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 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 708. In Vitro Activity of Plazomicin vs. Clinical Isolates of Gram-Negative Bacilli, Including Aminoglycoside Nonsusceptible and Multidrug-Resistant Subsets, Recovered from Patients Across Canada as Part of the CANWARD study, 2011–2018

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S319-S319
Author(s):  
Andrew Walkty ◽  
Heather Adam ◽  
Melanie Baxter ◽  
Philippe Lagace-Wiens ◽  
James Karlowsky ◽  
...  
Keyword(s):  
Multidrug Resistant ◽  
Vitro Activity ◽  
Clinical Isolates ◽  
In Vitro Activity ◽  
Gram Negative ◽  
E Coli ◽  
The Us ◽  
Us Fda ◽  
Tract Infections

Abstract Background Plazomicin (PLZ) is a next-generation aminoglycoside currently approved by the US FDA for the treatment of complicated urinary tract infections, including pyelonephritis. The purpose of this study was to evaluate the in vitro activity of PLZ against a large collection of Gram-negative bacilli obtained from patients attending Canadian hospitals. Methods Annually from 2011 to 2018, sentinel hospitals across Canada submitted blood, respiratory, urine, and wound isolates from patients attending ERs, medical and surgical wards, hospital clinics, and ICUs (CANWARD). Susceptibility testing was performed using broth microdilution (and breakpoints) as described by CLSI (FDA breakpoints used for PLZ). Results See table. S, susceptible; NS, nonsusceptible; ESBL, extended-spectrum β-lactamase; MDR, multidrug-resistant (NS to antimicrobials from three or more classes); n.d., not defined. Conclusion PLZ demonstrated excellent in vitro activity vs. E. coli and K. pneumoniae clinical isolates, including aminoglycoside NS, ESBL-positive, and MDR subsets. Disclosures All authors: No reported disclosures.

scholarly journals Evaluation of In Vitro Activity of Ceftaroline Tested against Streptococcus pneumoniae Isolates from United States Hospitals: Results from 7 Years of the AWARE Surveillance Program (2010–2016)

2017 ◽  
Vol 4 (suppl_1) ◽  
pp. S378-S378
Author(s):  
Michael A Pfaller ◽  
Rodrigo E Mendes ◽  
Leonard R Duncan ◽  
Robert K Flamm ◽  
Helio S Sader
Keyword(s):  
United States ◽  
The United States ◽  
Multidrug Resistant ◽  
Vitro Activity ◽  
Surveillance Program ◽  
In Vitro Activity ◽  
Amoxicillin Clavulanate ◽  
Infection Types ◽  
Research Grant

Abstract Background Ceftaroline (CPT) is a broad-spectrum cephalosporin with activity against S. pneumoniae (SPN), including multidrug-resistant (MDR) strains. CPT fosamil is approved for clinical use in the United States (US) to treat community-acquired bacterial pneumonia (CABP). The AWARE Program monitors the in vitro activity of CPT against clinical bacteria from various infection types. We evaluated the activity of CPT against isolated SPN clinical isolates from US hospitals collected in 2010 through 2016. Methods A total of 8,768 isolates were consecutively collected (1 per patient) from 47 medical centers in 2010–2016 and tested for susceptibility (S) to CPT and comparator agents using CLSI broth microdilution methods. Resistant subgroups included isolates that were nonsusceptible (NS) to penicillin (PCN), ceftriaxone (CRO), amoxicillin-clavulanate (AMC), erythromycin (ERY), clindamycin (CM), and levofloxacin (LEV) as well as MDR (NS to ≥3 classes of agents) and extensively drug resistant (XDR; NS to ≥5 classes). Results CPT inhibited 99.99% of SPN isolates at ≤0.5 mg/L (only 1 isolate had a CPT MIC of 1 mg/L) and remained active against all SPN-resistant (R) subgroups, including PCN-NS (8.7% at ≥4 mg/L), CRO-NS (6.9% at ≥2 mg/L), MDR (21.7%), and XDR (8.4%) strains. CPT activity remained stable against all R subgroups each year. MDR and XDR frequency decreased from 25.0% and 14.1% in 2011 to 17.8% and 3.2% in 2015, respectively; and S to PCN, CRO, AMC, CM, trimethoprim-sulfamethoxazole (TMX), and tetracycline (TET) increased in the same period (Table). The CPT-NS isolate had multiple substitutions in the penicillin binding proteins (PBP), mainly PBP2x, when compared with reference sequences, and showed 31 amino acid alterations in MurM. For MDR isolates, CPT (99.9%S), tigecycline (99.9%S), linezolid (100.0%S), and vancomycin (100.0%S) were the most active agents. Conclusion CPT demonstrated potent and consistent (2010–2016) activity against SPN, including several R phenotypes and the less S serotypes. SPN S to many antibiotics increased from 2011 to 2015, but remained stable in 2015–2016. Increases in S rates could be related to the anti-pneumococcal vaccine PVC-13 introduced in 2010. Disclosures M. A. Pfaller, Allergan: Research Contractor, Research grant; R. E. Mendes, Allergan: Research Contractor, Research grant; L. R. Duncan, Allergan: Research Contractor, Research grant; R. K. Flamm, Allergan: Research Contractor, Research grant; H. S. Sader, Allergan: Research Contractor, Research grant

