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| ID | Type | Description | Link |
|---|---|---|---|
| 5UM1AI104681-12 | U.S. NIH Grant/Contract | View source |
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This is a Phase 2b clinical study, multicenter, randomized, open-label, assessor-blinded, superiority study. The study will compare dalbavancin to standard of care antibiotic therapy for the completion of therapy in patients with complicated bacteremia or right-sided native valve Infective Endocarditis (IE) caused by S. aureus who have cleared their baseline bacteremia. Approximately 200 subjects will be randomized 1:1 to receive either dalbavancin or a standard of care antibiotic regimen that is based upon the identification and antibiotic susceptibility pattern of the baseline organism. Subjects randomized to the dalbavancin treatment group will receive 2 doses of dalbavancin intravenously (IV) 1 week apart (1500 mg on Day 1 and Day 8 after randomization, with renal dose adjustment if appropriate). Subjects randomized to the standard of care antibiotic therapy treatment group will receive an antibiotic regimen considered to be standard of care based on the methicillin susceptibility pattern of the pathogen isolated at baseline for a duration of 4 to 6 weeks and up to 8 weeks for patients with vertebral osteomyelitis/discitis. The primary objective is to compare the Desirability of Outcome Ranking (DOOR) at Day 70 of dalbavancin to that of standard of care antibiotic therapy used to consolidate therapy for the treatment of subjects with complicated S. aureus bacteremia in the intent-to-treat population (ITT).
This is a Phase 2b clinical study, multicenter, randomized, open-label, assessor-blinded, superiority study. The study will compare dalbavancin to standard of care antibiotic therapy for the completion of therapy in patients with complicated bacteremia or right-sided native valve Infective Endocarditis (IE) caused by S. aureus who have cleared their baseline bacteremia. Approximately 200 subjects will be randomized 1:1 to receive either dalbavancin or a standard of care antibiotic regimen that is based upon the identification and antibiotic susceptibility pattern of the baseline organism. Subjects randomized to the dalbavancin treatment group will receive 2 doses of dalbavancin intravenously (IV) 1 week apart (1500 mg on Day 1 and Day 8 after randomization, with renal dose adjustment if appropriate). Subjects randomized to the standard of care antibiotic therapy treatment group will receive an antibiotic regimen considered to be standard of care based on the methicillin susceptibility pattern of the pathogen isolated at baseline for a duration of 4 to 6 weeks and up to 8 weeks for patients with vertebral osteomyelitis/discitis. The primary objective is to compare the Desirability of Outcome Ranking (DOOR) at Day 70 of dalbavancin to that of standard of care antibiotic therapy used to consolidate therapy for the treatment of subjects with complicated S. aureus bacteremia in the intent-to-treat population (ITT). The secondary objectives are 1) to compare the clinical outcomes of dalbavancin with the standard of care antibiotic therapy at day 70 in the modified intent-to-treat population (mITT). 2) to compare the safety of dalbavancin with that of the standard of care treatment in the modified intent-to-treat population (mITT). 3) to compare each individual component of the Desirability of Outcome Ranking (DOOR) outcome by treatment arm, in the intent-to-treat population.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Arm 1 (Dalbavancin) | Experimental | Dalbavancin 1500 mg will be administrated intravenously (IV) over 30 (-/+10) minutes on Day 1 and 1500 mg IV over 30 (-/+10) minutes on Day 8, renally dose-adjusted to 1125 mg for subjects with Creatinine Clearance (CrCl) <30 and not on dialysis. N=100 |
|
| Arm 2 (Standard of Care) | Active Comparator | For Methicillin-sensitive Staphylococcus aureus (MSSA): nafcillin (2 g will be administrated intravenously (IV) every 4 hours for 4-6 weeks) OR oxacillin (2 g will be administrated intravenously (IV) every 4 hours for 4-6 weeks OR cefazolin (2 g will be administrated intravenously (IV) every 8 hours for 4-6 weeks) For Methicillin-resistant Staphylococcus aureus (MRSA): vancomycin (dose per local standard of care × 4-6 weeks) OR daptomycin (6-10 mg/kg will be administrated intravenously (IV) daily for 4-6 weeks). N=100 |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Cefazolin | Drug | Cefazolin is a semisynthetic cephalosporin analog with broad-spectrum antibiotic action due to inhibition of bacterial cell wall synthesis. Cefazolin (2 g will be administrated intravenously (IV) every 8 hours for 4-6 weeks) |
| Measure | Description | Time Frame |
|---|---|---|
| Desirability of Outcome Ranking (DOOR) | DOOR is a composite endpoint assessed by: (1) Clinical Failure: Lack of resolution of clinical signs and symptoms of S. aureus bacteremia such that no additional antibiotic therapy is required or anticipated for its treatment; (2) Infectious Complications such as: Endocarditis, New evidence of metastatic foci of infection, relapse - isolation of baseline S. aureus pathogen from a blood culture drawn after randomization, readmission for subsequent care of indication under study, need for additional unplanned source control procedures, or change in antibiotic therapy due to inadequate clinical response; (3) Serious Adverse Events (SAEs); (4) Adverse Events (AEs) Leading to Study Drug Discontinuation; and (5) Death. Clinical failure and infectious complications were assessed by a blinded adjudication committee. Participants missing clinical failure were treated as having clinical failure for calculation of DOOR. | Day 70 |
| Measure | Description | Time Frame |
|---|---|---|
| Frequency of Clinical Efficacy | Number of participants that had clinical efficacy at Day 70. Clinical efficacy is defined as none of: (1) Clinical Failure: Lack of resolution of clinical signs and symptoms of S. aureus bacteremia such that no additional antibiotic therapy is required or anticipated for its treatment; (2) Infectious Complications such as: Endocarditis, New evidence of metastatic foci of infection, relapse - isolation of baseline S. aureus pathogen from a blood culture drawn after randomization, readmission for subsequent care of indication under study, need for additional unplanned source control procedures, or change in antibiotic therapy due to inadequate clinical response; and (3) Death. Clinical failure and infectious complications are assessed by a blinded adjudication committee. Participants missing clinical failure are treated as not having clinical efficacy. |
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Inclusion Criteria:
Written informed consent obtained from the patient or legally authorized representative before the initiation of any study-specific procedures.
