Torsten Hoppe-Tichy

Pharmacokinetic and pharmaceutic interaction between digoxin and Cremophor RH40

The pharmacokinetics of digoxin is modulated by the efflux pump P‐glycoprotein. Cremophor EL (BASF Aktiengesellschaft, Ludwigshafen, Germany) (polyoxyl 35 castor oil), a castor oil derivative used to improve the solubilization of drugs and vitamins, has been shown to inhibit this membrane transporter in vitro and in vivo. So far, no study in humans has evaluated the effect of Cremophor RH40 (BASF Aktiengesellschaft) (polyoxyl 40 hydrogenated castor oil) on P‐glycoprotein.

Prevention of intravenous drug incompatibilities in an intensive care unit

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.

Tigecycline for the treatment of patients with severe sepsis or septic shock: a drug use evaluation in a surgical intensive care unit

OBJECTIVES 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. METHODS 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. RESULTS 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%. CONCLUSIONS 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.

Substandard anti-malarial drugs in Burkina Faso

BackgroundThere 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.MethodsA 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.ResultsOverall, 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.ConclusionThese 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.

Prospective pilot intervention study to prevent medication errors in drugs administered to children by mouth or gastric tube: a programme for nurses, physicians and parents

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<0.001) in nurses and from 28/29 (96.6%) to 2/36 (5.6%, p<0.001) in parents. Errors in predefined categories concerning tablet dissolution, tablet storage, oral liquids, tablet splitting, administration by gastric tube and others were all considerably less frequent after the intervention (each p<0.001). Conclusion Errors of drug administration by mouth and gastric tube represent a considerable and often neglected drug-related problem in paediatric inpatients. Targeted quality-improvement programmes can substantially and rapidly reduce error prevalence. Appropriate teaching and training of both nurses and parents supported by pamphlets was a highly efficient way to reduce error prevalence.

A Risk Profile for Invasive Aspergillosis in Liver Transplant Recipients

AbstractBackground: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.Methods: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.Results: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).Conclusion: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.

Implementation of Practice Guidelines for Antifungal Therapy in a Surgical Intensive Care Unit and Its Impact on Use and Costs

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.

Current challenges in European oncology pharmacy practice

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.

Influence of the stationary phase on the stability of thalidomide and comparison of different methods for the quantification of thalidomide in tablets using high-temperature liquid chromatography

In this paper, three different HPLC methods for the quantification of thalidomide in tablets were developed and compared. The comparison of a conventional method at 30 degrees C with two high-temperature methods at 180 degrees C showed equal results. Using high-temperature HPLC (HT-HPLC), faster analysis times could be achieved. We have also focused on analyte stability and could show that the stationary phase has a pronounced effect on the on-column degradation of thalidomide at high temperatures. Virtually no degradation occurs if a polystyrene divinylbenzene column is used, whereas thalidomide is completely degraded at 180 degrees C when a carbon clad zirconium dioxide column is used.

Efficacy of caspofungin in invasive candidiasis and candidemia – de‐escalation strategy

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.