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

In Vitro Activity of Imipenem/Relebactam and Ceftolozane/Tazobactam Against Clinical Isolates of Gram-negative Bacilli With Difficult-to-Treat Resistance and Multidrug-resistant Phenotypes—Study for Monitoring Antimicrobial Resistance Trends, United States 2015–2017

2020 ◽  
Author(s):  
James A Karlowsky ◽  
Sibylle H Lob ◽  
Janet Raddatz ◽  
Daryl D DePestel ◽  
Katherine Young ◽  
...  
Keyword(s):  
Multidrug Resistant ◽  
Vitro Activity ◽  
In Vitro Activity ◽  
First Line ◽  
Clin Microbiol Infect ◽  
Gram Negative ◽  
Novel Approach ◽  
The Us ◽  
Urinary Isolates

Abstract Background Multidrug-resistant (MDR) bacteria are frequently defined using the criteria established by Magiorakos et al [Clin Microbiol Infect 2012;18:268–81]. Difficult-to-treat resistance (DTR) [Kadri et al, Clin Infect Dis 2018;67:1803–14] is a novel approach to defining resistance in gram-negative bacilli focusing on treatment-limiting resistance to first-line agents (all β-lactams and fluoroquinolones). Methods Clinical and Laboratory Standards Institute–defined broth microdilution minimum inhibitory concentrations (MICs) were determined for imipenem/relebactam, ceftolozane/tazobactam, and comparators against respiratory, intraabdominal, and urinary isolates of Enterobacterales (n = 10 516) and Pseudomonas aeruginosa (n = 2732) collected in 26 US hospitals in 2015–2017. Results Among all Enterobacterales, 1.0% of isolates were DTR and 15.6% were MDR; 8.4% of P. aeruginosa isolates were DTR and 32.4% were MDR. MDR rates for Enterobacterales and DTR and MDR rates for P. aeruginosa were significantly higher (P < .05) in isolates collected in intensive care units (ICUs) than in non-ICUs and in respiratory tract isolates than in intraabdominal or urinary tract isolates. In addition, 82.4% of DTR and 92.1% of MDR Enterobacterales and 62.2% of DTR and 82.2% of MDR P. aeruginosa were imipenem/relebactam-susceptible, and 1.5% of DTR and 65.8% of MDR Enterobacterales and 67.5% of DTR and 84.0% of MDR P. aeruginosa were ceftolozane/tazobactam-susceptible. Conclusions MDR phenotypes defined using the Magiorakos criteria may overcall treatment-limiting resistance in gram-negative bacilli. In the US, DTR Enterobacterales were infrequent, while MDR Enterobacterales isolates and DTR and MDR P. aeruginosa were common. Imipenem/relebactam (Enterobacterales, P. aeruginosa) and ceftolozane/tazobactam (P. aeruginosa) retained in vitro activity against most DTR and MDR isolates.