Patients > / = to 18 years old.
A diagnosis of complicated Staphylococcus aureus (either Methicillin-sensitive Staphylococcus aureus or Methicillin-resistant Staphylococcus aureus) bloodstream infection.
Treated with effective antibiotic therapy for at least 72 hours (maximum 10 days).*
*Ten consecutive days prior to randomization is the maximum allowed treatment duration. If a subject has received intermittent or incomplete therapy earlier in the treatment course for this episode of S. aureus bacteremia, then discuss with the protocol PI and DMID Medical Officer prior to enrollment.
Subsequent defervescence for at least 24 hours and clearance of bacteremia from the qualifying pathogen (at Screening), with negative blood culture incubated for at least 48 hours.**
**Two negative blood cultures incubated for 48 hours are preferred. However, if only a single blood culture set is drawn, no growth at 48 hours will be considered adequate to demonstrate clearance. If more than one culture set is drawn, all must show no growth at 48 hours to be considered evidence of clearance (e.g., 1 of 2 positive cultures would still be considered as ongoing bacteremia).
Provider willing to treat with either dalbavancin for two doses, or standard of care intravenous monotherapy for at least 4 and no more than 8 weeks from randomization.
Patients must be willing and able, if discharged, to return to the hospital or designated clinic for scheduled treatment, laboratory tests, or other procedures as required by the protocol.
According to the site Principal Investigator or sub-investigator assessment, patients must be expected to survive with appropriate antibiotic therapy and appropriate supportive care throughout the study.
Exclusion Criteria:
Uncomplicated bacteremia.*
*Uncomplicated Staphylococcus aureus bacteremia is defined as all of the following: exclusion of endocarditis by echocardiography; catheter-associated bacteremia and removal of catheter; no implanted prostheses; follow-up blood cultures drawn within 48 hours after initial set that do not grow screening pathogen and all follow-up blood cultures thereafter do not grow the screening pathogen; defervescence within 72 hours of initiating effective therapy; and no evidence of metastatic sites of infection.
Infectious Central Nervous System events, including septic emboli, ischemic or hemorrhagic stroke, epidural abscess, or meningitis (prior/unrelated Central Nervous System events are not exclusion criteria).
Known or suspected left-sided endocarditis or presence of a perivalvular abscess.
Planned right-sided valve replacement surgery in the first 3 days following randomization.
Presence of prosthetic heart valve, cardiac device** UNLESS removal is planned within 4 days post-randomization.
**Implantable cardioverter defibrillator (ICD), permanent pacemaker, valve support ring, ventricular assist device (VAD).
Presence of intravascular graft or intravascular material*** UNLESS removal is planned within 4 days post-randomization
***Excluding cardiac stents, inferior vena cava filters in place for >6 weeks, vascular stents in place for >6 weeks, non-hemodialysis grafts in place >90 days, and hemodialysis grafts not used within the past 12 months and not previously infected. A fistula constructed from native veins or a biologic vascular graft (without synthetic graft material) does not count as intravascular graft/material.
Infected prosthetic joint or extravascular hardware UNLESS removal is planned within 4 days post-randomization OR hardware was placed >60 days before bacteremia and clinically appears uninfected.
Polymicrobial bacteremia unless the non-Staphylococcus aureus organism is a contaminant.****
****Note: If a gram-negative bacteremia or fungemia develops after the qualifying S. aureus blood culture, AND the patient does not have right-sided endocarditis, AND the infection can be treated with an antibiotic without efficacy against the patient's S. aureus isolate (e.g. aztreonam), then the patient may remain eligible. Discussion with the DMID Medical Officer is strongly encouraged.
Significant hepatic insufficiency (Child-Pugh class C or aspartate transaminase (AST)/alanine aminotransferase (ALT) values >5x Upper Limit Normal at the time of randomization).
Immunosuppression*****
*****On chemotherapy or immunotherapy for active hematologic malignancy expected to cause > 7 days of absolute neutrophil count (ANC) < 100 cells/mm3, recent bone marrow transplant (in the past 90 days), solid organ transplantation within prior 3 months or receipt of augmented immunosuppression for rejection within 3 months, chronic granulomatous disease, human immunodeficiency virus (HIV) infection with a cluster of differentiation 4 (CD4) cell count < 50 cells/mm3 based on last known measurement or patient-reported value.
History of hypersensitivity reaction to dalbavancin or other drugs of the glycopeptide class of antibiotics.
Treatment with either dalbavancin or oritavancin in the 60 days prior to enrollment.
Infection with Staphylococcus aureus not susceptible to dalbavancin (dalbavancin mean inhibitory concentration Minimum Inhibitory Concentration (MIC) > 0.25 µg/mL) or vancomycin (vancomycin Minimum Inhibitory Concentration (MIC) > 2 µg/mL).
