# Dalbavancin treatment for prosthetic joint infections in real-life: a national cohort study and literature review

Morgan Matt, Clara Duran, Johan Courjon, Romain Lotte, Vincent Le Moing, Boris Monnin, Patricia Pavese, Pascal Chavanet, Lydie Khatchatourian, Pierre Tattevin, et al.

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## To cite this version:

Morgan Matt, Clara Duran, Johan Courjon, Romain Lotte, Vincent Le Moing, et al. Dalbavancin treatment for prosthetic joint infections in real-life: a national cohort study and literature review. Journal of Global Antimicrobial Resistance, 2021, 25, pp.341-345. 10.1016/j.jgar.2021.03.026. hal-03372914v2

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# Dalbavancin treatment for prosthetic joint infections in real-life: a national cohort study and literature review

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Morgan Matt<sup>a</sup>, Clara Duran<sup>a</sup>, Johan Courjon<sup>b</sup>, Romain Lotte<sup>c</sup>, Vincent Le Moing<sup>d</sup>, Boris Monnin<sup>d</sup>, Patricia Pavese<sup>e</sup>, Pascal Chavanet<sup>f</sup>, Lydie Khatchatourian<sup>g</sup>, Pierre Tattevin<sup>h</sup>, Vincent Cattoir<sup>i</sup>, Catherine Lechiche<sup>j</sup>, Gabriella Illes<sup>k</sup>, Flore Lacassin-Beller<sup>k</sup>, Eric Senneville<sup>l</sup>, Aurélien Dinh<sup>a,*</sup>, on behalf of the Dalbavancin French Study Group

## ARTICLE INFO

**Article history:**
Received 2 November 2020
Revised 15 March 2021
Accepted 27 March 2021
Available online 4 May 2021

Editor: S. Stefani

**Keywords:**
Dalbavancin
Prosthetic joint infection
PJI
Staphylococci

## ABSTRACT

**Objectives:** Dalbavancin is a long-lasting lipoglycopeptide active against Gram-positive bacteria, especially methicillin-resistant staphylococci. Few data are available on dalbavancin use for treatment of prosthetic joint infections (PJIs). We describe a cohort of patients treated for PJI with dalbavancin and review the literature regarding this condition.

**Methods:** All adult patients with PJI from the French dalbavancin national cohort from 1 June 2017 to 1 January 2019 were included. We collected clinical and microbiological characteristics and outcome through a standardised questionnaire. Clinical cure was defined as absence of clinical signs of infection at last visit. Failure was a composite criterion defined by persistence or reappearance of signs of infection, and/or switch to suppressive antibiotic treatment and/or death from infection. The literature review was performed using PubMed.

**Results:** Seventeen patients were included. Bacteria were identified in 16 cases: *Staphylococcus aureus* (*n* = 10), including methicillin-resistant S. aureus (*n* = 1); and coagulase-negative staphylococci (*n* = 10), including methicillin-resistant *Staphylococcus epidermidis* (*n* = 4). Sixteen patients (94.1%) had received antibiotic therapy prior to dalbavancin use (mean of 2.2 ± 1.3 lines). Clinical cure was achieved in 8/17 patients after a median follow-up of 299.0 (IQR 97.0–476.0) days. We reviewed all cases of PJI treated with dalbavancin available in the literature and the overall clinical cure was estimated at 73.1%.

**Conclusion:** Our study and literature data suggest that use of dalbavancin in PJI could be considered, even as salvage therapy. Dalbavancin appears to be a safe and easy treatment for patients with staphylococcal PJIs.

© 2021 The Authors. Published by Elsevier Ltd on behalf of International Society for Antimicrobial Chemotherapy.

