Role of therapeutic drug monitoring in pulmonary infections : use and potential for expanded use of dried blood spot samples

Respiratory tract infections are among the most common infections in men. We reviewed literature to document their pharmacological treatments, and the extent to which therapeutic drug monitoring (TDM) is needed during treatment. We subsequently examined potential use of dried blood spots as sample procedure for TDM. TDM was found to be an important component of clinical care for many (but not all) pulmonary infections. For gentamicin, linezolid, voriconazole and posaconazole dried blood spot methods and their use in TDM were already evident in literature. For glycopeptides, beta-lactam antibiotics and fluoroquinolones it was determined that development of a dried blood spot (DBS) method could be useful. This review identifies specific antibiotics for which development of DBS methods could support the optimization of treatment of pulmonary infections

The endocarditis team

Endocarditis is een ernstig ziektebeeld met een hoge mortaliteit en morbiditeit. In de klinische praktijk proberen we de behandeling van deze patiënten te verbeteren door goede en snelle diagnostiek en door tijdig adequate antibiotische en zo nodig chirurgische therapie te starten. In de nieuwste richtlijnen wordt het begrip ‘endocarditisteam’ geïntroduceerd als cruciaal onderdeel in de verbetering van de zorg voor patiënten met (een verdenking op) endocarditis. Er wordt gesteld dat endocarditis een multidisciplinaire aanpak vraagt omdat het een ziekte is met een grote variatie in presentatie, waarvoor expertise nodig is van verschillende specialisaties, en ook omdat patiënten in een vroege fase dienen te worden besproken in een chirurgisch team. Observationele studies tonen een belangrijke reductie in de mortaliteit van endocarditispatiënten die zijn besproken in een endocarditisteam.Dit artikel bespreekt de ervaringen met het opzetten van een endocarditisteam in twee verschillende regio’s in Nederland (Rotterdam-​Rijnmond en Groningen). Wat is belangrijk als het gaat om de structuur en functie van een endocarditisteam? Het opzetten van een endocarditisteam kan lastig zijn. Daarom geven we enkele praktische tips. Ten slotte wordt de toegevoegde waarde van een operationeel endocarditisteam geïllustreerd aan de hand van een casus.Endocarditis is a life-​threatening disease with high mortality and morbidity. In clinical practice, we try to improve the outcome of patients with endocarditis by implementing a better and faster diagnostic workup, a timely start of antimicrobial therapy and an early surgical intervention if required. In the most recent update of the guidelines for the management of patients with endocarditis, an Endocarditis team is put forward as crucial part in the improvement of care for patients with (suspected) endocarditis. They state that endocarditis requires a multidisciplinary approach since patients present with highly variable signs and symptoms, need a high-​standard of care from several medical specialists, and need to be discussed in a surgical team early in the course of the disease. Observational studies support this implementation by showing a marked decrease in mortality after dicussing endocarditis patients in an Endocarditis team. This article discusses the experience with the implementation of an Endocarditis team in two different regions of the Netherlands (Rotterdam-​Rijnmond and Groningen). Which aspects are important for the structure and function of an Endocarditis team? The setting up of an Endocarditis team can be difficult, therefore we provide some practical advice. Finally, an illustrative case is presented

Immune response to varicella-zoster virus before and after renal transplantation

Background: Herpes zoster (HZ) risk is high in renal transplant recipients. Vaccination prior to transplantation may provide a useful strategy for the prevention of HZ in the posttranplantation period. However, it is not known whether immunity to varicella-zoster virus (VZV) is affected due to treatment surrounding transplantation. Methods: Both humoral and cellular immunity to VZV were determined prior to and 2-3 years after renal transplantation in 60 adult patients, and 62 matched healthy controls. VZV-specific cellular immunity was measured by an interferon gamma (IFN gamma) enzyme-linked immunospot (ELISpot) assay and by analyzing T-cell functionality using flowcytometry. VZV-IgG levels were measured using an in-house glycoprotein enzyme-linked immunosorbent assay (gpELISA). Results: Using paired analysis, it was determined that numbers of IFN gamma-producing cells did not change after transplantation, but were significantly lower in transplant recipients after transplantation than in controls (p = 0.028). Patients in whom the post-transplant period was complicated by rejection or any acute infection (excluding HZ) had a lower number of IFN gamma-producing cells than patients who did not. VZV IgG levels did not differ from controls, but a significant decrease was observed after transplantation (p <0.0001). Conclusions: VZV-specific cellular immunity, which is essential in the prevention of HZ, did not markedly change in patients following renal transplantation. This suggests that preventive vaccination before transplantation may be beneficial. Our results extend knowledge on VZV immunity after transplantation, vital when considering strategies for the prevention of HZ in these patients

Efficacy of Antibiotic Suppressive Therapy in Patients with a Prosthetic Joint Infection

Introduction: For chronic prosthetic joint infections (PJI), complete removal of the infected prosthesis is necessary in order to cure the infection. Unfortunately, a subgroup of patients is not able to undergo a revision surgery due to high surgical risk. Alternatively, these patients can be treated with antibiotic suppressive therapy (AST) to suppress the infection. Aim: To evaluate the efficacy and tolerability of AST. Methods: We retrospectively collected data (period 2009-2015) from patients with a PJI (of hip, knee or shoulder) who were treated with AST at the University Medical Center Groningen, the Netherlands. AST was defined as antibiotic treatment for PJI that was started after the usual 3 months of antibiotic treatment. The time of follow-up was defined from the time point AST was started. Treatment was considered as failed, when the patient still experienced joint pain, when surgical intervention (debridement, removal, arthrodesis or amputation) was needed to control the infection and/or when death occurred due to the infection. Results: We included 21 patients with a median age of 67 years (range 21 - 88) and with a median follow-up of 21 months (range 3 - 81). Coagulase negative staphylococci (CNS) (n=6), S. aureus (n=6) and polymicrobial flora (n=4) were the most frequently found causative pathogens. Most patients with CNS and S. aureus were treated with minocycline (67%) and clindamycin (83%) as AST, respectively. Overall, treatment was successful in 67% of patients. Failure was due to persistent joint pain (n=1), surgical intervention because of an uncontrolled infection (n=3), and death due the infection (n=3). We observed a treatment success of 90% in patients with a 'standard' prosthesis (n=11), compared to only 50% in patients with a tumor-prosthesis (n=10). Also, treatment was successful in 83% of patients with a CNS as causative microorganism for the infection, compared to 50% in patients with a S. aureus. Patients who failed on AST had a higher ESR in comparison to patients with a successful treatment (mean 73 ± 25SD versus 32 ± 19SD mm/hour (p = 0.007), respectively. 43% of patients experienced side effects and led to a switch of antibiotic treatment or a dose adjustment in almost all of these patients. Conclusions: Removal of the implant remains first choice in patients with chronic PJI. However, AST is a reasonable alternative treatment option in a subgroup of patients with a PJI who are no candidate for revision surgery, in particular in patients with a 'standard' prosthesis and/or CNS as the causative micro-organism