UNASSIGNED: We assessed the efficacy and safety of dalbavancin, a long-acting lipoglycopeptide with activity against Gram-positive pathogens, for treatment of acute bacterial skin and skin structure infections (ABSSSI) in patients with high body mass index (BMI) and/or diabetes.
UNASSIGNED: Data from two phase 3 trials of dalbavancin (1000 mg intravenous [IV], day 1; 500 mg IV, day 8) versus comparator and one phase 3b trial of single-dose (1500 mg IV, day 1) versus 2-dose (1000 mg IV, day 1; 500 mg IV, day 8) dalbavancin in adults with ABSSSI were pooled and summarized separately by baseline BMI and diabetes status. Clinical success at 48 to 72 hours (≥20% reduction in lesion size), end of treatment ([EOT] day 14), and day 28 was evaluated in the intent-to-treat (ITT) and microbiological ITT (microITT) populations. Safety data were reported in patients who received ≥1 dose of study drug.
UNASSIGNED: In the dalbavancin ITT population (BMI, n = 2001; diabetes, n = 2010), at 48 to 72 hours (and EOT) clinical success was achieved in 89.3% (EOT, 90.9%) of patients with normal BMI and 78.9% to 87.6% (EOT, 91.0% to 95.2%) of patients with elevated BMI. Clinical success after dalbavancin treatment was achieved in 82.4% (EOT, 90.8%) of patients with diabetes and 86.0% (EOT, 91.6%) of patients without diabetes. Similar trends were observed for infections due to methicillin-resistant Staphylococcus aureus or methicillin-susceptible S aureus (microITT population).
UNASSIGNED: Dalbavancin is effective, with sustained clinical success rates in patients with obesity or diabetes, with a similar safety profile across patient groups.

BACKGROUND: The treatment of acute bacterial skin and skin structure infections (ABSSSI) usually involves intravenous (i.v.) antibiotics requiring hospitalisation and increasing hospital costs. Since 2014, dalbavancin is approved for ABSSSIs treatment. However, evidence of its health economic impact on the German healthcare system is still limited.
METHODS: Diagnosis-related groups (DRG) based cost analysis was used to evaluate real-world data (RWD) from a German tertiary care center. All patients treated with i.v. antibiotics in the Department of Dermatology and Venereology at the University Hospital of Cologne were included to detect potential cost savings from a payer perspective. Thus, for the inpatient care German diagnosis-related groups (G-DRG) tariffs, length of stay (LOS), main- and secondary DRG-diagnoses and for the outpatient setting \'Einheitlicher Bewertungsmaßstab\' (EBM) codes were evaluated.
RESULTS: This retrospective study identified 480 inpatient cases treated for ABSSSI between January 2016 until December 2020. Complete cost data were available for 433 cases and the detection of long-hospital-stay patients based on surcharges for exceeding the upper limit LOS led to 125 cases (29%) including 67 females (54%) and 58 males (46%) with an overall mean age of 63.6 years; all treated for International Classification of Diseases (ICD -10th revision) code A46 \'erysipelas\'. A sub-analysis focussed on DRG J64B with a total of 92 cases exceeding the upper limit LOS by a median of 3 days resulted in a median surcharge of €636 (mean value €749; SD €589; IQR €459-€785) per case. In comparison, we calculated outpatient treatment costs of approximately €55 per case. Thus, further treatment of these patients in an outpatient setting before exceeding the upper limit LOS might result in a cost-saving potential of approximately €581 per case.
CONCLUSIONS: Dalbavancin appears a cost-efficient option to reduce inpatient treatment costs by transitioning to an outpatient setting of patients with ABSSSI potentially exceeding the upper limit LOS.

