scholarly journals 333. Tedizolid Activity against Gram-Positive Bacterial Isolates Causing Bone and Joint Infections in the United States (2015–2019)

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S238-S238
Author(s):  
Cecilia G Carvalhaes ◽  
Helio S Sader ◽  
Jennifer M Streit ◽  
Mariana Castanheira ◽  
Rodrigo E Mendes
Keyword(s):  
Chemical Diversity ◽  
Vitro Activity ◽  
In Vitro Activity ◽  
Gram Positive ◽  
Joint Infections ◽  
Bone And Joint Infections ◽  
The Us ◽  
Center Research ◽  
Research Grant

Abstract Background Prolonged systemic antibiotic courses are frequently used to manage difficult-to-treat bone and joint infections (BJI). Tedizolid has been considered as a therapy candidate for BJI in adults and children. This study assessed the in vitro activity of tedizolid and comparator agents against a contemporary collection of Gram-positive (GP) isolates causing BJI in the US. Methods A total of 310 Staphylococcus aureus (SA), 79 β-hemolytic streptococci (BHS), 52 coagulase-negative staphylococci (CoNS), and 37 Enterococcus faecalis isolates were included in this study. These isolates were collected from patients with BJI from 30 medical centers in the US between 2015 and 2019 as a part of the Surveillance of Tedizolid Activity and Resistance (STAR) Program. Bacterial identification was confirmed by MALDI-TOF MS. MIC results were obtained by reference CLSI broth microdilution methods and interpretations used CLSI guidelines. Results Tedizolid (MIC50/90, 0.12/0.25 mg/L) inhibited all SA at the CLSI breakpoint (≤0.5 mg/L) including methicillin-resistant SA (MRSA; 35.8% of SA; MIC50/90, 0.12/0.25 mg/L). Linezolid, vancomycin, and daptomycin had 100% susceptibility rates against SA isolates (Table). All CoNS isolates were inhibited by tedizolid at ≤0.5 mg/L. Tedizolid was active against all BHS (100% susceptible) as follows: S. pyogenes (n=24; MIC50/90, 0.12/0.25 mg/L), S. agalactiae (n=44; MIC50/90, 0.12/0.25 mg/L), and S. dysgalactiae (n= 11; MIC50/90, 0.25/0.25 mg/L). Penicillin, linezolid, vancomycin, and daptomycin also were active against BHS (100% susceptible). Tedizolid (MIC50/90, 0.25/0.25 mg/L; 100% susceptible) was 4- to 8-fold more potent than linezolid (MIC50/90, 1/1 mg/L) and vancomycin (MIC50/90, 1/2 mg/L) against E. faecalis. GP isolates resistant to oxazolidinone were not observed. Conclusion Tedizolid demonstrated potent in vitro activity against this collection of contemporary GP isolates causing BJI in US hospitals. Tedizolid and comparator agents showed high susceptibility rates against the most frequent organisms and organism groups, including MRSA. These findings support the clinical development of tedizolid as an additional option for treating BJI caused by GP pathogens. Table 1 Disclosures Cecilia G. Carvalhaes, MD, PhD, A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)Allergan (Research Grant or Support)Cidara Therapeutics (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Fox Chase Chemical Diversity Center (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Merck (Research Grant or Support)Merck (Research Grant or Support)Merck & Co, Inc. (Research Grant or Support)Pfizer (Research Grant or Support) Helio S. Sader, MD, PhD, A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)Allergan (Research Grant or Support)Allergan (Research Grant or Support)Allergan (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Melinta (Research Grant or Support)Merck (Research Grant or Support)Merck (Research Grant or Support)Paratek Pharma, LLC (Research Grant or Support)Pfizer (Research Grant or Support) Jennifer M. Streit, BS, A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)Allergan (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Merck (Research Grant or Support)Paratek Pharma, LLC (Research Grant or Support) Mariana Castanheira, PhD, 1928 Diagnostics (Research Grant or Support)A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)Allergan (Research Grant or Support)Allergan (Research Grant or Support)Amplyx Pharmaceuticals (Research Grant or Support)Cidara Therapeutics (Research Grant or Support)Cidara Therapeutics (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Fox Chase Chemical Diversity Center (Research Grant or Support)GlaxoSmithKline (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Merck (Research Grant or Support)Merck (Research Grant or Support)Merck & Co, Inc. (Research Grant or Support)Merck & Co, Inc. (Research Grant or Support)Paratek Pharma, LLC (Research Grant or Support)Pfizer (Research Grant or Support)Qpex Biopharma (Research Grant or Support) Rodrigo E. Mendes, PhD, A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)Allergan (Research Grant or Support)Allergan (Research Grant or Support)Basilea Pharmaceutica International, Ltd (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Department of Health and Human Services (Research Grant or Support)GlaxoSmithKline (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Merck (Research Grant or Support)Merck (Research Grant or Support)Pfizer (Research Grant or Support)

