Antibiotic prophylaxis in gastrointestinal endoscopy



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8. COLONISATION OF VASCULAR GRAFTS/STENTS AND ORTHOPAEDIC, NEUROSURGICAL AND OTHER NON-CARDIAC PROSTHESES
8.1 It has been suggested that some delayed infections of orthopaedic, neurosurgical and

other prostheses may be due to haematogenous spread of bacteria following endoscopy or surgery. If so, the incidence of such infections might be reduced by more widespread use of antibiotic prophylaxis in both dentistry and endoscopy. As bacteraemia occurs during activities as trivial and as frequent as tooth brushing (10,11), there appears to be minimal benefit from such treatment. Lifelong antibiotic prophylaxis for all patients with orthopaedic, neurosurgical and other implanted prosthetic materials would be more logical but adverse effects would almost certainly outweigh any potential benefit.


8.2 We are in agreement with the American Society of Colon and Rectal Surgeons in their view that the risk following colonic and rectal endoscopy is low for patients with orthopaedic prostheses, central nervous system vascular shunts, penile prostheses, intra ocular lenses, pacemakers and local tissue augmentation materials (64). We do not recommend the use

of prophylactic antibiotics in this setting.


8.3 Expert opinion has suggested that patients who have undergone vascular grafting and/or endovascular stenting within the preceding 3 months should be treated in the same manner as patients at moderate endocarditis risk. Selective antibiotic prophylaxis should be administered to cover the endoscopic procedures commonly associated with bacteraemia (Table 4).

9. PERCUTANEOUS ENDOSCOPIC GASTROTOMY (PEG)
Early evaluations of single-dose intravenous cephalosporins failed to demonstrate efficacy in the prevention of peristomal infections (65,66). The last ten years have witnessed a wealth of controlled trials in this area. The evidence from these is consistent and indicates that antibiotic prophylaxis is effective at reducing wound infection rates using a single dose of an appropriate antibiotic (67-74). A meta-analysis also comes out in favour of antibiotic prophylaxis, suggesting a number needed to treat of 5.7 to prevent one peristomal infection (75). A second or third generation cephalosporin or co-amoxiclav given intravenously are both effective, and there is also some evidence that antibiotic prophylaxis is cost-effective (76). Many patients who claim to be allergic to penicillin will have previously received a cephalosporin without incident, and, cefuroxime can be used in this setting. Cefuroxime can be given safely to most patients who have a history of penicillin allergy (77), but should be avoided in people who have a clear history of anaphylaxis with penicillin and/or cephalosporins. In such circumstances an infusion of clindamycin (300mg in adults) will cover staphylococci and most streptococci excluding enterococci.
Three areas of uncertainty remain on this topic. Firstly many patients undergoing PEG are already receiving courses of broad-spectrum antibiotics, and there is some evidence that wound infections are less common in this group (65, 67, 73). Such patients may not need further prophylaxis, and the use of additional antibiotics could predispose to methicillin-resistant Staphylococcus aureus (MRSA) colonisation. Secondly, the most common end-point in clinical trials of antibiotic prophylaxis is the development of peristomal wound infections, many of which are of doubtful clinical importance. Notwithstanding this caveat, there is some evidence that single-dose intravenous antibiotic may help in preventing more serious infections such as aspiration pneumonia (68, 71, 74). Thirdly, a significant proportion of peristomal infections are MRSA-related, particularly in patients with nasopharyngeal colonisation (78.79). It has recently been suggested that MRSA decolonisation using oral and nasally delivered preparations might reduce the risk of MRSA-related peristomal infection in such patients (80). The possible role of prophylaxis with vancomycin in patients with MRSA colonisation requiring PEG remains to be determined.


