 2018
    Co-Authors: M A Pfaller, Helio S Sader, Robert K Flamm, M Castanheira, Rodrigo E Mendes
    Abstract:

    Objectives The in vitro activity of oritavancin was assessed against clinically relevant Gram-positive pathogens causing infections in cancer patients in European and US hospitals. Methods A total of 1357 Gram-positive cocci (GPC) were included. Isolates were predominantly from bloodstream infections (54.6%). The most frequently isolated GPC were Staphylococcus aureus (43.6%), CoNS (14.4%) and Enterococcus spp. (22.0%). Results Oritavancin (99.8% susceptible) showed modal MIC, MIC50 and MIC90 results of 0.015, 0.015-0.03 and 0.06 mg/L, respectively, when tested against S. aureus, regardless of methicillin susceptibility or geographical region. CoNS isolates from the USA demonstrated an MIC90 of oritavancin (MIC90, 0.12 mg/L) that was slightly higher than that for isolates from European countries (MIC90 0.06 mg/L). Oritavancin inhibited all Enterococcus faecalis and Enterococcus faecium, including VRE, at ≤ 0.25 mg/L. Oritavancin exhibited MIC50 results of 0.03 and 0.008-0.015 mg/L when tested against isolates of β-haemolytic streptococci and viridans group streptococci, respectively, regardless of geographical region. Conclusions Oritavancin had potent activity in vitro against this contemporary collection of European and US GPC isolates from cancer patients.

  • surveillance of omadacycline activity tested against clinical isolates from the united states and europe as part of the 2016 sentry antimicrobial surveillance program
    Antimicrobial Agents and Chemotherapy, 2018
    Co-Authors: Michael A Pfaller, Michael D Huband, Dee Shortridge, Robert K Flamm
    Abstract:

    Omadacycline was tested against 21,000 bacterial isolates collected prospectively from medical centers in Europe and the United States during 2016. Omadacycline was active against Staphylococcus aureus (MIC50/MIC90, 0.12/0.25 mg/liter), including methicillin-resistant S. aureus (MRSA); streptococci (MIC50/MIC90, 0.06/0.12 mg/liter), including Streptococcus pneumoniae, viridans group streptococci, and beta-hemolytic streptococci; Enterobacteriaceae, including Escherichia coli (MIC50/MIC90, 0.5/2 mg/liter); Haemophilus influenzae (MIC50/MIC90, 1/1 mg/liter); and Moraxella catarrhalis (MIC50/MIC90, 0.25/0.25 mg/liter). Omadacycline merits further study in serious infections where resistant pathogens may be encountered.

Helio S Sader - One of the best experts on this subject based on the ideXlab platform.

  • Antimicrobial Susceptibility of Pseudomonas aeruginosa to Ceftazidime-Avibactam, Ceftolozane-Tazobactam, Piperacillin-Tazobactam, and Meropenem Stratified by U.S. Census Divisions: Results from the 2017 INFORM Program.
    Antimicrobial agents and chemotherapy, 2018
    Co-Authors: Helio S Sader, Robert K Flamm, Cecilia G Carvalhaes, Mariana Castanheira
    Abstract:

    Pseudomonas aeruginosa isolates (n = 1,909) were collected from 70 U.S. medical centers, and their susceptibilities were tested using the broth microdilution method. Ceftazidime-avibactam (MIC50/MIC90, 2/8 mg/liter) and ceftolozane-tazobactam (MIC50/MIC90, 0.5/2 mg/liter) were the most active (i.e., had the highest susceptibility rates) compounds after colistin, with national susceptibility rates of 96.9% and 97.5%, respectively. Overall, piperacillin-tazobactam (MIC50/MIC90, 4/128 mg/liter) and meropenem (MIC50/MIC90, 0.5/16 mg/liter) were active against 77.5% and 76.0% of the isolates, respectively. Susceptibility variations across census divisions were documented for many antimicrobials.

