Oritavancin Research Articles

734. Trend Analysis of Oritavancin and Comparator Agents Activity against Enterococcus Causing Infections in US Medical Centers between 2017–2019 and 2022

Abstract Background A new formulation of oritavancin (ORI) to be infused over 1 hour for the treatment of skin and skin structure infections was approved in 2021 by the US FDA. The activity of ORI and its comparators against Enterococcus (ENT) and resistant (R) subsets from US medical centers was evaluated comparatively between 2022 and 2017–2019. Methods 4,462 ENT, including 246/2,556 E. faecalis (EF) from 2022 and 2017–2019, respectively, 148/1,348 E. faecium (EFM), and 14/150 other ENT were collected (1/patient) from 34 US medical centers. Isolates were identified by MALDI-TOF MS and standard microbiology tests and susceptibility (S) tested by CLSI broth microdilution. CLSI clinical breakpoints (BPs) and VanA/VanB phenotypes were used. ORI BPs against vancomycin (VAN)-S EF were applied to all ENT. Results ORI activity against ENT from 2022 (MIC50/90, 0.015/0.03 mg/L) was similar to 2017–2019 (MIC50/90, 0.015/0.06 mg/L; Table). ORI inhibited 97.5%/98.9% of ENT from 2022/2017–2019 at ≤ 0.12 mg/L. VAN and linezolid (LZD) inhibited 97.2%/98.4% and 99.6%/99.6% of ENT from 2022/2017–2019, at the respective BPs. ORI, VAN, LZD and daptomycin (DAP) showed stable S rates ( > 96%) against EF. ORI remained active against 57.1/53.1% of VAN-R EF. VanA rates in VAN-R EF from 2022 and 2017–2019 were 85.7%/93.8%. ORI inhibited the 3 VanB EF isolates at ≤ 0.03 mg/L. LZD and DAP remained active against VAN-R EF (100%). Similar activity was noted for ORI against EFM from 2022 (MIC50/90, 0.008/0.06 mg/L) and 2017–2019 (MIC50/90, 0.008/0.03 mg/L). The EFM S rate to VAN was 35.1% in 2017–2019 and 39.2% in 2022. The S rates to ORI (VAN-S EF BPs) and LZD remained stable ( > 98%) as well as rates of DAP susceptible dose-dependent (SDD; 96.6% in 2022 and 99.5% in 2017–2019). The VanB phenotype increased from 7.8% in 2017–2019 to 20.0% in 2022. ORI inhibited all VanB and 98.5% of VanA EFM at ≤ 0.12 mg/L. LZD inhibited 98.6%/99.4% of VanA EFM isolates in 2022/2017–2022. The DAP SDD rate slightly decreased against VanA EFM (99.7% to 93.1%). ORI and comparators were active against other ENT. Conclusion ORI exhibited potent and stable activity against ENT clinical isolates, including VAN-R EFM in US. An increase in VanB EFM phenotype and a slight decrease in the DAP SDD rates in VAN-R EFM subsets were noted over time. Disclosures Cecilia G. Carvalhaes, MD, PhD, AbbVie: Grant/Research Support|bioMerieux: Grant/Research Support|Cipla: Grant/Research Support|CorMedix: Grant/Research Support|Melinta: Grant/Research Support|Pfizer: Grant/Research Support Rodrigo E. Mendes, PhD, AbbVie: Grant/Research Support|Basilea: Grant/Research Support|Cipla: Grant/Research Support|Entasis: Grant/Research Support|GSK: Grant/Research Support|Paratek: Grant/Research Support|Pfizer: Grant/Research Support|Shionogi: Grant/Research Support Dee Shortridge, PhD, Melinta: Grant/Research Support|Shionogi: Grant/Research Support Mariana Castanheira, PhD, AbbVie: Grant/Research Support|Basilea: Grant/Research Support|bioMerieux: Grant/Research Support|Cipla: Grant/Research Support|CorMedix: Grant/Research Support|Entasis: Grant/Research Support|Melinta: Grant/Research Support|Paratek: Grant/Research Support|Pfizer: Grant/Research Support|Shionogi: Grant/Research Support

The Clinical Efficacy of Multidose Oritavancin: A Systematic Review.

