#92: What Is the Optimal Management of Patients Immunosuppressed with the Anti-compliment Monoclonal Antibody, Eculizumab? A Case Report and Review

2021 ◽  
Vol 10 (Supplement_1) ◽  
pp. S12-S12
Author(s):  
I Tinoco ◽  
A Jarrell ◽  
L Correa ◽  
J Bissler ◽  
J DeVincenzo ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Renal Failure ◽  
Antibiotic Prophylaxis ◽  
Neisseria Meningitidis ◽  
Paroxysmal Nocturnal Hemoglobinuria ◽  
Neisseria Species ◽  
E Coli ◽  
Increased Risk ◽  
Prescribing Information ◽  
Rabbit Complement

Abstract Background Patients with deficiencies of terminal components of complement are at hundreds to thousands fold increased risk of severe and fatal Neisseria spp. infections compared with the general population. Eculizumab is a newly approved monoclonal antibody C5 complement inhibitor. It is indicated for the treatment of atypical hemolytic uremic syndrome (atypical HUS), myasthenia gravis, and paroxysmal nocturnal hemoglobinuria. Because of the complement-depleting effect of Eculizumab dosing (Soliris®, Alexion Pharmaceuticals, Munich, Germany), patients are immunosuppressed for specific infectious pathogens (including Neisseria species) against which protection partially relies on normal complement activity. Because Eculizumab treatment is associated with a dramatically increased risk of Neisseria species. infections, recommendations for Neisseria meningitidis vaccination and antibiotic prophylaxis are contained in Eculizumab prescribing information. However, the most appropriate prevention of infections after Eculizumab has yet to be determined. Methods Case report and literature review. Results A previously healthy 7-year-old male was diagnosed with atypical HUS which included renal failure progressing to dialysis, persistent thrombocytopenia, hemolytic anemia, and hemoglobinuria. Stool cultures and a stool multiplex PCR panel did not detect Shiga-like producing E. coli nor E. coli O157/H7. Eculizumab dosing was therefore planned and Infectious Diseases consultation was obtained for appropriate preventions. The FDA Prescribing Information recommends Neisseria meningitidis vaccination before starting Eculizumab or, if immediate Eculizumab is necessary, to use antibiotic prophylaxis until 2 weeks after vaccination. The accepted protective titer after meningococcal vaccination is population based and uses the serum bactericidal assay (SBA). An antibody titer of >1:4 (human compliment) or 1:8 (rabbit complement) is considered protective. However, this “gold standard” assay incorporates the use of exogenous human or rabbit complement. The protective SBA titers in subjects with terminal complement component deficiencies may not be properly assessed using these same SBA titer protective thresholds. Furthermore, serious meningococcal infections have occurred after appropriate vaccination in patients receiving chronic Eculizumab treatments (ie for paroxysmal nocturnal hemoglobinuria). Finally, SBA protective levels after single Neisseria meningitidis vaccination have not been achieved in majorities of patients with renal failure receiving dialysis and or transplant immunosuppression. Conclusions The current Eculizumab prescribing information recommendations for vaccination and antimicrobial prophylaxis may be inadequate to prevent serious Neisseria infections. Repeated Neisseria meningitidis vaccination and extended antibiotic prophylaxis may afford better protection in patients chronically dosed with Eculizumab.

scholarly journals A Case of Fulminant Meningococcemia: It Is All in the Complement

2017 ◽  
Vol 2017 ◽  
pp. 1-3 ◽  
Author(s):  
Kellie L. Hawkins ◽  
Mariah Hoffman ◽  
Sonia Okuyama ◽  
Sarah E. Rowan
Keyword(s):  
Monoclonal Antibody ◽  
Risk Factor ◽  
Antibiotic Prophylaxis ◽  
Neisseria Meningitidis ◽  
Paroxysmal Nocturnal Hemoglobinuria ◽  
Complement Deficiency ◽  
Biologic Agent ◽  
Meningococcal Infection ◽  
Increased Risk ◽  
Life Threatening