scholarly journals In vitro activity of tedizolid and comparator agents against Gram-positive pathogens responsible for bone and joint infections

2017 ◽  
Vol 66 (10) ◽  
pp. 1374-1378 ◽  
Author(s):  
Pauline Ract ◽  
Caroline Piau-Couapel ◽  
Fabrice Compain ◽  
Michel Auzou ◽  
Jocelyn Michon ◽  
...  
Keyword(s):  
Vitro Activity ◽  
In Vitro Activity ◽  
Gram Positive ◽  
Joint Infections ◽  
Bone And Joint Infections

scholarly journals 1253. In Vitro Activity of Omadacycline against 7000 Bacterial Pathogens from the United States Stratified by Infection Type (2019)

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S644-S644
Author(s):  
Michael D Huband ◽  
Michael A Pfaller ◽  
Jennifer M Streit ◽  
Helio S Sader ◽  
Mariana Castanheira
Keyword(s):  
United States ◽  
The United States ◽  
Chemical Diversity ◽  
Vitro Activity ◽  
Multiple Infection ◽  
In Vitro Activity ◽  
Infection Types ◽  
Center Research ◽  
Research Grant

Abstract Background Omadacycline (OMC) is a new aminomethylcycline antibacterial drug belonging to the tetracycline class, for intravenous or oral administration. It is well tolerated and has proven effective in the treatment of a variety of bacterial infections. OMC is active against bacterial strains expressing the most common clinically relevant tetracycline resistance mechanisms, namely efflux and ribosomal protection. Methods 7,000 clinical isolates were collected during 2019 in the SENTRY Surveillance Program from 31 medical centers in the United States (US). Isolates were obtained from bloodstream infection (23.8%), skin and skin structure infection (21.6%), pneumonia in hospitalized patients (22.7%), urinary tract infection (14.5%), intraabdominal infection (6.2%), community acquired respiratory tract infection (10.3%) and other infection types (0.9%). Identifications were confirmed by MALDI-TOF. One isolate/patient/infection episode was tested. Broth microdilution susceptibility testing was conducted according to CLSI M07 (2018) and M100 (2020) guidelines. Results were interpreted using US FDA and CLSI breakpoint criteria. Results OMC demonstrated potent in vitro activity against Staphylococcus aureus isolates representing multiple infection types (MIC90, 0.12-0.25 mg/L; 94.7%-99.0% susceptible [S]) including MRSA (MIC90, 0.25 mg/L; 96.5% S) (Table). All S. lugdunensis (MIC90, 0.06 mg/L), Enterococcus faecalis (MIC90, 0.12-0.25 mg/L), and Haemophilus influenzae (MIC90, 1 mg/L) isolates were S to OMC. OMC was active against Streptococcus pyogenes isolates from SSSI (MIC90, 0.12 mg/L; 93.3%-98.5%S) including macrolide-resistant (R) strains. Similarly, S. pneumoniae isolates from RTI were S to OMC (MIC90, 0.06-0.12 mg/L; 98.8%-100%S) regardless of resistance to tetracycline or penicillin. Overall, 90.2%-93.6% of Enterobacter cloacae (MIC90, 4 mg/L) and 89.7%-94.7% of Klebsiella pneumoniae (MIC90, 4-8 mg/L) isolates from multiple infection types were S to OMC. Conclusion OMC demonstrated potent in vitro activity against Gram-positive and -negative bacterial pathogens from multiple infection types including SSSI and RTI and isolates displaying resistance to tetracycline, macrolides, and penicillin. Table 1 Disclosures Michael A. Pfaller, MD, Amplyx Pharmaceuticals (Research Grant or Support)Basilea Pharmaceutica International, Ltd (Research Grant or Support)Cidara Therapeutics (Research Grant or Support)Cidara Therapeutics (Research Grant or Support)Department of Health and Human Services (Research Grant or Support)Fox Chase Chemical Diversity Center (Research Grant or Support)Paratek Pharma, LLC (Research Grant or Support) Jennifer M. Streit, BS, A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)Allergan (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Merck (Research Grant or Support)Paratek Pharma, LLC (Research Grant or Support) Helio S. Sader, MD, PhD, A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)Allergan (Research Grant or Support)Allergan (Research Grant or Support)Allergan (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Melinta (Research Grant or Support)Merck (Research Grant or Support)Merck (Research Grant or Support)Paratek Pharma, LLC (Research Grant or Support)Pfizer (Research Grant or Support) Mariana Castanheira, PhD, 1928 Diagnostics (Research Grant or Support)A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)Allergan (Research Grant or Support)Allergan (Research Grant or Support)Amplyx Pharmaceuticals (Research Grant or Support)Cidara Therapeutics (Research Grant or Support)Cidara Therapeutics (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Fox Chase Chemical Diversity Center (Research Grant or Support)GlaxoSmithKline (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Merck (Research Grant or Support)Merck (Research Grant or Support)Merck & Co, Inc. (Research Grant or Support)Merck & Co, Inc. (Research Grant or Support)Paratek Pharma, LLC (Research Grant or Support)Pfizer (Research Grant or Support)Qpex Biopharma (Research Grant or Support)

