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This study evaluated the in vitro antimicrobial activity of telavancin against a large collection of Gram-positive pathogens of clinical importance, which were collected worldwide from 2015 through 2017, including methicillin-resistant Staphylococcus aureus (MRSA), coagulase-negative staphylococci, Enterococcus spp., β-hemolytic streptococci (BHS), Streptococcus pneumoniae , and viridans group streptococci (VGS). This report completes 7 years of continuous surveillance data for telavancin using the approved reference method for in vitro testing methodology that includes the addition of polysorbate 80. For isolates collected from 2015 through 2017, telavancin exhibited potent activity against the following species and groups that have Clinical and Laboratory Standards Institute (CLSI)-approved interpretive criteria: MRSA (MIC 90 value, 0.06 μg/mL; 100% susceptible), vancomycin-susceptible Enterococcus faecalis (MIC 90 value, 0.25 μg/mL; 99.9% susceptible), BHS (MIC 90 value, 0.03 μg/mL; 100% susceptible), and VGS (MIC 90 value, 0.03 μg/mL; 99.0% susceptible). Importantly, telavancin maintained excellent antimicrobial activity against multidrug-resistant subsets of these pathogen groups and against ceftaroline-nonsusceptible (telavancin MIC 90 value, 0.06 μg/mL; 100% susceptible) and ceftaroline-resistant (telavancin MIC 90 value, 0.12 μg/mL; 100% susceptible) S. aureus isolates.

Activities of tedizolid and comparators were evaluated against gram-positive isolates responsible for skin and skin structure infections, pneumonia, and bloodstream infections. Non-duplicate gram-positive isolates (8011) were collected from 20 European countries/regions. Tedizolid (0.12 mg/L) showed similar results of minimum inhibitory concentration required to inhibit the growth of 50% of organisms (MIC 50 ) regardless of pathogen/group or infection type, except for coagulase-negative staphylococci, Enterococcus faecalis , and viridans group streptococci (VGS), against which tedizolid had MIC 50 values of 0.06, 0.25, and 0.06 mg/L, respectively. Similar results of tedizolid MIC 50 and minimum inhibitory concentration required to inhibit the growth of 90% of organisms (MIC 90 ) (MIC 50/90 , 0.12/0.12 mg/L) were obtained against methicillin-resistant Staphylococcus aureus and methicillin-susceptible S. aureus . Tedizolid, linezolid, and daptomycin were active against enterococci. Tedizolid (MIC 90 , 0.12-0.25 mg/L), ceftaroline (MIC 90 , 0.12 mg/L), and vancomycin (MIC 90 , 0.25-0.5 mg/L) had the lowest MIC 90 values against Streptococcus pneumoniae and VGS, whereas ceftaroline (MIC 90 , ≤0.015 mg/L), penicillin (MIC 90 , ≤0.06 mg/L), ceftriaxone (MIC 90 , ≤0.06-0.12 mg/L), and tedizolid (MIC 90 , 0.12 mg/L) were the most potent against β-haemolytic streptococci. Tedizolid displayed potent activity against gram-positive isolates from Europe, regardless of infection type.

Ceftobiprole medocaril, the prodrug of ceftobiprole, is an advanced-generation cephalosporin that is approved in many European and non-European countries for the treatment of adults with hospital-acquired pneumonia (excluding ventilator-associated pneumonia) and community-acquired pneumonia and is currently being evaluated in a global phase 3 clinical trial of patients with Staphylococcus aureus bacteremia. This study investigated the in vitro activity of ceftobiprole and comparators against a total of 5466 gram-positive and -negative isolates from bloodstream infections (BSIs) that were collected in the United States during 2016 and 2017 as part of the SENTRY Antimicrobial Surveillance Program. Ceftobiprole was highly active (isolates were >99% susceptible) against S. aureus (including methicillin-resistant S. aureus), coagulase-negative staphylococci, Enterococcus faecalis, streptococci, and non-extended-spectrum β-lactamase (non-ESBL) phenotype Enterobacteriaceae. As expected, lower activities were observed against Enterococcus faecium, ESBL-phenotype Enterobacteriaceae, Pseudomonas aeruginosa, and Acinetobacter baumannii. These results support further clinical evaluation of ceftobiprole for the treatment of BSIs caused by susceptible organisms., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: The management of endocarditis requires aggressive and prolonged antimicrobial treatment. We evaluated the in vitro activity of dalbavancin against bacteria from patients with infective endocarditis., Methods: A total of 626 Gram-positive organisms were collected from patients with a diagnosis of bacterial endocarditis in the USA (n = 222) and Europe (n = 404) from 2007 to 2017 via the SENTRY Antimicrobial Surveillance Program and were tested for susceptibility to dalbavancin and comparators by broth microdilution., Results: The most common organisms were Staphylococcus aureus (48.4%), Enterococcus faecalis (19.6%) and viridans group streptococci (VGS; 12.5%). Dalbavancin and daptomycin showed complete activity (100.0% susceptibility per CLSI criteria) against S. aureus, but dalbavancin MIC values were 4- to 8-fold lower. Vancomycin, linezolid and teicoplanin were also active against all S. aureus when CLSI criteria were applied. Ceftaroline was active against all MSSA (MIC90 0.25 mg/L) and 78.4% of MRSA isolates at ≤1 mg/L. All E. faecalis isolates were susceptible to ampicillin, daptomycin and linezolid, whereas 97.6% of isolates were susceptible to dalbavancin (MIC90 0.06 mg/L) and 96.7% were susceptible to vancomycin (MIC90 2 mg/L). All VGS and CoNS isolates were susceptible to dalbavancin, daptomycin, vancomycin and linezolid. Against Enterococcus faecium, 65.7% of isolates were inhibited by ≤0.25 mg/L dalbavancin and 62.9% were vancomycin susceptible., Conclusions: Dalbavancin exhibited potent in vitro activity against a large collection of Gram-positive isolates recovered from patients with endocarditis in US and European medical centres. These results support further investigations to determine the role of dalbavancin in the treatment of infective endocarditis., (© The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Ceftobiprole is an advanced cephalosporin with potent activity against Gram-positive and Gram-negative bacteria that has been approved in many European and non-European countries to treat community- and hospital-acquired pneumonia (excluding ventilator-associated pneumonia). This study reports on the activity of ceftobiprole against a large set of clinical isolates obtained from hospitalized patients in the United States in 2016 that caused serious infections, including pneumonia, bacteremia, and skin and skin structure infections. To assess any potential temporal changes in ceftobiprole activity, the 2016 results were compared to corresponding MIC data from a 2006 U.S. survey that included key target pathogens. Ceftobiprole exhibited potent activity against Staphylococcus aureus (including methicillin-resistant S. aureus isolates, which were 99.3% susceptible), coagulase-negative staphylococci (100% susceptible), Enterococcus faecalis (100% susceptible), Streptococcus pneumoniae (99.7% susceptible), and other tested streptococci. Similarly, ceftobiprole was highly active against Enterobacteriaceae isolates that did not exhibit an extended-spectrum β-lactamase (ESBL) phenotype, including Escherichia coli (99.8% susceptible) and Klebsiella pneumoniae (99.6% susceptible). A total of 99.6% of all Haemophilus influenzae and Moraxella catarrhalis isolates were inhibited at ≤1 mg/liter ceftobiprole, and 72.7% of the Pseudomonas aeruginosa isolates were susceptible to ceftobiprole. With the exception of decreased cephalosporin susceptibility among Enterobacteriaceae isolates, which correlates with an increased prevalence of ESBL-producing isolates, ceftobiprole had similar activities against the isolate sets collected in 2006 and 2016. Therefore, ceftobiprole remains highly active when tested in vitro against a large number of current Gram-positive or Gram-negative pathogens that cause serious infections., (Copyright © 2018 American Society for Microbiology.)

