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Background It is known that drug shortages represent a major challenge for all stakeholders involved in the process, but there is little evidence regarding insights into patients′ awareness and perspectives. This study aimed to investigate the patients-perceived drug shortages experience and their view on outcomes in different European hospital settings. Furthermore, we wanted to explore information preferences on drug shortages. Methods A retrospective, cross sectional, a mixed method study was conducted in six European hospital settings. One hospital (H) from each of this country agreed to participate: Bosnia and Herzegovina (H-BiH), Croatia (H-CR), Germany (H-GE), Greece (H-GR), Serbia (H-SE) and Poland (H-PO). Recruitment and data collection was conducted over 27 months from November 2017 until January 2020. Overall, we surveyed 607 patients which completed paper-based questionnaire. Questions related to: general information (demographic data), basic knowledge on drug shortages, drug shortages experienced during hospitalization and information preferences on drug shortage. Differences between hospital settings were analyzed using Chi-squared test or Fisher’s exact test. For more complex contingency tables, Monte Carlo simulations (N = 2000) were applied for Fisher’s test. Post-hoc hospital-wise analyses were performed using Fisher’s exact tests. False discovery rate was controlled using the Bonferroni method. Analyses were performed using R: a language and environment for statistical computing (v 3.6.3). Results 6 % of patients reported experiences with drug shortages while hospitalized which led to a deterioration of their health. The majority of affected patients were hospitalized at hematology and/or oncology wards in H-BiH, H-PO and H-GE. H-BiH had the highest number of affected patients (18.1 %, N = 19/105, p N = 1/100, p = 0.001). In addition, 82.5 %, (N = 501/607) of respondents wanted to be informed of alternative treatment options if there was a drug shortage without a generic substitute available. Majority of these patients (66.4 %, N = 386/501) prefer to be informed by a healthcare professional. Conclusions Although drug shortages led to serious medical consequences, our findings show that most of the patients did not perceive shortages as a problem. One possible interpretation is that good hospital management practices by healthcare professionals helped to mitigate the perceived impact of shortages. Our study highlights the importance of a good communication especially between patients and healthcare professionals in whom our patients have the greatest trust.

At inpatient admission, the timeliness and completeness of the Germany-wide standardised medication list ("Bundeseinheitlicher Medikationsplan") often seems inappropriate. It is also unclear which characteristics of the lists increase the probability of discrepancies.A total of 100 medication lists of elective patients of a surgical clinic were retrospectively evaluated with regard to potential discrepancies compared to the standardised medication reconciliation. The discprepancies were assigned to 7 categories: drug taken is missing on the list, drug on the list is no longer taken, strength or dosage is missing at the list or is incorrect, or the documented dosage form is different. Advice on patient safety, involved drugs and dosage forms were also recorded. Multivariate analyses were used to investigate the influence of the timeliness, number of drugs and issuing medical specialty of the lists on the type and number of discrepancies.Compared to the medication reconciliation, 78 % (78/100) of the lists showed discrepancies. A total of 226 deviations (2.3 ± 0.6 deviations/list) were documented. Most often, a drug was missing from the list (n = 103). Of all recommendations, 64 % (83/177) concerned the perioperative management of anticoagulants (n = 55) and antidiabetics (n = 28), corresponding to 62 % (62/100) of the lists. In the multivariate analysis, only the risk of incorrect information on strength and dosage increased significantly with the age of the lists (p = 0.047) and was more than twice as high when the list was more than one month old.The timeliness, completeness and aspects of patient safety must be comprehensively validated. Medication lists that are older than 1 month should be checked particularly critically with regard to information on strength and dosage and the plan should be updated accordingly at regular intervals.Bei stationärer Aufnahme scheint die Aktualität und Vollständigkeit des Bundeseinheitlichen Medikationsplans häufig nicht gegeben. Ebenso ist unklar, welche Charakteristiken der Pläne die Wahrscheinlichkeit für Diskrepanzen erhöhen.Retrospektiv wurden deshalb 100 Pläne, die zur Arzneimittelanamnese elektiver Patienten einer chirurgischen Klinik mitgebracht wurden, geprüft, ob und welche Abweichungen bestanden. Die Abweichungen wurden 7 Kategorien zugeordnet: Arzneimittel, das in der Anamnese erfasst wurde, fehlt auf dem Plan, Arzneimittel auf dem Plan wird nicht mehr eingenommen, Stärke oder Dosierung fehlt auf dem Plan bzw. ist falsch oder die Darreichungsform ist falsch dokumentiert. Hinweise zur Arzneimitteltherapiesicherheit, involvierte Arzneimittel und -formen wurden ebenfalls erfasst. Mithilfe multivariater Analysen wurde der Einfluss der Aktualität, der Anzahl der Arzneimittel und der ausstellenden Facharztdisziplin der Pläne auf die Art und Anzahl an Diskrepanzen untersucht.Zur Arzneimittelanamnese wiesen 78 % (78/100) der Pläne Abweichungen auf. Insgesamt wurden 226 Abweichungen (2,3 ± 0,6 Abweichungen/Anamnese) dokumentiert. Am häufigsten fehlte ein Arzneimittel auf dem Plan (n = 103). Von allen Hinweisen und Empfehlungen betrafen 64 % (83/177) das perioperative Management von Antithrombotika (n = 55) und Antidiabetika (n = 28). In der multivariaten Analyse stieg nur das Risiko für fehlerhafte Angaben bei Stärke und Dosierung mit dem Alter der Pläne signifikant (p = 0,047) und war um mehr als das 2-fache erhöht, wenn der Plan älter als einen Monat war.Die Aktualität, Vollständigkeit und Aspekte der Arzneimitteltherapiesicherheit des Bundeseinheitlichen Medikationsplans sollten umfassend und gezielt im Anamnesegespräch validiert werden. In der Praxis sollten Pläne, die älter als 1 Monat sind, besonders kritisch hinsichtlich Angaben zu Stärke und Dosierung geprüft und der Plan entsprechend regelmäßig aktualisiert werden.