Tedizolid in vitro activity against Gram-positive clinical isolates causing bone and joint infections in hospitals in the USA and Europe (2014–17)

2019 ◽  
Vol 74 (7) ◽  
pp. 1928-1933 ◽  
Author(s):  
Cecilia G Carvalhaes ◽  
Hélio S Sader ◽  
Robert K Flamm ◽  
Rodrigo E Mendes
Keyword(s):  
Healthcare Providers ◽  
Antibiotic Use ◽  
Vitro Activity ◽  
In Vitro Activity ◽  
Gram Positive ◽  
Joint Infections ◽  
Bone And Joint Infections ◽  
The Usa ◽  
Adults And Children

Abstract Background Despite the advances in current healthcare, bone and joint infections (BJIs) are a major clinical challenge that frequently involve prolonged systemic antibiotic use. Healthcare providers consider tedizolid an attractive candidate for therapy in adults and children with BJI. Objectives We tested tedizolid against a US and European collection of Gram-positive BJI isolates (n = 797) consecutively collected from 2014 to 2017. Methods Organisms were tested by broth microdilution susceptibility methods following current CLSI guidelines and interpreted by both CLSI and EUCAST breakpoint criteria. Results Staphylococcus aureus (59.3%; 58.6% in the USA and 60.4% in Europe) was the most common pathogen with a 29.6% MRSA rate and tedizolid MIC50/90 of 0.12/0.25 mg/L (100% susceptible). CoNS (15.0% of BJI in adults and <5% in children) had tedizolid MIC50/90 values of 0.12/0.12 mg/L (99.1% susceptible). Tedizolid exhibited MIC50/90 values of 0.12/0.25 mg/L for all streptococci and enterococci. Overall, high susceptibility rates (>95%) for vancomycin, daptomycin and linezolid were observed and, based on MIC90 values, tedizolid (MIC90 0.12–0.25 mg/L) was 4- to 8-fold more potent than linezolid (MIC90 0.5–2  mg/L) against this collection of Gram-positive pathogens causing BJI. Conclusions This study showed that tedizolid had potent in vitro activity against contemporary Gram-positive cocci causing BJI in adults and children in US and European hospitals.

scholarly journals Antimicrobial Activity of Dalbavancin and Comparator Agents Tested against Gram-Positive Clinical Isolates Causing Bone and Joint Infections in United States (US) Medical Centers (2011–2016)

