meropenem and Skin-Diseases

Monte Carlo simulation is often used to predict the cumulative fraction of response (CFR) for antibiotics, but the relevance of these predictions to outcomes in humans has not been well studied. We compared the CFR for meropenem 500 mg every 8h against pathogens causing complicated skin and skin structure infections from a randomised, multicentre clinical trial with clinical response (CR) and microbiological response (MR). A population pharmacokinetic model was utilised to estimate pharmacokinetic parameters for 96 clinically evaluable patients with pathogen and minimum inhibitory concentration (MIC) data available. A 1000-subject Monte Carlo simulation was performed to estimate bacteriostatic (20% of time serum concentration above the MIC (T>MIC)) and bactericidal (40% T>MIC) exposures for comparison. Only the bactericidal CFR versus the CR was not statistically different (92% CR versus 91.9% CFR; 95% confidence interval of the difference, -7.7% to 4.2%), whilst bacteriostatic CFRs overestimated actual CR and MR. This study demonstrates that the use of Monte Carlo simulation to predict the CR of meropenem in complicated skin and skin structures is accurate.

Topics: Anti-Infective Agents; Bacterial Infections; Humans; Meropenem; Microbial Sensitivity Tests; Monte Carlo Method; Outcome Assessment, Health Care; Skin Diseases; Thienamycins

Multidrug resistant Gram-negative bacterial infections are an increasing public health threat due to rapidly rising resistance toward β-lactam antibiotics. The hydrolytic enzymes called β-lactamases are responsible for a large proportion of the resistance phenotype. β-Lactamase inhibitors (BLIs) can be administered in combination with β-lactam antibiotics to negate the action of the β-lactamases, thereby restoring activity of the β-lactam. Newly developed BLIs offer some advantage over older BLIs in terms of enzymatic spectrum but are limited to the intravenous route of administration. Reported here is a novel, orally bioavailable diazabicyclooctane (DBO) β-lactamase inhibitor. This new DBO, ETX1317, contains an endocyclic carbon-carbon double bond and a fluoroacetate activating group and exhibits broad spectrum activity against class A, C, and D serine β-lactamases. The ester prodrug of ETX1317, ETX0282, is orally bioavailable and, in combination with cefpodoxime proxetil, is currently in development as an oral therapy for multidrug resistant and carbapenem-resistant

Topics: Administration, Oral; Animals; Anti-Bacterial Agents; Azabicyclo Compounds; beta-Lactamase Inhibitors; beta-Lactamases; Drug Design; Drug Evaluation, Preclinical; Gram-Negative Bacteria; Gram-Positive Bacteria; Half-Life; Humans; Mice; Microbial Sensitivity Tests; Penicillin-Binding Proteins; Prodrugs; Protein Binding; Rats; Skin Diseases; Structure-Activity Relationship

Nosocomial infections after spinal surgery are relatively uncommon but potentially serious. The goal of diagnostic evaluation is to determine the extent of infection and identify the microorganism involved. Neuroimaging provides accurate information on correct topography, localization and propagation of the infection. Microbiological data are able to give aetiological causes. In this patient with severe, chronic polymicrobial spine infection with epidural abscess and CSF fistula due to multidrug-resistant organisms, the cure was achieved with long-term antimicrobial specific therapy with quinupristin-dalfopristin (50 days) and linezolid (100 days) with mild side effects. This positive result was due to combined medical and surgical treatment.

Topics: Acetamides; Anti-Bacterial Agents; Bacteria; Cerebrospinal Fluid; Combined Modality Therapy; Cross Infection; Curettage; Device Removal; Discitis; Epidural Abscess; Female; Fistula; Fluconazole; Fungi; Humans; Internal Fixators; Laminectomy; Linezolid; Lumbar Vertebrae; Meropenem; Methicillin Resistance; Middle Aged; Osteomyelitis; Oxazolidinones; Parkinson Disease; Prosthesis-Related Infections; Reoperation; Skin Diseases; Spinal Diseases; Spinal Stenosis; Staphylococcal Infections; Thienamycins; Virginiamycin