scholarly journals Antimicrobial Activity of Dalbavancin Tested against Staphylococcus aureus with Decreased Susceptibility to Glycopeptides, Daptomycin, and/or Linezolid from United States (US) Medical Centers

2017 ◽  
Vol 4 (suppl_1) ◽  
pp. S378-S378
Author(s):  
Helio S Sader ◽  
Rodrigo E Mendes ◽  
Leonard R Duncan ◽  
Michael A Pfaller ◽  
Robert K Flamm
Keyword(s):  
Antimicrobial Agents ◽  
European Medicines Agency ◽  
In Vitro Activity ◽  
Large Collection ◽  
Skin Structure ◽  
Medical Centers ◽  
Serious Infections ◽  
The Us ◽  
Research Grant

Abstract Background Dalbavancin (DALBA) was approved by the US Food and Drug Administration (2014) and European Medicines Agency (2015) for treating acute bacterial skin and skin structure infections. Dalbavancin activity was assessed against a large collection of S. aureus clinical isolates with decreased susceptibility (S) to key antimicrobial agents used to treat severe S. aureus infections. Methods The organism collection included isolates with decreased S to vancomycin (VAN; MIC ≥2 μg/mL; n = 1,141), daptomycin (DAPTO; MIC ≥2 μg/mL [resistant (R) per CLSI and EUCAST]; n = 48), telavancin (TLV; MIC ≥0.12 μg/mL; n = 73), teicoplanin (TEICO; MIC ≥4 μg/mL [non-S (NS) per EUCAST]; n = 143), and/or linezolid (LNZ; MIC ≥8 μg/mL [R per CLSI and EUCAST]; n = 25). Isolates were selected among 59,903 US isolates tested in 2002–2016. S testing was performed by CLSI methods and MIC results were interpreted per CLSI and EUCAST criteria. Results Only 8 of 59,903 (0.01%) S. aureus isolates tested were categorized as DALBA-NS (MIC, >0.25 μg/mL). DALBA retained activity against 99.3% of isolates with VAN MICs of ≥2 μg/mL (Table), whereas DAPTO (MIC50/90, 0.5/1 μg/mL) and LNZ (MIC50/90, 1/2 μg/mL) were active against 96.8% and 99.6% of isolates, respectively. DALBA (Table) and VAN (MIC50/90, 2/2 μg/mL) retained activity against 95.8% of DAPTO-NS S. aureus. When tested against TEICO-NS (EUCAST) isolates, S rates for DALBA, DAPTO, VAN, and LNZ were 95.1%, 95.8%, 97.9%, and 100.0%, respectively; and DALBA was 4- to 32-fold more potent than these comparator agents. All LNZ-R isolates (100.0%) were S to DALBA (MIC50/90, 0.06/0.06 μg/mL), DAPTO (MIC50/90, 0.5/0.5 μg/mL), and VAN (MIC50/90, 1/2 μg/mL), but DALBA was 8- and 16- to 32-fold more potent than DAPTO and VAN, respectively. MRSA rates ranged from 71.2–96.0% among these R subsets. Conclusion DALBA retained potent in vitro activity against S. aureus isolates, displaying decreased susceptibility to agents commonly used to treat serious infections and was consistently more potent than comparator agents. Disclosures H. S. Sader, Allergan: Research Contractor, Research grant; R. E. Mendes, Allergan: Research Contractor, Research grant; L. R. Duncan, Allergan: Research Contractor, Research grant; M. A. Pfaller, Allergan: Research Contractor, Research grant; R. K. Flamm, Allergan: Research Contractor, Research grant

scholarly journals 1226. In Vitro Activity of Tebipenem and Comparators Against Enterobacterales Collected from Patients with Bloodstream Infections as Part of the 2019 Global STEWARD Surveillance Program

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S702-S702
Author(s):  
Ian A Critchley ◽  
Nicole Cotroneo ◽  
Rodrigo E Mendes ◽  
Michael J Pucci
Keyword(s):  
Bloodstream Infections ◽  
Clinical Development ◽  
Asia Pacific ◽  
Surveillance Program ◽  
In Vitro Activity ◽  
Medical Centers ◽  
Oral Agents ◽  
The Us ◽  
Research Grant