This study updates the distribution and trends of Gram-positive organisms causing bloodstream infections (BSIs) in the United States (US) and Europe during 2010-2016. In vitro activities of oritavancin and comparators were also evaluated. Staphylococcus aureus, Enterococcus spp., and coagulase-negative staphylococci (CoNS) were the most common organisms in both regions. The proportion of methicillin-resistant S. aureus (MRSA) among all isolates declined (from 11.5% to 9.9%) in the US, a trend also noted for methicillin resistance rates within S. aureus (from 45.7% to 41.9%). MRSA rates (4.1% to 4.2%) in Europe remained stable during 2013-2016. Enterococcus faecalis (7.0-5.2%) and E. faecium (5.1-3.0%) rates declined in the US while remaining stable in Europe (4.5-5.7% and 3.3-4.7%, respectively). Rates for CoNS increased in the US; no temporal trends were noted in Europe. Oritavancin (MIC 50/90 , 0.03/0.06 µg/mL) inhibited 99.7-99.8% of S. aureus from both regions at ≤0.12 µg/mL and inhibited 96.8-97.9% of E. faecalis and 99.1-99.9% of E. faecium at this concentration. Oritavancin inhibited 99.7% of streptococci at the susceptible breakpoint. This study updates the distribution of pathogens causing BSI in the US and Europe. The in vitro activity for oritavancin against BSI pathogens supports its further development for bacteraemia.

Objectives: To report the linezolid activity, resistance mechanisms and epidemiological typing of selected isolates observed during the 2016 Zyvox® Annual Appraisal of Potency and Spectrum (ZAAPS) programme., Methods: A total of 8325 organisms were consecutively collected from 76 centres in 42 countries (excluding the USA). Broth microdilution susceptibility testing was performed and isolates displaying linezolid MICs of ≥4 mg/L were molecularly characterized., Results: Linezolid inhibited 99.8% of all Gram-positive pathogens at the respective susceptible breakpoints and showed a modal MIC of 1 mg/L, except for CoNS, for which the modal MIC result was 0.5 mg/L. Among isolates displaying linezolid MICs of ≥4 mg/L, one Staphylococcus aureus (linezolid MIC of 4 mg/L) harboured cfr and belonged to ST72, while four CoNS (MICs of 16-32 mg/L; ST2) showed drug target alterations. Two Enterococcus faecium (ST117) from a single site in Rome were linezolid non-susceptible (MICs of 8 mg/L) and had G2576T mutations. Eight linezolid-non-susceptible Enterococcus faecalis (MICs of 4 mg/L; 4 sites in 4 countries; ST256, ST480, ST766 and ST775) carried optrA and isolates carrying optrA from the same medical centre were genetically related. One Streptococcus gallolyticus (MIC of 4 mg/L) and one Streptococcus mitis (MIC of 16 mg/L) carried optrA and G2576T mutations, respectively., Conclusions: These results document the continued long-term in vitro potency of linezolid. Alterations in the 23S rRNA and/or L3/L4 proteins remain the main oxazolidinone resistance mechanisms in E. faecium and CoNS, whereas optrA emerged as the sole mechanism in E. faecalis. Surveillance and infection control will be important strategies to detect optrA and prevent it from disseminating.

The in vitro activity of oritavancin was assessed against 44,715 gram-positive pathogens causing infections in European and United States (US) hospitals (2010-2014). There were no substantive differences (>±2-fold dilution) in oritavancin MIC 50 or MIC 90 values for different species/organism groups over time or by region. Oritavancin (99.9% susceptible) showed modal MIC, MIC 50 , and MIC 90 results of 0.03, 0.03, and 0.06-0.12 mg/L when tested against Staphylococcus aureus, regardless of methicillin susceptibility, year, or region. Coagulase-negative staphylococci from the US and Europe demonstrated equal MIC 50 values for oritavancin (MIC 50 , 0.03 mg/L). Oritavancin inhibited 99.9% of Enterococcus faecalis and all E. faecium at ≤0.5 mg/L, including vancomycin-resistant isolates. Oritavancin exhibited MIC 50 results of 0.03 and ≤0.008 mg/L when tested against β-hemolytic and viridans group streptococci isolates, respectively, regardless of geographical region. Oritavancin maintained potent activity in vitro against this contemporary collection of European and US gram-positive isolates over 5 years (2010-2014)., (Copyright © 2018. Published by Elsevier Inc.)

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.

Objectives: This study provides an in vitro analysis of dalbavancin activity against isolates causing skin and skin-structure infections (SSSIs) in children., Methods: A total of 770 Staphylococcus aureus, 167 β-haemolytic streptococci (BHS), 42 coagulase-negative staphylococci (CoNS), 25 Enterococcus faecalis and 13 viridans group streptococci (VGS) were collected from children (<18years old) in the USA (2014-2015)., Results: Dalbavancin had MIC 50/90 values of 0.03/0.06μg/mL against S. aureus and CoNS, including methicillin-resistant (MRSA) and -susceptible (MSSA) isolates. Dalbavancin MICs were 8-32-fold lower than those of daptomycin (MIC 50/90 , 0.25/0.5μg/mL), vancomycin (MIC 50/90 , 0.5/1μg/mL) and linezolid (MIC 50/90 , 1/1μg/mL) against MRSA. These agents showed 100.0% susceptibility against MRSA, and clindamycin also had a high (92.7%) susceptibility rate. Dalbavancin (MIC 50/90 , 0.03/0.06μg/mL) and daptomycin (MIC 50/90 , 0.25/0.5μg/mL) were the most active agents against CoNS. When tested against E. faecalis, dalbavancin was up to 32-fold more active than ampicillin (MIC 50/90 , ≤0.5/1μg/mL), daptomycin (MIC 50/90 , 1/1μg/mL), linezolid (MIC 50/90 , 1/2μg/mL) and vancomycin (MIC 50/90 , 1/2μg/mL). Dalbavancin (MIC 50/90 , 0.008/0.03μg/mL), ceftriaxone (MIC 50/90 , ≤0.06/≤0.06μg/mL) and penicillin (MIC 50/90 , ≤0.06/≤0.06μg/mL) were the most active against BHS. VGS isolates were susceptible to dalbavancin (MIC 100 , 0.03μg/mL), with MICs 32-64-fold lower than daptomycin (MIC 50/90 , 0.5/0.5μg/mL), linezolid (MIC 50/90 , 0.5/1μg/mL) and vancomycin (MIC 50/90 , 0.5/0.5μg/mL)., Conclusions: Approved agents available for the treatment of SSSI in children are limited. Dalbavancin demonstrated potent in vitro activity against isolates causing SSSI in children. Developing dalbavancin for SSSI treatment in children is warranted, provided safety and tolerability are satisfactory., (Copyright © 2017. Published by Elsevier Ltd.)