The mortality of patients with sepsis and septic shock is still unacceptably high. An effective antibiotic treatment within 1 h of recognition of sepsis is an important target of sepsis treatment. Delays lead to an increase in mortality;therefore, structured treatment concepts form a rational foundation, taking relevant diagnostic and treatment steps into consideration. In addition to the assumed focus and individual risks of each patient, local resistance patterns and specific problem pathogens must be taken into account for selection of anti-infection treatment. Many pathophysiological alterations influence the pharmacokinetics of antibiotics during sepsis. The principle of standard dosing should be abandoned and replaced by an individual treatment approach with stronger weighting of the pharmacokinetics/pharmacodynamics (PK/PD) index of the substance groups. Although this is not yet the clinical standard, prolonged (or continuous) infusion of beta-lactam antibiotics and therapeutic drug monitoring (TDM) can help to achieve defined PK targets. Prolonged infusion is sufficient without TDM but for continuous infusion TDM is basically necessary. A further argument for individual PK/PD-oriented antibiotic approaches is the increasing number of infections due to multidrug resistant pathogens (MDR) in the intensive care unit. For effective treatment antibiotic stewardship teams (ABS team) are becoming more established. Interdisciplinary cooperation of the ABS team with infectiologists, microbiologists and clinical pharmacists leads not only to a rational administration of antibiotics but also has a positive influence on the outcome. The gold standards for pathogen detection are still culture-based detection and microbiological resistance testing for the various antibiotic groups. Despite the rapid investigation time, novel polymerase chain reaction (PCR)-based procedures for pathogen identification and resistance determination, are currently only an adjunct to routine sepsis diagnostics due to the limited number of studies, high costs and limited availability. In complicated septic courses with multiple anti-infective treatment or recurrent sepsis, PCR-based procedures can be used in addition to therapy monitoring and diagnostics. Novel antibiotics represent potent alternatives in the treatment of MDR infections. Due to the often defined spectrum of pathogens and the practically absent resistance, they are suitable for targeted treatment of severe MDR infections (therapy escalation).

The present review assessed the evidence on risk factors for the occurrence of adverse health outcomes after discharge (i.e. unplanned readmission or adverse drug event after discharge) that are potentially modifiable by clinical pharmacist interventions. The findings were compared with patient characteristics reported in guidelines that supposedly indicate a high risk of drug-related problems. First, guidelines and risk assessment tools were searched for patient characteristics indicating a high risk of drug-related problems. Second, a systematic PubMed search was conducted to identify risk factors significantly associated with adverse health outcomes after discharge that are potentially modifiable by a clinical pharmacist intervention. After the PubMed search, 37 studies were included, reporting 16 risk factors. Only seven of 34 patient characteristics mentioned in pertinent guidelines corresponded to one of these risk factors. Diabetes mellitus (n = 11), chronic obstructive lung disease (n = 9), obesity (n = 7), smoking (n = 5) and polypharmacy (n = 5) were the risk factors reported most frequently in the studies. Additionally, single studies also found associations of adverse health outcomes with different drug classes {e.g. warfarin [hazard ratio 1.50; odds ratio (OR) 3.52], furosemide [OR 2.25] or high beta-blocker starting doses [OR 3.10]}. Although several modifiable risk factors were found, many patient characteristics supposedly indicating a high risk of drug-related problems were not part of the assessed risk factors in the context of an increased risk of adverse health outcomes after discharge. Therefore, an obligatory set of modifiable patient characteristics should be created and implemented in future studies investigating the risk for adverse health outcomes after discharge.

Introduction: While medicine shortages are complex, their mitigation is more of a challenge. Prospective risk assessment as a means to mitigate possible shortages, has yet to be applied equally across healthcare settings. The aims of this study have been to: 1) gain insight into risk-prevention against possible medicine shortages among healthcare experts; 2) review existing strategies for minimizing patient-health risks through applied risk assessment; and 3) learn from experiences related to application in practice. Methodology: A semi-structured questionnaire focusing on medicine shortages was distributed electronically to members of the European Cooperation in Science and Technology (COST) Action 15105 (28 member countries) and to hospital pharmacists of the European Association of Hospital Pharmacists (EAHP) (including associated healthcare professionals). Their answers were subjected to both qualitative and quantitative analysis (Microsoft Office Excel 2010 and IBM SPSS Statistics®) with descriptive statistics based on the distribution of responses. Their proportional difference was tested by the chi-square test and Fisher's exact test for independence. Differences in the observed ordinal variables were tested by the Mann-Whitney or Kruskal-Wallis test. The qualitative data were tabulated and recombined with the quantitative data to observe, uncover and interpret meanings and patterns. Results: The participants (61.7%) are aware of the use of risk assessment procedures as a coping strategy for medicine shortages, and named the particular risk assessment procedure they are familiar with failure mode and effect analysis (FMEA) (26.4%), root cause analysis (RCA) (23.5%), the healthcare FMEA (HFMEA) (14.7%), and the hazard analysis and critical control point (HACCP) (14.7%). Only 29.4% report risk assessment as integrated into mitigation strategy protocols. Risk assessment is typically conducted within multidisciplinary teams (35.3%). Whereas 14.7% participants were aware of legislation stipulating risk assessment implementation in shortages, 88.2% claimed not to have reported their findings to their respective official institutions. 85.3% consider risk assessment a useful mitigation strategy. Conclusion: The study indicates a lack of systematically organized tools used to prospectively analyze clinical as well as operationalized risk stemming from medicine shortages in healthcare. There is also a lack of legal instruments and sufficient data confirming the necessity and usefulness of risk assessment in mitigating medicine shortages in Europe. © Copyright © 2020 Miljković, Godman, Kovačević, Polidori, Tzimis, Hoppe-Tichy, Saar, Antofie, Horvath, De Rijdt, Vida, Kkolou, Preece, Tubić, Peppard, Martinez, Yubero, Haddad, Rajinac, Zelić, Jenzer, Tartar, Gitler, Jeske, Davidescu, Beraud, Kuruc-Poje, Haag, Fischer, Sviestina, Ljubojević, Markestad, Vujić-Aleksić, Nežić, Crkvenčić, Linnolahti, Ašanin, Duborija-Kovačević, Bochenek, Huys and Miljković.

Objectives Clinical pharmacy services in German hospitals appear to be underdeveloped compared with other European countries. However, recent developments have increased the interest in expanding these services. Detailed data about the current state of clinical pharmacy services in Germany are lacking. This survey establishes the current level of pharmacy services in Germany and the barriers to implementation. Methods An online survey conducted in 2017 was distributed to directors of all 389 German hospital pharmacies. The survey contained 26 questions addressing hospital and pharmacy characteristics, clinical pharmacy services provided, the number of clinical pharmacists and the frequency as well as the quality assurance of these services. Results There were 133 responses (34%). Of these, 84 (63%) pharmacies provided some form of clinical pharmacy services. Based on the 389 contacted pharmacies, a clinical pharmacy service is available in at least 22% of hospital pharmacies in Germany. On average there are 2.4 full-time equivalent (FTE) clinical pharmacists per hospital employed, although there is a wide variation in numbers (0.3–22 FTE) and service provision between hospitals. Clinical pharmacy services are generally provided on a daily or weekly basis, with a principal focus on general surgery, critical care and general medicine wards. Conclusions This is the first survey providing a detailed picture of clinical pharmacy services in Germany. There is wide variation in clinical service provision among hospitals, with some hospitals having developed a comprehensive range of clinical services. Compared with other countries, particularly the UK where the focus has shifted to provision of 7-day clinical services, the gap in clinical pharmacy services remains large. The focus should be turned to refining clinical pharmacy services in hospital admissions and discharge planning while also improving Health IT, the opportunities for specialisation and aligning education in accordance with the EAHP common training framework.