Abstract Background Bloodstream infections (BSI) are a significant cause of morbidity and mortality. Enterobacterales (ENT) are frequently implicated in BSI with an increase in organisms producing extended-spectrum β-lactamase (ESBL). This challenges a possible transition to current oral agents due to co-resistance. Carbapenems are active against ESBL-ENT and tebipenem (TBP) is a new oral carbapenem in clinical development. The aim of the study was to assess resistance (R) among BSI isolates and activity of TBP and comparators against ENT collected in a 2019 surveillance study. Methods 2612 ENT from BSI were centrally tested by reference broth microdilution. Isolates were from medical centers in the US, Europe (EU), Latin America (LA) and Asia Pacific (AP). MIC results were interpreted according to CLSI, including ESBL assignment. CRE were sequenced to identify carbapenemase genes. Results Among the ENT, non-susceptibility (NS) rates to ceftazidime, levofloxacin were 20.4 and 27.0%, respectively, and R to trimethoprim-sulfamethoxazole was 31.1%. NS rates for ertapenem (ETP) and MER were 4.9 and 2.7%, respectively. MIC90s for TBP, ETP and MER were 0.12, 0.12 and 0.06 µg/mL, respectively. The MIC90 for TBP was 0.06 µg/mL for ENT from the US and 0.12 µg/mL for isolates from EU, LA and AP. Escherichia coli (EC) was the most prevalent (52% of ENT isolates) and the MIC90 for TBP ranged from 0.015 µg/mL for isolates in the US/EU to 0.03 µg/mL for isolates in LA/AP. ESBL-EC ranged from 15.7% in US to 34.3% in LA. TBP was active against ESBL-EC with an MIC90 of 0.03 µg/mL. Klebsiella pneumoniae (KP) accounted for 22.7% of BSI caused by ENT and TBP MIC90 ranged from 0.06 µg/mL for KP in US to >8 µg/mL in EU, LA and AP. MER-R KP ranged from 2.4% in US to 14.9% in LA. KPC-2, -3 and NDM were the most prevalent carbapenemases. TBP MIC90 values for MER-S ESBL KP in EU, LA and AP were ≤0.12 µg/mL. Conclusion TBP activity was similar to ETP and MER against ENT responsible for BSI. R to oral agents was compromised by ESBL co-resistance. TBP was among the most active agents against EC isolates and ESBL phenotypes. Among KP, TBP was more active against isolates from US where prevalence of CRE was lower than EU, LA and AP. TBP may be considered as an alternative oral option for BSI caused by non-CRE ESBL-producing ENT. Disclosures Ian A. Critchley, Ph.D., Spero Therapeutics (Employee, Shareholder) Nicole Cotroneo, Spero Therapeutics (Employee, Shareholder) Rodrigo E. Mendes, PhD, AbbVie (Research Grant or Support)AbbVie (formerly Allergan) (Research Grant or Support)Cipla Therapeutics (Research Grant or Support)Cipla USA Inc. (Research Grant or Support)ContraFect Corporation (Research Grant or Support)GlaxoSmithKline, LLC (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Melinta Therapeutics, LLC (Research Grant or Support)Nabriva Therapeutics (Research Grant or Support)Pfizer, Inc. (Research Grant or Support)Shionogi (Research Grant or Support)Spero Therapeutics (Research Grant or Support)

scholarly journals Antimicrobial Activity of Ceftazidime-Avibactam and Comparator Agents Tested against Enterobacteriaceae and Pseudomonas aeruginosa from United States (US) Medical Centers Stratified by Infection Type (2015–2016)

2017 ◽  
Vol 4 (suppl_1) ◽  
pp. S378-S378
Author(s):  
Helio S Sader ◽  
Mariana Castanheira ◽  
Leonard R Duncan ◽  
Robert K Flamm
Keyword(s):  
Infection Type ◽  
Broth Microdilution ◽  
Large Collection ◽  
Skin Structure ◽  
Highly Active ◽  
Medical Centers ◽  
Carbapenem Resistant ◽  
Infection Types ◽  
Research Grant