Oritavancin (ORI) is a semisynthetic lipoglycopeptide approved as a single 1200 mg dose intravenous infusion for the treatment of acute bacterial skin and skin structure infections (ABSSSIs) caused by Gram-positive organisms in adults. The pharmacokinetic/pharmacodynamic (PK/PD) linear kinetic profile and long terminal half-life (~393 h) of ORI make it therapeutically attractive for the treatment of other Gram-positive infections for which prolonged therapy is needed. Multidose regimens are adopted in real-world clinical practice with promising results, but aggregated efficacy data are still lacking. A comprehensive search on PubMed/Medline, Scopus, Cochrane and Google Scholar databases was performed to include papers published up to the end of January 2023. All articles on ORI multiple doses usage, including case reports, with quantitative data and relevant clinical information were included. Two reviewers independently assessed papers against the inclusion/exclusion criteria and for methodological quality. Differences in opinion were adjudicated by a third party. From 1751 potentially relevant papers identified by this search, a total of 16 studies met the inclusion criteria and were processed further in the final data analysis. We extracted data concerning clinical response, bacteriologic response, mortality and adverse events (AEs). From the 16 included papers, 301 cases of treatment with multidose ORIs were identified. Multidose regimens comprised an initial ORI dose of 1200 mg followed by 1200 mg or 800 mg subsequent doses with a varying total number and frequency of reinfusions. The most often treated infections and isolates were osteomyelitis (148; 54.4%), ABSSSI (35; 12.9%) and cellulitis (14; 5.1%); and MRSA (121), MSSA (66), CoNS (17), E. faecalis (13) and E. faecium (12), respectively. Clinical cure and improvement by multidose ORI regimens were observed in 85% (231/272) and 8% (22/272) patients, respectively. Multidose ORI was safe and well tolerated; the most frequent AEs were infusion-related reactions and hypoglycemia. A multidose ORI regimen may be beneficial in treating other Gram-positive infections besides ABSSSIs, with a good safety profile. Further studies are warranted to ascertain the superiority of one multidose ORI scheme or posology over the other.

Oritavancin vs Standard of Care for Treatment of Nonendovascular Gram-Positive Bloodstream Infections.

Data is limited comparing oritavancin (ORT) to the standard-of-care (SOC) for the treatment gram-positive blood stream infections (BSI). This was a retrospective study of all patients in the Veteran's Affairs Health Care System treated with at least 1 dose of oritavancin or at least 5 days of vancomycin, daptomycin, ceftaroline, ampicillin, ampicillin-sulbactam, nafcillin, oxacillin, or cefazolin for a documented gram-positive BSI from 1 January 2015 to 30 June 2021. Patients with polymicrobial blood cultures or positive cultures from other sites were included if the organisms were sensitive to the incident antimicrobial; no concomitant antimicrobials could be used once the incident agent was started. Individuals were also excluded if they were diagnosed with endocarditis, had a neutrophil count 96-hours of treatment before the incident antimicrobial was started.The primary composite outcome was clinical failure, defined as all-cause mortality within 30-days from the end of therapy, or blood cultures positive for the incident organisms ≥72 hours after administration of the first dose and ≤30 days after the administration of the final dose of the study antimicrobial, or any drug or line-related readmissions within 30-days of hospital discharge. Two hundred-forty patients were identified for screening with 96 meeting criteria (27 in ORT and 69 in SOC groups). Baseline characteristics were generally balanced between groups except more patients in the ORT group received >96-hours of treatment before the incident antimicrobial was started (70.3% (19/27) vs 13.04% 9/69); P < .001). The pathogen most prevalent was methicillin susceptible Staphylococcus aureus (MSSA) (ORT 33.3% (9/27) vs SOC 46.4% (32/69)). Clinical failure occurred in 7.4% (2/27) in the ORT group and 17.4% (12/69) in SOC (P = .34). No components of the primary outcome were significantly different between groups, but AKI did occur more commonly in the SOC group (27.5% (19/69) vs 3.7% (1/27); P = .01). ORT appears to be a safe and effective option when directly compared to the SOC for non-endocarditis BSIs.