  • antimicrobial activity of oritavancin and comparator agents when tested against gram positive bacterial isolates causing infections in cancer patients 2014 16
    Journal of Antimicrobial Chemotherapy, 2018
    Co-Authors: M A Pfaller, Helio S Sader, Robert K Flamm, M Castanheira, Rodrigo E Mendes
    Abstract:

    Objectives The in vitro activity of oritavancin was assessed against clinically relevant Gram-positive pathogens causing infections in cancer patients in European and US hospitals. Methods A total of 1357 Gram-positive cocci (GPC) were included. Isolates were predominantly from bloodstream infections (54.6%). The most frequently isolated GPC were Staphylococcus aureus (43.6%), CoNS (14.4%) and Enterococcus spp. (22.0%). Results Oritavancin (99.8% susceptible) showed modal MIC, MIC50 and MIC90 results of 0.015, 0.015-0.03 and 0.06 mg/L, respectively, when tested against S. aureus, regardless of methicillin susceptibility or geographical region. CoNS isolates from the USA demonstrated an MIC90 of oritavancin (MIC90, 0.12 mg/L) that was slightly higher than that for isolates from European countries (MIC90 0.06 mg/L). Oritavancin inhibited all Enterococcus faecalis and Enterococcus faecium, including VRE, at ≤ 0.25 mg/L. Oritavancin exhibited MIC50 results of 0.03 and 0.008-0.015 mg/L when tested against isolates of β-haemolytic streptococci and viridans group streptococci, respectively, regardless of geographical region. Conclusions Oritavancin had potent activity in vitro against this contemporary collection of European and US GPC isolates from cancer patients.

  • antimicrobial activities of aztreonam avibactam and comparator agents against contemporary 2016 clinical enterobacteriaceae isolates
    Antimicrobial Agents and Chemotherapy, 2017
    Co-Authors: Helio S Sader, Rodrigo E Mendes, Robert K Flamm, Michael A Pfaller, Dee Shortridge, Mariana Castanheira
    Abstract:

    A total of 10,451 contemporary (2016) Enterobacteriaceae isolates from 84 U.S. medical centers and 116 metallo-β-lactamase- and/or OXA-48-like-producing Enterobacteriaceae isolates from other countries were tested against aztreonam-avibactam and comparators. All U.S. isolates were inhibited at aztreonam-avibactam MICs of ≤8 μg/ml (MIC50, ≤0.03 μg/ml; MIC90, 0.12 μg/ml), including Klebsiella pneumoniae carbapenemase-producing isolates (n = 102; MIC50, 0.25 μg/ml; MIC90, 0.5 μg/ml), multidrug-resistant isolates (n = 876; MIC50, 0.06 μg/ml; MIC90, 0.25 μg/ml), and extensively drug-resistant isolates (n = 111; MIC50, 0.12 μg/ml; MIC90, 0.5 μg/ml). The highest aztreonam-avibactam MIC value among ex-U.S. isolates was 4 μg/ml.

  • Ceftaroline activity tested against viridans group streptococci from US hospitals
    Diagnostic Microbiology and Infectious Disease, 2015
    Co-Authors: Helio S Sader, Mariana Castanheira, David J Farrell, Rodrigo E Mendes, Robert K Flamm, Paul R. Rhomberg, Ronald N. Jones
    Abstract:

    A total of 840 clinically relevant viridans group streptococci (VGS) isolates (1/patient episode) were collected from 71 US medical centers in 2013-2014. These organisms were tested for susceptibility by reference broth microdilution methods against ceftaroline and selected comparator agents. All isolates were speciated by matrix-assisted laser desorption ionization-time-of-flight (MALDI-TOF) mass spectrometry and were primarily from skin/soft tissue (32.6%) and bloodstream (32.3%) infections. Ceftaroline was highly active against all VGS species/groups with MIC50 and MIC90 values ranging from ≤0.015 to 0.03μg/mL and ≤0.015 to 0.06μg/mL, respectively. The highest ceftaroline MIC value was only 0.5μg/mL (0.5% of strains) and ceftaroline (MIC50/90, 0.03/0.06μg/mL) was 8-fold more active than ceftriaxone (MIC50/90, 0.25/0.5μg/mL). The VGS groups most susceptible to ceftaroline were Streptococcus mutans and Streptococcus bovis (MIC90, ≤0.015μg/mL), whereas the highest ceftaroline MIC values were observed among Streptococcus mitis and Streptococcus sanguinis groups. In summary, ceftaroline exhibited potent in vitro activity against VGS, including many uncommonly isolated species/groups for which very limited susceptibility information is currently available to guide therapy.