Objectives: To report the linezolid in vitro activity obtained during the 2015 ZAAPS Program., Methods: In total, 7587 organisms causing documented infections were consecutively collected in 65 centres in 32 ex-USA countries. Broth microdilution susceptibility testing was performed. Isolates displaying linezolid MIC results of ≥ 4 mg/L were molecularly characterized., Results: Linezolid inhibited >99.9% of Staphylococcus aureus at ≤ 2 mg/L, with MIC50 results of 1 mg/L, regardless of methicillin resistance. A similar linezolid MIC50 result (0.5 mg/L) was observed for CoNS, with the vast majority of isolates (99.7%) also inhibited at ≤ 2 mg/L. Three CoNS (linezolid MIC, 16-64 mg/L) from Italy were found to contain alterations in the 23S rRNA and/or L3/L4 ribosomal proteins. One isolate also harboured cfr. Linezolid exhibited consistent modal MIC and MIC50 results (1 mg/L) for enterococci regardless of species or vancomycin resistance. One Enterococcus faecalis (linezolid MIC, 8 mg/L) from Galway, Ireland, carried optrA. One Enterococcus faecium (linezolid MIC, 16 mg/L) from Italy contained a G2576T mutation in the 23S rRNA. All Streptococcus pneumoniae, viridans group streptococci and β-haemolytic streptococci were inhibited by linezolid at ≤ 2, ≤ 2 and ≤ 1 mg/L, respectively, with equivalent MIC90 results (1 mg/L for all groups)., Conclusions: These results document the continued long-term and stable in vitro potency of linezolid and a limited number of isolates with decreased susceptibility to linezolid (MIC, ≥4 mg/L). The latter isolates showed primarily mutations in the 23S rRNA gene and/or L3/L4 proteins, with plasmid-mediated resistance (cfr and optrA) also present, albeit at a low prevalence., (© The Author 2017. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

A total of 8,072 gram-positive isolates collected from 69 medical centers among all 9 U.S. Census Divisions during the 2015 SENTRY Antimicrobial Surveillance Program were included. Telavancin had minimal inhibitory concentration (MIC) 50 and MIC 90 values of 0.03/0.06 μg/mL, respectively, against methicillin-susceptible (MSSA) and methicillin-resistant Staphylococcus aureus (MRSA). Similar activity was also observed among coagulase-negative staphylococci (MIC 50/90 , 0.03/0.06 μg/ml; 100.0% inhibited by ≤0.12 μg/ml). Telavancin was active against vancomycin-susceptible Enterococcus faecalis (MIC 50/90 , 0.12/0.12 μg/ml) and Enterococcus faecium (MIC 50/90 , 0.03/0.06 μg/ml), but was less active against vancomycin-resistant E. faecium (MIC 90 , >2 μg/ml) and E. faecalis (MIC 90 , >2 μg/ml). Streptococci showed modal MIC results of 0.008 μg/ml (Streptococcus pneumoniae) to 0.015 μg/ml (β-hemolytic streptococci and viridans group streptococci). Potency variations for telavancin within Census Divisions were not observed. Telavancin remains potent in vitro against indicated pathogens recovered from U.S. medical centers (2015).

Objectives: Telavancin activity was measured against Gram-positive pathogens collected worldwide during 2014 using the revised broth microdilution testing method. The results were compared with previous reports., Methods: A total of 10552 isolates from 86 sites located in 32 countries were included as part of the Telavancin International Surveillance Program for the Americas, Europe and Asia-Pacific., Results: Telavancin had MIC 50 and MIC 90 values of 0.03μg/mL and 0.06μg/mL, respectively, against Staphylococcus aureus, regardless of methicillin susceptibility, and inhibited all S. aureus isolates at the CLSI breakpoint (≤0.12μg/mL). Telavancin was eight-fold more active than daptomycin (MIC 50/90 , 0.25/0.5μg/mL) and 16-32-fold more active than vancomycin (MIC 50/90 , 1/1μg/mL) and linezolid (MIC 50/90 , 1/1μg/mL) against methicillin-resistant S. aureus (MRSA). Telavancin was also active against coagulase-negative staphylococci isolates (MIC 50/90 , 0.06/0.06μg/mL). Vancomycin-susceptible Enterococcus faecalis isolates (n=718) were all inhibited by telavancin (MIC 50/90 , 0.12/0.12μg/mL) at ≤0.25μg/mL (CLSI breakpoint), except for a single isolate (MIC, 0.5μg/mL). All Enterococcus faecium and E. faecalis isolates with telavancin MICs of ≥0.5μg/mL and ≥1μg/mL, respectively, had a VanA phenotype. Based on the MIC 90 values, telavancin was at least eight-fold more potent than comparators against vancomycin-susceptible enterococci. With the exception of Streptococcus agalactiae (MIC 50 , 0.03μg/mL), all tested species of streptococci exhibited telavancin MIC 50 values of ≤0.015μg/mL., Conclusions: These in vitro results from 2014 highlight the potent in vitro activity of telavancin and demonstrate that its activity was virtually unchanged compared with the corresponding 2013 telavancin surveillance results., (Copyright © 2017 International Society for Chemotherapy of Infection and Cancer. Published by Elsevier Ltd. All rights reserved.)