646. Activity of Oritavancin and Comparator Agents Against Coagulase-negative Staphylococci Causing Bloodstream Infections in US Medical Centers (2017-2019)

Abstract Background Coagulase-negative staphylococci (CoNS) is a common organism group implicated in catheter-related bloodstream infection (BSI) and infective endocarditis. Prompt appropriate antimicrobial therapy is crucial for suspected or confirmed invasive infections. The in vitro activity of oritavancin (ORI) and comparators was evaluated against CoNS causing BSI in US medical centers. Methods 587 CoNS isolates (1/patient) were consecutively collected in 30 US centers in 2017-2019. Bacterial identification was performed by MALDI-TOF, and susceptibility testing using CLSI broth microdilution methodology in a central laboratory. CLSI breakpoints were applied for comparators and the ORI susceptible (S) breakpoint for S. aureus (≤0.12 mg/L) was used for in vitro comparison only. Results The most common species were S. epidermidis (Sepi; 62.4%; 366), followed by S. hominis (Shom; 13.1%; 77), S. capitis (Scap; 7.3%; 43), S. lugdunensis (Slug; 5.1%; 30), and S. haemolyticus (Shae; 4.3%; 25). 12 other species represented &amp;lt; 10 (1.5%) isolates each. Overall, 59.1% of isolates were methicillin-resistant (MR), with the highest rate in Sepi (73.2%), followed by Shae (68.0%), Shom (46.8%), and Scap (30.2%). No MR isolates were detected in Slug. ORI (MIC50/90, 0.06/0.12 mg/L) inhibited 96.1% of CoNS at ≤0.12 mg/L. Linezolid (LZD; MIC50/90, 1/1 mg/L; 96.4%S), daptomycin (DAP; MIC50/90, 0.25/0.5 mg/L; 100%S), and vancomycin (VAN; MIC50/90, 1/2 mg/L; 100%S) were also active against CoNS. ORI displayed similar MIC50 (0.03-0.06 mg/L) and MIC90 (0.12-0.25 mg/L) values against Sepi, Shom, Scap, and Shae, and inhibited 96.0%, 96.1%, 97.7%, and 84.0% of these isolates at ≤0.12 mg/L, respectively. All Slug isolates were inhibited by ORI at ≤0.015 mg/L. ORI inhibited 94.8% of all MRCoNS at ≤0.12 mg/L, and 95.5%, 94.4%, 92.3%, and 82.4% of MR Sepi, Shom, Scap, and Shae species, respectively. VAN, DAP, and LZD inhibited 100.0%, 100.0%, and 93.9% of MRCoNS isolates at their susceptible breakpoints, respectively. Conclusion ORI was highly active and inhibited ≥96% of all CoNS and individual species ( &amp;gt;10 isolates) at ≤0.12 mg/L, regardless of methicillin profile, except for Shae. VAN, DAP, and LZD were also active against CoNS causing BSI in US medical centres. Disclosures Cecilia G. Carvalhaes, MD, PhD, AbbVie: Grant/Research Support|Cidara: Grant/Research Support|Melinta: Grant/Research Support|Pfizer: Grant/Research Support Helio S. Sader, MD, PhD, AbbVie: Grant/Research Support|Cidara: Grant/Research Support|Melinta: Grant/Research Support|Nabriva Therapeutics: Grant/Research Support|Pfizer: Grant/Research Support Jennifer M. Streit, BS, MT(ASCP), Cidara: Grant/Research Support|GSK: Grant/Research Support|Melinta: Grant/Research Support|Shionogi: Grant/Research Support Rodrigo E. Mendes, PhD, AbbVie: Grant/Research Support|Cidara: Grant/Research Support|GSK: Grant/Research Support|Melinta: Grant/Research Support|Nabriva Therapeutics: Grant/Research Support|Office for Assistant Secretary of Defense for Health Affairs: Grant/Research Support|Pfizer: Grant/Research Support|Shionogi: Grant/Research Support|Spero Therapeutics: Grant/Research Support.

