Treatment and prevention of oropharyngeal candidiasis.

As more potent antibacterial drugs are used to combat infections and as more patients with impaired defenses against infection are treated, other organisms, like fungi, have become important pathogens. Fungi of all types may appear in this setting, but Candida species are the most common, usually beginning as an infection in the oropharynx. Although oropharyngeal candidiasis usually remains localized, it may spread elsewhere, leading to a fatal outcome. Controversy still exists regarding the best drug to prevent or treat oropharyngeal candidiasis, but clotrimazole given as a troche may be the best choice at the moment owing to its high clinical success rate, safety, cost effectiveness, and high patient acceptability. There remains a need for more randomized and controlled studies comparing the efficacy of nystatin, ketoconazole, and clotrimazole in high-risk patients in whom invasive candidiasis remains a frequent problem.

Bacteriologic contamination of intravenous infusion delivery systems in an intensive care unit.

Seventy intensive care unit patients were admitted to a double-blind prospective study to determine the level of contamination associated with the admixture and administration of intravenous solutions and whether intravenous filtersets prevented bacteremia. Patients were randomly assigned a 0.22 micron filterset (real filter) or a filter cartridge without a 0.22 micron membrane (blank filter) on all possible intravenous lines. Forty-six (14.1 percent) real filtersets and 38 (11.3 percent) blank filtersets were found to be contaminated, and overall 30 patients (42.4 percent) were found to have extrinsically contaminated intravenous administration systems at least once during the study. Bacterial adherence to the plastic cartridge was demonstrated to be responsible for culture-positive blank filtersets. Staphylococcus epidermidis was the organism most frequently isolated from real and blank filtersets. Epidemiologic surveillance identified 10 patients with blank filtersets and three patients with real filtersets with clinically significant hospital-acquired bacteremias during the study period. It is concluded that a significant level of extrinsic contamination of intravenous infusion delivery systems occurred on the intensive care unit; documented clinically significant nosocomial bacteremias occurred less often in those patients who had a 0.22 micron bacterial retention filter on all possible intravenous lines.

Total nutrient admixture: a review.

The TNA system of nutritional support has become very popular and offers some unique advantages over the traditional method of administering TPN to hospitalized and home patients. However, these advantages as outlined in this review, must be carefully weighed against potential disadvantages before the TNA system is employed as a nutritional support modality. It should also be noted that the stability of TNA systems is not well established since many stability studies do not provide specific information regarding formulations tested. In addition, many studies do not utilize methods to determine the entire spectrum of particle size and distribution. Droplet size in TNA systems attain a diameter several times larger than the 0.2 to 0.4 micron of manufacturer's lipid emulsions and naturally occurring chylomicrons. Although the administration of the TNA system has not been associated with any acute toxicity, the long-term consequences of infusing droplets larger than 0.4 micron is not definitely known. In addition, the biological implications of using the TNA system need to be elucidated. Subtle differences in the properties of the lipid emulsion can affect the way it is metabolized by the body. Wretlind has mentioned that two apparently similar soybean oil emulsions, Intralipid, and Lipofundin are handled differently by the body. Minor differences in the phospholipid layer of the droplets were postulated as a cause. Certainly the nature of the emulsifying layer of phospholipid on TNA system droplets is modified and therefore may be metabolized differently. The recent report of enhanced growth of microorganisms in TNA systems is also worrisome.(ABSTRACT TRUNCATED AT 250 WORDS)

The growth of microorganisms in total parenteral nutrition admixtures.

Total nutrient admixtures (TNAs) containing glucose, amino acids, and lipid emulsion in one container and amino acid/dextrose solutions [conventional total parenteral nutrition (TPN) formulations] were studied in a controlled laboratory experiment for their ability to support the growth of microorganisms. Both TNA and conventional TPN formulations for peripheral and central venous administration with standard additives were inoculated with microorganisms to provide 10(1)-10(2) colony-forming units/ml (CFU/ml) of Staphylococcus epidermidis, Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, and Candida albicans. The admixtures were stored at room temperature and samples for quantitative microbiology were taken at time 0, 6, 12, 24, 48, 72, and 96 hr. K. pneumoniae, E. coli, and P. aeruginosa were able to proliferate in central TNAs, but the growth of these organisms was retarded in conventional TPN solutions. In the peripheral formulations, K. pneumoniae and E. coli proliferated in both the TNA and conventional TPN systems, whereas P. aeruginosa grew well only in the peripheral TNA. S. epidermidis was not able to grow in any admixtures tested; however, C. albicans grew well in all admixtures, but growth was slower in the conventional central TPN. In conclusion, peripheral and central TNAs supported the growth of microorganisms significantly better than conventional TPN solutions.

