Real world use of dalbavancin for bone and joint infections: a retrospective case series in adults and children

Abstract

Background

Bone and joint infections (BJIs) often require prolonged parenteral therapy, with challenges of hospitalization and vascular access [1–4]. Dalbavancin, a long-acting lipoglycopeptide, enables once-weekly dosing [7–10]. This study reports real-world outcomes of dalbavancin, used off-label in adults and children with BJIs.

Methods

We conducted a retrospective, single-centre case series of 14 consecutive patients (10 adults, 4 paediatric) with Gram-positive BJIs treated between January 2024 and April 2025. All received ≥ 3 weekly dalbavancin doses (definitive therapy), with oral step-down to complete a total treatment course of 8–12 weeks. Demographics, microbiology, therapy and outcomes were assessed with ≥ 6 months follow-up. MICs were tested using E-test strips; results interpreted using CLSI 2021 breakpoints [12]. Off-label nature of therapy was noted.

Results

Median age was 36 years (range 5–80), including 4 paediatric patients. MRSA accounted for 57% of the isolates. Dalbavancin MICs were consistently low (≤ 0.064 mg/L) [12, 14]. Median prior antibiotic exposure was 10 days before switch over to dalbavancin. All patients achieved end-of-therapy cure defined as the resolution of signs and symptoms of infection with no requirement for additional antibiotics for the primary infection and no recurrence. At 6 months, 92.9% patients remained infection-free while one patient who was still under follow up, showed sustained clinical improvement. Therapy was well tolerated with only two mild, self-limiting adverse events but all paediatric patients tolerated therapy well with no adverse events.

Conclusion

Dalbavancin, used off-label, demonstrated high level of efficacy, tolerability and outpatient feasibility in this small consecutive cohort, supporting its potential role as a treatment option for complex BJIs, including paediatric and bacteraemia-associated cases. Its pharmacokinetics enable streamlined therapy and reduced healthcare utilisation, supporting its role as a valuable therapeutic option for outpatient parenteral therapy [17-19, 21].

Introduction

Bone and joint infections (BJIs), including osteomyelitis, septic arthritis and spondylodiscitis are challenging due to deep-seated pathology, biofilm formation and prolonged intravenous (IV) therapy requirements. Conventional management relies on weeks of vancomycin or daptomycin, necessitating long-term vascular access and exposing patients to risks of catheter-related infection, nephrotoxicity and high healthcare costs [1–4].

Methicillin-resistant Staphylococcus aureus (MRSA) remains the most problematic pathogen [5, 6]. While vancomycin has been the mainstay, limitations such as nephrotoxicity, therapeutic drug monitoring, and “MIC creep” highlight the need for alternatives [6]. Other options like daptomycin and linezolid also have constraints, including daily dosing, myelotoxicity and expense.

Dalbavancin, a second-generation lipoglycopeptide, offers potent Gram-positive activity, including against MRSA and an exceptionally long half-life (~ 347 h), enabling once-weekly dosing [7, 8].

While approved for acute bacterial skin and skin structure infections, its use in BJIs, especially paediatric, is off-label. Increasing case series suggest utility [9–18].

However, data in heterogeneous cohorts especially those including paediatric patients, bacteraemia, and implant-associated disease remain limited. This retrospective case series describes real-world outcomes of 14 patients treated with dalbavancin as a definitive therapy for BJIs, contributing evidence on efficacy, safety and pragmatic utility in real-world care with evaluating MIC values relative to comparator agents and highlight dalbavancin’s role in OPAT.

Methods

Study design and patient selection

A retrospective, observational case series was conducted for all patients who received at least three doses of dalbavancin for the treatment of a confirmed Gram-positive BJI at our institution between January 2024 and April 2025. The study was approved by the Institutional Review Board with a waiver for informed consent due to its retrospective nature. Inclusion criteria: age ≥ 1 year, confirmed osteomyelitis, septic arthritis, spondylodiscitis or implant-associated infection (clinical, radiological and microbiological), dalbavancin as definitive therapy (≥ 3 weekly doses) and ≥ 6 months follow-up. Exclusion criteria: polymicrobial infection requiring Gram-negative/antifungal therapy, incomplete dalbavancin therapy.