430. Oritavancin Activity Against Gram-positive Pathogens Causing Bloodstream Infections in Hematology/Oncology and Transplant Units in US Medical Centers (2010-2019)

Abstract Background Patients undergoing hematologic, oncologic, and/or transplant treatment are at risk for infections. Appropriate antimicrobial management is crucial for patients with suspected or confirmed bloodstream infections (BSI). We evaluated the in vitro activity of oritavancin (ORI) and comparators against Gram-positive (GP) isolates causing BSI in patients from hematology/oncology and transplant units (HTU) in US medical centers. Methods 1,217 isolates (1/patient) were consecutively collected from HTU patients in 33 US hospitals during 2010-2019. Isolates were identified by MALDI-TOF and/or standard microbiological testing methods, and susceptibility (S) tested by CLSI reference broth microdilution in a central laboratory. CLSI breakpoints were applied. Results Enterococcus spp. (overall, 36.1%; E. faecium [EFM], 20.2%; E. faecalis [EF], 14.3%) and S. aureus (SA, 35.7%; 36.4% methicillin-resistant [MRSA]) were the most common organism groups, followed by coagulase-negative Staphylococcus (CoNS; 11.8%; 76.4% MR), Viridans group streptococci (VHS; 9.6%), and beta-haemolytic streptococci (BHS; 3.5%). ORI inhibited 96.7%/98.9% of EFM/EF at ≤0.12mg/L (S breakpoint for vancomycin [VAN]-S EF). Ampicillin (100.0%S), linezolid (LZD; 100.0%S), daptomycin (DAP; 98.3%S), and VAN (97.1%S) were also active against EF. Only ORI (96.7%S) and LZD (100.0%S) remained active against EFM. A VRE phenotype and elevated daptomycin MIC (2-4 mg/L) were noted in 72.8% and 55.3% of EFM, with ORI inhibiting 95.5% and 95.6% of these isolates at ≤0.12mg/L, respectively. ORI displayed equivalent MIC50/90 (0.03/0.06 mg/L) values against MSSA (99.3%S) and MRSA (99.4%S). ORI inhibited 95.5% of MRCoNS at ≤0.12mg/L (SA breakpoint). VAN, DAP, and LZD remained active against MRSA and MRCoNS. ORI was also active against BHS (MIC50/90, 0.03/0.25 mg/L; 95.2%S) and VGS (MIC50/90, 0.015/0.25 mg/L; 96.6%S) as was VAN (100.0%), DAP (100.0%), and LZD (100.0%/99.1%S, respectively). Conclusion VRE EFM, MRCoNS, and MRSA rates were generally high in BSI GP isolates recovered from patients in HTU. ORI was highly active and inhibited &amp;gt; 95% of isolates at MIC of ≤ 0.12mg/L from this unique collection, including R subsets such as VAN-R EFM, EFM displaying elevated DAP MIC (2-4 mg/L), MRSA, and MRCoNS. Disclosures Cecilia G. Carvalhaes, MD, PhD, AbbVie: Grant/Research Support|Cidara: Grant/Research Support|Melinta: Grant/Research Support|Pfizer: Grant/Research Support Dee Shortridge, PhD, AbbVie: Grant/Research Support|JMI Laboratory: Employee|Melinta: Grant/Research Support|Menarini: Grant/Research Support|Shionogi: Grant/Research Support Helio S. Sader, MD, PhD, AbbVie: Grant/Research Support|Cidara: Grant/Research Support|Melinta: Grant/Research Support|Nabriva Therapeutics: Grant/Research Support|Pfizer: Grant/Research Support Rodrigo E. Mendes, PhD, AbbVie: Grant/Research Support|Cidara: Grant/Research Support|GSK: Grant/Research Support|Melinta: Grant/Research Support|Nabriva Therapeutics: Grant/Research Support|Office for Assistant Secretary of Defense for Health Affairs: Grant/Research Support|Pfizer: Grant/Research Support|Shionogi: Grant/Research Support|Spero Therapeutics: Grant/Research Support.