Abstract Background We evaluated and compared the in vitro activities of ceftazidime-avibactam (CAZ-AVI) and comparators against of Enterobacteriaceae (ENT) and P. aeruginosa (PSA) from various infection types. Methods 23,440 isolates composed of 19,249 ENT and 4,191 PSA were consecutively collected from 85 US hospitals and tested for susceptibility (S) by broth microdilution methods in a central monitoring laboratory (JMI Laboratories). The antimicrobial S and frequency of key resistance (R) phenotypes, such as multidrug-R (MDR) and extensively drug-R (XDR) among others, were assessed and stratified by these infection types: bloodstream (BSI; 3,434 isolates; 14.7%), pneumonia (6,439; 27.5%), skin/skin structure (SSSI; 4,134; 17.6%), intra-abdominal (IAI; 951; 4.1%), urinary tract (UTI; 7,873; 33.6%), and others combined (609; 2.6%). Results CAZ-AVI was active against 99.9% to 100.0% of ENT and 97.0% (pneumonia) to 99.4% (UTI) of PSA isolates. S rates were consistently lower among ENT from pneumonia compared with other infection types for β-lactams such as CAZ (82.3% vs. 87.1–90.8%), piperacillin-tazobactam (P-T; 87.5% vs. 90.2–95.6%) and meropenem (MEM; 96.8% vs. 98.4–99.4%). S to gentamicin (GEN) was also generally lower among isolates from pneumonia, whereas S to levofloxacin (LEV) and colistin (COL) were lowest among BSI and SSSI isolates, respectively. The occurrence of MDR, XDR, and carbapenem-resistant ENT (CRE) phenotypes were markedly higher among isolates from patients with pneumonia compared with other infection types (Table). Among PSA, S rates for CAZ, P-T, and GEN were lowest among isolates from pneumonia, whereas S to MEM was similar among isolates from BSI, pneumonia, and IAI (77.3–77.9%), and S to LEV was markedly lower among UTI isolates (67.1%). The frequency of PSA isolates with MDR and XDR phenotypes, as well as non-S to CAZ, MER, and P-T, were also highest among isolates from patients with pneumonia (Table). Conclusion Antimicrobial S rates were generally lower among ENT and PSA isolates from patients with pneumonia compared with other infections. CAZ-AVI was highly active against a large collection of contemporary ENT and PSA isolates from US hospitals (2015–2016), including MDR and XDR organisms, regardless of the infection type. Disclosures H. S. Sader, Allergan: Research Contractor, Research grant; M. Castanheira, Allergan: Research Contractor, Research grant; L. R. Duncan, Allergan: Research Contractor, Research grant; R. K. Flamm, Allergan: Research Contractor, Research grant

scholarly journals 1369. Oritavancin Activity Against Methicillin-Resistant S. aureus (MRSA) Isolates Causing Skin and Skin Structure Infections in US Hospitals (2017-2019)

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S770-S771
Author(s):  
Cecilia G Carvalhaes ◽  
Helio S Sader ◽  
Dee Shortridge ◽  
Jennifer M Streit ◽  
Rodrigo E Mendes
Keyword(s):  
Multidrug Resistant ◽  
Vitro Activity ◽  
In Vitro Activity ◽  
Services Research ◽  
Department Of Health ◽  
Medical Centers ◽  
The Us ◽  
Us Fda ◽  
Research Grant