Planned treatment with concomitant systemic antibacterial therapy with potential efficacy against the patient's qualifying Staphylococcus aureus isolate, other than that allowed in the protocol.
Pregnant/ nursing females.
Females of childbearing potential must have a negative pregnancy test****** within 48h of randomization and use effective contraception for trial duration.
******If the serum pregnancy test results cannot be obtained before randomization, a urine pregnancy test may be used for enrollment.
Other medical or psychiatric condition that may, in the judgment of the investigator, increase the risk of study participation or interfere with interpretation of study results.
Unwilling or unable to follow study procedures.
Treatment with an investigational drug within 30 days preceding the first dose of study medication.
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Alabama Hospital - Infectious Diseases | Birmingham | Alabama | 35233 | United States | ||
| University of California Davis Medical Center - Internal Medicine - Infectious Disease |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 41999282 | Derived | Lodise TP, Turner NA, Hamasaki T, Fishbane N, Ghazaryan V, Wall A, Ge L, Wu Q, Zeng L, Riccobene T, Patel R, Zaharoff S, Rappo U, Evans S, Fowler VG Jr, Chambers HF, Holland TL; Antibacterial Resistance Leadership Group. Pharmacokinetics of Dalbavancin in Complicated Staphylococcus aureus Bacteremia: A Secondary Analysis of the DOTS Randomized Clinical Trial. JAMA Netw Open. 2026 Apr 1;9(4):e2611652. doi: 10.1001/jamanetworkopen.2026.11652. | |
| 40802264 | Derived |
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Participants were recruited from 23 clinical sites within the United States and Canada. The first participant was enrolled on April 22, 2021, and the last participant was enrolled on July 6, 2023.
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| ID | Title | Description |
|---|---|---|
| FG000 | Dalbavancin | Dalbavancin 1500 mg administrated intravenously (IV) over 30 (-/+10) minutes on Day 1 and 1500 mg IV over 30 (-/+10) minutes on Day 8, renally dose-adjusted to 1125 mg for participants with Creatinine Clearance (CrCl) <30 and not on dialysis. Dalbavancin: A second-generation lipoglycopeptide antibiotic synthesized from a fermentation product of Nonomuraea species |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Sep 29, 2023 | Jun 20, 2024 |
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| Dalbavancin | Drug | A second-generation lipoglycopeptide antibiotic synthesized from a fermentation product of Nonomuraea species |
|
| Daptomycin | Drug | Daptomycin (USA) or Cubicin (Spain) is a cyclic lipopeptide antibiotic that inhibits gram-positive bacteria. Daptomycin (6-10 mg/kg will be administrated intravenously (IV) daily for 4-6 weeks |
|
| Nafcillin | Drug | Nafcillin is a semi-synthetic antibiotic related to penicillin. Nafcillin (2 g will be administrated intravenously (IV) every 4 hours for 4-6 weeks) |
|
| Oxacillin | Drug | Oxacillin is an antibiotic used in resistant staphylococci infections. Oxacillin (2 g will be administrated intravenously (IV) every 4 hours for 4-6 weeks |
|
| Vancomycin | Drug | Vancomycin is a glycopeptide antibiotic product of the organism Amycolatopsis orientalis. Vancomycin (dose per local standard of care × 4-6 weeks) |
|
| Day 70 |
| Frequency of SAEs | Number of participants that experience any SAEs from Day 1 to study completion (Day 70 or Day 180 for participants in the osteomyelitis subset). An AE is considered serious if, in the view of either the site principal investigator or sponsor, it results in: death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, or a congenital anomaly/birth defect. | Day 1 through Day 180 |
| Frequency of AEs Leading to Study Drug Discontinuation | Number of participants that experience any AEs leading to study drug discontinuation from Day 1 to study completion (Day 70 or Day 180 for participants in the osteomyelitis subset). | Day 1 through Day 180 |
| Frequency of Clinical Failure (A Component of DOOR) | Number of participants who had clinical failure at Day 70, used for DOOR at Day 70. Clinical Failure is defined as lack of resolution of clinical signs and symptoms of S. aureus bacteremia such that no additional antibiotic therapy is required or anticipated for its treatment. Clinical failure is assessed by a blinded adjudication committee. Participants missing clinical failure are treated as having clinical failure. | Day 70 |
| Frequency of Infectious Complications (A Component of DOOR) | Number of participants that experience any infectious complications from Day 1 through Day 70, used for DOOR at Day 70. Infectious complications include endocarditis, new evidence of metastatic foci of infection, relapse - isolation of baseline S. aureus pathogen from a blood culture drawn after randomization, readmission for subsequent care of indication under study, need for additional unplanned source control procedures, or change in antibiotic therapy due to inadequate clinical response. Infectious complications are assessed by a blinded adjudication committee. | Day 1 through Day 70 |
| Frequency of SAEs (A Component of DOOR) | Number of participants that experience any SAEs from Day 1 to Day 70, used for DOOR at Day 70. An AE is considered serious if, in the view of either the site principal investigator or sponsor, it results in: death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, or a congenital anomaly/birth defect. | Day 1 through Day 70 |
