The levels of vancomycin in the blood and the wound after the local treatment of bone and soft-tissue infection with antibiotic-loaded calcium sulphate as carrier material.

AIMS: Calcium sulphate (CaSO4) is a resorbable material that can be used simultaneously as filler of a dead space and as a carrier for the local application of antibiotics. Our aim was to describe the systemic exposure and the wound fluid concentrations of vancomycin in patients treated with vancomycin-loaded CaSO4 as an adjunct to the routine therapy of bone and joint infections. PATIENTS AND METHODS: A total of 680 post-operative blood and 233 wound fluid samples were available for analysis from 94 implantations performed in 87 patients for various infective indications. Up to 6 g of vancomycin were used. Non-compartmental pharmacokinetic analysis was performed on the data from 37 patients treated for an infection of the hip. RESULTS: The overall systemic exposure remained within a safe range, even in patients with post-operative renal failure, none requiring removal of the pellets. Local concentrations were approximately ten times higher than with polymethylmethacrylate (PMMA) as a carrier, but remained below reported cell toxicity thresholds. Decreasing concentrations in wound fluid were observed over several weeks, but remained above the common minimum inhibitory concentrations for Staphylococcus up to three months post-operatively. CONCLUSION: This study provides the first pharmacokinetic description of the local application of vancomycin with CaSO4 as a carrier, documenting slow release, systemic safety and a release profile far more interesting than from PMMA. In particular, considering in vitro data, concentrations of vancomycin active against staphylococcal biofilm were seen for several weeks. Cite this article: Bone Joint J 2017;99-B:1537-44.

[Pharmacovigilance update]. / Pharmacovigilance.

Main pharmacovigilance updates in 2012 are reviewed here. Dabigatran: elderly patients with renal failure are at higher risk of bleeding. Dual renin-angiotensin-aldosterone system blockade comprising aliskiren is harmful. Incretins: low risk of acute pancreatitis. Interaction between fusidic acid and statins: many reports of rhabdomyolysis. Interactions between boceprevir/telaprevir and antiretroviral therapies: complex, but manageable. Citalopram, ondansetron: maximum recommended doses are reduced. Atomoxetine: significant increase in blood pressure and heart rate in a fraction of exposed patients. Agomelatine: elevated liver enzymes are common. Fingolimod: bradycardia and heart blocks after first dose - stronger safety recommendations regarding use in patients with heart conditions and strengthened cardiovascular monitoring.

[Pharmacovigilance]. / Pharmacovigilance.

Main pharmacovigilance updates in 2011 are reviewed. Dronedarone: Serious cardio-vascular and hepatic adverse reactions for a questionable efficacy. Long-term proton pump inhibitors: A cause of hypomagnesemia. Bisphosphonates: A risk of atypical femoral fractures. Dasatinib: Cases of pulmonary arterial hypertension reported. Lenalidomide: A risk of second primary malignancies. Daptomycine: Cases of eosinophilic pneumonia reported. Tigecycline: Inferior to comparators. Drotrecogin alfa: Market withdrawal due to lack of efficacy. Nimesulide: More hepatotoxic than other NSAIDs. Topiramate: Evidence of teratogenicity (oral clefts). Valproate: Impaired cognitive development in addition to well-known teratogenicity. Antipsychotics in late pregnancy: A risk of neonatal complications.

[Serotonin syndrome: review and case series from the Swiss pharmacovigilance system]. / Syndrome sérotoninergique: mise au point et revue des cas annoncés en Suisse.

Serotonin syndrome is a potential adverse reaction to drugs increasing serotoninergic activity in the nervous system, some of them being frequently prescribed, such as antidepressant drugs. As clinical presentation is variable and often aspecific, diagnosing serotonin syndrome can be a challenge, particularly in mild cases. Serious forms can be lethal. The aim of this article is to increase practitioners awareness of this syndrome by reviewing current knowledge on physiopathology, clinical presentation and therapy. We also analyzed the 102 cases notified to Swissmedic from 1998 to 2009, focusing on patients profile and suspected drugs.

[Antimicrobial agents and renal elimination: towards individual dosage adjustment?]. / Agents anti-infectieux et fonction réna!e: vers des posologies sur mesure ?

The efficacy and safety of anti-infective treatments are associated with the drug blood concentration profile, which is directly correlated with a dosing adjustment to the individual patient's condition. Dosing adjustments to the renal function recommended in reference books are often imprecise and infrequently applied in clinical practice. The recent generalisation of the KDOQI (Kidney Disease Outcome Quality Initiative) staging of chronically impaired renal function represents an opportunity to review and refine the dosing recommendations in patients with renal insufficiency. The literature has been reviewed and compared to a predictive model of the fraction of drug cleared by the kidney based on the Dettli's principle. Revised drug dosing recommendations integrating these predictive parameters are proposed.

[Pharmacovigilance update]. / Pharmacovigilance.

Main pharmacovigilance updates are reviewed. Rosiglitazone and sibutramine have been suspended due to cardiovascular risks. The safety profile of H1N1 vaccines is similar to the established profile of seasonal influenza vaccines. Paroxetine reduces the benefit of tamoxifen. The use of serotoninergic antidepressants in pregnancy is still disputed. The risk of venous thromboembolism could be higher with oral combined contraceptives containing drospirenone compared to those containing levonorgestrel. Prolonged QT and PR intervals have been observed with saquinavir. The correct use of transdermal patches is reviewed with the example of rivastigmine. Aseptic meningitis is a rare adverse reaction of lamotrigine. An increased risk of fractures after long term use of proton pump inhibitors is suspected.