10. Antibiotics in variceal bleeding
Bacterial infections occur within 48 hours of admission in about 20% of patients with cirrhosis with upper gastrointestinal bleeding (81). Variceal sclerotherapy in the emergency setting commonly causes bacteraemia (43). Prognosis in terms of rebleeding, failure to control bleeding, and in-hospital outcome is worsened in patients with associated bacterial infection. (82,83). In a meta-analysis of five controlled trials of antibiotic prophylaxis in patients with variceal bleeding, their use was associated with significantly improved short term survival (84). A Cochrane review also suggests that patients with cirrhosis and upper gastrointestinal bleeding should receive antibiotic prophylaxis (85). Patients with suspected variceal bleeding should already have been commenced on antibiotics before endoscopy. There is limited evidence to suggest superiority of any particular regimen in this setting (86) but a combination of cefuroxime and metronidazole, or co-amoxiclav alone, are reasonable choices. Intravenous ceftriaxone has been shown to reduce infection risk more effectively than oral norfloxacin in one study (87). Third or fourth-generation cephalosporins (or co-amoxyclav) should be employed in patients with co-existing spontaneous bacterial peritonitis (88).

11. ENDOSCOPIC ULTRASOUND

Although bacteraemia following endoscopic ultrasound (EUS) with fine needle aspiration (FNA) is uncommon (89-91), infective complications can occur following aspiration of pancreatic cystic lesions (92-96). It is therefore recommended that endocarditis prophylaxis is given to patients at moderate or high cardiac risk undergoing EUS-guided therapeutic endoscopy. Patients at low risk may require antibiotic cover for therapy, especially if there is a possibility of pre-existing infection within a cyst or cavity being treated. Endoscopic ultrasound guided FNA does not require antibiotic prophylaxis unless the patient is at high endocarditis risk (97).



12. ANTIBIOTIC RECOMMENDATIONS


    1. Ampicillin and amoxicillin

Gram-positive bacteria, especially streptococci and enterococci, cause most infective endocarditis. Because of the possibility sequelae from enterococcal bacteraemia, particularly after instrumentation of the lower gastrointestinal tract, ampicillin or amoxicillin

are preferred to penicillin for prophylaxis. All three are effective in killing most oral streptococci.
12.2 Aminoglycosides
The use of an aminoglycoside such as gentamicin increases the bactericidal power of ampicillin or amoxicillin against streptococci and enterococci. Although the use of one or two doses only of gentamicin confers negligible risk of nephro-or ototoxicity, care must be taken in patients with a history of pre-existing renal impairment and/or a history of gentamicin nephrotoxicity. Gentamicin is also active against most aerobic coliforms (and most Pseudomonas sp.) and is also suitable for use in neutropaenic patients.
12.3 Ciprofloxacin
Ciprofloxacin has good antimicrobial activity against aerobic gram-negative bacteria but is much less active against many gram-positive species, including enterococci. It is therefore not suitable for prevention of endocarditis but is widely used for the prevention of gram-negative sepsis after ERCP (98-101). Oral ciprofloxacin is considerably cheaper than the intravenous preparation and results in adequate blood concentrations.
12.4 Glycopeptides

Glycopeptides such as vancomycin or teicoplanin, with a very broad spectrum of activity against gram-positive bacteria, have a role when the patient has been exposed in the recent past to penicillin, ampicillin or amoxicillin, and in patients who are allergic to penicillins. However, though still uncommon in the UK, vancomycin resistant enterococci (VRE) are being encountered with increasing frequency in some hospitals. Teicoplanin is recommended in preference to vancomycin for two reasons; firstly it is simpler and quicker to administer, and secondly more sustained blood levels occur following a single dose (49).


12.5 Other beta lactam agents

The incidence of enterococcal infections is increasing rapidly in some countries at present, often associated with heavy use of cephalosporins. Cephalosporins have no activity against enterococci and are therefore inappropriate for endocarditis prophylaxis. As they have an overall broad spectrum of activity (particularly against coliforms) and are present in bowel contents, extensive use of cephalosporins has been associated with outbreaks of



Clostridium difficile enterocolitis. Ureidopenicillins, for example piperacillin, are also broad spectrum agents but with limited activity against most strains of staphylococci. Like cephalosporins, they may provoke Clostridium difficile enterocolitis.

