Description and analysis of hospital pharmacies in Madagascar.

OBJECTIVE: Madagascar's health care system has operated without formal hospital pharmacies for more than two decades. The gradual integration of pharmacists in public hospitals since 2012 will allow the structuring of this field. This study was conducted to characterize the current situation regarding all aspects relating to the general functioning of hospital pharmacies and the services provided. METHODS: This qualitative research used semi-structured interviews. Interviewees' perceptions about the general organization and functioning of hospital pharmacies and details on services provided were collected. The 16 interviewees were Ministry of Health staff members involved in hospital pharmacy, hospital directors, medical staff members and hospital pharmacy managers. Interviews were recorded, translated into French if conducted in Malagasy, and fully transcribed. Verbatim transcripts were coded according to the themes of hospital pharmacy and topical content analysis was performed. RESULTS: The principal issue perceived by interviewees was the heterogeneity of the system in terms of technical and financing management, with a main impact on the restocking of pharmaceutical products. The drug supply chain is not under control: no internal procedure has been established for the selection of pharmaceutical products, the quantification of needs is complex, stock management is difficult to supervise, a standard prescription protocol is lacking, dispensing is performed by unqualified staff, no pharmaceutical preparation is manufactured in the hospitals and administration occurs without pharmaceutical support. CONCLUSIONS: Progressive structuring of efficient hospital pharmacy services using the Basel statements for the future of hospital pharmacy is urgently needed to improve health care in Madagascar.

Impact of Real-Time Therapeutic Drug Monitoring on the Prescription of Antibiotics in Burn Patients Requiring Admission to the Intensive Care Unit.

As pharmacokinetics after burn trauma are difficult to predict, we conducted a 3-year prospective, monocentric, randomized, controlled trial to determine the extent of under- and overdosing of antibiotics and further evaluate the impact of systematic therapeutic drug monitoring (TDM) with same-day real-time dose adaptation to reach and maintain antibiotic concentrations within the therapeutic range. Forty-five consecutive burn patients treated with antibiotics were prospectively screened. Forty fulfilled the inclusion criteria; after one patient refused to participate and one withdrew consent, 19 were randomly assigned to an intervention group (patients with real-time antibiotic concentration determination and subsequent adaptations) and 19 were randomly assigned to a standard-of-care group (patients with antibiotic administration at the physician's discretion without real-time TDM). Seventy-three infection episodes were analyzed. Before the intervention, only 46/82 (56%) initial trough concentrations fell within the range. There was no difference between groups in the initial trough concentrations (adjusted hazard ratio = 1.39 [95% confidence interval {CI}, 0.81 to 2.39], P = 0.227) or the time to reach the target. However, thanks to real-time dose adjustments, the trough concentrations of the intervention group remained more within the predefined range (57/77 [74.0%] versus 48/85 [56.5%]; adjusted odd ratio [OR] = 2.34 [95% CI, 1.17 to 4.81], P = 0.018), more days were spent within the target range (193 days/297 days on antibiotics [65.0%] versus 171 days/311 days in antibiotics [55.0%]; adjusted OR = 1.64 [95% CI, 1.16 to 2.32], P = 0.005), and fewer results were below the target trough concentrations (25/118 [21.2%] versus 44/126 [34.9%]; adjusted OR = 0.47 [95% CI, 0.26 to 0.87], P = 0.015). No difference in infection outcomes was observed between the study groups. Systematic TDM with same-day real-time dose adaptation was effective in reaching and maintaining therapeutic antibiotic concentrations in infected burn patients, which prevented both over- and underdosing. A larger multicentric study is needed to further evaluate the impact of this strategy on infection outcomes and the emergence of antibiotic resistance during long-term burn treatment. (This study was registered with the ClinicalTrials.gov platform under registration no. NCT01965340 on 27 September 2013.).

Does the type of parenteral lipids matter? A clinical hint in critical illness.

