MRSA
Experimental TherapeuticsPharmacodynamics of ClpP-Activating Antibiotic Combinations against Gram-Positive PathogensIt is often difficult to cure endocarditis, osteomyelitis, and device-associated infections caused by Gram-positive pathogens, despite therapy with clinically appropriate antibiotics. This may be due to antibiotic tolerance or resistance development. Acyldepsipeptides (ADEPs) are a class of bactericidal compounds active against a variety of clinically important Gram-positive bacteria, including staphylococci, streptococci, and...
Mechanisms of ResistanceThe Sle1 Cell Wall Amidase Is Essential for β-Lactam Resistance in Community-Acquired Methicillin-Resistant Staphylococcus aureus USA300Most clinically relevant methicillin-resistant Staphylococcus aureus (MRSA) strains have become resistant to β-lactams antibiotics through horizontal acquisition of the mecA gene encoding PBP2a, a peptidoglycan transpeptidase with low affinity for β-lactams. The level of resistance conferred by mecA is, however, strain dependent, and the mechanisms...
SusceptibilitySusceptibility of Methicillin-Resistant Staphylococcus aureus to Five Quinazolinone AntibacterialsThe in vitro activities of five quinazolinone antibacterials, compounds Q1 to Q5, were tested against 210 strains of methicillin-resistant Staphylococcus aureus (MRSA). The MIC50/MIC90 values (in μg/ml) were as follows: Q1, 0.5/2; Q2, 1/4; Q3, 2/4; Q4, 0.06/0.25; and Q5, 0.125/0.5.
Mechanisms of ResistanceRoles of Lytic Transglycosylases in Biofilm Formation and β-Lactam Resistance in Methicillin-Resistant Staphylococcus aureusStaphylococcus aureus is responsible for numerous community outbreaks and is one of the most frequent causes of nosocomial infections with significant morbidity and mortality. While the function of lytic transglycosylases (LTs) in relation to cell division, biofilm formation, and antibiotic resistance has been determined for several bacteria, their role in...
Editor's Pick MinireviewAntimicrobial Resistance in Methicillin-Resistant Staphylococcus aureus to Newer Antimicrobial AgentsInfections caused by methicillin-resistant Staphylococcus aureus (MRSA) result in significant morbidity and mortality for patients in both community and health care settings. This is primarily due to the difficulty in treating MRSA, which is often resistant to multiple classes of antibiotics.
Editor's Pick Letter to the EditorIs Daptomycin plus Ceftaroline the Way To Go for Methicillin-Resistant Staphylococcus aureus Bacteremia?
Mechanisms of ResistanceEmergence of Oxacillin Resistance in Stealth Methicillin-Resistant Staphylococcus aureus Due to mecA Sequence InstabilityStaphylococcus aureus strains that possess a mecA gene but are phenotypically susceptible to oxacillin and cefoxitin (OS-MRSA) have been recognized for over a decade and are a challenge for diagnostic laboratories. The mechanisms underlying the discrepancy vary from isolate to isolate.
Experimental TherapeuticsIn Vivo Pharmacokinetic/Pharmacodynamic Targets of Levonadifloxacin against Staphylococcus aureus in a Neutropenic Murine Lung Infection ModelLevonadifloxacin is a novel benzoquinolizine subclass of fluoroquinolone, active against quinolone-resistant Staphylococcus aureus. A phase 3 trial for levonadifloxacin and its oral prodrug was recently completed. The present study identified area under the concentration-time curve for the free, unbound fraction of a drug divided by the MIC (fAUC/MIC) as an...
Experimental TherapeuticsEfficacy of a Multimechanistic Monoclonal Antibody Combination against Staphylococcus aureus Surgical Site Infections in MiceSurgical site infections (SSIs) are commonly caused by Staphylococcus aureus. We report that a combination of three monoclonal antibodies (MEDI6389) that neutralize S. aureus alpha-toxin, clumping factor A, and four leukocidins (LukSF, LukED, HlgAB, and HlgCB) plus vancomycin had enhanced efficacy...
PharmacologyValidation and Application of an HPLC-DAD Method for Routine Therapeutic Drug Monitoring of CeftobiproleCeftobiprole is a fifth-generation cephalosporin approved for the treatment of pneumonia, with a broad antibacterial spectrum, including potent activity against methicillin-resistant Staphylococcus aureus. As for the other cephalosporins, high pharmacokinetic variability and concentration-dependent neurotoxicity are expected.