Data collection

Standardised abstraction by two investigators. Demographics, comorbidities, infection type, microbiology, therapy with concomitant surgical interventions and outcomes along with safety profile were extracted from records. Definitions were aligned with IDSA osteomyelitis criteria [6]. Prior antibiotics (median duration 10 days, range 5–14) were administered for the same infection episode before switching to dalbavancin as definitive therapy.

Definitions

• Clinical Cure: Resolution of signs and symptoms of infection (e.g., pain, erythema, swelling, drainage), normalization or significant improvement of inflammatory markers (CRP and ESR), and no requirement for additional systemic antibiotic therapy for the primary infection at EOT.

• Recurrence: The reappearance of signs and symptoms of infection at the original site within 6 months after completing dalbavancin therapy, requiring a new course of antimicrobial therapy or surgical intervention.

• AE: Any untoward medical occurrence in a patient administered a pharmaceutical product, which did not necessarily have a causal relationship with the treatment.

Microbiological methods

Specimens (tissue, bone, pus, synovial fluid, blood) were processed per standard laboratory protocols. Isolation and identification of pathogens were performed using the VITEK 2 Compact automated system (bioMérieux, France). Antimicrobial susceptibility testing (AST) was conducted and interpreted according to the CLSI M100 2021 and EUCAST v7.1 breakpoints [19]. Dalbavancin MICs tested by E-test (bioMérieux) on Mueller-Hinton agar, without polysorbate-80. Interpreted per CLSI 2021 (susceptible ≤ 0.25 mg/L) [19]. QC strains used: S. aureus ATCC 29,213, E. faecalis ATCC 29,212. Limitations of E-test interpretation acknowledged [20, 21] (Fig. 1).

Fig. 1.

Potent in vitro activity of dalbavancin

Visual confirmation of a low dalbavancin MIC (0.064 mg/L) via E-test strip from a patient with osteomyelitis, demonstrating potent activity against the causative pathogen well below the susceptibility breakpoint.

Descriptive statistics were used for data analysis. Categorical variables were expressed as counts and percentages. For the primary outcome of clinical cure rate, the 95% confidence interval was calculated using the rule of three (3/n) to account for the small sample size and the observation of zero events. Software: SPSS v27. Missing data noted explicitly.

Results

This section presents an integrated summary of the patient demographics, infection characteristics, microbiological data, treatment regimens, clinical outcomes, and safety analyses for the cohort of 14 patients (10 adults, 4 paediatric) treated with dalbavancin.

Cohort demographics and clinical characteristics

A total of 14 patients with confirmed Gram-positive bone and joint infections (BJIs) were included in this retrospective case series. The cohort consisted of 10 adults (71.4%) and 4 paediatric patients (28.6%), with a median age of 36 years (interquartile range: 12–58 years, range 5–80 years). The majority were male (11/14, 78.6%). Common comorbidities included diabetes mellitus (4/14, 28.6%) and hypertension (3/14, 21.4%). Importantly, no patients had baseline renal or hepatic impairment that would contraindicate dalbavancin use (Table 1).

Table 1.

Baseline demographics and clinical characteristics (n = 14)