Objectives: The objective of this study was to report the linezolid in vitro activity observed during the Zyvox(®) Annual Appraisal of Potency and Spectrum (ZAAPS) programme for 2014., Methods: In total, 7541 organisms causing documented infections were consecutively collected in 66 centres in 33 countries, excluding the USA. Susceptibility testing was performed by broth microdilution. Isolates displaying linezolid MIC results of ≥4 mg/L were molecularly characterized., Results: Linezolid inhibited all Staphylococcus aureus at ≤2 mg/L, with MIC50 results of 1 mg/L, regardless of methicillin resistance. A similar linezolid MIC50 result (i.e. 0.5 mg/L) was observed against CoNS, with the vast majority of isolates (99.4%) also inhibited at ≤2 mg/L. Six CoNS that exhibited elevated linezolid MIC values were found to contain alterations in the 23S rRNA and/or L3 ribosomal protein. Linezolid exhibited consistent modal MIC and MIC50 results (1 mg/L) against enterococci, regardless of species or vancomycin resistance. Three Enterococcus faecalis from Galway and Dublin (Ireland) and Kelantan (Malaysia) showed MIC results of 4 to 8 mg/L and carried optrA. All Streptococcus pneumoniae, viridans-group streptococci and β-haemolytic streptococci were inhibited by linezolid at ≤2, ≤2 and ≤1 mg/L, respectively, with equivalent MIC90 results (1 mg/L for all groups)., Conclusions: These results document the continued long-term and stable in vitro potency of linezolid and reveal a limited number of isolates with decreased susceptibility to linezolid (i.e. MIC ≥4 mg/L). The latter isolates primarily showed mutations in the 23S rRNA gene and/or L3 protein, but cfr was not detected. Moreover, this study shows that isolates carrying the newly described ABC transporter optrA are not restricted to China., (© The Author 2016. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Objectives: To reassess the activity of telavancin when tested against Gram-positive clinical pathogens recovered from hospitalized patients in European and adjacent regions using a revised broth microdilution method., Methods: 11 601 consecutive, non-duplicate isolates originating from 36 institutions among 18 countries recovered between 2011 and 2013 were tested for susceptibility using a revised broth microdilution method for telavancin. Interpretive telavancin breakpoints appropriate for the method were those recently approved by the FDA and EUCAST, as available., Results: Telavancin (MIC50/90, 0.03/0.06 mg/l; 100.0% susceptible) was equally potent against methicillin-susceptible ((MSSA) and methicillin-resistant (MRSA) Staphylococcus aureus. All Enterococcus faecalis was susceptible to telavancin (MIC50/90, 0.12/0.12 mg/l) and inhibited at the susceptibility breakpoint (i.e. ≤ 0.25 mg/l), except for VanA-phenotype vancomycin-resistant isolates (telavancin MIC, >1 mg/l). Telavancin ( ≤ 0.015/0.03 mg/l) was active against vancomycin-susceptible Enterococcus faecium, while higher MIC values were obtained for VanA strains. Telavancin (both MIC50 and MIC90, ≤ 0.015 mg/l) was potent against Streptococcus pneumoniae, beta-haemolytic streptococci (MIC50/90, ≤ 0.015/0.06 mg/l) and viridans group streptococci (MIC50/90, ≤ 0.015/0.03 mg/l)., Conclusions: Telavancin exhibited potent activity against this contemporary (2011-2013) collection of organisms, inhibiting indicated pathogens at or below the FDA/EUCAST-approved breakpoints for susceptibility. VanA-phenotype enterococci were less susceptible to telavancin, a feature observed using the previous testing method. These results redefine telavancin's activity against isolates from Europe.

A revised broth microdilution susceptibility testing method for telavancin was approved by the Food and Drug Administration (FDA). Telavancin activity was assessed against Gram-positive pathogens collected worldwide (2013) using the revised method. A total of 12,346 isolates from 90 sites were included as part of the Telavancin International Surveillance Program for the Americas, Europe, and Asia-Pacific. Telavancin had MIC50 and MIC90 values of 0.03 and 0.06 μg/mL, respectively, against staphylococci, regardless of methicillin susceptibility, and inhibited all Staphylococcus aureus at ≤0.12 μg/mL (revised FDA breakpoint). Telavancin was 8-fold more active than daptomycin (MIC50/90, 0.25/0.5 μg/mL) and 16- to 32-fold more active than vancomycin (MIC50/90, 1/1 μg/mL) and linezolid (MIC50/90, 1/1 μg/mL) against methicillin-resistant S. aureus. All 692 vancomycin-susceptible Enterococcus faecalis were inhibited by telavancin (MIC50/90, 0.12/0.12 μg/mL) at ≤0.25 μg/mL (FDA breakpoint), except for 1 strain (MIC, 0.5 μg/mL). All Enterococcus faecium and E. faecalis with telavancin MIC values of ≥0.5 and ≥1 μg/mL, respectively, had a VanA phenotype. A comparison data analysis based on the MIC90 demonstrated that telavancin was at least 8-fold more potent than comparators against vancomycin-susceptible enterococci. Streptococci showed telavancin MIC50 values of ≤0.015 μg/mL, except for Streptococcus agalactiae (MIC50, 0.03 μg/mL). These in vitro results obtained by the recently approved susceptibility testing method establish a new benchmark of telavancin activity worldwide., (Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: To assess oritavancin activity in vitro against clinically relevant Gram-positive pathogens causing skin and soft-tissue infections (SSTIs) in European and US hospitals., Methods: 13 262 consecutive and unique isolates deemed to be responsible for SSTIs were included. Isolates originated from 36 and 27 institutions in Europe (Israel included) and the USA, respectively, between 2010 and 2013., Results: Oritavancin (98.8% susceptible) showed modal MIC, MIC50 and MIC90 results of 0.03, 0.03 and 0.06 mg/L, respectively, for Staphylococcus aureus. CoNS from the USA (MIC50, 0.015 mg/L) demonstrated an MIC50 value of oritavancin slightly lower than those from Europe (MIC50, 0.03 mg/L). Overall, vancomycin-resistant (VanA-phenotype) Enterococcus faecalis had oritavancin MICs (MIC50/90, 0.25/0.5 mg/L) that were 16-fold higher than those obtained for vancomycin-susceptible isolates (MIC50/90, 0.015/0.03 mg/L; 99.2%-99.8% susceptible); nevertheless, oritavancin inhibited all VanA E. faecalis at ≤0.5 mg/L. Equivalent oritavancin MICs (MIC50/90, 0.004/0.008 mg/L) were noted for all VanB and vancomycin-susceptible Enterococcus faecium, while higher MICs (MIC50/90, 0.03/0.12 mg/L) were obtained for VanA strains. Oritavancin had low MICs against the overall populations of Streptococcus pyogenes (MIC50/90, 0.03/0.12 mg/L; 98.4%-98.6% susceptible), Streptococcus agalactiae (MIC50/90, 0.03/0.06 mg/L; 97.9%-98.0% susceptible) and the Streptococcus anginosus group (MIC50/90, 0.008/0.015 mg/L; 100.0% susceptible), with slightly higher MICs for Streptococcus dysgalactiae (MIC50/90, 0.06/0.25 mg/L; ≥98.3% susceptible)., Conclusions: Oritavancin had potent activity in vitro against this contemporary collection of European and US isolates causing SSTIs. These results describe oritavancin activity against Gram-positive pathogens collected shortly prior to its regulatory approval in the USA., (© The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Objectives: To assess the oritavancin spectrum and activity against 2811 rarer species of coagulase-negative staphylococci (CoNS), streptococci and other Gram-positive species., Methods: A total of 2057 CoNS (14 species), 674 streptococci (7 groups) and 80 other Gram-positive species (3 genera) collected over a 5 year period as part of the SENTRY Program (2008-12) were included. Isolates were primarily identified by the participating laboratory and identification was confirmed by the reference monitoring laboratory (JMI Laboratories, North Liberty, IA, USA). Isolates were tested for susceptibility by broth microdilution following the CLSI M07-A9 and M100-S23 documents., Results: Overall, oritavancin was active against all CoNS (MIC50/MIC90, 0.015/0.06 mg/L), with MIC50 values of ≤0.008-0.03 mg/L. Streptococci exhibited oritavancin MIC50 results of ≤0.008 mg/L, except for the Streptococcus bovis (0.03 mg/L), Streptococcus dysgalactiae (0.06 mg/L) and Streptococcus salivarius/vestibularis (0.06 mg/L) groups. Micrococcus spp., Listeria monocytogenes and Corynebacterium spp. had oritavancin MIC50 results of ≤0.008 mg/L., Conclusions: This study expands the oritavancin in vitro data against several species of Gram-positive organisms., (© The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Linezolid, approved for clinical use since 2000, has become an important addition to the anti-Gram-positive infection armamentarium. This oxazolidinone drug has in vitro and in vivo activity against essentially all Gram-positive organisms, including methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE). The in vitro activity of linezolid was well documented prior to its clinical application, and several ongoing surveillance studies demonstrated consistent and potent results during the subsequent years of clinical use. Emergence of resistance has been limited and associated with invasive procedures, deep organ involvement, presence of foreign material and mainly prolonged therapy. Non-susceptible organisms usually demonstrate alterations in the 23S rRNA target, which remain the main resistance mechanism observed in enterococci; although a few reports have described the detection of cfr-mediated resistance in Enterococcus faecalis. S. aureus isolates non-susceptible to linezolid remain rare in large surveillance studies. Most isolates harbour 23S rRNA mutations; however, cfr-carrying MRSA isolates have been observed in the United States and elsewhere. It is still uncertain whether the occurrences of such isolates are becoming more prevalent. Coagulase-negative isolates (CoNS) resistant to linezolid were uncommon following clinical approval. Surveillance data have indicated that CoNS isolates, mainly Staphylococcus epidermidis, currently account for the majority of Gram-positive organisms displaying elevated MIC results to linezolid. In addition, these isolates frequently demonstrate complex and numerous resistance mechanisms, such as alterations in the ribosomal proteins L3 and/or L4 and/or presence of cfr and/or modifications in 23S rRNA. The knowledge acquired during the past decades on this initially used oxazolidinone has been utilized for developing new candidate agents, such as tedizolid and radezolid, and as linezolid patents soon begin to expire, generic brands will certainly become available. These events will likely establish a new chapter for this successful class of antimicrobial agents., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