OBJECTIVES: In 2013, the PharmaHelp device was introduced to daily patient care at the University Hospital of Heidelberg in order to improve process and staff safety and health. It is a semiautomated device located in a safety workbench for aseptic preparation with weight-and-visual-supported process check as well as radio-frequency identification of bags and vials. METHODS: After qualification and a training period, several high-admixture-volume drugs were chosen stepwise to be prepared by the device. During a reporting period of 6 months, the number of processed production runs and produced bags were assessed as well as the productivity per hour of the device based on the processed admixing volume and time consumption for manual preprocessing and postprocessing steps. RESULTS: Weight conformity tests of 246 processed bags in 11 admixing-volume ranges showed 99.19% with a deviation of

Epidemiologische Studien der letzten Jahre belegen sowohl eine steigende Inzidenz invasiver Pilzinfektionen als auch ein zunehmendes Problem mit Therapieversagen auf Intensivstationen. In bis zu 70 % der Falle zeigt sich ein Nichtansprechen der primaren antimykotischen Therapie abhangig von der auslosenden Spezies bzw. von vorliegenden Grunderkrankungen. Der vorliegende Review-Beitrag soll fur das Thema des Therapieversagens sensibilisieren, die klinischen Umstande des Therapieversagens beschreiben sowie ein systematisches Vorgehen bei Verdacht auf ein Scheitern der primaren antimykotischen Therapie vorschlagen.

Background Relevant inhospital adverse drug events (ADE) are often documented in clinical administrative data (CAD) using ICD-10 codes (International Classification of Diagnosis Related Diseases, 10th revision). In a previous propensity matched cohort study, we analysed the CAD of 48 072 inpatients of a university hospital for potentially preventable inpatient ADE affecting length of stay. From a hospital’s perspective, particularly ICD-10 codes coding for drug induced renal failure, appeared to be preventable. Purpose We aimed to evaluate causes and conditions leading to renal failure in hospital and develop prevention strategies. Material and methods We assessed the validity of such codes in patient records and evaluated whether acute renal failure occurred during the hospital stay. Using the updated causality score by Begaud et al , we currently assess, using 2 independent reviewers, whether acute renal failure was drug related. 1 Based on root cause analyses, preventive strategies will be developed. Results The records of 69 patients were analysed (mean age 62 years (range 23–94), 33% women). 26 cases (38%) had a known history of renal failure or were hospitalised because of acute renal failure. In 43 cases (62%), the adverse event occurred in hospital. Nearly half of these cases (n=20) had a known history of renal failure. The pilot results of four randomly selected cases of this ongoing assessment revealed 6 suspect drugs with a high imputability to the ADE (1 drug with level I4 and 5 drugs with level I6 out of 7 possible scores from I0 to I6). As conceivable prevention strategies, we identified a priori dose adjustment and/or longer intravenous application duration for nephrotoxic drugs (eg, aciclovir) in patients with a known history of renal failure. Conclusion Unless CAD do not explicitly flag inpatient ICD-10 codes, CAD based ADE identification is laborious, and adequate risk management by the hospital is challenging. Screening for (pre-existing) renal (dys)function at the stage of hospitalisation for appropriate dose adjustment could prove a promising preventive strategy for our hospital. References and/or acknowledgements 1. Arimone Y, et al. Updating the French method for the causality assessment of adverse drug reactions. Therapie2013;68:69–76. No conflict of interest

It is being increasingly recognised by clinicians and scientists that participants in randomised clinical trials (RCTs) of antibiotics of last resort do not represent the patients who will later be treated with these drugs. Data on this subject are limited and have not been investigated systematically. This observational study aimed to examine this hypothesis quantitatively, using the example of tigecycline. To evaluate the influence of recruitment, patients eligible for clinical trials were retrospectively compared with ineligible patients regarding baseline and clinical characteristics as well as outcome parameters, e.g. length of hospital stay, intensive care unit (ICU) stay, ventilation and mortality. The clinical characteristics of 187 patients illustrated differences in the nature and severity of disease, co-morbidities and outcome. Eligible and ineligible patients differed in a number of parameters, e.g. median APACHE II score (15.5 vs. 28.0), number of liver transplantations (5% vs. 18%; P = 0.048), septic shock (21% vs. 49%; P = 0.001), need for mechanical ventilation (30% vs. 79%; P < 0.001), mean length of ICU stay (19.3 days vs. 40.7 days) and death (19% vs. 46%; P = 0.001). Critically ill patients were under-represented in clinical trials. Moreover, only a minority of patients in clinical practice (13%) were potentially eligible for a pivotal RCT. The disparities likely result from strict exclusion criteria in RCTs and recruitment bias. These data emphasise the importance of including critically ill patients in RCTs of antibiotics against multiresistant bacteria in order to account for those who will later be treated.

Invasive fungal disease (IFD) causes increasing morbidity and mortality in haematological cancer patients. Reliable cost data for treating IFD in German hospitals is not available. Objective of the study was to determine the institutional cost of treating the IFD. Data were obtained by retrospective chart review in German hospitals. Patients had either newly diagnosed or relapsed acute myeloid leukaemia (AML) or myelodysplastic syndrome (MDS). Direct medical cost was calculated from hospital provider's perspective. A total of 108 patients were enrolled at 5 tertiary care hospitals, 36 IFD patients and 72 controls. The vast majority of IFD patients (74%) were diagnosed with invasive aspergillosis. On average, the hospital stay for IFD patients was 12 days longer than in control patients. All patients in the IFD group and 89% of patients in the control group received antifungal drugs. Mean direct costs per patient were €51,517 in the IFD group and €30,454 in the control group. Incremental costs of €21,063 were dominated by cost for antifungal drugs (36%), hospital stay (32%) and blood products (23%). From the perspective of hospitals in Germany the economic burden of IFD in patients with AML or MDS is substantial. Therefore, prevention of IFD is necessary with respect to both clinical and economic reasons.

The authors describe two cases of successful and safe posaconazole use in patients of a surgical intensive care unit of a university hospital.

