1. CYCLED ENTERAL ANTIBIOTICS IN SUSPECTED SMALL BOWEL BACTERIAL OVERGROWTH SYNDROME - A REVIEW OF PRACTICE IN A CANADIAN TERTIARY NEONATAL CARE CENTER
Allison Callejas, MD1,2; Amitava Sur, MD1,3; Claudia Olivera, MD1,4; Boris Kuzeljevc1; Julia Panczuk, MD1
1 Department of Pediatrics, University of British Columbia, Canada; 2 Hospital Escuela Universitario, Honduras, 3Department of Neonatology, Princess Anne Hospital, University Hospital Southampton 4 Hospital Mario Catarino Rivas, Honduras
OBJECTIVES
BACKGROUND
DISCUSSION
Describe the demographic characteristics of infants diagnosed with SBS in the last 5 years in our NICU.
Compare clinical, laboratory and radiological characteristics between SBS infants who received CEA for suspected SBBO vs those who did not.
Analyze variables associated with the use of CEA among SBS patients.
Short bowel syndrome (SBS) is a clinical spectrum of disorders that occurs after resection of a large portion of small intestine, defined as prolonged need for TPN > 42 days post-resection, or residual bowel length < 25% expected 1.
Neonatal SBS is a cause of substantial morbidity & mortality, posing great challenges in interdisciplinary nutritional management & resource requirements for ongoing care2.
Incidence of surgical SBS is 0.7% VLBW infants. In Canada, reported overall incidence of SBS is 24.5/ live births2.
Major causes in neonates include NEC (35%), intestinal atresia (25%), gastroschisis (15%), malrotation and volvulus (14%)1.
Small bowel bacterial overgrowth (SBBO) occurs in up to 60 % of SBS patients3, and is caused by replacement of normal colonizing microbiome of the intestine by pathological flora, increasing clinical morbidity.
Current gold standard for diagnosing SBBO = colony count of >105 CFU/mL in intestinal aspirate or presence of colonic flora (often not clinically feasible)
Without specific markers for SBBO, clinicians may use surrogate features to guide a decision to treat, including: stoma outputs > 40ml/kg/day3, abnormal abdominal X-ray, feeding intolerance, elemental formula trial, or poor growth.
Cycled enteral antibiotics (CEA) are one of the few treatments practiced in SBBO, although there are no established guidelines & clinical practice varies.
Our current regime for treatment of suspected SBBO:
- Gentamicin PO 5mg/kg/dose Q12H X 7days, then
- Metronidazole PO 10mg/kg/dose Q12H X 7 days, then
- No antibiotics X 7 days, and restart cycle again
Retrospective cohort study of infants with SBS admitted from May December 2014 to BC Women’s & Children’s Hospital NICU and followed by our interdisciplinary Complex Nutrition Team.
Exclusions:
Infants with surgical SBS where CEA were initiated for suspected SBBO but which were stopped due to culture-proven sepsis.
Demographic & clinical data were collected from medical charts, including rationale for starting CEA if available.
Laboratory data (urea, pH, conjugated bilirubin, AG, electrolytes), abdominal x-ray results, weights, and stool outputs were collected at 3 time points:
2 weeks prior to starting CEA in those treated; at half full enteral feeds (80mL/kg/d) in those not treated
Within 1 week of starting CEA; within 2 weeks of reaching half full feeds in those not treated
After 2 CEA cycles (6 weeks post-CEA); at full feeds (160mL/kg/d) if attained in those not treated
This small descriptive study highlights the main clinical, laboratory and radiographic features of infants with SBS who have been treated with CEA for suspected SBBO in our institution.
The incidence of SBS in the past 5 years was less than that previously reported, likely due to advancements in neonatal care and NEC prevention (the most common etiology of SBS).
>50% of infants with SBS received treatment with CEA for suspected SBBO, which approximates the reported incidence of SBBO.
Poor weight gain and failure of elemental formula were significant predictors for CEA use. Bowel dilatation on X-ray was also common.
Of the 12 patients who did not achieve intestinal autonomy at discharge, 75% were treated for SBBO, which may be reflective of their degree of intestinal failure.