Abstract Background MRSA remains an important cause of community-onset (CA) and nosocomial (NA)- SSSI. Oritavancin (ORI) is a lipoglycopeptide antibiotic with activity against S. aureus, including MRSA and multidrug-resistant (MDR) strains. ORI was approved for clinical use by the US FDA to treat ABSSSI with a single 1,200 mg infusion over 1 (Kimyrsa) or 3 (Orbactiv) hours. This study evaluated the activity of ORI against MRSA isolates causing SSSI from US medical centers. Methods A total of 3,792 S. aureus isolates were consecutively collected (1 per patient) from 31 medical centers in 2017-2019 and tested for susceptibility (S) to ORI and comparators using CLSI broth microdilution methods. Among 1,582 (41.7%) MRSA isolates, 1,379 (87.2%) were reported as CA-MRSA and 203 (12.8%) as NA-MRSA. CA-MRSA isolates were evaluated by resistance (R) subgroups, including clindamycin (CLI-R; n=283; 20.5%), levofloxacin (LEV-R; n=831; 60.3%), MDR (non-susceptible to ≥3 classes of agents; n=816; 59.2%), and extensively drug resistant (XDR; non-susceptible to ≥5 classes; n=47; 3.4%). Results Overall, ORI inhibited 99.9% of all S. aureus isolates at the susceptible breakpoint (≤0.12 mg/L; 99.9% of MSSA and 100% of MRSA; Table). S rates were generally comparable between NA-MRSA and CA-MRSA isolates for ORI (100%S) and linezolid (LZD, 100%S) but lower susceptibility was observed for NA-MRSA compared to CA-MRSA for CLI (71.9%S vs. 79.1%S), LEV (31.0%S vs. 39.4%S), and trimethoprim-sulfamethoxazole (TMP-SMX; 91.1%S vs. 96.9%S). ORI was active against MRSA (MIC50/90, 0.03/0.03 mg/L), regardless of infection status (NA, MIC50/90, 0.03/0.06 mg/L; CA, MIC50/90, 0.03/0.03 mg/L). ORI and LZD remained active (100%S) against all CA-MRSA subsets: CLI-R, LEV-R, MDR, and XDR. Limited activity of CLI (69.9%S) and LEV (13.1%S) was observed against MRSA and each R subset, whereas TMP-SMX had >90%S for all MSSA, MRSA, and R subsets, except XDR. Conclusion ORI exhibited potent in vitro activity against MRSA, regardless of the infection onset or R subset, in contrast to many comparators that lack activity against both, CA-MRSA and NA-MRSA. This in vitro activity, combined with the infusion time options provided to clinicians, suggests ORI is a favorable agent for treating SSSI in the US caused by MRSA, including MDR and XDR strains. Disclosures Cecilia G. Carvalhaes, MD, PhD, AbbVie (formerly Allergan) (Research Grant or Support)Cidara Therapeutics, Inc. (Research Grant or Support)Cipla Therapeutics (Research Grant or Support)Cipla USA Inc. (Research Grant or Support)Melinta Therapeutics, LLC (Research Grant or Support)Pfizer, Inc. (Research Grant or Support) Helio S. Sader, MD, PhD, FIDSA, AbbVie (formerly Allergan) (Research Grant or Support)Basilea Pharmaceutica International, Ltd. (Research Grant or Support)Cipla Therapeutics (Research Grant or Support)Cipla USA Inc. (Research Grant or Support)Department of Health and Human Services (Research Grant or Support, Contract no. HHSO100201600002C)Melinta Therapeutics, LLC (Research Grant or Support)Nabriva Therapeutics (Research Grant or Support)Pfizer, Inc. (Research Grant or Support)Shionogi (Research Grant or Support)Spero Therapeutics (Research Grant or Support) Dee Shortridge, PhD, AbbVie (formerly Allergan) (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Melinta Therapeutics, LLC (Research Grant or Support)Shionogi (Research Grant or Support) Jennifer M. Streit, BS, GlaxoSmithKline, LLC (Research Grant or Support)Melinta Therapeutics, LLC (Research Grant or Support)Shionogi (Research Grant or Support)Spero Therapeutics (Research Grant or Support) Rodrigo E. Mendes, PhD, AbbVie (Research Grant or Support)AbbVie (formerly Allergan) (Research Grant or Support)Cipla Therapeutics (Research Grant or Support)Cipla USA Inc. (Research Grant or Support)ContraFect Corporation (Research Grant or Support)GlaxoSmithKline, LLC (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Melinta Therapeutics, LLC (Research Grant or Support)Nabriva Therapeutics (Research Grant or Support)Pfizer, Inc. (Research Grant or Support)Shionogi (Research Grant or Support)Spero Therapeutics (Research Grant or Support)

