Antimicrobial agents and chemotherapy
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Antimicrob. Agents Chemother. · Nov 2012
High rate of qacA- and qacB-positive methicillin-resistant Staphylococcus aureus isolates from chlorhexidine-impregnated catheter-related bloodstream infections.
Chlorhexidine has been widely used for infection control. Although the use of chlorhexidine-impregnated catheters has reduced catheter-related infections, chlorhexidine-resistant Staphylococcus aureus has emerged. The correlation between the existence of the chlorhexidine-resistant genes qacA and qacB (qacA/B) in methicillin-resistant Staphylococcus aureus (MRSA) isolates and the effectiveness of chlorhexidine-impregnated catheters in the prevention of MRSA infections is unknown. ⋯ Results of PCR analyses showed that 3.3% (n = 2) of MSSA and 43.8% (n = 42) of MRSA isolates harbored qacA/B and 5% (n = 3) of MSSA and 25% (n = 24) of MRSA isolates contained smr. With multivariate logistic regression analyses, the significant risk factors for definite CRBSI with chlorhexidine-impregnated catheters were determined to be S. aureus isolates with qacA/B and a chlorhexidine MIC of ≥2 μg/ml (odds ratios [OR], 9.264 and 8.137, respectively, in all 156 S. aureus isolates and 6.097 and 4.373, respectively, in the 96 MRSA isolates). Further prospective studies are needed to investigate the transmission of these biocide-resistant genes.
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Antimicrob. Agents Chemother. · Nov 2012
Has the emergence of community-associated methicillin-resistant Staphylococcus aureus increased trimethoprim-sulfamethoxazole use and resistance?: a 10-year time series analysis.
There are an increasing number of indications for trimethoprim-sulfamethoxazole use, including skin and soft tissue infections due to community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA). Assessing the relationship between rates of use and antibiotic resistance is important for maintaining the expected efficacy of this drug for guideline-recommended conditions. Using interrupted time series analysis, we aimed to determine whether the 2005 emergence of CA-MRSA and recommendations of trimethoprim-sulfamethoxazole as the preferred therapy were associated with changes in trimethoprim-sulfamethoxazole use and susceptibility rates. ⋯ The changes in susceptibility rates of S. aureus to trimethoprim-sulfamethoxazole and to methicillin were also not significantly different. The CA-MRSA period is associated with a significant increase in use of trimethoprim-sulfamethoxazole but not with significant changes in the rates of susceptibilities among clinical isolates. There is also no evidence for selection of organisms with increased resistance to other antimicrobials in relation to increased trimethoprim-sulfamethoxazole use.
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Antimicrob. Agents Chemother. · Nov 2012
Pyrazinamide may improve fluoroquinolone-based treatment of multidrug-resistant tuberculosis.
The role of pyrazinamide in the current treatment of multidrug-resistant (MDR) tuberculosis (TB) is uncertain. From a territory-wide registry of MDR-TB cases diagnosed between 1995 and 2009, we assembled a cohort of 194 patients with MDR pulmonary TB given fluoroquinolone-containing regimens. Stratified by pyrazinamide use and susceptibility, there were 83 users with pyrazinamide-susceptible MDR-TB (subgroup A), 24 users with pyrazinamide-resistant MDR-TB (subgroup B), 40 nonusers with pyrazinamide-susceptible MDR-TB (subgroup C), and 47 nonusers with pyrazinamide-resistant MDR-TB (subgroup D). ⋯ Comparison of pyrazinamide users showed that pyrazinamide increased the incidence proportion of early culture conversion and that of cure or treatment completion by a best estimate of 38% for both. This magnitude of change exceeded the 15 to 20% increase in the 2-month culture conversion rate of drug-susceptible TB that results from adding pyrazinamide to isoniazid and rifampin. Pyrazinamide is likely important in fluoroquinolone-based treatment of MDR-TB.
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Antimicrob. Agents Chemother. · Oct 2012
Antibacterial activities of iron chelators against common nosocomial pathogens.
The activities of iron chelators (deferoxamine, deferiprone, Apo6619, and VK28) were evaluated against type strains of Acinetobacter baumannii, Pseudomonas aeruginosa, Staphylococcus aureus, Klebsiella pneumoniae, and Escherichia coli. Deferiprone, Apo6619, and VK28 each inhibited growth in standard and RPMI tissue culture medium, while deferoxamine had no effect. Additionally, time-kill assays revealed that VK28 had a bacteriostatic effect against S. aureus. Therefore, these newly developed iron chelators might provide a nontraditional approach for treatment of bacterial infections.
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Antimicrob. Agents Chemother. · Sep 2012
Broadening the spectrum of β-lactam antibiotics through inhibition of signal peptidase type I.
The resistance of methicillin-resistant Staphylococcus aureus (MRSA) to all β-lactam classes limits treatment options for serious infections involving this organism. Our goal is to discover new agents that restore the activity of β-lactams against MRSA, an approach that has led to the discovery of two classes of natural product antibiotics, a cyclic depsipeptide (krisynomycin) and a lipoglycopeptide (actinocarbasin), which potentiate the activity of imipenem against MRSA strain COL. We report here that these imipenem synergists are inhibitors of the bacterial type I signal peptidase SpsB, a serine protease that is required for the secretion of proteins that are exported through the Sec and Tat systems. ⋯ Synergy is restricted to β-lactam antibiotics and is not observed with other antibiotic classes. We propose that the SpsB inhibitors synergize with β-lactams by preventing the signal peptidase-mediated secretion of proteins required for β-lactam resistance. Combinations of SpsB inhibitors and β-lactams may expand the utility of these widely prescribed antibiotics to treat MRSA infections, analogous to β-lactamase inhibitors which restored the utility of this antibiotic class for the treatment of resistant Gram-negative infections.