1845. Oritavancin Compared to the Standard-of-Care for the Treatment of Gram-positive Blood Stream Infections

Abstract Background Data is limited comparing oritavancin (ORT) to the standard-of-care (SOC) for the treatment gram-positive blood stream infections (BSI). Methods This was a retrospective study of all patients in the Veteran’s Affairs Health Care System treated with at least 1 dose of oritavancin or at least 5 days of vancomycin, daptomycin, ceftaroline, ampicillin, ampicillin-sulbactam, nafcillin, oxacillin, or cefazolin for a documented gram-positive BSI from 1 January 2015 to 30 June 2021. Patients with polymicrobial blood cultures or positive cultures from other sites were included if the organisms were sensitive to the incident antimicrobial; no concomitant antimicrobials could be used once the incident agent was started. Individuals were also excluded if they were diagnosed with endocarditis, had a neutrophil count &amp;lt; 500 cells/mm3, or had a diagnosis of Human Immunodeficiency Virus (HIV) on their problem list. The primary composite outcome was clinical failure, defined as all-cause mortality within 30-days from the end of therapy, or blood cultures positive for the incident organisms ≥72 hours after administration of the first dose and ≤30 days after the administration of the final dose of the study antimicrobial, or any drug or line-related readmissions within 30-days of hospital discharge. Secondary outcomes included all-cause 30-day readmission and rates of acute kidney injury (AKI). Results Two hundred-forty patients were identified for screening with 96 meeting criteria (27 in ORT and 69 in SOC groups). Baseline characteristics were generally balanced between groups except more patients in the ORT group received &amp;gt; 96-hours of treatment before the incident antimicrobial was started (70.3% (19/27) vs. 13.04% (9/69); p&amp;lt;0.001). The pathogen most prevalent was methicillin-susceptible Staphylococcus aureus (MSSA) (ORT 33.3% (9/27) vs. SOC 46.4% (32/69)). Clinical failure occurred in 7.4% (2/27) in the ORT group and 17.4% (12/69) in SOC (p=0.34). No components of the primary outcome were significantly different between groups, but AKI did occur more commonly in the SOC group (27.5% (19/69) vs. 3.7% (1/27); p=0.01). Conclusion ORT appears to be a safe and effective option when directly compared to the SOC for non-endocarditis BSIs. Disclosures Ryan P. Moenster, Pharm.D., FIDSA, Melinta Therapeutics: Grant/Research Support|Melinta Therapeutics: Honoraria.

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

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 &amp;gt;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)

1629. Vancomycin Resistance in Enterococcus faecium Clinical Isolates Responsible for Bloodstream Infections in US Hospitals Over Ten Years (2010-2019) and Activity of Oritavancin