Objective of the study The purpose of this prospective intervention study was to assess the number of patients with Y-site incompatibilities before and after implementation of quality improvement measures to prevent incompatibilities consisting of a focused instruction for pantoprazole as a drug frequently involved in incompatible drug pairs and of a recommendation to use 4-lumen instead of 3-lumen catheters to increase the number of available central infusion lines. Setting Cardiovascular intensive care unit where several standard operating procedures (SOPs) dealing with compatibility were already in place. Method In a prospective intervention study, patients’ IV medication was assessed for potential incompatibilities using a database containing compatibility information on approximately 60,000 drug pairs. In a first period, routine administration was monitored in 53 consecutive patients (control group). Then, quality improvement measures were implemented recommending a purging procedure before and after bolus administration of pantoprazole as a drug frequently causing incompatibilities in this setting. Additionally, the use of 4-lumen instead of 3-lumen catheters was suggested whenever considered useful by the responsible physicians. The monitoring was repeated during a second period in another 58 patients consecutively admitted to the same unit (intervention group). Main outcome measure Overall number of patients with at least one incompatible drug pair and number of patients receiving incompatible pantoprazole combinations. Results The number of patients receiving incompatible pantoprazole combinations decreased from 15 of the 15 patients receiving pantoprazole (100.0%) in controls to 9/16 (56.2%) in the intervention group (P < 0.01). The overall number of patients with incompatibilities was not influenced by the intervention with 36/58 (62.1%) compared to controls with 38/53 (71.7%, P = 0.28). The fraction of central lines contributed by four lumen central catheters was larger due to the intervention (80/168 lines, 47.6%) compared to controls (16/184, 8.7%, P < 0.001). Only sporadically there were incompatible combinations of drugs governed by the already existing SOPs. Conclusion In an intensive care setting with good SOP adherence, purging before and after administration decreased the respective incompatibility rate whereas the use of 4-lumen instead of 3- lumen catheters had not the expected benefit on separating drug pairs.

Background. The demand for pharmacy cancer services is expected to at least double over the next 10 years, as the population ages and new treatments are introduced. Safe and efficient handling of cytotoxic products minimises risks to staff and reduces medication errors. Objectives. To identify and describe strategies for coping safely and effectively with heavier workloads in the hospital oncology pharmacy, currently and in the future. Methods. The PubMed database was searched for literature on approaches to safe handling of antineoplastic agents and to decreasing medication errors in the hospital pharmacy. Articles that were judged to be of prime importance to the hospital oncologist were reviewed. These safety concepts are put into the context of contemporary hospital oncology pharmacy practice through discussion of key issues, including increased demand, the role of the pharmacist in determining the hospital formulary, and growth in patient preferences for oral chemotherapy. Recommendations on best practices are also provided, based on relevant literature and author experience. Conclusions. Efficient, safe hospital pharmacy operations can be aided by capacity planning, dose banding, and knowledge of novel products and procedures that can reduce risks to health while increasing the number of patients who are safely treated. Consideration may also be given to the economic role of oncology pharmacists in formulary development. J Oncol Pharm Practice (2010) 16: 9—18.

Given the high incidence (1.5%–10%) of invasive aspergillosis (IA) after liver transplantation and the associated mortality, prophylaxis according to the patients’ circumstances is a reasonable approach. The purpose of this investigation was to determine the effect and significance of risk factors for IA in a specialized transplantation center. We collected data from patients who underwent liver transplantation at the Transplantation Center of the University Hospital Heidelberg (Germany) between December 2001 and December 2004 in a specifically designed database for retrospective analysis. Invasive aspergillosiswas defined according to the European Organization for Research and Treatment of Cancer classifications. Univariate analysis and logistic regression were performed to assess the influence of each assumed risk factor. A total of 195 liver transplantationswere performed in 170 patients, with two patients (1.2%) developing a proven IA, seven (4.1%) developing a probable IA, and five developing a possible IA (2.9%). All patients received oral itraconazole prophylaxis. Of these 14 patients with proven, probable or possible IA, 13 died within 4 weeks after the initial diagnosis; this represents 33.3% of all patients with a fatal outcome. Univariate significant factors were retransplantation (p = 0.004), cytomegalovirus (CMV) infection (p = 0.024), dialysis (p < 0.001), renal insufficiency (p = 0.05), thrombocytopenia (p = 0.001), and leukocytopenia (p = 0.002). Multivariate analysis showed an independent influence of CMV infection (OR 6.032, 95% CI 1.446–25.163) and dialysis (OR 14.985, 95%CI 2.936–76.486). The rate of IA found in this investigation is within the range reported in published studies. Based on our data, extended antifungal prophylaxis should be given to liver transplant patients with specific risk factors, such as renal insufficiency, requirement for dialysis, CMV infection, or thrombocytopenia. Additional focus should be on the prevention of CMV infections.

Incompatibility of drug solutions administered through a common line may jeopardize the safety and effectiveness of i.v. drug therapies.[1][1] We recently reported that, in the absence of dedicated preventive strategies, incompatibilities are alarmingly frequent in an intensive care setting.[2][2]

Background: Considering the complexity of diagnosis, high costs of therapy and high morbidity and mortality of systemic fungal infections, antifungal therapy of intensive care patients should follow clearly defined guidelines. We outline the impact of a standardised practice of antifungal treatment in an interdisciplinary surgical intensive care unit of a university hospital. Methods: Therapy was intended to be optimised by implementation of standardised practice guidelines supported by the clinical pharmacist. Costs for antifungal agents during a period of 18 months before and after implementation of the practice guidelines were compared, respectively. Results: The intervention was associated with a significant decrease in use of antifungal agents. Analysis of data revealed a reduction in costs by 50%. This could substantially be attributed to the implementation of the practice guidelines. Conclusion: The implementation of standardised practice guidelines for antifungal therapy in intensive care units decreased the use of selected antifungal agents and resulted in substantial reduction in expenditure on antifungal agents.

Aging-associated nitro-oxidative stress causes tissue injury and activates proinflammatory pathways that play an important role in the pathogenesis of aging-associated cardiovascular dysfunction. It has been recently reported, that the copper(II)-aspirinate complex (CuAsp) exerts not only the well-known anti-inflammatory and platelet antiaggregating effects of aspirin, but, due to its superoxide dismutase mimetic activity, it acts as a potent antioxidant as well. In this study we investigated the effects of CuAsp on aging-associated myocardial and endothelial dysfunction.Aging and young rats were treated for 3 weeks with vehicle, or with CuAsp (200 mg/kg per day per os). Left ventricular pressure-volume relations were measured by using a microtip pressure-volume conductance catheter, and indexes of contractility (e.g., slope of end-systolic pressure-volume relationships [ESPVR] [E(es)], and dP/dt(max) - end-diastolic volume [EDV]) were calculated. In organ bath experiments for isometric tension with isolated aortic rings, endothelium-dependent and -independent vasorelaxation were investigated by using acetylcholine and sodium nitroprusside. When compared to the young controls, aging rats showed impaired left ventricular contractility (E(es), 0.51 +/- 0.04 vs. 2.16 +/- 0.28 mmHg/microL; dP/dt(max) - EDV, 10.71 +/- 2.02 vs. 37.23 +/- 4.18 mmHg/sec per microL; p0.05) and a marked endothelial dysfunction (maximal relaxation to acetylcholine: 66.66 +/- 1.30 vs. 87.09 +/- 1.35%; p0.05). Treatment with CuAsp resulted in reduced nitro-oxidative stress, improved cardiac function (E(es), 1.21 +/- 0.17 vs. 0.51 +/- 0.04 mmHg/microL; dP/dt(max) - EDV, 23.40 +/- 3.34 vs. 10.71 +/- 2.02 mmHg/sec per microL; p0.05) and higher vasorelaxation to acetylcholine in aging animals (94.83 +/- 0.73 vs. 66.66 +/- 1.30%; p0.05). The treatment did not influence the cardiovascular functions of young rats.Our results demonstrate that oxidative stress and inflammatory pathways contribute to the pathogenesis of cardiovascular dysfunction in the aging organism, which can be reversed by CuAsp.