12.6 Immunocompromised patients
Neutropenia predisposes to septicaemia after endoscopy (9), though the magnitude of the increased risk is not clear. Patients with severe neutropenia (<0.5 x109 /litre) who are febrile should have already been established on empirical antibiotic therapy according to local haematology protocols. Afebrile patients with a neutrophil count below 0.5 x109 /litre should be offered antibiotic prophylaxis for those gastrointestinal endoscopic procedures which are known to be associated with a high risk of bacteraemia (Table 1). Gram-negative aerobic (and less frequently anaerobic) bacteria including Escherichia coli are the most likely pathogens in these conditions and the choice of prophylactic antibiotics should reflect the local sensitivities of organisms.
There are no data to establish whether patients with a normal neutrophil count but who are nevertheless immunocompromised (e.g. through drug treatment following organ transplantation) are at an increased risk of infective complications following endoscopy. Until such time as data become available we do not recommend antibiotic prophylaxis routinely for this group. Routine antibiotic prophylaxis is not recommended in patients with HIV infection.
13. CONCLUSIONS AND SUGGESTED TOPICS FOR FURTHER RESEARCH
13.1. Endocarditis is an illness that can be associated with devastating and/or life-threatening complications. While the evidence favouring antibiotic prophylaxis is limited, there is increasing consensus among cardiology, microbiology and gastroenterology specialty groups that the spectrum of cover should be extended to encompass patients at moderate cardiac risk undergoing therapeutic procedures associated with a high risk of bacteraemia. In order to better understand the true risk of post-procedure endocarditis it would be useful if specialist societies could gather a database of endocarditis following endoscopy.
13.2. Percutaneous endoscopic gastrostomy: There is good evidence favouring antibiotic prophylaxis in the prevention of PEG-associated wound infection, but there is uncertainty regarding its value in the prevention of more serious infections such as peritonitis or aspiration pneumonia. MRSA, and its importance in such wound infections, is worthy of further study. The report that the risk may be reduced by local measures, such as oral disinfection, requires confirmation.
13.3. ERCP: The strategy of selective administration of prophylactic antibiotics to patients with biliary obstruction (according to the criteria set out in 7.2.4 and 7.2.5), with immediate antibiotic commencement in patients for whom suboptimal drainage is achieved, deserves prospective evaluation. There should be better understanding of the frequency with which quinolone-resistant gram negative bacteria complicate therapeutic ERCP. Ciprofloxacin resistance is becoming increasingly common, and for patients undergoing ERCP would be expected to be more of a problem in patients with a history of prior biliary manipulations, such as sphincterotomy and/or stent insertion for stones, primary sclerosing cholangitis or malignant disease. There is a need to perform multicentre studies of cholangitis and bacteraemia following repeat ERCP in patients with a history of prior therapeutic ERCP.


    1. Immunosuppressed patients. Antibiotic prophylaxis for therapeutic endoscopy is recommended for patients with neutropaenia, advanced haematological malignancy and a history of liver transplantation. It remains unclear whether patients on immunosuppressive agents are at increased risk of infective complications following therapeutic endoscopy, and prophylaxis is not recommended for such patients. It is likely that a large multicentre collaboration would be required in order to address this topic.


14. FOOTNOTE

At the time of our completing the final draft of these guidelines, the American Heart Association published their 2007 advice that antibiotics need not be administered to patients solely for the indication of preventing endocarditis following gastrointestinal or genitourinary procedures (102). For the time being we continue to recommend endocarditis prophylaxis in selected circumstances until further information is available.


15. ACKNOWLEDGMENTS

Professor Mike Bramble was the author of the preceding version of these guidelines. Some changes to this version were made on advice from Prof Peter Cotton. Dr Norman Simmons and Dr David Durack commented helpfully on earlier versions of this report. The Working Party was chaired by Robin H Teague, Torbay Hospital, and valuable advice and assistance was given by Suzannah J Eykyn, Emeritus Professor of Microbiology, Guys and St Thomas’s Hospitals.



16. AUTHORSHIP

This guideline was prepared by members of the Endoscopy Committee of the British Society of Gastroenterology, with valuable assistance from members of the British Cardiac Society and British Society for Antimicrobial Chemotherapy.