2017 ◽  
Vol 4 (suppl_1) ◽  
pp. S373-S373
Author(s):  
Helio S Sader ◽  
Rodrigo E Mendes ◽  
Robert K Flamm ◽  
Michael A Pfaller
Keyword(s):  
Active Agent ◽  
Coagulase Negative Staphylococci ◽  
Gram Positive ◽  
Joint Infections ◽  
Bone And Joint Infections ◽  
Prosthetic Joint ◽  
Prosthetic Joint Infections ◽  
Viridans Group Streptococci ◽  
Research Grant

Abstract Background Bone and joint infections (BJI) comprise a series of disorders, including septic arthritis, osteomyelitis, and prosthetic joint infections. We evaluated the activity of dalbavancin (DALBA) against pathogens isolated from BJI in US hospitals. Methods A total of 744 organisms collected from 55 hospitals in 2011–2016 were evaluated, including 463 S. aureus, 88 coagulase-negative staphylococci (CoNS), 104 β-haemolytic streptococci (BHS), 60 E. faecalis, and 29 viridans group streptococci (VGS). Bacteria were identified by standard algorithms and MALDI-TOF-MS. Susceptibility testing was performed by CLSI methods (M07-A10); interpretation of MIC results used CLSI (2017) and EUCAST (2017) criteria. Results S. aureus (62.2%) was the most common pathogen associated with BJI, followed by BHS (14.0%) and CoNS (11.8%). All S. aureus (41.5% methicillin-resistant [MRSA]) isolates were susceptible (S) to DALBA, linezolid (LNZ), teicoplanin (TEI) and vancomycin (VAN), while daptomycin (DAPTO) and clindamycin (CLI) showed susceptibility rates of 99.8% and 87.7% (CLSI), respectively. DALBA MIC results (MIC50/90, ≤0.03/0.06 μg/mL) were ≥8-fold lower compared with DAPTO (MIC50/90, 0.25/0.5 μg/mL) against all S. aureus. Among CoNS, (61.4% MRSA), DALBA (MIC50/90, ≤0.03/0.06 μg/mL) was the most potent agent, followed by DAPTO (MIC50/90, 0.25/0.5 μg/mL), LNZ (MIC50/90, 0.5/1 μg/mL), and VAN (MIC50/90, 1/2 μg/mL). DALBA inhibited all E. faecalis isolates at ≤0.25 μg/mL (FDA S breakpoint), except for 3 VAN-resistant (VanA) isolates. High susceptibility rates for ampicillin (98.3%; CLSI), DAPTO (100.0%), LNZ (100.0%), TEI (93.3%) and VAN (93.3%) were obtained against E. faecalis. DALBA, DAPTO, LNZ, ceftriaxone, penicillin, and VAN were active against all BHS (100.0%S), while DALBA (MIC50/90, ≤0.03/0.06 μg/mL; 100.0%S) was the most active agent against VGS, inhibiting all isolates at ≤0.06 μg/mL. Ceftriaxone, LNZ, DAPTO, and VAN were also active against VGS (93.1 – 100.0%S; CLSI), whereas CLI (82.8%S) had marginal activity. Conclusion DALBA demonstrated potent in vitro activity against common gram-positive isolates causing BJI (2011–2016) and appears to be a viable candidate for treating BJI/osteomyelitis caused by gram-positive cocci. Disclosures H. S. Sader, Allergan: Research Contractor, Research grant; R. E. Mendes, Allergan: Research Contractor, Research grant; R. K. Flamm, Allergan: Research Contractor, Research grant; M. A. Pfaller, Allergan: Research Contractor, Research grant

scholarly journals Activity of Tedizolid against Gram-Positive Clinical Isolates Causing Nosocomial- and Community-Acquired Infections in United States Hospitals (2014–2016)