Objective Medication errors are frequent in a hospital setting and often caused by inappropriate drug handling. Systematic strategies for their prevention however are still lacking. We developed and applied a classification model to categorise medication handling errors and defined the urgency of correction on the basis of these findings. Setting Nurses on medical wards (including intensive and intermediate care units) of a 1,680-bed teaching hospital. Method In a prospective observational study we evaluated the prevalence of 20 predefined medication handling errors on the ward. In a concurrent questionnaire survey, we assessed the knowledge of the nurses on medication handling. The severity of errors observed in individual areas was scored considering prevalence, potential risk of an error, and the involved drug. These scores and the prevalence of corresponding knowledge deficits were used to define the urgency of preventive strategies according to a four-field decision matrix. Main outcome measure Prevalence and potential risk of medication handling errors, corresponding knowledge deficits in nurses committing the errors, and priority of quality improvement. Results In 1,376 observed processes 833 medication handling errors were detected. Errors concerning preparation (mean 0.88 errors per observed process [95% CI: 0.81–0.96], N = 645) were more frequent than administration errors (0.36 [0.32–0.41], N = 701, P

Candida species constitute the majority of nosocomial fungal pathogens in non-neutropenic patients. Candida infections are still connected with substantial mortality. Recent epidemiological observations indicate a shift to non-albicans species, especially because of a rise of infections caused by C. glabrata, which frequently shows fluconazole-resistance. New therapeutic options like caspofungin, as the first licensed echinocandin, new broad-spectrum azoles, and lipid preparations of amphotericin B emerged in the last decade as efficient alternatives to fluconazole and amphotercin B deoxycholate. In invasive candidiasis, a delayed treatment initiation is associated with an increased mortality, thus risk stratification and empirical therapy strategies become vitally important. This review reflects the efficacy of caspofungin in the treatment of Candida infections, especially in the setting of empirical therapy in critically ill patients, and considers the option of de-escalation to fluconazole.

Changes in drug treatment are frequently mandatory with hospital admission and discharge because hospital drug formularies are generally restricted to about 3000 drugs as compared to the many times this number – 62,000 in Germany – that are commercially available. Without computerised support, the process involved with switching drugs to a corresponding generic or a therapeutic equivalent is time-consuming and error-prone. We have developed and tested a standardised interchange algorithm for subsequent implementation into a computerised decision support system that switches drugs to the corresponding generic or a therapeutic equivalent if they are not listed on the hospital drug formulary. The algorithm was retrospectively applied to the medication regimens of 120 patients (774 prescribed drugs containing 886 active ingredients) at their time of admission to surgical wards. Of the prescribed drugs, 52.8% (409/774) were part of the hospital drug formulary, thereby rendering a switch unnecessary. The 365 drugs not listed consisted of 392 active ingredients that were successfully switched to a corresponding generic (84.7%) or a therapeutic equivalent (10.2%). No specific switching procedures were defined for only 2.3% (20/886) of the active ingredients. In these cases, the drugs were either discontinued (4/20) or special drug classes, current diseases or co-medication required manual switching (8/20), or the drugs were continued unchanged and ordered from a wholesaler (8/20). Using a standardised interchange algorithm, pre-admission drug regimens can successfully be switched to drugs on a hospital drug formulary. These findings suggest that a computerised decision support system will likely be useful to support this important practice.

Die effektive Antibiotikabehandlung stellt neben der chirurgischen Sanierung einen der Eckpfeiler des therapeutischen Managements von Patienten mit postoperativer Sepsis dar. Die initiale Wahl und der fruhe Zeitpunkt der antimikrobiellen Therapie sind fur den Ausgang einer komplizierten intraabdominellen Infektion hochst entscheidend, da eine nichtadaquate Antibiotikatherapie zu verzogerter Heilung, langerem Krankenhausaufenthalt und hoherer Letalitat fuhrt. Tigecyclin ist eine wichtige therapeutische Option in der Behandlung von Infektionen, die durch multiresistente grampositive und gramnegative Erreger, einschlieslich Vancomycin-resistenter Enterokokken (VRE), verursacht werden. Eine grose randomisierte Studie (Patienten mit APACHE-II-Score >30 ausgeschlossen, durchschnittlicher APACHE-II-Score 6) konnte zeigen, dass Tigecyclin dem Imipenem/Cilastatin in der Behandlung von komplizierten intraabdominellen Infektionen nicht unterlegen ist. Jedoch ist bisher kein Fall mit septischem Schock, verursacht durch VRE, und klinischer Heilung berichtet. Im Folgenden wird der Fall eines Patienten mit postoperativer Peritonitis und schwerem septischen Schock (APACHE-II-Score 34) berichtet. Die chirurgische Sanierung beinhaltete das Einlegen von Spuldrainagen. Aufgrund des mikrobiologischen Befundes wurde antibiogrammgerecht eine Monotherapie mit Tigecyclin durchgefuhrt, die zu einem klinischen Erfolg fuhrte. Tigecyclin stellt eine neue Therapiealternative bei intraabdominellen Infektionen dar und ist als Monotherapie aus medizinokonomischer Sicht interessant.

Levofloxacin is a third-generation fluoroquinolone with a broad spectrum of antibacterial activity, comprising enterobacteria, non-fermenters, Gram-positive cocci and some anaerobic species. Members of these species are common pathogens in acute and chronic cholecystitis. This suggests that levofloxacin may be used as peri-operative prophylaxis in gall-bladder surgery. The purpose of our study was to determine serum and tissue levels of levofloxacin in cholecystectomy patients following pre-operative dosing.Patients with gall-bladder surgery were given levofloxacin 500 mg as a single dose either intravenously (iv) or orally pre-operatively, at the treating physician's decision. Gall-bladder tissue and serum samples were collected, and drug concentrations were determined by HPLC with fluorescence detection. Additionally, all tissue samples underwent routine microbiological diagnostics. MICs for aerobic isolates were determined using the Etest.A total of 61 patients (48 female, 13 male) were included. The medians of the levofloxacin concentrations in serum were 11.37 mg/L (iv) and 9.65 mg/L (oral), and in gall-bladder tissue they were 15.61 mg/kg (iv) and 17.93 mg/kg (oral). Eleven pathogens were isolated from gall-bladder samples. Post-operative wound infection was observed in two of the 61 patients.Our data suggest that levofloxacin may be considered for peri-operative prophylaxis in biliary tract surgery.