  • telavancin in vitro activity against a collection of methicillin resistant staphylococcus aureus isolates including resistant subsets from the united states
    Antimicrobial Agents and Chemotherapy, 2015
    Co-Authors: Rodrigo E Mendes, Helio S Sader, David J Farrell, Robert K Flamm, Ronald N. Jones
    Abstract:

    Telavancin had MIC50, MIC90, and MIC100 values of 0.03, 0.06, and 0.12 μg/ml, respectively, against methicillin-susceptible Staphylococcus aureus, methicillin-resistant S. aureus (MRSA), and non-multidrug-resistant (non-MDR) and MDR subsets. MRSA with elevated MIC values for vancomycin (2 to 4 μg/ml) or daptomycin (1 to 2 μg/ml) had telavancin MIC50 (0.06 μg/ml) values 2-fold higher than those of isolates with lower MIC results (MIC50, 0.03 μg/ml). However, telavancin had MIC90 and MIC100 results of 0.06 and 0.12 μg/ml (100% susceptible), respectively, regardless of the MRSA subset.

Rodrigo E Mendes - One of the best experts on this subject based on the ideXlab platform.

  • in vitro activity of plazomicin against gram negative and gram positive isolates collected from u s hospitals and comparative activities of aminoglycosides against carbapenem resistant enterobacteriaceae and isolates carrying carbapenemase genes
    Antimicrobial Agents and Chemotherapy, 2018
    Co-Authors: Mariana Castanheira, Rodrigo E Mendes, Andrew P Davis, Alisa W Serio, Kevin M Krause, Robert K Flamm
    Abstract:

    Plazomicin and comparator agents were tested by using the CLSI reference broth microdilution method against 4,825 clinical isolates collected during 2014 and 2015 in 70 U.S. hospitals as part of the ALERT (Antimicrobial Longitudinal Evaluation and Resistance Trends) program. Plazomicin (MIC50/MIC90, 0.5/2 μg/ml) inhibited 99.2% of 4,362 Enterobacteriaceae at ≤4 μg/ml. Amikacin, gentamicin, and tobramycin inhibited 98.9%, 90.3%, and 90.3% of these isolates, respectively, by applying CLSI breakpoints. The activities of plazomicin were similar among Enterobacteriaceae species, with MIC50 values ranging from 0.25 to 1 μg/ml, with the exception of Proteus mirabilis and indole-positive Proteeae that displayed MIC50 values of 2 μg/ml. For 97 carbapenem-resistant Enterobacteriaceae (CRE), which included 87 isolates carrying blaKPC, plazomicin inhibited all but 1 isolate at ≤2 μg/ml (99.0% and 98.9%, respectively). Amikacin and gentamicin inhibited 64.9% and 56.7% of the CRE isolates at the respective CLSI breakpoints. Plazomicin inhibited 96.5 and 95.5% of the gentamicin-resistant isolates, 96.9 and 96.5% of the tobramycin-resistant isolates, and 64.3 and 90.0% of the amikacin-resistant isolates according to CLSI and EUCAST breakpoints, respectively. The activities of plazomicin against Pseudomonas aeruginosa (MIC50/MIC90, 4/16 μg/ml) and Acinetobacter species (MIC50/MIC90, 2/16 μg/ml) isolates were similar. Plazomicin was active against coagulase-negative staphylococci (MIC50/MIC90, 0.12/0.5 μg/ml) and Staphylococcus aureus (MIC50/MIC90, 0.5/0.5 μg/ml) but had limited activity against Enterococcus spp. (MIC50/MIC90, 16/64 μg/ml) and Streptococcus pneumoniae (MIC50/MIC90, 32/64 μg/ml). Plazomicin activity against the Enterobacteriaceae tested, including CRE and isolates carrying blaKPC from U.S. hospitals, supports the development plan for plazomicin to treat serious infections caused by resistant Enterobacteriaceae in patients with limited treatment options.