Sr. no	Sex & Age	Weight	Co-morbidity	Diagnosis	Surgical Intervention	Pathogen	Prior antibiotics	Duration of therapy	ADR	Clinical cure EOT	6 months follow-up
1	12 years, Male	28 kg	–	Acute right calcaneum OM + MRSA bacteraemia	I&D + antibiotic impregnated beads	MSSA	Cipro floxacin, Linezolid	8 weeks	–	Yes	Healed
2	10 years Male	26 kg	–	Acute right proximal tibia OM + MRSA bacteraemia	I&D + antibiotic impregnated beads	MRSA	–	12 weeks	–	Yes	Healed
3	26 years Male	72 kg	–	Chronic left tibia OM	I&D + antibiotic impregnated beads	MR-CoNS S.hemolyticus	Linezolid, TMP-SMX	12 weeks	–	Yes	Healed
4	43 years Male	76 kg	HTN, HBsAg+	Acute right tibia OM – implant related	I&D + implant removal	MSSA	–	12 weeks	–	Yes implant removed	Healed
5	38 years Male	69 kg	–	Acute on chronic right proximal tibia OM	I&D + antibiotic impregnated beads	MSSA	Amoxycillin Clavulanic acid, Linezolid, Cipro floxacin	12 weeks	IV infusion site pruritis	Yes	Healed
6	58 years Male	74 kg	DM	Acute left shoulder OM	I&D + antibiotic impregnated beads	MRSA	Vanco mycin	12 weeks	–	Yes	Healed
7	13 years Male	27 kg	–	Acute on chronic left humerus OM	I&D + antibiotic impregnated beads	MSSA	CloxacillinTMP-SMX	12 weeks	–	Yes	Healed
8	34 years Male	68 kg	–	Acute on chromic right proximal tibia OM	I&D + implant removal	MRSA	Linezolid, Metronidazole, Amoxicillin-Clavulanic acid	12 weeks	–	Yes	Healed
9	76 years Male	58 kg	DM	Acute right elbow septic arthritis – implant related	I&D + implant removal	MRSA	Linezolid	8 weeks	–	Yes implant removed	Healed
10	80 years Male	55 kg	HTN	Acute lumbar spondylodiscitis	Lumbar fixation and debridement	MSSA	-	15 weeks	–	Yes	Healed
11	5years Male	18 kg	–	Acute Tibia OM + MRSA bacteraemia	I&D + antibiotic impregnated beads	MRSA	Amoxycillin-Clavulanic, Linezolid	10 weeks	–	Yes	Healed
12	58 years Female	62 kg	HTN	Acute Thoraco-lumbar spondylodiscitis	Dorso lumbar fixation with debridement	MRSA	Meropenem	16 weeks	–	Yes	Ongoing
13	53 years Male	64 kg	DM, HTN, IHD	Chronic right elbow OM	I&D	MSSA	Linezolid, Doxycycline	12 weeks	Infusion related chills	Yes	Healed
14	65 years Female	58 kg	DM	Right otitis media with acute on chronic skull base OM	Mastoidectomy	MRSA	Ciprofloxacin, Minocycline	16 weeks	–	Yes	Healed

Sr. no: Serial Number; Co-morbidity: HTN: Hypertension, DM: Diabetes Mellitus, IHD: Ischemic Heart Disease, HBsAg+: Hepatitis B surface Antigen Positive, Diagnosis: OM: Osteomyelitis, MRSA: Methicillin-resistant Staphylococcus aureus, MSSA: Methicillin-susceptible Staphylococcus aureus, MR-CoNS: Methicillin-resistant Coagulase-Negative Staphylococci, Surgical Intervention: I&D: Incision and Drainage, Prior antibiotics: TMP-SMX: Trimethoprim-Sulfamethoxazole, ADR: Adverse Drug Reaction, IV: Intravenous; Clinical cure EOT: Clinical cure at End of Therapy, 6 months follow-up: Clinical status at the 6-month follow-up visit

Demographics and treatment outcomes of a case series demonstrating the successful use of long-course Dalbavancin therapy for complex bone and joint infections, including 3 cases with bacteraemia and prior treatment failure.

The most frequent infection type was osteomyelitis (10/14, 71.4%), followed by spondylodiscitis (2/14, 14.3%), septic arthritis (1/14, 7.1%), and skull base osteomyelitis secondary to otitis media (1/14, 7.1%). Two cases (14.3%) were implant-associated, and three (21.4%) were associated with concomitant S. aureus bacteraemia.

Microbiological profile

All infections were monomicrobial. Methicillin-resistant Staphylococcus aureus (MRSA) was isolated in 8 patients (57.1%), methicillin-susceptible S. aureus (MSSA) in 5 (35.7%), and methicillin-resistant coagulase-negative staphylococcus (MR-CoNS) in 1 (7.1%) (Fig. 2).

Fig. 2.

