Implementing a new antibiotic allergy protocol in clinical practice: well-trusted but not used.

BACKGROUND: Suboptimal antibiotic prescriptions in patients with an antibiotic allergy label lead to increased incidence of adverse events and antimicrobial resistance (AMR). An antibiotic allergy protocol was developed in a Dutch academic hospital guiding optimal and safe antibiotic use in potentially penicillin-allergic patients. Informed by previous studies of implementation processes in clinical care, we studied the implementation of this protocol. METHODS: Medical professionals in the Departments of Surgery, Internal Medicine, and Pulmonary Care were interviewed. Additionally, focus groups were conducted in Internal Medicine and Pulmonary Care to validate the outcomes of the interviews. RESULTS: Dissemination of the protocol via the regular online hospital-wide guidance system did not have a significant impact on the knowledge about or use of the protocol. If healthcare professionals found the protocol, they thought it was valuable and expressed trust in the expertise embodied in it. However, its use in practice was rather minimal. Interviewees doubted the accuracy of the patient's histories about their previous adverse drug reactions, and/or the information in their medical records and concluded that adherence to the expert guideline was needlessly risky. They felt the acute allergic reaction risk for a patient outweighed the risk of suboptimal therapy or future AMR. CONCLUSIONS: For successful implementation and dissemination of the protocol, the accessibility of the protocol, the information about the actual risks of following the protocol and the registration of allergic history should be improved. However, whether this actually results in improvement also depends on changes in the hospital culture and organization.

[Cross-allergy to penicillins and cephalosporins: problematic when prescribing cephalosporins?] / Kruisallergie van penicillines met cefalosporines.

Penicillin allergy is commonly reported and often influences selection of antimicrobial treatment. Due to concerns about cross-allergic reactions, other beta-lactams - particularly cephalosporins - may also be avoided. This too often results in less effective treatment, more side effects and overconsumption of reserve antimicrobial agents. Most patients (> 90%) with a penicillin allergy label are not truly allergic, i.e., they do not have an 'immediate type' (IgE-mediated) allergy when tested. Based on current data, even in patients with a true penicillin allergy, the risk of severe cross-allergic reactions to cephalosporins is very low. Clinicians tend to overestimate this risk: this dilemma can be resolved with a systematic appraisal of risk probabilities. The limited risk of a true penicillin allergy being present and the subsequent low risk of a cross-allergic reaction to cephalosporins generally outweighs the disadvantages of selecting an alternative (non-beta-lactam) antimicrobial regimen.

Non-myeloablative allogeneic stem cell transplantation: a new treatment option for acquired angioedema?

INTRODUCTION: Acquired angioedema is a rare disorder causing recurrent life-threatening angioedema, due to decreased activity of C1 esterase inhibitor. CASE REPORT: A 57-year-old man presented to our hospital with recurrent swelling of the hands, lips, tongue, scrotum and throat. Lab examination showed the presence of an IgM kappa monoclonal antibody. Additional analysis showed that in the IgM fraction autoantibody activity against C1 esterase inhibitor was present. This confirmed the diagnosis of acquired angioedema in the presence of lymphoplasmacytic lymphoma. Despite standard therapy, there was an increase in the episodes of laryngeal oedema. Therefore it was decided to perform a non-myeloablative allogeneic haematopoietic stem cell transplantation, with his HLA-identical brother as donor. The post-transplantation course was without complications. Five years following alloSCT he is in complete remission without symptoms and with increased C1 esterase inhibitor activity. DISCUSSION: In this case all other known treatment options for severe acquired angioedema failed. This is the first case describing treatment of severe acquired angioedema, caused by lymphoplasmacytic lymphoma, with an alloSCT.

Chronicity index and mesangial IgG deposition are risk factors for hypertension and renal failure in early IgA nephropathy.

To determine the natural history in early immunoglobulin A (IgA) nephropathy, we evaluated the long-term follow-up of 27 normotensive nonazotemic adult idiopathic IgA nephropathy patients with chronic hematuria who derived from a prospective regional epidemiological study of glomerulonephritis conducted between 1978 and 1984. As controls, 17 thin glomerular basement membrane (GBM) patients, 24 patients with normal renal tissue, and nine patients with miscellaneous nephropathies were followed up. Median follow-up was 11 years (range, 8 to 14 years). Renal biopsies, performed within 2 years after patient identification, were scored semiquantitatively in terms of activity and chronicity indices, using a modified National Institutes of Health (NIH) scoring system. During follow-up, two patients with IgA nephropathy went into histological remission, and 12 IgA nephropathy patients showed disease progression, of whom three developed renal failure. Initial proteinuria over 1 g/d was associated with a high activity score, extracapillary lesions, and late onset of uremia. Mesangial IgG deposition and a higher initial chronicity index were associated with development of hypertension during follow-up. In the multivariate analysis, a high initial chronicity index, erythrocyturia, and mesangial IgG deposition are independent determinants of progression of disease. We conclude that in patients with IgA nephropathy, identified early in the course of disease, erythrocyturia, a high chronicity index, and mesangial IgG deposition in the presence of normal renal function are risk factors for decreased renal survival. Disappearance of hematuria is associated with remission of IgA nephropathy immunopathologically and low activity and chronicity indices at initial biopsy.

