Inhalation technique practical skills and knowledge among physicians and nurses in two pediatric emergency settings.

Introduction: Correct technique with a pressurized metered-dose inhaler (pMDI) equipped with a valved holding chamber (VHC) or spacer provides an important advantage for adequate control of asthma and virus-induced wheezing in young children. The aim of this study was to assess the ability and knowledge of physicians and nurses to use a pMDI with a masked VHC in two pediatric emergency units.Methods: Study design: Two-center observational study. Inhaler use technique was assessed in 50 physicians and 50 nurses using a child mannequin and a validated videotaped nine-step scoring method. The participants' knowledge was evaluated by a questionnaire.Results: The inhalation technique was perfectly mastered by 49% of the study participants and almost perfectly mastered by another 34% (mean score 8.3 ± 0.7; range 5-9). Nurses were more likely than doctors to demonstrate the technique perfectly (66% vs. 32%, p < 0.05). The two most common errors were forgetting to shake the pMDI between two consecutive puffs (38% of the participants) and putting the patient in an incorrect position (11%). About half of the participants reported that they checked each patient's inhalation technique at every opportunity and knew how to clean the VHC. A large majority did not employ a reliable method to determine the amount of medication remaining in pMDIs without a counter.Conclusion: Healthcare professionals' practical skills and knowledge on inhalation therapy were not completely mastered and could be improved with a mandatory training program.

Incident reports versus direct observation to identify medication errors and risk factors in hospitalised newborns.

Newborns are often exposed to medication errors in hospitals. Identification and understanding the causes and risk factors associated with medication errors will help to improve the effectiveness of medication. We sought to compare voluntary incident reports and direct observation in the identification of medication errors. We also identified corresponding risk factors in order to establish measures to prevent medication errors. Medication errors identified by a clinical pharmacist and those recorded in our incident reporting system by caregivers were analysed. Main outcomes were rates, type and severity of medication error, and other variables related to medication errors. Ultimately, 383 medication errors were identified by the clinical pharmacist, and two medication errors were declared by caregivers. Prescription errors accounted for 38.4%, preparation errors for 16.2%, and administration errors for 45.4%. The two variables significantly related to the occurrence of medication errors were gestational age < 32.0 weeks (p = 0.04) and the number of drugs prescribed (p < 0.01).Conclusion: Caregivers underreported the true rate of medication errors. Most medication errors were caused by inattention and could have been limited by simplifying the medication process. Risk of medication errors is increased in newborns < 32.0 weeks and increases with the number of drugs prescribed to each patient. What is Known: • Newborns in hospitals are particularly susceptible to medication errors. • Identification and understanding the reasons for medication errors should help us to establish preventive measures to reduce the occurrence of such errors. What is New: • Direct observation of the medication process, though time consuming, is essential to accurately assess the frequency of medication errors, which are underreported by caregivers. Most medication errors are caused by inattention and could be limited by simplifying the medication process. • The risk of medication errors was significantly increased in very preterm newborns (< 32 weeks) and when the number of prescription per patient increased.

A bundle with a preformatted medical order sheet and an introductory course to reduce prescription errors in neonates.

The objective of this study was to assess whether the introduction of a new preformatted medical order sheet coupled with an introductory course affected prescription quality and the frequency of errors during the prescription stage in a neonatal intensive care unit (NICU). Two-phase observational study consisting of two consecutive 4-month phases: pre-intervention (phase 0) and post-intervention (phase I) conducted in an 11-bed NICU in a Swiss university hospital. Interventions consisted of the introduction of a new preformatted medical order sheet with explicit information supplied, coupled with a staff introductory course on appropriate prescription and medication errors. The main outcomes measured were formal aspects of prescription and frequency and nature of prescription errors. Eighty-three and 81 patients were included in phase 0 and phase I, respectively. A total of 505 handwritten prescriptions in phase 0 and 525 in phase I were analysed. The rate of prescription errors decreased significantly from 28.9% in phase 0 to 13.5% in phase I (p < 0.05). Compared with phase 0, dose errors, name confusion and errors in frequency and rate of drug administration decreased in phase I, from 5.4 to 2.7% (p < 0.05), 5.9 to 0.2% (p < 0.05), 3.6 to 0.2% (p < 0.05), and 4.7 to 2.1% (p < 0.05), respectively. The rate of incomplete and ambiguous prescriptions decreased from 44.2 to 25.7 and 8.5 to 3.2% (p < 0.05), respectively. CONCLUSION: Inexpensive and simple interventions can improve the intelligibility of prescriptions and reduce medication errors. WHAT IS KNOWN: Medication errors are frequent in NICUs and prescription is one of the most critical steps. CPOE reduce prescription errors, but their implementation is not available everywhere. WHAT IS NEW: Preformatted medical order sheet coupled with an introductory course decrease medication errors in a NICU. Preformatted medical order sheet is an inexpensive and readily implemented alternative to CPOE.