This is an open access article under the CC BY license ([http://creativecommons.org/licenses/by/4.0/](http://creativecommons.org/licenses/by/4.0/))

<footnote><sup>a</sup> *Infectious Disease Unit, Raymond-Poincaré University Hospital, AP-HP Paris Saclay University, Garches, France*</footnote>

<footnote><sup>b</sup> *Infectious Disease Unit, University Hospital of Nice, Nice, France*</footnote>

<footnote><sup>c</sup> *Microbiology Laboratory, University Hospital of Nice, Nice, France*</footnote>

<footnote><sup>d</sup> *Infectious Disease Department, University Hospital of Montpellier, Montpellier, France*</footnote>

<footnote><sup>e</sup> *Infectious Disease Unit, University Hospital of Grenoble, Grenoble, France*</footnote>

<footnote><sup>f</sup> *Infectious Disease Department, University Hospital of Dijon, Dijon, France*</footnote>

<footnote><sup>g</sup> *Infectious Disease Unit, Cornouaille Hospital, Quimper, France*</footnote>

<footnote><sup>h</sup> *Infectious Disease Unit, Pontchaillou University Hospital, Rennes, France*</footnote>

<footnote><sup>i</sup> *Microbiology Laboratory, Pontchaillou University Hospital, Rennes, France*</footnote>

<footnote><sup>j</sup> *Infectious Disease Unit, Carémeau University Hospital, Nîmes, France*</footnote>

<footnote><sup>k</sup> *Infectious Disease Unit, Hospital of Mont-de-Marsan, Mont-de-Marsan, France*</footnote>

<footnote><sup>l</sup> *Infectious Disease Unit, Hospital of Tourcoing, Tourcoing, France*</footnote>

<footnote>* Corresponding author. Tel.: +33 1 47 10 44 32; fax: +33 1 47 10 77 90.
E-mail address: aurelien.dinh@aphp.fr (A. Dinh).</footnote>
# 1. Introduction

D albavancin is a lipoglycopeptide antibiotic with broad-spectrum activity against Gram-positive bacteria, especially methicillin-resistant *Staphylococcus aureus* [1,2], and long-lasting activity (15 days). The pharmacokinetic properties and administration patterns of dalbavancin could be useful for the treatment of bone and joint infections, especially prosthetic joints infections (PJIs) [3]. Moreover, some in vitro models have shown that dalbavancin is active against staphylococci in biofilms [4]. To date, only a few clinical data are available for PJIs [5,6].

Here we describe a series of patients treated for a PJI with dalbavancin among a previously described national cohort [7].

# 2. Materials and methods

Patients treated with dalbavancin for PJI were selected from the study population previously included in the 'French national cohort of first use of dalbavancin' [7]. All adult patients with PJI treated with at least one dose of dalbavancin from 1 June 2017 to 1 January 2019 were included. The prescribers noted in a standardised questionnaire the following information: type of PJI; specimen results and microbiological characteristics; reason(s) for dalbavancin use; dose and duration of dalbavancin treatment; adverse drug reactions; and outcome at last visit.

Patients were informed that their clinical data could be used, after anonymisation, for research purposes. The research was conducted in accordance with the Declaration of Helsinki.

Immunosuppression was defined as the presence of asplenia, neutropenia, agammaglobulinemia, organ transplant, haematological malignancy, known human immunodeficiency virus (HIV) infection and CD4+ count <400/mm³, or Child-Pugh class C cirrhosis. We considered corticosteroid use (i.e. daily dose >20 mg of prednisolone or equivalent), chemotherapy, cyclophosphamide, azathioprine and cyclosporine as immunosuppressive treatments. Liver failure was defined by coagulation factor V level ≤50% and/or hepatic encephalopathy.

D albavancin minimum inhibitory concentrations (MICs) were determined by the agar dilution or broth microdilution method. Breakpoints were as defined by the European Committee on Antimicrobial Susceptibility Testing (EUCAST) [8].

Outcome was evaluated by the investigators at the patient's last visit. Clinical cure was defined as the absence of clinical signs of infection confirmed by the physician in charge. Failure was a composite criterion defined as persistence or reappearance of signs of infection (with or without microbiological identification), and/or switch to suppressive antibiotic treatment and/or death from infection.

A literature review was performed in the PubMed database using the search terms 'dalbavancin', 'bone and joint infection', 'prosthetic joint infection' and 'implant-associated infections'. We considered cure status as stated by the study authors, and all others status as failures. When no data were specific to the PJI population, they were considered as unavailable. Patients with implant-associated infections were included in the literature review, except for overall outcome [5].