Miles C Allison, Royal Gwent Hospital, Newport

Jonathan AT Sandoe, Leeds Teaching Hospitals NHS Trust

Richard Tighe, Norwich and Norfolk University Hospital

Iain A Simpson, Southampton University Hospitals NHS Trust

Roger J Hall, Norwich and Norfolk University Hospital

Thomas SJ Elliott, University Hospital Birmingham NHS Foundation Trust


Correspondence should be sent to Chris Romaya, British Society of Gastroenterology, 3 St Andrews Place, Regents Park, London NW1 4LB. c.romaya@mailbox.ulcc.ac.uk
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  1. Mehal WZ, Culshaw KD, Tillotson GS, Chapman RW. Antibiotic prophylaxis for ERCP: a randomized clinical trial comparing ciprofloxacin and cefuroxime in 200 patients at high risk of cholangitis. Eur J Gastroenterol Hepatol 1995; 7: 841-5.




  1. Davis AJ, Kolios G, Alveyn CG, Robertson DA. Antibiotic prophylaxis for ERCP: a comparison of oral ciprofloxacin with intravenous cephazolin in the prophylaxis of high-risk patients. Aliment Pharmacol Ther 1998; 12: 207-11.




  1. Wilson W, Taubert KA, Gewitz M, et al.
    Prevention of Infective Endocarditis. Guidelines from the American Heart Association. A guideline from the American Heart Association Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee, Council on Cardiovascular Disease in the Young, and the Council on Clinical Cardiology, Council on Cardiovascular Surgery and Anesthesia, and the Quality of Care and Outcomes Research Interdisciplinary Working Group. Circulation 2007; in press (e publication ).

.

Table 1: Approximate incidence of bacteraemia in immunocompetent individuals undergoing gastrointestinal endoscopy. Comparable figures for barium enema and dental manipulation are given for comparison.





Bacteremia:


BSG review (5)

Nelson et al (8)

Rectal digital examination

Rigid proctosigmoidoscopy

Barium enema

Tooth brushing

Dental extraction

Colonoscopy

Diagnostic OGD +/- biopsy

Flexible sigmoidoscopy

ERCP (no duct occlusion)

ERCP (duct occluded)

Variceal band ligation

Sclerotherapy

Oesophageal dilatation/prosthesis

Oesophageal laser therapy

EUS + FNA


4%

5-9%


11%

25%


30-60%

2-4%


4%
6%

11%


6%

10-50%
34-54%

35%

0-6% (Refs 89-91)


7.6%

4.4%

4.1%


0.5%

6.4%


18%

8.8%


14.6%

0%


Table 2. Case reports of infective endocarditis occurring within weeks after endoscopic procedures



Type of endoscopy


Author

Reference

Patient details

Oesophageal bougienage


Yin et al
Niv et al
Breuer et al

14
15
16

Known mitral regurgitation
Known MV prolapse
No known prior valve disease

Variceal sclerotherapy

Baskin et al
Wong et al


17
18

Prosthetic valve (failure of prophylaxis)

Native valve



Diagnostic OGD +/- biopsy

Pritchard et al
Logan et al
Rumfeld et al
Montalko et al
Pentimone et al
Cho et al

19
20
21
22
23
24

Prosthetic aortic valve replacement
Known MV prolapse
MV stenosis ( patient also had RIH repair)

MV prolapse (symptoms predated OGD in patient on steroids)



Young man; no known cardiac disease

Valvular heart disease















Lower GI

Rodriguez et al
Rigilano et al
Watanakunakorn et al
Greco et al
Norfleet
Giusti de Marle et al

25
26
27
28
29
30

Rheumatic mixed valve disease following flexible sigmoidoscopy

MV prolapse, rigid sigmoidoscopy


Known aortic stenosis, following polypectomy

Polypectomy


Aortic regurgitation: flexible sigmoidoscopy for polyp follow up

Mixed AVD, colonoscopy















Table 3. Endocarditis risk stratification according to cardiac pathology (1,2,6)





High risk

Previous endocarditis

Prosthetic heart valves (tissue or mechanical)

Surgically constructed systemic pulmonary shunts or intra-thoracic vascular conduits

Complex cyanotic congenital heart disease (see Section 6.3)).