Stability of omeprazole in an extemporaneously prepared oral liquid.

The stability of omeprazole 2 mg/mL. in an extemporaneously prepared oral liquid was studied. The contents of five 20-mg omeprazole capsules were mixed with 50 mL of 8.4% sodium bicarbonate solution in a Luer-Lok syringe. Three vials of this liquid were prepared for storage at 24, 5, and -20 degrees C. A 3-mL. sample of each was taken initially and on days 1, 2, 3, 4, 6, 8, 10, 12, 14, 18, 22, 26, and 30 and assayed by high-performance liquid chromatography. The liquids stored at 5 degrees C and at -20 degrees C did not change color during the study period, but the color of the liquid stored at 24 degrees C changed from white to brown. There were no significant changes in the omeprazole concentrations of the liquids stored at 5 and -20 degrees C during the study period, but the omeprazole concentration of the liquid stored at 24 degrees C was < 90% of the initial concentration on day 18. Omeprazole 2 mg/mL in an oral liquid compounded extemporaneously from capsules and sodium bicarbonate injection was stable for up to 14 days at 24 degrees C and for up to 30 days at 5 and -20 degrees C.

Stability of granisetron hydrochloride in an extemporaneously prepared oral liquid.

The stability of granisetron 0.2 mg/mL (as the hydrochloride salt) in an extemporaneously prepared oral liquid was studied. Twelve 1-mg granisetron tablets were pulverized and suspended in 30 mL of distilled water. This mixture was then diluted with cherry syrup to produce a 60-mL oral liquid with a granisetron concentration of 0.2 mg/mL. Half of the preparation was stored at 5 degrees C, and half was stored at 24 degrees C. Samples were taken on days 0, 1, 2, 3, 4, 6, 8, 10, 12, and 14 and assayed by high-performance liquid chromatography. There was no change in the liquid's color, consistency, or pH, and the concentrations of granisetron ranged from 97% to 104% of initial concentration during the 14 days at 5 and 24 degrees C. Granisetron 0.2 mg/mL (as the hydrochloride salt) in an extemporaneously prepared oral liquid was stable for up to 14 days.

Pharmacokinetic comparison of omeprazole capsules and a simplified omeprazole suspension.

The pharmacokinetics of omeprazole delayed-release capsules and a simplified omeprazole suspension (SOS) were studied. Seven healthy volunteers randomly received either one 20-mg omeprazole delayed-release capsule or SOS (omeprazole 20 mg in 10 mL) for seven days before being crossed over to the opposite treatment for seven more days after a two-week washout period. On days 1 and 7, blood samples were drawn at intervals up to 360 minutes after drug administration. Plasma omeprazole concentrations were determined by a validated high-performance liquid chromatographic method, and pharmacokinetic values were determined. Area under the concentration-versus-time curve (AUC) from zero to six hours, AUC from time zero to infinity (AUC0-infinity), and maximum plasma concentration (Cmax) increased by 102%, 113%, and 85%, respectively, after seven days of treatment with the capsule. AUC0-infinity for SOS on day 1 was 58% of that for the capsule (p = 0.0141), and on day 7 it was 49% of that for the capsule (p = 0.0044). AUC0-infinity for SOS increased by 85% from day 1 to 7, but the difference was not significant. Cmax for SOS on day 1 was twice that for the capsule (p = 0.0014), but by day 7 the difference between the two formulations was negligible. Time to Cmax (tmax) for SOS on days 1 and 7 was shorter than for the capsule by 82% (p < 0.0001) and 70% (p < 0.0006), respectively. After one week of therapy, omeprazole absorption was faster and tmax was 70% shorter for SOS than for the capsule formulation, but AUC0-infinity was 49% lower for SOS.

A historical perspective and review of the safety of lipid emulsion in pregnancy.

Total parenteral nutrition for pregnant patients is essential to maintain or restore optimal nutritional status for both the mother and fetus when adequate protein and caloric intake by the oral or enteral route is not feasible. This report reviews the safety of intravenous lipid emulsions in total parenteral nutrition programs for pregnant patients. Controversy regarding the adverse effects of intravenous lipid emulsion when administered to pregnant patients is based on early reports of the use of cottonseed oil lipid emulsions. The adverse effects reported included infarction of the placenta, ketonemia, increased myometrial activity, and induction of labor. In 32 subsequent case reports in which soybean oil- or soybean/safflower oil-based emulsions were used in total parenteral nutrition programs for pregnant patients, there was no relationship apparent between onset of labor and harmful maternal or fetal effects associated with the administration of lipid emulsion. It appears that the currently available soybean and soybean/safflower lipid-based emulsions can be safely administered to pregnant patients.