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 Activity of Delafloxacin When Tested Against Bacterial Surveillance Isolates Collected in the US and Europe During 2014–2016 as Part of a Global Surveillance Program

2017 ◽  
Vol 4 (suppl_1) ◽  
pp. S373-S374 ◽  
Author(s):  
Robert K Flamm ◽  
Dee Shortridge ◽  
Michael D Huband ◽  
Sandra McCurdy ◽  
Michael A Pfaller
Keyword(s):  
Susceptibility Testing ◽  
Multidrug Resistant ◽  
Surveillance Program ◽  
Coagulase Negative Staphylococci ◽  
Phase 3 ◽  
Highly Active ◽  
Medical Centers ◽  
The Us ◽  
Us Fda ◽  
Research Grant

Abstract Background Delafloxacin (DLX) is an investigational anionic fluoroquinolone with an NDA that is under US FDA review to treat acute bacterial skin and skin structure infections and is undergoing Phase 3 studies to treat community-acquired bacterial pneumonia. Methods A total of 36,683 Gram-positive (GP) and -negative (GN) bacteria isolated during 2014–2016 were selected from medical centers in the US and Europe. Susceptibility testing (S) was performed by frozen-form broth microdilution methods for DLX and comparators. Results DLX was very active against Staphylococcus aureus (SA, n = 9,355; MIC50/90, 0.008/0.5 mg/L) while the levofloxacin (LEV) MIC50/90 was 0.25/>4 mg/L (67.9%S). The MIC50/90 for methicillin-resistant SA (MRSA) was 0.12/1 mg/L. For MRSA, all isolates were S to vancomycin and daptomycin (DAP), linezolid and tigecycline (TGC) S was ≥99.9%. Decreased rates of S were noted for LEV (29.8%), clindamycin (72.9%), and erythromycin (17.3/17.8%; CLSI/EUCAST). Minocycline (MIC50/90, 0.12/0.25 mg/L), ceftaroline (MIC50/90, 0.25/0.5 mg/L), DAP (MIC50/90, 0.5/0.5 mg/L), and DLX (MIC50/90, 0.015/0.5 mg/L) were the most active agents tested against coagulase-negative staphylococci. Against Streptococcus pneumoniae (SPN), the MIC50/90 for DLX (0.015/0.03 mg/L) and TGC (0.03/0.06 mg/L) were the lowest among the agents tested. The DLX MIC50/90 values did not vary among the penicillin-S, -intermediate, and -R subgroups of SPN. The MIC50/90 values for DLX against S. pyogenes and S. agalactiae were 0.015/0.03 mg/L. DLX was highly active against Haemophilus influenzae. The DLX MIC50/90 (≤0.001/0.004 mg/L) was the same for β-lactamase positive and negative H. influenzae. Against Enterobacteriaceae, 76.0% of DLX MIC values were ≤1 mg/L. Susceptibility to LEV was 80.8%, and S to ceftriaxone, ceftazidime (CAZ), and cefepime ranged from 78.5–86.3%. A total of 72.6% of Pseudomonas aeruginosa isolates exhibited DLX MIC values ≤1 mg/L, while LEV S was 73.2% and CAZ was 81.6%. The MIC50/90 for both DLX and LEV were 0.5/>4 mg/L, respectively. Conclusion DLX was active against a broad range of GP and GN bacteria, including MRSA and multidrug-resistant SPN. DLX merits further study as therapy in infections in which these organisms may occur. Disclosures R. K. Flamm, Melinta Therapeutics: Research Contractor, Research grant D. Shortridge, Melinta Therapeutics: Research Contractor, Research grant M. D. Huband, Melinta Therapeutics: Research Contractor, Research grant S. McCurdy, Melinta Therapeutics: Employee, Salary M. A. Pfaller, Melinta Therapeutics: Research Contractor, Research grant

scholarly journals Cefepime-Zidebactam (WCK 5222) Activity Tested against Gram-negative Organisms Causing Bloodstream Infections Worldwide

2017 ◽  
Vol 4 (suppl_1) ◽  
pp. S374-S375 ◽  
Author(s):  
Helio S Sader ◽  
Mariana Castanheira ◽  
Jennifer M Streit ◽  
Leonard R Duncan ◽  
Robert K Flamm
Keyword(s):  
Bloodstream Infections ◽  
Multidrug Resistant ◽  
Vitro Activity ◽  
Asia Pacific ◽  
In Vitro Activity ◽  
Gram Negative ◽  
Microdilution Method ◽  
Broth Microdilution Method ◽  
Research Grant