Background Enterococcus faecium (EFM) causes difficult-to-treat infections due to its intrinsic resistance (R) and ability to acquire R to many antimicrobials. This study evaluated the vancomycin (VAN)-R rates over time and the activity of oritavancin (ORI) against a collection of EFM causing bloodstream infections (BSI).MethodsA total of 1,081 BSI EFM isolates collected from 36 US hospitals in a prevalence mode design during 2010-2019 were evaluated. Bacterial identification was confirmed by MALDI-TOF MS. Susceptibility testing was performed by reference broth microdilution. For comparison, the ORI breakpoint for VAN-susceptible E. faecalis was applied to EFM. Isolates were characterized as VanA or VanB phenotypes based on their susceptibility (S) to VAN and teicoplanin (TEC). The VanB phenotype was confirmed by PCR and/or whole genome sequencing.ResultsOverall, 72.3% (782/1,081) of EFM were VAN-R (Table). VanA was the most common phenotype (97.7%; 764/782). The yearly VAN-R rates decreased from 81.8% in 2010 to 58.7% in 2019. A total of 18 (2.3%) isolates exhibited a VanB phenotype (TEC MIC, 0.5-8 mg/L); however, the vanB gene only was confirmed in 9 EFM isolates (TEC MIC, 0.5-1 mg/L), which were all collected in 2010-2012. The remaining 9 (50.0%) VanB phenotype EFM isolates carried a vanA gene (TEC MIC, 4-8 mg/L). ORI was very active against VAN-susceptible EFM (MIC50/90, ≤ 0.008/≤0.008/mg/L), VanA (MIC50/90, 0.03/0.12 mg/L; MIC100, 0.5 mg/L), and VanB (MIC50/90, ≤ 0.008/0.015 mg/L; MIC100, 0.03 mg/L) subsets. Only linezolid (LZD) and ORI (MIC, ≤ 0.12 mg/L) showed > 95.0%S against EFM and VAN-R subsets. Daptomycin (DAP)-R rarely was observed (0.8%), but it was more frequently found in the last 5 years. However, 49.9% of EFM isolates showed elevated DAP MICs (2 and 4 mg/L). ORI inhibited 77.8%, and 100.0% of DAP-R and LZD-nonsusceptible EFM isolates at ≤ 0.12 mg/L, respectively.ConclusionVAN-R rates among EFM causing BSI in the US decreased during 2010-2019. VanA remains the most common phenotype, whereas vanB-carrying isolates became rarer in later years. Interestingly, half of VanB-phenotype isolates carried a vanA gene. ORI was very active against EFM causing BSI, including isolates R to VAN, DAP, and/or nonsusceptible to LZD.Table 1 DisclosuresCecilia 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)

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

BackgroundBone 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.MethodsA 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).ResultsMethicillin 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; >99.0%S) and levofloxacin (> 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.ConclusionMRSA 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 DisclosuresCecilia 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)

New Antibiotics for the Treatment of Acute Bacterial Skin and Soft Tissue Infections in Pediatrics

Acute bacterial skin and soft tissue infections (aSSTIs) are a large group of diseases that can involve exclusively the skin or also the underlying subcutaneous tissues, fascia, or muscles. Despite differences in the localization and severity, all these diseases are due mainly to Gram-positive bacteria, especially Staphylococcus aureus and Streptococcus pyogenes. aSSTI incidence increased considerably in the early years of this century due to the emergence and diffusion of community-acquired methicillin-resistant S. aureus (CA-MRSA). Despite the availability of antibiotics effective against CA-MRSA, problems of resistance to these drugs and risks of significant adverse events have emerged. In this paper, the present knowledge on the potential role new antibiotics for the treatment of pediatric aSSTIs is discussed. The most recent molecules that have been licensed for the treatment of aSSTIs include ozenoxacin (OZ), ceftaroline fosamil (CF), dalbavancin (DA), oritavancin (OR), tedizolid (TD), delafloxacin (DL), and omadacycline (OM). However, only OZ and CF have been licensed for use in children with aSSTIs, although the superiority of these antibiotics to those routinely used for the treatment of aSSTIs should be further demonstrated. Waiting for additional studies, OZ and CF should be prescribed for aSSTI treatment in the presence of the potential failure of old molecules.

Comparisons of 30-Day Admission and 30-Day Total Healthcare Costs Between Patients Who Were Treated With Oritavancin or Vancomycin for a Skin Infection in the Outpatient Setting.

ObjectiveHospital admission is a key cost driver among patients with skin and soft tissue infections (SSTI). Data suggest that many SSTI patients are hospitalized unnecessarily and can be managed effectively and safely in an outpatient setting at a substantially lower cost. Oritavancin (ORI) is a single-dose treatment that has the potential to shift care from the inpatient to the outpatient setting. This study sought to compare the 30-day hospital admission rates and mean healthcare costs among SSTI patients who received outpatient ORI or vancomycin (VAN).MethodOver a 1-year period, outpatient prescription claims for VAN and ORI among patients with SSTIs and no hospitalization in past 3 days were for VAN and ORI were analyzed using a retrospective cohort analysis of the Truven Health MarketScan Databases.ResultsDuring the study period, 120 and 6695 patients who received ORI and VAN, respectively, met inclusion criteria. Groups were well matched at baseline. After covariate adjustment, patients who received ORI had a significantly lower 30- day admission rate versus patients who received VAN (6.1% vs 16.2%, respectively; P = .003). Mean healthcare costs 30-day post index were comparable between ORI and VAN patients ($12 695 vs $12 717, respectively; P = 1.0).ConclusionsResults suggest that ORI provides a single-dose alternative to multidose VAN for treatment of SSTI in the outpatient setting and may result in lower 30-day hospital admission rates.

