Table S1: Search strategy in OVID MEDLINE

  1. (telavancin or dalbavancin or oritavancin).mp
  2. random$.tw
  3. multicenter study.pt
  4. randomized controlled trial.pt
  5. controlled clinical trial.pt
  6. clinical trial.pt
  7. experiment$.tw
  8. (time adj series).tw
  9. (pretest or pre test or (posttest or post test)).tw
  10. random allocation/
  11. impact.tw
  12. intervention?.tw
  13. chang$.tw
  14. evaluation studies/
  15. evaluat$.tw
  16. effect?.tw
  17. comparative study/
  18. compar$.tw
  19. or/2-18
  20. editorial.pt
  21. letter.pt
  22. comment.pt
  23. or/20-22
  24. animals/
  25. humans/
  26. 24 not 25
  27. 23 or 26
  28. 19 not 27
  29. 1 and 28

Table S2: Study characteristics

Author, year / Population / Intervention
Comparison
Sample size (intervention; comparison) / Outcomes
Telavancin
Stryjewski, 2005 (FAST I) / Adults with cSSTI
(1) caused by a suspected or confirmed gram-positive organism,
(2) defined by the presence of a major abscess requiring surgical drainage, an infected burn, deep extensive cellulitis, or an infected wound or ulcer,
(3) with a purulent drainage fluid or collection specimen or at least ≥ 3 systemic or local signs of acute infection
Mean age was 44 years. More than half the patients were male (60%) and white (64%). Most common diagnoses were major abscess (48%) followed by deep and/or extensive cellulitis (37%). Common predisposing factors were recent surgical procedures (35%), diabetes (26%) and trauma (20%). SIRS/sepsis not reported. / IV telavancin 7.5 mg/kg once daily for 4-14 days
IV vancomycin 1 g every 12h, 2 g nafcillin every 6h, 2 g oxacillin every 6h, or 0.5-1 g cloxacillin every 6h for 4-14 days
167 (84; 83) / Clinical response (7-14 days after last dose of study medication) defined as resolution of signs & symptoms or improvement requiring no further therapy: all patients; among those infected with S.aureus; among those infected with MRSA
Overall and serious adverse events (through 7-14 days after end of therapy)
Stryjewski, 2006 (FAST II) / Adults with cSSTI
(1) caused by a suspected or confirmed gram-positive organism,
(2) defined by the presence of a major abscess requiring surgical drainage, an infected burn, d
eep extensive cellulitis, or an infected wound or ulcer,
(3) with a purulent drainage fluid or collection specimen or at least ≥ 3 systemic or local signs of acute infection
Mean age was 44 years. More than half the patients were male (60%) and white (65%). Most common diagnoses were major abscess (58%) followed by deep and/or extensive cellulitis (29%). Common predisposing factors were recent surgical procedures (33%), trauma (21%) and diabetes (16%). SIRS/sepsis not reported. / IV telavancin 10 mg/kg once daily for 4-14 days
IV vancomycin 1 g every 12h, 2 g nafcillin every 6h, 2 g oxacillin every 6h, or 0.5-1 g cloxacillin every 6h for 4-14 days
195 (100; 95) / Clinical response (7-14 days after last dose of study medication) defined as resolution of signs & symptoms or improvement requiring no further therapy: all patients; among those infected with S.aureus; among those infected with MRSA
Overall and serious adverse events (through 7-14 days after end of therapy)
Stryjewski, 2008 (ATLAS) / Adults with cSSTI
(1) caused by a suspected or confirmed gram-positive organism,
(2) defined by the presence of a major abscess requiring surgical drainage, an infected burn, deep extensive cellulitis, or an infected wound or ulcer,
(3) with a purulent drainage fluid or collection specimen or at least ≥ 3 systemic or local signs of acute infection
Mean age was 49 years. More than half were men (58%) and majority were white (78%). Major abscess (43%) and deep and/or extensive cellulitis (37%) were the most common infections. Diabetes (25%) and trauma (20%) were frequent in both study groups. SIRS/sepsis not reported. / IV telavancin 10 mg/kg once daily for 7-14 days
IV vancomycin 1 g every 12h for 7-14 days
