Dalbavancin for outpatient parenteral antimicrobial therapy of skin and soft tissue infections in a returning traveller
Skin and soft tissue infections (SSTIs) are among the most common health problems in travellers returning from tropical and subtropical countries. Importantly, the prevalence of Staphylococcus aureus, the most common pathogen for purulent SSTIs, with specific drug resistance, such as methicillin resistant Staphylococcus aureus (MRSA) and those expressing virulence genes, such as Panton-Valentine-leukocidin is higher in tropical regions than in most high resource settings. This poses challenges for the empirical antimicrobial treatment of SSTIs in returning travellers. This short report describes a patient with a recent travel history to Hong Kong, Singapore and the Philippines who presented with multiple mosquito bites on both upper extremities and secondary bacterial superinfection. He had previously been prescribed oral beta-lactam antimicrobial therapy but lacked adherence to this treatment. Based on the risk for MRSA infection and problems with treatment adherence to oral therapy an outpatient parenteral antimicrobial therapy with dalbavancin was administered on days 0 and 7. Microbiological culture confirmed presence of MRSA and clinical follow-up demonstrated complete remission of the SSTI within 2 weeks. Dalbavancin is a promising treatment option for empirical parenteral treatment of SSTIs in returning travellers, a population at high risk for beta-lactam resistant S. aureus skin infections.
KeywordsDalbavancin MRSA Staphylococcus aureus SSTI Travel medicine
Skin and soft tissue infections (SSTIs) are among the most common health problems in travellers returning from tropical and subtropical countries . Insect bites by blood-feeding arthropods constitute risk factors by creating entry sites for microorganisms, such as Staphylococcus aureus, the most common pathogen for purulent SSTIs. Studies have shown that S. aureus strains resistant to methicillin or encoding for exotoxins such as Panton-Valentine-leukocidin (PVL) are more prevalent in tropical regions than in most high resource settings [2, 3, 4]. While infection with methicillin-resistant Staphylococcus aureus (MRSA) limits the choice of available antimicrobial agents, PVL-positive strains of S. aureus are associated with unfavorable clinical outcomes [4, 5]. This pattern of drug resistance poses challenges for the empirical treatment of SSTIs in patients with a travel history to tropical countries. In addition, treatment adherence is often limited in multiple dose drug regimens further impacting the treatment outcomes of SSTIs [6, 7, 8].
Dalbavancin, a novel lipoglycopeptide, has been registered for the parenteral treatment of SSTIs [9, 10, 11, 12, 13, 14]. It has specific activity against Gram positive pathogens including MRSA. Importantly, based on its long elimination half-life it may be administered as a single dose therapy or in two divided doses within a 7-day interval. These two features, a high antibacterial activity and a long plasma half-life, make dalbavancin suitable for outpatient parenteral antimicrobial treatment (OPAT) of SSTIs. The OPAT is an approach of patient management associated with improved patient comfort, lower risk for nosocomial complications and cost savings for the health care system [15, 16].
In this short report, we present a case of an SSTI in a returning traveller from the tropics and outline the potential benefits that OPAT with dalbavancin could have for the empiric antimicrobial treatment of SSTIs in this population.
A 35-year-old male patient presented at the emergency unit of the hospital with cellulitis following multiple insect bites. The patient had returned 2 days earlier from a 3 week journey to Hong Kong, Singapore and the Philippines. During the last few days of his travel, he identified multiple insect bites on his arms, which soon became swollen and pruritic. Having undergone a traditional Filipino massage with ample application of massage oils on his body including the upper extremities, the swelling, inflammation and pruritus significantly deteriorated. Upon arrival in Austria, the patient attended the emergency department and was diagnosed with bacterial superinfection of mosquito bites. An oral beta-lactam antimicrobial treatment was prescribed and the patient discharged. The patient attended the infectious disease outpatient clinic of the hospital 2 days later with chills and a history of fever. The patient reported not to have taken the prescribed antibiotics since the first consultation. In physical examination five highly painful lesions of superinfected mosquito bites of the forearms were measured as up to 7 cm in diameter with marked signs of inflammation. Palpation was suggestive for abscess formation within the SSTI. Furthermore, tender axillary lymph nodes were palpated during physical examination. Subsequently a sterile needle was used to puncture all five abscesses, which resulted in abundant drainage of pus. Laboratory tests showed a slight elevation of the C‑reactive protein (2.1 mg/dl; normal range <0.5 mg/dl) and normal leukocyte counts (7.89×109/l).