| Frequency of AEs Leading to Study Drug Discontinuation (A Component of DOOR) | Number of participants that experience any AEs leading to study drug discontinuation from Day 1 to Day 70, used for DOOR at Day 70. | Day 1 through Day 70 |
| Frequency of All-Cause Mortality (A Component of DOOR) | Number of participants who passed away from Day 1 to Day 70, used for DOOR at Day 70. | Day 1 through Day 70 |
| Sacramento |
| California |
| 95817-1460 |
| United States |
| Harbor UCLA Medical Center - Medicine - Infectious Diseases | Torrance | California | 90502-2006 | United States |
| Torrance Memorial Medical Center | Torrance | California | 90505 | United States |
| University of Florida Health - Shands Hospital - Division of Infectious Diseases and Global Medicine | Gainesville | Florida | 32610 | United States |
| University of South Florida Health - Internal Medicine | Tampa | Florida | 22612 | United States |
| Rush University Medical Center | Chicago | Illinois | 60612 | United States |
| Ochsner Health - Ochsner Medical Center - Department of Infectious Diseases | New Orleans | Louisiana | 70121 | United States |
| Henry Ford Health System - Henry Ford Hospital | Detroit | Michigan | 48202-2608 | United States |
| Corewell Health - Infectious Disease | Royal Oak | Michigan | 48073-6757 | United States |
| University of Nebraska Medical Center - Infectious Diseases | Omaha | Nebraska | 68198-5400 | United States |
| South Jersey Infectious Disease | Somers Point | New Jersey | 08244 | United States |
| New York Presbyterian Hospital - Weill Cornell Medical Center - Infectious Diseases | New York | New York | 10065-4870 | United States |
| SUNY Upstate Medical University - Infectious Disease Division | Syracuse | New York | 13210 | United States |
| Atrium Health ID Consultants & Infusion Care Specialists | Charlotte | North Carolina | 28209 | United States |
| Duke University Hospital - Infectious Diseases | Durham | North Carolina | 27710 | United States |
| East Carolina University - Infectious Diseases and Tropical/Travel Medicine Clinic | Greenville | North Carolina | 27834-9997 | United States |
| Wake Forest Baptist Medical Center | Winston-Salem | North Carolina | 27157 | United States |
| Oregon Health and Science University - Adult Infectious Diseases Clinic | Portland | Oregon | 97239-3098 | United States |
| University of Pittsburgh - Medicine - Infectious Diseases | Pittsburgh | Pennsylvania | 15213 | United States |
| Prisma Health - Greenville Health System - Infectious Disease | Greenville | South Carolina | 29605 | United States |
| The University of Texas - MD Anderson Cancer Center - Infectious Diseases | Houston | Texas | 77030-4000 | United States |
| Carilion Roanoke Memorial Hospital | Roanoke | Virginia | 24014 | United States |
| McGill University Health Centre | Montreal | Canada |
| Turner NA, Hamasaki T, Doernberg SB, Lodise TP, King HA, Ghazaryan V, Cosgrove SE, Jenkins TC, Liu C, Sharma S, Zaharoff S, Wahid L, Renard VJ, Cook P, Raad I, Hachem R, Chaftari AM, Sims M, DeMarco C, Miller LG, McCarthy MW, Morse CG, Lucasti C, Forrest GN, Cherabuddi K, Polk C, Fazili T, Rupp ME, Thompson GR 3rd, Kim K, Strnad L, Schnee AE, McKinnell JA, Ramesh M, Silveira FP, McCarty TP, Lee TC, McDonald EG, Paolino K, Wiegand K, Wall A, Riccobene T, Patel R, Rappo U, Evans S, Chambers HF, Fowler VG Jr, Holland TL; Antibacterial Resistance Leadership Group. Dalbavancin for Treatment of Staphylococcus aureus Bacteremia: The DOTS Randomized Clinical Trial. JAMA. 2025 Aug 13:e2512543. doi: 10.1001/jama.2025.12543. Online ahead of print. |
| 35578360 | Derived | Turner NA, Zaharoff S, King H, Evans S, Hamasaki T, Lodise T, Ghazaryan V, Beresnev T, Riccobene T, Patel R, Doernberg SB, Rappo U, Fowler VG Jr, Holland TL; Antibacterial Resistance Leadership Group (ARLG). Dalbavancin as an option for treatment of S. aureus bacteremia (DOTS): study protocol for a phase 2b, multicenter, randomized, open-label clinical trial. Trials. 2022 May 16;23(1):407. doi: 10.1186/s13063-022-06370-1. |
| FG001 | Standard of Care | For Methicillin-sensitive Staphylococcus aureus (MSSA): nafcillin (2 g administrated intravenously (IV) every 4 hours for 4-6 weeks) OR oxacillin (2 g administrated IV every 4 hours for 4-6 weeks OR cefazolin (2 g administrated IV every 8 hours for 4-6 weeks). For Methicillin-resistant Staphylococcus aureus (MRSA): vancomycin (dose per local standard of care × 4-6 weeks) OR daptomycin (6-10 mg/kg administrated IV daily for 4-6 weeks). Cefazolin: Cefazolin is a semisynthetic cephalosporin analog with broad-spectrum antibiotic action due to inhibition of bacterial cell wall synthesis. Daptomycin: Daptomycin (USA) or Cubicin (Spain) is a cyclic lipopeptide antibiotic that inhibits gram-positive bacteria. Nafcillin: Nafcillin is a semi-synthetic antibiotic related to penicillin. Oxacillin: Oxacillin is an antibiotic used in resistant staphylococci infections. Vancomycin: Vancomycin is a glycopeptide antibiotic product of the organism Amycolatopsis orientalis. |
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| NOT COMPLETED |
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The intent-to-treat (ITT) population includes all randomized participants.