BACKGROUND & AIMS: An altered lipid profile is common among intensive care unit (ICU) patients, but evidence regarding the impact of different fatty acid (FA) emulsions administered to patients requiring parenteral nutrition (PN) is scarce. This study aimed to compare the plasma triglycerides (TG) response to two types of commercial lipid emulsions: a structured mixture of long- and medium-chain triglycerides (LCT/MCT) or LCTs with n-9 FA (LCT+) in ICU patients. METHODS: In this retrospective observational study conducted in a multidisciplinary ICU: two groups were defined by the type of emulsion used. Inclusion criteria were: consecutive patients on PN staying ≥4 days with one TG determination before commencing PN and at least one during PN. Recorded variables included energy intake, amount and type of nutritional lipids, propofol dose, glucose and protein intake, laboratory parameters, and all drugs received. Hypertriglyceridemia (hyperTG) was defined as TG >2 mmol/L. RESULTS: The dynamic impact of the emulsion was analyzed in 187/757 patients completing the inclusion criteria (112 LCT/MCT and 75 LCT+). The demographic variables, severity indices, diagnostic categories, and outcomes did not differ between the two groups. Seventy-seven patients (41%) presented hyperTG. Both groups received similar daily energy (1604 versus 1511 kcal/day), lipids (60 versus 61 g/day), and glucose intake (233 versus 197 g/day). There was no increase of TG concentration in those receiving the LCT/MCT emulsion compared to those receiving the LCT+ emulsion (0 and 0.2 mmol/L, respectively, p < 0.05). CONCLUSION: LCT/MCT emulsions are associated with a less pronounced increase of plasma TG levels than LCT+ emulsions.

Impact of antibiotic use on carbapenem resistance in Pseudomonas aeruginosa: is there a role for antibiotic diversity?

In this study, we aimed to evaluate the relationship between the rates of resistance of Pseudomonas aeruginosa to carbapenems and the levels and diversity of antibiotic consumption. Data were retrospectively collected from 20 acute care hospitals across 3 regions of Switzerland between 2006 and 2010. The main outcome of the present study was the rate of resistance to carbapenems among P. aeruginosa. Putative predictors included the total antibiotic consumption and carbapenem consumption in defined daily doses per 100 bed days, the proportion of very broad-spectrum antibiotics used, and the Peterson index. The present study confirmed a correlation between carbapenem use and carbapenem resistance rates at the hospital and regional levels. The impact of diversifying the range of antibiotics used against P. aeruginosa resistance was suggested by (i) a positive correlation in multivariate analysis between the above-mentioned resistance and the proportion of consumed antibiotics having a very broad spectrum of activity (coefficient = 1.77; 95% confidence interval, 0.58 to 2.96; P < 0.01) and (ii) a negative correlation between the resistance and diversity of antibiotic use as measured by the Peterson homogeneity index (coefficient = -0.52; P < 0.05). We conclude that promoting heterogeneity plus parsimony in the use of antibiotics appears to be a valuable strategy for minimizing the spread of carbapenem resistance in P. aeruginosa in hospitals.

Hypertriglyceridemia: a potential side effect of propofol sedation in critical illness.

PURPOSE: Hypertriglyceridemia (hyperTG) is common among intensive care unit (ICU) patients, but knowledge about hyperTG risk factors is scarce. The present study aims to identify risk factors favoring its development in patients requiring prolonged ICU treatment. METHODS: Prospective observational study in the medicosurgical ICU of a university teaching hospital. All consecutive patients staying ≥4 days were enrolled. Potential risk factors were recorded: pathology, energy intake, amount and type of nutritional lipids, intake of propofol, glucose intake, laboratory parameters, and drugs. Triglyceride (TG) levels were assessed three times weekly. Statistics was based on two-way analysis of variance (ANOVA) and linear regression with potential risk factors. RESULTS: Out of 1,301 consecutive admissions, 220 patients were eligible, of whom 99 (45 %) presented hyperTG (triglycerides >2 mmol/L). HyperTG patients were younger, heavier, with more brain injury and multiple trauma. Intake of propofol (mg/kg/h) and lipids' propofol had the highest correlation with plasma TG (r (2) = 0.28 and 0.26, respectively, both p < 0.001). Infection and inflammation were associated with development of hyperTG [C-reactive protein (CRP), r (2) = 0.19, p = 0.004]. No strong association could be found with nutritional lipids or other risk factors. Outcome was similar in normo- and hyperTG patients. CONCLUSIONS: HyperTG is frequent in the ICU but is not associated with adverse outcome. Propofol and accompanying lipid emulsion are the strongest risk factors. Our results suggest that plasma TG should be monitored at least twice weekly in patients on propofol. The clinical consequences of propofol-related hyperTG should be investigated in further studies.

Changes in the use of broad-spectrum antibiotics after cefepime shortage: a time series analysis.