Moderate risk

Previously diagnosed acquired valvular heart disease with echocardiographic demonstration of substantial regurgitation

Mitral valve prolapse with mitral regurgitation and/or thickened valve leaflets

Non-cyanotic ongenital cardiac defects, e.g. patent ductus arteriosus, coarctation of aorta, ventricular septal defect, primum atrial septal defect, bicuspid aortic valve

Other structural cardiac abnormalities, eg hypertrophic obstructive cardiomyopathy, aortic root replacement


Low risk

All other patients


Table 4. Recommendations for antibiotic prophylaxis in gastrointestinal endoscopic practice

(+ = antibiotic cover is indicated)

Procedure

High risk patient
(prosthetic valve, previous IE, surgical thoracic vascular conduit, complex congential heart disease: See Table 3)

Moderate risk patient
(e.g. mitral valve prolapse with Echocardiographic demonstration of substantial leaflet pathology and regurgitation: See Table 3)

Low risk

patient

OGD (+/- biopsy, banding)

+

-

-

Colonoscopy (+/- polyp)

+

-

-

Flexible sigmoidoscopy

+

-

-

Oesophageal dilatation and/or stenting

+

+

-

Variceal Sclerotherapy

+

+

-

ERCP (straightforward)

+

-

-

ERCP (obstructed system or pseudocyst)

+

+

+ if unable to decompress

PEG

+

+

+

Thermal procedure

(e.g. laser, heater probe, argon plasma coagulation)



+

+

-

Endoscopic ultrasound

for diagnosis/staging/FNA



+

-

-

Endoscopic ultrasound guided therapy

+

+

Case by

Case basis



Colonic stenting

+

+

-



Table 5. Summary of recommended prophylactic antibiotic regimens for gastrointestinal endoscopy.




Scenario

Antibiotics


Dose/route

Comment

1) Endocarditis risk

All patients at high risk of endocarditis (Table 3), plus all patients at moderate risk of endocarditis undergoing certain therapeutic procedures (Table 4)



Ampicillin or amoxicillin
PLUS

Gentamicin



1 gram

(for those aged <5yr give 250mg, for those aged 5-10 years give 500mg)


1.5mg/kg iv

Single i.v. dose just before procedure or at time of administering sedation

Give over 2-3 minutes



2) Patients as (1) above who are allergic to Penicillin

Teicoplanin
PLUS

Gentamicin




400mg iv

(6mg/kg for children. Seek specialist advice for neonates)


1.5mg/kg iv

i.v over half an hour just before procedure

Give over 2-3 minutes



Procedures










3) ERCP for following patient groups:

a) endocarditis risk


As above








b) ongoing cholangitis or sepsis elsewhere

Be guided by recent culture results




Seek advice from clinical microbiologist

c) obstructed biliary tree and/or pancreatic pseudocyst
[NOTE this is only routinely recommended for patients with pancreatic pseudocyst, or those for whom complete drainage is unlikely to be achieved at a single ERCP – (see section 7.2.5) BUT a full course of antibiotics becomes mandatory if adequate biliary decompression is not achieved during the procedure. For antibiotics to cover a repeat ERCP see 7.2.4]

Ciprofloxacin

OR

Gentamicin



750mg orally

1.5mg/kg i.v.



60-90 minutes before procedure
Not recommended in children

Administer over 2-3 minutes




d) Immunosuppressed (including post liver transplant, and neutropaenia (<0.5x109/l)

As (c) PLUS

Amoxicillin OR

Vancomycin


1gram i.v.

20mg/kg i.v.



Amoxicillin given as single i.v. dose

Vancomycin infused over at least one hour



4) PERCUTANEOUS ENDOSCOPIC GASTROSTOMY (PEG)


Co-amoxiclav

OR

Cefuroxime



1.2g i.v.

750mg i.v.



Slow iv injection or infusion just before procedure. Clindamycin 300mg i.v. can be used if past anaphylaxis with penicillin/cephalosporin

5) VARICEAL BLEEDING

Be guided by local liver unit practice




Cefotaxime is used in preference to cefuroxime in patients with SBP

St Elsewhere’s NHS Trust

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