2017 ◽  
Vol 4 (suppl_1) ◽  
pp. S371-S371
Author(s):  
Rodrigo E Mendes ◽  
Dee Shortridge ◽  
S J Ryan Arends ◽  
Helio S Sader ◽  
Mariana Castanheira ◽  
...  
Keyword(s):  
Infection Type ◽  
Bacterial Species ◽  
In Vitro Activity ◽  
Gram Positive ◽  
The Us ◽  
Star Program ◽  
Different Origins ◽  
Hospital Acquired ◽  
Research Grant

Abstract Background Tedizolid (TZD) was approved for the treatment of acute bacterial skin and skin structure infections and is also under investigation for the treatment of hospital-acquired (HA) bacterial pneumonia. The activity of TZD and comparators were evaluated against gram-positive (GP) pathogens causing community (CA)-acquired and HA infections in the US. Methods During the Surveillance of Tedizolid Activity and Resistance (STAR) Program, 10,091 GP isolates were recovered from patients in 31 US hospitals. Isolates were identified by standard biochemical algorithms and MALDI-TOF MS. Susceptibility (S) testing followed CLSI methods and CLSI/EUCAST interpretation. CA and HA infections were defined based on CDC criteria. Results TZD (MIC50/90, 0.12/0.12 µg/mL; 100.0%S) showed equivalent MIC50 and MIC90 values against MSSA and MRSA, regardless of infection type or origin of isolate (Table). Linezolid (LZD; MIC50/90, 0.5–1/1 µg/mL; 100.0%S), daptomycin (DAP; MIC50/90, 0.25/0.5 µg/mL; 99.5–100.0%S), vancomycin (VAN; MIC50/90, 0.5–1/1 µg/mL; 100.0%S) and trimethoprim-sulfamethoxazole (MIC50/90, ≤0.5/≤0.5 µg/mL; 93.0–99.5%S) were also active throughout against MSSA and MRSA, while MICs for other agents varied. TZD (MIC50/90, 0.12/0.25 µg/mL; 100.0%S) activities were consistent against E. faecalis causing various infections from different origins, as were LZD (MIC50/90, 1/1 µg/mL; 100.0%S), ampicillin (MIC50/90, 1/1–2 µg/mL; 100.0%S), DAP (MIC50/90, 1/1–2 µg/mL; 100.0%S), and VAN (MIC50/90, 1/2 µg/mL; 94.9–97.0%S), although these agents had MIC50 and MIC90 values 4- to 8-fold higher than TZD. TZD (MIC50/90, 0.12/0.25 µg/mL), LZD (MIC50/90, 1/1–2 µg/mL; 97.6–100.0%S) and DAP (MIC50/90, 1/2–4 µg/mL; 97.4–100.0%S) were active in vitro against E. faecium, regardless of infection type. S. pneumoniae isolates were S to several drugs tested, and ceftaroline showed the lowest MICs (MIC50/90, ≤0.015/0.06 µg/mL; 100.0%S). Conclusion TZD had potent in vitro activity against GP isolates causing CA and HA infections in US hospitals, regardless of infection site or bacterial species. The TZD in vitro potency was also generally higher than clinically available comparator agents. Disclosures R. E. Mendes, Merck: Research Contractor, Research grant; &#x2028;D. Shortridge, Merck: Research Contractor, Research grant; S. J. R. Arends, Merck: Research Contractor, Research grant; H. S. Sader, Merck: Research Contractor, Research grant; M. Castanheira, Merck: Research Contractor, Research grant; &#x2028;R. K. Flamm, Merck: Research Contractor, Research grant

scholarly journals In-vitro activity of teicoplanin and ceftriaxone in combination against pathogens involved in paediatric bone and joint infections

1996 ◽  
Vol 38 (4) ◽  
pp. 713-718
Author(s):  
Sylvie Lhopital ◽  
Stéphane Bonacorsi ◽  
Catherine Doit ◽  
Anna Sandin ◽  
Edouard Bingen
Keyword(s):  
Vitro Activity ◽  
In Vitro Activity ◽  
Joint Infections ◽  
Bone And Joint Infections

scholarly journals 327. Oritavancin Activity against Staphylococcus aureus Isolates Causing Bone and Joint Infections in European Hospitals (2010–2019)

