Efficacy of Combination Antibiotic Therapy for Refractory Pediatric Inflammatory Bowel Disease

Abstract

Background Recent studies have shown that oral combination antibiotics may improve disease course in refractory inflammatory bowel disease (IBD). Here, we describe the use of combination oral antibiotics as salvage therapy in refractory ulcerative colitis (UC), Crohn’s colitis, and IBD-unclassified (IBD-U) at a large pediatric IBD center. Methods Clinical response, disease activity indices, adverse events, and clinical outcomes were measured up to 1 year after antibiotic treatment in this retrospective cohort study of children with medically refractory IBD colitis. Results Sixty-three patients with refractory UC, Crohn’s colitis, and IBD-U (median age [interquartile range {IQR}], 15.3 [11.2–16.5] years; median disease duration [IQR], 1.2 [0.41–4.6] years) received a combination of 3 or 4 oral antibiotics (most commonly amoxicillin, metronidazole, and either doxycycline or ciprofloxacin) for a median (IQR) of 29 (21–58) days. Thirty-four patients (54%) were deemed corticosteroid-refractory or -dependent, with the majority (62/63) having a previous or present loss of response or primary nonresponse to anti–tumor necrosis factor alpha (anti-TNFα) therapy. Use of combination antibiotics led to a significant decrease in median Pediatric Ulcerative Colitis Activity Index (PUCAI) score (IQR) from 55 (40–65) to 10 (0–40; P < 0.0001) over 3 ± 1 weeks, with 25/63 (39.7%) patients achieving clinical remission (PUCAI <10 points). The clinical benefits of oral antibiotics were independent of anti-TNFα therapy optimization. Among children entering clinical remission (n = 25), only 1 patient required surgery at 1-year follow-up, vs 10 patients in the nonresponder group. Negative predictors of response to combination antibiotics were exposure to doxycycline (odds ratio [OR], 0.25; 95% CI, 0.08–0.76) and PUCAI ≥65 at baseline (OR, 0.2; 95% CI, 0.05–0.74). Conclusions Oral combination antibiotics appears to be an effective rescue and steroid-sparing therapy to induce remission in the short term in patients failing a biologic.

Colitis susceptibility in mice with reactive oxygen species deficiency is mediated by mucus barrier and immune defense defects

“…Even more effective was antibiotic treatment. CGD patients are often placed on antimicrobial prophylaxis, and non-absorbable antibiotics were also beneficial in a cohort of pediatric IBD patients, [42][43][44] suggesting that reducing certain phyla or the overall bacterial load might be a promising treatment.…”

Antibiotics in pediatric inflammatory bowel diseases: a systematic review

“…The results showed that combination therapy may serve as effective rescue or steroidsparing therapy in this population. Additionally, children who responded to antibiotic therapy showed a similar positive response to a second course of treatment for a disease flare [78]. Effectiveness in steroid resistant UC was also seen by Kordy et al [79].…”

“…There have been a few descriptive studies on the use of antibiotics in clinical practice (Table 4). The biggest retrospective cohort comes from Breton et al, who retrospectively reported on 63 children with moderate to severely active IBDcolitis (CD 42.8%, UC 36.5%, IBD-U 20.6%), refractory to steroids or failing a biological [78]. A combination of 3-5 oral antibiotics (amoxicillin, doxycycline, metronidazole, ciprofloxacin, vancomycin) led to clinical response in 65.3% children and clinical remission in 39.7%.…”

Physiologically based pharmacokinetic‐pharmacodynamic evaluation of meropenem plus fosfomycin in paediatrics

“…There is an increasing use of combination antibiotic therapies, such as salvage regimens for multidrug‐resistant infections, especially those due to β‐lactamases and carbapenemases 48–50 . The current study is an important addition to the evaluation of suitable dosing regimens for combination antibiotic therapy against multidrug‐resistant bacteria, especially in the paediatric population.…”