ppi-0903 and Diabetic-Foot

Foot infections are a major cause of morbidity in people with diabetes and the most common cause of diabetes-related hospitalization and lower extremity amputation. Staphylococcus aureus is by far the most frequent species isolated from these infections. In particular, methicillin-resistant S. aureus (MRSA) has emerged as a major clinical and epidemiological problem in hospitals. MRSA strains have the ability to be resistant to most β-lactam antibiotics, but also to a wide range of other antimicrobials, making infections difficult to manage and very costly to treat. To date, there are two fifth-generation cephalosporins generally efficacious against MRSA, ceftaroline and ceftobripole, sharing a similar spectrum. Biofilm formation is one of the most important virulence traits of S. aureus. Biofilm growth plays an important role during infection by providing defence against several antagonistic mechanisms. In this study, we analysed the antimicrobial susceptibility patterns of biofilm-producing S. aureus strains isolated from diabetic foot infections. The antibiotic minimum inhibitory concentration (MIC) was determined for ten antimicrobial compounds, along with the minimum biofilm inhibitory concentration (MBIC) and minimum biofilm eradication concentration (MBEC), followed by PCR identification of genetic determinants of biofilm production and antimicrobial resistance.. Results demonstrate that very high concentrations of the most used antibiotics in treating diabetic foot infections (DFI) are required to inhibit S. aureus biofilms in vitro, which may explain why monotherapy with these agents frequently fails to eradicate biofilm infections. In fact, biofilms were resistant to antibiotics at concentrations 10-1000 times greater than the ones required to kill free-living or planktonic cells. The only antibiotics able to inhibit biofilm eradication on 50 % of isolates were ceftaroline and gentamicin.. The results suggest that the antibiotic susceptibility patterns cannot be applied to biofilm established infections. Selection of antimicrobial therapy is a critical step in DFI and should aim at overcoming biofilm disease in order to optimize the outcomes of this complex pathology.

Topics: Anti-Bacterial Agents; beta-Lactams; Biofilms; Ceftaroline; Cephalosporins; Diabetic Foot; Gentamicins; Humans; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Polymerase Chain Reaction; Staphylococcal Infections; Staphylococcus aureus

To ascertain which demographic, clinical, and microbiological factors might affect clinical outcomes of patients with diabetic foot infections, excluding known osteomyelitis, by analysing Clinical Assessment Program and Teflaro® Utilization Registry study data of patients treated with ceftaroline fosamil.. At participating study centres, we collected data by randomized selection and chart review, including patient demographics, co-morbidities, infecting pathogens, antibiotic use, surgical interventions, and clinical response. Evaluable patients were those with data sufficient to determine clinical outcome. Clinical success was defined as clinical cure with no use of other antibiotics or clinical improvement with a switch to oral antibiotic therapy at the end of intravenous ceftaroline fosamil treatment.. Among 201 patients (mean age 61.7 years, mean body mass index 33.2 and 57% male patients), 40% had peripheral vascular disease. Prior antibiotic therapy had been given to 161 (80%) of the patients, most commonly with vancomycin and/or piperacillin-tazobactam. Patients received ceftaroline fosamil for mean duration of 6.1 days (range 1-30), as monotherapy in 130 (65%) patients and concurrently with other antibiotics in 71 (35%). Bacterial pathogens were identified in 114 (57%) of the patients; methicillin-resistant Staphylococcus aureus and methicillin-sensitive S. aureus were isolated from 56 (49%) and 28 (25%) of culture-positive patients respectively. Clinical success was noted in 81% of patients and was not significantly associated with co-morbidities, pathogen type, or need for surgical intervention.. Ceftaroline fosamil treatment of diabetic foot infections was associated with high clinical success, including inpatients with obesity, co-morbidities, or methicillin-resistant Staphylococcus aureus or mixed infections or requiring surgical intervention.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Body Mass Index; Ceftaroline; Cephalosporins; Cohort Studies; Comorbidity; Diabetic Foot; Drug Monitoring; Drug Therapy, Combination; Female; Humans; Infusions, Intravenous; Male; Methicillin-Resistant Staphylococcus aureus; Middle Aged; Obesity; Overweight; Retrospective Studies; Staphylococcal Infections; Staphylococcus aureus