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| ID | Title | Description |
|---|---|---|
| BG000 | Dalbavancin | Dalbavancin 1500 mg administrated intravenously (IV) over 30 (-/+10) minutes on Day 1 and 1500 mg IV over 30 (-/+10) minutes on Day 8, renally dose-adjusted to 1125 mg for participants with Creatinine Clearance (CrCl) <30 and not on dialysis. Dalbavancin: A second-generation lipoglycopeptide antibiotic synthesized from a fermentation product of Nonomuraea species |
| BG001 | Standard of Care | For Methicillin-sensitive Staphylococcus aureus (MSSA): nafcillin (2 g administrated intravenously (IV) every 4 hours for 4-6 weeks) OR oxacillin (2 g administrated IV every 4 hours for 4-6 weeks OR cefazolin (2 g administrated IV every 8 hours for 4-6 weeks). For Methicillin-resistant Staphylococcus aureus (MRSA): vancomycin (dose per local standard of care × 4-6 weeks) OR daptomycin (6-10 mg/kg administrated IV daily for 4-6 weeks). Cefazolin: Cefazolin is a semisynthetic cephalosporin analog with broad-spectrum antibiotic action due to inhibition of bacterial cell wall synthesis. Daptomycin: Daptomycin (USA) or Cubicin (Spain) is a cyclic lipopeptide antibiotic that inhibits gram-positive bacteria. Nafcillin: Nafcillin is a semi-synthetic antibiotic related to penicillin. Oxacillin: Oxacillin is an antibiotic used in resistant staphylococci infections. Vancomycin: Vancomycin is a glycopeptide antibiotic product of the organism Amycolatopsis orientalis. |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
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| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
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| Baseline Pathogen | Count of Participants | Participants |
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| Body Mass Index (BMI) | Mean | Standard Deviation | kg/m^2 |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Primary | Desirability of Outcome Ranking (DOOR) | DOOR is a composite endpoint assessed by: (1) Clinical Failure: Lack of resolution of clinical signs and symptoms of S. aureus bacteremia such that no additional antibiotic therapy is required or anticipated for its treatment; (2) Infectious Complications such as: Endocarditis, New evidence of metastatic foci of infection, relapse - isolation of baseline S. aureus pathogen from a blood culture drawn after randomization, readmission for subsequent care of indication under study, need for additional unplanned source control procedures, or change in antibiotic therapy due to inadequate clinical response; (3) Serious Adverse Events (SAEs); (4) Adverse Events (AEs) Leading to Study Drug Discontinuation; and (5) Death. Clinical failure and infectious complications were assessed by a blinded adjudication committee. Participants missing clinical failure were treated as having clinical failure for calculation of DOOR. | The intent-to-treat (ITT) population includes all randomized participants. | Posted | Count of Participants | Participants | Day 70 |
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| Secondary | Frequency of Clinical Efficacy | Number of participants that had clinical efficacy at Day 70. Clinical efficacy is defined as none of: (1) Clinical Failure: Lack of resolution of clinical signs and symptoms of S. aureus bacteremia such that no additional antibiotic therapy is required or anticipated for its treatment; (2) Infectious Complications such as: Endocarditis, New evidence of metastatic foci of infection, relapse - isolation of baseline S. aureus pathogen from a blood culture drawn after randomization, readmission for subsequent care of indication under study, need for additional unplanned source control procedures, or change in antibiotic therapy due to inadequate clinical response; and (3) Death. Clinical failure and infectious complications are assessed by a blinded adjudication committee. Participants missing clinical failure are treated as not having clinical efficacy. | The modified intent-to-treat (mITT) population includes all randomized participants who received at least one dose of study drug. | Posted | Count of Participants | Participants | Day 70 |
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| Secondary | Frequency of SAEs | Number of participants that experience any SAEs from Day 1 to study completion (Day 70 or Day 180 for participants in the osteomyelitis subset). An AE is considered serious if, in the view of either the site principal investigator or sponsor, it results in: death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, or a congenital anomaly/birth defect. | The mITT population includes all randomized participants who received at least one dose of study drug. | Posted | Count of Participants | Participants | Day 1 through Day 180 |
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| Secondary | Frequency of AEs Leading to Study Drug Discontinuation | Number of participants that experience any AEs leading to study drug discontinuation from Day 1 to study completion (Day 70 or Day 180 for participants in the osteomyelitis subset). | The mITT population includes all randomized participants who received at least one dose of study drug. | Posted | Count of Participants | Participants | Day 1 through Day 180 |
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| Secondary | Frequency of Clinical Failure (A Component of DOOR) | Number of participants who had clinical failure at Day 70, used for DOOR at Day 70. Clinical Failure is defined as lack of resolution of clinical signs and symptoms of S. aureus bacteremia such that no additional antibiotic therapy is required or anticipated for its treatment. Clinical failure is assessed by a blinded adjudication committee. Participants missing clinical failure are treated as having clinical failure. | The ITT population includes all randomized participants. | Posted | Count of Participants | Participants | Day 70 |
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| Secondary | Frequency of Infectious Complications (A Component of DOOR) | Number of participants that experience any infectious complications from Day 1 through Day 70, used for DOOR at Day 70. Infectious complications include endocarditis, new evidence of metastatic foci of infection, relapse - isolation of baseline S. aureus pathogen from a blood culture drawn after randomization, readmission for subsequent care of indication under study, need for additional unplanned source control procedures, or change in antibiotic therapy due to inadequate clinical response. Infectious complications are assessed by a blinded adjudication committee. | The ITT population includes all randomized participants. | Posted | Count of Participants | Participants | Day 1 through Day 70 |
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| Secondary | Frequency of SAEs (A Component of DOOR) | Number of participants that experience any SAEs from Day 1 to Day 70, used for DOOR at Day 70. An AE is considered serious if, in the view of either the site principal investigator or sponsor, it results in: death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, or a congenital anomaly/birth defect. | The ITT population includes all randomized participants. | Posted | Count of Participants | Participants | Day 1 through Day 70 |
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| Secondary | Frequency of AEs Leading to Study Drug Discontinuation (A Component of DOOR) | Number of participants that experience any AEs leading to study drug discontinuation from Day 1 to Day 70, used for DOOR at Day 70. | The ITT population includes all randomized participants. | Posted | Count of Participants | Participants | Day 1 through Day 70 |
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| Secondary | Frequency of All-Cause Mortality (A Component of DOOR) | Number of participants who passed away from Day 1 to Day 70, used for DOOR at Day 70. | The ITT population includes all randomized participants. | Posted | Count of Participants | Participants | Day 1 through Day 70 |
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All unsolicited AEs grade 3 or higher, including laboratory abnormalities, as well as adverse events of special interest (AESIs) of any severity from time of first dose of study drug (i.e., dalbavancin or standard of care antibiotic) after randomization through follow-up (Day 70 or Day 180 for participants in osteomyelitis subset) were reported.
