Previous antibiotic use and the development of Kawasaki disease: a matched pair case‐control study

Fukazawa, Mitsuharu; Fukazawa, Mitsuru; Nanishi, Etsuro; Nishio, Hisanori; Ichihara, Kiyoshi; Ohga, Shouichi

doi:10.1111/ped.14255

Cited by 22 publications

(11 citation statements)

References 17 publications

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“…Furthermore, the strong association between KD and allergic diseases ( 99 – 101 ) in which dysbiosis plays an important role ( 102 ) also supports this perspective. Recent observations of a potential association between previous antibiotic therapy and development of KD also supports our hypothesis ( 103 ). In this study, the median interval between the final dose of antibiotics and the onset of KD was 2.5 months, which was insufficient time for restoration of the gut microbiota and complete resolution of dysbiosis caused by antibiotic use ( 104 ).…”

Section: Novel Perspectives On Kd Pathogenesissupporting

confidence: 88%

Our Evolving Understanding of Kawasaki Disease Pathogenesis: Role of the Gut Microbiota

Kaneko

Akagawa

et al. 2020

Front. Immunol.

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The etiology of KD has been studied comprehensively but remains largely unknown. The disease seems to result from the interplay of genetic and environmental susceptibility factors with infectious triggers, followed by a subsequent abnormal immune response characterized by increased levels of inflammatory cytokines and chemokines during the acute phase. Evidence has mounted to suggest that an imbalance between T helper 17 cells (Th17s) and regulatory T cells (Tregs) is associated with aberrant immune responses in KD. Recent advances in culture-independent techniques for detection and identification of intestinal commensal bacteria enabled the discovery that Th17 and Treg differentiation are regulated by short chain fatty acids (SCFAs), in particular butyrate, produced by the gut microbiota. This finding provided a mechanistic link between dysbiosis, defined as changes in the composition of the gut microbiota, and various inflammatory diseases. On this basis, we propose that dysbiosis, with reduced production of SCFAs leading to imbalances of Th17s/Tregs, could be involved in the etiology of KD. A pilot study supported this hypothesis, as only fecal concentrations of butyrate were significantly reduced in KD patients among SCFAs. This evolving perspective prompted us to undertake metagenomic analyses of bacterial DNA from the feces of KD patients who were antibiotic-naïve at diagnosis. Simultaneous measurements of Th17s/Tregs in peripheral blood and SCFA concentrations in feces would provide valuable information regarding the association between dysbiosis and dysregulated immune responses in KD.

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Section: Novel Perspectives On Kd Pathogenesissupporting

confidence: 88%

Our Evolving Understanding of Kawasaki Disease Pathogenesis: Role of the Gut Microbiota

Kaneko

Akagawa

et al. 2020

Front. Immunol.

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“…According to Seung Beom Han's report,[28]in a university hospital in Seoul from 2015 to 2016,the antibiotic use rate in the acute phase of children with KD was 54.3%.For children with KD,the di culty of early diagnosis of the disease,the markedly elevated blood counts,and persistent fever,as well as the signi cant increase in the incidence of incomplete KD in recent years,have forced clinicians to use antibiotics more.But antibiotics are not considered to be helpful in the treatment of KD,and even the ineffectiveness of antibiotic treatment is an important clue for clinicians to be alert to KD.Its use not only increases the risk of acute liver damage in children with KD,but also increases the incidence of liver damage after IVIG treatment after discontinuation of antibiotics.According to the report of Mitsuharu Fukazawa Jr. et al, [29] this may be related to the disturbance of intestinal ora associated with antibiotic use and the increased liver burden caused by the metabolism of antibiotics in the liver.…”

Section: Discussionmentioning

confidence: 99%

Factors associated with liver injury after intravenous gamma globulin treatment in children with Kawasaki disease