Eculizumab is a novel monoclonal antibody that inhibits complement-mediated hemolysis in patients with paroxysmal nocturnal hemoglobinuria (PNH). Complement deficiency is a well-known risk factor for meningococcal infection. We describe a case of a young patient with PNH treated with eculizumab who presented with a life-threatening case of nongroupable meningococcemia. As this new biologic agent becomes more widely prescribed, providers should be aware of the increased risk of meningococcemia. In addition to vaccination, providers may consider the use of oral penicillin for antibiotic prophylaxis against Neisseria meningitidis in these cases of functional complement deficiency.

scholarly journals Monoclonal Antibodies Specific for Neisseria meningitidis Group B Polysaccharide and Their Peptide Mimotopes

2001 ◽  
Vol 69 (5) ◽  
pp. 3335-3342 ◽  
Author(s):  
J. S. Shin ◽  
J. S. Lin ◽  
P. W. Anderson ◽  
R. A. Insel ◽  
M. H. Nahm
Keyword(s):  
Amino Acids ◽  
Monoclonal Antibodies ◽  
Neisseria Meningitidis ◽  
The Other ◽  
Human Complement ◽  
E Coli ◽  
Peptide Mimotopes ◽  
Group B ◽  
K 12 ◽  
Rabbit Complement

ABSTRACT From five mice immunized with Escherichia coli K1 bacteria, we produced 12 immunoglobulin M hybridomas secreting monoclonal antibodies (MAbs) that bind to Neisseria meningitidis group B (NMGB). The 12 MAbs also bound the capsular polysaccharide (PS) of E. coli K1 [which, like NMGB, is α(2-8)-linked polysialic acid (PSA)] and bound to EV36, a nonpathogenic E. coli K-12 strain producing α(2-8) PSA. Except for HmenB5, which cross-reacted with N. meningitidis group C, none of the MAbs bound to N. meningitidis groups A, C, and Y. Of the 12 MAbs, 6 were autoantibodies as defined by binding to CHP-134, a neuroblastoma cell line expressing short-chain α(2-8) PSA; five of these MAbs killed NMGB in the presence of rabbit complement, and two also killed NMGB with human complement. The other six MAbs, however, were nonautoreactive; all killed NMGB with rabbit complement, and five killed NMGB with human complement. To obtain peptide mimotopes of NMGB PS, four of the nonautoreactive MAbs (HmenB2, HmenB3, HmenB13, and HmenB14) were used to screen two types of phage libraries, one with a linear peptide of 7 amino acids and the other with a circular peptide of 7 amino acids inserted between two linked cysteines. We obtained 86 phage clones that bound to the screening MAb in the absence but not in the presence of E. coli K1 PSA in solution. The clones contained 31 linear and 4 circular mimotopes expressing unique sequences. These mimotopes nonrandomly expressed amino acids and were different from previously described mimotopes for NMGB PS. The new mimotopes may be useful in producing a vaccine(s) capable of eliciting anti-NMGB antibodies not reactive with neuronal tissue.

Purification of Urokinase from Complex Mixtures Using Immobilized Monoclonal Antibody Against Urokinase Light Chain

1983 ◽  
Vol 49 (01) ◽  
pp. 024-027 ◽  
Author(s):  
David Vetterlein ◽  
Gary J Calton
Keyword(s):  
Monoclonal Antibody ◽  
Light Chain ◽  
Culture Media ◽  
Biological Fluids ◽  
Single Step ◽  
High Yield ◽  
Step Method ◽  
Commercial Preparation ◽  
E Coli ◽  
Tissue Culture Media

SummaryThe preparation of a monoclonal antibody (MAB) against high molecular weight (HMW) urokinase light chain (20,000 Mr) is described. This MAB was immobilized and the resulting immunosorbent was used to isolate urokinase starting with an impure commercial preparation, fresh urine, spent tissue culture media, or E. coli broth without preliminary dialysis or concentration steps. Monospecific antibodies appear to provide a rapid single step method of purifying urokinase, in high yield, from a variety of biological fluids.