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Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Dalbavancin | Dalbavancin 1500 mg administrated intravenously (IV) over 30 (-/+10) minutes on Day 1 and 1500 mg IV over 30 (-/+10) minutes on Day 8, renally dose-adjusted to 1125 mg for participants with Creatinine Clearance (CrCl) <30 and not on dialysis. Dalbavancin: A second-generation lipoglycopeptide antibiotic synthesized from a fermentation product of Nonomuraea species | 5 | 100 | 43 | 100 | 5 | 100 |
| EG001 | Standard of Care | For Methicillin-sensitive Staphylococcus aureus (MSSA): nafcillin (2 g administrated intravenously (IV) every 4 hours for 4-6 weeks) OR oxacillin (2 g administrated IV every 4 hours for 4-6 weeks OR cefazolin (2 g administrated IV every 8 hours for 4-6 weeks). For Methicillin-resistant Staphylococcus aureus (MRSA): vancomycin (dose per local standard of care × 4-6 weeks) OR daptomycin (6-10 mg/kg administrated IV daily for 4-6 weeks). Cefazolin: Cefazolin is a semisynthetic cephalosporin analog with broad-spectrum antibiotic action due to inhibition of bacterial cell wall synthesis. Daptomycin: Daptomycin (USA) or Cubicin (Spain) is a cyclic lipopeptide antibiotic that inhibits gram-positive bacteria. Nafcillin: Nafcillin is a semi-synthetic antibiotic related to penicillin. Oxacillin: Oxacillin is an antibiotic used in resistant staphylococci infections. Vancomycin: Vancomycin is a glycopeptide antibiotic product of the organism Amycolatopsis orientalis. | 4 | 100 | 37 | 100 | 1 | 100 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Leukopenia | Blood and lymphatic system disorders | MedDRA V26.0 | Non-systematic Assessment |
| |
| Anaemia | Blood and lymphatic system disorders | MedDRA V26.0 | Non-systematic Assessment |
| |
| Cytopenia | Blood and lymphatic system disorders | MedDRA V26.0 | Non-systematic Assessment |
| |
| Febrile neutropenia | Blood and lymphatic system disorders | MedDRA V26.0 | Non-systematic Assessment |
| |
| Haemolytic anaemia | Blood and lymphatic system disorders | MedDRA V26.0 | Non-systematic Assessment |
| |
| Sickle cell anaemia with crisis | Blood and lymphatic system disorders | MedDRA V26.0 | Non-systematic Assessment |
| |
| Cardiac arrest | Cardiac disorders | MedDRA V26.0 | Non-systematic Assessment |
| |
| Acute myocardial infarction | Cardiac disorders | MedDRA V26.0 | Non-systematic Assessment |
| |
| Atrial fibrillation | Cardiac disorders | MedDRA V26.0 | Non-systematic Assessment |
| |
| Cardiac failure | Cardiac disorders | MedDRA V26.0 | Non-systematic Assessment |
| |
| Cardiac failure chronic | Cardiac disorders | MedDRA V26.0 | Non-systematic Assessment |
| |
| Cardiac failure congestive | Cardiac disorders | MedDRA V26.0 | Non-systematic Assessment |
| |
| Hypertensive heart disease | Cardiac disorders | MedDRA V26.0 | Non-systematic Assessment |
| |
| Pulseless electrical activity | Cardiac disorders | MedDRA V26.0 | Non-systematic Assessment |
| |
| Death | General disorders | MedDRA V26.0 | Non-systematic Assessment |
| |
| Chest pain | General disorders | MedDRA V26.0 | Non-systematic Assessment |
| |
| Complication associated with device | General disorders | MedDRA V26.0 | Non-systematic Assessment |
| |
| Drug withdrawal syndrome | General disorders | MedDRA V26.0 | Non-systematic Assessment |
| |
| Oedema peripheral | General disorders | MedDRA V26.0 | Non-systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA V26.0 | Non-systematic Assessment |
| |
| Sepsis | Infections and infestations | MedDRA V26.0 | Non-systematic Assessment |
| |
| Abscess | Infections and infestations | MedDRA V26.0 | Non-systematic Assessment |
| |
| Arthritis bacterial | Infections and infestations | MedDRA V26.0 | Non-systematic Assessment |
| |
| Bacteraemia | Infections and infestations | MedDRA V26.0 | Non-systematic Assessment |
| |
| Bacteriuria | Infections and infestations | MedDRA V26.0 | Non-systematic Assessment |
| |
| COVID-19 | Infections and infestations | MedDRA V26.0 | Non-systematic Assessment |
| |
| COVID-19 pneumonia | Infections and infestations | MedDRA V26.0 | Non-systematic Assessment |
| |
| Cellulitis | Infections and infestations | MedDRA V26.0 | Non-systematic Assessment |
| |
| Diabetic foot infection | Infections and infestations | MedDRA V26.0 | Non-systematic Assessment |
| |
| Extradural abscess | Infections and infestations | MedDRA V26.0 | Non-systematic Assessment |
| |
| Infection | Infections and infestations | MedDRA V26.0 | Non-systematic Assessment |
| |
| Intervertebral discitis | Infections and infestations | MedDRA V26.0 | Non-systematic Assessment |
