Antimicrobial agents and chemotherapy
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Antimicrob. Agents Chemother. · Dec 2012
Ceftobiprole efficacy in vitro against Panton-Valentine leukocidin production and in vivo against community-associated methicillin-resistant Staphylococcus aureus osteomyelitis in rabbits.
Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) can cause osteomyelitis with severe sepsis and/or local complications in which a Panton-Valentine leukocidin (PVL) role is suspected. In vitro sub-MIC antibiotic effects on growth and PVL production by 11 PVL(+) MRSA strains, including the major CA-MRSA clones (USA300, including the LAC strain; USA400; and USA1000), and 11 PVL(+) methicillin-susceptible S. aureus (MSSA) strains were tested in microplate culture. Time-kill analyses with ceftobiprole at its MIC were also run with LAC. ⋯ In vivo, the mean log(10) CFU/g of bone for ceftobiprole (1.44 ± 0.40) was significantly lower than that for vancomycin (2.37 ± 1.22) (P = 0.034), with 7/10 versus 5/11 bones sterilized, respectively. Combination with rifampin enhanced ceftobiprole (1.16 ± 0.04 CFU/g of bone [P = 0.056], 11/11 sterile bones) and vancomycin (1.23 ± 0.06 CFU/g [P = 0.011], 11/11 sterile bones) efficacies. Ceftobiprole bactericidal activity and the rifampin anti-PVL effect could play a role in these findings, which should be of interest for treating CA-MRSA osteomyelitis.
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Antimicrob. Agents Chemother. · Dec 2012
Virulent bacteriophages can target O104:H4 enteroaggregative Escherichia coli in the mouse intestine.
In vivo bacteriophage targeting of enteroaggregative Escherichia coli (EAEC) was assessed using a mouse intestinal model of colonization with the O104:H4 55989Str strain and a cocktail of three virulent bacteriophages. The colonization model was shown to mimic asymptomatic intestinal carriage found in humans. The addition of the cocktail to drinking water for 24 h strongly decreased ileal and weakly decreased fecal 55989Str concentrations in a dose-dependent manner. ⋯ These transient decreases were independent of the mouse microbiota, as similar results were obtained with axenic mice. We studied the infectivity of each bacteriophage in the ileal and fecal environments and found that 55989Str bacteria in the mouse ileum were permissive to all three bacteriophages, whereas those in the feces were permissive to only one bacteriophage. Our results provide the first demonstration that bacterial permissivity to infection with virulent bacteriophages is not uniform throughout the gut; this highlights the need for a detailed characterization of the interactions between bacteria and bacteriophages in vivo for the further development of phage therapy targeting intestinal pathogens found in the gut of asymptomatic human carriers.
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Antimicrob. Agents Chemother. · Nov 2012
Randomized Controlled Trial Comparative StudyA randomized, evaluator-blind, phase 2 study comparing the safety and efficacy of omadacycline to those of linezolid for treatment of complicated skin and skin structure infections.
A randomized, investigator-blind, multicenter phase 2 trial involving patients with complicated skin and skin structure infections (cSSSI) compared the safety and efficacy of omadacycline, a broad-spectrum agent with activity against methicillin-resistant Staphylococcus aureus (MRSA), to those of linezolid (with or without aztreonam). Patients were randomized 1:1 to omadacycline (100 mg intravenously [i.v.] once a day [QD] with an option to transition to 200 mg orally QD) or linezolid (600 mg i.v. twice daily [BID] with an option to transition to 600 mg orally BID) at 11 U. S. sites. ⋯ Rates of successful clinical response in the intent-to-treat (ITT) and clinical evaluable (CE) populations favored omadacycline (ITT, 88.3% versus 75.9%; 95% confidence interval [CI], 1.9 to 22.9; CE, 98.0% versus 93.2%; 95% CI, -1.7 to 11.3). For microbiologically evaluable (ME) patients with S. aureus infections, the clinical success rates were 97.2% (70/72) in omadacycline-treated and 92.7% (51/55) in linezolid-treated patients. This phase 2 experience supports conclusions that omadacycline is well tolerated in cSSSI patients and that this aminomethylcycline has potential to be an effective treatment for serious skin infections.
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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.