The recent travel history to the tropics was considered as a risk factor for infection with MRSA and possibly also with a PVL expressing strain. Therefore, a swab of every lesion was sent for further microbiological analysis including nasal and multiple skin swabs to screen for colonization by MRSA. Based on the elevated risk of MRSA and lack of treatment adherence, OPAT with dalbavancin was initiated immediately. The first administration of 1000 mg dalbavancin was well-tolerated and the drained wounds were adequately covered with medical dressings. Thus, the patient was discharged and scheduled for a follow-up visit 1 week later. During the scheduled follow-up visit the patient reported that the chills had stopped within 24 h of dalbavancin administration. Microbiological test results confirmed the presence of MRSA in all abscesses and nasal mucosa. The putrid SSTI had largely convalesced, no further pus drained on application of manual pressure and tenderness had ceased. The second dose of dalbavancin (500 mg) was administered intravenously 7 days after initiation of treatment and a nasal ointment containing mupirocin was prescribed. Another follow-up visit was scheduled for the following week. When the patient appeared for this visit, complete remission had been achieved and no side effects were reported.
Strong geographic variability in microbiological epidemiology of SSTIs
Skin and soft tissue infections (SSTIs) are among the most common health problems in travellers returning from tropical and subtropical countries and S. aureus, is the most common pathogen of purulent SSTIs . Furthermore, there is evidence for a strong regional variability regarding the prevalence of S. aureus strains with specific drug resistance patterns and virulence factors [2, 3, 4]. An epidemiological study conducted in Sweden with returning travellers and immigrants, respectively, demonstrated that compared to Western Europeans the odds of being colonized by MRSA increases by a factor of 31.2 for people coming from South America, by 36.5 for people coming from East Asia, by 43.0 for people coming from Oceania and the Pacific Islands, by 46.4 for people coming from Sub-Saharan Africa and by 59.0 for people coming from North Africa including the Middle East . By contrast, people arriving from Southern Europe (OR 2.4) as well as returnees from Central and Eastern Europe (OR 2.8) had comparatively lower odds . Another study conducted in Germany investigated predictors associated with carriage of PVL-positive S. aureus in returning travellers presenting with an SSTI. They found that arriving from Africa increased the odds of PVL-positive S. aureus carriage by the factor of 4.2 (p = 0.005), by 3.3 (p = 0.3) if returning from the Middle East or Central Asia and by 3.4 (p = 0.1) if returning from Australia/Pacific .
Problems encountered in empirical oral antimicrobial therapy in certain migrant and traveller populations
This specific microbiological epidemiology may negatively impact treatment outcomes of conventional empirical antimicrobial therapy when prescribed for certain migrant and traveller populations. Good practice demands the prescription of the narrowest antimicrobial spectrum therapy as possible, usually oral beta-lactam antibiotics, which are not efficacious against MRSA. Furthermore, the choice of empirical antimicrobial therapies needs to be tailored according to the local microbiological epidemiology of the respective infection, including specific drug resistance patterns in order to remain efficacious . Therefore, an adaptation of empirical antimicrobial regimens that are common practice in a certain setting may be highly warranted if the attending physician suspects an altered etiological microbiology. Also, SSTIs with PVL-positive S. aureus may qualify for an adaptation of usual oral antimicrobial chemotherapies as they occur in both methicillin-sensitive S. aureus (MSSA) and MRSA and can be associated with unfavorable clinical outcomes, secondary spread of primary lesions and further with reduced antibiotic susceptibility [2, 4, 19].
Another issue that needs to be considered when infections with potentially virulent microbes are suspected is the inherent difficulties of oral drug delivery modes. Research has demonstrated that non-adherence to oral antimicrobial therapies occurs globally in both high-resource and low-resource settings and non-adherence was higher when the dosing regimen was more complex and the time period of drug administration was lengthier [6, 7, 8, 20, 21, 22, 23, 24, 25, 26]. Several publications in the field of malaria have even investigated in more detail the tremendous difficulties that multiple day oral therapies can entail on several stages of individual case management, thereby severely impacting on treatment outcomes [6, 7, 8, 23, 24, 25]. Artemisinin-combination therapies (ACTs), the state-of-the-art medicines for the treatment of uncomplicated malaria, have an almost ideal efficacy of above 95% in well-monitored clinical trials but may drop to an effectiveness of 77.8% under real-life conditions, due to patients’ difficulties adhering to the right schedule of drug dosing i. e. daily doses over 3 days [25, 27]. A similar study has been conducted with oral quinine, possessing an efficacy of 90% if multiple doses per day are given for multiple days, whose effectiveness dropped to 60% under real-life conditions [6, 28]. Of even more concern, studies have demonstrated that the effectiveness of ACTs may further drop down to 37% if additional healthcare system factors are considered [8, 23]. Therefore, single-dose treatments have been proposed to narrow this efficacy-effectiveness gap . As demonstrated in this manuscript, patients with difficulties adhering to multiple doses of an oral therapy may greatly benefit from treatment courses entailing only few and preferably only one dose.
