Antibiotic use: is appropriateness expensive?

Antibiotics are prone to misuse. In this study, 37% of 600 antibiotic prescriptions in three hospitals were considered unnecessary. When antibiotic therapy was indicated, 45% were considered to be inadequate. In multivariate analyses, the indicated treatments were found to be more expensive than the unjustified ones, probably because the latter were more often oral regimens. However, for indicated treatments, the cost of adequate and inadequate treatments did not differ significantly.

Impact of an interdisciplinary strategy on antibiotic use: a prospective controlled study in three hospitals.

OBJECTIVES: Evaluation of the impact of the implementation of practice guidelines, with or without their reinforcement by a pharmacist, on the intra-hospital use of antibiotics. MATERIALS AND METHODS: The duration of antibiotic treatment, their cost, and the length of patient stay were compared in three secondary-care hospitals, before and after interventions that were designed to promote rational antibiotic use. After randomization, hospital A received no intervention (control), local practice guidelines were implemented in hospital B (low grade intervention), and these guidelines were reinforced by a clinical pharmacist in hospital C (high grade intervention). Adherence to the guidelines was measured in hospitals B and C. Multivariable statistical analyses were carried out to adjust for confounding factors. RESULTS: None of the outcomes measured in the 1200 included patients decreased between the two study periods in any hospital. Hospital A was significantly and independently associated with an increase in the duration of antibiotic treatments, the cost of antibiotics (acquisition and global costs), and the length of stay. Although these differences were not statistically significant, increases in hospital B were higher than in hospital C. Adherence to guidelines was significantly higher in hospital C. CONCLUSIONS: Even though interdisciplinary interventions aiming at rationalizing antibiotic use could not diminish the duration of treatments, their costs or the length of stay, they proved useful to control the progression of these parameters.

Use of broad spectrum antibiotics in six non-university Swiss hospitals.

PRINCIPLES: Broad-spectrum antibiotics (BSAs) are costly and prone to misuse. Their use is associated with the emergence of resistant bacteria. This article describes the first step of an interhospital programme for the appropriate use of BSAs. METHODS: BSAs were defined as the i.v. antibiotics present in the formulary shared by the six participating institutions and considered to be antipseudomonal agents (i.e. cefepime, ceftazidime, ciprofloxacin, imipenem, meropenem, piperacillin/tazobactam) plus trovafloxacin. Annual utilisation rates and interhospital comparisons were provided to each institution using the "defined daily dosages" (DDDs) of the World Health Organization. RESULTS: From 1997 to 1999, the overall utilisation rate of BSAs increased from 20.6 treatment days (TD)/1000 patient days (PD) to 36.5 TD/1000 PD. Significant interhospital differences were detected (range: 12.1 TD/1000 PD in 1997-66.5 TD/1000 PD in 1999). The highest relative risk for treatment with any BSA for each individual hospital in comparison to the others was determined for 1999 (RR = 2.92; 95% confidence interval: 2.81-3.04). In 1999, the most frequently used BSAs were cefepime, imipenem, and piperacillin/tazobactam respectively. CONCLUSIONS: Although this programme does not provide information on the indications for using BSAs in various hospitals, it helps to identify those institutions where the selection pressure for resistant bacteria is highest, and that could particularly benefit from specific interventions aiming at decreasing this pressure and controlling drug expenditure. Moreover, the feedback of utilisation rates and interhospital comparisons to the prescribing physicians might have a positive impact on BSA use.

[Hospital pharmacy: partner in the health care team]. / Pharmacie de l'hôptial: partenaire de l'équipe de soins.

The hospital pharmacy is responsible for providing each patient with the required drug treatment. This goal can be fulfilled by constant adaptation of the pharmaceutical services to the needs of the medical and nursing staff, hospital administration and other technical services. The goals and the functional relationship between the different activities of a hospital pharmacy are reviewed. The specific organisation of the Sierre-Loèche hospital pharmacy is presented. Centralisation of some services of the district hospital pharmacy within the central pharmacy of the "Institut Central des Hôpitaux Valaisans" provides the hospital with the required services. Pharmaceutical counseling based on a regular activity of the pharmacist within the health care team is a prerequisite to adapt organisation and services to the requirements of the clinical situation.

Interference of metamizol (dipyrone) on the determination of creatinine with the Kodak dry chemistry slide comparison with the enzymatic method from Boehringer.

In order to eliminate positive interferences that take place with the Jaffé technique, the Kodak Ektachem and Boehringer Mannheim Companies have chosen an enzymatic method for the determination of creatinine in serum and urine. Pathological and clinical samples often contain metabolites in elevated concentrations or exogenous compounds such as drugs or toxic compounds. We noticed that patients receiving metamizol-containing drugs showed unusually low values of creatinine when determined with an Ektachem analyser. We investigated the effect of the main metabolites of this prodrug on the creatinine enzymatic methods of Kodak and Boehringer. We concluded that methyl-amino-antipyrine, the active substance after administration of metamizol (prop. INN) was responsible for the interference, and that no reliable determination of creatinine could be performed with these methods in the serum of patients receiving this drug.

[Clinical education of pharmacists: the Sion Model]. / Klinische Schulung des Apothekers: das Modell Sion.