UNASSIGNED: This study compared the clinical efficacy and safety of anti-methicillin-resistant Staphylococcus aureus (MRSA) quinolones for treating acute bacterial skin and skin structure infections (ABSSSIs).
UNASSIGNED: PubMed, Embase, and the Cochrane Central Register of Controlled Trials were searched for relevant articles from inception to 21 July 2021. RCTs comparing the clinical efficacy and safety of anti-MRSA quinolones with other antibiotics for treating adult patients with ABSSSIs were included.
UNASSIGNED: Six RCTs were included. A total of 1,264 and 1,307 participants received the anti-MRSA quinolone-based study group and the control group. In the study group receiving anti-MRSA quinolone-based treatment, 935, 246, and 83 patients received delafloxacin, levonadifloxacin, and acorafloxacin, respectively. No significant difference was observed in the clinical cure rate at test of cure between the study and control groups (OR, 1.08; 95% CI, 0.91-1.29; I2 = 0%). In patients with MRSA-associated ABSSSIs, the clinical cure rate (OR, 1.09; 95% CI, 0.71-1.65; I2 = 0%) and microbiological response rate (OR, 1.24; 95% CI, 0.48-3.21; I2 = 0%) of anti-MRSA quinolones were similar to those of other antibiotics.
UNASSIGNED: The efficacy of anti-MRSA quinolone-based treatment is comparable to that of other anti-MRSA antibiotics for treating ABSSSIs.

This systematic review and meta-analysis of randomized controlled trials (RCTs) compared the clinical efficacy and safety of anti-MRSA cephalosporin and vancomycin-based treatment in treating acute bacterial skin and skin structure infections (ABSSSIs). PubMed, Embase, Cochrane Central Register of Controlled Trials, Turning Research into Practice, and ClinicalTrials.gov databases were searched for relevant articles from inception to 15 June 2020. RCTs comparing the clinical efficacy and safety of anti-MRSA cephalosporin with those of vancomycin-based regimens in treating adult patients with ABSSSIs were included. The primary and secondary outcomes were clinical response at the test-of-cure assessments and risk of adverse events (AEs), respectively. Eight RCTs were enrolled. The clinical response rate was not significantly different between anti-MRSA cephalosporin and vancomycin-based treatments (odds ratio [OR], 1.05; 95% CI, 0.90-1.23; I2 = 0%). Except for major cutaneous abscesses in which anti-MRSA cephalosporin-based treatment was associated with a lower clinical response rate than vancomycin-based treatment (OR, 0.62; 95% CI, 0.40-0.97; I2 = 0%), other subgroup analyses according to the type of cephalosporin (ceftaroline or ceftobiprole), type of infection, and different pathogens did not show significant differences in clinical response. Anti-MRSA cephalosporin-based treatment was only associated with a higher risk of nausea than vancomycin-based treatment (OR, 1.41; 95% CI, 1.07-1.85; I2 = 0%). In treating ABSSSIs, the clinical efficacy of anti-MRSA cephalosporin is comparable to that of vancomycin-based treatment, except in major cutaneous abscesses. In addition to nausea, anti-MRSA cephalosporin was as tolerable as vancomycin-based treatment.

Nowadays, the incidence of acute bacterial skin and skin structure infection (ABSSSI) is increasing. The increased bioavailability and reduced drug resistance of antibiotics are crucial to obtain a more effective treatment response in these infections. These favorable properties could be achieved by different drug delivery systems such as liposomes. In this study, nanosized, radiolabeled tedizolid phosphate liposomal formulations were prepared and evaluated with their in vitro cellular binding capacity and biocompatible profile for topical treatment of ABSSSI. Liposomes were characterized by evaluation of their visual inspection, particle size (about 190-270 nm), zeta potential value (around 0), and encapsulation efficiency (nearly 10%). The release rate of tedizolid phosphate from liposomes was also studied using dialysis membranes and evaluated kinetically. The stability of formulations was observed at three different temperatures and humidity conditions for 28 days. Afterward, liposomes were labeled with 99mTc, and the optimal amount of reducing agent (stannous chloride) was determined as 500 μg in this direct labeling procedure. All liposome formulations were successfully radiolabeled with high efficiency and exhibited high radiochemical purity (> 80%) during 6 h in different media. Furthermore, the cellular bindings of liposomal formulations were evaluated in human skin fibroblast cells by measuring the radioactivity. Higher radioactivity values were obtained in CCD-1070Sk cells incubated by liposome formulations compared to sodium pertechnetate. This finding suggested that liposomal formulation increased the cellular binding of radioactivity. By the result of our study, nanosized, tedizolid phosphate encapsulated liposome formulation was found to be a favorable carrier system in the treatment of ABSSSI.

