Explore the vast range of titles available.

Background. Acute bacterial skin and skin structure infections (ABSSSIs) are a cause of significant morbidity and therapy can be a burden to the healthcare system. New antibiotics that simplify treatment and avoid hospitalization are needed. This study compared the safety and efficacy of a single intravenous infusion of 1500 mg of dalbavancin to the 2-dose regimen. Methods. This study was a randomized, double-blind trial in patients aged >18 years with ABSSSIs. Patients were randomized to dalbavancin 1500 mg either as a single intravenous (IV) infusion or 1000 mg IV on day 1 followed 1 week later by 500 mg IV. The primary endpoint was a ≥20% reduction in the area of erythema at 48–72 hours in the intent-to-treat population. Noninferiority was to be declared if the lower limit of the 95% confidence interval (CI) on the difference in the outcomes was greater than −10%. Clinical outcome was also assessed at days 14 and 28. Results. Six hundred ninety-eight patients were randomized. Demographic characteristics were similar on each regimen, although there were more patients with methicillin-resistant Staphylococcus aureus (MRSA) at baseline on the 2-dose regimen (36/210 [17.1%] vs 61/220 [27.7%]). Dalbavancin delivered as a single dose was noninferior to a 2-dose regimen (81.4% vs 84.2%; difference, −2.9% [95% CI, −8.5% to 2.8%]). Clinical outcomes were also similar at day 14 (84.0% vs 84.8%), day 28 (84.5% vs 85.1%), and day 14 in clinically evaluable patients with MRSA in a baseline culture (92.9% vs 95.3%) in the single-and 2-dose regimens, respectively. Treatment-emergent adverse events occurred in 20.1% of the single-dose patients and 19.9% on the 2-dose regimen. Conclusions. A single 1500-mg infusion of dalbavancin is noninferior to a 2-dose regimen, has a similar safety profile, and removes logistical constraints related to delivery of the second dose. Clinical Trials Registration. NCT02127970.

Treatment of acute bacterial skin infection is becoming more complicated as antimicrobial resistance increases. In this trial of dalbavancin, a lipoglycopeptide with a long half-life, once-weekly dosing was shown to be noninferior to vancomycin–linezolid for treating infection. Acute bacterial skin and skin-structure infections are among the most common reasons for the hospitalization of adults in the United States today. 1 These infections are caused most often by Staphylococcus aureus and streptococci. 2 Methicillin-resistant S. aureus (MRSA) accounts for many of these infections and presents a particular treatment challenge because current therapies are limited by toxicity, resistance, or the lack of an oral formulation. 3 Associated medical costs are substantial. 4 Dalbavancin (Durata Therapeutics) is a lipoglycopeptide antibiotic agent with in vitro and in vivo activity against gram-positive pathogens, including a minimal inhibitory concentration (MIC) required to inhibit the growth of 90% . . .

Background. Dalbavancin, a novel lipoglycopeptide with a pharmacokinetic profile that allows weekly dosing, is active against gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA). The efficacy of dalbavancin for treatment of skin and skin structure infections (SSSIs) was demonstrated in a phase 2 study. Methods. In a phase 3 noninferiority study, patients with complicated SSSIs, including infections known or suspected to involve MRSA, were randomized (ratio, 2 : 1) in a double-blind manner to receive dalbavancin (1000 mg given intravenously on day 1 and 500 mg given intravenously on day 8) or linezolid (600 mg given intravenously or intravenously/orally every 12 h for 14 days). Efficacy was assessed by determining clinical and microbiological responses at the end of therapy and at the test-of-cure visit. Relapses were identified by additional follow-up ∼1 month later. Results. MRSA was identified in 51% of patients from whom a pathogen was isolated at baseline. Dalbavancin and linezolid demonstrated comparable clinical efficacy in the clinically evaluable population at the test-of-cure visit (88.9% and 91.2% success, respectively). The rate of clinical success at the end of therapy was >90% in both arms. Less than 1.0% of patients in either treatment arm experienced relapse after the test-of-cure visit. Both treatments yielded successful microbiological response in excess of 85% among microbiologically evaluable patients at end of therapy and at the test-of-cure visit for all pathogens combined, for all S. aureus strains, and for MRSA. Gastrointestinal symptoms were among the most common adverse events in both arms. A higher proportion of patients in the linezolid arm reported adverse events that were judged by the investigator to be probably/possibly related to treatment (dalbavancin arm, 25.4% of subjects; linezolid arm, 32.2% of subjects). Conclusions. Two doses of dalbavancin (1000 mg given on day 1 followed by 500 mg given on day 8) were as well tolerated and as effective as linezolid given twice daily for 14 days for the treatment of patients with complicated SSSI, including those infected with MRSA.