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; 
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; 
R. K. Flamm, Merck: Research Contractor, Research grant

scholarly journals 1320. In Vitro Activity of Lefamulin against Staphylococcus aureus Isolated from the Lower Respiratory Tract of Children with Cystic Fibrosis

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S748-S749
Author(s):  
Helio S Sader ◽  
Susanne Paukner ◽  
Steven P Gelone ◽  
S J Ryan Arends ◽  
Rodrigo E Mendes
Keyword(s):  
Cystic Fibrosis ◽  
Costa Rica ◽  
Respiratory Tract ◽  
Lower Respiratory Tract ◽  
Vitro Activity ◽  
In Vitro Activity ◽  
Services Research ◽  
The Us ◽  
Research Grant

Abstract Background Lefamulin is a first-in-class, oral and IV pleuromutilin antibiotic approved in the US, EU, and Canada for the treatment of community-acquired bacterial pneumonia (CABP) in adults. Lefamulin inhibits bacterial protein synthesis via a unique mechanism of action and its potency against S. aureus has been well established. We evaluated the in vitro activity of lefamulin against S. aureus from patients with cystic fibrosis (CF). Methods Unique isolates (n=224) were collected from the lower respiratory tract (LRT) of children (≤17 years old) with CF and LRT infection. Organisms were from qualified respiratory specimens and determined to be the probable cause of infection by the participant center. The isolates were collected in 2018-2020 from 22 medical centers in 11 countries and tested by broth microdilution methods at JMI Laboratories. Most isolates were from the US (43.3%), Spain (24.1%), France (20.5%), and Costa Rica (7.1%). Results Lefamulin was highly active against the CF S. aureus collection (MIC5090, 0.06/0.12 mg/L), with 99.6% of isolates inhibited at ≤0.25 mg/L, consistent with the susceptible [S] breakpoint published by the US FDA, CLSI, and EUCAST. Only 1 lefamulin-non-S (MIC, 1 mg/L) isolate was observed, a methicillin-susceptible (MSSA) collected in Costa Rica in 2018 and carrying a vga(A) gene. Lefamulin retained potent activity against methicillin-resistant (R) S. aureus (MRSA, n=52; MIC50/90, 0.06/0.12 mg/L), azithromycin-R (n=115; MIC50/90, 0.06/0.12 mg/L), levofloxacin-R (n=23; MIC50/90, 0.06/0.12 mg/L), clindamycin-R (n=11; MIC50/90, 0.06/0.12 mg/L), and gentamicin-R (n=9; MIC range of 0.03-0.12 mg/L) isolates as well as those isolates with multiple resistance phenotypes. Against MRSA, susceptibility to azithromycin was 23.5% and to levofloxacin 64.7%. All isolates were susceptible to vancomycin, linezolid and ceftaroline (Table). Among isolates from the US (n=97), the MRSA rate was 30.9% and all isolates were Lefamulin-S (MIC5090, 0.06/0.12 mg/L). Conclusion Lefamulin demonstrated potent in vitro antibacterial activity against S. aureus from children with CF, regardless of resistance phenotype. Lefamulin may represent a valuable treatment option for CF patients with S. aureus LRT infections. Disclosures Helio S. Sader, MD, PhD, FIDSA, AbbVie (formerly Allergan) (Research Grant or Support)Basilea Pharmaceutica International, Ltd. (Research Grant or Support)Cipla Therapeutics (Research Grant or Support)Cipla USA Inc. (Research Grant or Support)Department of Health and Human Services (Research Grant or Support, Contract no. HHSO100201600002C)Melinta Therapeutics, LLC (Research Grant or Support)Nabriva Therapeutics (Research Grant or Support)Pfizer, Inc. (Research Grant or Support)Shionogi (Research Grant or Support)Spero Therapeutics (Research Grant or Support) Susanne Paukner, PhD, Nabriva Therapeutics GmbH (Employee) Steven P. Gelone, PharmD, Nabriva Therapeutics US, Inc. (Employee) S J Ryan Arends, PhD, AbbVie (formerly Allergan) (Research Grant or Support)GlaxoSmithKline, LLC (Research Grant or Support)Melinta Therapeutics, LLC (Research Grant or Support)Nabriva Therapeutics (Research Grant or Support)Spero Therapeutics (Research Grant or Support) Rodrigo E. Mendes, PhD, AbbVie (Research Grant or Support)AbbVie (formerly Allergan) (Research Grant or Support)Cipla Therapeutics (Research Grant or Support)Cipla USA Inc. (Research Grant or Support)ContraFect Corporation (Research Grant or Support)GlaxoSmithKline, LLC (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Melinta Therapeutics, LLC (Research Grant or Support)Nabriva Therapeutics (Research Grant or Support)Pfizer, Inc. (Research Grant or Support)Shionogi (Research Grant or Support)Spero Therapeutics (Research Grant or Support)

