UNASSIGNED: This systematic review and meta-analysis aimed to investigate the clinical efficacy and safety of novel lipoglycopeptides in treating acute bacterial skin and skin structure infections (ABSSSIs).
UNASSIGNED: PubMed, Embase, Cochrane Central Register of Controlled Trials, Turning Research into Practice, and ClinicalTrials.gov were searched from inception to 20 May 2021. Randomized controlled trials (RCTs) comparing the clinical efficacy and safety of lipoglycopeptides with other comparators in treating adult patients with ABSSSIs were included. The primary outcome was clinical response.
UNASSIGNED: Eight RCTs (6416 patients; lipoglycopeptides: 3359, comparators: 3057) were enrolled. Clinical response rate was not significantly different between lipoglycopeptides and comparators at early-clinical-evaluation (odds ratio [95% confidence interval]: 1.01 [0.85-1.20], I2 = 34%), end-of-treatment (0.94 [0.80-1.11], I2 = 0%), and test-of-cure (1.05 [0.85-1.30], I2 = 0%). Lipoglycopeptides showed a similar overall microbiological eradication rate (1.12 [0.90-1.38], I2 = 21%) but a borderline higher microbiological eradication rate for methicillin-resistant Staphylococcus aureus (1.37 [1.00-1.86], I2 = 0%) than the comparators. Lipoglycopeptides were not associated with a higher risk than comparators.
UNASSIGNED: Lipoglycopeptides can achieve similar clinical and microbiological responses to other comparators in treating ABSSSIs. In addition, lipoglycopeptides are as tolerable as their comparators.

This study aimed to evaluate the efficacy and safety of oritavancin (ORI) versus comparators for the treatment of acute bacterial skin and skin-structure infections (ABSSSIs) based on available clinical studies.
PubMed, Cochrane Library and Embase were searched from database inception to 28 July 2020 to identify clinical studies assessing the efficacy and safety of ORI and comparator antibiotics for the treatment of ABSSSIs. Primary efficacy outcome, investigator-assessed clinical cure, lesion size reduction ≥20%, additional post-treatment antibiotics, and 30-day emergency room (ER) visits and readmission were assessed as efficacy outcomes. Adverse events (AEs) and mortality were assessed as safety outcomes. I2 statistic was calculated for heterogeneity, and a fixed-effects or random-effects model was used for estimation of the risk ratio (RR).
A total of 9213 patients from two randomised clinical trials (RCTs) and four cohort studies were included in this meta-analysis. ORI was statistically non-inferior to control agents in all efficacy and safety outcomes. Moreover, ORI significantly reduced the occurrence of 30-day readmission (RR = 0.42; P = 0.0004) and drug-related AEs (RR = 0.78; P = 0.002). In the subgroup analysis, ORI also had a lower rate of 30-day ER visits in the outpatient setting (RR = 0.34; P < 0.00001).
ORI was not inferior to comparators for the treatment of ABSSSIs. Meanwhile, it showed advantages in reducing the rate of readmission and drug-related AEs. More high-quality and large-scale RCTs are required to further confirm the efficacy and safety of ORI. [Trial registration: PROSPERO ID: CRD42020201942].

Glycopeptides have an established role in the management of infective endocarditis, and feature in current treatment guidelines. Newer lipoglycopeptide agents (dalbavancin, telavancin and oritavancin), which are analogues of glycopeptides with structural modifications giving rise to added novel mechanisms of antimicrobial activity, are approved for the treatment of Gram-positive skin and skin structure infections, and also for nosocomial pneumonia (only telavancin has approval for the latter indication). Recent evidence has also emerged to support their use in the treatment of bone and joint infections. This article reviews the current literature on dalbavancin and telavancin in the treatment of infective endocarditis, a condition for which the role of these agents is yet to be established.

