J%ournnl

of

Hospital

I~~fection

Prevention retrograde C. G. Alveyn,

Department Microbiology,

(199 1) 19 (Supplement

C),

6540

of sepsis following endoscopic cholangiopancreatography

D. A. F. Robertson, R. Wright, G. Tillotsont

J. A. Lowes”

and

of Medicine II, University of Southampton, “Departmtwt oj Southampton General Hospital a?ld TBayey UK Ltd, A’ewbuq

Summary:

Oral ciprofloxacin \vas studied as a prophylactic antimicrobial agent in highand lobv-risk patients undergoing endoscopic retrograde cholangiography. Ciprofloxacin appeared to be effective, good serum levels kvere attained, and the drug compared favourably on grounds of cost and convenience with a parenterally-administered cephalosporin. Keywords: Endoscopic chemoprophglaxis.

retrograde

cholangiography

; cipvofioxncirl;

infection;

Introduction

Since its introduction in 1968,’ endoscopic retrograde cholangiopancreatography (ERCP) has become a well-established technique in the management of patients with hepatobiliary disorders. ‘The procedure provides useful diagnostic information regarding pathology in the biliary tree, and is of particular value in the investigation of the jaundiced patient. ERCP also has considerable therapeutic potential. The sphincter of Oddi may be cut to facilitate removal of gallstones from the bile duct,* and in patients with inoperable malignant biliary obstruction, an endobiliary prosthesis (stent) may be placed to relieve jaundice.” ERCP is generally a safe procedure in experienced hands with a mortality of O-l-0.2%.’ The most important complications are pancreatitis, sepsis (ascending cholangitis and septicaemia), instrumental injury and haemorrhage. Bacteraemia occurs in 2 to 4.8% of cases, but in most of these patients is inapparent.” ’ Clinically significant sepsis is less common, occurring in 0.37 to 0.8% of patients undergoing ERCP.X Its importance lies in the fact that sepsis is the commonest cause of mortality due to this procedure, with a case fatality rate of 8 to 20%.‘~“~“’ Infection is largely confined to patients with obstructed biliary or pancreatic ducts.“,” Various measures should be taken to minimize the risk of infection at ERCP. Radiographic contrast solutions must be sterile, and the vrolume of contrast Correspondence to: Dr C. G. Aheyn, Dept. of hledicinc Block, Southampton General FIospital, Tremona Road,

II, Level D, South Labmatory Southampton SO’) 1XY.

and Patholog)

66

C. G. Alveyn

et al.

injected should be the minimum necessary to obtain suitable radiographs. Endoscopes should be disinfected carefully between patients. It is now common practice to use two or more instruments in rotation during an ERCP session to facilitate disinfection. Guidelines for the disinfection of endoscopy equipment have recently been published by a Working Party of the British Society of Gastroenterology. l2 If an obstructed biliary tree is demonstrated at ERCP, the obstruction must be relieved as soon as possible. This may be achieved during the procedure by manoeuvres such as endoscopic sphincterotomy (ES) and extraction of gallstones, or by the placement of a stent. Should endoscopic treatment of biliary obstruction fail, then urgent percutaneous drainage or surgery is essential. Prophylactic antibiotics are now commonly given to high-risk patients (i.e. those with clinical or radiological evidence of biliary obstruction) prior to ERCP. This has become accepted practice, despite the absence of prospective controlled trials. There is, however, retrospective evidence to suggest that sepsis is more likely to complicate ERCP in high-risk subjects if no antimicrobial agents have been administered beforehand.” Various antibiotics have been employed for prophylaxis prior to ERCP. These include ampicillin and gentamicin’; mezlocillint3; and cephalosporins such as cephazolin and cefuroxime. 14,15However, there have been few direct comparisons of these drugs, and the optimum prophylactic regimen has yet to be determined. The organisms commonly causing bacteraemia after ERCP” and found in infected bile at operationI are enterobacteria, faecal streptococci, Staphylococcus epidermidis and Bacteroides spp. The gut is presumed to be the source of most of these, although cross-infection via contaminated endoscopes has been incriminated in the case of Pseudomonas and S. epidermidis.““7 Ciprofloxacin is a novel 4-quinolone antimicrobial agent which is thought to act principally by inhibiting bacterial DNA gyrase. It has a broad of activity against many Gram-positive and especially spectrum Gram-negative organisms, including pseudomonads. High biliary concentrations of the drug are achieved after a single oral dose.18 We have studied oral ciprofloxacin as a prophylactic agent in low- and high-risk patients undergoing ERCP. Patients

and

methods

All patients underwent physical examination and an upper abdominal ultrasound scan prior to ERCP. Patients with jaundice and/or ultrasonographic evidence of biliary obstruction were considered to be at high risk of infection. All others were classified as low risk. ‘Low-risk’ patients Forty-seven patients with no clinical or radiological evidence of biliary obstruction (‘low risk’) were studied (Table I). These patients were

