Teicoplanin

Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a pandemic worldwide. Currently, however, no effective drug or vaccine is available to treat or prevent the resulting coronavirus disease 2019 (COVID-19). Here, we report our discovery of a promising anti-COVID-19 drug candidate, the lipoglycopeptide antibiotic dalbavancin, based on virtual screening of the FDA-approved peptide drug library combined with in vitro and in vivo functional antiviral assays. Our results showed that dalbavancin directly binds to human angiotensin-converting enzyme 2 (ACE2) with high affinity, thereby blocking its interaction with the SARS-CoV-2 spike protein. Furthermore, dalbavancin effectively prevents SARS-CoV-2 replication in Vero E6 cells with an EC50 of ~12 nM. In both mouse and rhesus macaque models, viral replication and histopathological injuries caused by SARS-CoV-2 infection are significantly inhibited by dalbavancin administration. Given its high safety and long plasma half-life (8-10 days) shown in previous clinical trials, our data indicate that dalbavancin is a promising anti-COVID-19 drug candidate.

Emerging resistance to colistin in clinical Acinetobacter baumannii isolates is of growing concern. Since current treatment options for these strains are extremely limited, we investigated the in vitro activities of various antimicrobial combinations against colistin-resistant A. baumannii Nine clinical isolates (8 from bacteremia cases and 1 from a pneumonia case) of colistin-resistant A. baumannii were collected in Asan Medical Center, Seoul, South Korea, between January 2010 and December 2012. To screen for potential synergistic effects, multiple combinations of two antimicrobials among 12 commercially available agents were tested using the multiple-combination bactericidal test (MCBT). Checkerboard tests were performed to validate these results. Among the 9 colistin-resistant strains, 6 were pandrug resistant and 3 were extensively drug resistant. With MCBT, the most effective combinations were colistin-rifampin and colistin-teicoplanin; both combinations showed synergistic effect against 8 of 9 strains. Colistin-aztreonam, colistin-meropenem, and colistin-vancomycin combinations showed synergy against seven strains. Colistin was the most common constituent of antimicrobial combinations that were active against colistin-resistant A. baumannii Checkerboard tests were then conducted in colistin-based combinations. Notably, colistin-rifampin showed synergism against all nine strains (100%). Both colistin-vancomycin and colistin-teicoplanin showed either synergy or partial synergy. Colistin combined with another β-lactam agent (aztreonam, ceftazidime, or meropenem) showed a relatively moderate effect. Colistin combined with ampicillin-sulbactam, tigecycline, amikacin, azithromycin, or trimethoprim-sulfamethoxazole demonstrated limited synergism. Using MCBT and checkerboard tests, we found that only colistin-based combinations, particularly those with rifampin, glycopeptides, or β-lactams, may confer therapeutic benefits against colistin-resistant A. baumannii.

Activity of dalbavancin against methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-resistant Staphylococcus epidermidis (MRSE) in biofilm was investigated and the microbicidal biofilm concentrations (MBC) were determined. Biofilms obtained from ten MRSA and ten MRSE bloodstream isolates, collected from patients in the General Hospital of Vienna between 2012 and 2015, were incubated with dalbavancin in trypticase soy broth (TSB) in serial dilution from 0.0625 mg/l to 256 mg/l using a microtiter plate biofilm model. The plates were incubated for 24 h at 37 ° C and 50% humidity. Biofilms were fixed with 2.5% glutaraldehyde and stained with crystal violet. Subsequently the optical density (OD620) was used to measure the MBC, defined as the concentration of dalbavancin leading to a 50% reduction of biofilm. MBC for MRSA was 1 mg/l-4 mg/l (minimal inhibitory concentrations (MIC) 0.0312 mg/l-0.064 mg/l). MBC for MRSE was 2 mg/l-16 mg/l (MIC 0.023 mg/l-0.0625 mg/l). Dalbavancin successfully reduced MRSA and MRSE in biofilms, and therefore provides a promising option for the treatment of biofilm-associated infections.

PurposeInfective endocarditis (IE) requires prolonged intravenous antibiotic therapy, leading to extended hospitalization and increased morbidity. Dalbavancin, a long-acting antibiotic with excellent tissue penetration and a favorable safety profile, can be a promising alternative. This systematic review aimed to investigate the current literature regarding the use of dalbavancin for infective endocarditis.MethodsA systematic search of PubMed and Scopus was conducted according to PRISMA guidelines. Eligible studies included adult patients (≥ 18 years) with IE diagnosed by the modified Duke criteria, treated with dalbavancin as monotherapy or sequential/consolidation therapy. Data extraction included demographics, type of IE, causative pathogen, dosing regimen, surgical intervention, adverse events, and outcomes. Descriptive analyses were performed.ResultsThirty-eight studies including 565 patients were analyzed. The overall cure rate was 88.0%, with a similar success rate across native valve (90.1%), prosthetic valve (90.0%), and cardiac device-related IE (86.0%). Staphylococcus aureus, Coagulase-negative staphylococci (CNS), Streptococcus spp., and Enterococcus faecalis were the most common pathogens. Cure rates were comparable among most pathogens, though a lower cure rate was evident in infections due to Enterococcus faecalis compared to Streptococcus spp. (80.7% vs. 96.6%, p = 0.008). An effective antimicrobial exposure of 2 weeks had similar success rate compared to a longer period of effective antimicrobial exposure (p = 0.31). Adverse events were rare (2.9%), with mild rash being the most common.ConclusionsDalbavancin demonstrates high cure rates and excellent tolerability in IE, and could offer an attractive alternative to conventional prolonged intravenous therapy. Further randomized controlled trials are warranted to define standardized protocols.