fosfomycin and Staphylococcal-Skin-Infections

The gap between the emergence of antibiotic resistance and new antibiotic development has drawn attention to old antibiotics whose spectrum of coverage frequently comprises highly resistant bacteria. However, these antibiotics have frequently not undergone the structured process of antibiotic development of modern antibiotics, from pharmacokinetic/pharmacodynamic (PK/PD) studies establishing safe and effective dosing, establishment of susceptibility breakpoints, to clinical trials establishing clinical safety and effectiveness. In this review, we highlight the gaps for which we need old antibiotics in community- and hospital-acquired infections. Reviewing recently published and ongoing randomised controlled trials (RCTs) shows advances in our understanding of the efficacy and effectiveness of oral fosfomycin, mecillinam and nitrofurantoin for cystitis, and of trimethoprim/sulfamethoxazole for complicated skin infections caused by methicillin-resistant Staphylococcus aureus (MRSA) in the community. Summarising older evidence shows the inferiority of chloramphenicol versus modern antibiotics for severe infections. We lack studies on severe infections caused by carbapenem-resistant Gram-negative bacteria and other multidrug-resistant (MDR) bacteria in hospitalised and critically ill patients; ongoing studies assessing colistin and intravenous fosfomycin might fill in some gaps. In the re-development process of old antibiotics, we mandate modern PK/PD studies comprising special populations as well as RCTs addressing the target population of patients in need of these antibiotics powered to examine patient-relevant outcomes. Structured antibiotic re-development from the laboratory to evidence-based treatment recommendations requires public funding, multidisciplinary collaboration, international co-ordination, and methods to streamline the recruitment of critically ill patients infected by MDR bacteria.

Topics: Amdinocillin; Anti-Bacterial Agents; Carbapenem-Resistant Enterobacteriaceae; Cross Infection; Drug Combinations; Drug Resistance, Multiple, Bacterial; Evidence-Based Medicine; Fosfomycin; Humans; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Nitrofurantoin; Staphylococcal Skin Infections; Sulfamethizole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

MRSA is a major concern in community settings and in health care. The emergence of biofilms and persister cells substantially increases its antimicrobial resistance. It is very urgent to develop new antimicrobials to solve this problem.. Idarubicin was profiled to assess its antimicrobial effects. We investigated the antimicrobial effects of idarubicin against MRSA by time-kill analysis. The antibiofilm efficacy of idarubicin was assessed by crystal violet and XTT staining, followed by laser confocal microscopy observation. The mechanisms underlying the antimicrobial effects were studied by transmission electron microscopy, all-atom molecular dynamic simulations, SYTOX staining, surface plasma resonance, and DNA gyrase inhibition assay. Further, we addressed the antimicrobial efficacy in wound and subcutaneous abscess infection. Idarubicin kills MRSA cells by disrupting the lipid bilayers and interrupting the DNA topoisomerase IIA subunits, and idarubicin shows synergistic antimicrobial effects with fosfomycin. Through synergy with a single dose treatment fosfomycin and the addition of the cell protector amifostine, the cytotoxicity and cardiotoxicity of idarubicin were significantly reduced without affecting its antimicrobial effects. Idarubicin alone or in combination with fosfomycin exhibited considerable efficacy in a subcutaneous abscess mouse model of MRSA infection. In addition, idarubicin also showed a low probability of causing resistance and good postantibiotic effects.. Idarubicin and its analogs have the potential to become a new class of antimicrobials for the treatment of MRSA-related infections.

Topics: Animals; Anti-Bacterial Agents; Biofilms; Drug Repositioning; Drug Synergism; Female; Fosfomycin; Idarubicin; Methicillin-Resistant Staphylococcus aureus; Mice; Mice, Inbred C57BL; Microbial Sensitivity Tests; Molecular Dynamics Simulation; Specific Pathogen-Free Organisms; Staphylococcal Skin Infections

Clinical efficacy of a composition of nanostructuared silicon dioxide and fosfomycin in treating the skin abscess induced by Staphylococcus aureus inoculation in rabbits has been studied. It is established that the proposed composition of silicon dioxide nanoparticles and fosfomycin exhibits higher therapeutic potential in treating local purulent-septic process in skin of test animals. The therapy with this composition reduced the number of abscesses in the skin by 50% after two days of application and by 80 - 90% after five days of therapy as compared to therapy with application of chloramphenicol liniment (15.0 vs. 4.0 and 7.0 vs. 2.0, respectively).

Topics: Animals; Anti-Bacterial Agents; Chloramphenicol; Drug Compounding; Fosfomycin; Male; Nanoparticles; Polymers; Rabbits; Silicon Dioxide; Skin; Staphylococcal Skin Infections; Staphylococcus aureus; Treatment Outcome

Appropriate antimicrobial therapy and surgical intervention may be required in diabetic patients presenting with severe bacterial foot infection. Methicillin-resistant Staphylococcus aureus (MRSA) agents such as fosfomycin are increasingly in demand because of recent concern regarding vancomycin and daptomycin efficacy and constant use. Intravenous fosfomycin is approved for the therapy of severe soft tissue infections and is highly active against methicillin-susceptible S. aureus and MRSA. in the present study we investigated fosfomycin's ability to penetrate bone tissue in diabetic patients suffering from severe bacterial foot infection.. The well established microdialysis technique was utilized to determine fosfomycin concentrations in metatarsal bone in nine patients scheduled for partial bone resection due to bacterial foot infection and osteomyelitis. Plasma and unaffected subcutaneous adipose tissue served as reference compartments.. After a single intravenous dose of approximately 100 mg of fosfomycin per kg of body weight, the mean C(max), T(max) and AUC(0-6) for bone were 96.4 mg/L, 3.9 h and 330.0 mg x h/L, respectively. The degree of tissue penetration as determined by the ratios of the AUC(0-6) for bone to plasma and for subcutaneous adipose tissue to plasma were 0.43 +/- 0.04 and 0.76 +/- 0.05, respectively.. On the basis of relevant pharmacokinetic-pharmacodynamic indices, it seems that fosfomycin is an effective antibiotic for the treatment of deep-seated diabetic foot infections with osseous matrix involvement.

Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; Bone and Bones; Diabetic Foot; Female; Fosfomycin; Humans; Injections, Intravenous; Male; Middle Aged; Skin; Staphylococcal Skin Infections