We evaluated the clinical efficacy and safety of teicoplanin according to the pharmacokinetics (PK) therapeutic level achieved in patients with renal dysfunction. Target trough concentration (C min ) was ≥15–30 μg/ml which has been recommended in patients with normal renal function. Adult patients (estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m 2 ) who were treated by teicoplanin were included in the study. We adopted two types of regimen for the initial 3 days: the conventional regimen, and the enhanced loading regimen (10 mg/kg twice daily on the 1st day, followed by 6.7–10 mg/kg once daily for the 2nd and 3rd days]. Two hundred and eighty-eight patients were evaluated for safety, and 106 patients with methicillin-resistant Staphylococcus aureus (MRSA) infections were evaluated for clinical efficacy. A significantly higher success rate was obtained in patients who achieved the target initial C min compared with those that did not (75.0 % vs 50.0 %, p  = 0.008). In a multivariate analysis, initial C min ≥15 μg/ml was an independent factor for clinical success (adjusted odds ratio: 4.20, 95 % confidence interval: 1.34–13.15). In patients with 15–30 μg/ml of maximal C min during therapy, nephrotoxicity occurred in 13.1 %, and hepatotoxicity in 2.6 %, and these incidences were not significantly higher compared with those patients with <15 μg/ml. In conclusion, achievement of C min of 15–30 μg/ml without delay was necessary to improve clinical outcomes for the treatment by teicoplanin in patients with renal dysfunction. Further investigation is required regarding the optimal loading regimen to achieve the therapeutic levels in those patients.

Background and Objectives Dalbavancin is a novel, once-weekly glycopeptide antibiotic approved for treatment of acute bacterial skin infections. Given the importance of understanding any pharmacokinetic variability across different patient populations, a double-blind, placebo-controlled study was conducted to evaluate the pharmacokinetics, safety, and tolerability of a single 500-mg and a single 1000-mg intravenous dose of dalbavancin in healthy Japanese subjects. Methods Ten subjects received intravenous dalbavancin 1000 mg, five subjects received intravenous dalbavancin 500 mg, and three subjects received intravenous placebo. Results After a single infusion of dalbavancin, the maximal plasma concentration ( C max ) and area under the plasma concentration–time curve (AUC) increased in a proportional manner from 500 mg to 1000 mg ( C max : 157 μg/ml and 299 μg/ml; AUC last : 10,850 μg·h/ml and 22,679 μg·h/ml, on the 500-mg and 1000-mg regimens, respectively) with low inter-subject variability. The mean terminal phase half-life ( t 1/2 ) was 204 and 193 h after the 500-mg and 1000-mg dose, respectively. Clearance and volume of distribution were similar for the two dose concentrations. Treatment-emergent adverse events reported were considered to be of mild intensity. There were no relevant changes in laboratory values or vital signs over time in subjects in either treatment group. Conclusions Overall, dalbavancin 500 mg and dalbavancin 1000 mg, administered as a single 30-min infusion, was well tolerated in this population and resulted in plasma exposures similar to those in non-Asians.