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 highly sensitive LC-tandem MS assay for the measurement in plasma and in urine of salbutamol administered by nebulization during mechanical ventilation in healthy volunteers.

The new-generation nebulizers are commonly used for the administration of salbutamol in mechanically ventilated patients. The different modes of administration and new devices have not been compared. We developed a liquid chromatography-tandem mass spectrometry method for the determination of concentrations as low as 0.05 ng/mL of salbutamol, corresponding to the desired plasma concentration after inhalation. Salbutamol quantification was performed by reverse-phase HPLC. Analyte quantification was performed by electrospray ionization-triple quadrupole mass spectrometry using selected reaction monitoring detection ESI in the positive mode. The method was validated over concentrations ranging from 0.05 to 100 ng/mL in plasma and from 0.18 to 135 ng/mL in urine. The method is precise, with mean inter-day coefficient of variation (CV%) within 3.1-8.3% in plasma and 1.3-3.9% in urine, as well as accurate. The proposed method was found to reach the required sensitivity for the evaluation of different nebulizers as well as nebulization modes. The present assay was applied to examine whether salbutamol urine levels, normalized with the creatinine levels, correlated with the plasma concentrations. A suitable, convenient and noninvasive method of monitoring patients receiving salbutamol by mechanical ventilation could be implemented.

The hospital pharmacist: an important contributor to improved patient safety in the hospital.

Injectable drugs are high-risk products and their reconstitution in hospital wards is a potential source of errors. Thus, in order to secure the reconstitution process and thereby improve safety, the pharmacy department of Lausanne University Hospital is focusing on developing ready-to-use forms (CIVAS). These preparations are compounded in controlled clean rooms and are analyzed prior to release. In the intensive care unit, amiodarone 12.5 mg/mL in glucose 5% is one of the high-risk preparations, which has led the pharmacy to develop a ready-to-use solution. To this end, a one-year stability study was initiated, and the preliminary results (after six months) are illustrated here. A stability-indicating HPLC method was developed and validated for monitoring the concentration of amiodarone. Batches were stored at 5 °C and 30 °C, which were analyzed immediately after preparation, after one, two, four and six months of storage. The pH and osmolality values were monitored at the respective time intervals. It was observed that after six months, all the results were within specifications. However, the pH values started to decrease after two months when amiodarone was stored at 30 °C. After six months, a degradation peak appeared on the chromatogram of these solutions, which suggested that amiodarone is more stable at 5 °C. The preliminary results obtained in this study indicated that injectable amiodarone solutions are stable for six months under refrigerated storage conditions. The study is ongoing.

Randomized clinical trial to assess the protective efficacy of a Plasmodium vivax CS synthetic vaccine.

A randomized, double-blind, controlled vaccine clinical trial was conducted to assess, as the primary outcome, the safety and protective efficacy of the Plasmodium vivax circumsporozoite (CS) protein in healthy malaria-naïve (phase IIa) and semi-immune (phase IIb) volunteers. Participants (n = 35) were randomly selected from a larger group (n = 121) and further divided into naïve (n = 17) and semi-immune (n = 18) groups and were immunized at months 0, 2, and 6 with PvCS formulated in Montanide ISA-51 adjuvant or placebo (adjuvant alone). Specific antibodies and IFN-γ responses to PvCS were determined as secondary outcome; all experimental volunteers developed specific IgG and IFN-γ. Three months after the last immunization, all participants were subjected to controlled human malaria infection. All naive controls became infected and drastic parasitemia reduction, including sterile protection, developed in several experimental volunteers in phase IIa (6/11) (54%, 95% CI 0.25-0.84) and phase IIb (7/11) (64%, 95% CI 0.35-0.92). However, no difference in parasitemia was observed between the phase IIb experimental and control subgroups. In conclusion, this study demonstrates significant protection in both naïve and semi-immune volunteers, encouraging further PvCS vaccine clinical development. Trial registration number NCT02083068. This trial was funded by Colciencias (grant 529-2009), NHLBI (grant RHL086488 A), and MVDC/CIV Foundation (grant 2014-1206).