Abstract Background Zidebactam (ZID), a bicyclo-acyl hydrazide, is a β-lactam enhancer with a dual mechanism of action involving selective and high binding affinity to Gram-negative (GN) PBP2 and β-lactamase inhibition. We evaluated the in vitro activity of cefepime (FEP) combined with ZID against GN organisms causing bloodstream infections (BSI) in hospitals worldwide. Methods A total of 2,094 isolates from 105 medical centers were evaluated. Isolates were collected from Europe (1,050), USA (331), Latin America (LA; 200) and the Asia-Pacific region (AP; 393) in 2015, and China (120) in 2013 by the SENTRY Program. Susceptibility (S) testing was performed by reference broth microdilution method against FEP-ZID (1:1 ratio) and comparators. The collection included 1,809 Enterobacteriaceae (ENT), 170 P. aeruginosa (PSA) and 115 Acinetobacter spp. (ASP). Results FEP-ZID was very active against ENT (MIC50/90 of ≤0.03/0.12 μg/mL) with 99.9 and 100.0% of isolates inhibited at ≤4/4 and ≤8/8 μg/mL, respectively, and retained potent activity against carbapenem-resistant (CRE; n = 44; MIC50/90, 1/4 μg/mL), multidrug-resistant (MDR), and extensively drug-resistant (XDR) isolates (Table). Amikacin (AMK; MIC50/90, 2/4 μg/mL; 97.7% S) was also very active against ENT, and colistin (COL; MIC50/90, 0.12/>8 μg/mL) inhibited only 87.3% of isolates at ≤2 μg/mL. FEP-ZID was highly active against PSA, including isolates resistant to other antipseudomonal β-lactams, MDR (MIC50/90, 4/8 μg/mL) and XDR (MIC50/90, 4/8 μg/mL) isolates. Among the comparators, COL (MIC50/90 of ≤0.5/1 μg/mL; 100.0% S) and AMK (MIC50/90, 4/16 μg/mL; 91.2% S) were the most active agents against PSA. FEP-ZID (MIC50/90, 16/32 μg/mL) was 4-fold more active than FEP against ASP. Conclusion FEP-ZID (WCK 5222) exhibited potent in vitro activity against a large worldwide collection of GN isolates from BSI, including MDR and XDR isolates. These results support further clinical development of WCK 5222 for treating BSI. Disclosures H. S. Sader, Wockhardt Bio Ag: Research Contractor, Research grant; M. Castanheira, Wockhardt Bio Ag: Research Contractor, Research grant; J. M. Streit, Wockhardt Bio Ag: Research Contractor, Research grant; L. R. Duncan, Wockhardt Bio Ag: Research Contractor, Research grant; R. K. Flamm, Wock: Research Contractor, Research 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 Antimicrobial Activity and Spectrum of PPI-0903M (T-91825), a Novel Cephalosporin, Tested against a Worldwide Collection of Clinical Strains

2005 ◽  
Vol 49 (8) ◽  
pp. 3501-3512 ◽  
Author(s):  
Helio S. Sader ◽  
Thomas R. Fritsche ◽  
Koné Kaniga ◽  
Yigong Ge ◽  
Ronald N. Jones
Keyword(s):  
Antimicrobial Activity ◽  
Multidrug Resistant ◽  
Vitro Activity ◽  
In Vitro Activity ◽  
Gram Positive ◽  
Gram Negative ◽  
Similar Activity ◽  
Gram Positive Bacteria ◽  
Medical Centers

ABSTRACT PPI-0903M is a novel N-phosphono-type cephalosporin active against oxacillin-resistant staphylococci and many other gram-positive organisms. This study evaluated the in vitro activity and spectrum of PPI-0903M against 1,478 recent clinical isolates collected from 80 medical centers (22 countries). PPI-0903M demonstrated broader in vitro activity against gram-positive bacteria, particularly against multidrug-resistant staphylococci and streptococci of current clinical concern, than currently available extended-spectrum cephalosporins while maintaining similar activity against gram-negative pathogens.

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