Ren

et al. 2022

Preprint

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Background: The etiology of liver injury in children with Kawasaki disease(KD) is not yet clear.It is common for children who are responded to intravenous gamma globulin (IVIG) therapy to develop liver injury after IVIG treatment. This research is to explore related factors of liver injury after IVIG treatment in children with KD who responded retrospectively to IVIG.Methods: A total of 806 children with KD were included in this analysis. The clinical characteristics, laboratory findings, and drug use before IVIG were collected. Difference analysis, ROC curve analysis and logistic regression analysis were performed to obtain possible risk factors for liver injury after IVIG treatment.Results: Among the clinical symptoms of the two groups of children, children with lymphadenopathy had a lower risk of developing liver injury after IVIG treatment(p=0.040),while there were no significant differences in other symptoms. Among laboratory indicators, the liver injury group had higher levels of platelet(PLT),eosinophil(EO) and brain natriuretic peptide(BNP) levels and lower hemoglobin(HB),erythrocyte sedimentation rate(ESR) and prothrombin time(PT) levels before IVIG treatment (p<0.05).There were no significant difference in c-reactive protein(CRP) and Procalcitonin(PCT)(p>0.05).The use of antibiotics, dipyridamole and aspirin doses between two groups had statistically significant differences(p>0.05).Further ROC curve analysis of aspirin dose found the optimal cut-off point of aspirin was 34.7 mg/(k*d)(the 95% CI: 0.504-0.601,p=0.026).The logistic regression analysis showed high-dose aspirin (≥34.7mg/(kg*d))was a risk factor for liver damage after IVIG treatment in KD children. Further multivariate regression analysis prompted that the use of antibiotics and higher doses of aspirin(≥34.7mg/(kg*d))in the acute phase were independent risk factors for liver injury after IVIG treatment in children with KD(Antibiotic use: OR=2.195,95%CI:1.206-3.994,p=0.01;Aspirin use: OR=1.526,95%CI:1.083-2.151,p=0.016).Conclusions: For KD children with normal liver function in the acute phase, the younger the age of KD onset, the smaller the weight, the absence of lymphadenopathy, and more elevated PLT,EO, BNP, reduced HB,ESR and PT in acute stage, the more likely to develop liver injury after treatment. There was no significant correlation between the degree of systemic inflammation(levels of CRP and PCT)in the acute phase and liver damage after IVIG treatment. The use of antibiotics and high-dose aspirin in the acute phase may be the risk factors for liver function damage after IVIG treatment in KD children.

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“…14,15 Additionally, antibiotic exposure has been directly associated with the development of systemic inflammatory states and poor outcomes seemingly unrelated to the initial indication for exposure. 7,[16][17][18] Furthermore, the microbiome has been shown to be associated with patient outcomes following injury. 19,20 A healthy commensal host microbiome plays an immunoregulatory role which can be disrupted by antibiotic exposure and stress.…”

Section: Discussionmentioning

confidence: 99%

Prior Antibiotic Exposure Is Associated With Reoperation After Elective Non-colorectal Surgery

Guidry

Medvecz

Adams

et al. 2022

The American Surgeon

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Background Recent antibiotic exposure has previously been associated with poor outcomes following elective surgery. The purpose of this study is to evaluate the impact of prior recent antibiotic exposure in a multicenter cohort of Veterans Affairs patients undergoing elective non-colorectal surgery. Methods This is a retrospective cohort study of the Veterans Affairs Surgical Quality Improvement Program, including elective, non-cardiovascular, non-colorectal surgery from 2013 to 2017. Outpatient antibiotic exposure within 90 days prior to surgery was identified from the Veterans Affairs outpatient pharmacy database and matched with each case. Primary outcomes included serious complication, any complication, any infection, or surgical site infection. Secondary outcomes included 30-day mortality, length of stay, and Clostridioides difficile infection. Results Of 21,112 eligible patients, 2885 (13.7%) were exposed to antibiotics within 90 days prior to surgery with a duration of 7 (IQR: 5-10) days and prescribed 42 (IQR: 21-64) days prior to surgical intervention. Compared to non-exposed patients, exposed patients had higher unadjusted complication rates, increased length of stay, and rates of return to the operating. Exposure was independently associated with return to the operating room (OR: 1.39; 99% CI: 1.05-1.84). Conclusions Among Veterans, recent antibiotic exposure within 90 days of elective surgery was associated with a 39% increase in the odds of return to the operating room. Further work is needed to evaluate the effects of antibiotic exposure and dysbiosis on surgical outcomes.

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Previous antibiotic use and the development of Kawasaki disease: a matched pair case‐control study

Cited by 22 publications

References 17 publications

Our Evolving Understanding of Kawasaki Disease Pathogenesis: Role of the Gut Microbiota

Our Evolving Understanding of Kawasaki Disease Pathogenesis: Role of the Gut Microbiota

Factors associated with liver injury after intravenous gamma globulin treatment in children with Kawasaki disease

Prior Antibiotic Exposure Is Associated With Reoperation After Elective Non-colorectal Surgery

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