Substance P-induced skin inflammation is not modulated by a single dose of sitagliptin in human volunteers.

Substance P (SP), an undecapeptide belonging to the tachykinin family, is released during the activation of sensory nerves, and causes vasodilation, edema and pain through activation of tissular Neurokinin 1 receptors. SP proinflammatory effects are terminated by angiotensin converting enzyme (ACE) and neutral endopeptidase (NEP), while the aminopeptidase dipeptidylpeptidase IV (DPPIV) can also play a role. The aim of this randomized, crossover, double-blind study was to assess the cutaneous vasoreactivity (flare and wheal reaction, burning pain sensation) to intradermal injection of ascending doses of SP in six volunteers receiving a single therapeutic dose of the DPPIV inhibitor sitagliptin or a matching placebo. Cutaneous SP challenges produced the expected, dose-dependent flare and wheal response, while eliciting mild to moderate local pain sensation with little dose dependency. However, no differences were shown in the responses observed under sitagliptin compared with placebo, while the study would have been sufficiently powered to detect a clinically relevant increase in sensitivity to SP. The results of this pilot study are in line with proteolytic cleavage of SP by ACE and NEP compensating the blockade of DPPIV to prevent an augmentation of its proinflammatory action.

The bioavailability of bromazepam, omeprazole and paracetamol given by nasogastric feeding tube.

AIMS: To characterize and compare the pharmacokinetic profiles of bromazepam, omeprazole and paracetamol when administered by the oral and nasogastric routes to the same healthy cohort of volunteers. METHODS: In a prospective, monocentric, randomized crossover study, eight healthy volunteers received the three drugs by the oral (OR) and nasogastric routes (NT). Sequential plasma samples were analyzed by high-performance liquid chromatography-UV, pharmacokinetic parameters (Cmax, AUC(0-infinity), t(1/2), k(e), tmax) were compared statistically, and Cmax, AUC(0-infinity) and t(max) were analyzed for bioequivalence. RESULTS: A statistically significant difference was seen in the AUC(0-infinity) of bromazepam, with nasogastric administration decreasing availability by about 25%: AUC(OR) = 2501 ng mL(-1) h; AUC(NT) = 1855 ng mL(-1) h (p < 0.05); ratio (geometric mean) = 0.74 [90% confidence interval (CI) 0.64-0.87]. However, this does not appear to be clinically relevant given the usual dosage range and the drug's half-life (approx. 30 h). A large interindividual variability in omeprazole parameters prevented any statistical conclusion from being drawn in terms of both modes of administration despite their similar average profile: AUC(OR) = 579 ng mL(-1) h; AUC(NT) = 587 ng mL(-1) h (p > 0.05); ratio (geometric mean) = 1.01 (90% CI 0.64-1.61). An extended study with a larger number of subjects may possibly provide clearer answers. The narrow 90% confidence limits of paracetamol indicate bioequivalence: AUC(OR) = 37 microg mL(-1) h; AUC(NT) = 41 microg mL(-1) h(p > 0.05); ratio (geometric mean) = 1.12 (90% CI 0.98-1.28). CONCLUSION: The results of this study show that the nasogastric route of administration does not appear to cause marked, clinically unsuitable alterations in the bioavailability of the tested drugs.

Impact of a computerized physician order entry system on compliance with prescription accuracy requirements.

