Carbapenems and subsequent multiresistant bloodstream infection: does treatment duration matter?

It has been proposed that initial empirical broad-spectrum antibiotic therapy will result in better clinical outcomes and that shorter courses will reduce the 'collateral damage' of promoting antibiotic resistance. There are few data from Intensive Care Units (ICUs) that support this latter conclusion. A prospective observational study was undertaken at the National University Hospital, Singapore, to examine the relationship between duration of carbapenem therapy and subsequent nosocomial multidrug-resistant (MDR) bloodstream infection (BSI). Over a 2-year period, 415 ICU patients receiving empirical carbapenem therapy were prospectively followed. MDR BSI occurred on 35 occasions in 31 patients, comprising 21 carbapenem-resistant Acinetobacter baumannii, 3 carbapenem-resistant Pseudomonas aeruginosa and 11 meticillin-resistant Staphylococcus aureus (MRSA). There was no difference in the duration of carbapenems for those who developed MDR BSI compared with those who did not [median duration 8 days (range 3-23 days) vs. 9 days (range 3-59 days); P=0.78]. On multivariate analysis using the Cox proportional hazard model the hazard ratio was 0.935 (P=0.070). In this cohort of critically ill patients, a shorter duration of carbapenem therapy was not shown to protect against subsequent development of MDR BSI. Strategies that depend primarily on reducing broad-spectrum antibiotic duration may be inadequate in preventing the emergence of MDR organisms.

[Distribution of 5-FU in rat plasma and liver tissue after local 5-FU infusion].

OBJECTIVE: To study the distribution of 5-FU in rat plasma and liver tissue following systemic or local 5-FU infusion. METHODS: 5-FU was administered at the dose of 20 mg/kg systemically via bolus injection through the jugular vein or locally via infusion through the hepatic artery and portal vein of the rats. High-performance liquid chromatography was used to measure 5-FU concentration in the plasma and liver tissue, and the pharmacokinetic parameters, penetration rate and therapeutic dominance of 5-FU were calculated. RESULTS: Systemic administration of 5-FU resulted in the peak 5-FU concentration (Cmax) and area under curve (AUC) in the liver tissue of 13.79-/+4.56 microg/g and 342.20-/+108.20 microg.min(-1).g(-1)g-1, with the plasma Cmax and AUC of 36.85-/+5.96 microg/g and 842.00-/+158.00 microg.min(-1).ml(-1), respectively. Local 5-FU administration through the hepatic artery resulted in Cmax and AUC in the liver tissue of 29.58-/+4.30 microg/g and 794.60-/+115.40 microg.min(-1).g(-1) and Cmax and AUC in the plasma of 24.39-/+4.63 microg/g and 639.70-/+133.80 microg.min(-1).ml(-1), respectively. After administration through the portal vein, the Cmax and AUC of 5-FU was 28.21-/+4.46 microg/g and 733.60-/+180.3 microg.min(-1).g(-1) in the liver tissue, and 21.02-/+4.06 microg/ml and 529.80-/+111.50 microg.min(-1).ml(-1) in the plasma, respectively. CONCLUSION: Compared with systemic venous bolus injection, administration through the hepatic artery and portal vein can significantly increase 5-FU concentration in the liver, and decrease its concentration in the peripheral blood.