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HYPOTHESIS: Risk factors for Candida infection in surgical intensive care units (SICUs) change over time. Risk factor progression may influence Candida colonization and infection. DESIGN: Multicenter cohort survey. SETTING: Three urban teaching institutions. PATIENTS: A total of 301 consecutively admitted patients in SICUs for 5 or more days. MAIN OUTCOME MEASURES: Assessment of patients on SICU days 1, 3, 4, 6, and 8 and SICU discharge for risk factors, Candida colonization, and antifungal use. Candida colonization status was categorized as noncolonized (NC), locally colonized (LC) if 1 site was involved, and disseminated infection (DI) if 2 or more sites or candidemia were involved. RESULTS: The most frequent risk factors in the 301 patients enrolled were presence of peripheral and central intravenous catheters, bladder catheters, mechanical ventilation, and lack of enteral or intravenous nutrition. Early risk factors included total parenteral nutrition or central catheter at SICU day 1 and previous SICU admissions or surgical procedures. Peak number of risk factors (mean +/- SD) were as follows: 7.2 +/- 2.6 in NC (n = 229), 9.2 +/- 2.3 in LC (n = 45), and 9.2 +/- 2.6 in DI (n = 27). These numbers were reached at day 8 in the NC and LC groups and day 4 in the DI group. The LC and DI groups had more risk factors on each SICU day than the NC group and longer median SICU length of stay (28 days in the DI group vs 11 and 19 days in the NC and LC groups, respectively). Antifungal therapy, while used most frequently in the DI group, was initiated later for this group than in NC and LC groups. CONCLUSIONS: Risk factors for Candida infection in SICU patients change over time. Patients with DI demonstrate a greater number of and more rapid increase in risk factors than patients in the LC and NC groups. Presence of early risk factors at the time of SICU admission, a high incidence of risk factors, or a rapid increase in risk factors should prompt clinicians to obtain surveillance fungal cultures and consider empirical antifungal therapy.

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We evaluated the differences in antimicrobial susceptibility among hospitals in three different integrated healthcare systems. Each system provided antibiogram-susceptibility reports from representative hospitals. Reports were analyzed for statistically significant differences between hospitals in a given system for nine important organisms. We found numerous significant interhospital differences in antimicrobial-susceptibility patterns within health systems. For this reason, the practice of combining antibiotic-susceptibility data into a systemwide antibiogram should be discouraged.

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Evaluation of the cost-effectiveness of antibiotic regimens has become an essential part of drug selection for pharmacists and physicians. However, these evaluations can be complicated, time-consuming, and, if the data used are not based on local conditions, misleading. The computer program Dare to Compare 98 was developed to provide an analysis of empiric antibiotic regimens. The Infectious Disease Challenge portion of the program lists the commonly identified pathogens in specific infectious diseases. The Antibiogram Susceptibility Reports section generates susceptibility reports based on local antibiogram data or data from institutions nationwide that have similar demographic profiles. Susceptibility information is combined with cost data in the Quality/Cost Index section. Comparison of the quality and cost index values allows the user to determine which regimens provide the optimal microbiologic activity and cost values for treatment of a particular infectious disease based on local data. Thus Dare to Compare 98 can help pharmacists and physicians evaluate antibiotic regimens and their suitability for inclusion in formularies and disease-management algorithms.

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Providing quality care to patients at the lowest cost is of primary concern to hospitals, clinics, managed care organizations, integrated health systems, and other health care providers operating in a prospective payment environment. Therapy Cost 2000 can help health care providers and decision-makers in a variety of settings reach the goal of cost-effective, high-quality patient care.