Formulaic methods of estimating calorie requirements in mechanically ventilated obese patients: a reappraisal.

A variety of formulae are used by clinicians to estimate calorie requirements in hospitalized obese patients. Many of these formulae have been validated by determining their correlation to calorie requirements as determined by indirect calorimetry (IC). The use of correlation coefficients (CC) in this manner may be misleading. A more appropriate statistical methods, limits of agreement (LA), for comparing clinical measurements has recently been described by Bland and Altman. We obtained a total of 188 IC measurements on 113 obese (> 120% IBW), mechanically ventilated patients. These were compared by CC and LA to seven formulaic methods of determining calorie requirements. All formulae correlate significantly with IC. Analysis by LA indicated acceptable bias in several formulae (eg, 21 kcal/kg, Ireton-Jones obese patients (IJ), Ireton-Jones ventilatory patients, (VEE); however, the uniform lack of precision demonstrated by all formulae renders their clinical utility questionable.

Strategy for developing a safe and cost-effective H2-receptor antagonist program.

The pharmacy staff of a community tertiary-care hospital evaluated efficacy and safety before addressing cost considerations in the transition to a capitation program with cimetidine as the preferred H2-receptor antagonist. Safety concerns were resolved by permitting the use of an alternative drug certain patients considered to be at high risk. Despite initial resistance to mandatory participation in the program, the physician and nursing staffs have grown supportive, and the annual cost savings, which include the costs of labor and supplies as well as acquisition, have been substantial.

Cost analysis of fentanyl and remifentanil in coronary artery bypass graft surgery without cardiopulmonary bypass.

BACKGROUND: Opiates such as remifentanil have the potential to reduce time to extubation (TTE), shorten length of stay (LOS) and lower hospital costs, because of a short duration of action. However, the cost of remifentanil is approximately ten times higher than longer-acting opiates like fentanyl. OBJECTIVES: The objective of this analysis was to compare TTE, LOS and total hospital costs between patients who received remifentanil and fentanyl during off-pump bypass surgery. METHODS: The study was prospective and observational in design. Consecutive patients who underwent off-pump cardiac bypass surgery and received either remifentanil or fentanyl from September 1998 to August 1999 were screened for study entry. Patient bills and charges were converted to costs using hospital cost-to-charge ratios. The percent of patients' extubated in the operating room (OR), LOS and hospital costs were compared between the groups. RESULTS: The baseline demographics (age: 66 +/- 12 years mean +/- SD; female 36%) and intraoperative variables were similar between the remifentanil (n=39) and fentanyl (n=20) groups. Patients given remifentanil during surgery were significantly more likely to be extubated in the OR than patients given fentanyl (15 vs. 64%; P < 0.001). Mean LOS was similar in both groups (7.3 +/- 3.1 vs. 8.3 +/- 2.7 days; P=0.27). Patients who received remifentanil incurred lower pulmonary function testing ($0 +/- 0 vs. $34 +/- 103; P=0.045), recovery room ($31 +/- 40 vs. $65 +/- 33; P=0.002) and lower ward costs ($3973 +/- 1719 vs. $4808 +/- 1794; P=0.09) than patients who received fentanyl. Anesthesia costs were higher among patients who received remifentanil ($476 +/- 102 vs. $416 +/- 130; P=0.06). Medical and surgical supplies, OR, intensive care unit, laboratory, respiratory therapy, pharmacy, radiology and transfusion costs were similar between the two groups. The total cost was $15 272 +/- 5556 and $15 616 +/- 4169 in the remifentanil and fentanyl groups, respectively (P=0.81). CONCLUSION: Remifentanil, when used in off-pump bypass surgery, is associated with an increased likelihood of extubation in the OR. However, LOS and total hospital costs remain unchanged.

Stability of famotidine in an extemporaneously prepared oral liquid.