The original cefepime product was withdrawn from the Swiss market in January 2007 and replaced by a generic 10 months later. The goals of the study were to assess the impact of this cefepime shortage on the use and costs of alternative broad-spectrum antibiotics, on antibiotic policy, and on resistance of Pseudomonas aeruginosa toward carbapenems, ceftazidime, and piperacillin-tazobactam. A generalized regression-based interrupted time series model assessed how much the shortage changed the monthly use and costs of cefepime and of selected alternative broad-spectrum antibiotics (ceftazidime, imipenem-cilastatin, meropenem, piperacillin-tazobactam) in 15 Swiss acute care hospitals from January 2005 to December 2008. Resistance of P. aeruginosa was compared before and after the cefepime shortage. There was a statistically significant increase in the consumption of piperacillin-tazobactam in hospitals with definitive interruption of cefepime supply and of meropenem in hospitals with transient interruption of cefepime supply. Consumption of each alternative antibiotic tended to increase during the cefepime shortage and to decrease when the cefepime generic was released. These shifts were associated with significantly higher overall costs. There was no significant change in hospitals with uninterrupted cefepime supply. The alternative antibiotics for which an increase in consumption showed the strongest association with a progression of resistance were the carbapenems. The use of alternative antibiotics after cefepime withdrawal was associated with a significant increase in piperacillin-tazobactam and meropenem use and in overall costs and with a decrease in susceptibility of P. aeruginosa in hospitals. This warrants caution with regard to shortages and withdrawals of antibiotics.

Hospital antibiotic consumption in Switzerland: comparison of a multicultural country with Europe.

The consumption of antibiotics in the inpatient setting of Switzerland was assessed to determine possible differences between linguistic regions, and to compare these results with European results. Data on antibiotic consumption were obtained from a sentinel network representing 54% of the national acute care hospitals, and from a private drug market monitoring company. Aggregated data were converted into defined daily doses (DDD). The total consumption density in Switzerland was close to the median consumption reported in European surveys. Between 2004 and 2008, the total consumption of systemic antibiotics rose from 46.1 to 54.0 DDD per 100 occupied bed-days in the entire hospitals, and from 101.6 to 114.3 DDD per 100 occupied bed-days in the intensive care units. Regional differences were observed for total consumption and among antibiotic classes. Hospitals in the Italian-speaking region showed a significantly higher consumption density, followed by the French- and German-speaking regions. Hospitals in the Italian-speaking region also had a higher consumption of fluoroquinolones, in line with the reported differences between Italy, Germany and France. Antibiotic consumption in acute care hospitals in Switzerland is close to the European median with a relatively low consumption in intensive care units. Some of the patterns of variation in consumption levels noticed among European countries are also observed among the cultural regions of Switzerland.

[Generic drugs and legal incentives: which impact?]. / Génériques et article 38a OPAS: quel impact?

The dispositions that regulate generic substitution in Switzerland have been recently revised, and impose definite incentives on prescribers. The benefits and drawbacks associated with the prescription of generic drugs are reviewed, considering the viewpoints of patients, practitioners and third party payers. While the initial prescription of a generic drug raises no specific concerns, the generic switch during long-term treatment may require some caution. The advantages of using International Nonproprietary Names (INN) for drug prescription are discussed. A renewal of prescription habits would be welcomed however several practical issues would have to find rational solutions.

[Generic drug prescribing: pilot study on the impact of the new drug pricing system on costs and potential savings]. / Prescription de médicaments génériques: impact du nouveau système de prix sur les coûts et les économies potentielles.

The impact of a systematic generic substitution and of the new drug pricing system (implemented in 2002 for cost saving reasons) on prescription cost was computed on the basis of prescriptions delivered in January 1999 for patients leaving our university hospital. A total of 3,099 prescriptions, representing 5,514 drugs, were delivered in one month, of which 335 (6%) were excluded (drug not available in 2002 or magistral preparations). Forced generic prescription would have saved 3,8% of global costs, while the new drug pricing system would have increased costs between 1,1% and 8,0%. In this specific setting, savings linked with forced generic drug prescription was weak (4 to 5%), and the expected savings of the new drug pricing system were not observed.

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.

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.

Evaluation of nurses' errors associated in the preparation and administration of medication in a pediatric intensive care unit.

