. 2020 Oct 28;21:73. doi: 10.1186/s40360-020-00452-z

Table 2.

Comparison of long acting lipoglycopeptide studies that included persons who use drugs

Citation, year, LAL(s)	Patients	Organisms	Indications	Number of doses	Results	Outcomes & Definitions
Stewart et al. 2017 [12] ORI	▪ Total: 10 ▪ PWID: 4 (40%) PWID only ▪ Males: 0 ▪ Average age: 37 years (range 26–53)	PWID ▪ MSSA: 2 ▪ GBS: 1 ▪ Enterococci: 1	PWID ▪ GBS BSI + IE ▪ E. faecalis BSI ▪ BSI + bone/joint ▪ BSI + psoas abscess	PWID ▪ 1 dose = 4/4	PWID (n = 4) ▪ Cure: 1/4 ▪ Failure: 2/4 ▪ LTFU: 1/4	▪ Clinical cure: resolution of all clinical signs/symptoms of infection (afebrile, normalization of WBC/ESR), no additional infection-related hospital admissions, no additional antibiotic therapy required for the initial indication treated with ORI, infection clearance with sterile blood cultures where indicated. ▪ Failure: worsening of current infection or new/recurrent signs or symptoms of infection requiring a change in antibiotics or additional antibiotic therapy. ▪ Not clinically evaluable: patients who were LTFU. ▪ ADRs: based on reporting by prescribing physician and follow-up with patients after administration (timeframe not specified).
Morrisette et al. 2019 [14] DAL + ORI	▪ Total: 56 ▪ PWUD: 17 (30%) PWUD only ▪ Males: 12 (71%) ▪ Average age: 34.5 years (SD + 10.9) ▪ DAL: 12 /17 ▪ ORI: 4/17 ▪ Both: 1/17	PWUD ▪ MSSA: 8 (47%) ▪ MRSA: 5 (29%) ▪ E. faecalis: 1 (6%) ▪ VRE: 1 (6%) ▪ Other: 2 (12%) (unknown or mixed)	PWUD ▪ ABSSSI: 6 (35%) ▪ OM: 6 (35%) ▪ IE: 3 (18%) ▪ Other: 2 (12%)	PWUD ▪ Median = 1 (IQR 1–2)	PWUD (n = 17) ▪ Success: 13/17 (77%) ▪ Failure: 1/17 (6%) ▪ Unknown: 3/17 1 patient counted as both a failure and success as they failed oritavancin but were subsequently cured with dalbavancin.	▪ Clinical success: no further clinical or microbiological evidence of active infection (resolution of signs/symptoms related to bacterial infection and clearance of cultures if applicable) without need for further gram-positive therapy due to clinical worsening within 60 days of last dose of LAL. ▪ Clinical failure: lack of clinical response, relapse with the primary infection within 60 days of last LAL dose, need for alternative gram-positive therapy due to clinical worsening during LAL therapy, or death. ▪ ADRs: any potential ADR occurring during or within 7 days of LAL infusion.
Bork et al. 2019 [15] DAL	▪ Total: 28 ▪ PWUD: 19 (68%) ▪ PWID: 16/19 (57%) All patients ▪ Males: 26 (93%) ▪ Median age: 52 years (IQR 21.5)	All patients ▪ MRSA: 8 (29%) ▪ MSSA: 6 (21%) ▪ CoNS: 4 (14%) ▪ Mixed GP: 8 (29%) ▪ Unknown: 5 (18%)	All patients ▪ Bone: 13 (46%) ▪ Endovascular: 6 (21%) ▪ BSI: 4 (14%) ▪ Other: 5 (18%)	All patients ▪ Average = 3 ▪ Site 1: 1.5 ▪ Site 2: 5.5	Substance Abusers (n = 19) ▪ Success: 10/13 (77%) ▪ Failure: 3/13 (23%) ▪ LTFU: 6/19	▪ Primary outcome: proportion of patients with 30 day clinical cure (30 days after planned DAL course). ▪ Secondary outcomes: 90 day clinical cure; ADRs ▪ Clinical cure: composite of resolution of clinical signs of infection (erythema, swelling, pain); afebrile; normalization of CRP/ESR/WBC; source control; resolution of radiographic signs of infection and/or microbiologic clearance of organisms. If readmitted for infection then considered failure. ▪ Clinical failure: due to (1) death, (2) intolerance or AE, (3) lack of access to subsequent DAL, (4) lack of source control, (5) worsening signs of infection or relapse. ▪ ADRs: anything likely to be associated w/ DAL based on specific ADE and temporal relationship with DAL (specific timeframe not provided).