The stability of famotidine in an extemporaneously prepared oral liquid stored at 4 and 24 degrees C for 30 days was studied. Famotidine liquid was prepared by pulverizing and suspending 12 40-mg tablets in distilled water. This mixture was diluted with cherry syrup to a total volume of 60 mL, resulting in a famotidine concentration of 8 mg/mL. The liquid was divided into two 30-mL amber glass bottles and stored at 4 degrees C and at room temperature (24 degrees C). Samples from each of the two bottles were assayed for famotidine content by high-performance liquid chromatography. Each sample was assayed in duplicate at time 0 and on days 2, 5, 10, 15, 20, 25 and 30. The concentration of famotidine remained above 90% of original concentration for 20 days at 4 degrees C and for 15 days at room temperature. After 30 days, famotidine concentration was reduced by 15% and 24% at 4 degrees C and room temperature respectively. Famotidine liquid 8 mg/mL compounded extemporaneously from tablets was stable for 20 days at 4 degrees C and for 15 days at 24 degrees C.

The inhibitory effect of parenteral nutrition on recovery of neutrophil locomotory function in blunt trauma.

Twenty patients were investigated to determine whether total parenteral nutrition (TPN) influences the recovery of neutrophil (PMN) locomotory dysfunction in blunt trauma. Half were given TPN consisting of amino acids, glucose, electrolytes, and trace minerals, and half were given intravenous (I.V.) fluids consisting of 5% glucose in water or saline, electrolytes, and trace minerals. PMN locomotion was assayed using micropore filters. Analysis of the data by general linear modeling showed that PMN locomotion in TPN patients was significantly slower during the first 3 to 4 days postinjury. By sequential analysis, improved PMN function in the group not given TPN (NO TPN) occurred less than 95% of the time. TPN with amino acids and glucose may worsen and delay the recovery of PMN locomotory responses in blunt trauma, but the preference ratio of NO TPN:TPN for better PMN function was less than 95:5.

Multidisciplinary program for promoting single prophylactic doses of cefazolin in obstetrical and gynecological surgical procedures.

A multidisciplinary cost-containment program for promoting the use of single prophylactic doses of cefazolin for obstetrical and gynecological surgical procedures is described. Following a one-month review of patient charts to identify the antimicrobial regimens used most frequently for prophylaxis in obstetrical and gynecological surgical procedures, the department of pharmacy services, with the cooperation of the pharmacy and therapeutics (P&T) committee and the departments of obstetrics and gynecology and infectious diseases, implemented an educational program to promote the use of single doses of cefazolin for surgical prophylaxis. The program included inservice education and distribution of letters of support and a therapeutics newsletter. Drug stocking patterns in the operating and delivery rooms were changed to make cefazolin more accessible, and the P&T committee formally restricted the use of prophylactic antimicrobial agents in obstetrical and gynecological surgical procedures to single doses of cefazolin unless a consulting infectious-disease physician recommended otherwise. Compliance with the program increased as each step was implemented; data collected 16 months after the program was initiated demonstrated a compliance rate of 78.8%. Based on comparison of data collected before initiation and six months after initiation of the program, an actual cost savings of +7,125 was realized, which extrapolates to +14,250 annually. No apparent adverse effects on patient care were noted. The multidisciplinary approach to promoting the use of single doses of cefazolin was effective.

Selenium deficiency and fatal cardiomyopathy in a patient receiving long-term home parenteral nutrition.

Fatal cardiomyopathy in a patient who received home parenteral nutrition (HPN) for eight years is reported, and the relationship of selenium deficiency to cardiomyopathy and other adverse effects is discussed. A 42-year-old white man with Crohn's disease who was receiving HPN was admitted to the hospital with severe chest pain and dyspnea. During the three days following admission, his symptoms of congestive heart failure and compensated metabolic acidosis persisted despite treatment. On hospital day 6, the patient developed increased ventricular irritability and refractory ventricular fibrillation and died. At autopsy, the heart weighted 500 g, all chambers were dilated, and the myocardium was grossly flabby. Extremely low concentrations of selenium (5-12% of normal) were found in plasma, heart, liver, and kidney tissue samples. The pathological findings in this patient were similar to those in two previously reported cases and strongly suggest that the fatal cardiomyopathy was secondary to selenium deficiency. Selenium is an integral part of the enzyme glutathione peroxidase, which plays an important role in the metabolism of tissues and organs. For metabolically stable patients receiving total parenteral nutrition, the suggested selenious acid dosage is 25-60 micrograms/day for adults and 1.4-30 micrograms/kg/day for pediatric patients. In selenium-depleted adults, a dosage of 100 micrograms/day administered intravenously for 21-31 days has been recommended to reverse symptoms. All HPN patients and hospitalized patients receiving extended parenteral nutrition should be monitored for selenium deficiency and given supplements if necessary.