  • antimicrobial activity of oritavancin and comparator agents when tested against gram positive bacterial isolates causing infections in cancer patients 2014 16
    Journal of Antimicrobial Chemotherapy, 2018
    Co-Authors: M A Pfaller, Helio S Sader, Robert K Flamm, M Castanheira, Rodrigo E Mendes
    Abstract:

    Objectives The in vitro activity of oritavancin was assessed against clinically relevant Gram-positive pathogens causing infections in cancer patients in European and US hospitals. Methods A total of 1357 Gram-positive cocci (GPC) were included. Isolates were predominantly from bloodstream infections (54.6%). The most frequently isolated GPC were Staphylococcus aureus (43.6%), CoNS (14.4%) and Enterococcus spp. (22.0%). Results Oritavancin (99.8% susceptible) showed modal MIC, MIC50 and MIC90 results of 0.015, 0.015-0.03 and 0.06 mg/L, respectively, when tested against S. aureus, regardless of methicillin susceptibility or geographical region. CoNS isolates from the USA demonstrated an MIC90 of oritavancin (MIC90, 0.12 mg/L) that was slightly higher than that for isolates from European countries (MIC90 0.06 mg/L). Oritavancin inhibited all Enterococcus faecalis and Enterococcus faecium, including VRE, at ≤ 0.25 mg/L. Oritavancin exhibited MIC50 results of 0.03 and 0.008-0.015 mg/L when tested against isolates of β-haemolytic streptococci and viridans group streptococci, respectively, regardless of geographical region. Conclusions Oritavancin had potent activity in vitro against this contemporary collection of European and US GPC isolates from cancer patients.

  • antimicrobial activities of aztreonam avibactam and comparator agents against contemporary 2016 clinical enterobacteriaceae isolates
    Antimicrobial Agents and Chemotherapy, 2017
    Co-Authors: Helio S Sader, Rodrigo E Mendes, Robert K Flamm, Michael A Pfaller, Dee Shortridge, Mariana Castanheira
    Abstract:

    A total of 10,451 contemporary (2016) Enterobacteriaceae isolates from 84 U.S. medical centers and 116 metallo-β-lactamase- and/or OXA-48-like-producing Enterobacteriaceae isolates from other countries were tested against aztreonam-avibactam and comparators. All U.S. isolates were inhibited at aztreonam-avibactam MICs of ≤8 μg/ml (MIC50, ≤0.03 μg/ml; MIC90, 0.12 μg/ml), including Klebsiella pneumoniae carbapenemase-producing isolates (n = 102; MIC50, 0.25 μg/ml; MIC90, 0.5 μg/ml), multidrug-resistant isolates (n = 876; MIC50, 0.06 μg/ml; MIC90, 0.25 μg/ml), and extensively drug-resistant isolates (n = 111; MIC50, 0.12 μg/ml; MIC90, 0.5 μg/ml). The highest aztreonam-avibactam MIC value among ex-U.S. isolates was 4 μg/ml.

  • Ceftaroline activity tested against viridans group streptococci from US hospitals
    Diagnostic Microbiology and Infectious Disease, 2015
    Co-Authors: Helio S Sader, Mariana Castanheira, David J Farrell, Rodrigo E Mendes, Robert K Flamm, Paul R. Rhomberg, Ronald N. Jones
    Abstract:

    A total of 840 clinically relevant viridans group streptococci (VGS) isolates (1/patient episode) were collected from 71 US medical centers in 2013-2014. These organisms were tested for susceptibility by reference broth microdilution methods against ceftaroline and selected comparator agents. All isolates were speciated by matrix-assisted laser desorption ionization-time-of-flight (MALDI-TOF) mass spectrometry and were primarily from skin/soft tissue (32.6%) and bloodstream (32.3%) infections. Ceftaroline was highly active against all VGS species/groups with MIC50 and MIC90 values ranging from ≤0.015 to 0.03μg/mL and ≤0.015 to 0.06μg/mL, respectively. The highest ceftaroline MIC value was only 0.5μg/mL (0.5% of strains) and ceftaroline (MIC50/90, 0.03/0.06μg/mL) was 8-fold more active than ceftriaxone (MIC50/90, 0.25/0.5μg/mL). The VGS groups most susceptible to ceftaroline were Streptococcus mutans and Streptococcus bovis (MIC90, ≤0.015μg/mL), whereas the highest ceftaroline MIC values were observed among Streptococcus mitis and Streptococcus sanguinis groups. In summary, ceftaroline exhibited potent in vitro activity against VGS, including many uncommonly isolated species/groups for which very limited susceptibility information is currently available to guide therapy.