Comparison of decay rates of faecal indicator organisms in recreational coastal water and sediment

2002 ◽  
Vol 2 (3) ◽  
pp. 131-138 ◽  
Author(s):  
D.L. Craig ◽  
H.J. Fallowfield ◽  
N.J. Cromar
Keyword(s):  
Water Column ◽  
Coastal Water ◽  
Decay Rates ◽  
Organic Carbon Content ◽  
Indicator Organisms ◽  
Filtration Method ◽  
E Coli ◽  
Water And Sediment ◽  
Increased Risk ◽  
High Organic Carbon Content

A laboratory based microcosm study utilising intact non-sterile sediment cores was undertaken to determine the survival of the faecal indicator organisms Escherichia coli, Enterococcus faecium and somatic coliphage in both recreational coastal water and sediment. Overlying water was inoculated with the test organisms and incubated at 10°C, 20°C or 30°C. E. coli, enterococcus and coliphage were enumerated from the water column and sediment by the membrane filtration method, Enterolert (IDEXX Laboratories) and the double-agar overlay methods respectively on days 0, 1, 2, 7, 14 and 28 following inoculation. It was demonstrated that for all organisms, greater decay (k; d-1) occurred in the water column compared to sediment. Sediment characteristics were found to influence decay, with lowest decay rates observed in sediment consisting of high organic carbon content and small particle size. Decay of E. coli was significantly greater in both the water column and sediment compared with enterococcus and coliphage under all conditions. Decay of enterococcus was found to closely resemble that of coliphage decay. Survival of all organisms was inversely related to temperature, with greatest decay at 30°C. However, increased temperature had a less significant impact on survival of enterococcus and coliphage compared with E. coli. The importance of this study for estimating risk from recreational exposure is great if some pathogenic microorganisms behave similarly to the organisms tested in this study. In particular if survival rates of pathogens are similar to enterococcus and coliphage, then their ability to accumulate in coastal sediment may lead to an increased risk of exposure if these organisms are resuspended into the water column due to natural turbulence or human recreational activity.

The Effect of Mianserin on Lifespan of Caenorhabditis elegans is Abolished by Glucose

2021 ◽  
Vol 13 ◽  
Author(s):  
Abdullah Almotayri ◽  
Jency Thomas ◽  
Mihiri Munasinghe ◽  
Markandeya Jois
Keyword(s):  
Caenorhabditis Elegans ◽  
Scaffolding Protein ◽  
Lifespan Extension ◽  
Wild Type ◽  
E Coli ◽  
C Elegans ◽  
Risk Of Death ◽  
Increased Risk ◽  
Antidepressant Use ◽  
Extension Effect

Background: The antidepressant mianserin has been shown to extend the lifespan of Caenorhabditis elegans (C. elegans), a well-established model organism used in aging research. The extension of lifespan in C. elegans was shown to be dependent on increased expression of the scaffolding protein (ANK3/unc-44). In contrast, antidepressant use in humans is associated with an increased risk of death. The C. elegans in the laboratory are fed Escherichia coli (E. coli), a diet high in protein and low in carbohydrate, whereas a typical human diet is high in carbohydrates. We hypothesized that dietary carbohydrates might mitigate the lifespan-extension effect of mianserin. Objective: To investigate the effect of glucose added to the diet of C. elegans on the lifespan-extension effect of mianserin. Methods: Wild-type Bristol N2 and ANK3/unc-44 inactivating mutants were cultured on agar plates containing nematode growth medium and fed E. coli. Treatment groups included (C) control, (M50) 50 μM mianserin, (G) 73 mM glucose, and (M50G) 50 μM mianserin and 73 mM glucose. Lifespan was determined by monitoring the worms until they died. Statistical analysis was performed using the Kaplan-Meier version of the log-rank test. Results: Mianserin treatment resulted in a 12% increase in lifespan (P<0.05) of wild-type Bristol N2 worms but reduced lifespan by 6% in ANK3/unc-44 mutants, consistent with previous research. The addition of glucose to the diet reduced the lifespan of both strains of worms and abolished the lifespan-extension by mianserin. Conclusion: The addition of glucose to the diet of C. elegans abolishes the lifespan-extension effects of mianserin.

