Drug-drug interaction: decreased posaconazole trough concentrations during concomitant flucloxacillin treatment.

BACKGROUND AND OBJECTIVES: Posaconazole is used as prophylaxis of invasive fungal disease in immune-compromised haematological patients with prolonged neutropenia after intensive chemotherapy. During routine therapeutic drug monitoring of posaconazole, we repeatedly observed low posaconazole serum concentrations in patients that were concomitantly treated with flucloxacillin. A possible interaction between flucloxacillin and posaconazole was explored in this case series. PATIENTS AND METHODS: Posaconazole trough serum concentrations during and before/after flucloxacillin treatment were collected from 10 patients. RESULTS: With a median concentration of 0.5 mg/L (IQR 0.3-0.6), the posaconazole trough serum concentration decreased by 47% during flucloxacillin treatment compared with the concentration before/after flucloxacillin treatment (0.9 mg/L, IQR 0.6-1.3). As a result, the posaconazole target trough concentration of ≥0.7 mg/L was only achieved in five out of nine patients during flucloxacillin treatment. CONCLUSIONS: Careful monitoring of posaconazole serum trough concentrations is recommended when concomitant use of flucloxacillin cannot be avoided.

Anti-glycoprotein antibodies and sequestration pattern of indium-labeled platelets in immune thrombocytopenia.

Antiglycoprotein (anti-GP) antibodies play an important role in the pathophysiology of immune thrombocytopenia (ITP). The sequestration pattern of platelets in the spleen and liver can be studied with 111In-labeled autologous platelet scans. No studies have investigated the role of anti-GP antibodies in sequestration patterns in ITP patients. In this study, we examined the association between antibodies and (1) platelet sequestration site and (2) clearance rate of platelets. All ITP patients receiving an 111In-labeled autologous platelet study between 2014 and 2018 were included. Antibodies were measured using the direct MAIPA method to determine the presence and titer of anti-GPIIb/IIIa, anti-GPIb/IX, and anti-GPV antibodies. Multivariate regression models were used to study the association between anti-GP antibodies, sequestration site, and clearance rate. Seventy-four patients were included, with a mean age of 36 years. Forty-seven percent of the patients showed a predominantly splenic sequestration pattern, 29% mixed, and 25% a hepatic pattern. In 53% of the patients, anti-GP antibodies were detected. Regression models showed a significant association between splenic sequestration and GPV autoantibodies. Furthermore, in patients where antibodies were present, the clearance rate was higher in patients with a splenic sequestration. Anti-GPV antibodies are associated with a splenic sequestration pattern in ITP patients. These associations provide insight into the possible pathophysiological mechanisms of ITP, which may lead to better detection and treatment of this partly idiopathic and prevalent disease.

Serum and Prostatic Tissue Concentrations of Cefazolin, Ciprofloxacin and Fosfomycin after Prophylactic Use for Transurethral Resection of the Prostate.

The optimal drug of choice, its time of administration and duration of antibiotic prophylaxis in patient undergoing a TURP procedure are still matters of debate. In this study, we evaluated the concentrations of cefazolin, ciprofloxacin and fosfomycin in the human prostate in a cohort of men undergoing TURP. We compared prostate tissue concentrations to the serum concentrations and MICs of common uropathogens, to determine the appropriateness of the current presurgical prophylactic antibiotics and to gain supportive data about the suitability of fosfomycin for antibiotic prophylaxis in men undergoing urological procedures of the prostate. After a single intravenous dose of cefazoline or an oral dose of ciprofloxacin prior to TURP, concentrations in serum and prostate tissue of well above the MIC (EUCAST breakpoint) of common uropathogens (Enterobacterales) were reached, and both antibiotics seem potentially effective in preventing postsurgical infections. A single dose of oral and intravenous administration of fosfomycin both led to serum concentrations above the MIC for uncomplicated urinary tract infections (8 µg/mL). The MIC for other infections (32 µg/mL) was only reached after a single dose of intravenous fosfomycin. We were unable to detect fosfomycin concentrations in prostate tissue.

Patient-Reported Burden of Adverse Drug Reactions Attributed to Biologics Used for Immune-Mediated Inflammatory Diseases.

INTRODUCTION: Although the burden of adverse drug reactions (ADRs) has a significant impact on patients' quality of life, thorough knowledge about patients' perspectives on the burden of ADRs attributed to biologics is lacking. OBJECTIVES: This study was conducted to gain insight into the patient burden of ADRs experienced with biologic use. METHODS: The Dutch Biologic Monitor is a prospective, multicentre, event monitoring cohort system including information collected by web-based questionnaires from patients using biologics, mainly for immune-mediated inflammatory diseases (IMIDs). Patients were asked to complete bimonthly questionnaires on biologics used, indication for the biologic, experienced ADRs, consequences of ADRs and burden on a five-point Likert-type scale, ranging from 1 (no burden) to 5 (very high burden). We assessed potential factors associated with patient-reported burden of ADRs. RESULTS: A total of 1355 patients completed 6293 questionnaires between 1 January 2017 and 1 May 2019. Almost half of the patients (665 patients, 49%), 69% with rheumatic diseases and 31% with other diseases, collectively reported 1720 unique ADRs. Infections and musculoskeletal complaints were the most burdensome ADRs and injection-site reactions were the least burdensome. ADRs leading to healthcare professional contact were more burdensome than ADRs without healthcare professional contact. Smoking, respiratory and psychiatric comorbidities were associated with higher burden of ADRs. Crohn's disease, use of adalimumab and use of sulfasalazine as combination therapy were associated with lower burden of ADRs. CONCLUSIONS: The patient perspective gives important insights into the burden of ADRs experienced with biologics. This information could be used by healthcare professionals to optimise treatment with biologics.

Short article: Switching to a infliximab biosimilar: short-term results of clinical monitoring in patients with inflammatory bowel disease.

OBJECTIVE: Currently, a biosimilar of Remicade is available (CT-P13). Switching patients from Remicade to a biosimilar is still under debate, especially for patients with inflammatory bowel disease (IBD). In a retrospective study, we investigated the feasibility and safety of switching patients with IBD from Remicade to a biosimilar infliximab. PATIENTS AND METHODS: At two large general hospitals in The Netherlands, adult patients with a diagnosis of Crohn's disease or ulcerative colitis being treated with Remicade were asked to switch to the biosimilar infliximab (CT-P13). After switching, patients were closely monitored by assessing disease activity and evaluating disease-specific measures (serum C-reactive protein and fecal calprotectin). Adverse effects were recorded and serum infliximab concentrations measured. All parameters were assessed at baseline (t=0) and after two infusions with biosimilar infliximab (±week 16). RESULTS: Among 197 patients with IBD switched to the biosimilar infliximab (∼77%), and no difference in disease activity was observed. Disease-specific measures did not differ between baseline and after two infusions with the biosimilar. Apart from one infusion-related reaction, no serious or unexpected adverse reactions were reported. Serum trough concentrations did not differ between baseline and after switching [median: 4.1 µg/ml (range: 0.03-22 µg/ml) vs. 4.6 µg/ml (range: 0.03-22 µg/ml); P=0.08, n=98]. CONCLUSION: These data suggest that switching patients with IBD to the biosimilar infliximab is safe in clinical practice. After the switch, no clinically relevant differences were observed in disease activity, adverse effects, and serum infliximab concentrations.