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The effect of sucralfate on the pharmacokinetics of fleroxacin was assessed in 20 healthy male volunteers. The study was of a two-way crossover design in which subjects were randomized to one of the following two regimens at the time of entry: (i) a single 400-mg dose of fleroxacin alone or (ii) a 400-mg dose of fleroxacin given once and 1 g of sucralfate given every 6 h starting 24 h before fleroxacin treatment and continuing for 48 h after fleroxacin treatment. Blood samples were collected immediately before fleroxacin administration and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, and 48 h postdosing. Fleroxacin concentrations in plasma and urine were determined by high-performance liquid chromatography. While concurrent of fleroxacin and sucralfate resulted in a decrease in the area under the plasma concentration-time curve, a decrease in the maximum concentration, and an increase in the time to the maximum concentration (P < 0.05), these changes were modest compared with the interaction of other quinolones with sucralfate. The relative bioavailability of fleroxacin given with sucralfate, calculated from the area under the concentration-time curve, was 76% compared with that of fleroxacin alone. This is significantly better than the bioavailabilities of other quinolones (1.8 to 12.3%) when they are administered with sucralfate.

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The penetration of multiple-dose concentrations of oral fleroxacin (400 mg every 24 h) and ciprofloxacin (500 mg every 12 h) into skin blister fluid in 12 healthy volunteers was determined in a randomized crossover study. Serum, blister fluid, and paper disk samples were analyzed by large-plate microbiologic assay. The mean areas under the concentration-time curve (AUC) for serum were 88.6 and 18.2 micrograms.h/ml/70 kg for fleroxacin and ciprofloxacin, respectively. The mean AUC for blister fluid and paper disks were 71.2 and 15.0 micrograms.h/ml/70 kg and 77.8 and 15.4 micrograms.h/ml/70 kg for fleroxacin and ciprofloxacin, respectively. Calculated penetration into interstitial fluid ranged from 74 to 92% for fleroxacin and 56 to 96% for ciprofloxacin; penetration was calculated by using the ratio of maximum drug concentration or AUC in blister fluid and paper disks to maximum drug concentration or AUC in serum. There was no significant difference between fleroxacin and ciprofloxacin in the percent penetration into skin blister fluid.

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The relative bioavailability of a single oral dose of temafloxacin given with and without enteral feeding was determined in 18 healthy male volunteers in a randomised crossover study. Subjects were administered 600mg of temafloxacin orally as an intact tablet, or a crushed tablet suspended in water administered through a nasogastric tube with or without an enteral feeding solution [Osmolite (Ross) 100 ml/h started 2h before administration of temafloxacin and continued for 4h postdose]. Plasma samples were analysed by a high performance liquid chromatographic technique. Mean peak plasma concentrations (Cmax) for the oral tablet, crushed tablet, and crushed tablet with enteral feeding solution were 3.95 +/- 1.02, 4.85 +/- 0.69, and 4.69 +/- 0.61 mg/L/70kg, respectively, and mean calculated area under the concentration-time curve from time 0 to 48h (AUC(0-48h)) values were 48.1 +/- 11.0, 54.5 +/- 6.52, and 49.7 +/- 5.89 mg/L.h/70kg, respectively. In terms of AUC(0-48h) and Cmax, the relative bioavailability of temafloxacin after nasogastric delivery of crushed temafloxacin given with and without an enteral feeding solution was equivalent to the reference oral regimen.

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Heparin-induced thrombocytopenia and thrombosis can occur with both low-dose and high-dose heparin. Clinicians should be aware of this syndrome, and platelet counts should be monitored prior to initiating heparin and during the course of therapy. The treatment of heparin-induced thrombocytopenia is variable depending on the use of heparin in each individual patient. Treatment options include discontinuation of heparin, initiation of warfarin in place of heparin, and possibly switching from bovine to porcine heparin in milder cases. Intravenous immunoglobin is the most recent treatment option reported for heparin-induced thrombocytopenia and thrombosis. The patient with heparin-induced thrombocytopenia and thrombosis requiring emergency cardiac surgery and reexposure to heparin is more difficult to manage. Aspirin given with dipyridamole or Iloprost have both been reported to be successful in managing this group of patients. Heparin is a commonly used drug in all areas of medicine. The early recognition and treatment of heparin-induced thrombocytopenia and thrombosis has resulted in a reduction in the morbidity associated with this syndrome.

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