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 1054. Activity of a Anti-staphylococcal Lysin, LSVT-1701: In vitro Susceptibility of Staphylococcus aureus and Coagulase-Negative Staphylococci (CoNS) Global Clinical Isolates (2002 to 2019)

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S618-S619
Author(s):  
David Huang ◽  
Helio S Sader ◽  
Paul R Rhomberg ◽  
Katyna Borroto-Esoda ◽  
Eric Gaukel
Keyword(s):  
The United States ◽  
Vitro Activity ◽  
Clinical Isolates ◽  
Asia Pacific ◽  
In Vitro Activity ◽  
Coagulase Negative Staphylococci ◽  
Medical Centers ◽  
Broth Microdilution Method ◽  
Research Grant

Abstract Background LSVT-1701, formerly SAL200, is a novel, recombinantly-produced, bacteriophage-encoded lysin that specifically targets staphylococci via cell wall enzymatic hydrolysis. We reported the in vitro activity of LSVT-1701 against clinical isolates of S. aureus and coagulase-negative staphylococci (CoNS) collected worldwide. Methods LSVT-1701 and comparators were tested against 415 S. aureus (n=315) and CoNS (n=100) clinical isolates expressing various resistance phenotypes. The isolates were collected in 2002-2019 from medical centers located in the United States (50 medical centers; 174 isolates; 41.9% overall), Europe (37 medical centers; 140 isolates; 33.7% overall), Asia-Pacific region (15 medical centers; 55 isolates; 13.3% overall), and Latin America (12 medical centers; 46 isolates; 11.1% overall). These isolates originated mostly from the year 2019 (n=323).The isolates were susceptibility tested by the CLSI broth microdilution method. MIC interpretations were based on CLSI and EUCAST criteria where available. Results LSVT-1701 was highly active against S. aureus and CoNS isolates with MIC90 values of 2 mg/L for all S. aureus, methicillin-susceptible S. aureus (MSSA), methicillin-resistant S. aureus (MRSA), and CoNS (Table). The highest LSVT-1701 MIC values were 4 and 8 mg/L among S. aureus and CoNS, respectively. LSVT-1701 retained potent activity against S. aureus isolates showing resistance or decreased susceptibility to oxacillin, vancomycin, teicoplanin, telavancin, linezolid, daptomycin, ceftaroline, or lefamulin; MIC50 values ranged from 0.5 to 1 mg/L and MIC90 values ranged from 1 to 4 mg/L among S. aureus resistant subsets. Summary of LSVT-1701 activity against S. aureus, CoNS and resistant subsets Conclusion LSVT-1701 demonstrated potent in vitro activity against contemporary clinical isolates of S. aureus and CoNS collected from medical centers worldwide and against resistant S. aureus isolates with uncommon resistance phenotypes. The results of this study support further clinical development of LSVT-1701 to treat staphylococcal infections. Disclosures David Huang, MD, PhD, Lysovant (Consultant) Helio S. Sader, MD, PhD, FIDSA, AbbVie (formerly Allergan) (Research Grant or Support)Basilea Pharmaceutica International, Ltd. (Research Grant or Support)Cipla Therapeutics (Research Grant or Support)Cipla USA Inc. (Research Grant or Support)Department of Health and Human Services (Research Grant or Support, Contract no. HHSO100201600002C)Melinta Therapeutics, LLC (Research Grant or Support)Nabriva Therapeutics (Research Grant or Support)Pfizer, Inc. (Research Grant or Support)Shionogi (Research Grant or Support)Spero Therapeutics (Research Grant or Support) Paul R Rhomberg, Cidara Therapeutics, Inc. (Research Grant or Support)Pfizer, Inc. (Research Grant or Support) Katyna Borroto-Esoda, PhD, Lysovant (Consultant) Eric Gaukel, BS, Lysovant (Employee)

scholarly journals Antimicrobial Activity of Ceftazidime-Avibactam Tested against Multidrug-Resistant Enterobacteriaceae and Pseudomonas aeruginosa Isolates from United States (US) Medical Centers (2013–2016)

