Search

Surveillance data and literature have shown a worldwide increase in infections with resistant bacteria, which has led to increased prescriptions of carbapenems, which in turn has led to increased carbapenem resistance. There is also an increasing use of carbapenems in the Netherlands, a county usually very conservative in antibiotic use. Carbapenem sparing strategies are essential in an attempt to prevent further rise of infections caused by carbapenem resistant bacteria. This article discusses carbapenem sparing strategies with old forgotten antibiotics and novel antibiotics from a Dutch perspective.

Objectives: Antimicrobial Stewardship Programs commonly have an in-hospital focus. Little is known about the quality of antimicrobial use in hospital outpatient clinics. We investigated the extent and appropriateness of antimicrobial prescriptions in the outpatient clinics of three hospitals., Methods: From June 2018 to January 2019, we performed ten point prevalence surveys in outpatient clinics of one university hospital and two large teaching hospitals. All prophylactic and therapeutic prescriptions were retrieved from the electronic medical records. Appropriateness was defined as being in accordance with guidelines. Furthermore, we investigated the extent to which the dose was adjusted to renal function and documentation of an antibiotic plan in the case notes., Results: We retrieved 720 prescriptions for antimicrobial drugs, of which 173 prescriptions (24%) were prophylactic. A guideline was present for 95% of prescriptions, of which the guideline non-adherence rate was 25.6% (n = 42/164) for prophylaxis and 43.1% (n = 224/520) for therapy. Of all inappropriate prescriptions (n = 266), inappropriate prescriptions for skin and soft tissue infections (n = 60/226) and amoxicillin-clavulanic acid (n = 67/266) made up the largest proportion. In only 13 of 138 patients with impaired or unknown renal function the dosage regimen was adjusted. Amoxicillin-clavulanic acid was the drug for which most often renal function was not taken into account. In 94.6% of prescriptions the antibiotic plan was documented., Conclusions: In hospital outpatient clinics, a substantial part of therapeutics were inappropriately prescribed. Amoxicillin-clavulanic acid was the most inappropriately prescribed drug, due to non-adherence to the guidelines and because dose adjustment to renal function was often not considered.

Introduction: Haemophilia A is an inherited bleeding disorder characterised by factor VIII (FVIII) deficiency. In patients with non-severe haemophilia A, surgery and bleeding are the main indications for treatment with FVIII concentrate. A recent study reported that standard dosing frequently results in FVIII levels (FVIII:C) below or above FVIII target ranges, leading to respectively a bleeding risk or excessive costs. In addition, FVIII concentrate treatment carries a risk of development of neutralising antibodies. An alternative is desmopressin, which releases endogenous FVIII and von Willebrand factor. In most patients with non-severe haemophilia A, desmopressin alone is not enough to achieve FVIII target levels during surgery or bleeding. We hypothesise that combined pharmacokinetic (PK)-guided administration of desmopressin and FVIII concentrate may improve dosing accuracy and reduces FVIII concentrate consumption., Methods and Analysis: In the DAVID study, 50 patients with non-severe haemophilia A (FVIII:C ≥0.01 IU/mL) with a bleeding episode or undergoing surgery will receive desmopressin and FVIII concentrate combination treatment. The necessary dose of FVIII concentrate to reach FVIII target levels after desmopressin administration will be calculated with a population PK model. The primary endpoint is the proportion of patients reaching FVIII target levels during the first 72 hours after start of the combination treatment. This approach was successfully tested in one pilot patient who received perioperative combination treatment., Ethics and Dissemination: The DAVID study was approved by the medical ethics committee of the Erasmus MC. Results of the study will be communicated trough publication in international scientific journals and presentation at (inter)national conferences., Trial Registration Number: NTR5383; Pre-results., Competing Interests: Competing interests: LMS: received reimbursement from CSL-Behring for attending a symposium, not related to this study. MHC: received unrestricted research/educational funding for various projects as well as travel fees from the following institutions and companies: ZonMW, Innovatiefonds, Pfizer, Baxalta/Shire, Bayer Schering Pharma, Novo Nordisk, Novartis, Roche and CSL Behring, all not related to this study. RMvH, EAMB, MC, MHED, LN, SP: nothing to disclose relevant to the DAVID study. KF: is a member of the European Hemophilia Treatment and Standardization Board sponsored by Baxter, has received unrestricted research grants from CSL Behring and Bayer and has given lectures at educational symposiums organized by Pfizer, Bayer and Baxter. JE: received research funding from CSL Behring and honorarium for educational activity from Roche, not related to this study. BAPL-vG: received unrestricted educational grants from Baxter and CSL Behring and speaker fees from Sanquin. KM: research support from Bayer, Sanquin and Pfizer; speaker fees from Bayer, Sanquin, Boehringer Ingelheim, BMS and Aspen; consulting fees from Uniqure, not related to this study; FWGL: received unrestricted research grants from CSL-Behring and Baxalta/Shire not related to this study. He is consulant for Shire, NovoNordisk and UniQure. Fees go to the university. RAAM: received personal fees from Merck Sharp & Dohme and Zeria and grants from Bayer, UCB Pharma and Hoffman La Roche with no involvement in this study. MJHAK: received unrestricted research grants from Pfizer, Innovatiefonds and Ferring with no involvement in this study., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Cardiac and cerebrovascular events in hypertensive patients are related to specific features of the 24-hour diurnal blood pressure (BP) profile (i.e., daytime and nighttime BP, nocturnal dip (ND), and morning surge (MS)). This investigation aimed to characterize 24-hour diurnal systolic BP (SBP) with parameters that correlate directly with daytime and nighttime SBP, ND, and MS using nonlinear mixed effects modeling., Methods: Ambulatory 24-hour SBP measurements (ABPM) of 196 nontreated subjects from three ethnic groups were available. A population model was parameterized in NONMEM to estimate and evaluate the parameters baseline SBP (BSL), nadir (minimum SBP during the night), and change (SBP difference between day and night). Associations were tested between these parameters and patient-related factors to explain interindividual variability., Results: The diurnal SBP profile was adequately described as the sum of 2 cosine functions. The following typical values (interindividual variability) were found: BSL = 139 mm Hg (11%); nadir = 122 mm Hg (14%); change = 25 mm Hg (52%), and residual error = 12 mm Hg. The model parameters correlate well with daytime and nighttime SBP, ND, and MS (R (2) = 0.50-0.92). During covariate analysis, ethnicity was found to be associated with change; change was 40% higher in white Dutch subjects and 26.8% higher in South Asians than in blacks., Conclusions: The developed population model allows simultaneous estimation of BSL, nadir, and change for all individuals in the investigated population, regardless of individual number of SBP measurements. Ethnicity was associated with change. The model provides a tool to evaluate and optimize the sampling frequency for 24-hour ABPM.