Quantitative variables are presented as the mean ± standard deviation or the median and interquartile range (IQR). Qualitative variables are presented as the number of occurrences and relative frequencies. All statistical analyses were performed using SPSS Statistics v.17.0 (SPSS Inc., Chicago, IL, USA).

# 3. Results

A total of 17 patients from eight French hospitals were included in the study. Table 1 presents the patients' characteristics

at baseline and reasons for dalbavancin use according to outcome.

The main types of PJI were hip prosthesis (n = 8; 47.1%) and knee prosthesis (n = 6; 35.3%). Bacteria were documented in 16/17 cases, including 5 polymicrobial infections, with Gram-negative bacteria in 3 cases. *Staphylococcus aureus* was isolated in 10 cases (62.5%), with methicillin resistance in only 1 case (6.3%), and coagulase-negative staphylococci (CoNS) also in 10 cases (62.5%), with methicillin resistance in 4 cases (25.0%). Four patients (23.5%) presented concomitant bacteraemia.

The median MICs of dalbavancin were 0.064 mg/L (range, 0.047–0.064 mg/L) for *S. aureus* and 0.023 mg/L (range, 0.006–0.094 mg/L) for CoNS, without difference according to susceptibility to methicillin.

Among the 17 patients, 16 received surgical management associated with antibiotic therapy, which was mostly (9/16) debridement and implant retention (DAIR). The median number of previous surgeries for septic reason on the site before dalbavancin use was 1.5 in the cure group and 3.0 in the failure group.

Only one patient received dalbavancin as first-line treatment. The median duration of previous antibiotic therapy was 34.5 days (IQR, 31.3–46.8 days).

The most frequent reason for dalbavancin use was an adverse event of previous antibiotic treatment (n = 8). Dalbavancin was also used to simplify the treatment to allow an early hospital discharge (n = 5), to better adherence (n = 4), to improve patient's autonomy (n = 3) or because of impossible venous access (n = 2). Finally, two patients had bacteria resistant to the previous antibiotic treatment, and only one patient had clinical failure of previous antibiotic treatment.

The preferential administration scheme of dalbavancin was 1500 mg at Day 1 and 1500 mg at Day 7 (n = 8; 47.1%). The different dalbavancin treatment regimens are described in Table 1.

D albavancin was prescribed as monotherapy in eight patients (47.1%). In the 9 remaining patients, associated antibiotics used were tetracyclines (n = 3; 33.3%), trimethoprim/sulfamethoxazole (n = 2; 22.2%), fluoroquinolones (n = 2; 22.2%), rifampicin (n = 1; 11.1%) and clindamycin (n = 1; 11.1%). No adverse events among the 17 patients were reported.

The median (IQR) duration of follow-up was 299.0 (97.0–476.0) days. Latest patient evaluation showed clinical cure in 8/17 patients, among whom 6 received dalbavancin as monotherapy. Two patients died due to PJI. Four relapses were reported, including three without microbiological identification and one superinfection. Lastly, three patients received an antibiotic suppressive treatment, including two patients who received dalbavancin as outpatient parenteral antimicrobial therapy (OPAT) at hospital discharge.

The main difference between the cure and failure groups was the number of severe patients in the failure group, with one sepsis, one septic shock and one patient managed without surgery.

Table 2 presents all cases of PJI treated with dalbavancin available in the literature. Most studies reported patients with various infectious diseases due to Gram-positive cocci, including skin and soft-tissue infections and bone and joint infections. A total of 102 Gram-positive cocci-related PJIs were reported, with a predominance of CoNS (n = 59). Regarding the scheme of dalbavancin administration, 1000 mg followed by 500 mg weekly was used in most cases. The overall clinical cure was estimated at 73.1% (n = 68/93, excluding the results of the study by Morata et al. as the specific rate of clinical cure in PJIs was not described in their article).

