rifampin and dalbavancin

The anti-biofilm efficacy of dalbavancin (DAL) has been evaluated in static models. The comparative activity of DAL alone and with rifampicin (RIF) against biofilm-embedded methicillin-resistant Staphylococcus aureus (MRSA) was evaluated using an in vitro pharmacokinetic/pharmacodynamic (PK/PD) model.. Two MRSA strains (HUB-4, HUB-5) were evaluated with the Calgary Device System and the dynamic CDC-Biofilm Reactor over 144 h. Dosage regimens simulated the human PK of DAL (1500 mg, single dose), vancomycin (VAN) (1000 mg/12 h) and linezolid (LZD) (600 mg/12 h), alone and with RIF (600 mg/24 h). Efficacy was evaluated by assessing log10CFU/mL changes (ΔlogCFU/mL) and screening for resistance was conducted.. The minimal biofilm inhibitory/eradication concentrations of DAL were 0.25/16 mg/L (HUB-4) and 0.25/8 mg/L (HUB-5). In the PK/PD analysis, DAL alone showed limited efficacy but no development of resistance. Adding RIF improved the activities of DAL, VAN, and LZD, but RIF-resistant strains appeared over time in all cases. DAL-RIF was bactericidal against HUB-4 in the absence of resistance at 72 h and 144 h (ΔlogCFU/mL: -3.54±0.83, -4.32±0.12, respectively), an effect that was only achieved by LZD-RIF at 144 h (-3.33 ± 0.66). DAL-RIF activity against HUB-5 was impaired by RIF resistance to a greater extent than other combinations and this combination had no bactericidal effect.. The anti-biofilm efficacy of DAL was improved significantly by adding RIF. Although DAL resistance did not occur, RIF resistance appeared in all combination therapies and decreased their efficacy over time. DAL-RIF in vitro treatment appears to be a promising anti-biofilm therapy, but further studies are needed to evaluate the efficacy and risk of resistance in vivo.

Topics: Anti-Bacterial Agents; Biofilms; Humans; Linezolid; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Rifampin; Teicoplanin; Vancomycin

Dalbavancin is a novel glycopeptide antibiotic approved for the treatment of acute bacterial skin and skin structure infections (ABSSSIs). It is characterized by a potent activity against numerous Gram-positive pathogens, a long elimination half-life and a favorable safety profile. Most recently, its application for the treatment of periprosthetic joint infections (PJIs) was introduced. The aim of this study was to proof our hypothesis, that dalbavancin shows superior efficacy against staphylococcal biofilms on polyethylene (PE) disk devices compared with vancomycin and additive behavior in combination with rifampicin. Staphylococcus aureus biofilms were formed on PE disk devices for 96 h and subsequently treated with dalbavancin, vancomycin, rifampicin and dalbavancin-rifampicin combination at different concentrations. Quantification of antibacterial activity was determined by counting colony forming units (CFU/ml) after sonification of the PE, serial dilution of the bacterial suspension and plating on agar-plates. Biofilms were additionally life/dead-stained and visualized using fluorescence microscopy. Dalbavancin presented superior anti-biofilm activity compared to vancomycin. Additive effects of the combination dalbavancin and rifampicin were registered. Dalbavancin combined with rifampicin presents promising anti-biofilm activity characteristics in vitro. Further in vivo studies are necessary to establish recommendations for the general use of dalbavancin in the treatment of PJIs.

Topics: Agar; Anti-Bacterial Agents; Biofilms; Drug Synergism; Glycopeptides; Humans; In Vitro Techniques; Microbial Sensitivity Tests; Microscopy, Fluorescence; Polyethylene; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Stem Cells; Teicoplanin; Vancomycin

The determination of antibiotic potency against bacterial strains by assessment of their minimum inhibitory concentration normally uses a standardized broth microdilution assay procedure developed more than 50 years ago. However, certain antibiotics require modified assay conditions in order to observe optimal activity. For example, daptomycin requires medium supplemented with Ca

Topics: Aminoglycosides; Anti-Bacterial Agents; Calcium; Ciprofloxacin; Colistin; Culture Media; Depsipeptides; Escherichia coli; Factor Analysis, Statistical; Lipoglycopeptides; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Oxacillin; Penicillin G; Plastics; Polymyxin B; Polysorbates; Rifampin; Teicoplanin; Trimethoprim; Vancomycin

A deep sternal wound infection (DSWI) can become a severe complication after cardiac surgery, with in-hospital mortality rates reaching up to 35%. Staphylococci, particularly methicillin resistant Staphylococcus aureus (MRSA), play important roles in its etiology.. This case report presents a patient who underwent coronary artery bypass surgery, and suffered postoperatively from a DSWI caused by MRSA. The pathogen was susceptible to vancomycin and rifampicin in vitro; however, this therapy was clinically ineffective. Both clinical improvement and MRSA eradication were achieved after surgical debridement of the wound and the intravenous administration of dalbavancin.. We decided to administer dalbavancin because of its convenient pharmacological profile. The patient's tolerance of the antimicrobial was good, the biochemical markers of inflammation returned to the normal ranges, and the microbiological results one week after the dalbavancin administration were negative. A good clinical outcome was achieved with both the surgery and antimicrobial administration. In this case, dalbavancin was more effective in the treatment of the sternal and surrounding tissue infections caused by MRSA, when compared to vancomycin.

Topics: Anti-Bacterial Agents; Coronary Artery Bypass; Debridement; Humans; Male; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Middle Aged; Rifampin; ST Elevation Myocardial Infarction; Staphylococcal Infections; Sternum; Surgical Wound Infection; Teicoplanin; Vancomycin

The activity of dalbavancin, a representative of the lipoglycopeptide antibiotics, alone and in combination with rifampicin, was investigated against meticillin-resistant Staphylococcus aureus (MRSA) in a foreign-body infection model in guinea pigs. The MIC, MBC and time-kill profile of dalbavancin were determined for MRSA ATCC 43300 in the logarithmic (MBC(log)) and stationary (MBC(stat)) growth phases. The pharmacokinetic profile of dalbavancin was determined in sterile cage fluid in guinea pigs. The activity of intraperitoneal dalbavancin (40, 60 or 80 mg/kg as a single dose), rifampicin (12.5 mg/kg/12 h for 4 days) and their combination was assessed against planktonic and biofilm MRSA. The MIC of dalbavancin was 0.078 mg/L; MBC(log) and MBC(stat) were both >128× MIC. In time-kill studies, bacterial reduction of 3log(10)CFU/mL was achieved after 48 h at ≥32× MIC (logarithmic growth) and at ≥1× MIC (stationary growth). Dalbavancin was neither synergistic nor antagonistic with rifampicin, and prevented the emergence of rifampicin resistance in vitro. The half-life of dalbavancin in cage fluid was 35.8-45.4 h and the concentration remained above the MIC of MRSA during 7 days after a single dose. Dalbavancin reduced planktonic MRSA in cage fluid at high dose (60 mg/kg and 80 mg/kg) but failed to eradicate biofilm MRSA from cages. In combination with rifampicin, dalbavancin at 80 mg/kg cured 36% of infected cages, and emergence of rifampicin resistance was completely prevented. Dalbavancin at 80 mg/kg and in combination with rifampicin eradicated approximately one-third of cage-associated MRSA infections and prevented emergence of rifampicin resistance.

Topics: Animals; Anti-Bacterial Agents; Biofilms; Drug Resistance, Bacterial; Drug Therapy, Combination; Guinea Pigs; Male; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Prostheses and Implants; Rifampin; Staphylococcal Infections; Teicoplanin