Dominic Störzinger

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.

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.

Development and validation of a high-performance liquid chromatography assay for posaconazole utilizing solid-phase extraction

Abstract Background: Posaconazole is a new broad-spectrum triazole antifungal drug that is used in prophylaxis and therapy of opportunistic fungal infections in immunocompromised patients. Up to now, it is available as an oral suspension only. Due to variable systemic availability known from other azoles, such as itraconazole, it is important to measure blood levels, especially in patients undergoing abdominal surgery which may influence the intestinal resorption. Methods: A sensitive and selective high-performance liquid chromatography method for the precise determination of posaconazole and the internal standard clotrimazole in human plasma was developed and validated. Samples were extracted using solid-phase extraction and separated on a reversed-phase C8 column (150×4.6 mm, 5 μm) using phosphate buffer (pH 6.7, 0.04 M):acetonitrile:methanol (43:49:8, v/v/v) as mobile phase. UV detection was performed at 260 nm. Results: This method showed that a lower limit of quantification was 50 ng/mL and the limit of detection 3 ng/mL. Linearity was tested in the range from 50 to 5000 ng/mL (r2=0.9998). Mean recovery was 86%. Conclusions: The method proved to be a useful tool for therapeutic drug monitoring. It is specific, precise and showed excellent reproducibility as well as a favourable accuracy. Clin Chem Lab Med 2008;46:1747–51.

Posaconazole in intensive care patients I: invasive fungal infections in surgical intensive care and case presentation

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.

Plasma Concentrations of Posaconazole Administered via Nasogastric Tube in Patients in a Surgical Intensive Care Unit

ABSTRACT 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.

Knowledge and training needs of nurses and physicians on unsuitable drugs for patients with dysphagia or feeding tubes

Patients with dysphagia or feeding tubes can apply peroral drugs only if they are already liquid or easily transferable into a liquid formulation (e.g. effervescent tablets). If appropriate drugs are lacking, solid drugs must be crushed and/or suspended (Bankhead et al. 2009). Crushing and suspending of modified-release formulations or carcinogenic, mutagenic or reprotoxic (CMR) drugs is a challenging task. Improper drug modification may endanger the patient (Cornish 2005) or the preparing person (Dranitsaris et al. 2005). Most summaries of product characteristics do not list information regarding drug modification or safety aspects. However, in over 60% of sustained-release drugs pharmaceutical companies use specific suffixes in their drug names such as SR, chrono or prolong to highlight specific galenic formulations. Thus, these suffixes may provide a first hint that a drug is potentially inappropriate for drug modification. It has repeatedly been shown that nurses often lack comprehensive knowledge about sustained-release suffixes (Hanssens et al. 2006, Dashti-Khavidaki et al. 2012) and that they are not fully aware of basic safety precautions during drug administration (Kosgeroglu et al. 2006) indicating possible safety risks (Simonsen et al. 2011). In theory, this risk could be minimised if physicians considered these aspects already in their prescriptions, provided that respective knowledge is pertinent.

More than just crushing: a prospective pre‐post intervention study to reduce drug preparation errors in patients with feeding tubes

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.

Best practice strategies to safeguard drug prescribing and drug administration: an anthology of expert views and opinions

Background While evidence on implementation of medication safety strategies is increasing, reasons for selecting and relinquishing distinct strategies and details on implementation are typically not shared in published literature. Objective We aimed to collect and structure expert information resulting from implementing medication safety strategies to provide advice for decision-makers. Setting Medication safety experts with clinical expertise from thirteen hospitals throughout twelve European and North American countries shared their experience in workshop meetings, on-site-visits and remote structured interviews. Methods We performed an expert-based, in-depth assessment of implementation of best-practice strategies to improve drug prescribing and drug administration. Main outcome measures Workflow, variability and recommended medication safety strategies in drug prescribing and drug administration processes. Results According to the experts, institutions chose strategies that targeted process steps known to be particularly error-prone in the respective setting. Often, the selection was channeled by local constraints such as the e-health equipment and critically modulated by national context factors. In our study, the experts favored electronic prescribing with clinical decision support and medication reconciliation as most promising interventions. They agreed that self-assessment and introduction of medication safety boards were crucial to satisfy the setting-specific differences and foster successful implementation. Conclusion While general evidence for implementation of strategies to improve medication safety exists, successful selection and adaptation of a distinct strategy requires a thorough knowledge of the institute-specific constraints and an ongoing monitoring and adjustment of the implemented measures.

Posaconazole as part of the antifungal armamentarium in the intensive care unit – case reports from a surgical ICU

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

New Approaches to Anti-infective Treatment of Ventilator-Associated Respiratory Infections caused by Pseudomonas aeruginosa

Study background: The purpose of this study was to evaluate recent strategies for anti-infective treatment in patients suffering from ventilator-associated respiratory infections caused by P. aeruginosa and to assess the riskbenefit profile of inhaled tobramycin.Methods: Electronic health records of patients suffering from respiratory infections caused by P. aeruginosa from 2011-2014 were retrospectively screened.Results: In 81 patients, P. aeruginosa was found in respiratory secretions, of which 26 patients suffered from ventilator-associated pneumonia (VAP), whereas 55 patients only fulfilled criteria of ventilator-associated tracheitis (VAT). Inhaled tobramycin was used in 14 patients with VAP and 31 patients with VAT. In this context, inhaled tobramycin was shown to be safe (e.g. no bronchoconstriction or systemic toxicity) and did not result in an increase of tobramycin resistant strains in respiratory secretions at 90 days following study inclusion. However, a clear clinical benefit (e.g. reduced need for i.v. antibiotics) could not be shown.\Conclusion: Inhaled tobramycin was shown to be a suitable approach with a favorable risk profile to treat patients suffering from respiratory infections (VAP, VAT) caused by P. aeruginosa. The clinical benefit needs to be reevaluated in a larger prospective investigation.