Current and future options for treating complicated skin and soft tissue infections: focus on fluoroquinolones and long-acting lipoglycopeptide antibiotics

Abstract

Bacterial skin and soft tissue infections are among the most common bacterial infections and constitute a major burden for patients and healthcare systems. Care is complicated by the variety of potential pathogens, some with resistance to previously effective antimicrobial agents, the wide spectrum of clinical presentations and the risk of progression to life-threatening forms. More-efficient care pathways are needed that can reduce hospital admissions and length of stay, while maintaining a high quality of care and adhering to antimicrobial stewardship principles. Several agents approved recently for treating acute bacterial skin and skin structure infections have characteristics that meet these requirements. We address the clinical and pharmacological characteristics of the fourth-generation fluoroquinolone delafloxacin, and the long-acting lipoglycopeptide agents dalbavancin and oritavancin.

Current approach to skin and soft tissue infections. Thinking about continuity of care

“…to oral route [ 43 , 50 ]. Dalbavancin and oritavancin are characterized by the presence of an additional hydrophobic moiety, which determine their long half-lives (terminal half-life of 336 and 393 hours, respectively) but, most importantly, markedly improve their antimicrobial activity by increasing their membrane affinity and thus their concentration near the target [ 23 , 45 , 46 , 48 , 49 , 51 ]. Long-acting lipoglycopeptide antimicrobials represent another strategy for achieving ED.…”

Rapid diagnostics for skin and soft tissue infections: the current landscape and future potential

“…Indeed, the routine implementation of the GeneXpert MRSA/SA SSTI assay in patients deemed at-risk for this pathogen has been shown to allow a significant reduction in the duration of empirical anti-MRSA drugs (average, 1-day reduction) along with lower treatment costs, length of stay, and incidence of Clostridioides difficile infections [71,72 ▪ ]. Conversely, the fast detection of MRSA/MSSA in SSTI samples might permit a more precocious administration of long-lasting agents such as lipoglycopeptides and an earlier discharge in patients not requiring hospitalization [73]. Besides, the usefulness of RDMT to detect other pathogens potentially responsible for complicated SSTI – especially Enterobacterales, nonfermenting Gram-negative bacteria and anaerobes – remains limited due to the paucity of commercialized assays.…”

Left ventricular assist device-associated driveline infections as a specific form of complicated skin and soft tissue infection/acute bacterial skin and skin structure infection – issues and therapeutic options

“…Skin and soft tissue infections (SSTIs) include a variety of bacterial infections of the skin and subcutaneous tissue, muscle, and fascia and range from mild to serious life-threatening infections [18 ▪ ,22,24,25]. Older age, immunosenescence or immunocompromising conditions, obesity, trauma, and comorbidities such as diabetes mellitus or cardiopulmonary or hepatorenal disease are the main risk factors for SSTIs [26] and a substantial proportion of SSTIs is associated with hospitalization and significant morbidity [18 ▪ ,22,24–28]. SSTIs are usually classified according to the causative pathogen with its associated toxins or enzymes, and their clinical presentation and severity [26].…”

“…S. aureus (including MRSA) and coagulase-negative staphylococci (CoNS) are the most common pathogens associated with ABSSSIs, followed by Pseudomonas aeruginosa and S. pyogenes . Less common bacteria include other Streptococcus species, other Gram-negative bacteria such as Enterobacterales , and fungal pathogens [ 20 , 27 ].…”

“…Guidelines for treatment of ABSSSIs and SSTIs [ 20 , 23 ▪▪ ] are similar to the guidelines for treatment of DLIs, but – in contrast to the guidelines for DLIs – also include recommendations for specific antibiotics to be used. Recently approved novel antibiotics (such as dalbavancin, oritavancin, and delafloxacin) add to the available treatment options for ABSSSIs [ 27 , 36 ]. Considering the similarities between DLI and ABSSSI with regards to the pathogens involved, these antibiotics could also be beneficial for patients with DLIs [ 37 , 38 ].…”