Chemoprophylaxis Table

for ERCP

I Characteristics of ‘low-risk’ patients dence of complications following ERCP Ciprofloxacin

X0. of patients iXlale:female blean age (yrs) Septicaemia Pancreatitis Death Adverse effects * Skin

Table

II.

which

rash

* Diarrhoea;

inci-

23 9:14 52 0 3 0 1*

spontaneously

I- ’

resolved spontaneously. present in stool; therapy.

cytotoxin

metronidazole

resolved

and

Placebo

24 14:lO 60 0 2 0 0

Characteristics of ‘high-risk’ complications following

No. of patients Male:female Mean age (years) Mean bilirubin pmol Septicaemia Pancreatitis Death Adverse reactions

d@cile

67

patients ERCP

and incidence

Ciprofloxacin

Cephazolin

41 25:16 71 156 0 2 1 1*

43 19:24 71 179

** Diarrhoea resolved following

of

2 0 1** with Clos~idium cefuroxime and

undergoing investigation mainly for upper abdominal pain. In a double-blind, placebo-controlled study ‘low-risk’ patients were randomized to receive either ciprofloxacin 750 mg orally (N = 24) or placebo (N = 23) as a single dose at least 90 min before ERCP. ‘High-risk’ patients Eighty-four ‘high-risk’ patients were studied (Table II). These patients were randomized openly to receive either ciprofloxacin 750 mg twice daily by mouth or cephazolin 1 g twice daily intravenously. Each drug was commenced at least 90 min before ERCP and was continued for 3 days. Measurements Prior to ERCP: liver function tests, full blood count, plasma amylase; immediately after ERCP: blood cultures (aerobic and anaerobic), serum ciprofloxacin concentration; 16-24 hours after ERCP: blood cultures, plasma amylase.

68

C. G. Alveyn

et al.

End points Patient records were reviewed after 7 days for the occurrence of: septicaemia (proven by blood culture); pancreatitis (abdominal pain and plasma amylase 11000 u 1-i); death; or adverse reactions to trial drugs. Results

Results for ‘low-risk’ patients are summarized in Table I. No patient in this group became septicaemic. Five patients developed acute pancreatitis after ERCP; there was no significant difference in the incidence of pancreatititis between active treatment and placebo. Table II shows the results for ‘high-risk’ patients. Two cases of septicaemia occurred, both in patients randomized to cephazolin. The organisms responsible were Bacteroides fragilis and Escherichia coli, and both patients recovered following appropriate antimicrobial therapy. One 85-year-old patient with pre-existing renal failure and carcinoma of the pancreas who received ciprofloxacin died shortly after the procedure without evidence of sepsis. There was no difference in the incidence of pancreatitis or adverse reactions between the ciprofloxacin and cephazolin patients, and the difference in the incidence of septicaemia was not significant. Figure 1 shows the serum ciprofloxacin concentrations achieved by the end of the ERCP in the first 31 patients (high- and low-risk) receiving ciprofloxacin. Ciprofloxacin was undetectable in the serum of low-risk patients randomized to placebo and high-risk patients randomized to cephazolin.

Discussion

These preliminary data suggest that oral ciprofloxacin is an appropriate drug for antimicrobial prophylaxis in patients undergoing ERCP. No infective complications have been observed in 65 subjects who received the drug prior to ERCP, and it was well tolerated. Good serum concentrations at the end of the procedure were obtained in most patients. Three subjects who were randomized to oral ciprofloxacin had undetectable serum levels (Figure 1). Subsequent investigation revealed that these patients had either experienced difficulty in swallowing the tablets or had vomited shortly after receiving the medication, and medical staff had not been alerted. Owing to occasional logistic problems, some patients received ciprofloxacin less than 90 min prior to the commencement of ERCP. However, even in these subjects, adequate serum concentrations were achieved (Figure 1). Ciprofloxacin tablets dispersed rapidly in the gut and caused no technical difficulties during ERCP. Most other antibiotics used for prophylaxis prior to ERCP must be given parenterally. The fact that ciprofloxacin is effective when administered

Chemoprophylaxis

for

ERCP

69

l

:: l

l

-: .