A small percentage of patients with skin infections later develop necrotizing fasciitis (NF). Diagnostic testing is needed to identify patients with skin infections at low risk of NF who could be discharged from the emergency department (ED) after antibiotic initiation. Elevated lactate has been associated with NF; existing estimates of the frequency of NF are based on retrospective reviews, and cases often lack testing for lactate. We present the incidence of patients with skin infections who developed NF and their baseline lactates. In four phase-3 trials, 2883 adults with complicated or acute bacterial skin and skin structure infections were randomized to dalbavancin or comparator, with early and late follow-up visits through Day 28. We prospectively collected baseline plasma lactates in one trial to assess an association with NF. NF was diagnosed in 3/2883 patients (0.1%); all three survived. In the study with prospectively collected baseline lactates (n = 622), 15/622 (2.4%) had a lactate ≥4 millimoles per liter (mmol/L), including 3/622 (0.5%) with a lactate ≥7 mmol/L. NF was not seen in patients with a lactate <4 mmol/L; NF was seen in 1/15 (6.7%) with a lactate ≥4 mmol/L, including 1/3 (33.3%) with lactate ≥7 mmol/L. NF incidence within 72 hours of antibiotic initiation in patients with complicated or acute bacterial skin and skin structure infections was extremely low (0.1%) and occurred in 6.7% with a lactate ≥4 mmol/L. Lactate <4 mmol/L can be used to identify patients at low risk of NF who could be safely discharged from the ED after antibiotic initiation.

Background and Objective Dalbavancin is increasingly used for the long-term treatment of chronic osteoarticular infections. A population pharmacokinetic/pharmacodynamic (PK/PD) analysis for assessing the relationship between dalbavancin exposure and C-reactive protein (C-RP) over time was conducted. Methods Non-linear mixed-effect modeling was fitted to dalbavancin and C-RP concentrations. Monte Carlo simulations assessed the weekly percentage of C-RP reduction associated with different dosing regimens, starting from baseline to < 1 mg/dL. Results A total of 45 patients were retrospectively included in the analysis. The PK of dalbavancin was described by a two-compartment model, and the PD of C-RP was described by an indirect turnover maximum inhibition model. The total dalbavancin concentration model estimate producing 50% of maximum C-RP production inhibition (IC 50 ) was 0.70 mg/L. Monte Carlo simulations showed that in patients with staphylococcal osteoarticular infections targeting total dalbavancin concentrations at > 14.5 mg/L at any time point may achieve C-RP production inhibition over time in > 95% of patients. Based on this, the findings showed that a cumulative dose of 3000 mg administered in the first 3 weeks may lead to a > 90% C-RP decrease versus baseline in approximately 5–6 weeks. In patients needing treatment prolongation, an additional 1500 mg dose after this period may maintain C-RP concentrations < 1 mg/dL for other 3 weeks. Conclusions A decrease in C-RP is related to dalbavancin exposure in osteoarticular infections. Targeting dalbavancin plasma concentrations above the efficacy threshold may be associated with effective treatment.

