Introduction

Top Abstract Introduction Participants and methods Results Discussion References

Percutaneous endoscopic gastrostomy is commonly used for long term enteral feeding of patients with severe dysphagia.^1-5 The most common complication is peristomal wound infection,^5-11 and some centres routinely use antibiotic prophylaxis. ^{2 12} Conflicting results, however, have been obtained in prospective clinical trials of antibiotic prophylaxis in percutaneous endoscopic gastrostomy, and its value in reducing wound infection rates is controversial.^8-11 To resolve the issue, we planned a large, prospective, randomised, double blind, multicentre study of antibiotic prophylaxis in percutaneous endoscopic gastrostomy.

	Participants and methods

Top Abstract Introduction Participants and methods Results Discussion References

Eligible patients were at least 18 years of age and were referred for percutaneous endoscopic gastrostomy because of dysphagia. Exclusion criteria were a contraindication to percutaneous endoscopic gastrostomy; known allergy to a penicillin, treatment with any antibiotic within the past 4 days, neutropenia (<500 cells/µl), or serum creatinine concentration >300 µmol/l. Patients could be entered into the study only once. Written informed consent was required, and the study was approved by the ethics boards of the participating centres.

We conducted a double blind, placebo controlled, clinical trial at six German hospitals and the full version of this manuscript is reported on the BMJ's website according to the CONSORT statement. The trial was prematurely stopped after an adaptive interim analysis showed a significantly higher infection rate in the control group.

About 30 minutes before endoscopy patients received either 2.2 g co-amoxiclav or identical appearing saline by short intravenous infusion. Percutaneous endoscopic gastrostomy was performed by the thread pull method.¹

The patients were followed for at least 7 days. Monitoring included the measurement of body temperature three times daily, recording of peritoneal irritation and abdominal pain, and assessment of potential adverse events and clinical complications.

The peristomal region was examined daily, cleaned, and bandaged dry without antiseptic ointments. Peristomal erythema, induration, and wound secretions were noted and scored as proposed by Jain et al.⁹ When purulent secretion was suspected we collected material for microscopy and culture. Peristomal wound infection was defined either as a score >8 points or as microscopic evidence of suppurating secretion. The infection was considered clinically important if surgery or systemic antibiotics were required. We recorded the occurrence of peristomal wound infection as defined above and of any other infection that required surgery or systemic antibiotics within 7 days after gastrostomy as a primary efficacy variable.

Fisher's exact test was used to compare proportions. Wilcoxon's test was used to assess quantitative variables. The time to onset of infection was analysed by Kaplan-Meier estimates and a log rank test.

	Results

Top Abstract Introduction Participants and methods Results Discussion References

Of the 106 patients enrolled, 97 were included in the intention to treat anlysis and 84 were evaluable according to protocol. Three patients developed non-infectious complications including bleeding, hypotension, and peritoneal irritation with abdominal pain. None of these complications was fatal.

Most of the patients had dysphagia due to malignant disease (65%), and many patients had serious comorbidity (76%). Patients in both arms had comparable baseline characteristics (table 1).

View larger version (17K): [in this window] Kaplan-Meier plots showing time to infection (any site) and time to clinically important wound infection (requiring medical or surgical treatment) after percutaneous endoscopic gastrostomy among 84 evaluable patients receiving co-amoxiclav or placebo for prophylaxis. P values are from log rank tests

Eight of 41 (20%) patients in the antibiotic arm developed any infection compared with 28 of 43 (65%) patients receiving placebo (P<0.001). Peristomal wound infection was diagnosed in six (15%) patients who had received co-amoxiclav and 19 (44%) who had received placebo (P=0.004). Only one patient who received co-amoxiclav developed clinically important wound infection compared with 11 who received placebo (P=0.003). The figure shows the time to infection in the two groups.

An intention to treat analysis confirmed the differences in infection rates (table 2).

A total of 20 adverse events were reported in 19 patients who received co-amoxiclav and 26 in 18 patients who received placebo. Adverse events that were possibly or probably related to the study medication included nausea (one patient) and seizure (one) in the co-amoxiclav group and vomiting (one) and suspected allergic exanthema (one) in the placebo group. Seven patients in the antibiotic arm and eight in the placebo arm died within 30 days after gastrostomy. One patient in the antibiotic arm died of pneumonia (on day 16) compared with three in the placebo arm (days 5, 10, and 21); the remaining deaths were due to underlying disease.

	Discussion

Top Abstract Introduction Participants and methods Results Discussion References

Our study shows that antibiotic prophylaxis with a single dose of co-amoxiclav reduces infection after percutaneous endoscopic gastrostomy. The study was larger than previous studies of antibiotic prophylaxis in percutaneous endoscopic gastrostomy,^8-11 two of which found no reduction in the incidence of peristomal wound infection.^{8 11}

We studied mainly patients at increased risk of infection such as cancer patients and patients admitted to hospital for various reasons. Many of our ambulatory, healthier patients were not randomised because they could not be followed up for at least 7 days. Malignancy has previously been associated with an increased risk of complication after percutaneous endoscopic gastrostomy. ^{13 14} The risk of infectious complications after percutaneous endoscopic gastrostomy is high: in one study the overall incidence of infection was 42%,¹⁰ and patients receiving placebo had a 32% increased risk of wound infection.⁹ Previous studies have reported low rates of wound infection requiring treatment among patients given antibiotic prophylaxis.^{9 10} These rates are comparable with the 2% that we observed.

The choice of prophylactic regimen is unlikely to account for the differing results of previous trials. A single dose of co-amoxiclav (and probably of other comparable antibiotics) may be sufficient prophylaxis against wound infections after percutaneous endoscopic gastrostomy, as it is for prophylaxis in gastrointestinal surgery.¹⁵

The mortality within 30 days after gastrostomy was in both groups similar to that reported in other studies.^16-18 Although we observed a lower rate of non-wound infections (including pneumonia) in antibiotic recipients than placebo recipients, this did not seem to affect survival. This is not surprising since a single dose of an antibiotic is unlikely to affect rates of infection and associated complications several weeks later.

We recommend giving antibiotic prophylaxis before percutaneous endoscopic gastrostomy. It is well tolerated, easy to perform, and reduces morbidity and the need for treatment because of infection. Our results show that a single intravenous dose of co-amoxiclav is effective.

	Acknowledgments

We thank Birgit Hay and Beate Maute for data management and Martina Kron, department of clinical documentation and biometry, University of Ulm, for performing the interim analysis.

Contributors: WVK was the study coordinator and principal investigator and was responsible for data analysis and interpretation. GP and AH participated in the study design and data interpretation. KM participated in the study design and acted as monitoring supervisor. SG, HGL, JL, and WH were local investigators and participated in the data interpretation. All authors contributed to revision of the manuscript. GP and WVK are guarantors.

	Footnotes

Funding: The study was in part supported by a clinical research grant from SmithKline Beecham Pharma, München, Germany.

Competing interests: KM is employed by SmithKline Beecham, which makes co-amoxiclav.

	References

Top Abstract Introduction Participants and methods Results Discussion References

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(Accepted 26 March 1999)