Thin GBM nephropathy: premature glomerular obsolescence is associated with hypertension and late onset renal failure.

Thin glomerular basement membrane (GBM) nephropathy, also called familial benign hematuria, is characterized by chronic hematuria and uniform thinning of the lamina densa of the glomerular basement membrane. It generally holds an excellent renal prognosis. Alport syndrome in early stages can also show attenuation of the GBM; conversely, renal insufficiency has been reported in familial benign hematuria. To discern early Alport syndrome from thin GBM nephropathy, we carried out a prospective epidemiological study in which 19 normotensive and non-azotemic adult patients with chronic microscopic (18 of 19) and macroscopic (1 of 19) hematuria and biopsy-proven thin GBM nephropathy were followed for a median of 12 years (range 9 to 15 years). Renal biopsies of thin GBM patients at entry showed an increased incidence of focal global glomerulosclerosis when compared to disease controls as IgA nephropathy (P = 0.047) and normal renal tissue (P = 0.0075). All renal biopsies showed the presence of the Goodpasture antigen when tested immunohistochemically. Presence of Alport syndrome was excluded clinically as none of the patients had complaints of hearing loss or abnormalities by audiography and ophthalmology. At the end of follow-up, the incidence of hypertension in thin GBM nephropathy (35%) exceeded that of healthy clinical controls (P = 0.048), and one hypertensive patient developed mild renal failure. In the normotensive patients, the glomerular filtration rate at follow-up as measured by inulin clearance was reduced in three out of seven; these were over 50 years of age. Although no family members were known to have renal disease at inclusion, within four families six elderly first degree relatives had developed unexplained renal insufficiency at the end of follow-up. Thus, thin GBM nephropathy predisposes to premature glomerular obsolescence, leading in time to increased incidences of hypertension and late onset renal insufficiency.

A prospective study of the natural history of idiopathic non-proteinuric hematuria.

In a prospective study of idiopathic glomerulonephritis we determined the natural history of 49 adult patients (12 primary IgA nephropathy, 13 thin GBM nephropathy, 20 normal renal tissue and 4 miscellaneous nephropathies) who presented with idiopathic non-proteinuric non-azotemic hematuria of at least six months duration, in the absence of hypertension and with a negative urological work-up. The median follow-up was 11 years with a range of 8 to 14 years. At the end of the follow-up, renal function had remained stable in all subsets except for those with miscellaneous disease. Hematuria was still present in all patients with thin GBM nephropathy, in all but two patients with IgA nephropathy who went into immunopathological remission, in three out of four miscellaneous nephropathies, and in seven out of 20 patients with normal renal tissue. Of the latter patients five had a history suggestive of urolithiasis at follow-up, which was in the absence of hypercalciuria and hyperuricosuria. Seven thin GBM patients, five IgA nephropathy patients and three miscellaneous nephropathies developed hypertension; the incidence of hypertension in each subset was significantly higher than in patients with normal renal tissue. This study shows that in young adults with idiopathic chronic non-proteinuric hematuria of four years duration, renal biopsy will give a definite diagnosis in 86% of the patients, and that those patients with so-called minor glomerular diseases are at high risk for hypertension. Those patients with normal renal tissue have a high incidence of urolithiasis and should have a urological follow-up.

Parkinsonism in alcohol withdrawal: case report and review of the literature.

A case of severe, acute parkinsonism occurring in a 60-year-old man after cessation of chronic alcohol consumption, is reported. He recovered completely in 3 months without specific therapy. The literature on alcohol withdrawal parkinsonism including nine other cases, is reviewed.

Small cell lung cancer with paraneoplastic nephrotic syndrome.

We present a case of nephrotic syndrome, associated with small cell lung carcinoma. Renal biopsy revealed membranous glomerulonephritis, probably due to immune complex deposition with tumour antigen. Complete remission of the small cell lung carcinoma after chemotherapy was followed by regression of the nephrotic syndrome. This regression persisted even when brain metastases developed, without simultaneous relapse of tumour outside the central nervous system.