Acute bacterial skin and skin structure infections (ABSSSIs) are one of the most common types of infections due to methicillin-resistant Staphylococcus aureus (MRSA). The standard of care for ABSSSI includes glycopeptides such as vancomycin, teicoplanin, oxazolidinones and fluoroquinolones, which are potent broad-spectrum antibacterial agents. Unfortunately, due to indiscriminate utilization, resistance to these agents is rising and identification of novel agents is an urgent unmet medical need. In this context, levonadifloxacin (WCK-771) is a novel, hydrate arginine salt of nadifloxacin with improved bactericidal activity against MRSA as well as fluoroquinolone-resistant S. aureus by targeting bacterial DNA supercoiling enzymes DNA gyrase and topoisomerase IV. Levonadifloxacin displays a broad-spectrum bactericidal activity against Gram-positive and Gram-negative bacteria, atypical bacteria, anaerobic bacteria and bioterror pathogens with a very low frequency of mutation. Levonadifloxacin also displays improved activity under low pH biofilm environments. The drug has successfully completed phase I, phase II and phase III clinical trials in India. The U.S. Food and Drug Administration (FDA) granted a Qualified Infectious Disease Product (QIDP) designation to levonadifloxacin for the treatment of MRSA infections in August 2014.

National guidelines for pneumonia (PNA), urinary tract infection (UTI), and acute bacterial skin and skin structure infection (ABSSSI) do not address treatment duration for infections associated with bacteremia. We evaluated clinical outcomes of patients receiving shorter (5-9 days) versus longer (10-15 days) duration of antibiotics.
This was a multicenter retrospective cohort study of inpatients with uncomplicated PNA, UTI, or ABSSSI and associated bacteremia. The primary outcome was clinical failure, a composite of rehospitalization, reinitiation of antibiotics, or all-cause mortality within 30 days of antibiotic completion. Secondary outcomes included individual components of the primary outcome, Clostridioides difficile infection, and antibiotic-related adverse effects necessitating change in therapy. A propensity score-weighted logistic regression model was used to mitigate potential bias associated with nonrandom assignment of treatment duration.
Of 408 patients included, 123 received a shorter treatment duration (median 8 days) and 285 received a longer duration (median 13 days). In the propensity-weighted analysis, the probability of the primary outcome was 13.5% in the shorter group and 11.1% in the longer group (average treatment effect, 2.4%; odds ratio [OR], 1.25; 95% confidence interval [CI], .65-2.40; P = .505). However, shorter courses were associated with higher probability of restarting antibiotics (OR, 1.62; 95% CI, 1.01-2.61; P = .046) and C. difficile infection (OR, 4.01; 95% CI, 2.21-7.59; P < .0001).
Shorter courses of antibiotic treatment for PNA, UTI, and ABSSSI with bacteremia were not associated with increased overall risk of clinical failure; however, prospective studies are needed to further evaluate the effectiveness of shorter treatment durations.

