Safety and efficacy of continuous flush systems for arterial and pulmonary artery catheters.

Air embolism and static pressure errors have been attributed to continuous infusion systems. Experiments show that the primary source of air bubbles in such a system is the drip chamber. A drip chamber that minimizes this problem was tested and is recommended. Pressure errors due to the flush system are shown to be clinically insignificant. Fast flushing through a central arterial catheter is shown to be a minimal hazard.

Discovery of MC-02,331, a new cephalosporin exhibiting potent activity against methicillin-resistant Staphylococcus aureus.

A systematic approach toward building activity against methicillin-resistant staphylococci into the cephalosporin class of beta-lactam antibiotics is described. Initial work focused on finding the optimal linkage between the cephem nucleus and a biphenyl pharmacophore, which established that a thio linkage afforded potent activity in vitro. Efforts to optimize this activity by altering substitution on the pharmacophore afforded iodophenylthio analog MC-02,002, which although highly potent against MRSA, was also highly bound to serum proteins. Further work to decrease serum protein binding showed that replacement of the iodo substituent by the positively-charged isothiouronium group afforded potent activity and reduced serum binding, but insufficient aqueous solubility. Solubility was enhanced by incorporation of a second positively-charged group into the 7-acyl substituent. Such derivatives (MC-02,171 and MC-02,306) lacked sufficient stability to staphylococcal beta-lactamase enzymes. The second positive charge was incorporated into the cephem 3-substituent in order to utilize the beta-lactamase-stable aminothiazolyl(oximino)acetyl class of 7-substituents. These efforts culminated with the discovery of bis(isothiouroniummethyl)phenylthio analog MC-02,331, whose profile is acceptable with respect to potency against MRSA, serum binding, aqueous solubility, and beta-lactamase stability.

Use of a chlorhexidine dressing to reduce microbial colonization of epidural catheters.

We performed a prospective randomized controlled trial to assess the efficacy of a chlorhexidine dressing in reducing the microbial flora at the insertion site of epidural catheters. These catheters were used for acute pain management and were dressed either by a standardized method or with a CHX/urethane sponge composite. Microbial colonization of the catheter developed in 9 of 31 controls (29.0%) and 1 of 26 (3.8%) catheters with the CHX dressing (P less than 0.05%). The CHX dressing caused no adverse effects. The data suggest that delivery of antiseptic to the catheter wound site reduces catheter colonization with a possible reduction in the risk of epidural catheter-related infection.