There was a significant decrease in conjugated bilirubin at 6 weeks among those treated with CEA. Stomal outputs significantly decreased over time among treated compared to non-treated infants. There were no differences in weight gain or other laboratory parameters between the two groups, however, a trend towards reduced incidence of post-surgical sepsis among treated infants was noted, which has previously been reported5.
The observed bilirubin drop could be attributed to weaning of TPN with increasing enteral feeds. The lack of other significant findings in clinical parameters or morbidity indicators could be due to the study’s small sample size, retrospective nature, or may reflect apparent variation in clinical practice in diagnosing & treating SBBO with CEA.
RESULTS
Figure 2: Indication for initiating CEA among infants treated (n=30).
52 patients in total were diagnosed with SBS, 30 (58%) of whom were treated with CEA for suspected SBBO
The incidence of SBS was 14/1000 NICU admissions, lower than previously reported in literature
Figure 1: Etiology of SBS
Table 1: Demographics and morbidity among infants with SBS.
Received CEA (30)
No CEA (n=22)
Gender (%)
Male : Female
19 (63%) : 11 (37 %)
12 (55%) : 10 (45%)
Gestational age (wks) (median, IQR)
32 (23, 41)
35 (23, 42)
Birth weight (gms)
1922 (490, 3520)
2055 (585, 3826)
Ileocecal valve present
Yes : No
28 (93%) : 2 (7%)
15 (68%) : 7 (32%)
Stoma present
16 (53%) : 14 (47%)
20 (91%) : 2 (9%)
Length of residual bowel4
<40 cm cm
>100 cm
8 (27%)
10 (33%)
9 (30%)
5 (23%)
10 (45%)
6 (27%)
Morbidity indicators:
LOS after initial OR (days)
117 (84, 189)
115 (74, 190)
Total TPN days
Discharged home on TPN
99 (65, 137)
9 (31%)
97 (60, 153)
3 (14%)
Infants with sepsis
11 (37%) *(p=0.055)
16 (67%)
Died in hospital
1 (3%)
3 (13%)
Figure 3: Median stomal output comparison 6 weeks post CEA (p=0.038).
METHODS
CONCLUSIONS
Figure 4: Comparison of mean laboratory values among infants who were treated with CEA and those who were not .
CEA treatment may have important clinical benefits such as improved weight gain and reduction in stomal outputs and cholestasis among SBS infants suffering from SBBO.
As CEA is among the only practiced therapeutic intervention for treating SBBO, development of improved diagnostic capabilities, prospective studies, and a comprehensive guideline for suspected SBBO & CEA treatment may be helpful to reduce practice variation and better inform our management of these complex patients.
Figure 1: Etiology of SBS among study infants (n=52).
REFERENCES
1. Wales PW et al. Neonatal short bowel syndrome: population-based estimates. J. Ped. Surg 2004; 39:690-5
2. Cole, CR, Hansen, N. Very low birth weight preterm infants with surgical short bowel syndrome: Incidence, Morbidity and Mortality and growth outcomes at 18 to 24 months Pediatrics 2008; 122:e573
3. Wessel, JJ et al Nutritional management of infants with short bowel syndrome. Semin Perinatol 2007; 31:104-11
4. Goulet, et al; Outcome and long-term growth after extensive small bowel resection in the neonatal period: a survey of 87 children. Eur J Pediatr Surg Apr;15(2):
5. Dobson et al; Cycled enteral antibiotics reduce sepsis rates in paediatric patients on long term parenteral nutrition for intestinal failure. Aliment Pharmacol Ther 2011;34:
Regression analysis: Lack of adequate weight gain 2 weeks prior was found to significantly influence the decision to use CEA (p= 0.007, OR=0.07, CI= ), as did the failure of trial of elemental formula (p=0.049, OR=4.42, CI= ). Growth deficits were common: 93% of those treated had poor weight gain pre-treatment, and 50% remained such after completed course. 59% in non-treated group remained below expected weight gain throughout.
Subgroup analysis of SBS patients treated with CEA showed significant decrease in conjugated bilirubin over time (p<0.05) (Fig 4), though no change in serum pH, urea, or weight gain after treatment. Stomal outputs significantly decreased over time among treated compared to non-treated infants (Fig 3).