BACKGROUND: There is increasing interest in the use of oritavancin and dalbavancin for complicated Gram-positive infections as an alternative to in-hospital intravenous or outpatient antimicrobial therapy.
OBJECTIVE: To evaluate the efficacy and safety of long-acting lipoglycopeptides (laLGPs) in patients with osteoarticular, cardiovascular, intravascular-catheter-related and other complicated infections.
METHODS: A systematic literature search was performed using \'dalbavancin\' and \'oritavancin\' as search terms. For inclusion in this review, studies had to include at least one human subject treated for an indication other than acute bacterial skin and skin structure infections. The primary outcome for this review was clinical success as defined by each individual study, and patients were stratified by type of infection.
RESULTS: In total, 38 studies (18 randomized controlled trials/case series and 20 case reports) met the inclusion criteria. The most common off-label indication for oritavancin and dalbavancin was osteoarticular infection, with a median success rate of 73% [interquartile range (IQR) 58-85%] among the 14 studies with more than one patient. The success rate for endocarditis and cardiac-device-related infections was 68% (IQR 56-86%) among nine studies, and the success rate for catheter-related bloodstream infection was 75% (IQR 59-90%) among seven studies. Among the 16 studies of almost 700 patients receiving laLGPs, there were 98 reports of adverse events, resulting in 13% of treated patients reporting an event.
CONCLUSIONS: This review provides evidence that laLGPs are safe and efficacious for osteoarticular, cardiovascular, intravascular-catheter-related and other complicated infections. Further research is needed to confirm these results.

Treatment of serious gram-positive infections presents multiple challenges. Treatment often results in prolonged hospitalization for administration of intravenous antimicrobials and presents an inefficient use of hospital resources. Prolonged hospitalization is typically also unfavorable to patient preferences and potentially subjects patients to additional health care-associated complications. Current strategies of transition to outpatient settings-outpatient parenteral antimicrobial therapy and use of oral antibiotics-often do not adequately serve vulnerable populations for whom there is often no alternative to inpatient therapy. Specifically, people who use drugs, those who cannot reliably adhere to unsupervised treatment (poor mental or physical health), people with complicating life circumstances (e.g., homelessness, incarceration, rural location), and those with inadequate health insurance remain hospitalized for weeks longer than persons without such conditions. We suspected that long-acting lipoglycopeptides (laLGP), such as dalbavancin and oritavancin, may be useful in patient transitions to outpatient settings. Thus, we conducted a search of the peer-reviewed literature using the PubMed, Google Scholar, and MEDLINE databases. Based on accumulating literature, it appears that laLGPs offer a reliable alternative therapeutic strategy that addresses many of the personal and systemic barriers to the traditional transitioning approaches. Current evidence also suggests that these agents may be cost-effective from patient, payer, and hospital perspectives. Barriers to broader use of laLGPs include, among others, a relative lack of prospective data regarding efficacy in serious infections, a narrow United States Food and Drug Administration-approved indication restricted to only acute bacterial skin and skin structure infections, and lack of reimbursement infrastructure for inpatient settings.

Osteomyelitis remains difficult to treat, typically requiring a prolonged course of intravenous (i.v.) antibiotics. The optimal route and duration of antibiotics remains ill-defined due to limited prospective clinical trials. Oritavancin is a long-acting, semisynthetic lipoglycopeptide antibiotic with rapid concentration-dependent bactericidal activity against many Gram-positive organisms. Favourable pharmacokinetics makes oritavancin an appealing alternative to currently available antibiotics requiring daily infusion to decrease the risk of vascular access complications associated with outpatient antimicrobial therapy. The purpose of this study was to report the outcomes of nine patients with chronic osteomyelitis receiving multidose oritavancin. Using electronic medical records, patients aged ≥18 years treated with i.v. oritavancin between September 2015 and April 2018 at Downtown Dublin Wound Center, a hospital-owned outpatient wound care clinic and infusion centre affiliated with Meadows Regional Health System in Dublin, GA, were identified. Of 12 cases reviewed, 9 patients received at least two doses of i.v. oritavancin for the treatment of chronic osteomyelitis. All nine patients experienced clinical cure at 6-month follow-up after the last dose of oritavancin. Multidose oritavancin was found to be a safe and efficacious option for chronic osteomyelitis when treatment options are limited by patient complexities or barriers in their ability to access healthcare services.