  • telavancin in vitro activity against a collection of methicillin resistant staphylococcus aureus isolates including resistant subsets from the united states
    Antimicrobial Agents and Chemotherapy, 2015
    Co-Authors: Rodrigo E Mendes, Helio S Sader, David J Farrell, Robert K Flamm, Ronald N. Jones
    Abstract:

    Telavancin had MIC50, MIC90, and MIC100 values of 0.03, 0.06, and 0.12 μg/ml, respectively, against methicillin-susceptible Staphylococcus aureus, methicillin-resistant S. aureus (MRSA), and non-multidrug-resistant (non-MDR) and MDR subsets. MRSA with elevated MIC values for vancomycin (2 to 4 μg/ml) or daptomycin (1 to 2 μg/ml) had telavancin MIC50 (0.06 μg/ml) values 2-fold higher than those of isolates with lower MIC results (MIC50, 0.03 μg/ml). However, telavancin had MIC90 and MIC100 results of 0.06 and 0.12 μg/ml (100% susceptible), respectively, regardless of the MRSA subset.

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  • Ceftaroline activity tested against viridans group streptococci from US hospitals
    Diagnostic Microbiology and Infectious Disease, 2015
    Co-Authors: Helio S Sader, Mariana Castanheira, David J Farrell, Rodrigo E Mendes, Robert K Flamm, Paul R. Rhomberg, Ronald N. Jones
    Abstract:

    A total of 840 clinically relevant viridans group streptococci (VGS) isolates (1/patient episode) were collected from 71 US medical centers in 2013-2014. These organisms were tested for susceptibility by reference broth microdilution methods against ceftaroline and selected comparator agents. All isolates were speciated by matrix-assisted laser desorption ionization-time-of-flight (MALDI-TOF) mass spectrometry and were primarily from skin/soft tissue (32.6%) and bloodstream (32.3%) infections. Ceftaroline was highly active against all VGS species/groups with MIC50 and MIC90 values ranging from ≤0.015 to 0.03μg/mL and ≤0.015 to 0.06μg/mL, respectively. The highest ceftaroline MIC value was only 0.5μg/mL (0.5% of strains) and ceftaroline (MIC50/90, 0.03/0.06μg/mL) was 8-fold more active than ceftriaxone (MIC50/90, 0.25/0.5μg/mL). The VGS groups most susceptible to ceftaroline were Streptococcus mutans and Streptococcus bovis (MIC90, ≤0.015μg/mL), whereas the highest ceftaroline MIC values were observed among Streptococcus mitis and Streptococcus sanguinis groups. In summary, ceftaroline exhibited potent in vitro activity against VGS, including many uncommonly isolated species/groups for which very limited susceptibility information is currently available to guide therapy.

  • telavancin in vitro activity against a collection of methicillin resistant staphylococcus aureus isolates including resistant subsets from the united states
    Antimicrobial Agents and Chemotherapy, 2015
    Co-Authors: Rodrigo E Mendes, Helio S Sader, David J Farrell, Robert K Flamm, Ronald N. Jones
    Abstract:

    Telavancin had MIC50, MIC90, and MIC100 values of 0.03, 0.06, and 0.12 μg/ml, respectively, against methicillin-susceptible Staphylococcus aureus, methicillin-resistant S. aureus (MRSA), and non-multidrug-resistant (non-MDR) and MDR subsets. MRSA with elevated MIC values for vancomycin (2 to 4 μg/ml) or daptomycin (1 to 2 μg/ml) had telavancin MIC50 (0.06 μg/ml) values 2-fold higher than those of isolates with lower MIC results (MIC50, 0.03 μg/ml). However, telavancin had MIC90 and MIC100 results of 0.06 and 0.12 μg/ml (100% susceptible), respectively, regardless of the MRSA subset.