[Pharmacovigilance update]. / Pharmacovigilance update.

Main pharmacovigilance signals and alerts issued in 2009 are reviewed. Efalizumab was withdrawn from the market due to increased risks, including progressive multifocal leukoencephalopathy (PML) and questionable efficacy. New cases of PML are still being reported with rituximab and natalizumab. Rare cases of pure red cell aplasia have been observed with mycophenate. Gastrointestinal perforation, severe skin rashes and various ocular disorders have been reported during erlotinib use. Severe skin rashes have been related to etravirine. Acute renal failure and pancreatitis can occur with exenatide. A link between sitagliptin and pancreatitis is suspected. Raised concerns of causality between insuline glargine and malignant tumors are not supported by strong evidence. Proton pump inhibitors seem to blunt clopidogrel benefit. Aliskiren can cause angioedema.

[Pharmacovigilance update]. / Pharmacovigilance.

The observations of pharmacovigilance reported during 2007 reflect an increasing attention towards drug-induced augmentation of the incidence of common disorders. New substances are thus to be added to the list of risk factors susceptible to favour cardiovascular events (tegaserod, rosiglitazone, erythropoïetin, aprotinine) or psychiatric disorders (dopaminergic agonists, rimonabant). The evaluation of the security profile of new medicines remains challenging. Besides biological investigations of questionable relevance and clinical trial of inconstant efficiency towards safety outcomes, the role of pharmacovigilance notifications by practitioners remains of paramount importance.

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

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

[Trends in drug therapy]. / Pharmacovigitance--pharmaco-épidémiologie.

This article reviews some recent aspects of pharmacovigilance, of interest to the practitioner: biphosphonates and osteonecrosis of the jaw, antidepressants and suicide, antipsychotics and increased mortality risk and cerebrovascular events, withdrawal syndrome after in utero exposure to antidepressants SSRI, NSAIDs and increased cardiovascular events, cancer and topical immunosuppressants, visual loss and treatment of erectile dysfunction, valvulopathy and dopaminergic agonists. Risk-benefit assessment of drugs is a dynamic process. One must keep in mind that the data on the relationship between drugs and the clinical picture are of variable quality and that the size of the risk is often difficult to assess.

[Hyponatremia: an unusual case report]. / Hyponatrémie: une histoire en deux temps....

Hyponatremia is a frequent finding and asks for a rapid diagnostic evaluation. We report a case of recurrent hyponatremia secondary to an adrenal insufficiency of medicamentous and tuberculous origin. This case illustrates the importance of a rapid etiologic diagnosis of hyponatremia and allows us to review adrenal insufficiency of tuberculous origin. It also stresses the danger of potential drug interactions in case of corticosteroid substitution.

Rate, type, and cost of adverse drug reactions in emergency department admissions.

Background: Adverse drug reactions (ADRs) are a threat to patients' health and quality of life, and can generate significant expenses. They are generally underreported, with different rates in different health care systems. Methods: We conducted a 6-month survey of all primary admissions to the medical emergency department of a university hospital and assessed the rate, characteristics, avoidability, and marginal costs of ADRs. Results: A total of 7% of all admissions were mainly caused by ADRs. The most frequent were gastrointestinal bleeding (22.3%) and febrile neutropenia (14.4%). Anticancer drugs were involved in 22.7% of the cases, and anticoagulants, analgesics, and non-steroidal anti-inflammatory drugs in 8% each. Physicians had prescribed 70% of these drugs. Patients were predominantly treated in intermediate care units and ordinary wards. The mean cost per case amounted to CHF 3586+/-342, or a total of CHF 821204 over the 6-month-period (1 CHF=0.56 US$=0.87 Euro). A total of 67% were considered definitely imputable to drug effects and 32% were retrospectively regarded as avoidable. Conclusions: Interventions aimed at reducing the incidence of ADRs should be directed towards both patient education and physician training. This could save hospitals admissions and money, and could be used as an indicator of prescription quality.

Wegener's granulomatosis: description of a case where cutaneous involvement was correlated with elevation of the c-ANCA titer.

Wegener's granulomatosis is a systemic disease characterized by necrotizing granulomas and vasculitis involving the upper and lower respiratory tract as well as the kidneys. Cutaneous manifestations consist mainly of papules or papulonecrotic lesions. c-ANCA are known to be a valuable adjunct for the diagnosis and follow-up of Wegener's granulomatosis with systemic involvement. We report the case of a 49-year-old man with Wegener's granulomatosis who developed two relapses of the disease with cutaneous manifestation and who presented with concomitant elevation of the c-ANCA and more precisely the subset PR3-ANCA during the acute phase of the disease.

[Necrotizing fasciitis: apropos of a case]. / La fascite necrotizzante: a proposito di un caso.

Necrotizing fasciitis is an infection which involves soft tissues up to the fascia, with wide areas of necrosis, and is mainly caused by group A beta-hemolytic Streptococcus. The Authors report a case recently observed and after an accurate review of the Literature, taking into account the most recent pathogenetic knowledges, confirm the necessity of an early diagnosis based on clinical criteria but above all on histological biopsy. The treatment is mainly surgical, and allows, together with the medical treatment, to subdue the rapid progression of the infection which notwithstanding maintains an high mortality rate.