INTRODUCTION Allogeneic stem cell transplant (allo-SCT) patients are at high risk for severe life threatening bacterial infections. Although the prevalence and pattern of resistance varies among centres and countries, there is a growing global problem of resistance to antibiotics. The consequent increased use of broad spectrum antibiotics and injudicious antibiotic policies have contributed to the selection of multidrug resistant (MDR) pathogens. Translocation of organisms which normally colonize the gut into the bloodstream during the febrile neutropenia (FN) has long been postulated as a pathogenic factor for life threatening gram negative infections. This hypothesis had led to utilization of various methods of peritransplant gut decontamination. Our centre has a policy of performing surveillance stool cultures for all patients prior to transplant. While initially our antibiotic policy was independent of any surveillance culture, over recent years stool surveillance culture sensitivity has guided our choice of first line antibiotics in the post transplant FN. This retrospective analysis is aimed at comparing the outcomes of empirical versus surveillance stool culture guided selection of antibiotics in the immediate post allo-SCT FN. METHODOLOGY This was a retrospective analysis of 190 allo SCT patients from January 2008 to December 2014 at our centre. During the post transplant FN, patients were categorized into two groups. Group-1 (Empirical: n=48) received first line broad spectrum antibiotics as per our hospital policy i.e. cefoperazone + sulbactum combination with amikacin. Group-2 (Surveillance based: n=119) received first line antibiotics based on sensitivity pattern of stool surveillance culture. In both groups, escalation to second line antibiotics (carbapenems with or without colistin or tigecycline) was done if defervescence did not occur in 24-48 hours or blood cultures grew a resistant organism or if there was any clinical deterioration. The primary endpoint was defervescence rate after first line antibiotics in both groups. Secondary endpoints were need for second line antibiotics, duration of total antibiotic use, concordance between blood and surveillance stool culture, incidence and causes of mortality, prevalence of MDR organisms in stool surveillance culture and change in trend of resistant organisms in stool surveillance cultures over last 7 years. RESULTS One ninety patients underwent allo-SCT from January 2008 to December 2014.The median age of the cohort was 26 years (range 3-57 years) with 136 males and 54 females. The diagnoses were AML-75, ALL-46, CML-19, aplastic anemia-18, MDS-12 and others-20. Group 1 (Empirical) had 48 patients, while 119 were in Group 2 (Surveillance based). Twenty three patients did not have any growth in stool surveillance. In group 1, defervescence to first line antibiotics occurred in 23 (48 %) patients, whereas in group 2, it occurred in 78 (66 %) patients (P= 0.05). Defervescence within 24 hours was seen in 18 (37.5 %) patients in group 1 and 67 (56.3 %) patients in group 2 (P= 0.0425). In group 2, 34.5 % patients required escalation to second line antibiotics, compared to 54 % patients in group 1 (P = 0.0294). The median duration of total antibiotic use was 17.5 days in group 1 and 18 days in group 2 (P= NS). The concordance between blood culture and surveillance stool culture was seen in 3 (1.76 %) patients. There was no significant difference in infection related mortality between the two groups as shown in the figure 1. The prevalence of resistant organisms in the baseline surveillance stool culture changed between the periods 2008-2011 and 2012-2014. The incidence of extended spectrum beta lactamase (ESBL) organisms decreased from 79.66 % in 2008-2011 to 62.1 % in 2012-2014 (P = 0.0351). The incidence of carbapenem resistant (15.25 % vs. 25.26 %), colistin resistant (1.69 % vs. 2.1 %) and vancomycin resistant enterococcus (VRE: 3.38 % vs. 10.52 %) increased from 2008-2011 to 2012-2014 period. The increase in the combined incidence of carbapenem resistant, colistin resistant and VRE was from 20.32 % to 37.86 % (P = 0.0351). CONCLUSION Stool surveillance guided antibiotic usage leads to earlier defervescence in higher number of patients, while also reducing the need for second line antibiotics in patients undergoing allo-SCT. A randomized study is required to prove the importance of stool surveillance in this setting. Disclosures No relevant conflicts of interest to declare.