| |
| Osteomyelitis | Infections and infestations | MedDRA V26.0 | Non-systematic Assessment |
| |
| Osteomyelitis acute | Infections and infestations | MedDRA V26.0 | Non-systematic Assessment |
| |
| Osteomyelitis chronic | Infections and infestations | MedDRA V26.0 | Non-systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA V26.0 | Non-systematic Assessment |
| |
| Pneumonia aspiration | Infections and infestations | MedDRA V26.0 | Non-systematic Assessment |
| |
| Pneumonia bacterial | Infections and infestations | MedDRA V26.0 | Non-systematic Assessment |
| |
| Prostate infection | Infections and infestations | MedDRA V26.0 | Non-systematic Assessment |
| |
| Proteus infection | Infections and infestations | MedDRA V26.0 | Non-systematic Assessment |
| |
| Pseudomonal sepsis | Infections and infestations | MedDRA V26.0 | Non-systematic Assessment |
| |
| Pyelonephritis | Infections and infestations | MedDRA V26.0 | Non-systematic Assessment |
| |
| Septic pulmonary embolism | Infections and infestations | MedDRA V26.0 | Non-systematic Assessment |
| |
| Septic shock | Infections and infestations | MedDRA V26.0 | Non-systematic Assessment |
| |
| Splenic abscess | Infections and infestations | MedDRA V26.0 | Non-systematic Assessment |
| |
| Staphylococcal bacteraemia | Infections and infestations | MedDRA V26.0 | Non-systematic Assessment |
| |
| Staphylococcal infection | Infections and infestations | MedDRA V26.0 | Non-systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA V26.0 | Non-systematic Assessment |
| |
| Vascular device infection | Infections and infestations | MedDRA V26.0 | Non-systematic Assessment |
| |
| Overdose | Injury, poisoning and procedural complications | MedDRA V26.0 | Non-systematic Assessment |
| |
| Ankle fracture | Injury, poisoning and procedural complications | MedDRA V26.0 | Non-systematic Assessment |
| |
| Fall | Injury, poisoning and procedural complications | MedDRA V26.0 | Non-systematic Assessment |
| |
| Infusion related reaction | Injury, poisoning and procedural complications | MedDRA V26.0 | Non-systematic Assessment |
| |
| Vascular access complication | Injury, poisoning and procedural complications | MedDRA V26.0 | Non-systematic Assessment |
| |
| Wound dehiscence | Injury, poisoning and procedural complications | MedDRA V26.0 | Non-systematic Assessment |
| |
| Acute kidney injury | Renal and urinary disorders | MedDRA V26.0 | Non-systematic Assessment |
| |
| Renal failure | Renal and urinary disorders | MedDRA V26.0 | Non-systematic Assessment |
| |
| Haematuria | Renal and urinary disorders | MedDRA V26.0 | Non-systematic Assessment |
| |
| Nephrolithiasis | Renal and urinary disorders | MedDRA V26.0 | Non-systematic Assessment |
| |
| Renal colic | Renal and urinary disorders | MedDRA V26.0 | Non-systematic Assessment |
| |
| Acute respiratory failure | Respiratory, thoracic and mediastinal disorders | MedDRA V26.0 | Non-systematic Assessment |
| |
| Respiratory failure | Respiratory, thoracic and mediastinal disorders | MedDRA V26.0 | Non-systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA V26.0 | Non-systematic Assessment |
| |
| Eosinophilic pneumonia | Respiratory, thoracic and mediastinal disorders | MedDRA V26.0 | Non-systematic Assessment |
| |
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA V26.0 | Non-systematic Assessment |
| |
| Hypoxia | Respiratory, thoracic and mediastinal disorders | MedDRA V26.0 | Non-systematic Assessment |
| |
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | MedDRA V26.0 | Non-systematic Assessment |
| |
| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | MedDRA V26.0 | Non-systematic Assessment |
| |
| Colitis | Gastrointestinal disorders | MedDRA V26.0 | Non-systematic Assessment |
| |
| Faecaloma | Gastrointestinal disorders | MedDRA V26.0 | Non-systematic Assessment |
| |
| Gastrointestinal haemorrhage | Gastrointestinal disorders | MedDRA V26.0 | Non-systematic Assessment |
| |
| Varices oesophageal | Gastrointestinal disorders | MedDRA V26.0 | Non-systematic Assessment |
| |
| Cholecystitis acute | Hepatobiliary disorders | MedDRA V26.0 | Non-systematic Assessment |
| |
| Hepatic failure | Hepatobiliary disorders | MedDRA V26.0 | Non-systematic Assessment |
| |
| Diabetic ketoacidosis | Metabolism and nutrition disorders | MedDRA V26.0 | Non-systematic Assessment |
| |
| Hypoglycaemia | Metabolism and nutrition disorders | MedDRA V26.0 | Non-systematic Assessment |
| |
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA V26.0 | Non-systematic Assessment |
| |
| Lactic acidosis | Metabolism and nutrition disorders | MedDRA V26.0 | Non-systematic Assessment |