In the European component of the Regional Resistance Surveillance study for 2011, a total of 21 countries were monitored for antimicrobial resistance patterns including Belgium, Bulgaria (BU), Croatia, Czech Republic, France (F), Germany (GE), Greece (GR), Ireland (IR), Israel (IS), Italy (IT), Poland (PO), Portugal (PT), Romania (RO), Russia (RU), Slovakia (SK), Slovenia, Spain, Sweden (SW), Turkey (T), Ukraine, and United Kingdom. Results from testing 12,572 strains (100 [BU] to 1535 [F] per nation) were interpreted by contemporary published breakpoints. Samples from 47 hospitals were reference tested against agents such as amikacin (AMK), cefoperazone/sulbactam (C/S), colistin (COL), levofloxacin, linezolid (LZD), tigecycline (TIG), vancomycin (VAN), and 21 others. Among Staphylococcus aureus, LZD (MIC90, 2 μg/mL), TIG (MIC90, 0.12 μg/mL), and VAN (MIC90, 1 μg/mL) exhibited complete coverage and methicillin resistance rates among nations (average, 31%) ranged from 0.9% (SW) to 60.0-60.2% (PT, SK). Seven LZD-resistant coagulase-negative staphylococci (only 1.1% resistance overall) were noted in 5 nations, and a Staphylococcus simulans strain (MIC, 8 μg/mL from RO) had L3 mutations (N130D, G152A, F147S, A157R); also 6 LZD-resistant enterococci were detected in 3 countries (GE, IR, T). VAN-resistant enterococci (10% overall; 84% VanA) were found in 14 countries, highest in GE and IR (23.0%). The ESBL phenotype rate for Escherichia coli was 20.1% (range, 0.9% [SW] to 70.0-89.7% [BU, RU]), best inhibited by COL (100.0% S), TIG (100.0%), AMK (83.3-94.1%), C/S (81.0%), and carbapenems (>99.0%; resistant strains in IS and T). Klebsiella spp. had greater ESBL rates (45.7% overall, range 2.5-100.0%), as well as carbapenem resistance (8.3% overall, greatest in BU, GR, IS, IT, PO, RO, RU, T). Non-fermentative Gram-negative bacilli (Pseudomonas aeruginosa, Acinetobacter [ACB]) were generally less susceptible, except against COL (99.2-99.6% S) and TIG (95.0% inhibited at ≤2 μg/mL; ACB only). The following carbapenemases were detected: VIM-1 (2 countries); IMP-1 (1 from T); KPC-2 or -3 (2 countries); VIM-4 (1 from PO), NDM-1 (2 in RO; 2 centers); and OXA-48 or -162 (5 from T; 2 centers). European surveillance sampling demonstrates a wide array of resistant isolates, less prevalent among Gram-positive cocci that remain inhibited by several available agents. However, beta-lactamase-mediated mechanisms have spread widely among Gram-negative bacilli, especially across the Eastern and Southern European nations, severely limiting infection chemotherapy and necessitating escalated antimicrobial stewardship., (© 2014.)

The LEADER surveillance program monitors the in vitro activity of linezolid and comparator agents against Gram-positive bacteria in the United States. In its eighth consecutive year (2011), a total of 60 medical centers from the United States, including seven medical centers specializing in children's health care contributed a total of 7,303 Gram-positive pathogens. The MIC(90) value for Staphylococcus aureus was 2 μg/ml, and for coagulase-negative staphylococci, enterococci, Streptococcus pneumoniae, β-hemolytic streptococci, and viridans group streptococci, the MIC(90) was 1 μg/ml. The "all organism" linezolid-resistant and nonsusceptible rate was only 0.19%.

A total of 15,480 Gram-positive pathogens were collected from 89 sites in the United States, Europe, the Asia-Pacific region, and Latin America in 2010. Telavancin was active against indicated Staphylococcus aureus (MIC(50/90), 0.12/0.25 μg/ml), vancomycin-susceptible Enterococcus faecalis (MIC(50/90), 0.5/0.5 μg/ml), and beta-hemolytic (MIC(50/90), 0.06/0.12 μg/ml) and viridans group streptococcus (MIC(50/90), 0.03/0.06 μg/ml) isolates. These MIC results showed potency for telavancin equal to or greater than that of comparators. These in vitro data confirm a continued potent activity of telavancin when tested against contemporary Gram-positive clinical isolates.