Bryson-Cahn et al. 2019 [16] DAL	▪ Total: 32 ▪ PWUD: 32 (100%) ▪ PWID: 28 (88%) ▪ Homeless: 15 (47%) All patients (PWUD) ▪ Males: 23 (72%) ▪ Average age: 38 years (IQR 25–50)	PWUD ▪ MRSA: 28 (88%) ▪ In the IE group: -MSSA = 2 -MRSA = 7 Other organisms not reported.	PWUD ▪ IE: 9 ▪ BSI: 14 - Joint: 2 - Epidural abscess: 3 - Thrombophlebitis: 2 ▪ Bone: 7 - Spine: 3 - Extremity: 4 ▪ Joint: 2 (without BSI)	PWUD ▪ 1 dose = 22 ▪ 2 doses = 7 ▪ 3 doses = 2 ▪ 5 doses = 1	PWUD (n = 32) ▪ Success: 18/32 (56%) ▪ Failure: 4/32 (13%) ▪ LTFU: 10/32 (31%) ▪ Completed therapy: 17/32 (53%)	▪ Clinical response: patient had a follow-up visit within 1 year at HMC or a neighboring hospital, linked through a common EMR, without evidence for an ongoing or relapsed infection, regardless of whether they completed the intended course of therapy. ▪ LTFU: patient did not have a subsequent encounter to evaluate their infection at either the ID clinic or another institution linked via EMR within 1 year. ▪ All-cause readmission: hospital readmission within 30 days from previous discharge. ▪ ADRs: not defined/reported.
Brownell et al. 2020 [13] ORI	▪ Total: ▪ 75 safety analysis ▪ 73 efficacy analysis ▪ PWID: 10 (13.3%)	All patients: ▪ MSSA: 23 (31.5%) ▪ MRSA: 13 (17.8%) ▪ CoNS: 4 (5.8%) ▪ VRE: 4 (5.8%)	All patients: ABSSSI: 25 Diabetic foot infection: 3 IE: 4 Line infection: 2 Other: 5 OM/Septic arthritis: 10 Pneumonia: 5 Prosthetic device infection: 3 Sepsis: 5 Surgical wound infection: 12 PWID: numbers not reported OM, IE, Prosthetic device infection, Surgical wound infection	All patients: 1–32	All patients: n = 73 Cure: 34/73 (46.6%) Improvement: 34/73 (46.6%) Failure: 5/73 (6.8%) PWID (n = 10) Cure or improvement: 7/10 (70%)	• Clinical outcomes were reviewed within 28 days of the end of therapy. Safety outcomes were reviewed out to 30 days after ORI. • Clinical cure: resolution of signs and symptoms of infection without the need for further treatment after the completion of ORI • Clinical improvement: recovery from infectious signs and symptoms with the need for subsequent gram-positive therapy after the completion of the ORI • Clinical failure: progression of infectious signs and symptoms and need for alternative gram-positive therapy during the ORI course
Ahiskali et al. 2020 ORI	▪ Total = 24 ▪ PWUD: 24 (100%) ▪ PWID: 24 (100%) ▪ Homeless: 16 (67%) All patients (PWUD) ▪ Males: 16 (70%) ▪ Average age: 41 years (range 22–64)	PWUD ▪ MRSA: 14 (58%) ▪ MSSA: 8 (33%) ▪ Streptococci: 2 ▪ Unknown: 1	PWUD ▪ Bone/Joint: 14 - Bone: 9 Spine: 5/9 - Joint: 5 ▪ BSI: 12 ▪ IE: 2 Patients may be counted in multiple categories.	PWUD ▪ 1 dose = 13 ▪ 2 doses = 7 ▪ 3 doses = 1 ▪ 4 doses = 1 ▪ 6 doses = 2	PWUD (n = 24) ▪ Success: 19/24 (79%) - I/C = 5 ▪ Failure: 3/24 (13%) - I/F = 1 ▪ LTFU: 2/24 (8%) ▪ Completed therapy: 19/24 (79%)	▪ Outcomes were reviewed out to 60 days after the final ORI infusion. ▪ Clinical cure: resolution of signs and symptoms of infection (fever, WBC, ESR) without need for additional antimicrobial therapy following completion of ORI (excluding long term suppressive antibiotics for retained hardware). ▪ Failure: progression of infection and need for alternative therapy. ▪ Incomplete cure/failure: incomplete adherence to therapy. ▪ LTFU: no notes or data available in EMR after final ORI dose. ▪ ADRs: collected up to 6 weeks from last dose or until LTFU.

