Background The increasing incidence of candidemia and emergence of drug resistant Candida (C.) species are major concerns worldwide. Long-term surveillance studies are needed. Methods The Fungal Infection Network of Switzerland (FUNGINOS) conducted a 15-year (2004-2018) nationwide epidemiological study of candidemia. Hospital-based incidence of candidemia, Candida species distribution, antifungal susceptibility and consumption were stratified in three periods (2004-2008, 2009-2013, 2014-2018). Population-based incidence over the period 2009-2018 derived from the Swiss Antibiotic Resistance Surveillance System (ANRESIS). Results A total of 2,273 Candida blood isolates were studied. Population and hospital-based annual incidence of candidemia increased from 2.96 to 4.20/100,000 inhabitants (p=0.022) and 0.86 to 0.99/10,000 patient-days (p=0.124), respectively. The proportion of C. albicans decreased significantly from 60% to 53% (p=0.0023), whereas C. glabrata increased from 18% to 27% (p<0.0001). Other non-albicans Candida species remained stable. C. glabrata bloodstream infections occurred predominantly in the age group 18-40 and above 65 years. A higher proportional increase of C. glabrata was recorded in wards (18% to 29%, p<0.0001) versus intensive care units (19% to 24%, p=0.22). According to CLSI, non-susceptibility to fluconazole in C. albicans was observed in 1% of isolates, and anidulafungin and micafungin non-susceptibility in 2% of C. albicans and C. glabrata. Fluconazole consumption, the most frequently used antifungal, remained stable, whereas use of mold-active triazoles and echinocandins increased significantly in the last decade (p<0.0001). Conclusions Over the 15-year period, the incidence of candidemia increased. A species shift toward C. glabrata was recently observed, concurring with increased consumption of mold-active triazoles.
Background and objectives: The chemical contamination during the preparation of cytotoxics remains a serious problem in hospital pharmacies and the operators could contribute to this risk during their manipulations. A validation protocol was developed using a non-toxic, highly detectable tracer, quinine dihydrochloride. Method: Further, a method for a high recovery extraction and quantification of this marker, and a protocol covering the critical operations of cytotoxic preparation, was developed and validated. Various devices were used to fill the syringes and perfusion bags. All the filled containers and used materials were collected at the end of the protocol and the tracer was extracted in water. The contaminated water was analyzed by fluorimetry. The number of spots on the working pads was counted under ultraviolet light. During a total of 28 sessions, the procedure was applied by 20 different operators. Results: The mean cumulated quantities of contamination were 6.2 µL (0.6–23.8) and >10 spots (0–20), which was considered as high. No correlation was observed between the contamination rate and the operator’s experience. Conclusion: This validation protocol facilitates controlling the operators’ working ‘cleanliness’ and helps to improve the initial and continuing training. This simple test presents an effective answer for the important issue of the chemical safety of operators.
A heavily immunosuppressed, 43-kg, 9-year-old patient was recovering from a bone marrow transplant. Primary prophylaxis against invasive fungal infections was liposomal amphotericin B (AmBisome®, 2.3 mg/kg [100 mg] two times per week). Once home, following a first amphotericin B infusion, he presented with strong diarrhoea and vomiting; this was repeated after the second infusion. The clinical situation worsened rapidly and the patient was rehospitalised. On admission, he presented with acute renal failure. During the 2-week hospitalisation, renal function recovered progressively. A few days after returning home, a new administration of amphotericin B was again followed by diarrhoea and vomiting, together with shivering and fever. The child was again rapidly rehospitalised. Investigation revealed that the community pharmacist, relying on drug software, had selected an inappropriate substitute drug: the patient had been administered amphotericin B deoxycholate (Fungizone®) and not liposomal amphotericin B. Depending on the indication, intravenous AmBisome® is usually administered at a dose between 3 and 5 mg/kg bodyweight; this dose can be increased to up to 10 mg/kg/day. Intravenous Fungizone®, however, should be administered using an initial dose of 0.25 mg/kg bodyweight, up to a recommended 1-mg/kg/day dose. The child had thus received 100 mg of Fungizone®, or ten times the recommended dose.
Introduction BRAF and MEK inhibitors have been approved for use in metastatic melanoma therapies. All of them are administered as oral capsules or pills. We report two cases treated applying an alternative method of vemurafenib or debrafenib-trametinib administration in patients unable to swallow. Case Report The first case involved a 38-year-old man who was referred to a dermatologist for dysphagia and anorexia. After a computerized tomography (CT) scan it was concluded that the dysphagia was due to compression by mediastinal metastasis in a context of metastatic BRAF mutant melanoma. The second case involved a 35-year-old man who was diagnosed in March 2017 with melanoma of the back of the hand. Several months later a positron emission tomography (PET)/CT scan was performed. It revealed multiple disseminated metastasis. Management & Outcome: The first patient presented total dysphagia and was unable to swallow pills. It was decided to dissolve vemurafenib in order to facilitate administration. Dysphagia was improved 48 hours later, and oral feeding was reintroduced. Due to severe tablet phobia, the second patient was unable to swallow pills. Dabrafenib capsules were emptied and trametinib pills were grinded. One month later, we noted improved health associated with reduction of the metastases. Discussion Our study highlights the possibility of crushing or dissolving BRAF and MEK inhibitors in metastatic melanoma patients for whom it is impossible to swallow pills, eliciting a response and achieving significant if temporary clinical benefit.
e13067 Background: Ribociclib is, for now, the only CDK4/6 inhibitor having demonstrated a statistically significant increase of overall survival in first-line in hormone receptor-positive, HER2-negative advanced breast cancer. One of the limiting toxicities of ribociclib is the occurrence of grade III/IV hepatobiliary toxicity in approximately 5% of patients. It contraindicates the reintroduction of the drug. Therapeutic options after this type of adverse event are challenging because there are very limited data regarding cross reactivity in risk for hepatic injury between ribociclib, palbociclib or abemaciclib. Methods: We describe a cohort of 28 patients who presented with grade III and/or IV ribociclib-induced hepatitis and who subsequently received another CDK4/6 inhibitor. Cases were collected from the French pharmacovigilance database and additional cases were obtained through institutional databases. Data were retrospectively obtained from patients’ reports. Results: Twenty-eight patients, from 11 centers, presented a grade III (71%, 20 patients) or a grade IV (29%, 8 patients) transaminase elevation with ribociclib. Median transaminase elevation was 12.3 x ULN (upper limit normal) for AST and 15.2 x ULN for ALT. This toxicity occurred within the first 6 months of treatment for all patients except one. Ribociclib was associated with letrozole in 21 patients, fulvestrant in 5 patients and anastrozole or exemestane in 2 patients. No acute liver failure occurred. All patients switched to another CDK4/6 inhibitor (23 patients - 82% - palbociclib and 5 - 18% - abemaciclib) without significant reoccurrence of liver toxicities. Four patients (14%) presented a transient grade 1 or 2 hepatic toxicity (all of them with palbociclib), 20 patients (71%) received the second CDK4/6 inhibitor at full dose. The median follow-up was 16 months. Conclusions: Treatment with palbociclib or abemaciclib after grade III or IV transaminase elevation due to ribociclib is feasible and none of the patients in this cohort exhibited reoccurrence of significant liver toxicity afterwards. Ribociclib liver toxicity occurs mainly during the first 6 months of treatment and takes several months to recover. [Table: see text]
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