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S235-S236
Author(s):  
Cecilia G Carvalhaes ◽  
Jennifer M Streit ◽  
Helio S Sader ◽  
Rodrigo E Mendes
Keyword(s):  
Staphylococcus Aureus ◽  
Western Europe ◽  
Methicillin Resistance ◽  
Chemical Diversity ◽  
Surveillance Program ◽  
Services Research ◽  
Joint Infections ◽  
Bone And Joint Infections ◽  
Research Grant

Abstract Background Bone and joint infections (BJI) frequently are caused by Staphylococcus aureus (SA), and since prolonged therapy courses typically are required, agents with convenient administration are preferred. Oritavancin (ORI) is a long-acting lipoglycopeptide approved as a single dose regimen for treating skin and skin structure infections. This study evaluates the activity of ORI and comparators against SA causing BJI in European (EU) hospitals. Methods A total of 575 SA isolates from the SENTRY Antimicrobial Surveillance Program causing BJI in 15 EU countries from 2010 to 2019 were included. Bacterial identification was confirmed by MALDI-TOF MS. Broth microdilution susceptibility (S) testing and interpretation was performed following current CLSI guidelines. The activities of ORI and comparators were evaluated across the years and by EU region: western Europe (W-EU; 491 isolates) and eastern EU/Mediterranean region (E-EU; 84 isolates). Results Methicillin resistance (MRSA) was observed in 20.5% of SA (18.5% in W-EU and 32.1% in E-EU), ranging from 31.1% in 2011 to 14.6% in 2016. MRSA rates were slightly lower in 2016–2019 (14.6%-19.2%) than previous years (2011–2013; 24.4%-31.1%). ORI exhibited 100.0% susceptibility across the entire SA collection with yearly MIC50 and MIC90 variations within 1 doubling dilutions (MIC50 and MIC90, 0.015–0.03 and 0.03–0.06 mg/L, respectively), regardless the MRSA phenotype or EU region. Daptomycin, vancomycin, teicoplanin, and linezolid also showed complete coverage against SA. Clindamycin (CLI; &gt;99.0%S) and levofloxacin (&gt; 95.0%S) were active against methicillin-susceptible SA, but less active against MRSA (67.8%S and 16.1%S, respectively). E-EU MRSA isolates displayed lower S rates than W-EU MRSA isolates to ceftaroline (83.3% vs. 90.6%), CLI (44.4% vs. 74.7%) and tetracycline (66.7% vs. 89.0%), respectively. Conclusion MRSA rates among isolates causing BJI varied within regions. Although several drugs were in vitro active against MSSA, options remained limited against MRSA. ORI showed in vitro activity against the entire collection of European SA isolates and may be a consideration for treating BJI with the convenience of drug administration. Table 1 Disclosures Cecilia G. Carvalhaes, MD, PhD, A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)Allergan (Research Grant or Support)Cidara Therapeutics (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Fox Chase Chemical Diversity Center (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Merck (Research Grant or Support)Merck (Research Grant or Support)Merck & Co, Inc. (Research Grant or Support)Pfizer (Research Grant or Support) Jennifer M. Streit, BS, A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)Allergan (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Merck (Research Grant or Support)Paratek Pharma, LLC (Research Grant or Support) Helio S. Sader, MD, PhD, A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)Allergan (Research Grant or Support)Allergan (Research Grant or Support)Allergan (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Melinta (Research Grant or Support)Merck (Research Grant or Support)Merck (Research Grant or Support)Paratek Pharma, LLC (Research Grant or Support)Pfizer (Research Grant or Support) Rodrigo E. Mendes, PhD, A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)Allergan (Research Grant or Support)Allergan (Research Grant or Support)Basilea Pharmaceutica International, Ltd (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Department of Health and Human Services (Research Grant or Support)GlaxoSmithKline (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Merck (Research Grant or Support)Merck (Research Grant or Support)Pfizer (Research Grant or Support)

scholarly journals In Vitro Activity of Omadacycline and Comparator Compounds Against Gram-positive Isolates Collected in the USA During 2016 as Part of a Global Surveillance Program