BACKGROUND: Admissions for acute bacterial skin and skin structure infections (ABSSSI) are often prolonged because of intravenous (IV) antibiotics. Use of a long-acting IV antibiotic may reduce length of stay (LOS) on a hospitalist service. The ENHANCE ABSSSI trial sought to determine the impact on LOS and work productivity in patients treated with a long-acting IV antibiotic, dalbavancin, vs. usual care at an urban tertiary-care center.
METHODS: A single-center, pre- vs. post-period pragmatic trial at Weill-Cornell Medical Center assessed usual care for consecutively enrolled admitted ABSSSI patients during an observational period (pre-period). Identification and treatment of eligible admitted ABSSSI patients with dalbavancin were implemented in the post-period. Those with life-threatening infections, requiring multiple antibiotics/intensive care, or with unstable comorbidities were excluded. Outcomes were assessed over a 44-day follow-up period.
RESULTS: Of 48 and 43 patients enrolled, respectively, in the pre- and post-periods, mean infection-related LOS was reduced in the post-period (3.2 days vs. 4.8 days; P = 0.003). Similar results were found in an adjusted LOS analysis. Work productivity and activity impairment outcomes significantly improved in the post-period (P ≤ 0.01). Complete response rates were similar: 50% (pre-period) and 57% (post-period). Among AEs identified, 17% (n = 7) were found to have possible causal relation to dalbavancin in the post-period. Few AEs were serious (n = 3; 7% post-period versus n = 1; 2% pre-period).
CONCLUSIONS: After implementing the ENHANCE ABSSSI pathway, LOS was significantly reduced by almost 2 days, with potential improvements in work productivity and ability to complete daily activities.
BACKGROUND: ClinicalTrials.gov identifier, NCT03233438.
BACKGROUND: Allergan plc.

This meta-analysis aims to assess the efficacy and safety of tedizolid, compared to linezolid, in the treatment of acute bacterial skin and skin structure infection (ABSSSI). PubMed, Web of Science, EBSCO (Elton B. Stephens Co.), Cochrane Library, Ovid Medline and Embase databases were accessed until 18 July 2019. Only randomized controlled trials (RCTs) comparing the efficacy of tedizolid with linezolid for adult patients with ABSSSIs were included. The outcomes included the clinical response, microbiological response, and risk of adverse events (AEs). A total of four RCTs involving 2056 adult patients with ABSSSI were enrolled. The early clinical response rate was 79.6% and 80.5% for patients receiving tedizolid and linezolid, respectively. The pooled analysis showed that tedizolid had a non-inferior early clinical response rate to linezolid (odds ratio (OR) = 0.96, 95% confidence interval (CI) = 0.77-1.19, I2 = 0%). The early response rate was similar between tedizolid and linezolid among patients with cellulitis/erysipelas (75.1% vs. 77.1%; OR = 0.90, 95% CI = 0.64-1.27, I2 = 25%), major cutaneous abscess (85.1% vs. 86.8%; OR = 0.93, 95% CI = 0.42-2.03, I2 = 37%) and wound infection (85.9% vs. 82.6%; OR = 1.29, 95% CI = 0.66-2.51, I2 = 45%). For methicillin-resistant Staphylococcus aureus patients, tedizolid had a favorable microbiological response rate of 95.2% which was comparable to linezolid (94%) (OR = 1.19, 95% CI = 0.49-2.90, I2 = 0%). In addition to the similar risk of treatment-emergent AEs (a serious event, the discontinuation of the study drug due to AEs and mortality between tedizolid and linezolid), tedizolid was associated with a lower risk of nausea, vomiting and abnormal neutrophil count than linezolid. In conclusion, once-daily tedizolid (200 mg for six days) compared to linezolid (600 mg twice-daily for 10 days) was non-inferior in efficacy in the treatment of ABSSSI. Besides, tedizolid was generally as well tolerated as linezolid, and had a lower incidence of gastrointestinal AEs and bone marrow suppression than linezolid.

Dalbavancin is indicated for the treatment of acute bacterial skin and skin structure infections caused by susceptible gram-positive microorganisms. This analysis represents the update of the population pharmacokinetics (popPK) modeling and target attainment simulations performed with data from the single-dose safety and efficacy study and an unrelated but substantial revision of the preclinical pharmacokinetic/pharmacodynamic target (fAUC/MIC, free area under concentration-time curve/minimum inhibitory concentration ratio). A 3-compartment distribution model with first-order elimination provided an appropriate fit, with typical dalbavancin clearance of 0.05 L/h and total volume of distribution of ∼15 L. Impact of intrinsic factors was modest, although statistically significant (P < .05) relationships with total clearance were found for the following covariates: creatinine clearance, weight, and albumin - dose adjustment was only indicated for severe renal impairment. Under the new nonclinical target, simulations of the popPK model projected that >99% of subjects would achieve the nonclinical target at MIC values up to and including 2 mg/L.