The Use of Dalbavancin with a Dermal Substitute Application – a Case Report

Introduction

The application of dermal substitutes is currently becoming increasingly important in the local therapy of a wide range of acute and chronic full-thickness wounds [1]. Dermal substitutes provide two basic functions of the cutaneous dermal layer: control of pain and scarring. They act as matrices or scaffolds, promote new tissue growth and enhance wound healing. The control of the whole process of scarring after the application of dermal substitutes also leads to a reduction in the risk of pathological scars – hypertrophic or keloid scars [2].

One of the biggest challenges associated with the application of dermal substitutes in general is the risk of developing infectious complications – skin and soft tissue infections (SSTIs). A specific subunit of SSTIs, acute bacterial skin and soft tissue infections (ABSSTIs), is defined as a SSTI with a proven bacterial causative agent together with a minimum affected area of 75 cm² [3].

In this case report, we present a complicated case of multiple SSTIs in a young woman at high risk of developing phlebitis and significant intolerance to a variety of antimicrobials, in which we managed to control the dramatic picture with dalbavancin.

Case report

We describe the case of a 39-year-old woman with skin defects after fasciotomy of the left upper extremity and repeated SSTIs in various locations (neck, upper extremity and chest) caused by Streptococcus viridans and Staphylococcus epidermidis. As for medical history, she suffered from bronchial asthma, congenital deficiency of factor VII, antiphospholipid antibodies, cyclic leukopenia with neutropenia and phagocytic disorder, hypothyreosis after semithyreidectomy due to papillary carcinoma of the thyroid gland, sarcoidosis of lungs, endometriosis grade IV, repeated dysmicrobias and hypomotility of intestines. Furthermore, she had a history of repetitive phlebothrombosis, thrombophlebitis and acute disseminated intravascular coagulation.

Skin defects arose as a complication of a contusion of the left hemithorax, infraction of the ribs (left side) with hematoma followed by an infection. Despite the targeted antimicrobial therapy combined with Streptococcus viridans autovaccine, an abscess progressed along the tendon of the musculus pectoralis major to the left arm, causing massive swelling of the left forearm with paresthesia of the fingers. A fasciotomy of the left arm and forearm was performed. After many revisions of skin defects under general anesthesia, defects were finally covered with Matriderm® and STSG (split-thickness skin grafts) in total on 1.5% TBSA (total body surface area) (Figure 1).The introduction of a peripheral venous cannula guided by ultrasonography in the operating theatre led to a development of phlebothrombosis. Because of that, the cannula was extracted and dalbavancin therapy initiated (1-hour infusion) in accordance with the microbiological results. No further phlebothromboses occurred. The skin defect completely healed and the patient was discharged to our outpatient care and outpatient parenteral antibiotic therapy (outpatient parenteral antibiotic therapy (OPAT)) with C-reactive protein level of 2.7 mg/L. Over the next month, weekly follow-up visits were made and dalbavancin was applied three more times.

Discussion

The treatment of SSTIs is often complicated, in particular due to the ever-increasing resistance of pathogens resulting in the failure of standard antimicrobial treatment. New resistant strains keep emerging at a pace that the development of new drugs can match only with difficulties. Nevertheless, several promising antimicrobials have been registered in recent years.

Dalbavancin (trade names Dalvance® in the US and Xydalba® in Europe) is one such very potent antimicrobial drug with unique pharmacokinetic properties, suitable for long-term therapy. Dalbavancin is a bactericidal antibiotic from the lipoglycopeptide class (the second generation of glycopeptides). Lipoglycopeptides exert their bactericidal activity by binding to the D-alanyl-D-alanine residue on growing peptidoglycan chains, preventing transpeptidation and transglycosylation of disaccharide subunits and hence cell-wall formation. Even though the molecule of dalbavancin itself was defined in the 1980s, it was only approved for clinical application in 2014 (FDA – Food and Drug Administration and EMA – European Medicines Agency) [4]. SSTIs of adults constitute the only approved indication for dalbavancin. Dalbavancin is considered a potent drug effective against a wide spectrum of gram-positive bacteria – in particular, against Staphylococcus aureus including MRSA (methicillin-resistant Staphylococcus aureus), Streptococcus sp., and Enterococcus sp. [4].