# 4. Discussion

Optimal management of PJIs is the combination of surgery and effective antibiotic therapy based on microbiological documentation at baseline and reasons for dalbavancin use according to outcome.
<table><caption>**Table 1**
Demographics, baseline characteristics and description of dalbavancin use in study patients</caption><thead><tr><th>Characteristic</th><th>Total (N = 17)</th><th>Success (N = 8)</th><th>Failure (N = 9)</th></tr></thead><tbody><tr><td>Age (years) [median (IQR)]</td><td>69.0 (62.0–75.0)</td><td>66.5 (60.5–71.3)</td><td>73.0 (64.0–80.0)</td></tr><tr><td>Sex ratio (M/F)</td><td>1.43</td><td>3.00</td><td>0.80</td></tr><tr><td>Length of hospitalisation (days) [median (IQR)]</td><td>15.5 (9.3–25.0)</td><td>17.0 (8.5–27.5)</td><td>14.0 (10.5–19.5)</td></tr><tr><td>Co-morbidities [n (%)]</td><td></td><td></td><td></td></tr><tr><td>Heart failure</td><td>5 (29.4)</td><td>4 (50.0)</td><td>1 (11.1)</td></tr><tr><td>Chronic renal failure</td><td>4 (23.5)</td><td>3 (37.5)</td><td>1 (11.1)</td></tr><tr><td>Liver failure</td><td>2 (11.8)</td><td>1 (12.5)</td><td>1 (11.1)</td></tr><tr><td>Neurological disease</td><td>2 (11.8)</td><td>2 (25.0)</td><td>0 (0)</td></tr><tr><td>Immunosuppression</td><td>6 (35.3)</td><td>3 (37.5)</td><td>3 (33.3)</td></tr><tr><td>Cancer chemotherapy</td><td>1 (5.9)</td><td>1 (12.5)</td><td>0 (0)</td></tr><tr><td>Immunosuppressive treatment</td><td>1 (5.9)<sup>a</sup></td><td>0 (0)</td><td>1 (11.1)</td></tr><tr><td>Diabetes mellitus</td><td>4 (23.5)</td><td>2 (25.0)</td><td>2 (22.2)</td></tr><tr><td>Renal clearance (mL/min) [median (IQR)]</td><td>87.5 (56.9–104.4)</td><td>88.3 (52.5–101.4)</td><td>87.5 (58.8–104.4)</td></tr><tr><td>Site of prosthesis [n (%)]</td><td></td><td></td><td></td></tr><tr><td>Hip</td><td>8 (47.1)</td><td>4 (50.0)</td><td>4 (44.4)</td></tr><tr><td>Knee</td><td>6 (35.3)</td><td>4 (50.0)</td><td>2 (22.2)</td></tr><tr><td>Shoulder</td><td>1 (5.9)</td><td>0 (0)</td><td>1 (11.1)</td></tr><tr><td>Ankle</td><td>1 (5.9)</td><td>0 (0)</td><td>1 (11.1)</td></tr><tr><td>Elbow</td><td>1 (5.9)</td><td>0 (0)</td><td>1 (11.1)</td></tr><tr><td>Positive blood cultures [n (%)]</td><td>4 (23.5)</td><td>1 (12.5)</td><td>3 (33.3)</td></tr><tr><td>Severity [n (%)]</td><td></td><td></td><td></td></tr><tr><td>Septic shock</td><td>1 (5.9)</td><td>0 (0)</td><td>1 (11.1)</td></tr><tr><td>Volume expansion</td><td>1 (5.9)</td><td>0 (0)</td><td>1 (11.1)</td></tr><tr><td>Before dalbavancin treatment</td><td></td><td></td><td></td></tr><tr><td>Biological analysis [median (IQR)]</td><td></td><td></td><td></td></tr><tr><td>White blood cell count (× 1000/L)</td><td>8.5 (7.1–10.9)</td><td>8.4 (7.0–10.3)</td><td>8.5 (8.1–14.3)</td></tr><tr><td>Haemoglobin (g/dL)</td><td>10.6 (9.6–12.9)</td><td>10.3 (9.4–11.6)</td><td>11.8 (9.8–13.3)</td></tr><tr><td>Absolute neutrophil count (× 1000/L)</td><td>5.8 (5.0–8.2)</td><td>5.5 (5.3–6.9)</td><td>6.0 (4.7–10.3)</td></tr><tr><td>Eosinophil count (× 1000/L)</td><td>0.2 (0.1–0.4)</td><td>0.3 (0.2–0.4)</td><td>0.2 (0.1–0.2)</td></tr><tr><td>C-reactive protein (mg/L)</td><td>41.0 (18.3–75.8)</td><td>21.0 (13.0–58.0)</td><td>41.0 (30.5–123.0)</td></tr><tr><td>Surgical treatment [n (%)]</td><td></td><td></td><td></td></tr><tr><td>DAIR</td><td>9 (52.9)</td><td>5 (62.5)</td><td>4 (44.4)</td></tr><tr><td>Exchange</td><td>5 (29.4)</td><td>2 (25.0)</td><td>3 (33.3)</td></tr><tr><td>Synovectomy</td><td>1 (5.9)</td><td>1 (12.5)</td><td>0 (0)</td></tr><tr><td>Joint aspiration</td><td>1 (5.9)</td><td>0 (0)</td><td>1 (11.1)</td></tr><tr><td>Previous antibiotic treatments [n (%)]</td><td>16 (94.1)</td><td>8 (100)</td><td>8 (88.9)</td></tr><tr><td>Number of lines [median (IQR)]</td><td>2.0 (1.0–3.0)</td><td>3.0 (1.8–4.0)</td><td>2.0 (1.0–3.0)</td></tr><tr><td>Duration (days) [median (IQR)]</td><td>34.5 (31.3–46.8)</td><td>33.0 (31.5–41.5)</td><td>36.0 (28.5–46.5)</td></tr><tr><td>Microbiology analysis [n (%)]</td><td></td><td></td><td></td></tr><tr><td>Documented infections</td><td>16 (94.1)</td><td>7 (87.5)</td><td>9 (100)</td></tr><tr><td>Polymicrobial infections</td><td>5 (31.3)</td><td>2 (28.6)</td><td>3 (33.3)</td></tr><tr><td>Staphylococcus spp.</td><td>16 (100)</td><td>7 (100)</td><td>9 (100)</td></tr><tr><td>Staphylococcus aureus</td><td>10 (62.5)</td><td>5 (71.4)</td><td>5 (55.6)</td></tr><tr><td>Methicillin-resistant S. aureus</td><td>1 (6.3)</td><td>1 (14.3)</td><td>0 (0)</td></tr><tr><td>Coagulase-negative staphylococci</td><td>10 (62.5)</td><td>4 (57.1)</td><td>6 (66.7)</td></tr><tr><td>Staphylococcus epidermidis</td><td>7 (43.8)</td><td>3 (42.9)</td><td>4 (44.4)</td></tr><tr><td>Methicillin-resistant S. epidermidis</td><td>4 (25.0)</td><td>2 (28.6)</td><td>2 (22.2)</td></tr><tr><td>Enterococcus faecalis</td><td>1 (6.3)</td><td>1 (14.3)</td><td>0 (0)</td></tr><tr><td>Reason for dalbavancin use [n (%)]<sup>b</sup></td><td></td><td></td><td></td></tr><tr><td>Clinical failure of previous antibiotic treatment</td><td>1 (5.9)</td><td>1 (12.5)</td><td>0 (0)</td></tr><tr><td>Adverse event of previous antibiotic treatment</td><td>8 (47.1)</td><td>4 (50.0)</td><td>4 (44.4)</td></tr><tr><td>Bacteria resistant to previous antibiotic treatment</td><td>2 (11.8)</td><td>0 (0)</td><td>2 (22.2)</td></tr><tr><td>Impossible venous access</td><td>2 (11.8)</td><td>1 (12.5)</td><td>1 (11.1)</td></tr><tr><td>Patient's autonomy</td><td>3 (17.6)</td><td>1 (12.5)</td><td>2 (22.2)</td></tr><tr><td>Early hospital discharge</td><td>5 (29.4)</td><td>1 (12.5)</td><td>4 (44.4)</td></tr><tr><td>Better compliance</td><td>4 (23.5)</td><td>1 (12.5)</td><td>3 (33.3)</td></tr><tr><td>Dalbavancin dosing regimen [n (%)]</td><td></td><td></td><td></td></tr><tr><td>1 dose, 1.5 g</td><td>3 (17.6)</td><td>2 (25.0)</td><td>1 (11.1)</td></tr><tr><td>2 doses, 7-day interval, 1.5 g × 2</td><td>8 (47.1)</td><td>4 (50.0)</td><td>4 (44.4)</td></tr><tr><td>2 doses, 14-day interval, 1.5 g, 1 g</td><td>1 (5.9)</td><td>0 (0)</td><td>1 (11.1)</td></tr><tr><td>3 doses, 7-day interval, 1.5 g × 3</td><td>1 (5.9)</td><td>0 (0)</td><td>1 (11.1)</td></tr><tr><td>7 doses, 7-day interval, 1 g × 1, 0.5 g × 6</td><td>1 (5.9)</td><td>1 (12.5)</td><td>0 (0)</td></tr><tr><td>10 doses, 14-day interval, 1 g × 1, 0.5 g × N</td><td>1 (5.9)</td><td>1 (12.5)</td><td>0 (0)</td></tr><tr><td>Suppressive, 21-day interval</td><td>2 (11.8)</td><td>0 (0)</td><td>2 (22.2)</td></tr><tr><td>1.5 g × 1, 0.5 g × N</td><td>1 (5.9)</td><td>0 (0)</td><td>1 (11.1)</td></tr><tr><td>1.5 g × 3, 0.5 g × N</td><td>1 (5.9)</td><td>0 (0)</td><td>1 (11.1)</td></tr></tbody></table>