Oritavancin is in the final stages of clinical development for treatment of acute bacterial skin and skin structure infections. This drug has demonstrated potent activity against staphylococci (minimum inhibitory concentration [MIC] for which 90% of isolates are inhibited [MIC(90)], 0.06 μg/mL), enterococci (MIC(90), ≤ 0.008 to 0.5 μg/mL), and streptococci (MIC(90), ≤ 0.008 to 0.12 μg/mL), including enhanced potency against vancomycin-resistant enterococci. During the clinical development of oritavancin, it was demonstrated that this molecule binds to plastic labware surfaces and that this feature was likely responsible for interlaboratory variability observed from in vitro investigations before 2006. Therefore, reference broth microdilution methods and MIC ranges for quality control strains were reestablished using media supplemented with a surfactant (polysorbate-80, 0.002%). These were followed by numerous experiments to reassess the in vitro characteristics of oritavancin; the results originating from those studies are summarized here. The oritavancin activity tested against a resistance surveillance collection of 12,367 Gram-positive clinical pathogens and resistant subsets from the United States (2008-2009) is also presented, with the highest MIC among staphylococci at only 0.25 μg/mL. In vitro results for oritavancin indicate wide potential use against Gram-positive pathogens.

This study updates the activity of telavancin against Gram-positive pathogens collected from USA hospitals (2007-2009). Telavancin (MIC(50/90), 0.12/0.25 μg/mL) was active against coagulase-negative staphylococci and methicillin-resistant Staphylococcus aureus (100% susceptible), for which only daptomycin (MIC(50/90), 0.25/0.5 μg/mL; 99% susceptible) and quinupristin/dalfopristin (MIC(50/90), ≤ 0.25-0.5/0.5 μg/mL; 99% susceptible) exhibited similar activity. Telavancin (MIC(50/90), 0.25/0.5 μg/mL) inhibited 96.5% of Enterococcus faecalis at the Food and Drug Administration breakpoint (MIC, ≤ 1 μg/mL), where ampicillin (99.9% susceptible), daptomycin (99.9% susceptible), and linezolid (100% susceptible) also demonstrated high-level coverage. Telavancin inhibited, respectively, 100.0% and 91.7% of VanB-phenotype E. faecalis and E. faecium at ≤ 1 μg/mL, whereas it was less active against VanA strains. Telavancin was uniformly active against Streptococcus pneumoniae and resistant subsets, and demonstrated good potency (MIC(90), 0.06-0.12 μg/mL) against other streptococci, regardless of resistance to other drugs. This assessment reveals potent activity of telavancin against Gram-positive isolates collected from USA hospitals with no evidence of emergence of resistance., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Objectives: The antimicrobial activity of telavancin against 2279 clinical Gram-positive cocci obtained from patients with nosocomial pneumonia [NP; including those with ventilator-acquired pneumonia (VAP)] located in numerous medical centres worldwide was evaluated., Methods: A contemporary collection of 2279 non-duplicate consecutive Gram-positive clinical isolates were submitted from 87 hospitals located in North America (913 isolates), Latin America (222 isolates), Europe (690 isolates), and the Asia-Pacific region (454 isolates) as part of the international telavancin surveillance programme for 2007-08. Isolates were tested for susceptibility by the reference broth microdilution method (with 2%-5% lysed horse blood added for testing of streptococci). Interpretive criteria were those from CLSI (M100-S20, 2010) except for telavancin, for which the susceptible breakpoints approved by the US FDA were applied., Results: Telavancin was highly active against Staphylococcus aureus (MIC(90), 0.25 mg/L; 100% susceptible), coagulase-negative staphylococci (MIC(90), 0.25 mg/L), Streptococcus pneumoniae (MIC(90), 0.03 mg/L), viridans group streptococci (MIC(90), 0.06 mg/L; 100% susceptible), β-haemolytic streptococci (MIC(90), 0.06 mg/L; 100% susceptible) and vancomycin-susceptible enterococci (MIC(90), 0.5 mg/L; 100% susceptible). Telavancin inhibited all staphylococci at ≤ 0.5 mg/L. Among enterococci non-susceptible to vancomycin (all Enterococcus faecium), telavancin was active against isolates exhibiting a VanB phenotype (MIC, 0.06-0.12 mg/L), but less potent against VanA strains (MIC, ≥ 2 mg/L)., Conclusions: Telavancin demonstrated equal or greater potency than the comparators (vancomycin, teicoplanin, daptomycin, linezolid and quinupristin/dalfopristin) against Gram-positive pathogens implicated in NP. Telavancin showed elevated MIC values only against enterococcus isolates showing a VanA phenotype. The continued appearance of multidrug-resistant pathogens among Gram-positive isolates, mainly S. aureus, necessitates the introduction of new agents and longitudinal surveillance to monitor for the potential emergence of resistance.

Telavancin was approved in the United States and Canada for the treatment of adult patients with complicated skin and skin-structure infections (cSSSI) caused by susceptible Gram-positive isolates. In this study, telavancin and comparator antimicrobial activities were determined against a total of 24,017 clinical isolates, including Staphylococcus aureus, coagulase-negative Staphylococcus spp. (CoNS), Enterococcus spp., and various Streptococcus spp. Overall, telavancin was highly active across all geographic regions for S. aureus (MIC(50/90), 0.12/0.25 microg/mL; 100.0% susceptible), CoNS (MIC(50/90), 0.12/0.25 microg/mL), vancomycin-susceptible Enterococcus faecalis (MIC(50/90), 0.25/0.5 microg/mL; 100.0% susceptible), Enterococcus faecium (MIC(50/90), 0.06/0.12 microg/mL), Streptococcus pneumoniae (MIC(50/90), < or =0.015/0.03 microg/mL), viridans group Streptococcus spp. (MIC(50/90), 0.03/0.06 microg/mL; 100.0% susceptible), and beta-hemolytic Streptococcus spp. (MIC(50/90), 0.03/0.12 microg/mL; 99.8% susceptible). Telavancin had potent activity against vancomycin-nonsusceptible, teicoplanin-susceptible (VanB) E. faecalis (MIC(50/90), 0.25/0.5 microg/mL) and E. faecium (MIC(50/90), 0.06/0.25 microg/mL). These in vitro results show continued activity for telavancin, which represents an important alternative available for treating cSSSI., (Copyright 2010 Elsevier Inc. All rights reserved.)