scholarly journals Risk Factors for and Mechanisms of COlistin Resistance Among Enterobacterales: Getting at the CORE of the Issue

2021 ◽  
Author(s):  
John P Mills ◽  
Laura J Rojas ◽  
Steve H Marshall ◽  
Susan D Rudin ◽  
Andrea M Hujer ◽  
...  
Keyword(s):  
Case Control Study ◽  
Clinical Isolates ◽  
Colistin Resistance ◽  
E Coli ◽  
The Core ◽  
Increased Risk ◽  
Recent Emergence ◽  
Enterobacter Species ◽  
Ann Arbor ◽  
Control Study

Abstract Background Despite the recent emergence of plasmid-mediated colistin resistance, the epidemiology and mechanisms of colistin-resistant Enterobacterales (CORE) infections remain poorly understood. Methods A case-case-control study was conducted utilizing routine clinical isolates obtained at a single tertiary health system in Ann Arbor, MI. Patients with CORE isolates from January 1st 2016 to March 31st 2017 were matched 1:1 with patients with colistin-susceptible Enterobacterales (COSE) and uninfected controls. Multivariable logistic regression was used to compare clinical and microbiologic features of patients with CORE and COSE to controls. A subset of available CORE isolates underwent whole genome sequencing to identify putative colistin resistance genes. Results Of 16,373 tested clinical isolates, 166 (0.99%) were colistin-resistant, representing 103 unique patients. Among 103 CORE isolates, 103 COSE isolates, and 102 uninfected controls, antibiotic exposure in the antecedent 90 days and age &gt; 55 years were predictors of both CORE and COSE. Of 33 isolates that underwent WGS, a large variety of mutations associated with colistin resistance were identified, including 4 mcr-1/mcr-1.1 genes and 4 pmrA/B mutations among 9 Escherichia coli isolates; 5 mgrB and 3 PmrA mutations among 8 Klebsiella pneumoniae isolates. Genetic mutations found in Enterobacter species were not associated with known phenotypic colistin resistance. Conclusions Increased age and prior antibiotic receipt were associated with increased risk for patients with CORE, and for patients with COSE. Mcr-1, pmrA/B, and mgrB were the predominant colistin resistance-associated mutations identified among E. coli and K. pneumoniae, respectively. Mechanisms of colistin resistance among Enterobacter species could not be determined.

Calcium phosphate product level as a predictor for arteriovenous fistula re-operations in patients with chronic renal failure

Vascular ◽  
2018 ◽  
Vol 27 (3) ◽  
pp. 284-290 ◽  
Author(s):  
Mehmet Erin Tüysüz ◽  
Mehmet Dedemoğlu
Keyword(s):  
Renal Failure ◽  
Chronic Renal Failure ◽  
Calcium Phosphate ◽  
Arteriovenous Fistula ◽  
Product Level ◽  
Increased Risk ◽  
High Calcium ◽  
Phosphate Product ◽  
Group 2 ◽  
Group 1