IQR, interquartile range; DAIR, debridement, antibiotics and implant retention; N: number of subsequent doses.

<footnote>a Methotrexate followed by corticosteroid treatment.</footnote>

<footnote>b Patients could have several reasons for dalbavancin use.</footnote>
<table><caption>**Table 2**
Review of studies of prosthetic joint infections (PJIs) treated by dalbavancin: bacteria, preferential administration regimen and outcome</caption><thead><tr><th>Author, year</th><th>Method</th><th>PJI [n (%)]</th><th>Bacteria involved [n (%)]</th><th>Preferential scheme [n (%)]</th><th>Monotherapy [n (%)]</th><th>Cure [n (%)]</th></tr></thead><tbody><tr><td>Bouza et al., 2018 [11]</td><td>Multicentric retrospective study All infections treated with dalbavancin (Spain)</td><td>n = 20/69 (29.0%)</td><td>MRSA (n = 3; 15.0%)<br>MSSA (n = 1; 5.0%)<br>CoNS (n = 13; 65.0%)<br>Enterococcus sp. (n = 1; 5.0%)<br>Other (n = 1; 5.0%)<br>Negative culture (n = 1; 5.0%)</td><td>N/A</td><td>N/A</td><td>16/20 (80.0%)</td></tr><tr><td>Wunsch et al., 2019 [10]</td><td>Multicentric retrospective study All infections treated with dalbavancin (Austria)</td><td>n = 32/101 (31.7%)</td><td>N/A</td><td>N/A</td><td>N/A</td><td>29/32 (90.6%)</td></tr><tr><td>Morata et al., 2019 [5]</td><td>Multicentric retrospective study All BJIs treated with at least one dose of dalbavancin (Spain)</td><td>PJI, n = 19<br>Implant-associated infection, n = 45</td><td>Among the implant-associated infection group (n = 45):<br>Polymicrobial (n = 5; 11.1%)<br>Staphylococcus epidermidis (n = 26; 57.8%)<br>MSSA (n = 4; 8.9%)<br>Staphylococcus lugdunensis (n = 2; 4.4%)<br>Staphylococcus capitis (n = 1; 2.2%)<br>Streptococcus pneumoniae (n = 1; 2.2%)<br>Enterococcus faecalis (n = 4; 8.9%)<br>Enterococcus faecium (n = 3; 6.4%)<br>Corynebacterium striatum (n = 2; 4.4%)<br>Anaerobes (n = 2; 4.4%)<br>Negative culture (n = 3; 6.7%)</td><td>N/A</td><td>Implant-associated infection group, (15/45; 33.3%)</td><td>Among the implant-associated infection group (n = 45):<br>31/45 (68.9%)<br>- Implant retention (n = 15; 33.3%)<br>- Implant removal (n = 16, 35.6%)</td></tr><tr><td>Tobudic et al., 2019 [9]</td><td>Monocentric retrospective study SSTI and BJI treated with dalbavancin (Austria)</td><td>n = 8/72 (11.1%)</td><td>N/A</td><td>N/A</td><td>N/A</td><td>3/8 (37.5%)</td></tr><tr><td>Buzón Martín et al., 2019 [6]</td><td>Monocentric retrospective study PJI treated with dalbavancin (Spain)</td><td>n = 16</td><td>CoNS (n = 7; 43.8%)<br>MRSA (n = 4; 25.0%)<br>E. faecium (n = 4; 25.0%)<br>E. faecalis (n = 1; 6.3%)</td><td>1500 mg d1, followed by 1000 mg every 14 days (n = 7; 87.5%)<br>1000 mg d1, followed by 500 mg weekly (n = 1; 12.5%)<br>Duration median (range): 