Adjuvant use of combination of antibiotics in acute severe ulcerative colitis: A placebo controlled randomized trial

Mishra, Shubhra; Mandavdhare, Harshal; Singh, Harjeet; Choudhury, Arup; Shah, Jimil; Ram, Sant; Kalsi, Dimple; Samanta, Jayanta; Prasad, K. N.; Sharma, Arun; Dutta, Usha; Sharma, Vishal

doi:10.1080/14787210.2021.1856656

Cited by 18 publications

(10 citation statements)

References 22 publications

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“…In consonance with recent reports of severe and fatal toxicity of thiopurine in those homozygous for NUDT15 polymorphisms, our study makes a strong case for pre-emptive testing for these in South Asian populations [ 22 , 23 ]. Further, in centers and populations where the biologic use is not common including those where steroids and cyclosporine (as second line therapy in acute severe colitis) continues to be used for IBD, azathioprine is an important drug for maintenance of remission and therefore preemptive testing of NUDT15 polymorphisms may help improve tolerance to thiopurine therapy [ 21 , 24 ].…”

Section: Discussionmentioning

confidence: 99%

TPMT and NUDT15 polymorphisms in thiopurine induced leucopenia in inflammatory bowel disease: a prospective study from India

et al. 2021

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Background Polymorphisms in thiopurine methyltransferase (TPMT) and Nudix hydrolase-15 (NUDT15) have been implicated as the predominant cause of thiopurine induced leukopenia in the Western countries and East Asia respectively. Exact role of these polymorphisms in South Asian population with inflammatory bowel disease (IBD) is uncertain. Methods We included consecutive patients with IBD who were initiated on thiopurines at a center in North India. The dosage of thiopurines was titrated using regular monitoring of hemogram and liver function tests. Three TPMT polymorphisms (c.238 G > C, c.460 G > A, and c.719A > G) and one NUDT15 polymorphism (c.415 C > T) were assessed. Comparison regarding incidence of leukopenia and maximum tolerated thiopurine dosage was performed between those with wild polymorphism and those with TPMT and NUDT15 polymorphisms, respectively. Results Of the 119 patients (61 males, mean age 36.8 ± 13.5 years), 105 (88.2%) had ulcerative colitis and 14 (11.8%) had Crohn’s disease. Leukopenia was noted in 33 (27.7%), gastrointestinal intolerance in 5 (4.2%) and pancreatitis in 2 (1.6%). TPMT polymorphisms were detected amongst five patients of whom 1 developed leukopenia. NUDT15 polymorphism was noted in 13 patients of whom 7 had leukopenia. The odds of developing leukopenia in TPMT polymorphism were non-significant (0.77, 95% CI:0.0822 to 7.2134, P = 0.819) but were significantly higher in those with NUDT15 polymorphism (3.5933, 1.1041 to 11.6951, P value: = 0.0336). Conclusion NUDT15 polymorphism was more frequent than TPMT polymorphisms and was associated with thiopurine induced leukopenia. However, the tested polymorphisms account for only 24.2% of the risk of thiopurine induced leukopenia.

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Section: Discussionmentioning

confidence: 99%

TPMT and NUDT15 polymorphisms in thiopurine induced leucopenia in inflammatory bowel disease: a prospective study from India

et al. 2021

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“…For instance, Mishra et al 21 administered a combination of ceftriaxone and metronidazole to acute severe patients, and the outcomes did not show a significant difference between the antibiotics and placebo groups. 21 Their primary outcome was on day 3, and their focus was exclusively on severe patients. Similarly, Chapman et al 17 treated severe patients with either metronidazole alone or placebo for 5 days, and the results indicated no significant difference in clinical improvement.…”

Section: Discussionmentioning

confidence: 99%

“…Several factors, such as the spectrum of antibiotics and duration of the intervention, appear to influence the effectiveness of antibiotics therapy. For instance, Mishra et al 21 administered a combination of ceftriaxone and metronidazole to acute severe patients, and the outcomes did not show a significant difference between the antibiotics and placebo groups. 21 Their primary outcome was on day 3, and their focus was exclusively on severe patients.…”

Section: Discussionmentioning

confidence: 99%

“… 20 However, in another randomised trial with severe acute UC patients, no difference in treatment outcome was observed between the treatment group given intravenous ceftriaxone and metronidazole on top of the standard care and the placebo group. 21 Collectively, meta-analyses have concluded that the effectiveness of antibiotics for active UC is statistically significant, with an odds ratio of 2.17 for UC improvement. 22 , 23 Accordingly, certain choices of antibiotics might contribute to suppressing increased UC disease activity, yet due to the heterogeneity of previous studies, it remains unclear which agents are effective for UC patients.…”

Section: Introductionmentioning

confidence: 99%

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Long-term outcomes of antibiotic combination therapy for ulcerative colitis

Nishikawa

Sato

Tsukinaga

et al. 2021

Therapeutic Advances in Chronic Disease

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Aims: An antibiotic combination of amoxicillin, tetracycline and metronidazole (ATM) is effective for ulcerative colitis (UC), but this regimen is discontinued in some cases due to adverse events. This study aimed to assess a revised combination, namely, amoxicillin, fosfomycin and metronidazole (AFM), in UC patients with the goal of reducing side effects while maintaining therapeutic efficacy. Methods: A prospective open-label trial was undertaken in 104 adult UC patients. A combination of oral amoxicillin (1500 mg), fosfomycin (3000 mg) and metronidazole (750 mg) was administered to patients daily for 2–4 weeks in addition to their conventional medication. Clinical assessment was performed using the Lichtiger index before treatment and at 0, 3, 6, 9 and 12 months and 2 and 3 years. Endoscopic evaluation was performed using the Mayo score before treatment and at 3 and 12 months. Results: The compliance rate was 99.2%. Response and remission rates were 80.8% and 63.5% at completion, 73.1% and 64.4% at 3 months, and 39.4% for both at 12 months, respectively. Of the 41 patients who were in remission at 12 months, 63.4% maintained that status until the 2-year follow-up. Similarly, 69.2% of those in remission at 2 years remained relapse free at the 3-year follow-up. Side effects were observed in 44.2% of the participants. Fever occurred in one patient (1.0%), which was lower than the rate observed with ATM therapy. Conclusion: These results indicate that AFM therapy induces remission and is appropriate for long-term maintenance of UC while producing fewer and milder adverse events than ATM therapy. Clinical trials: This study was registered in the University Hospital Medical Information Network (No. R000046546).

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“…Since only two agents, cyclosporine and infliximab, are currently standards of treatment in steroid refractory ASUC it is important not to deny the benefit of these drugs to eligible patients. In particular, cyclosporine is a cheap drug which can be used in most resource-constrained setting and therefore such recommendations should be based on evidence [2]. While hypomagnesemia is easily correctable, the correction of cholesterol levels is difficult and could potentially make a substantial group ineligible due to underlying malnutrition in these patients.…”

Section: Dear Editormentioning

confidence: 99%

Acute severe ulcerative colitis: management advice for internal medicine and emergency physicians—comment

2021

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Adjuvant use of combination of antibiotics in acute severe ulcerative colitis: A placebo controlled randomized trial

Cited by 18 publications

References 22 publications

TPMT and NUDT15 polymorphisms in thiopurine induced leucopenia in inflammatory bowel disease: a prospective study from India

TPMT and NUDT15 polymorphisms in thiopurine induced leucopenia in inflammatory bowel disease: a prospective study from India

Long-term outcomes of antibiotic combination therapy for ulcerative colitis

Acute severe ulcerative colitis: management advice for internal medicine and emergency physicians—comment

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