Fusidic acid (CEM-102) is a steroidal antimicrobial agent with focused Gram-positive activity that acts by preventing bacterial protein synthesis via interacting with elongation factor G. A collection of 114 wild-type isolates (> 80 species) was used to define the contemporary limits of fusidic acid spectrum against Gram-positive and Gram-negative species. Reference broth microdilution and anaerobic agar dilution methods were performed. Modifications of standardized test methods included adding 10% human serum and adjusting the medium pH to 5, 6, and 8. Synergy was assessed by the checkerboard method and time-kill studies. Mutational rates to resistance were determined at 4 x, 8 x, and 16 x MIC. Against Gram-positive pathogens, fusidic acid MIC values ranged from 0.06 to 32 microg/mL with the greatest potency against Staphylococcus aureus, Corynebacterium spp., and Micrococcus luteus (MIC results, 0.25, < or = 0.12, and < or = 0.5 microg/mL, respectively). Enterococci and streptococci were less susceptible (MIC ranges, 2-8 and 16-32 microg/mL, respectively). Fusidic acid activity against Gram-negative species was more limited (all MIC values, > or = 2 microg/mL) except for Empedobacter brevis, Moraxella catarrhalis and Neisseria meningitidis. A 4-fold increase in fusidic acid MIC results was observed when 10% serum was added to the broth. Decreasing medium pH to 5.0 to 6.0 negated the protein binding effects. Among the 8 antimicrobial combinations tested, gentamicin and rifampin enhanced the activity when combined with fusidic acid (no antagonism). Fusidic acid in vitro activity was most improved when combined with rifampin. Single-step mutational rates ranged from 1.2 x 10(-6) for 4x MIC to 9.8 x 10(-8) for 16 x MIC. In conclusion, these in vitro results for fusidic acid tested against contemporary strains confirm a persisting antimicrobial spectrum, especially against staphylococci and some other Gram-positive species., (2010 Elsevier Inc. All rights reserved.)

The LEADER Program was initiated in 2004 and monitors emerging linezolid resistance in sampled US medical centers. This report summarizes the data obtained in 2008, the 5th consecutive year. A total of 57 institutions participated in 2008 representing all 9 US census regions with 100 target organisms per site (6113 isolates, 101.9% compliance to protocol design). The organisms tested by reference broth microdilution methods were Staphylococcus aureus (3156), coagulase-negative staphylococci (CoNS; 856), enterococci (901), Streptococcus pneumoniae (619), and viridans group (223) or beta-hemolytic streptococci (358); also, D-test was used to determine inducible clindamycin resistance in Staphylococcus aureus. Linezolid remained very potent against all sampled species with MIC(90) results ranging from 1 microg/mL (streptococci and CoNS) to 2 microg/mL (Staphylococcus aureus and enterococci). Only 0.36% of sampled strains were nonsusceptible to linezolid, a slight decrease from 0.45% and 0.44% in 2006 and 2007, respectively. The nonsusceptible strains (22) were Staphylococcus aureus (3), CoNS (14), and Enterococcus faecium (5) each with defined target mutations (G2576T in 19 strains; T2504A in 1 strain), mobile cfr element (1 strain Staphylococcus epidermidis with an identical pulsed-field gel electrophoresis pattern to a cfr-positive Staphylococcus epidermidis isolated from the same center in LEADER 2007), or an unknown (1 strain) mechanism. The mobile cfr resistance found in a Staphylococcus aureus strain in 2007 was not observed in 2008. In conclusion, linezolid activity sampled by the 5th year of this LEADER Program showed sustained potency and spectrum (99.64% susceptibility levels). The nonsusceptible strain isolation rates remained stable and the plasmid-mediated ribosomal-based resistance mechanism that emerged in Staphylococcus aureus and Staphylococcus epidermidis strains in 2007 showed no evidence of dissemination or increased prevalence. However, there was evidence of cfr persistence with the S. epidermidis strain. The LEADER Program continues to be an effective and sensitive surveillance tool to detect and monitor novel oxazolidinone resistance phenotypes and genotypes.

The accuracy of antimicrobial susceptibility tests is a crucial step for the clinical management of patients with serious infections. They must be reliable and precise because they will guide antimicrobial therapy. Our main objective was to compare the results of susceptibility testing performed by the SENTRY coordinator laboratory with those reported by the participating Latin American medical centers. A total of 10,277 bacterial isolates were tested by the reference broth microdilution method at the coordinator laboratory in the United States. The tests were performed and interpreted following the National Committee for Clinical Laboratory Standards (NCCLS) recommendations. Ten antimicrobial agent-organism combinations were analyzed. The susceptibility methods utilized in each of the medical centers were also evaluated. Total agreement of the results was obtained in nearly 88% of the antimicrobial agent-organism combinations. "Very major" (false-susceptible results) and "major errors" (false-resistant results) were observed in 12% and 6% of the cases, respectively. The highest disagreements were observed for coagulase-negative Staphylococcus&#95;oxacillin (20% - very major error) and Burkholderia cepacia&#95;imipenem (21% - very major error). The susceptibility method with the highest agreement rate was Etest (92%) > PASCO (91%) > agar dilution (91%) > MicroScan (90%) > Vitek (87%). External quality assurance data obtained by surveillance programs such as the SENTRY Antimicrobial Surveillance Program are not only helpful for detecting the emergence of patterns of antimicrobial resistance, but also to monitor the performance of the participating microbiology laboratories.

Background: Many infections due to Gram-positive cocci (GPC; staphylococci, streptococci and enterococci) regularly involve prolonged systemic antibiotic use. Dalbavancin has demonstrated activity against GPC isolates and has been approved for the treatment of acute bacterial skin and skin structure infections (ABSSSIs) in adults.Objectives: To evaluate the activity of dalbavancin against GPC isolated from a variety of infection types in the USA and Europe.Methods: A total of 14 319 Staphylococcus aureus, 1992 CoNS, 3269 β-haemolytic streptococci (BHS), 2071 Enterococcus faecalis, 936 Enterococcus faecium, 71 Enterococcus gallinarum/casseliflavus and other Enterococcus spp., 3487 Streptococcus pneumoniae and 1063 viridans group streptococci (VGS) causing clinical infections were consecutively collected (2015-16) and tested for susceptibility by broth microdilution methods.Results: All S. aureus (36.4% MRSA) isolates were susceptible to dalbavancin, teicoplanin and vancomycin, while daptomycin and linezolid showed susceptibility rates of >99.9% (according to CLSI criteria). Dalbavancin MIC results were at least 16-fold lower than these comparators against all S. aureus. Dalbavancin was the most potent agent against CoNS [62.2%/59.6% methicillin-resistant (CLSI/EUCAST)], followed by daptomycin, linezolid and vancomycin. All vancomycin-susceptible E. faecalis isolates were inhibited by dalbavancin at ≤0.25 mg/L (FDA susceptible breakpoint). Dalbavancin was very active against BHS (MIC90 0.03 mg/L) and the most active agent against S. pneumoniae and VGS (highest MIC 0.25 mg/L). Ceftriaxone, daptomycin, levofloxacin and vancomycin were also active (93.5%-100.0% susceptible) against VGS, whereas clindamycin, erythromycin, penicillin and tetracycline had lower activity.Conclusions: Dalbavancin appears to be a viable candidate for treating serious infections caused by GPC. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The 2013 LEADER surveillance program monitored the in vitro activity of linezolid and comparator agents against Gram-positive bacteria at 60 medical centers in the United States. A total of 7183 pathogens were contributed from 6 predetermined pathogen groups. The groups were Staphylococcus aureus , coagulase-negative staphylococci, enterococci, Streptococcus pneumoniae , β-hemolytic streptococci, and viridans group streptococci. The MIC 90 value for each of the 6 pathogen groups was 1 μg/mL. Susceptibility of “all organisms” to linezolid was 99.83%. Only 12 isolates (2 S. aureus , 3 Staphylococcus epidermidis , 1 Streptococcus sanguinis , 5 Enterococcus faecium , and 1 Enterococcus faecalis ) were nonsusceptible to linezolid (0.17%). Three of these (2 S. aureus and 1 E. faecium ) harbored the cfr resistance mechanism. The findings indicate that linezolid activity remains stable, although there are examples of clonal dissemination within several monitored institutions. [ABSTRACT FROM AUTHOR]