Time after

first

dose

Figure 1. Serum ciprofloxacin concentrations (mg 1-l) ‘lo\\-risk’ (0) and ‘high-risk’ (0) patients. Broken concentrations aminimum inhibitory concentrations N = 31.

l

(mlr!i

after tirst oral dose of the drug in lines indicate range of serum (1IICs) f or most enterobacteria.

orally makes it a convenient drug for nursing and medical staff’ to administer. During this study, the cost to our district of ciprofloxacin 750 mg twice daily by mouth was 413.68, that of cephazolin 1 g twice dail! intravenously was E31.95 (three days’ treatment in each case). Oral ciprofloxacin thus compares favourably on grounds of cost and convenience Lvith a parenterally-administered cephalosporin. Ciprofloxacin prolongs and elevates plasma theophylline levels b!. inhibiting microsomal enzymes. -An alternative drug should therefore be used in patients taking theophylline. If oral ciprofloxacin is used for antimicrobial prophylaxis, the prescribing physician must ensure that the patient can reliably s~vallow oral medication, and is not nauseated. \Vhile ciprofloxacin appears to be a useful prophylactic agent for patients undergoing ERCI’, the optimum duration of treatment remains to be determined. In common \vith the experience of others \l:e found no evidence of sepsis in lo\v-risk subjects, whether randomized to ciprofjoxacin or placebo. Antimicrobial prophylaxis ma)- be unnecessar). in these patients. References 1. RlcCure \VS, Shorb a preliminary report. 2. Classen n1, &friiny 1975: 4: 371-374.

PE, IIloscovitz H. Endoscopic cannulatlon Ann Surg 196X; 167: 752-756. L. Endoscopic papillotomy and remowl

of the ampulln of gallstones.

of \‘arer: Ilr

A%Irtf J

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et al.

3. Shepherd HA, Royle G, Ross APR, Diba A, Arthur M, Colin-Jones D. Endoscopic biliary endoprosthesis in the palliation of malignant obstruction of the distal common bile duct: a randomized trial. Br J Surg 1988; 75: 1166-l 168. 4. Bilbao MK, Dotter CT, Lee TG, Katon RM. Complications of endoscopic retrograde cholangiopancreatography (ERCP). A study of 10 000 cases. Gastroenterology 1976; 70: 314320. 5. Mellow MH, Lewis RJ. Endoscopy-related bacteraemia. Arch Intern Med 1976; 136: 667-669. 6. Lam SK, Tsui JKC, Chan PKW, Wong KP, Ong GB. How often does bacteraemia occur following endoscopic retrograde cholangiopancreatography? Endoscopy 1977; 9: 231-234. 7. Dutta SK, Cox M, Williams RB, Eisenstat TE, Standiford HC. Prospective evaluation of the risk of bacteraemia and the role of antibiotics in ERCP. J Clin GastroenteroZ1983; 5: 325-329. 8. Cotton PB. Progress report-ERCP. Gut 1977; 18: 316-341. 9. Nebel OT, Silvis SE, Rogers G, Sugawa C, Mandelstam P. Complications associated with endoscopic retrograde cholangio-pancreatography. Results of the 1974 ASGE survey. Gastrointest Endosc, 1975; 22: 34-36. 10. Siegman-Igra Y, Spinrad S, Rattan J. Septic complications following endoscopic retrograde cholangio-pancreatography: the experience in Tel Aviv Medical Center. J Hasp Infect 1988; 12: 7-12. 11. Parker HW, Geenen JE, Bjork JT, Stewart ET. A prospective analysis of fever and bacteraemia following ERCP. Gastrointest Endosc 1979; 25: 102-l 03. 12. A Working Party of the British Society of Gastroenterology. Cleaning and disinfection of eouinment for gastrointestinal flexible endoscopv: . _ interim recommendations. Gut 1988; 29: 1134-1151. 13. Martin DF, Tweedle DEF. Endoscopic management of common duct stones without cholecvstectomv. Br 7 Su7~ 1987; 74: 209-211. 14. Leese T, Neop;olem& JP, Carr-Locke DL. Successes, failures, early complications and their management following endoscopic sphincterotomy: results in 394 consecutive patients from a single centre. Br J Surg 1985; 72: 215-219. 15. Neoptolemos JP, Carr-Locke DL. Antibiotic prophylaxis for endoscopic sphincterotomy (Letter). Gut 1988; 29: 874875. 16. Neoptolemos JP, Carr-Locke DL, Fossard DP. Prospective randomized study of preoperative endoscopic sphincterotomy versus surgery alone for common bile duct stones. Br MedJ 1987; 294: 470-474. 17. Earnshaw JJ, Clark AW, Thorn BT. Outbreak of Pseudomonas aeruginosa following endoscopic retrograde cholangiopancreatography. J Hasp Infect 1985; 6: 95-97. 18. Strachan CJL, Thorn BT. Proceedings of the 14th International Congress on Chemotherapy, Kyoto 1985; 1591-l 592.

Prevention of sepsis following endoscopic retrograde cholangiopancreatography.

Ora; ciprofloxacin was studied as a prophylactic antimicrobial agent in high- and low-risk patients undergoing endoscopic retrograde cholangiography. ...
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