Predominance of Methicillin-Resistant Staphylococci in Complex Bone and Joint Infections. Pathogen distribution pie chart revealing MRSA as the leading cause (57%) of Gram-positive BJIs in this cohort, underscoring the challenge of antimicrobial resistance in this setting

Dalbavancin MICs were consistently low (median 0.064 mg/L; range 0.032–0.064 mg/L, consistent with prior reports [13–15, 22]. All isolates demonstrated good susceptibility to dalbavancin, confirming robust in vitro activity [19] (Fig. 3).

Fig. 3.

Uniform and potent in vitro susceptibility to dalbavancin

Cumulative distribution of dalbavancin MIC values for all 14 Gram-positive isolates. All MICs cluster at the lowest end of the scale (≤ 0.064 mg/L), confirming consistent and excellent in vitro susceptibility against all staphylococcal pathogens, including MRSA. The vertical dashed line represents the susceptible breakpoint (≤ 0.25 mg/L) as defined by CLSI and EUCAST guidelines. All isolates exhibited MIC values well below this threshold, confirming uniform and excellent in vitro susceptibility.

Dalbavancin and Vancomycin were effective against all isolates.(100% susceptibility). >90% susceptibility was observed for linezolid, teicoplanin, and tetracycline. The data reveals high resistance to clindamycin (64.3% resistant), macrolides (Erythromycin, 71.4% resistant) and fluoroquinolones (ciprofloxacin/Levofloxacin, ~ 79% resistant) The Oxacillin susceptibility rate of 42.9% confirms that 57.1% of the isolates were MRSA, which aligns perfectly with our pathogen distribution data (Fig. 4).

Fig. 4.

Cumulative susceptibility profile of staphylococcal isolates (n = 14) to key antimicrobial agents: Antibiogram of staphylococcal isolates showing universal susceptibility to dalbavancin and vancomycin, contrasted with high resistance rates to fluoroquinolones, clindamycin, and beta-lactams, positioning dalbavancin as a critical therapeutic option. All isolates were susceptible to dalbavancin and vancomycin. High rates of resistance were observed to clindamycin, macrolides (erythromycin), fluoroquinolones (ciprofloxacin, levofloxacin), and beta-lactams (oxacillin)

A notable finding from the microbiological analysis was the consistent and potent in vitro activity of dalbavancin against all isolated pathogens. The dalbavancin MIC values were remarkably low, ranging from 0.032 to 0.064 mg/L, with a median of 0.064 mg/L.

Importantly, all 14 isolates demonstrated MIC values well below the established susceptibility breakpoint of ≤ 0.25 mg/L. (Table 2)

Table 2.

In vitro activity of Dalbavancin against Staphylococcal isolates from bone and joint infections: evaluation of our data with MIC profiles

Organism	Number of Isolates	Dalbavancin MIC Range (mg/L)	% Susceptible
All Isolates	14	0.032–0.064	100%
Methicillin-resistant S. aureus (MRSA)	8	0.064	100%
Methicillin-susceptible S. aureus (MSSA)	5	0.047–0.064	100%
Coagulase-Negative Staphylococci (CoNS)	1	0.032	100%

MICs were determined using E-test methodology. All MIC values were well below the established susceptibility breakpoint of ≤ 0.25 mg/L defined by both CLSI and EUCAST guidelines, confirming potent in vitro activity against all Gram-positive pathogens isolated in this cohort [19].

Treatment regimens

Furthermore, it is significant to highlight that all 14 patients included in this series were prescribed dalbavancin after failing to respond adequately to previous antibiotic regimens, which included agents such as linezolid, vancomycin, fluoroquinolones, and beta-lactams. This context emphasizes the critical role dalbavancin played as a definitive therapy in achieving a successful clinical outcome in these complex cases.

Among adults, all received a 1 g loading dose followed by 500 mg weekly. Paediatric patients (n= 4) received weight-based dosing: a loading dose of 22 mg/kg (range 18–22.5 mg/kg), followed by 18 mg/kg weekly (12 mg/kg in some cases). Each child received 3 weekly doses. The median treatment duration was 12 weeks (range 8–16 weeks). Outpatient administration was achieved in all cases, and 64.3% (9/14) had received prior antibiotic therapy. All outpatient dosing regimens aligned with PK data from prior studies [8, 10].