OBJECTIVE: To assess the change in non-compliant items in prescription orders following the implementation of a computerized physician order entry (CPOE) system named PreDiMed. SETTING: The department of internal medicine (39 and 38 beds) in two regional hospitals in Canton Vaud, Switzerland. METHOD: The prescription lines in 100 pre- and 100 post-implementation patients' files were classified according to three modes of administration (medicines for oral or other non-parenteral uses; medicines administered parenterally or via nasogastric tube; pro re nata (PRN), as needed) and analyzed for a number of relevant variables constitutive of medical prescriptions. MAIN OUTCOME MEASURE: The monitored variables depended on the pharmaceutical category and included mainly name of medicine, pharmaceutical form, posology and route of administration, diluting solution, flow rate and identification of prescriber. RESULTS: In 2,099 prescription lines, the total number of non-compliant items was 2,265 before CPOE implementation, or 1.079 non-compliant items per line. Two-thirds of these were due to missing information, and the remaining third to incomplete information. In 2,074 prescription lines post-CPOE implementation, the number of non-compliant items had decreased to 221, or 0.107 non-compliant item per line, a dramatic 10-fold decrease (chi(2) = 4615; P < 10(-6)). Limitations of the computerized system were the risk for erroneous items in some non-prefilled fields and ambiguity due to a field with doses shown on commercial products. CONCLUSION: The deployment of PreDiMed in two departments of internal medicine has led to a major improvement in formal aspects of physicians' prescriptions. Some limitations of the first version of PreDiMed were unveiled and are being corrected.

[Monitoring drug adherence for hypertensive and dyslipidemic patients in networks of community-based pharmacists and physicians]. / Suivi de l'adhésion thérapeutique des patients hypertendus ou dyslipi- démiques par les cercles de qualité médecins-pharmaciens.

Patient adherence is often poor for hypertension and dyslipidaemia. A monitoring of drug adherence might improve these risk factors control, but little is known in ambulatory care. We conducted a randomised controlled study in networks of community-based pharmacists and physicians in the canton of Fribourg to examine whether monitoring drug adherence with an electronic monitor (MEMS) would improve risk factor control among treated, but uncontrolled hypertensive and dyslipidemic patients. The results indicate that MEMS achieve a better blood pressure control and lipid profile, although its implementation requires considerable resources. The study also shows the value of collaboration between physicians and pharmacists in the field of patient adherence to improve ambulatory care of patients with cardiovascular risk factors.

Stability of prostaglandin E1 solutions stored in polypropylene syringes for continuous intravenous administration to newborns.

OBJECTIVE: We aimed to monitor the physicochemical stability of prostaglandin E1 (PGE1) 1.5 and 15 µg/mL in 10% dextrose stored in polypropylene syringes. METHODS: We developed a liquid chromatography-high resolution mass spectrometry (LC-HRMS) method to detect and quantify levels of PGE1. Method selectivity was performed with a mixture of PGE1 and its degradation products. Forced degradation tests were performed to determine which degradation products were most likely to form. PGE1 injection solutions in 10% dextrose were stored in unprotected and shielded-from-light polypropylene syringes in a climatic chamber. Samples were taken immediately after preparation (T0) and after 24, 48, 72 and 168 hours for analysis. PGE1 solutions were considered stable if ≥90.0% of the initial concentration was retained. RESULTS: The LC-HRMS method was validated in the range of 0.086-0.200µg/mL PGE1 with trueness values between 98.2% and 100.3%, and repeatability and intermediate precision values of <2.2%and <4.7%, respectively. The quantification and detection limits of the method were 0.086 and 0.026µg/mL, respectively. PGE1 and its degradation products were resolved chromatographically. PGE1 injection solutions were≥90.0%stable after 48hours in unprotected from light (UPL) syringes. The solutions remained clear without precipitation, colour or pH modification and subvisible particles within the permitted levels. Prostaglandin A1 was the sole degradation product observed. CONCLUSIONS: A LC-HRMS method to evaluate PGE1 stability in a 10% dextrose was developed and validated. PGE1 1.5 and 15µg/mL in 10% dextrose solution are stable for 48hours when stored at 30ºC in UPL polypropylene syringes.

Pharmacist intervention acceptance for the reduction of potentially inappropriate drug prescribing in acute psychiatry.