To assess critically oritavancin, a second-generation  lipoglycopeptide, for the treatment of Acute Bacterial Skin and Skin Structure Infections caused by susceptible Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus.
An evaluation report of oritavancin in Acute Bacterial Skin and Skin  Structure Infections was carried out according to the methodology of the Group  for drug evaluation, standardization and research in drug selection of the  Spanish Society of Hospital Pharmacy (SEFH)1, with the MADRE 4.0 program. A  search was made in PubMed, in the web www.clinicaltrials. gov, Embase,  PubMed and UptoDate. The European Medication Agency and Food and Drug  Administration evaluation reports were also used.
Single-dose oritavancin demonstrated its non-inferiority efficacy versus  vancomycin in Acute Bacterial Skin and Skin Structure  nfections, with a similar safety profile. Its potential advantage over other  therapeutic alternatives lies in its administration in single dose and in its no need for plasma levels monitoring, which would allow its administration on an outpatient basis. Regarding to the other alternative possibilities of oral  (linezolid, tedizolid) or IM (teicoplanin) treatment, oritavancin would improve the  adherence to the treatment. Although oritavancin could be more  efficient in certain scenarios (outpatient treatment versus inpatient treatment  with alternatives), there are no convincing studies in this regard so far. On the  other hand, alternative drugs above-mentioned, can also allow outpatient  treatment, reducing advantages of oritavancin and further increasing cost  differences. Therefore, given that the efficacy is similar to the alternatives, a  cost minimization analysis could be considered.
Oritavancin is comparable in terms of efficacy and safety to the  existing alternatives in Acute Bacterial Skin and Skin Structure Infections,  without improvements in the cost-effectiveness ratio, because of the proposed  positioning is to consider it for the treatment of  vancomycinresistant enterococcal infection in adult patients when the use of  linezolid or tedizolid is contraindicated.
Objetivo: Evaluar críticamente la oritavancina, lipoglicopéptido de segunda generación, para el tratamiento de la infección bacteriana aguda de la  piel y tejidos blandos causada por bacterias Gram-positivas susceptibles,  incluyendo Staphylococcus aureus resistente a meticilina.Método: Se realizó un informe de evaluación según la metodología del Grupo de Evaluación de Novedades, Estandarización e Investigación en Selección de  Medicamentos de la Sociedad Española de Farmacia Hospitalaria, con el  programa MADRE 4.0. Se llevó a cabo una búsqueda en PubMed, en  www.clinicaltrials.gov, Embase y UptoDate. También se utilizaron informes  publicados de agencias de evaluación.Resultados: La oritavancina en dosis única demostró no ser inferior a la vancomicina en Infección bacteriana aguda de la piel y tejidos blandos, con un perfil de seguridad similar. Sus ventajas potenciales frente a otras alternativas  terapéuticas radicarían en su administración en dosis única y en la no necesidad  de monitorización de los niveles plasmáticos (lo que posibilitaría su  administración ambulatoria), y en la mejora de la adherencia. Aunque podría ser  eficiente en determinados escenarios (tratamiento ambulatorio frente al  hospitalario con las alternativas), no hay estudios convincentes en este sentido.  Por otra parte, los fármacos alternativos por vía oral (linezolid, tedizolid) o IM  (teicoplanina) pueden permitir también el tratamiento ambulatorio, reduciendo  las ventajas de la oritavancina y agrandando las diferencias de coste. Dado que  su eficacia es similar a las alternativas, cabría considerar un análisis de  minimización de costes.Conclusiones: La oritavancina es de una eficacia y seguridad comparables a las alternativas existentes en Infección bacteriana aguda de la piel y tejidos blandos y no mejora la relación coste-efectividad, por lo que el posicionamiento  propuesto sería el tratamiento de la infección por enterococo resistente a  vancomicina en pacientes adultos cuando esté contraindicado el uso de linezolid  o tedizolid.