Abdominal surgery may affect intestinal absorption and the resulting levels of posaconazole in the blood. We measured plasma posaconazole levels in surgical intensive care unit (SICU) patients and tried to develop a predictive population pharmacokinetics model. A total of 270 samples from 15 patients receiving posaconazole via nasogastric tube were measured by high-performance liquid chromatography (HPLC). SICU patients showed lower plasma drug concentrations, a higher apparent clearance, and a higher volume of distribution than those in hematology patients, possibly due to poor absorption.

Glucocorticoids such as dexamethasone are widely co-prescribed with cytotoxic therapy because of their proapoptotic effects in lymphoid cancer, reduction of inflammation and edema and additional benefits. Concerns about glucocorticoid-induced therapy resistance, enhanced metastasis and reduced survival of patients are largely not considered. We analyzed dexamethasone-induced tumor progression in three established and one primary human pancreatic ductal adenocarcinoma (PDA) cell lines and in PDA tissue from patients and xenografts by FACS and western blot analysis, immunohistochemistry, MTT and wound assay, colony and spheroid formation, EMSA and in vivo tumor growth and metastasis of tumor xenografts on chicken eggs and mice. Dexamethasone in concentrations observed in plasma of patients favored epithelial–mesenchymal transition, self-renewal potential and cancer progression. Ras/JNK signaling, enhanced expression of TGFβ, vimentin, Notch-1 and SOX-2 and the inhibition of E-cadherin occurred. This was confirmed in patient and xenograft tissue, where dexamethasone induced tumor proliferation, gemcitabine resistance and metastasis. Inhibition of each TGFβ receptor-I, glucocorticoid receptor or JNK signaling partially reversed the dexamethasone-mediated effects, suggesting a complex signaling network. These data reveal that dexamethasone mediates progression by membrane effects and binding to glucocorticoid receptor.

SummaryPurpose Using clinical administrative data (CAD) of inpatients, we aimed to identify ICD-10 codes coding for potentially preventable inhospital adverse drug events (ADE) that affect the length of hospital stay (LOS) and thus patient well-being and cost. Methods We retrospectively assessed CAD of all inpatient stays in 2012 of a German university hospital. Predefined ICD-10 codes indicating ADE (ADE codes) were further specified based on expert ratings of the ADE mechanism and ADE preventability in clinical routine to particularly identify preventable inhospital ADE. In a propensity-matched cohort design, we compared patients with one or more ADE codes to control patients with regard to differences in LOS for three situations: all cases with an ADE code, cases with an inhospital ADE code, and cases with a preventable inhospital ADE code. Results Out of 54 032 cases analysed, in 8.3% (N=4 462) at least one ADE code was present. Nine of 128 evaluated ADE codes were rated as preventable in clinical routine, relating to 220 inpatients (4.9% of all identified inpatients with at least one ADE code and 0.4% of the entire cohort, respectively). Out of 48 072 evaluable inpatients for propensity score matching, 7 938 controls without ADE code and 4 006 cases with ADE code were selected. In all three settings, cases showed prolonged LOS vs controls (delta 1.13 d; 0.88 d and 1.88 d, respectively), significantly exceeding the maximum LOS as defined for each Diagnosis-Related Group. Conclusion Inpatients with ADE codes referring to inhospital, potentially preventable ADE exceeded the maximum hospital stay fully reimbursed by insurance companies, indicating unnecessary long and costly inpatient stays.

Summary What is known and objectives Incorrect drug preparation for patients with feeding tubes can result in harm for the patient and the preparing person. Combined intervention programs are effective tools to reduce such preparation errors. However, to date, intervention programs have been mostly tested in hospitals with computerized physician order entry (CPOE), unit-dose systems, or ward-based clinical pharmacists. Hence, the primary objective of this study was to develop and evaluate an intervention program tailored to hospitals without such preconditions. Methods We conducted a prospective pre-/post-intervention study on a gastroenterological intensive care unit (ICU) and a surgical ward for oral, dental and maxillofacial diseases (surgical ward). During the study periods, observers documented and evaluated drug preparation processes of all peroral drugs for patients with feeding tubes. The primary endpoint was the rate of inappropriately crushed and/or suspended solid peroral drugs in regards to all solid peroral drugs. Results and discussion Altogether, we evaluated 775 drug preparation processes of solid peroral drugs on the ICU and 975 on the surgical ward. The intervention program significantly reduced incorrect crushing and/or suspending of solid peroral drugs for administration to patients with feeding tubes from 9·8% to 4·2% (P

Background Drug administration in children is an error-prone task for nurses and parents because individual dose adjustment is often necessary, and suitable formulations for children are frequently lacking. Hence, in the absence of measures for their prevention, medication errors are likely to occur. Objective To assess the error prevalence in drug administration by mouth or gastric tube before and after implementing a programme for quality improvement for nurses and parents. Design, setting and participants Prospective, two-period cohort intervention study on a paediatric neurology ward of a university hospital where drug administration procedures of nurses and parents were consecutively monitored during the routine drug administration hours. Main outcomes measure Prevalence of administration errors before and after implementing instructions for appropriate drug administration, and a teaching and training programme supported by information pamphlets. Results Altogether, 1164 predefined administration tasks were assessed, 675 before and 489 after the intervention. Of these, 95.7% (after the intervention: 92.6%) were performed by nurses. Errors addressed by the intervention were reduced from 261/646 tasks (40.4%) to 36/453 (7.9%, p

Moxifloxacin, the newest fourth-generation fluoroquinolone, has a broad spectrum of antibacterial activity covering both Gram-positive and Gram-negative aerobic and anaerobic bacteria and is therefore very well suited for the treatment of biliary tract infections. The present study aimed to determine the penetration of moxifloxacin into gallbladder tissue to evaluate its antibiotic potential in this indication.Hospitalized patients with acute cholecystitis received a single, 1 h infusion of 400 mg of moxifloxacin before cholecystectomy. Serum and gallbladder wall tissue samples were collected during surgery, and the moxifloxacin concentrations were measured by HPLC.Sixteen patients (eight men and eight women) were included between January 2007 and April 2008. The time between start of infusion and gallbladder removal ranged from 50 min to 21 h 10 min. The serum concentration at the time of cholecystectomy was between 0.39 and 4.37 mg/L, and the tissue concentration between 1.73 and 17.08 mg/kg. The tissue-to-serum concentration ratio ranged from 1.72 to 6.33.The results show that moxifloxacin penetrates well into gallbladder tissue and is therefore a therapeutic option for biliary tract infection. The highest concentrations in serum and gallbladder tissue were measured shortly after the end of a 1 h infusion. As perioperative prophylaxis, moxifloxacin should therefore be administered 30-60 min before the first surgical incision.