Background Prescribing for the elderly is challenging. A previous observational study conducted in our geriatric psychiatry admission unit (GPAU) using STOPP/START criteria showed a high number of potentially inappropriate drug prescriptions (PIDPs). A clinical pharmacist was added to our GPAU as a strategy to reduce PIDPs. Objective The objective of the present study was to assess the impact of a clinical pharmacist on PIDPs by measuring acceptance rates of pharmacist interventions (PhIs). Setting This study was conducted at the GPAU of Lausanne University Hospital. Method The clinical pharmacist attended four GPAU meetings weekly. Complete medication reviews were performed daily. The clinical pharmacist conducted standard analyses based on clinical judgment and STOPP/START criteria assessment. A PhI was generated when a PIDP was detected. When a PhI was accepted, the PIDP was considered as eliminated. Acceptance rate of PhI was calculated (number of PhI accepted/total number of PhI). Main outcome measure PhIs acceptance rates. Results In a cohort of 102 patients seen between July 2013 and February 2014, a total of 697 PhIs (average 6.8/patient) were made based on standard evaluation (n = 479) and STOPP/START criteria (n = 243). The global acceptance rate was 68% (standard, 78%; STOPP/START, 47%). Conclusion Good PhIs acceptance rates demonstrated that a clinical pharmacist can reduce PIDPs in a GPAU. PhIs based on standard evaluation had a higher acceptance than those based on STOPP/START criteria, probably because they are better adapted to individual patients. However, these two evaluation approaches can be used in a complementary manner.

Unlicensed and off-label drug use in a Swiss paediatric university hospital.

BACKGROUND: Many medicines used in newborns, infants, children and adolescents are not licensed ("unlicensed") or are prescribed outside the terms of the marketing authorization ("off-label"). Several studies have shown that this is a common practice in various healthcare settings in the USA, Europe and Australia, but data are scarce in Switzerland. OBJECTIVES: The aim of our prospective study was to determine the proportion of unlicensed or off-label prescriptions in paediatric patients. METHODS: This pilot study was conducted prospectively over a six month period in the department of paediatrics of a university hospital. RESULTS: Sixty patients aged from three days to 14 years were included in the study. A total of 483 prescriptions were written for the patients. More than half of all prescriptions (247; 51%) followed the terms of the marketing authorization. 114 (24%) were unlicensed and 122 (25%) off-label. All patients received at least one unlicensed or offlabel medicine. CONCLUSION: The use of unlicensed or off-label medicines to treat children was found to be common. Co-operation between the pharmaceutical industry, national regulatory authorities, clinical researchers, healthcare professionals and parents is required in order to ensure that children do not remain "therapeutic orphans".

Antibiotic consumption to detect epidemics of Pseudomonas aeruginosa in a burn centre: A paradigm shift in the epidemiological surveillance of Pseudomonas aeruginosa nosocomial infections.

PURPOSE: The control of antibiotic resistance and nosocomial infections are major challenges for specialized burn centres. Early detection of those epidemic outbreaks is crucial to limit the human and financial burden. We hypothesize that data collected by antibiotic consumption medico-economic surveys could be used as warning signal to detect early nosocomial outbreaks. METHODS: A retrospective analysis was conducted that included all burn patients staying >48h on the Lausanne BICU (Burn Intensive Care Unit) between January 2001 and October 2012 who received systemic therapeutic antibiotics. Infection episodes were characterized according to predefined criteria. Antibiotic consumption data, obtained from the quarterly surveillance of drug consumption surveys, were translated into defined daily doses (DDDs). RESULTS: In total, 297 out of 414 burn patients stayed >48h, giving a total of 7458 'burn-days'. We identified 610 infection episodes (burn wound [32.0%], respiratory [31.1%], and catheter [21.8%]), from 774 microorganisms. Pseudomonas aeruginosa (26.2%), Staphylococcus aureus (11.5%), and Candida albicans (7.0%) were the main pathogens. We observed three distinct outbreaks of P. aeruginosa infections in 2002-2003, 2006, and 2009-2011. These outbreaks correlated with an increase in the DDDs of anti-Pseudomonas antibiotics. CONCLUSIONS: Our data support a paradigm shift in the epidemiological surveillance of nosocomial P. aeruginosa epidemics in burn centres, using the rise in antibiotic consumption as an early trigger to initiate the molecular typing of P. aeruginosa strains and the reinforcement of standard infection control procedures.

In vitro evaluation of bronchodilator drug delivery by jet nebulization during pediatric mechanical ventilation.