The main advantage of dalbavancin is its unique, very long, biological half-time reaching 15.5 days (372 hours). It must be strictly used in intravenous dosage form only. There is no need to reduce the dosage of dalbavancin in patients with impaired kidney or hepatic function. Moreover, it is associated with only low occurrence of side effects compared to the glycopeptides of the first generation. Two regimes for dalbavancin administration are currently approved: the primary regime comprises an initial dose of 1000 mg of dalbavancin followed by another dose of 500 mg dosage after 7 days. As of 2016, it is also possible to administer only a single dose of 1500 mg in a 30-minute infusion (proved as non-inferior) [5].

A wide range of antimicrobial agents have been compared to dalbavancin in SSTIs (or, to be more precise, ABSSTIs) treatment. Table 1 shows the comparison of dalbavancin and antimicrobial agents most commonly used in ABSSTIs treatment. It details the MIC (minimal inhibitory concentration) of individual drugs in particular gram-positive pathogens.

Mostly, the effectiveness of dalbavancin was compared to that of vancomycin or linezolid. In all such comparisons, the effectiveness of dalbavancin was the same as in the case of the comparator (87–94% of successfully treated patients with dalbavancin and 91–93% of successfully treated patients with the comparator, respectively) [6].

Another study reports a higher success rate in patients treated with dalbavancin (33 patients, 1000 mg on day 1, followed by 500 mg on day 8) compared to patients treated with SOC (standard of care) vancomycin (34 patients, 1 g/12 hours for 14 days in the treatment of gram-positive catheter infection). Moreover, the non-inferiority of dalbavancin (administered both as 1000 mg on day 1, followed by 500 mg on day 8, and as a single dose of 1,500 mg) compared to linezolid or linezolid in sequential treatment in the therapy of SSTI was also proven [7]. In osteomyelitis treatment, better 3-month outcomes were reported for dalbavancin than for SOC (vancomycin/daptomycin for MRSA and cefazolin for MSSA) [8].

Conclusion

Dalbavancin represents a very potent bactericidal antibiotic with the intended use in the treatment of SSTIs caused by gram-positive bacteria. Owing to the advantages mentioned above, this drug is preferred mainly for OPAT. The greatest limitation nowadays is the price of dalbavancin. However, the OPAT concept allows us to rationalise costs for antimicrobial therapy (costs for OPAT represented only 15–44% of the costs of treatment during the hospital stay, depending on the diagnosis and used antimicrobial drug). OPAT is more comfortable for patients from the psychosocial perspective as well [9]. Besides, as long-term catheterization is not needed, the occurrence of catheter-related infections is negligible. Thanks to good pharmacokinetic properties, dalbavancin penetrates not just the skin but bones and synovial fluid as well and we can see an increase in off-label administrations [10,11]. This off-label use has been only, reported in a limited number of publications; however, there are lots of current clinical trials aiming to prove the superiority of dalbavancin in the treatment of osteomyelitis, infectious endocarditis or bloodstream infections (NCT03091439, NCT03426761, NCT0314 8756) [5].

Role of authors: Lipový, Hladík: Summary, Introduction, Case report, Discussion, Conclusion, Figure 1; Borilova-Linhartova, Hanslianova: Summary, Introduction, Discussion, Conclusion, Table 1.

Conflict of interest: None declared.

Disclosure: All procedures performed in this study involving human participant were in accordance with the Helsinki declaration and its later amendments or comparable ethical standards.

Funding: This research was supported by Ministry of Health of the Czech Republic, Grant No. 17-29874A, Grant No. NV19-05-00214. and Grant No. NU20-05-00166. All rights reserved.

Corresponding author

Martin Hladík, MD

University Hospital Brno

Department of Burns and Plastic Surgery

Jihlavská 20

625 00 Brno, Czech Republic

e-mail: hladikm@gmail.com

Submitted: 02. 11. 2020

Accepted: 02. 12. 2020