Linezolid is an option for the treatment of infections caused by multiresistant Gram-positive bacteria. The survival of critically ill patients with acute renal failure (ARF) can be improved by increasing the dose of renal replacement therapy. Extended (daily) dialysis (ED) is a new and important approach to renal replacement therapy in intensive care units. The aim of the study was to evaluate the pharmacokinetics of linezolid in septic patients without ED and on ED, respectively.We studied the pharmacokinetics of linezolid in adult intensive care patients with sepsis (n = 5) and anuric septic patients with ARF being treated with ED (n = 10). Linezolid 600 mg was administered intravenously twice daily. The pharmacokinetic parameters, their variability, and possible covariates were analyzed using NONMEM.The pharmacokinetics of linezolid followed a two-compartment model with clearance (Cl) = 0.159 L h(-1) kg(-1) +/- 51% (population mean +/- interindividual variability), central volume of distribution (V(1)) = 0.273 L/kg +/- 21%, intercompartmental clearance (Q) = 0.369 L h(-1) kg(-1), and peripheral volume of distribution (V(2)) = 0.271 L/kg. The clearance in ED patients while on dialysis was increased by 3.5 L/h, and patients with liver transplantation/resection had their clearance reduced by 60%. Intra-individual variability was much smaller than inter-individual variability.Our results suggest that linezolid pharmacokinetics in critically ill patients with ARF undergoing ED is not comparable to that in healthy subjects and patients without ARF. The best method of managing linezolid dosage in such a complex group of patients, whose physiology can vary daily, would be to use therapeutic drug monitoring.

Purpose. The frequency of drug administration errors and incompatibilities between intravenous drugs before and after an intervention in an intensive care unit (ICU) is discussed. Methods. Critically ill adult patients with intoxications, multiorgan failure, and serious infections were included in a retrospective analysis and in a prospective two-period, one-sequence study. In the retrospective analysis, the most frequent brands of i.v. medications used in the ICU of a gastroenterologic department in a teaching hospital were identified. All possible combinations and resulting incompatibilities were defined. Based on the results, a standard operating procedure (SOP) was established to prevent frequent and well-documented incompatibilities among i.v. medications. In the prospective study, trained pharmacy students assessed incompatible coinfusions before and after SOP implementation. Results. In the retrospective analysis of 100 patients, 3617 brands of drug pairs were potentially given concurrently through one i.v. line and 7.2% of the drug pairs were incompatible. Antibiotics, such as piperacillin–tazobactam and imipenem–cilastatin, were the most frequent incompatible drug pairs. The newly developed SOP mandated that administration of these drugs be separated from all other drugs and suggested the use of an idle i.v. line for infusion whenever possible. In the prospective study of 50 patients, the frequency of incompatible drug pairs was reduced by the time of intervention from 5.8% to 2.4%. Incompatible drug pairs that were governed by the new SOP were reduced from 1.9% to 0.5%. Conclusion. Administration of incompatible i.v. drugs in critically ill patients was frequent but significantly reduced by procedural interventions with SOPs.

Critically ill patients after extended surgical procedures are at high risk for postoperative infections. Fungal infections play a substantial role for immunocompromised patients, e.g. after solid organ transplantation or under chronic corticoid therapy. Posaconazole, a new broad-spectrum triazole effective against Aspergillus and Candida species as well as many fungi that are resistant to other antifungals, is well tolerated and can be used as an alternative in salvage therapy. Posaconazole can be administered via gavage so that antifungal therapy can be switched from an expensive intravenously applied antifungal to oral posaconazole at an early stage. Two case reports are presented, which show that posaconazole was efficacious and well tolerated following antifungal therapy with another azole. It was administered without difficulty via gavage to a patient receiving artificial respiration and dialysis.

Background There is concern about an increasing infiltration of markets by substandard and fake medications against life-threatening diseases in developing countries. This is particularly worrying with regard to the increasing resistance development of Plasmodium falciparum against affordable anti-malarial medications, which has led to a change to more expensive drugs in most endemic countries. Methods A representative sample of modern anti-malarial medications from licensed (public and private pharmacies, community health workers) and illicit (market and street vendors, shops) sources has been collected in the Nouna Health District in north-western Burkina Faso in 2006. All drugs were tested for their quality with the standard procedures of the German Pharma Health Fund-Minilab. Detected low standard drugs were re-tested with European Pharmacopoeia 2.9.1 standards for disintegration and ultraviolet-visible spectroscopy at the laboratory of the Heidelberg University for confirmation. Results Overall, 86 anti-malarial drug samples were collected, of which 77 samples have been included in the final analysis. The sample consisted of 39/77 (50%) chloroquine, 10/77 (13%) pyrimethamine-sulphadoxine, 9/77 (12%) quinine, 6/77 (8%) amodiaquine, 9/77 (12%) artesunate, and 4/77 (5%) artemether-lumefantrine. 32/77 (42%) drug samples were found to be of poor quality, of which 28 samples failed the visual inspection, nine samples had substandard concentrations of the active ingredient, four samples showed poor disintegration, and one sample contained non of the stated active ingredient. The licensed and the illicit market contributed 5/47 (10.6%) and 27/30 (90.0%) samples of substandard drugs respectively. Conclusion These findings provide further evidence for the wide-spread existence of substandard anti-malarial medications in Africa and call for strengthening of the regulatory and quality control capacity of affected countries, particularly in view of the now wider available and substantially more costly artemisinin-based combination therapies.

Adequate antimicrobial therapy is crucial for the survival of critically ill patients with severe nosocomial infections. Tigecycline, the first available agent in the new class of glycylcyclines, is active against multiresistant gram-positive and gram-negative bacteria. The aim of this observational, retrospective evaluation was to assess tigecycline use patterns in a surgical intensive care unit (SICU) of a tertiary care centre.Data from 70 patients receiving tigecycline in the SICU were analysed. We reviewed tigecycline use in terms of demographic data and co-morbidities, disease severity, clinical indication, microbiology, therapy regimens and mortality. A logistic regression analysis was performed to identify prognostic factors for mortality.The majority of patients had co-morbidities such as cancer (51%) or renal replacement therapy (57%). The mean Acute Physiology and Chronic Health Evaluation (APACHE) II score of patients at admission was 27. Intra-abdominal infection was most frequently diagnosed (50% of patients); intra-abdominal infection and pneumonia were diagnosed in 14%. Methicillin-resistant Staphylococcus aureus was found in 16% of patients (colonization; infection: 6%) and vancomycin-resistant enterococci in 27% (colonization; infection: 21%). The mean duration of tigecycline therapy was 9 +/- 4 days; 76% of patients received tigecycline in combination, with 64% being treated second line. APACHE score and renal replacement were identified as predictive factors for mortality. SICU mortality was 30%.Tigecycline treatment of critically ill SICU patients with severe sepsis or septic shock appeared to result in remarkably low mortality. Tigecycline may be an important treatment option for septic patients with infections resistant to other available agents.