12 (6–32) weeks</td><td>n = 11 (68.8%)</td><td>12/16 (75.0%)</td></tr><tr><td>Present study</td><td>Multicentric retrospective study PJI treated with dalbavancin (France)</td><td>n = 17</td><td>Polymicrobial (n = 5; 29.4%)<br>MSSA (n = 9; 52.9%)<br>MRSA (n = 1; 5.9%)<br>Methicillin-susceptible CoNS (n = 6; 35.3%)<br>MRSE (n = 4; 23.5%)</td><td>1500 mg d1 + 500 mg d7, followed by 500 mg biweekly for 2 months (hip) or 3 months (knee) (n = 9; 56.3%)<br>Other regimens (n = 7; 43.8%)<br>1500 mg d1 (n = 3; 17.6%)<br>1500 mg d1 + 1500 mg d7 (n = 8; 47.1%)<br>Other regimens (n = 7; 41.2%)</td><td>n = 8 (47.1%)</td><td>8/17 (47.1%)</td></tr></tbody></table>

BJI, bone and joint infection; CoNS, coagulase-negative staphylococci; d, day; MRSA, methicillin-resistant *Staphylococcus aureus*; MRSE, methicillin-resistant *Staphylococcus epidermidis*; MSSA, methicillin-susceptible *S. aureus*; N/A, not available; SSTI, skin and soft-tissue infection.

tion. Dalbavancin is an antibiotic active against Gram-positive cocci with a long half-life and in vitro biofilm activity. There are few studies in the literature on the use of dalbavancin during bone and joint infection, especially PJI [5,9–11], and only one focused solely on PJI [6]. Here we describe the specific use of dalbavancin in PJI among a previously published French cohort of dalbavancin use in real life.

In our cohort, clinical cure was achieved in 8/17 patients (47.1%), which is lower than usually reported, despite the low MICs

of bacteria involved regarding EUCAST breakpoints (0.125 mg/L for staphylococci) [12].

However, in our study, dalbavancin was mostly used in salvage condition and polymicrobial infections. Polymicrobial infections occurred in five cases, which might explain the low cure rate of our study. Indeed, polymicrobial infections during PJI are infrequent and are associated with poor prognosis [13,14]. Moreover, as in everyday practice, our patients were older, had numerous comorbidities and had already benefited from several antibiotic ther-
apies compared with previous studies, as in everyday practice. Al-
though our sample size is small, our patients appeared more se-
vere in the failure group, with one sepsis, one septic shock and
one patient managed without surgery.

Also, Morata et al. reported a favourable outcome in 15/23 pa-
tients (65.2%) when the implant was retained and 16/21 (76.2%)
when the implant was removed, suggesting the paramount impor-
tance of effective surgery [5]. It is of note that most of our patients
were managed with DAIR.

Furthermore, in the literature review, we noted that CoNS (60.2%) were the most predominant pathogens, whereas in our study we noted one-half CoNS and one-half S. aureus.