Clinical and microbiological outcomes

At the end of therapy, all 14 patients achieved clinical cure (95% CI: 76.8–100%) defined as the resolution of signs and symptoms of infection with no requirement for additional antibiotics for the primary infection. The 95% confidence interval, calculated using the rule of three for small samples with 0 events, is approximately 77% to 100%.

At 6-month follow-up, 13 patients (92.9%) were infection free, while one patient was still under follow up but showed clinical improvement. (thoracolumbar spondylodiscitis). No relapses were recorded among patients with follow-up. Outcomes aligned with prior real-world cohorts [12–14, 16–18] (Fig. 5).

Fig. 5.

Sustained Treatment Success at Six-Month Follow-Up. Clinical outcomes demonstrating a high rate (92.9%) of sustained infection resolution six months after completing dalbavancin therapy, reinforcing its long-term efficacy in a complex patient cohort

Both implant-associated infections achieved cure after surgical intervention plus dalbavancin, and all 3 patients with concomitant bacteraemia achieved microbiological clearance with negative follow-up cultures.

Notably, one adult with spinal infection and paraplegia demonstrated neurological improvement (motor power grade 3).

The patient with temporal bone [skull base] osteomyelitis (a complex bone infection) recovered fully, consistent with dalbavancin’s known penetration into bone tissue.

Safety and tolerability

Dalbavancin was well tolerated, with no treatment discontinuations. Two mild, self-limiting adverse effects were noted: infusion-site itching (1 patient) and mild chills during infusion (1 patient). No hepatotoxicity or nephrotoxicity was documented.

Subgroup analyses

Paediatric patients (n = 4): All achieved clinical cure with good tolerance to weight-based dosing and no adverse events.

Adult patients (n = 10): All achieved cure; 2 experienced mild infusion-related reactions (20%).

Implant-associated infections (n = 2): Both achieved cure after combined surgical and antimicrobial management.

Concomitant bacteraemia (n = 3): All cleared bacteraemia with negative blood cultures.

Follow-up outcomes: At 6 months, 100% of paediatric patients were fully healed, compared with 80% of adults (p = 0.516).

Dalbavancin demonstrated high level efficacy (95% CI: 76.8–100%), a favourable safety profile, and successful outcomes across both adult and paediatric patients, including those with complex presentations (bacteraemia, implants, spinal infections).

Discussion

While a randomized controlled trial has established the efficacy of a two-dose dalbavancin regimen for osteomyelitis, data on extended weekly dosing in real-world settings, particularly in mixed adult-paediatric cohorts with complex infections, remains limited. Our series contributes practical insights into this specific application and adds to real-world evidence of efficacy and safety of dalbavancin for the treatment of BJIs [9, 12–14, 16, 23].

Outcomes were favourable, including in paediatric patients, a population underrepresented in prior studies [13, 14, 18]. Our regimen differed from Rappo’s RCT two-dose schedule [15], reflecting pragmatic OPAT use.

Our findings, demonstrating a 100% end-of-therapy cure rate and no relapses in patients with documented follow-up in a heterogeneous cohort that included paediatric patients, those with bacteraemia, and cases requiring surgical intervention, highlight its potential as a valuable therapeutic option for long-term parenteral therapy.

The most significant advantage of dalbavancin is its pharmacokinetic profile, which enables a once-weekly dosing regimen. This directly addresses a major challenge in BJI management: the requirement for prolonged IV antibiotic courses. By eliminating the need for long-term venous access, dalbavancin mitigates the risks of catheter-related bloodstream infections and thrombosis, reduces healthcare costs associated with nursing visits for drug administration, and significantly improves patient quality of life and adherence [9, 23]. In our cohort, the use of a 1 g/500 mg weekly regimen in most patients allowed for effective outpatient management from the outset of therapy.

The microbiological data from our series is highly reassuring. The dalbavancin MIC values for all isolates, including MRSA, were consistently and remarkably low (≤ 0.064 mg/L), which is well below the susceptible breakpoint [19]. This confirms potent in vitro activity and suggests a low risk of resistance development, a finding consistent with larger studies [10, 22].

The antibiogram also paints a familiar picture of multidrug-resistant staphylococci, where dalbavancin and vancomycin remain pillars of therapy, but resistance to fluoroquinolones and clindamycin is rampant, further justifying the choice of a potent lipoglycopeptide.