Background Taking a complete medical history of patients before hospital admission includes an accurate assessment of the current drug history which provides the basis for appropriate pharmacotherapy during the stay in hospital and at discharge as we know from the literature, this is best performed by a clinical pharmacist. Purpose To evaluate specific aspects of medicines reconciliation by pharmacists performed as part of the clinical routine. Material and methods Throughout a 4 week pilot phase, 178 patients were seen by a pharmacist for medicines reconciliation. During an interview, the current medicines were assessed including brand name, administration form and strength, dosing scheme and temporarily discontinued treatment. Moreover, information about patients’ allergies, intolerances and concomitant diseases was collected. After verifying the medicines (check for omissions, duplications, dosing errors or drug interactions), the appropriate medicines were switched to the hospital drug formulary. If drug-related problems were found the attending physician was informed by the clinical pharmacist and possible solutions were discussed. As a follow-up, patients’ medical records were reviewed and physicians’, nurses’ and pharmacists’ feedback on the project was evaluated. Results Clinical pharmacists performed medicines reconciliation as part of the clinical routine. In the pilot phase, 133 patients were regularly taking medicines and 36 brought a medicines list, however, this list was out-of-date or differed from patients’ statements in many cases. The average total time required per patient was 18 (2–80) min. Frequent discrepancies or medicines errors were associated with fixed combinations, statins, ASA and bridging of anticoagulants. Feedback was generally positive although process optimisation possibilities were identified. Conclusion Our project has shown the successful integration of a clinical pharmacist in the clinical routine of preadmission. Pharmaceutical interventions were largely accepted by the physicians, (potential) medicines errors and critical drugs could be revealed, and new SOPs will be created. We intend to continue the project. References and/or acknowledgements No conflict of interest.

OBJECTIVES Levofloxacin has a high bioavailability and a broad antibacterial spectrum which covers the common pathogens found in acute and chronic diabetic foot infections. The purpose of our study was to determine the serum and tissue concentrations of levofloxacin when administered orally in patients with infected diabetic foot ulcers and to compare these values with microbiological findings. PATIENTS AND METHODS Ten outpatients with diabetes and ulcerations of the lower extremity were included. All patients received oral levofloxacin therapy at a dose of 500 mg once daily. Wound tissue and serum samples were collected and levofloxacin concentrations determined by HPLC with fluorescence detection. Additionally, microbiological cultures were performed from swabs and debrided wound tissue, both before and after treatment. MICs of levofloxacin for all bacterial isolates were determined using the Etest. RESULTS Following oral treatment with levofloxacin for an average of 10 +/- 3.8 days, all patients received debridement at the affected limbs. The levofloxacin concentrations in necrotic wound tissue were between 2.33-23.23 mg/kg and between 0.12-6.41 mg/L in serum. Tissue-to-serum ratios of levofloxacin concentrations for each patient were >1.0. The MIC values for all 17 initially isolated bacteria were < or = 2 mg/L. In half of our patients, fluoroquinolones were one of the few oral monotherapy options where the spectrum covered all initially isolated pathogens. CONCLUSION Our data showed good tissue penetration of levofloxacin in diabetic foot ulcers. In combination with adequate surgical debridement, levofloxacin seems well suited to the treatment of skin structure infections of diabetics caused by susceptible organisms.

Objective Moxifloxacin is a recently developed fourth-generation methoxyquinolone with a broad spectrum of activity against both Gram-positive and Gram-negative aerobic bacteria and anaerobes. The aim of the present study was to assess the penetration of moxifloxacin into gastrointestinal (GI) mucosal tissues to evaluate its potential role as an antimicrobial drug in bacterial infections of the GI tract. Patients and methods Twenty-eight patients undergoing GI-tract surgery received 400 mg of moxifloxacin twice pre-operatively [eight patients orally (po) and 20 patients intravenously (iv)], of whom 22 completed the study. Mucosal tissues (three stomach, three small bowel and 16 colon) and serum samples were collected and moxifloxacin concentrations were measured by HPLC. Results The highest tissue concentrations were detected in the mucosa of the stomach (10.9 +/- 5.1 mg/kg), followed by colon mucosa (7.8 +/- 7.1 mg/kg after iv; 6.6 +/- 3.6 mg/kg after po) and small bowel mucosa (5.4 +/- 0.5 mg/kg). The tissue-to-serum ratio of moxifloxacin was 2.0 +/- 1.6 in the small bowel mucosa, 5.8 +/- 3.4 and 6.8 +/- 3.9 in the colon mucosa after po and iv administration, respectively, and 9.7 +/- 5.7 in the stomach mucosa. Conclusion Moxifloxacin penetrates into and accumulates in the mucosa of the stomach, small bowel and colon. The clinical applicability of moxifloxacin administration for bacterial GI-tract infections should be investigated in controlled trials.

Background Oral anticancer drugs still contain some of the most critical issues in terms of right use and compliance. Patients need to be advised and guided concerning dosing schedules, risks and important supportive measures. Package sizes distributed by the pharmaceutical industry often contain more doses than one patient needs especially for short-term stays in the hospital. Purpose Our goal was to dispense patient-individual unit doses of oral anticancer drugs based on individual computerised prescriptions. Materials and Methods For this purpose we implemented evidence-based treatment regimens in the prescription software to prevent errors and support the use of standardised treatment plans. Additionally patient information leaflets were created. The first drugs to be computerised in this way were capecitabine and temozolomide. Results Individualised dispensing of oral anticancer drugs allows more extensive pharmaceutical care of these patients. In view of the risks described above oral anticancer drugs have to undergo a pharmaceutical plausibility cheque and the amount has to be found suitable according to the treatment regime before dispensing. Moreover, the available instructions for use e.g. treatment schedules including supportive measures and the patient information brochure improve the information flow and the safe use. Conclusions Due to the positive feedback from the operators we are extending the procedure to all oral anticancer drugs. No conflict of interest.

A common problem in local cancer treatment is infection of the resulting superficial tumour necrosis. The malodorous oozing lesions not only severely interfere with the patient’s quality of life but may also result in serious sequelae such as accelerated wasting, sepsis, and death. We developed a new formulation of the well-known antiseptic drug Ethacridine lactate in powder form to prevent such infections in local antineoplastic therapy. In a pilot study, the powder was applied in four patients receiving either an intralesional treatment with a platinum-based gel in the course of a study or photodynamic therapy. In all four patients with cervical respectively facial wounds with a surface of up to 80 cm2 a virtually dry and odorless scabby lesion resulted with no signs of infection. These initial clinical experiences suggest that Ethacridine lactate powder may be of benefit in the prevention of infection in palliative intratumoural cancer treatment.

Objectives: The aim of the present study was to investigate plasma caspofungin levels in patients of a surgical intensive care unit (ICU). Methods: According to their demographic data caspofungin levels of 10 adult subjects (4 females and 6 males) were compared in a pairwise manner All patients Pair Age BW (kg) BS (m2) 1 (f) 47 vs 46 47 vs 48 1 45 vs 1 46 Table 1: demographics of the paired ICU patients