Dalbavancin for empirical therapy of SSTIs in returning travellers – a novel treatment indication?
Dalbavancin, a novel lipoglycopeptide, has been registered for the parenteral treatment of SSTIs and could prove to be helpful in the empirical treatment of SSTIs in returning travellers [9, 10, 11, 12, 13, 14, 29, 30]. It was shown in up to phase 3 randomized controlled trials that dalbavancin has specific activity against Gram positive pathogens including MRSA and is safe and well-tolerable [10, 29, 30]. Importantly, due to its long elimination half-life of 8.5–16.5 days it is certain that bactericidal drug plasma levels are constantly maintained . It may be effectively administered in its original formulation of one dose of 1000 mg at baseline and a follow-up dose of 500 mg 7 days later or as a single dose of 1500 mg [30, 31]. These two features, a high antibacterial activity and a long plasma half-life, make dalbavancin suitable for OPAT of SSTIs involving only one to two patient contacts, thereby being potentially apt to minimize the aforementioned efficacy-effectiveness gap. Depending on the setting, OPAT, an approach of patient management, may be implemented at the patient’s home or at a hospital outpatient clinic by a health care expert and is associated with improved patient comfort, lower risk for nosocomial complications and cost savings for the health care system [15, 16]. Thus, OPAT with dalbavancin for returning travellers with an SSTI may indeed prove beneficial in terms of clinical effectiveness and patient well-being. Contrarily, the high costs of dalbavancin make it difficult to predict whether a programmatic endorsement of OPAT with dalbavancin for this new indication would be cost-effective. Therefore, further evaluation through health economics research would be valuable.
Skin and soft tissue infections (SSTIs) in travellers returning from tropical and subtropical countries are common . Furthermore, this population bears an increased carriage risk for virulent S. aureus strains, such as MRSA or those being PVL-positive [2, 3, 4]. Parenteral therapy with dalbavancin may prove particularly promising in this setting, as it exerts activity against S. aureus including MRSA and proved to be efficacious, well-tolerated and safe in clinical trials [9, 10, 11, 12, 13, 14]. Due to a long elimination half-life, it is further suitable as OPAT, which can be administered intravenously either as single short therapy (1500 mg once) or in two divided doses on day 0 (1000 mg) and day 7 (500 mg) [30, 31]. This short report highlights the potential benefits of OPAT of SSTIs with dalbavancin in certain migrants and returning travellers. The OPAT with dalbavancin regimen adequately addresses likely problems of specific drug resistance as well as the impending efficacy-loss of multiple-dose oral therapies.
We thank Archchun Ariyarajah for proofreading the manuscript.
Compliance with ethical guidelines
Conflict of interest
J. Mischlinger, H. Lagler, N. Harrison and M. Ramharter declare that they have no competing interests.
This article does not contain any studies with human participants or animals performed by any of the authors. Consent was obtained from all patients identifiable from images or other information within the manuscript. In the case of underage patients, consent was obtained from a parent or legal guardian.
- 4.Zanger P, Nurjadi D, Schleucher R, Scherbaum H, Wolz C, Kremsner PG, et al. Import and spread of Panton-valentine Leukocidin-positive staphylococcus aureus through nasal carriage and skin infections in travelers returning from the tropics and subtropics. Clin Infect Dis. 2012;54(4):483–92.CrossRefPubMedGoogle Scholar
- 12.Eckmann C, Lawson W, Nathwani D, Solem CT, Stephens JM, Macahilig C, et al. Antibiotic treatment patterns across Europe in patients with complicated skin and soft-tissue infections due to meticillin-resistant Staphylococcus aureus: a plea for implementation of early switch and early discharge criteria. Int J Antimicrob Agents. 2014;44(1):56–64.CrossRefPubMedGoogle Scholar
- 25.Sondo P, Derra K, Diallo-Nakanabo S, Tarnagda Z, Zampa O, Kazienga A, et al. Effectiveness and safety of artemether-lumefantrine versus artesunate-amodiaquine for unsupervised treatment of uncomplicated falciparum malaria in patients of all age groups in Nanoro, Burkina Faso: a randomized open label trial. Malar J. 2015;14:325.CrossRefPubMedPubMedCentralGoogle Scholar
- 27.World Health Organisation. Guidelines for the treatment of malaria, 3rd ed. Geneva: WHO; 2015.Google Scholar