2017 ◽  
Vol 4 (suppl_1) ◽  
pp. S374-S374
Author(s):  
Michael D Huband ◽  
Michael a Pfaller ◽  
Helio S Sader ◽  
Robert K Flamm
Keyword(s):  
Resistance Mechanisms ◽  
Vitro Activity ◽  
Surveillance Program ◽  
Ionization Mass ◽  
In Vitro Activity ◽  
Coagulase Negative Staphylococci ◽  
Gram Positive ◽  
Resistant Strains ◽  
Research Grant

Abstract Background Omadacycline (OMC) is a broad spectrum aminomethylcycline antibacterial in late stage clinical development (PO and IV formulations) for treatment of acute bacterial skin and skin structure infections (ABSSSI) and community-acquired bacterial pneumonia (CABP). OMC has potent in vitro activity against gram-positive (GP) pathogens expressing common resistance mechanisms to penicillins, tetracyclines, fluoroquinolones and macrolides. Methods A total of 4,122 GP isolates were collected in 2016 from 30 USA medical centers and included 2,366 staphylococci, 1,252 streptococci and 504 enterococci. A single isolate/patient/infection episode was included. Identifications were confirmed by matrix-assisted laser desorption/ionization mass spectrometry and susceptibility (S) testing was performed using reference broth microdilution methods. Results OMC was equally active against methicillin-susceptible (55.1% MSSA) and -resistant (44.9% MRSA) Staphylococcus aureus (SA; MIC50/90, 0.12/0.25 µg/mL). All SA were S to daptomycin (DAP), linezolid (LZD) and vancomycin (VAN). In MRSA, S was lower for levofloxacin (LEV; 28.2%), clindamycin (CLI; 69.9%), and erythromycin (ERY; 10.9%). OMC (MIC50/90, 0.12/0.5 µg/mL) and tigecycline (TGC; MIC50/90, 0.06/12 µg/mL) were the most active agents against coagulase-negative staphylococci (CoNS) and methicillin-R CoNS. S. pneumoniae (including penicillin- [12.8% resistant], ceftriaxone- and ERY-resistant strains), viridans group streptococci (VGS) and β-hemolytic streptococci (including ERY and tetracycline resistant strains) were inhibited by low levels of OMC (MIC50/90 0.06/0.06–0.12 µg/mL) and TGC (MIC50/90 0.03–0.06/0.06–0.12 µg/mL). OMC was highly potent against enterococci (MIC50/90 0.12/0.25 µg/mL) including vancomycin-R isolates. Vancomycin resistance rates were 4.3% and 66.5% in E. faecalis and E. faecium, respectively. Conclusion OMC demonstrated potent activity against susceptible and resistant GP pathogens often associated with ABSSSI and CABP including staphylococci, S. pneumoniae, β-hemolytic streptococci, VGS and enterococci. These data support further omadacycline clinical studies, especially in infections where resistant GP isolates occur. Disclosures M. D. Huband, Paratek Pharma, LLC: Research Contractor, Research grant; M. A. Pfaller, Paratek Pharma, LLC: Research Contractor, Research grant; H. S. Sader, Paratek Pharma, LLC: Research Contractor, Research grant R. K. Flamm, Paratek Pharma, LLC: Research Contractor, Research grant

scholarly journals 1547. Activity of Tedizolid and Comparator Agents against Gram-Positive Bacterial Isolates Causing Skin and Skin Structure Infections in Pediatric Patients during 2015-2019 in the US

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S773-S773
Author(s):  
Cecilia G Carvalhaes ◽  
Helio S Sader ◽  
Paul R Rhomberg ◽  
Mariana Castanheira ◽  
Rodrigo E Mendes
Keyword(s):  
Pediatric Patients ◽  
Chemical Diversity ◽  
Services Research ◽  
Coagulase Negative Staphylococci ◽  
Gram Positive ◽  
Skin Structure ◽  
Broth Microdilution Method ◽  
The Us ◽  
Center Research ◽  
Research Grant