Objectives There is an increased calcium phosphate product level causing the formation of calcification in the arterial wall and thus decreased quality of fistula in patients with chronic renal failure. The purpose of our study is to verify the relationship between arteriovenous fistula re-operation and high calcium phosphate product level. Methods Seventy-nine consecutive patients with chronic renal failure between April 2016 and February 2018 were included in the study. Patients having calcium phosphate product level ≥50 mg2/dl2 were defined as group 1, whereas those having <50 mg2/dl2 were defined as group 2. Primary outcome of interest was the need for re-operation during the follow-up and to determine the risk factors for re-operation. To determine independent predictors for re-operation, multivariate logistic regression model was used. Results The rates of redo and tredo operation were significantly higher in group 1 compared to group 2 ( p = 0.01 and 0.04). In multivariate analysis, phosphate (OR: 1.84, 95% CI: 1.00–3.40, p = 0.05) and triglyceride (OR: 1.01, 95% CI: 1.00–1.02, p = 0.04) levels for redo operation and calcium phosphate product level (OR: 1.11, 95% CI: 1.01–1.22, p = 0.03) for tredo operation were found to be independent predictors. Conclusions High calcium phosphate product level leads to increased risk of arteriovenous fistula re-operation by causing arterial stiffness in this patient group. Additionally, these re-operations place additional burden on morbidity and cost efficacy. Thus, we recommend keeping the calcium phosphate product level at the optimal level in these patients to avoid both the risk of arteriovenous fistula re-operation and the other cardiovascular problems.

scholarly journals Prevention of venous thromboembolism in hospitalized patients with chronic kidney disease

2013 ◽  
pp. 269-276
Author(s):  
Marcora Mandreoli ◽  
Antonio Santoro
Keyword(s):  
Renal Failure ◽  
Venous Thromboembolism ◽  
Renal Disease ◽  
Case Reports ◽  
Current Evidence ◽  
High Morbidity ◽  
Medical Patients ◽  
Medically Ill ◽  
Increased Risk ◽  
Therapeutic Doses

Despite the high morbidity and mortality associated with venous thromboembolism in hospitalized medical patients with a number of risk factors, and large evidence that prophylaxis is effective, prophylaxis rates remain elusive in medically ill patients. Furthermore, in patients with renal failure, prophylaxis often is omitted or sub-optimal, due to fear of provoking hemorrhage. Patients with end-stage renal disease often have platelet deficits. Low molecular weight heparin (LMWH) therapy may also be difficult to manage in these cases because LMWH clearance is largely dependent on the kidneys. Administration of LMWH to patients with some degree of renal failure may lead to bioaccumulation of anti-Xa activity with an increased risk of bleeding. In recent years, LMWH has largely replaced unfractionated heparin (UFH) for the treatment and prophylaxis of thromboembolic disease. LMWHs have been shown to be superior to UFH in the prevention of venous thromboembolism. They are also easier to administer and do not require laboratory monitoring. However, several case reports and a metaanalysis indicate that the use of LMWHs at therapeutic doses in patients with advanced renal failure can be associated with major bleeding with serious adverse effects. In this paper, we review recent evidence supporting the safety of LMWHs at prophylactic doses in patients with mild or moderate renal disease. Current evidence suggests that bioaccumulation of enoxaparin (the most widely used LMWH) can occur when the drug is used at standard therapeutic doses in patients with severely impaired renal function. This risk can be reduced by empiric dose reduction or monitoring of anti-Xa heparin levels.

scholarly journals Recognizing Common Skin and Soft Tissue Infections in the Nephrology Clinic

2018 ◽  
Vol 47 (1-3) ◽  
pp. 259-264 ◽  
Author(s):  
Karen M.  Van de Velde-Kossmann
Keyword(s):  
Renal Failure ◽  
Soft Tissue ◽  
Early Recognition ◽  
Soft Tissue Infections ◽  
Patient Morbidity ◽  
Cost Of Health Care ◽  
Increased Risk ◽  
Patient Health ◽  
Common Skin ◽  
The Cost

Renal failure patients have an increased risk of infection, including skin and soft tissue infections. This increased susceptibility is multifactorial, due to the conditions causing the renal failure as well as complications of treatment and renal failure’s innate effects on patient health. These infections have a significant impact on patient morbidity, increased hospital and procedural demands, and the cost of health care. Many renal failure patients are seen regularly by their nephrology clinic caregivers due to the need for frequent dialysis and transplant monitoring. Familiarity with common skin and soft tissue infections by these caregivers allowing enhanced patient education, optimal infection prevention, and early recognition could significantly reduce the morbidity and cost of these disorders, such as diabetic foot syndrome, necrotizing fasciitis, and herpetic infections.

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