| |
| Arthritis | Musculoskeletal and connective tissue disorders | MedDRA V26.0 | Non-systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA V26.0 | Non-systematic Assessment |
| |
| Rhabdomyolysis | Musculoskeletal and connective tissue disorders | MedDRA V26.0 | Non-systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA V26.0 | Non-systematic Assessment |
| |
| Intracranial mass | Nervous system disorders | MedDRA V26.0 | Non-systematic Assessment |
| |
| Paraesthesia | Nervous system disorders | MedDRA V26.0 | Non-systematic Assessment |
| |
| Syncope | Nervous system disorders | MedDRA V26.0 | Non-systematic Assessment |
| |
| Transient ischaemic attack | Nervous system disorders | MedDRA V26.0 | Non-systematic Assessment |
| |
| Confusional state | Psychiatric disorders | MedDRA V26.0 | Non-systematic Assessment |
| |
| Delirium | Psychiatric disorders | MedDRA V26.0 | Non-systematic Assessment |
| |
| Major depression | Psychiatric disorders | MedDRA V26.0 | Non-systematic Assessment |
| |
| Suicidal ideation | Psychiatric disorders | MedDRA V26.0 | Non-systematic Assessment |
| |
| Ovarian mass | Reproductive system and breast disorders | MedDRA V26.0 | Non-systematic Assessment |
| |
| Acute myocardial infarction | Vascular disorders | MedDRA V26.0 | Non-systematic Assessment |
| |
| Hypotension | Vascular disorders | MedDRA V26.0 | Non-systematic Assessment |
| |
| Subclavian artery aneurysm | Vascular disorders | MedDRA V26.0 | Non-systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Aspartate aminotransferase increased | Investigations | MedDRA V26.0 | Non-systematic Assessment |
|
Not provided
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Thomas L. Holland, MD | Duke University | 919-613-4268 | thomas.holland@duke.edu |
| Prot_001.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Jan 3, 2024 | Jun 20, 2024 | SAP_002.pdf |
| ICF | No | No | Yes | Informed Consent Form | Jul 28, 2022 | Aug 30, 2023 | ICF_000.pdf |
| ID | Term |
|---|---|
| D016470 | Bacteremia |
| D013203 | Staphylococcal Infections |
| ID | Term |
|---|---|
| D001424 | Bacterial Infections |
| D001423 | Bacterial Infections and Mycoses |
| D007239 | Infections |
| D018805 | Sepsis |
| D018746 | Systemic Inflammatory Response Syndrome |
| D007249 | Inflammation |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D016908 | Gram-Positive Bacterial Infections |
Not provided
Not provided
| ID | Term |
|---|---|
| D002437 | Cefazolin |
| C469289 | dalbavancin |
| D017576 | Daptomycin |
| D009254 | Nafcillin |
| D010068 | Oxacillin |
| D014640 | Vancomycin |
| ID | Term |
|---|---|
| D002511 | Cephalosporins |
| D047090 | beta-Lactams |
| D007769 | Lactams |
| D000577 | Amides |
| D009930 | Organic Chemicals |
| D013843 | Thiazines |
| D013457 | Sulfur Compounds |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
| D010456 | Peptides, Cyclic |
| D047028 | Macrocyclic Compounds |
| D011083 | Polycyclic Compounds |
| D055666 | Lipopeptides |
| D008055 | Lipids |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
| D010406 | Penicillins |
| D006020 | Glycopeptides |
| D006001 | Glycoconjugates |
| D002241 | Carbohydrates |
Not provided
Not provided
| Male |
|
| Not Hispanic or Latino |
|
| Unknown or Not Reported |
|
| Asian |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
| United States |
|
| MSSA |
|
| Rank 3: Alive with two of clinical failure, infectious comp, or SAE or AE leading to trt discont |
|
| Rank 4: Alive with all of clinical failure, infectious comp, and SAE or AE leading to trt discont |
|
| Rank 5: Death |
|
For Methicillin-sensitive Staphylococcus aureus (MSSA): nafcillin (2 g administrated intravenously (IV) every 4 hours for 4-6 weeks) OR oxacillin (2 g administrated IV every 4 hours for 4-6 weeks OR cefazolin (2 g administrated IV every 8 hours for 4-6 weeks). For Methicillin-resistant Staphylococcus aureus (MRSA): vancomycin (dose per local standard of care × 4-6 weeks) OR daptomycin (6-10 mg/kg administrated IV daily for 4-6 weeks). Cefazolin: Cefazolin is a semisynthetic cephalosporin analog with broad-spectrum antibiotic action due to inhibition of bacterial cell wall synthesis. Daptomycin: Daptomycin (USA) or Cubicin (Spain) is a cyclic lipopeptide antibiotic that inhibits gram-positive bacteria. Nafcillin: Nafcillin is a semi-synthetic antibiotic related to penicillin. Oxacillin: Oxacillin is an antibiotic used in resistant staphylococci infections. Vancomycin: Vancomycin is a glycopeptide antibiotic product of the organism Amycolatopsis orientalis. |
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