1897 (928; 939) / Clinical response (7-14 days after end of therapy) defined as resolution of signs & symptoms or improvement requiring no further therapy: all patients; among those infected with S.aureus; among those infected with MRSA
Overall and serious adverse events (through 7-14 days after end of therapy)
Dalbavancin
Boucher, 2014 (DISCOVER) / Adults with cSSTI
(1) caused by a suspected or confirmed gram-positive organism,
(2) defined as cellulitis, major abscess or wound infection,
(3) with ≥ 1 systemic signs and ≥ 2 local signs of infection,
(4) thought to require at least 3 days of IV therapy
Mean age was 49 years. More than half were male (59%) and majority were white (89%). Cellulitis was the most common infection (53%) followed by major abscess (25%). About 51% patients met the criteria for SIRS. / IV dalbavancin 1 g on day 1, followed by 500 mg on day 8
IV vancomycin 1 g every 12h for at least 3 days, with an option to switch to oral linezolid, at a dose of 600 mg every 12 hours, to complete 10-14 days of therapy
1312 (659; 653) / Clinical response (at 48-72 hours & day 14-15) defined as cessation of erythema and no fever: all patients; among those infected with S.aureus; among those infected with MRSA
Overall and serious adverse events (through study period up to day 70)
Jauregui, 2005 / Adults with cSSTI
(1) caused by a suspected or confirmed gram-positive organism,
(2) defined as infection that involved deeper soft tissue or that required significant surgical intervention (e.g., major abscesses, major burns, traumatic or surgical wound infections, extensive/ulcerating cellulitis) or an SSTI known or suspected to be caused by MRSA,
(3) with ≥ 1 systemic signs and ≥ 2 local signs of infection,
(4) thought to require initial parenteral therapy
Mean age was 47 years. Majority were male (62%) and white (69%). Major abscesses (32%) and cellulitis (28%) were the predominant infection types. The predisposing cause was spontaneous in 50% of cases. SIRS/sepsis not reported. / IV dalbavancin 1 g on day 1, followed by 500 mg on day 8
IV linezolid 600 mg every 12h with a possible switch to oral route after at least 24h for a total duration of 14 days
854 (571; 283) / Clinical response (at 14±2 days) defined as improvement of signs and symptoms such that no further antibiotic therapy was warranted
Overall and serious adverse events (through study period up to day 42)
Oritavancin
Corey, 2014 (SOLO I) / Adults with cSSTI
(1) caused by a suspected or confirmed gram-positive organism,
(2) defined as wound infection, cellulitis, erysipelas or major cutaneous abscess)
(3) with ≥ 1 systemic signs and ≥ 2 local signs of infection
(4) thought to require at least 7 days of IV therapy
Mean age was 45 years. Patients were predominantly white (57%) and male (63%). 50% of patients had cellulitis and 30% had abscess. SIRS/sepsis not reported. / IV oritavancin 1200 mg as a single dose
IV vancomycin 1 g or 15 mg/kg every 12h for 7-10 days
968 (483; 485) / Clinical response (at 48-72 hours & 7-14 days after end of therapy) defined as investigator assessed clinical cure: all patients; among those infected with S.aureus; among those infected with MRSA
Overall and serious adverse events (through study period up to day 60)
Corey, 2015 (SOLO II) / Adults with cSSTI
(1) caused by a suspected or confirmed gram-positive organism,
(2) defined as wound infection, cellulitis, erysipelas or major cutaneous abscess)
(3) with ≥ 1 systemic signs and ≥ 2 local signs of infection
(4) thought to require at least 7 days of IV therapy
Mean age was 45 years. Patients were predominantly white (71%) and male (68%). 37% had wound infection, 33% had abscess and 31% had cellulitis. SIRS/sepsis not reported. / IV oritavancin 1200 mg as a single dose
IV vancomycin 1 g or 15 mg/kg every 12h for 7-10 days
1005 (503; 502) / Clinical response (at 48-72 hours & 7-14 days after end of therapy) defined as investigator assessed clinical cure: all patients; among those infected with S.aureus; among those infected with MRSA
Overall and serious adverse events (through study period up to day 60)