Objectives To summarize the activity and spectrum of linezolid and comparators tested against 7972 Gram-positive clinical isolates as part of the Zyvox® Annual Appraisal of Potency and Spectrum (ZAAPS) Program for 2012. Moreover, to provide molecular characterization for associated resistance mechanisms and epidemiological typing. Methods A total of 7972 isolates were collected from 73 medical centres (33 countries) on five continents. Isolates were tested for susceptibility by broth microdilution following the CLSI M07-A9 document. MIC interpretations were based on CLSI and EUCAST criteria. Results Linezolid showed MIC50 and MIC90 results of 1 and 2 mg/L, respectively, when tested against Staphylococcus aureus. These isolates were inhibited by linezolid at ≤2 mg/L, except for four S. aureus exhibiting higher MIC values (4–8 mg/L), which had cfr and/or target site mutations, including a first detection of cfr in an isolate from Brazil. Coagulase-negative staphylococci (CoNS) were susceptible to linezolid (MIC50/90, 0.5/1 mg/L), with only eight isolates exhibiting high MIC results (16–32 mg/L). These CoNS had cfr and/or single or multiple target site alterations in 23S rRNA and/or ribosomal proteins (L3, L4). The same species of linezolid-resistant CoNS collected from the same hospital were clonally related to those observed in previously surveyed years. Linezolid exhibited stable modal MIC and MIC50 results when tested against enterococci, regardless of the species or vancomycin resistance phenotype; in addition, linezolid inhibited all streptococci at ≤2 mg/L. Conclusions This surveillance report documents stable linezolid activity and susceptibility rates against a large and longitudinal collection of clinical isolates worldwide. [ABSTRACT FROM PUBLISHER]

Background Oritavancin (ORI) is a potent lipoglycopeptide with desirable PK/PD parameters for treating serious gram-positive infections. This study assessed the activity of ORI against Staphylococcus aureus (SA), Enterococcus faecalis (EF), and E. faecium (EFM) causing bloodstream infection (BSI), including infective endocarditis (IE) and daptomycin (DAP)- susceptible dose-dependent (SDD) vancomycin-resistant (VRE) subsets. We also evaluated the longitudinal activity of ORI. Methods A total of 5,469 SA, 1,157 EF, and 721 EFM were recovered from BSI in 35 US sites (2011–2018). Subsets of SA isolates causing IE (84) and EFM displaying DAP-SDD-VRE phenotypes (230) were included. Identification was confirmed by MALDI-TOF MS and isolates were tested for susceptibility (S) according to CLSI. Results Overall, ORI showed similar MIC50 (0.03 mg/L) and MIC90 results (0.06 mg/L) against MRSA and MSSA (figure) and the SA EC subset (41.7% MRSA; data not shown). Similar findings were noted for ORI tested against EF DAP-S (MIC50/90, 0.015/0.06 mg/L) and DAP-SDD (MIC50/90, 0.015/0.06 mg/L). ORI MIC values against DAP- and VAN-S EFM (MIC50/90, ≤0.008/0.015 mg/L) were at least 8-fold lower than those from DAP-SDD-VRE isolates (MIC50/90, 0.06/0.12 mg/L; 31.9% of all EFM), and all EFM were inhibited by ORI at ≤0.25 mg/L. The longitudinal analysis showed MRSA rates varying from 39.7% (2017) to 46.8% (2011), while the annual ORI MIC50 and MIC90 results were 0.015–0.06 mg/L and 0.03–0.12 mg/L, respectively, against MRSA during the 8-year period. ORI yearly MIC50 and MIC90 results were 0.015–0.03 mg/L and 0.03–0.12 mg/L against EF, respectively. MIC50 and MIC90 results of 0.008–0.03 mg/L and 0.03–0.12 mg/L, respectively, were obtained for ORI against the DAP-SDD EF subset each year. ORI MIC50 and MIC90 results of 0.03–0.06 and 0.06–0.12 mg/L were obtained annually against DAP-SDD-VRE (EFM), respectively. Conclusion ORI showed a potent activity against this collection of isolates causing BSI and IE in the USA, including resistant subsets requiring higher dosage regimens when treating serious infections. In addition, ORI maintained a stable potency throughout the 8-year study period with no apparent temporal trends. Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]

Bacterial organisms ( n  = 13,494) were consecutively collected in 2011–2014 from 21 Latin American medical centres (11 nations). Antimicrobial susceptibility was determined by broth microdilution at a central laboratory. Tigecycline was very active against Gram-positive organisms, with MIC 50/90 values of 0.06/0.06 µg/mL for Staphylococcus aureus ( n  = 2878), 0.06/0.12 µg/mL for coagulase-negative staphylococci ( n  = 880), 0.06/0.06 µg/mL for enterococci ( n  = 708) and ≤0.03/≤0.03–0.06 µg/mL for streptococci ( n  = 1352). All Gram-positive species exhibited 100.0% susceptibility (FDA and/or EUCAST criteria), except for Streptococcus pneumoniae (99.8% susceptible). The S. aureus oxacillin resistance rate varied from 28.0% (Brazil) to 55.0% (Argentina), and the overall vancomycin resistance rate was 15.5% ( Enterococcus faecium , 50.3%; and Enterococcus faecalis , 2.3%). The E. faecium vancomycin resistance rate varied from a low (26.3%) in Argentina to a high (71.7%) in Brazil. Against Enterobacteriaceae ( n  = 4543), tigecycline MIC 50/90 values were 0.25/1 µg/mL; 98.3% and 94.2% of strains were considered susceptible according to FDA and EUCAST breakpoints, respectively. Overall, 37.7% and 57.3% of Escherichia coli and Klebsiella pneumoniae exhibited the CLSI ESBL screening phenotype. The highest CLSI ESBL screening phenotype rates among E. coli and Klebsiella spp. strains were observed for isolates collected from Mexico (69.9%) and Chile (69.9%), respectively. Occurrence of carbapenem-resistant Enterobacteriaceae was substantially higher in Brazil (9.0%) and Argentina (6.3%) compared with Chile and Mexico (0.4–0.7%). Tigecycline was also active against Acinetobacter spp. (MIC 50/90 , 1/2 µg/mL; 92.3/72.1% inhibited at ≤2/≤1 µg/mL) and Stenotrophomonas maltophilia (MIC 50/90 , 0.5/2 µg/mL; 91.5/83.0% inhibited at ≤2/≤1 µg/mL). [ABSTRACT FROM AUTHOR]