A post-graduate training program in clinical pharmacy for pharmacists is described. The yearly program gives an overview of the various activities. A detailed description of one working day delivers insight into the activities of a clinical pharmacist in a department of internal medicine. Clinical education of a pharmacist should enable him to apply his knowledge in the context of a practical cooperation with physicians and nursing staff and to consider patient, counselling and medication as a unit.

Tissue oxygen tension and other indicators of blood loss or organ perfusion during graded hemorrhage.

Currently employed clinical indicators of perfusion provide inadequate warning of developing hazards caused by marginal perfusion in certain vital organs or "peripheral" tissues that are pivotal to postsurgical wound healing. In this study, mean arterial blood pressure, cardiac output, and transcutaneous and subcutaneous oxygen tensions (PtcO2 and PsqO2) were investigated during serial hemorrhage, as indicators of the degree of both hypovolemia and perfusion to specific tissues. Blood was removed in stages (10%, 20%, 30%, 40%, 55%, 60%, and 65% of original volume) from anesthetized dogs. Injections of variously radiolabeled microspheres allowed assessment of blood flow at each stage of hemorrhage in bone, brain, colon, heart, kidney, liver, muscle, pancreas, skin, small intestine, spleen, stomach, and subcutaneous tissue. PsqO2 was correlated more highly with blood volume lost than was PtcO2. Furthermore PsqO2 was more sensitive to blood loss than was either cardiac output or PtcO2 and, also during the early loss (0% to 40%), was more sensitive than mean arterial pressure. Some organs (e.g., pancreas) appeared to lose considerable blood flow with only small loss of blood volume, but their blood flow then stabilized at a low level despite further hemorrhage. Other organs, notably the kidney, appeared to be relatively unaffected by substantial loss of blood volume (20% to 40%), after which, however, their blood flow quite abruptly became sensitive to further hypovolemia. This explains why blood flow-related performance of the kidney (e.g., urine volume) may not adequately predict a developing hazard or peripheral perfusion. Some indicators were found to be better indexes of blood flow in some organs than in others (e.g., cardiac output and PsqO2 correlated more closely with skin, spleen, and intestinal flows [and one another] than with vital organ flows).

In vitro model for ciclosporin intestinal absorption in lipid vehicles.

The influence of lipid vehicles on the intestinal absorption of Ciclosporin was studied in vitro. The effect of the intestinal lipid digestion was considered on the partition of the drug from olive oil or middle-chain triglyceride (MCT) into phases of simulated intestinal content. The phases obtained after ultracentrifugation were analyzed for their Ciclosporin content and characterized for their lipid classes. For both lipid vehicles the presence of lipolysis products did not promote the partition of the drug into the aqueous phase. The absorption in vivo was not related to the drug amount in the aqueous phase and in the oil phase. Therefore, phase quantification in vitro cannot simulate the dynamics of in vivo absorption events following application of a poorly water-soluble drug in a lipid vehicle.

In vivo model for ciclosporin intestinal absorption in lipid vehicles.

The influence of lipid vehicles on the intestinal absorption of Ciclosporin was studied in vivo. The model takes into account the effect of the intestinal lipid digestion on the absorption after intraduodenal administration of [3H]Ciclosporin in olive oil or middle-chain triglyceride (MCT) to the bile duct-cannulated rat. Digested vehicles significantly promoted the absorption compared to nondigested vehicles. In the nondigested state, olive oil was a significantly better vehicle than MCT, whereas the difference between both lipids was only a trend in the digested state. Further studies with variants of this in vivo model should determine the influence of abnormalities of fat digestion and absorption on the pharmacokinetics and pharmacodynamics of a drug with a low therapeutical index.

On the dose dependency of cyclosporin A absorption and disposition in healthy volunteers.

The pharmacokinetics of Cyclosporin A (CyA, Sandimmune) was studied in 12 healthy male volunteers after oral dosing of 350 mg, 700 mg, and 1400 mg as a drinking solution. Blood samples were collected over 96 hr and analyzed by high pressure liquid chromatography. Concentration data were evaluated with model-independent and model-based linear pharmacokinetic concepts. Individual CyA concentration-time profiles in whole blood were well described by a two-compartment open model with zero-order absorption for all three doses. Comparison of pharmacokinetic parameters across doses indicates that both absorption and disposition are dose-dependent. Nonlinear disposition is suggested by the significant increase of the terminal half-life from 8.9 +/- 4.9 hr to 11.9 +/- 4.9 hr (mean +/- SD) after a 350 mg and a 1400 mg dose, respectively. Changes in the metabolic activity of the liver with concentration might be responsible for this phenomenon. In addition, the modeling approach indicated that bioavailability decreases with increasing dose. Moreover, the dependence of the rate of CyA absorption (zero-order rate constant) versus dose was well described by a hyperbola. The limited solubility of the drug in the gastrointestinal tract might be responsible for this behavior. The lag time (0.2-0.8 hr) was independent of dose. This value is similar to the time of gastric emptying in fasting volunteers. The duration of absorption for 11 of 12 subjects was in the range 2.5-3.5 hr over all doses and agrees well with the small intestine transit time. Some subjects showed a marked secondary peak at one or two doses, which could be adequately fitted by a model with two successive zero-order inputs. This double-peak behavior was ascribed to the influence of the food on gastric emptying. Dose dependency of disposition and absorption counterbalance each other in the usual dose range. This leads to an almost proportional increase of area under the blood CyA concentration-time profile with increasing dose.