OBJECTIVE: Skin and soft tissue infections (SSTIs) carry significant economic burden, as well as morbidity and mortality, especially when caused by methicillin-resistant Staphylococcus aureus (MRSA). Several new MRSA-active antibiotics have been developed, including semisynthetic glycopeptides (telavancin, dalbavancin and oritavancin). Of these, dalbavancin and oritavancin offer extended dosing intervals.
METHODS: We performed a systematic review, network meta-analysis and cost analysis to compare the newer glycopeptides to standard care and to each other for the treatment of complicated SSTIs (cSSTI). A search for randomized controlled trials (RCTs) was conducted in Medline, Embase and the Cochrane Central Register of Controlled Trials. We also developed a model to evaluate the costs associated with dalbavancin and oritavancin from the third-party payer perspective.
RESULTS: Seven RCTs met the inclusion criteria. Network meta-analyses suggested that the clinical response to telavancin, dalbavancin and oritavancin was similar to standard care (odds ratio (OR) 1.09, 95% confidence interval (CI) 0.90-1.33; OR 0.78, 95% CI 0.52-1.18; and OR 1.06, 95% CI 0.85-1.33, respectively). Head-to-head comparisons showed no difference in clinical response between oritavancin and dalbavancin (OR 1.36; 95% CI 0.85-2.18), oritavancin and telavancin (OR 0.98; 95% CI 0.72-1.31) or dalbavancin and telavancin (OR 0.72; 95% CI 0.45-1.13). Telavancin had a higher incidence of overall adverse events compared to standard care (OR 1.33; 95% CI 1.10-1.61). Compared to telavancin, there were fewer overall adverse events with dalbavancin (OR 0.58; 95% CI 0.45-0.76) and oritavancin (OR 0.71; 95% CI 0.55-0.92). Studies were of high quality overall. Our cost analyses demonstrated that dalbavancin and oritavancin were less costly compared to standard care under baseline assumptions and many scenarios evaluated. The use of dalbavancin could save third-party payers $1442 to $4803 per cSSTI, while the use of oritavancin could save $3571 to $6932 per cSSTI.
CONCLUSIONS: Dalbavancin and oritavancin demonstrate efficacy and safety comparable to standard care in well-designed RCTs and result in cost savings when standard care is treatment that covers MRSA.

Antimicrobial drug-resistance continues to force adaptation in our clinical practice. We explore new evidence regarding adjunctive antibiotic therapy for skin and soft tissue abscesses as well as duration of therapy for intra-abdominal abscesses. As new evidence refines optimal practice, it is essential to support clinicians in adopting practice patterns concordant with evidence-based guidelines. We review a simple approach that can \'nudge\' clinicians towards concordant practices. Finally, the use of novel antimicrobials will play an increasingly important role in contemporary therapy. We review five new antimicrobials recently FDA-approved for use in drug-resistant infections: dalbavancin, oritavancin, ceftaroline, ceftolozane-tazobactam, and ceftazidime-avibactam.

Oritavancin, telavancin, and dalbavancin are recently marketed lipoglycopeptides that exhibit remarkable differences to conventional molecules. While dalbavancin inhibits the late stages of peptidoglycan synthesis by mainly impairing transglycosylase activity, oritavancin and telavancin anchor in the bacterial membrane by the lipophilic side chain linked to their disaccharidic moiety, disrupting membrane integrity and causing bacteriolysis. Oritavancin keeps activity against vancomycin-resistant enterocococci, being a stronger inhibitor of transpeptidase than of transglycosylase activity. These molecules have potent activity against Gram-positive organisms, most notably staphylococci (including methicillin-resistant Staphylococcus aureus and to some extent vancomycin-intermediate S. aureus), streptococci (including multidrug-resistant pneumococci), and Clostridia. All agents are indicated for the treatment of acute bacterial skin and skin structure infections, and telavancin, for hospital-acquired and ventilator-associated bacterial pneumonia. While telavancin is administered daily at 10 mg/kg, the remarkably long half-lives of oritavancin and dalbavancin allow for infrequent dosing (single dose of 1200 mg for oritavancin and 1000 mg at day 1 followed by 500 mg at day 8 for dalbavancin), which could be exploited in the future for outpatient therapy. Among possible safety issues evidenced during clinical development were an increased risk of developing osteomyelitis with oritavancin; taste disturbance, nephrotoxicity, and risk of corrected QT interval prolongation (especially in the presence of at-risk co-medications) with telavancin; and elevation of hepatic enzymes with dalbavancin. Interference with coagulation tests has been reported with oritavancin and telavancin. These drugs proved non-inferior to conventional treatments in clinical trials but their advantages may be better evidenced upon future evaluation in more severe infections.