Antibiotic patterns associated with fungal colonization in critically ill surgical patients.

Fungal infections (FI) in surgical patients are increasing; mortality approaches 50 per cent. Prior studies identified factors predicting fungal colonization (FC) including broad spectrum antibiotics (BSA). This study investigates antibiotic patterns predicting FC. Other risk factors and outcomes are analyzed. A total of 72 consecutive SICU patients receiving > or = 7 days BSA were followed. None received prophylactic antifungals. Input data: Age, APACHE II, surgical procedure, lines, ulcer prophylaxis, TPN duration, antibiotic/antifungal regimen. Outcome data: FC, FI, length of SICU and hospital stay, mortality. A total of 32 patients (44%) developed FC; five (16%) developed FI (P = 0.08). All infected patients died (P = 0.0002). FC of GU (25%), respiratory (19%), and GI (19%) tracts were common. Multiple site colonization occurred in 25 per cent of colonized patients. Metronidazole and duration of ventilation predicted FC. APACHE II and TPN duration predicted mortality. Mortality occurred exclusively among patients requiring systemic antifungals. Among BSA, only metronidazole independently predisposed to FC. Other predictors of colonization and mortality agree with prior studies. The high mortality among patients requiring systemic antifungals implies that a more aggressive approach to prophylaxis may be warranted.

Differentiation of spinal and supraspinal opioid receptors by morphine tolerance.

Mice treated for 72 hrs with morphine (subcutaneously implanted pellets) were tested with a variety of opioid receptor agonists to examine the development of tolerance and cross-tolerance to their analgesic action. The development of spinal and supraspinal tolerance following morphine treatment was evaluated by administering compounds systemically (sc), intrathecally (IT) and intracerebroventricularly (ICV). Following morphine treatment, tolerance to morphine analgesia was observed following IT, ICV and sc administration. Chronic morphine treatment also produced cross-tolerance to the analgesic effects of the selective delta opioid receptor agonist [D-Pen2, D-Pen5]enkephalin (DPDPE) following IT and ICV administration. However, morphine treatment selectively produced cross-tolerance to ICV [D-Ala2, NMePhe4, Gly-ol5]enkephalin (DAGO) (mu receptor agonist) analgesia, without altering IT DAGO analgesia. These results suggest that brain and spinal cord receptors mediating the effects of DAGO differ in terms of the development of cross-tolerance to morphine; and suggest that tolerance to systemic morphine may be due to changes in spinal delta and brain mu and delta receptor mechanisms.

Chronic opioid antagonist treatment increases mu and delta receptor mediated spinal opioid analgesia.

Chronic systemic treatment with the opioid antagonist, naltrexone, increased the analgesic potency of intrathecally administered opioid agonists at spinal mu and delta receptors, but not at kappa receptors. These results indicate that, contrary to a previous report, opioid receptors in the spinal cord display up-regulation and supersensitivity and are no different in this regard from supraspinal receptors.