André Pannatier

Fluconazole prophylaxis prevents intra-abdominal candidiasis in high-risk surgical patients

OBJECTIVE To evaluate the efficacy and safety of intravenous fluconazole for the prevention of intra-abdominal Candida infections in high-risk surgical patients. DESIGN Randomized, prospective, double-blind, placebo-controlled study. SETTING Two university-affiliated hospitals in Switzerland. PATIENTS Forty-nine surgical patients with recurrent gastrointestinal perforations or anastomotic leakages. INTERVENTIONS Prophylaxis with intravenous fluconazole (400 mg per day) or placebo continued until resolution of the underlying surgical condition. MEASUREMENTS AND MAIN RESULTS Patients were evaluated daily, and specimens for culture were obtained three times per week during prophylaxis. The primary study end points were the frequency of and the time to intra-abdominal Candida infections. Secondary end points were the frequency of candidiasis (intra-abdominal and extra-abdominal) and the emergence or persistence of Candida colonization. Among patients who were not colonized at study entry, Candida was isolated from surveillance cultures during prophylaxis in 15% of the patients in the fluconazole group and in 62% of the patients in the placebo group (relative risk, 0.25; 95% confidence interval, 0.07 to 0.96; p = .04). Candida peritonitis occurred in one of 23 patients (4%) who received fluconazole and in seven of 20 patients (35%) who received placebo (relative risk, 0.12; 95% confidence interval, 0.02 to 0.93; p = .02). In addition, one catheter-related Candida albicans sepsis occurred in a fluconazole-treated patient. Thus, overall, candidiasis developed in two fluconazole patients and seven placebo patients (relative risk, 0.25; 95% confidence interval, 0.06 to 1.06; p = .06). C. albicans accounted for 87% of the Candida species isolated before or during prophylaxis, and all C. albicans strains were susceptible to fluconazole. Fluconazole was well tolerated, and adverse events occurred at similar frequencies in both treatment groups. CONCLUSIONS Fluconazole prophylaxis prevents colonization and invasive intra-abdominal Candida infections in high-risk surgical patients.

A 10-year survey of nutritional support in a surgical ICU: 1986–1995

Total parenteral nutrition (TPN) has long been considered the optimal nutrition technique in critically ill patients, but recently the use of enteral nutrition (EN) has increased. This study describes the evolution of the different nutritional support techniques in a surgical intensive care unit (ICU) in a university hospital, through (1) a global survey over 10 y assessing the evolution of the use of EN and TPN, and (2) a prospective study performed over 6 mo. Severity of illness and diagnostic categories were stable (n = 11,539 patients). From 1986 to 1990, the proportion of TPN administered increased from 10-25% of ICU days, decreasing to 10% thereafter. EN was used in about 5% of ICU days in 1986, and had increased to 30% of total ICU treatment days in 1995. The proportion of nutrients actually delivered to the patients was 75% with EN and 88% with TPN. Major changes in nutritional support have been observed since 1986. The frequency of nutritional support provided in general has increased to 40% of ICU treatment days. TPN has been largely overtaken by EN, with the risk of insufficient energy delivery, related to the difficulties of EN in the critically ill. These results reinforce the importance of continuous quality control by daily assessment of nutrient supply.

Effect of computerisation on the quality and safety of chemotherapy prescription

Background: Chemotherapy is prescribed according to protocols of several cycles. These protocols include not only therapeutic agents but also adjuvant solvents and inherent supportive care measures. Multiple errors can occur during the prescription, the transmission of documents and the drug delivery processes, and lead to potentially serious consequences. Objective: To assess the effect of a computerised physician order entry (CPOE) system on the number of errors in prescription recorded by the centralised chemotherapy unit of a pharmacy service in a university hospital. Patients and methods: Existing chemotherapy protocols were standardised by a multidisciplinary team (composed of a doctor, a pharmacist and a nurse) and a CPOE system was developed from a File Maker Pro database. Chemotherapy protocols were progressively introduced into the CPOE system. The effect of the system on prescribing errors was measured over 15 months before and 21 months after starting computerised protocol prescription. Errors were classified as major (dosage and drug name) and minor (volume or type of infusion solution). Results: Before computerisation, 141 errors were recorded for 940 prescribed chemotherapy regimens (15%). After introduction of the CPOE system, 75 errors were recorded for 1505 prescribed chemotherapy regimens (5%). Of these errors, 69 (92%) were recorded in prescriptions that did not use a computerised protocol. A dramatic decrease in the number of errors was noticeable when 50% of the chemotherapy protocols were prescribed through the CPOE system. Conclusion: Errors in chemotherapy prescription nearly disappeared after implementation of CPOE. The safety of chemotherapy prescription was markedly improved.