The objectives of this study were to determine the frequency and the types of errors which occur regarding the preparation and the administration of medication and to identify the main causes of these errors in a pediatric intensive care unit (PICU) at the University Hospital in Lausanne (Switzerland). In this prospective study, based on the observation of nurses' activities, the data were collected over a period of 10 weeks. The error classification was based on the American Society of Hospital Pharmacy (ASHP) definitions. The frequency of errors was calculated as the sum of all noted errors divided by the total administered drugs, plus the sum of all omitted drugs, multiplied by 100. The sum of all given doses plus all omitted doses gives the 'total opportunity for errors'. This total was 275 and the total frequency of errors was 26.9%. The most frequent errors were wrong-time errors (32.4%), wrong-administration-technique errors (32.4%) and preparation errors (23.0%). In relation with other studies conducted under comparable conditions, a lesser number of omissions and wrong-time errors were observed. On the contrary, administration-technique and dose-preparation errors were more frequent at our hospital. A program of systematic assistance and survey by professional pharmacists could improve the quality of the preparation and administration of medication in the PICU.

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.

[Evaluation of antibiotic use: a prospective study in a university hospital center]. / Evaluation de l'utilisation des antibiotiques: une étude prospective dans un centre hospitalier universitaire.

The inappropriate use of antibiotics has been documented by several studies. Most of these studies have been performed in the USA and there is very little data from Europe and Switzerland. A three-month prospective study was carried out at the University Medical Center of Lausanne in the departments of internal medicine, general surgery and traumatology. During this period, 2112 patients were hospitalized among whom 878 received one or more courses of antibiotic therapy: the treatment was given prophylactically in 35% of the cases and therapeutically in the other 65%. A total of 1165 antibiotic prescriptions were evaluated. The administration of the antibiotic was considered to be indicated in 96% of the cases. However, 24% of the prescriptions contained at least one error. 50% of the errors were observed in prophylactic treatments and most were related to the length of administration and the spectrum of the agents. The errors in therapeutic prescription were found mainly in indications for urinary and respiratory tract infections, and were related to the spectrum of the antibiotic and the length of treatment. It was calculated that the inappropriate use of antibiotics accounted for approximately 7% of the total costs of all antibiotics used. We estimated that half of this excess in costs could probably be saved by the introduction of simple corrective measures mainly directed at limiting the duration of administration.

A comparative study of formaldehyde detection using chromotropic acid, acetylacetone and HPLC in cosmetics and household cleaning products.

Chromotropic acid and acetylacetone methods for qualitative determination of formaldehyde were tested in parallel on 48 commercial samples, with high-performance liquid chromotography (HPLC) implemented for quantitative measure. In addition, interference with the detection of formaldehyde was investigated by analyzing 12 other aldehydes and ketones, 7 essential oils and 3 polysorbates. Throughout this comparative study, the disadvantages of the chromotropic acid method, of which 2 variants were used, were delineated and we found that the acetylacetone test proved to be a more efficient screening method for formaldehyde detection in a clinical laboratory.

Quantitative determination of particulate contamination in intravenous administration sets.

Particle counts were performed on 1,000 intravenous administration sets from ten suppliers on the Swiss market using a HIAC/Royco electronic counter. The following main conclusions may be drawn from the results of this study: --the small particles were the most numerous, regardless of the type of set; --the differences in the counts obtained for the different suppliers' sets tended to level off for particles larger than 10 microns; --the drip chamber and latex connector may be two important sources of particles; --the particulate contamination from the sets is relatively low compared with the amount of particles contained in the parenteral solutions.

Comparative study between liquid and solid media for the detection of bacterial contamination in intravenous solutions.

For the sterility testing of intravenous solutions, the Pharmacopeia recommend the use of liquid media. However, contamination by a single micro-organism during the test may lead to the inappropriate blocking of the release of the batch. An alternative method using solid media for culturing the membranes used in the filtration was therefore sought. With an artificial contamination with 10-100 colony-forming-units (cfu) of nine different micro-organisms, including those advocated by the Pharmacopeia, the feasibility of two different methods was assessed using two different intravenous solutions manufactured in our hospital. The results show that recoveries of minute amounts of bacteria using solid media and liquid media were similar. In all experiments there was a concordance in both positive and negative results. However, the batches of solutions have to be tested as quickly as possible after their preparation, whatever the method used, to avoid false-negative tests.

Efficacy and stability of two chlorine-containing antiseptics.

Dakin's solution and a chloroxydizer in a hypertonic sodium chloride solution were tested for bacteriological and clinical effectiveness and stability. No real difference in effectiveness was observed between the two products; however, only the chloroxydizer showed satisfactory stability at 150 days under the test storage conditions.