Abbreviations: ABSSSI – acute bacterial skin and skin structure infection; cSSTI – complicated skin and soft tissue infection; IV – intravenous; MRSA – methicillin-resistant Staphylococcus aureus; SIRS – systemic inflammatory response syndrome

Table S3: Results from pairwise and network meta-analysis for Clinical response – all patients (per-protocol analysis)

Treatment comparison / Number of studies / Pairwise meta-analysis / Network meta-analysis
Odds ratio (95% CI) / Odds ratio (95% CI)
Oritavancin vs. Standard care / 2 / 1.01 (0.71-1.45) / 1.02 (0.71-1.45)
Dalbavancin vs. Standard care / 2 / 0.79 (0.53-1.20) / 0.79 (0.53-1.20)
Telavancin vs. Standard care / 3 / 1.10 (0.82-1.48) / 1.10 (0.82-1.48)
Oritavancin vs. Dalbavancin / NA / NA / 1.28 (0.74-2.21)
Oritavancin vs. Telavancin / NA / NA / 0.92 (0.58 – 1.47)
Dalbavancin vs. Telavancin / NA / NA / 0.72 (0.43-1.20)

Table S4: Description of serious adverse events

Author, year / Intervention / Comparison
Telavancin
Stryjewski, 2005 (FAST I) / No description reported. No fatal outcomes reported.
Stryjewski, 2006 (FAST II) / 12 serious adverse events in 7 patients: disseminated intravascular coagulation, atrial fibrillation, gastrointestinal bleeding, lobar pneumonia, subcutaneous abscess, wound infection, myositis, suicidal ideation, renal failure, ileostomy, hypotension, and wound hemorrhage. No fatal outcomes reported. / 8 serious adverse events in 3 patients: multiorgan failure, liver failure, bacteremia, sepsis, renal failure, atelectasis, lung infiltration, and respiratory failure. No fatal outcomes reported.
Stryjewski, 2008 (ATLAS) / No description reported. 8 patients died in each group.
Dalbavancin
Boucher, 2014 (DISCOVER) / 2 treatment-related serious adverse events in 2 patients: cellulitis and anaphylactoid reaction. Remaining serious adverse events were deemed to be unrelated to treatment. 1 patient died. / 4 treatment-related serious adverse events in 4 patients: cellulitis, gastrointestinal disorder, toxic nephropathy, and renal failure. Remaining serious adverse events were deemed to be unrelated to treatment. 7 patients died.
Jauregui, 2005 / 1 treatment-related serious adverse event: leukopenia. Remaining serious adverse events were deemed to be unrelated to treatment. 2 patients died. / 2 treatment-related serious adverse events: thrombocytopenia and pancytopenia. Remaining serious adverse events were deemed to be unrelated to treatment. 2 patients died.
Oritavancin
Corey, 2014 (SOLO I) / 3 treatment-related serious adverse events but no description provided. 1 patient died. / 3 treatment-related serious adverse events but no description provided. 2 patients died.
Corey, 2015 (SOLO II) / Treatment-related adverse events that led to study discontinuation were cellulitis in 2 patients, infection in 2 patients and osteomyelitis in 2 patients. 5 patients reported osteomyelitis during study. 1 patient died. / Treatment-related adverse events that led to study discontinuation were cellulitis in 2 patients, infection in 0 patients and osteomyelitis in 0 patients. No patients reported osteomyelitis during study. 1 patient died.

Figure S1:Clinical response – all patients

Figure S2:Clinical response – patients infected with methicillin-resistant-Staphylococcus aureus

Figure S3: Clinical response – all patients (per protocol population)

Figure S4:Overall adverse events

Figure S5:Serious adverse events