Finally, in our study as well as in the literature, dalbavancin ad-
ministration schemes were heterogenous. The study plan of Rappo
et al. regarding the use of dalbavancin in osteomyelitis included
two doses of dalbavancin at a 1-week interval [3] and was the
main represented scheme in our study, even if the dosing scheme
varied.

The limits of our study and the review of the available data
were the small number of patients and the heterogeneity of mi-
crobiology and dalbavancin use including administration regimen
and dosage.

For all cases of PJI treated with dalbavancin available in the lit-
erature, the overall results were favourable in 68/93 cases (73.1%).
Regardless of the dose, the treatment appears to be well tolerated
as described in the literature [15].

5. Conclusions

Our study and literature data suggest that the use of dalba-
vancin in PJI could be considered, even in salvage therapy. Over-
all, dalbavancin appears to be a safe and easy treatment for the
management of outpatients. We need more prospective studies
and randomised clinical trials to confirm these preliminary results.
Moreover, the prolonged treatment for PJI requires an optimisa-
tion of administration schedules. Pharmacological assays of resid-
ual concentrations would allow standardisation of practices.

Acknowledgments

The authors acknowledge as co-authors all of the following Dal-
bavancin French Study Group members: Chandra Adjodah (Hos-
pital of Montreuil-sur-Mer); Assi Assi (Les Fleurs Clinic, Toulon);
Nicolas Baclet and Pierre Weyrich (University Hospital of Lille);
Odile Bouchard (Clinic of Avignon); Alexandre Bleibtreu (La Pitié-
Salpétrière University Hospital, AP-HP, Paris); Frédérique Bouc-
hand, Benjamin Davido, Aurélien Dinh, Clara Duran and Mor-
gan Matt (Raymond-Poincaré University Hospital, APHP, Garches);
David Boutoille and Raphaëlle Riou (University Hospital of Nantes);
Guillaume Brunin (Hospital of Boulogne-sur-Mer); Philippe Cabaret
(Saint Philibert-Saint Vincent de Paul Hospitals, GHICL, Lille); Fab-
rice Camou (University Hospital of Bordeaux); Daniel Carbognani
(Clinic of Perpignan); Pascal Chavanet (University Hospital of Di-
jon); Johan Courjon and Romain Lotte (University Hospital of Nice);
Pierre Delobel (University Hospital of Toulouse); Eric Denis (Hos-
pital of Antibes); Cédric Etienne (Hospital of Grasse); Hélène Fer-
rand (Hospital of Libourne); Gabriela Illes and Flore Lacassin-Beller
(Hospital of Mont-de-Marsan); Yves Imbert (Hospital of Agen);
Sophie Leautez-Nainville (Hospital of La-Roche-sur-Yon); Cather-
ine Lechiche (Carémeau University Hospital, Nîmes); Vincent Le
Moing and Boris Monnin (University Hospital of Montpellier);
Bouchra Loutfi (University Hospital of Mont-de-Marsan); Rafael

Mahieu (University Hospital of Angers); Natacha Mrozek (Univer-
sity Hospital of Clermont-Ferrand); Patricia Pavese (University Hos-
pital of Grenoble); Nicolas Rouanes (Hospital of Périgueux); Nicolas
Rouzic (University Hospital of Lorient); Eric Senneville (Hospital of
Tourcoing); Jean-Philippe Talarmin and Lydie Khatchatourian (Uni-
versity Hospital of Quimper); Pierre Tattevin and Silvia Limonta
(Pontchaillou University Hospital, Rennes).

Funding: None.

Competing interests: MM has received personal fees for congress support. All other authors declare no competing interests.

Ethical approval: Considering the retrospective study design,
data collection from pre-existing medical records, and respect for
the anonymity of the patients included (referred to as studies 'Hors
Loi Jardé' in France), no ethical approval or administrative approval
was necessary for this study. This study was submitted to the local
Data Protection Officer (DPO) and, upon approval, was identified in
the hospital study registry. The research was conducted in accor-
dance with the Declaration of Helsinki.

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