  • baseline activity of telavancin against gram positive clinical isolates responsible for documented infections in u s hospitals 2011 2012 as determined by the revised susceptibility testing method
    Antimicrobial Agents and Chemotherapy, 2015
    Co-Authors: Rodrigo E Mendes, Helio S Sader, David J Farrell, Robert K Flamm, Ronald N. Jones
    Abstract:

    Telavancin had MIC50 and MIC90 values of 0.03 and 0.06 μg/ml (100.0% susceptible), respectively, against methicillin-resistant and -susceptible Staphylococcus aureus. Telavancin was active against vancomycin-susceptible Enterococcus faecalis (MIC50/90, 0.12/0.12 μg/ml; 100% susceptible) and Enterococcus faecium (MIC50/90, 0.03/0.06 μg/ml), while higher MIC values were obtained against vancomycin-resistant E. faecium (MIC50/90, 1/2 μg/ml) and E. faecalis (MIC50/90, >2/>2 μg/ml). Streptococci showed telavancin modal MIC results of ≤ 0.015 μg/ml, except against Streptococcus agalactiae (i.e., 0.03 μg/ml). This study reestablishes the telavancin spectrum of activity against isolates recovered from the United States (2011-2012) using the revised broth microdilution method.

  • ceftobiprole activity against over 60 000 clinical bacterial pathogens isolated in europe turkey and israel from 2005 to 2010
    Antimicrobial Agents and Chemotherapy, 2014
    Co-Authors: David J Farrell, Helio S Sader, Robert K Flamm, Ronald N. Jones
    Abstract:

    Ceftobiprole medocaril is a newly approved drug in Europe for the treatment of hospital-acquired pneumonia (HAP) (excluding patients with ventilator-associated pneumonia but including ventilated HAP patients) and community-acquired pneumonia in adults. The aim of this study was to evaluate the in vitro antimicrobial activity of ceftobiprole against prevalent Gram-positive and -negative pathogens isolated in Europe, Turkey, and Israel during 2005 through 2010. A total of 60,084 consecutive, nonduplicate isolates from a wide variety of infections were collected from 33 medical centers. Species identification was confirmed, and all isolates were susceptibility tested using reference broth microdilution methods. Ceftobiprole had high activity against methicillin-susceptible Staphylococcus aureus (MSSA) (100.0% susceptible), methicillin-susceptible coagulase-negative staphylococci (CoNS), beta-hemolytic streptococci, and Streptococcus pneumoniae (99.3% susceptible), with MIC90 values of 0.25, 0.12, ≤0.06, and 0.5 μg/ml, respectively. Ceftobiprole was active against methicillin-resistant S. aureus (MRSA) (98.3% susceptible) and methicillin-resistant CoNS, having a MIC90 of 2 μg/ml. Ceftobiprole was active against Enterococcus faecalis (MIC50/90, 0.5/4 μg/ml) but not against most Enterococcus faecium isolates. Ceftobiprole was very potent against the majority of Enterobacteriaceae (87.3% susceptible), with >80% inhibited at ≤0.12 μg/ml. The potency of ceftobiprole against Pseudomonas aeruginosa (MIC50/90, 2/>8 μg/ml; 64.6% at MIC values of ≤4 μg/ml) was similar to that of ceftazidime (MIC50/90, 2/>16 μg/ml; 75.4% susceptible), but limited activity was observed against Acinetobacter spp. and Stenotrophomonas maltophilia. High activity was also observed against all Haemophilus influenzae (MIC90, ≤0.06 μg/ml) and Moraxella catarrhalis (MIC50/90, ≤0.06/0.25 μg/ml) isolates. Ceftobiprole demonstrated a wide spectrum of antimicrobial activity against this very large longitudinal sample of contemporary pathogens.

  • antimicrobial activity of ceftaroline tested against drug resistant subsets of streptococcus pneumoniae from u s medical centers
    Antimicrobial Agents and Chemotherapy, 2014
    Co-Authors: Robert K Flamm, Helio S Sader, David J Farrell, Ronald N. Jones
    Abstract:

    Streptococcus pneumoniae isolates (6,958) were collected from patients at 163 U.S. medical centers during 2009 through 2012. Isolates were evaluated for multidrug resistance (MDR) to penicillin, ceftriaxone, erythromycin, tetracycline, trimethoprim-sulfamethoxazole, and levofloxacin. Ceftaroline was 16-fold more potent than ceftriaxone (MIC50/MIC90, ≤0.25/2 μg/ml) against all isolates. For MDR isolates (35.2% of tested strains), ceftaroline (MIC50/MIC90, 0.06/0.25 μg/ml; 100.0% susceptible) was the most active agent tested, being 8-fold more potent than ceftriaxone (MIC50/MIC90, 0.5/2 μg/ml) and 16-fold more potent than penicillin (MIC50/MIC90, 1/4 μg/ml).