Evaluation of physicochemical incompatibilities during parenteral drug administration in a paediatric intensive care unit

Patients in paediatric intensive care units (PICU) often receive numerous medications by the parenteral route. Frequently two or more drugs are delivered simultaneously through the same line and the risk of physicochemical incompatibilities is thus important. The objectives of this study were 1) to identify prospectively the combinations of injectable drugs administered in the PICU of our university hospital and 2) to analyze them according to information found in the literature. The data were collected by a pharmacist over a 30-day period and classified in three categories: compatible, incompatible and undocumented. Nineteen patients were included in the study with a median age of 3.2 years. The mean number (± SD) of injectable drugs per patient and per day was 6.5 (± 2.8), for a total of 26 drugs and 7 solutes. 64 combinations of drugs were observed with 2 (31.3%), 3(45.3%), 4 (10.9%) or 5 (12.5%) drugs. 81 drug — drug and 94 drug — solute combinations were recorded. Among these, 151 (86.3%) were compatible, 6 (3.4%) incompatible and 18 (10.3%) undocumented. The incompatibilities included furosemide (Lasix®), a drug in alkaline solution and Vamina-Glucose®, a total parenteral nutrition solution. No clinical consequences resulting from drug incompatibilities were shown in this study. We suggest that in vitro compatibility tests on standard drug combinations, as well as a training program for nurses on drug incompatibility problems would sensitively increase the security of parenteral drug administration.

Enzymatic hydrolysis by mouse skin homogenates: Structure-metabolism relationships of para-nitrobenzoate esters☆

Abstract The hydrolysis of 8 alkyl esters of p-nitrobenzoic acid has been investigated in the presence of skin preparations from untreated mice, using as analytical technique a sensitive and specific gas chromatographic method. The hydrolysis reaction was shown to be enzyme-mediated, negligible or no abiotic hydrolysis taking place under the conditions of the study. The cutaneous esterase involved in the reaction was found to be located in the cytosol and to be stable to heat pretreatment up to 50°C. The initial rate of hydrolysis increased with increasing lipophilicity of the substrates and decreased with increasing steric bulk on the alpha-carbon; a highly significant QSAR equation was derived.

Albuterol delivery in an in vitro pediatric ventilator lung model: comparison of jet, ultrasonic, and mesh nebulizers.

Objective: To determine the influence of nebulizer types and nebulization modes on bronchodilator delivery in a mechanically ventilated pediatric lung model. Design: In vitro, laboratory study. Setting: Research laboratory of a university hospital. Interventions: Using albuterol as a marker, three nebulizer types (jet nebulizer, ultrasonic nebulizer, and vibrating-mesh nebulizer) were tested in three nebulization modes in a nonhumidified bench model mimicking the ventilatory pattern of a 10-kg infant. The amounts of albuterol deposited on the inspiratory filters (inhaled drug) at the end of the endotracheal tube, on the expiratory filters, and remaining in the nebulizers or in the ventilator circuit were determined. Particle size distribution of the nebulizers was also measured. Measurements and Main Results: The inhaled drug was 2.8% ± 0.5% for the jet nebulizer, 10.5% ± 2.3% for the ultrasonic nebulizer, and 5.4% ± 2.7% for the vibrating-mesh nebulizer in intermittent nebulization during the inspiratory phase (p < 0.01). The most efficient nebulizer was the vibrating-mesh nebulizer in continuous nebulization (13.3% ± 4.6%, p < 0.01). Depending on the nebulizers, a variable but important part of albuterol was observed as remaining in the nebulizers (jet and ultrasonic nebulizers), or being expired or lost in the ventilator circuit (all nebulizers). Only small particles (range 2.39–2.70 µm) reached the end of the endotracheal tube. Conclusions: Important differences between nebulizer types and nebulization modes were seen for albuterol deposition at the end of the endotracheal tube in an in vitro pediatric ventilator–lung model. New aerosol devices, such as ultrasonic and vibrating-mesh nebulizers, were more efficient than the jet nebulizer.

A theoretical conformational study of substituted O-anisamides as models of a class of dopamine antagonists

The quantum mechanical PCILO method has been used to investigate the conformational behaviour of N‐(2‐aminoethyl)‐ and N‐(2‐dimethylaminoethyl)‐o‐anisamide, two model molecules of substituted benzamides. The molecules are shown to have only limited conformational freedom due to the presence of two intramolecular hydrogen bonds acting as conformational locks. The molecules in their preferred conformation are characterized by a distance between the centre of the aromatic ring and the nitrogen atom of almost 6 Å, i.e. almost 1 Å longer than in the fully extended dopamine conformers. Some implications at the receptor level of this topographical dissimilarity are discussed.