2017 ◽  
Vol 4 (suppl_1) ◽  
pp. S376-S376
Author(s):  
Helio S Sader ◽  
Mariana Castanheira ◽  
Dee Shortridge ◽  
Rodrigo E Mendes ◽  
Robert K Flamm
Keyword(s):  
Multidrug Resistant ◽  
Drug Resistant ◽  
In Vitro Activity ◽  
Negative Results ◽  
Medical Centers ◽  
Carbapenem Resistant ◽  
Extensively Drug Resistant ◽  
Genes Encoding ◽  
Research Grant

Abstract Background The in vitro activity of ceftazidime-avibactam (CAZ-AVI) and many comparator agents were tested against various resistant subsets of organisms selected among 36,380 Enterobacteriaceae and 7,868 P. aeruginosa isolates. Methods Isolates were consecutively collected from 94 US hospitals in 2013–2016 and tested for susceptibility by reference broth microdilution methods in a central monitoring laboratory (JMI Laboratories) as part of the International Network for Optimal Resistance Monitoring (INFORM) program. Enterobacteriaceae strains with elevated CAZ-AVI MIC values (≥16 μg/mL) were evaluated for the presence of genes encoding extended-spectrum β-lactamases, KPC, NDM, and transferable AmpC enzymes. Results CAZ-AVI inhibited >99.9% of all Enterobacteriaceae at the susceptible (S) breakpoint of ≤8 μg/mL and was active against multidrug-resistant (MDR; n = 2,953; MIC50/90, 0.25/1 μg/mL; 99.2%S, extensively drug-resistant (XDR; n = 448; MIC50/90, 0.5/2 μg/mL; 97.8%S), and carbapenem-resistant isolates (CRE; n = 513; MIC50/90, 0.5/2 μg/mL; 97.5%S). Only 82.2% of MDR Enterobacteriaceae and 64.2% of ceftriaxone-nonsusceptible (NS) Klebsiella pneumoniae (n = 1,063) were meropenem-S. Among Enterobacter cloacae (n = 3,740; 22.2% ceftazidime-NS), 99.8% of isolates, including 99.3% of ceftazidime-NS isolates, were CAZ-AVI-S. Only 22 of 36,380 Enterobacteriaceae (0.06%) isolates were CAZ-AVI-NS, including 8 MBL-producers (0.02%) and 2 KPC-producing strains with porin alteration; the remaining 12 strains showed negative results for all β-lactamases tested. CAZ-AVI showed potent activity against P. aeruginosa (n = 7,868; MIC50/90, 2/4 μg/mL; 97.1% S), including meropenem-NS (n = 1,471; MIC50/90, 4/16 μg/mL; 87.2%S) and MDR (n = 1,562; MIC50/90, 4/16 μg/mL; 86.5%S) isolates, and inhibited 71.8% of isolates NS to meropenem, piperacillin-tazobactam, and ceftazidime (n = 628). Conclusion CAZ-AVI demonstrated potent activity against a large US collection (n = 44,248) of contemporary gram-negative bacilli, including organisms resistant to most currently available agents, such as CRE and meropenem-NS P. aeruginosa. Disclosures H. S. Sader, Allergan: Research Contractor, Research grant; M. Castanheira, Allergan: Research Contractor, Research grant; D. Shortridge, Allergan: Research Contractor, Research grant; R. E. Mendes, Allergan: Research Contractor, Research grant; R. K. Flamm, Allergan: Research Contractor, Research grant

Sign in / Sign up

Export Citation Format

Share Document