Background:Atopic dermatitis (AD) is a common skin condition with a prevalence of 2–10% in adults1. IL-4 and IL-13 play a key role in the pathogenesis. Dupilumab, a human IgG4 monoclonal antibody binding the alpha subunit of the IL-4 receptor, blocking IL-4 and IL-13 signaling, has important efficacy in this difficult to treat disease. We first reported a musculoskeletal (MSK) adverse effect of enthesis/arthritis developing in 3 patients in 20192.Objectives:To report the ongoing experience at our centre of this new clinical paradigm, incidence and patient progress including clinical presentation, imaging and management.Methods:Clinical and radiological data was collected from electronic case records of all cases presenting with features of enthesitis/arthritis between October 2018 and January 2021.Results:Since initiation of dupilumab at GSTT, approximately 400 adults with moderate-to-severe AD have received at least one dose. Of these, 23 patients (14 men, 9 women) had the clinical syndrome of inflammatory enthesitis/tenosynovitis/arthritis. Nine patients had both enthesitis and arthritis, 10 enthesitis, 3 enthesitis and tenosynovitis and 1 arthritis only. Four of these also reported new onset inflammatory back pain symptoms. None had a preceding history of arthritis or enthesitis. Median onset of symptoms following initiation of dupilumab was 4 months. However, onset of symptoms ranged between 2 weeks and 48 months. Imaging (US/MRI) was performed in 18 patients, 11 with Doppler US positive enthesitis confirming clinical findings. Most common sites were lateral epicondyles, achilles and patella tendons. Two patients with more disabling symptoms had MRI confirmed gluteus medius and hamstring enthesitis and arthritis. Spine and SI joint MRI in 4 patients was negative. Most patients had normal inflammatory markers except 2; CRP 117, ESR 96 and CRP 13, ESR 10. All patients had very good AD response to dupilumab, average EASI score before and after Dupilumab was 21 and 4.2 respectively. One patient developed skin manifestations of guttate psoriasis, with subsequent disabling arthritis/enthesitis. Due to the life-changing beneficial effect of dupilumab therapy most patients did not want to stop therapy. We used NSAID therapy, etoricoxib/celecoxib/naproxen for symptom relief which was usually partly effective allowing continuation of dupilumab treatment in most. Five patients with severe MSK symptoms stopped Dupilumab completely. Some patients temporarily paused therapy but re-started as their AD became worse, often changing from the usual 2 weekly to 4 weekly dosing. Most patients continuing dupilumab had persistent MSK symptoms. Four patients who stopped dupilumab were treated with baricitinib, which has potential efficacy for both MSK symptoms and AD. Two did not tolerate it and remained on NSAID therapy.Conclusion:These data further characterize a new syndrome of enthesitis and/or arthritis induced by Dupilumab. In those with mild MSK symptoms use of NSAIDs allows continuation of full-dose dupilumab, in moderate cases reducing dupilumab dose frequency plus NSAID therapy maintains function. Most patients had on-going MSK symptoms. In more severe cases JAKi therapy may be an effective strategy. Our initial hypothesis that inhibition of IL-4/13 by dupilumab triggers an IL-17/23/TNF-mediated inflammatory MSK syndrome in some patients is supported by a recent in vitro study3.References:[1]Beck L et al. Dupilumab Treatment in Adults with Moderate-to-Severe Atopic Dermatitis. July 10, 2014. N Engl J Med 2014; 371:130-139[2]Willsmore ZN et al. Development of inflammatory arthritis and enthesitis in patients on dupilumab: a case series. Br J Dermatol 2019; 0. doi:10.1111/bjd.18031.[3]Bridegwood C et al. Regulation of entheseal IL-23 expression by IL-4 and IL-13 as an explanation for arthropathy development under dupilumab therapy. Rheumatology (Oxford). 2020 Nov 30:keaa568. doi: 10.1093/rheumatology/keaa568Disclosure of Interests:Joseph Nathan: None declared., Catherine Hughes Speakers bureau: Presented for Abbvie, Samir Patel: None declared., Libin Mathew: None declared., Catherine Smith Grant/research support from: Grants/research support; Professor Smith is a PI/CoPI on a number of commercially supported studie (Abbvie, Janssen, Leo, Sanofi)., Andrew Pink Paid instructor for: Speaker or advisor to Lilly, Abbvie, Sanofi, Leo, Almirall, Novartis, Janssen, UCB, Galderma, BMS, La-Roche Posay, Richard Woolf: None declared., Bina Menon Speakers bureau: Presented for Abbvie, L Bruce Kirkham Grant/research support from: Professor Kirkham has received honoraria and/or research funding from AbbVie, Eli Lilly, Gilead, Janssen, Novartis, Pfizer and UCB.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.