Potential use of targeted enzymatic agents in the treatment of Staphylococcus aureus biofilm-related infections.

Staphylococcus aureus is a leading cause of healthcare-associated infections. The ability of S. aureus to attach and subsequently accumulate on the surfaces of implanted medical devices and in host tissues makes infections caused by this pathogen difficult to treat. Current treatments have been shown to have limited effect on surface-associated S. aureus, and may be enhanced by the addition of a dispersal agent. This study assessed the enzymatic agents dispersin B, lysostaphin, alpha amylase, V8 protease and serrapeptase, alone and in combination with vancomycin and rifampicin, against biofilms formed by meticillin-resistant and -susceptible strains of S. aureus. The efficacy of both antibiotics was enhanced when combined with any of the dispersal agents. Lysostaphin and serrapeptase were the most effective dispersal agents against all strains tested. These data indicate that combinations of biofilm dispersal agents and antibiotics may extend the therapeutic options for the treatment of S. aureus biofilm-associated infections.

Eradication of Staphylococcus aureus Catheter-Related Biofilm Infections Using ML:8 and Citrox.

Staphylococci are a leading cause of catheter-related infections (CRIs) due to biofilm formation. CRIs are typically managed by either device removal or systemic antibiotics, often in combination with catheter lock solutions (CLSs). CLSs provide high concentrations of the antimicrobial agent at the site of infection. However, the most effective CLSs against staphylococcal biofilm-associated infections have yet to be determined. The purpose of this study was to evaluate the efficacy and suitability of two newly described antimicrobial agents, ML:8 and Citrox, as CLSs against Staphylococcus aureus biofilms. ML:8 (1% [vol/vol]) and Citrox (1% [vol/vol]), containing caprylic acid and flavonoids, respectively, were used to treat S. aureus biofilms grown in vitro using newly described static and flow biofilm assays. Both agents reduced biofilm viability >97% after 24 h of treatment. Using a rat model of CRI, ML:8 was shown to inactivate early-stage S. aureus biofilms in vivo, while Citrox inactivated established, mature in vivo biofilms. Cytotoxicity and hemolytic activity of ML:8 and Citrox were equivalent to those of other commercially available CLSs. Neither ML:8 nor Citrox induced a cytokine response in human whole blood, and exposure of S. aureus to either agent for 90 days was not associated with any increase in resistance. Taken together, these data reveal the therapeutic potential of these agents for the treatment of S. aureus catheter-related biofilm infections.

In Vitro Approach for Identification of the Most Effective Agents for Antimicrobial Lock Therapy in the Treatment of Intravascular Catheter-Related Infections Caused by Staphylococcus aureus.

Infection of intravascular catheters by Staphylococcus aureus is a significant risk factor within the health care setting. To treat these infections and attempt salvage of an intravascular catheter, antimicrobial lock solutions (ALSs) are being increasingly used. However, the most effective ALSs against these biofilm-mediated infections have yet to be determined, and clinical practice varies greatly. The purpose of this study was to evaluate and compare the efficacies of antibiotics and antiseptics in current clinical use against biofilms produced by reference and clinical isolates of S. aureus Static and flow biofilm assays were developed using newly described in vivo-relevant conditions to examine the effect of each agent on S. aureus within the biofilm matrix. The antibiotics daptomycin, tigecycline, and rifampin and the antiseptics ethanol and Taurolock inactivated established S. aureus biofilms, while other commonly used antistaphylococcal antibiotics and antiseptic agents were less effective. These findings were confirmed by live/dead staining of S. aureus biofilms formed and treated within a flow cell model. The results from this study demonstrate the most effective clinically used agents and their concentrations which should be used within an ALS to treat S. aureus-mediated intravascular catheter-related infections.

Mupirocin resistance: clinical implications and potential alternatives for the eradication of MRSA.

Mupirocin 2% ointment is used either alone or with skin antiseptics as part of a comprehensive MRSA decolonization strategy. Increased mupirocin use predisposes to mupirocin resistance, which is significantly associated with persistent MRSA carriage. Mupirocin resistance as high as 81% has been reported. There is a strong association between previous mupirocin exposure and both low-level and high-level mupirocin resistance. High-level mupirocin resistance (mupA carriage) is also linked to MDR. Among MRSA isolates, the presence of the qacA and/or qacB gene, encoding resistance to chlorhexidine, ranges from 65% to 91%, which, along with mupirocin resistance, is associated with failed decolonization. This is of significant concern for patient care and infection prevention and control strategies as both these agents are used concurrently for decolonization. Increasing bacterial resistance necessitates the discovery or development of new antimicrobial therapies. These include, for example, polyhexanide, lysostaphin, ethanol, omiganan pentahydrochloride, tea tree oil, probiotics, bacteriophages and honey. However, few of these have been evaluated fully or extensively tested in clinical trials and this is required to in part address the implications of mupirocin resistance.

Acute epididymo-orchitis caused by Pseudomonas aeruginosa and treated with ciprofloxacin.

Acute epididymo-orchitis caused by Pseudomonas aeruginosa is relatively unusual but difficult to treat, especially in the elderly. We report three cases involving P. aeruginosa all of which concerned patients with preexisting genito-urinary disease. The properties of ciprofloxacin make it suitable for the treatment of this condition. Its use was followed by clinical cure in all three patients and eradication of P. aeruginosa in two of them.