Stress ulcer prophylaxis in non-critically ill patients: a prospective evaluation of current practice in a general surgery department.

RATIONALE, AIMS AND OBJECTIVES There is little evidence regarding the benefit of stress ulcer prophylaxis (SUP) outside a critical care setting. Overprescription of SUP is not devoid of risks. This prospective study aimed to evaluate the use of proton pump inhibitors (PPIs) for SUP in a general surgery department. METHOD Data collection was performed prospectively during an 8-week period on patients hospitalized in a general surgery department (58 beds) by pharmacists. Patients with a PPI prescription for the treatment of ulcers, gastro-oesophageal reflux disease, oesophagitis or epigastric pain were excluded. Patients admitted twice during the study period were not reincluded. The American Society of Health-System Pharmacists guidelines on SUP were used to assess the appropriateness of de novo PPI prescriptions. RESULTS Among 255 patients in the study, 138 (54%) received a prophylaxis with PPI, of which 86 (62%) were de novo PPI prescriptions. A total of 129 patients (94%) received esomeprazole (according to the hospital drug policy). The most frequent dosage was at 40 mg once daily. Use of PPI for SUP was evaluated in 67 patients. A total of 53 patients (79%) had no risk factors for SUP. Twelve and two patients had one or two risk factors, respectively. At discharge, PPI prophylaxis was continued in 33% of patients with a de novo PPI prescription. CONCLUSIONS This study highlights the overuse of PPIs in non-intensive care unit patients and the inappropriate continuation of PPI prescriptions at discharge. Treatment recommendations for SUP are needed to restrict PPI use for justified indications.

Impact of the introduction of real-time therapeutic drug monitoring on empirical doses of carbapenems in critically ill burn patients

PURPOSE Adequate empirical antibiotic dose selection for critically ill burn patients is difficult due to extreme variability in drug pharmacokinetics. Therapeutic drug monitoring (TDM) may aid antibiotic prescription and implementation of initial empirical antimicrobial dosage recommendations. This study evaluated how gradual TDM introduction altered empirical dosages of meropenem and imipenem/cilastatin in our burn ICU. METHODS Imipenem/cilastatin and meropenem use and daily empirical dosage at a five-bed burn ICU were analyzed retrospectively. Data for all burn admissions between 2001 and 2011 were extracted from the hospitals computerized information system. For each patient receiving a carbapenem, episodes of infection were reviewed and scored according to predefined criteria. Carbapenem trough serum levels were characterized. Prior to May 2007, TDM was available only by special request. Real-time carbapenem TDM was introduced in June 2007; it was initially available weekly and has been available 4 days a week since 2010. RESULTS Of 365 patients, 229 (63%) received antibiotics (109 received carbapenems). Of 23 TDM determinations for imipenem/cilastatin, none exceeded the predefined upper limit and 11 (47.8%) were insufficient; the number of TDM requests was correlated with daily dose (r=0.7). Similar numbers of inappropriate meropenem trough levels (30.4%) were below and above the upper limit. Real-time TDM introduction increased the empirical dose of imipenem/cilastatin, but not meropenem. CONCLUSIONS Real-time carbapenem TDM availability significantly altered the empirical daily dosage of imipenem/cilastatin at our burn ICU. Further studies are needed to evaluate the individual impact of TDM-based antibiotic adjustment on infection outcomes in these patients.

Development and Validation of an HPLC Method for the Simultaneous Monitoring of Bromazepam and Omeprazole

Abstract Bromazepam and omeprazole are frequently administered to hospitalized patients to decrease anxiety and prevent stress ulcers, respectively. In patients under enteral nutrition, these drugs are administered via a nasogastric feeding tube. However, this mode of administration renders their bioavailability highly variable, and calls for their therapeutic monitoring. Given the absence of published data on the compared bioavailability of the two drugs given orally or via a nasogastric feeding tube, we have developed a high performance liquid chromatography method with UV detection (HPLC‐UV) suitable for their simultaneous monitoring in human plasma. The method involves solid phase extraction of 2 mL plasma samples. Linearity was demonstrated in a concentration range of 5–100 ng/mL and 20–2000 ng/mL for bromazepam and omeprazole, respectively. The lower limit of quantification was 5 ng/mL and 20 mg/mL for bromazepam and omeprazole, respectively. The method proved its worth in the simultaneous monitoring of bromazepam and omeprazole administered to healthy volunteers.