Neutrophil membrane-derived extracellular vesicles (NEVs) exhibit exceptional targeted delivery capabilities, efficiently transporting antibiotics through biological barriers to infection sites and bacterial biofilms.This biomimetic system, combining teicoplanin-loaded neutrophil membranes for targeted anti-inflammatory therapy, is particularly effective against drug-resistant infections.Teicoplanin-loaded NEVs (Teic@NEV) offer dual benefits: strong antibacterial activity and immunomodulation by reducing neutrophil swarming and inflammation.NEV-based delivery outperforms conventional therapies with lower toxicity. The platform enables precise delivery across multiple inflammatory disease models, including pneumonia, osteomyelitis, and colitis, highlighting its significant potential for clinical translation. Methicillin-resistant Staphylococcus aureus (MRSA) pneumonia has a high clinical incidence and is associated with a significant mortality risk. The existence of intracellular pathogens and the infection-induced swarming of neutrophils exacerbate the challenges in treating pneumonia. Here, we addressed these issues by developing a platform based on neutrophilic membrane-camouflaged teicoplanin (Teic@NEV) to kill bacteria in tissue and prevent inflammatory lung injury associated with MRSA pneumonia. Teic@NEV improved the efficiency of drug entry into cells, meaningfully increasing the intracellular drug concentration in infected cells and eliminating intracellular MRSA. Moreover, Teic@NEV enhanced the penetration of teicoplanin into the biofilm and improved antimicrobial and antibiofilm activities in vitro. Surprisingly, Teic@NEV delivered teicoplanin specifically to sites of inflammation and reduced lung injury by hindering neutrophil swarming in vivo. Thus, this platform represents an effective strategy to limit neutrophil swarming and kill intracellular pathogens in patients with MRSA pneumonia, demonstrating its significant potential for use in clinical practice. [Display omitted] Neutrophil membrane-camouflaged teicoplanin (Teic@NEV) has shown promising preclinical results by utilizing neutrophil chemotaxis for targeted antibiotic delivery. However, several key challenges must be addressed before clinical translation. Current barriers include scalability limitations of the membrane compression manufacturing process, the potential immunogenicity of engineered membranes in human subjects, and the need for thorough safety evaluation in complex infection microenvironments. Overcoming these hurdles will require standardized Good Manufacturing Practice (GMP)-compliant production protocols, comprehensive immunoprofile characterization in primate models, and combinatorial efficacy testing with existing antibiotics. One promising approach to addressing potential immunogenicity is the development of an induced pluripotent stem cell (iPSC)-derived neutrophil therapeutic system, achieved through in vitro stem cell gene editing and differentiation for universal targeted therapy. The proposed iPSC-derived neutrophil platform provides an ideal resource for generating immune cells, with well-established methodologies enabling the derivation of various cell types, including neutrophils. However, this approach will require further research into stem cell differentiation controls and in vivo persistence before leveraging a neutrophil-based delivery platform for the treatment of inflammatory and infectious diseases. Teicoplanin-loaded neutrophil membrane-derived extracellular vesicles (Teic@NEV) represent a neutrophil-mimicking nanoplatform that concurrently eliminates methicillin-resistant Staphylococcus aureus (MRSA) infections and prevents inflammatory lung damage via targeted antibiotic delivery and pathological neutrophil swarm modulation, outperforming standard therapies.

Introduction Dalbavancin is an antibiotic characterized by an extended half-life and efficacy against methicillin-resistant Staphylococci . Currently, there are only narrative reviews summarizing the evidence about the use of dalbavancin for infective endocarditis (IE), many of which are focused primarily on its use as consolidation therapy. For this reason, we conducted a systematic review to describe the clinical efficacy and the safety of dalbavancin in IE treatment. Methods We searched for available evidence using the MEDLINE (PubMed), Embase, Scopus, Cochrane Library and Web of Science libraries, with no restrictions regarding the publication year. The risk of bias was performed using the Cochrane ROBINS-I tool for the comparative studies and the Newcastle-Ottawa Scale for descriptive studies. Results Nine studies were included. All of them were observational. Native valve endocarditis was the most common kind of IE found in the studies’ populations (128/263, 48.7%), followed by prosthetic valve endocarditis, and cardiovascular implantable electronic device-related endocarditis. Coagulase-negative Staphylococci were the most common pathogens isolated (83/269, 30.1%), followed by S. aureus , Enterococci spp and Streptococci spp. Five out of nine studies documented a clinical failure rate of less than 10%. Dalbavancin showed a favourable safety profile. Dalbavancin appears to be a promising option for the consolidation therapy of IE. However, further studies comparing dalbavancin with standard of care are needed. PROSPERO registration number CRD42023430032.

We conducted a prospective, randomized study to compare the efficacy of oral fusidic acid, oral metronidazole, oral vancomycin, and oral teicoplanin for the treatment of Clostridium difficile—associated diarrhea. Treatment resulted in clinical cure for 94% of the patients who were treated with vancomycin, 96% of those treated with teicoplanin, 93% of those treated with fusidic acid, and 94% of those treated with metronidazole. Clinical symptoms recurred in 16% of patients treated with vancomycin, 7% of those treated with teicoplanin, 28% of those treated with fusidic acid, and 16% of those treated with metronidazole. There was asymptomatic carriage of C. difficile toxin in 13% of patients treated with vancomycin,4% of those treated with teicoplanin, 24% of those treated with fusidicacid, and 16% of those treated with metronidazole. No adverse effectsrelated to therapy with vancomycin or teicoplanin were observed. Considering the costs of treatment, our findings suggest that metronidazole is the drug of choice for C. difficile—associated diarrhea and that glycopeptides should be reserved for patients who cannot tolerate metronidazole or who do not respond to treatment with this drug.