Abstract Background New strategies to treat acute bacterial skin and skin structure infections (ABSSSI) are needed due to the spread of methicillin-resistant Staphylococcus aureus (MRSA), a common multidrug resistant pathogen of ABSSSIs. Tedizolid (TZD) was approved by the US FDA for treating ABSSSI in adults and is under evaluation for treating pediatric patients. Accordingly, the activity of TZD and comparators was evaluated against clinical surveillance isolates collected from pediatric patients with SSSI in the US. Methods A total of 2,758 Gram-positive isolates were collected from pediatric patients with SSSIs in 33 sites in the US between 2015 and 2019 as part of the Surveillance of Tedizolid Activity and Resistance (STAR) Program. Bacterial identification was confirmed by MALDI-TOF MS and susceptibility (S) testing performed by the CLSI reference broth microdilution method. Current CLSI interpretative criteria was applied. Results S. aureus (SA; n=2,163; 78.4%) was the most frequent pathogen recovered from all age groups (≤ 1y; 2-5y; 6-12y; 13-17y), followed by β-hemolytic streptococci (BHS; n=460; 16.7%), and coagulase-negative staphylococci (CoNS; n=70; 2.5%). TZD was active against all SA (MIC50/90, 0.12/0.25 mg/L; 100% S). Equivalent TZD MIC50/90 values (0.12/0.25 mg/L) were observed against MRSA (n=886; 41.0%; MIC50/90, 0.12/0.25 mg/L) and methicillin susceptible (MSSA; MIC50/90, 0.12/0.25 mg/L) isolates, regardless the age group. TZD also was very active against BHS (MIC50/90, 0.12/0.25 mg/L; 100% S, regardless of species). TZD, linezolid, and daptomycin had 100.0% S rates against the main Gram-positive species and organism groups (Figure). Ceftaroline and clindamycin showed S rates of &gt;90% against MRSA, MSSA, S. pyogenes and S. dysgalactiae. Lower S rates were observed for clindamycin against VGS (88.2%) and S. agalactiae (64.1%). TZD was the most potent agent (MIC90, 0.25 mg/L) against Enterococcus faecalis (n=30, 1.1%), and a vancomycin-resistance phenotype was observed in 1 (3.3%) isolate. Conclusion TZD was highly active against Gram-positive clinical isolates responsible for SSSI in pediatric patients across US hospitals from a 5-year period. TZD was equipotent or more potent than comparators against MSSA and MRSA isolates. Table 1 Disclosures Cecilia G. Carvalhaes, MD, PhD, A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)Allergan (Research Grant or Support)Cidara Therapeutics (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Fox Chase Chemical Diversity Center (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Merck (Research Grant or Support)Merck (Research Grant or Support)Merck & Co, Inc. (Research Grant or Support)Pfizer (Research Grant or Support) Helio S. Sader, MD, PhD, A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)Allergan (Research Grant or Support)Allergan (Research Grant or Support)Allergan (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Melinta (Research Grant or Support)Merck (Research Grant or Support)Merck (Research Grant or Support)Paratek Pharma, LLC (Research Grant or Support)Pfizer (Research Grant or Support) Paul R. Rhomberg, n/a, Cidara Therapeutics (Research Grant or Support)Fox Chase Chemical Diversity Center (Research Grant or Support)Merck (Research Grant or Support) Mariana Castanheira, PhD, 1928 Diagnostics (Research Grant or Support)A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)Allergan (Research Grant or Support)Allergan (Research Grant or Support)Amplyx Pharmaceuticals (Research Grant or Support)Cidara Therapeutics (Research Grant or Support)Cidara Therapeutics (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Fox Chase Chemical Diversity Center (Research Grant or Support)GlaxoSmithKline (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Merck (Research Grant or Support)Merck (Research Grant or Support)Merck & Co, Inc. (Research Grant or Support)Merck & Co, Inc. (Research Grant or Support)Paratek Pharma, LLC (Research Grant or Support)Pfizer (Research Grant or Support)Qpex Biopharma (Research Grant or Support) Rodrigo E. Mendes, PhD, A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)Allergan (Research Grant or Support)Allergan (Research Grant or Support)Basilea Pharmaceutica International, Ltd (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Department of Health and Human Services (Research Grant or Support)GlaxoSmithKline (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Merck (Research Grant or Support)Merck (Research Grant or Support)Pfizer (Research Grant or Support)

Sign in / Sign up

Export Citation Format

Share Document