Citation, year, LAL(s)

Patients

Organisms

Indications

Number of doses

Results

Outcomes & Definitions

Stewart et al. 2017 [12]

ORI

▪ Total: 10

▪ PWID: 4 (40%)

PWID only

▪ Males: 0

▪ Average age: 37 years (range 26–53)

PWID

▪ MSSA: 2

▪ GBS: 1

▪ Enterococci: 1

PWID

▪ GBS BSI + IE

▪ E. faecalis BSI

▪ BSI + bone/joint

▪ BSI + psoas abscess

PWID

▪ 1 dose = 4/4

PWID (n = 4)

▪ Cure: 1/4

▪ Failure: 2/4

▪ LTFU: 1/4

▪ Clinical cure: resolution of all clinical signs/symptoms of infection (afebrile, normalization of WBC/ESR), no additional infection-related hospital admissions, no additional antibiotic therapy required for the initial indication treated with ORI, infection clearance with sterile blood cultures where indicated.

▪ Failure: worsening of current infection or new/recurrent signs or symptoms of infection requiring a change in antibiotics or additional antibiotic therapy.

▪ Not clinically evaluable: patients who were LTFU.

▪ ADRs: based on reporting by prescribing physician and follow-up with patients after administration (timeframe not specified).

Morrisette et al. 2019 [14]

DAL + ORI

▪ Total: 56

▪ PWUD: 17 (30%)

PWUD only

▪ Males: 12 (71%)

▪ Average age: 34.5 years (SD + 10.9)

▪ DAL: 12 /17

▪ ORI: 4/17

▪ Both: 1/17

PWUD

▪ MSSA: 8 (47%)

▪ MRSA: 5 (29%)

▪ E. faecalis: 1 (6%)

▪ VRE: 1 (6%)

▪ Other: 2 (12%)

(unknown or mixed)

PWUD

▪ ABSSSI: 6 (35%)

▪ OM: 6 (35%)

▪ IE: 3 (18%)

▪ Other: 2 (12%)

PWUD

▪ Median = 1 (IQR 1–2)

PWUD (n = 17)

▪ Success: 13/17 (77%)

▪ Failure: 1/17 (6%)

▪ Unknown: 3/17

1 patient counted as both a failure and success as they failed oritavancin but were subsequently cured with dalbavancin.

▪ Clinical success: no further clinical or microbiological evidence of active infection (resolution of signs/symptoms related to bacterial infection and clearance of cultures if applicable) without need for further gram-positive therapy due to clinical worsening within 60 days of last dose of LAL.

▪ Clinical failure: lack of clinical response, relapse with the primary infection within 60 days of last LAL dose, need for alternative gram-positive therapy due to clinical worsening during LAL therapy, or death.

▪ ADRs: any potential ADR occurring during or within 7 days of LAL infusion.

Bork et al. 2019 [15]

DAL

▪ Total: 28

▪ PWUD: 19 (68%)

▪ PWID: 16/19 (57%)

All patients

▪ Males: 26 (93%)

▪ Median age: 52 years (IQR 21.5)

All patients

▪ MRSA: 8 (29%)

▪ MSSA: 6 (21%)

▪ CoNS: 4 (14%)

▪ Mixed GP: 8 (29%)

▪ Unknown: 5 (18%)

All patients

▪ Bone: 13 (46%)

▪ Endovascular: 6 (21%)

▪ BSI: 4 (14%)

▪ Other: 5 (18%)

All patients

▪ Average = 3

▪ Site 1: 1.5

▪ Site 2: 5.5

Substance Abusers (n = 19)

▪ Success: 10/13 (77%)

▪ Failure: 3/13 (23%)

▪ LTFU: 6/19

▪ Primary outcome: proportion of patients with 30 day clinical cure (30 days after planned DAL course).

▪ Secondary outcomes: 90 day clinical cure; ADRs

▪ Clinical cure: composite of resolution of clinical signs of infection (erythema, swelling, pain); afebrile; normalization of CRP/ESR/WBC; source control; resolution of radiographic signs of infection and/or microbiologic clearance of organisms. If readmitted for infection then considered failure.

▪ Clinical failure: due to (1) death, (2) intolerance or AE, (3) lack of access to subsequent DAL, (4) lack of source control, (5) worsening signs of infection or relapse.

▪ ADRs: anything likely to be associated w/ DAL based on specific ADE and temporal relationship with DAL (specific timeframe not provided).

Bryson-Cahn et al. 2019 [16]

DAL

▪ Total: 32

▪ PWUD: 32 (100%)

▪ PWID: 28 (88%)

▪ Homeless: 15 (47%)

All patients (PWUD)

▪ Males: 23 (72%)

▪ Average age: 38 years (IQR 25–50)

PWUD

▪ MRSA: 28 (88%)

▪ In the IE group:

-MSSA = 2

-MRSA = 7

Other organisms not reported.

