International journal of antimicrobial agents
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Int. J. Antimicrob. Agents · Jun 2009
Case ReportsCharacterisation of a Staphylococcus aureus strain with progressive loss of susceptibility to vancomycin and daptomycin during therapy.
Following an initial response to vancomycin therapy, a patient with meticillin-resistant Staphylococcus aureus (MRSA) bacteraemia developed endocarditis, failed a second course of vancomycin and then failed daptomycin therapy. An increase in the vancomycin minimum inhibitory concentrations of four consecutive MRSA blood isolates from 2 microg/mL to 8 microg/mL was shown by Etest. Population analysis of four successive blood culture isolates recovered over the 10-week period showed that the MRSA strain became progressively less susceptible to both vancomycin and daptomycin. ⋯ Early detection of vancomycin-heteroresistant S. aureus isolates, which appeared to have clinical significance in this case, continues to be a challenge for the clinical laboratory. Development of suitable practical methods for this should be given priority. Concurrent development of resistance to vancomycin and daptomycin, whilst rare, must be considered in a patient who is unresponsive to daptomycin following vancomycin therapy.
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Int. J. Antimicrob. Agents · May 2009
Clinical TrialClinical cure of ventilator-associated pneumonia treated with piperacillin/tazobactam administered by continuous or intermittent infusion.
The standard mode of administration of piperacillin treatment is by intermittent infusion. However, continuous infusion may be advantageous as beta-lactam antibiotics exhibit time-dependent antibacterial activity. ⋯ Logistic regression analysis showed a higher probability of clinical cure of VAP by continuous compared with intermittent infusion when the microorganism responsible for VAP had a minimum inhibitory concentration (MIC) of 8 microg/mL [8/9 (88.9%) vs. 6/15 (40.0%); odds ratio (OR)=10.79, 95% confidence interval (CI) 1.01-588.24; P=0.049] or 16 microg/mL [7/8 (87.5%) vs. 1/6 (16.7%); OR=22.89, 95% CI 1.19-1880.78; P=0.03]. Thus, administration of PIP/TAZ by continuous infusion may be considered more effective than intermittent infusion for the treatment of VAP caused by Gram-negative bacteria when the MIC of the microorganism responsible for VAP is 8-16 microg/mL in patients without renal failure.
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Int. J. Antimicrob. Agents · May 2009
Pharmacokinetics of once-daily dosing of ertapenem in critically ill patients with severe sepsis.
Adequate data on the pharmacokinetics of once-daily administration of ertapenem in critically ill patients are largely lacking. This single-centre, prospective, open-label study was performed on a cohort of eight critically ill patients with severe sepsis with normal renal function treated with 1g of ertapenem once daily. Samples of venous blood and urine were collected before infusion and at specific time points in the 24-h post-infusion period. ⋯ Unbound levels failed to exceed a minimum inhibitory concentration of 1mg/L for more than 7.1h (30%) of the dosing interval in two patients. The highly variable and unpredictable intersubject pharmacokinetic parameters documented in this study resulted in suboptimal unbound concentrations in some patients. This raises the question as to whether ertapenem is an appropriate agent for initial use in critically ill patients with severe sepsis.
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Int. J. Antimicrob. Agents · Apr 2009
Ertapenem peritoneal fluid concentrations in adult surgical patients.
Ertapenem, a novel carbapenem, is approved for the treatment of mild to severe intra-abdominal infections (IAIs), although its in vivo concentrations in peritoneal fluid are unknown. The purpose of this study was to determine the peritoneal fluid concentration of ertapenem after a single 1 g intravenous dose. After informed consent, 21 patients (9 females and 12 males; mean+/-standard deviation (S. ⋯ The mean tissue/plasma ratio ranged from 46.7% to 83.1%. The mean peritoneal fluid concentrations were well above the MIC(90) (minimum inhibitory concentration for 90% of the organisms) for susceptible bacteria found in IAIs, especially Escherichia coli, viridans streptococci, Enterobacteriaceae, Klebsiella spp. and Bacteroides fragilis, during the entire sampling time. These pharmacokinetic results support the assumption that ertapenem might be suitable for the treatment of IAIs.