OBJECTIVE: To determine the influence of jet nebulizer brands and nebulization mode on albuterol 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, six jet nebulizers (Microneb NA420, Sidestream, Acorn II, Cirrus, Upmist, Micro Mist) were tested in four nebulization modes in a bench model mimicking the ventilatory pattern of a 10-kg infant (Galileo ventilator, Hamilton Medical). The amounts of albuterol deposited on the inspiratory filters at the end of the endotracheal tube were determined, as well as the pressure, flow profiles, and particle size distribution of the jet nebulizers. MEASUREMENTS AND MAIN RESULTS: Pooling the data of the six jet nebulizer brands (n = 30) indicated that intermittent nebulization during the expiratory phase was more efficient (6.5 +/- 2.5% of the initial dose, p < .001) than intermittent nebulization during the inspiratory phase (1.9 +/- 1.2%) and continuous nebulization with air from the ventilator (4.0 +/- 1.5%) or from an external source (4.2 +/- 1.4%). The particle size distribution at 6 L x min(-1) was between 2.81 and 3.30 microm. CONCLUSIONS: In our in vitro pediatric lung model, the quantity of inhaled drug was low. Jet nebulizer brands and nebulization modes significantly affected drug delivery, and in vitro models designed for adults cannot be extrapolated to infants.

Stop using the flotation technique and start weighing salbutamol pressurised metered-dose inhalers without dose counters.

Salbutamol pressurised metered-dose inhalers (pMDIs) are not equipped with dose counters outside the USA. The aim of this study was to describe a simple reproducible method for determining the number of doses remaining in a pMDI based on scale weight. With a laboratory scale, the mean weight of the canisters was 28.61 ± 0.10 g after priming and 14.84 ± 0.23 g after 200 puffs. Similar results were obtained with two common digital scales. We recommend weighing salbutamol canisters on a common digital scale, and replacing an old pMDI with a new one when the weight falls to ≤15 g.

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 hospital's 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.

Physicochemical aspects and efficiency of albuterol nebulization: comparison of three aerosol types in an in vitro pediatric model.

BACKGROUND: Advances in nebulizer design have produced both ultrasonic nebulizers and devices based on a vibrating mesh (vibrating mesh nebulizers), which are expected to enhance the efficiency of aerosol drug therapy. The aim of this study was to compare 4 different nebulizers, of 3 different types, in an in vitro model using albuterol delivery and physical characteristics as benchmarks. METHODS: The following nebulizers were tested: Sidestream Disposable jet nebulizer, Multisonic Infra Control ultrasonic nebulizer, and the Aerogen Pro and Aerogen Solo vibrating mesh nebulizers. Aerosol duration, temperature, and drug solution osmolality were measured during nebulization. Albuterol delivery was measured by a high-performance liquid chromatography system with fluorometric detection. The droplet size distribution was analyzed with a laser granulometer. RESULTS: The ultrasonic nebulizer was the fastest device based on the duration of nebulization; the jet nebulizer was the slowest. Solution temperature decreased during nebulization when the jet nebulizer and vibrating mesh nebulizers were used, but it increased with the ultrasonic nebulizer. Osmolality was stable during nebulization with the vibrating mesh nebulizers, but increased with the jet nebulizer and ultrasonic nebulizer, indicating solvent evaporation. Albuterol delivery was 1.6 and 2.3 times higher with the ultrasonic nebulizer and vibrating mesh nebulizers devices, respectively, than with the jet nebulizer. Particle size was significantly higher with the ultrasonic nebulizer. CONCLUSIONS: The in vitro model was effective for comparing nebulizer types, demonstrating important differences between nebulizer types. The new devices, both the ultrasonic nebulizers and vibrating mesh nebulizers, delivered more aerosolized drug than traditional jet nebulizers.

Effective treatment of invasive Aspergillus fumigatus infection using combinations of topical and systemic antifungals in a severely burned patient.

The authors describe an invasive Aspergillus fumigatus deep-burn wound infection in a severely burned patient that was successfully treated with a combination of topical terbinafine and systemic voriconazole antifungal therapy. To our knowledge, this is the first case report describing the effective control of an invasive deep-burn wound infection using this combination.