1928. Comparisons of 30-Day Admission and 30-Day Total Healthcare Costs Between Patients Who Were Treated With Oritavancin (ORI) or Vancomycin (VAN) for a Skin Infection in the Outpatient Setting

BackgroundHospital admission is a key cost driver in ABSSSI patients. Data suggest many ABSSSI patients are unnecessarily hospitalized and can be effectively and safely managed as outpatient (OP) at substantially lower cost. ORI a single-dose treatment has the potential to shift care from the inpatient (IP) to the OP setting in selected patients. In phase III trials, a single dose of ORI had comparable efficacy and safety to twice daily VAN for 7–10 days in ABSSSI patients who were treated in OP. Real-world comparative data on outcomes in ABSSSI patients using ORI in OP are limited. This study sought to compare the 30 day hospital admission rates and mean (standard deviation (SD)) healthcare costs among ABSSSI patients who received ORI or VAN as an OP.MethodsRetrospective cohort analysis of ORI and VAN patients in the Truven Health MarketScan® Databases in 2016. Inclusion criteria: age ≥18 years; OP claim for ORI or VAN (index day (d)); a diagnosis of skin infection ≤7 d prior and 3 d after the index day; no IP discharge in 3 d prior to index day; ≥180 d of continuous enrollment prior to index day; ≥60 d of continuous enrollment post index day. Outcomes: 30 d hospital admissions and 30 d total healthcare costs.ResultsIn 2016, 120 and 6,695 patients who received ORI and VAN, respectively, met inclusion criteria. Groups were well balanced at baseline (table). ORI patients had a significantly lower 30 d admission rate vs. VAN patients (5.8% vs. 16.2%, respectively, P = 0.002). Mean (SD) cost 30 d post index were comparable between ORI and VAN patients ($10,096 (8,865) vs. 12,779 (28,773), respectively, P = 0.3).ConclusionResults suggest ORI provides a single-dose alternative to multi-dose VAN for treatment of ABSSSI in OP and may result in lower 30 d hospital admission rates.ORIVANBaseline characteristicsMean (SD) age, years54.9 (16.8)52.8 (16.5)Mean (SD) Deyo Charlson comorbidity index1.3 (1.8)1.5 (2.2)Skin infection Cellulitis/abscess90.0%86.6% Wound infection10.0%14.4% Other skin infections17.5%14.0%Life-threatening condition13.3%12.%Non-life-threatening systemic symptoms14.2%19.1%Hospitalization during baseline43.3%36.1%Prior mean (SD) total healthcare costs$47,354 ($33,567)$35,183 ($74,109)Disclosures T. Lodise, Melinta Therapeutics, Inc.: Consultant, Consulting fee. E. Packnett, Melinta Therapeutics, Inc.: Research Contractor, Research grant. S. Armstrong, The Medicine’s Company: Employee, Salary. M. Redell, Melinta Therapeutics, Inc.: Employee and Shareholder, Salary.

1331The SOLO Studies: A Single-Dose of Oritavancin (ORI) Compared to 7-10 Days of Vancomycin (VAN) in the Treatment of Acute Bacterial Skin and Skin Structure Infections (ABSSSI)

1331The SOLO Studies: A Single-Dose of Oritavancin (ORI) Compared to 7-10 Days of Vancomycin (VAN) in the Treatment of Acute Bacterial Skin and Skin Structure Infections (ABSSSI)

FDA Approves Oritavancin for Skin Infections

On August 6, 2014, the FDA announced approval of oritavancin (Orbactiv), a glycopeptide antibiotic for treatment of acute bacterial skin and