PWUD

▪ IE: 9

▪ BSI: 14

- Joint: 2

- Epidural abscess: 3

- Thrombophlebitis: 2

▪ Bone: 7

- Spine: 3

- Extremity: 4

▪ Joint: 2

(without BSI)

PWUD

▪ 1 dose = 22

▪ 2 doses = 7

▪ 3 doses = 2

▪ 5 doses = 1

PWUD (n = 32)

▪ Success: 18/32 (56%)

▪ Failure: 4/32 (13%)

▪ LTFU: 10/32 (31%)

▪ Completed therapy: 17/32 (53%)

▪ Clinical response: patient had a follow-up visit within 1 year at HMC or a neighboring hospital, linked through a common EMR, without evidence for an ongoing or relapsed infection, regardless of whether they completed the intended course of therapy.

▪ LTFU: patient did not have a subsequent encounter to evaluate their infection at either the ID clinic or another institution linked via EMR within 1 year.

▪ All-cause readmission: hospital readmission within 30 days from previous discharge.

▪ ADRs: not defined/reported.

Brownell et al. 2020 [13]

ORI

▪ Total:

▪ 75 safety analysis

▪ 73 efficacy analysis

▪ PWID: 10 (13.3%)

All patients:

▪ MSSA: 23 (31.5%)

▪ MRSA: 13 (17.8%)

▪ CoNS: 4 (5.8%)

▪ VRE: 4 (5.8%)

All patients:

ABSSSI: 25

Diabetic foot infection: 3

IE: 4

Line infection: 2

Other: 5

OM/Septic arthritis: 10

Pneumonia: 5

Prosthetic device infection: 3

Sepsis: 5

Surgical wound infection: 12

PWID: numbers not reported

OM, IE, Prosthetic device infection, Surgical wound infection

All patients:

1–32

All patients: n = 73

Cure: 34/73 (46.6%)

Improvement: 34/73 (46.6%)

Failure: 5/73 (6.8%)

PWID (n = 10)

Cure or improvement: 7/10 (70%)

• Clinical outcomes were reviewed within 28 days of the end of therapy. Safety outcomes were reviewed out to 30 days after ORI.

• Clinical cure: resolution of signs and symptoms of infection without the need for further treatment after the completion of ORI

• Clinical improvement: recovery from infectious signs and symptoms with the need for subsequent gram-positive therapy after the completion of the ORI

• Clinical failure: progression of infectious signs and symptoms and need for alternative gram-positive therapy during the ORI course

Ahiskali et al. 2020

ORI

▪ Total = 24

▪ PWUD: 24 (100%)

▪ PWID: 24 (100%)

▪ Homeless: 16 (67%)

All patients (PWUD)

▪ Males: 16 (70%)

▪ Average age: 41 years (range 22–64)

PWUD

▪ MRSA: 14 (58%)

▪ MSSA: 8 (33%)

▪ Streptococci: 2

▪ Unknown: 1

PWUD

▪ Bone/Joint: 14

- Bone: 9

Spine: 5/9

- Joint: 5

▪ BSI: 12

▪ IE: 2

Patients may be counted in multiple categories.

PWUD

▪ 1 dose = 13

▪ 2 doses = 7

▪ 3 doses = 1

▪ 4 doses = 1

▪ 6 doses = 2

PWUD (n = 24)

▪ Success: 19/24 (79%)

- I/C = 5

▪ Failure: 3/24 (13%)

- I/F = 1

▪ LTFU: 2/24 (8%)

▪ Completed therapy: 19/24 (79%)

▪ Outcomes were reviewed out to 60 days after the final ORI infusion.

▪ Clinical cure: resolution of signs and symptoms of infection (fever, WBC, ESR) without need for additional antimicrobial therapy following completion of ORI (excluding long term suppressive antibiotics for retained hardware).

▪ Failure: progression of infection and need for alternative therapy.

▪ Incomplete cure/failure: incomplete adherence to therapy.

▪ LTFU: no notes or data available in EMR after final ORI dose.

▪ ADRs: collected up to 6 weeks from last dose or until LTFU.

Abbreviations: ABSSSI acute bacterial skin and skin structure infection, BSI bloodstream infection, CC clinical cure, CoNS coagulase-negative staphylococci, DAL dalbavancin, EMR electronic medical record, ESR erythrocyte sedimentation rate, GBS Group B Streptococcus, GP gram-positive, HW hardware, IE infective endocarditis, I/C incomplete adherence with cure, I/F incomplete adherence with failure, , IQR interquartile range, LTFU lost to follow-up, MSSA methicillin-susceptible Staphylococcus aureus, MRSA methicillin-resistant Staphylococcus aureus, OM osteomyelitis, ORI oritavancin, PWID persons who inject drugs, PWUD persons who use drugs, VRE vancomycin-resistant Enterococcus faecium, WBC white blood cell count