The safety profile observed was excellent. This aligns with the known safety profile of dalbavancin from clinical trials and other real-world studies, which report a lower rate of AEs compared to vancomycin, particularly with respect to nephrotoxicity[12, 24]. The ability to administer therapy without the need for therapeutic drug monitoring is another pragmatic advantage over vancomycin.

Strengths: Consecutive inclusion, clear definitions, and ≥ 6-month follow-up.

Antimicrobial stewardship: Dalbavancin simplifies outpatient therapy [1, 3, 9, 23] but high cost, off-label nature, prolonged half-life, lack of TDM, and emergent resistance warrant caution [20, 21]. Source control remains essential [6].

CNS: No claim of CNS penetration; dalbavancin has poor CSF penetration [15, 21].

The retrospective, single-centre design with a small sample size limit generalizability of the study. The absence of a comparator group prevents definitive efficacy comparisons with other antimicrobials. Furthermore, there is an inherent selection bias, as we only included patients who received at least three doses of dalbavancin, thereby excluding those who might have failed therapy early or were deemed unsuitable for this regimen. This high rate of clinical success was achieved within a comprehensive management strategy where most patients underwent indicated surgical intervention. Consequently, it is not possible to delineate the independent contribution of dalbavancin from that of source control.

Conclusion

Dalbavancin, though off-label for BJIs, demonstrated favourable outcomes and tolerability in this small consecutive series of adults and children.

Its unique pharmacokinetic profile facilitates a streamlined, entirely outpatient-based treatment model, effectively eliminating the need for long-term intravenous access and its associated complications. The potent in vitro activity, evidenced by consistently low MIC values, translated directly to a 100% rate of clinical cure in this challenging cohort of both adults and children. These findings suggest dalbavancin may be a highly effective and well tolerated alternative to traditional parenteral therapies, offering a simplified outpatient-based model for managing BJIs that can reduce cost of therapy and improve patient’s quality of life.

While source control remains fundamental, dalbavancin should be considered a potential alternative choice for definitive parenteral therapy in these settings. While it may represent a valuable treatment option, definitive conclusions require larger controlled studies [13–15, 17].

Abbreviations

AE

Adverse event

ABSSSI

Acute bacterial skin and skin structure infections

AST

Antimicrobial susceptibility testing

BJI

Bone and joint infection

CLSI

Clinical and laboratory standards institute

CNS

Central nervous system

CoNS

Coagulase-negative Staphylococci

CRP

C-reactive protein

ESR

Erythrocyte sedimentation rate

EUCAST

European Committee on Antimicrobial Susceptibility Testing

IQR

Interquartile range

OPAT

Outpatient parenteral antimicrobial therapy

SD

Standard deviation

Author contributions

Conceptualization: P.S.A., S.S., D.G; Data curation: P.S.A., S.S., D.G; Formal analysis: P.S.A., D.G.; Investigation: P.S.A., S.S., D.G., P.S.K., R.D. Methodology: P.S.A., S.S., D.G. Project administration: P.S.A. Resources: P.S.A., S.S., P.S.K., R.D. Supervision: P.S.A. Validation: P.S.A., D.G. Writing – original draft: P.S.A., S.S. Writing – review & editing: P.S.A., S.S., D.G., P.S.K., R.D.

Funding

None external; Dalbavancin (Dalbavan ^®) used for treatment in this case series was procured by the patients.

Data availability.

On request from the corresponding author.

Data availability

On request from the corresponding author.

Declarations

Ethics approval and consent to participate

This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Institutional Ethics Committee (IEC) of Maeers Vishwaraj Hospital, Pune. The IEC is duly registered with the Central Drugs Standard Control Organization (CDSCO), Government of India (Registration No. ECR/1138/Inst/MH/2018/RR-21). A waiver of informed consent was granted for this retrospective study. Due to the retrospective nature of this study, the institutional review board granted a waiver of informed consent in accordance with local ethics guidelines. All patient data were anonymized and handled in compliance with applicable privacy regulations.

Competing interests

The authors declare no competing interests.