Bacteremia during colonoscopy George Pelican, MD David Hentges, PhD James Butt, MD Thomas Haag, MS Rial Rolfe, MS David Hutcheson, PhD Columbia, Missouri
Bacteremia, including potentially pathogenic species of the fecal flora, was detected during colonoscopy in 6 of 22 patients when blood cultures were taken at frequent intervals during the first 15 minutes of the procedure. While transient bacteremia during colonoscopy may be insignificant for most patients, the implications are potentially more grave for those with valvular heart disease or compromised host defenses.
Transient bacteremia has been reported during sigmoidoSCOpY,'-3 urological manipulation,' periodontal procedures,S'. and dental extraction,' Although bacteremia during sigmoidoscopy was not detected by Buchman' and was rarely observed by Unterman,' it was observed by LeFrock 3 in 9,5%. Most recently, Shull" has demonstrated transient bacteremia to occur during upper gastrointestinal endoscopy. Colonoscopy has gained wide acceptance as a common diagnostic tool. Rafoth," Dickman,'° and Norfleet" have reported that bacteremia occurs in a negligible proportion of colonoscopic procedures. We studied the occurrence of bacteremia in patients undergoing colonoscopy without inflammatory bowel disease or underlying disease that compromised !:lost defenses. METHODS Clinical Methods. The study group was randomly selected and consisted of 36 patients (31 men and 5 women) who were referred to the University of Missouri Medical Center - Harry S Truman Veterans Administration Hospital gastroenterology group for either diagnostic or therapeutic
colonoscopy. Patients were excluded from the study for any of the following reasons: (a) antibiotic therapy during the preceding 7 days, (b) fever during the 7 days before the procedure, (c) indwelling urethral or intravenous catheters, and (d) inability to insert a plastic catheter into the left antecubital vein. In addition, the clinical record was reviewed for any evidence of infection. Informed consent was obtained from each patient. Indications for colonoscopy are outlined in Table 1. All patients were prepared by a clear liquid diet for 48 hours. Ten ounces of magnesium citrate at noon the preceding day and 20 milligrams of bisacodyl at 4 pm the afternoon of the preceding day were given. Saline enemas were adminisTable I Clinical indications for colonoscopy in study group Abnormal radiograph Gastrointestinal bleeding Abdominal pain Chronic diarrhea Miscellaneous indications
19 8 2 2 5
From the departments of Medicine, Microbiology, and Veterinary Medicine, University of Missouri Medical Center, Harry S Truman Veterans Hospital, and Sinclair Research Farm, University of Missouri, Columbia, Missouri. Reprint requests: James Butt, MO, 800 Stadium Road, Columbia, MO 65201. VOLUME 23, NO.1, 1976
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tered the morning of the procedure. All patients were premedicated with 0.4 mg atropine. Diazepam was given intravenously through the antecubital vein of the right arm. Meperidine was given as needed. Colonoscopes used were the Olympus CF (type MB2), Olympus CR (type LB), and ACMI F9A. Sample Collections. The left forearm was scrubbed with povidine-iodine for 5 minutes. A 16-gauge intravenous catheter was introduced into the left antecubital vein. Four ml of blood were removed using a heparin-rinsed, sterile syringe. Then, 0.2 ml of heparin (1000 units/ml) was injected into the intravenous needle exactly displacing the dead space of the needle. The syringe was removed and replaced with a new heparin-rinsed syringe. Samples were immediately placed in transport vials (Anaport). Samples were taken according to 1 of 2 schedules: (A) samples were taken before the introduction of the colonoscope, at 15-minute intervals after introduction of the colonoscope, and at 1 and 2 hours after colonoscopy was completed; or(B) samples were taken before colonoscopy, at 1,5, 10, and 15 minutes after the start of the procedure, and 30 minutes following termination of the procedure. Additional blood samples were collected at the time of biopsy, polypectomy, and during any fever and chills that occurred up to 4 hours after the procedure. Clinical Studies. Temperatures were recorded before colonoscopy and at l-hour intervals following the procedure for 4 hours. White blood cell counts were performed before colonoscopy. Single-blind studies by the clinician with seeded blood cultures showed that approximately 10 organisms per ml of blood could be added and detected unaffected by transport and culture techniques. The individual collecting the blood samples did not do the colonoscopy. Statistical analysis was carried out by Chi-square test. Microbiological Methods. The gassed, non-nutrient transport system (Ana port, Scott Laboratories) consisted of stoppered 10 ml vials, evacuated and replaced with oxygen-free C02, containing 0.1 ml of Virginia Polytechnic Institute (VPI) salts solution and a resazurin indicator. Culture Techniques. Immediately after collection of specimens, the sample transport vials, containing 3.5 ml of blood, were placed in an anaerobic glove box isolator similar to that described by Aranki et al.'2 Ten-fold serial dilutions of the cultures were prepared with VPI salts diluent. One ml of each dilution was flooded onto the surface of 2 previously dried, pre-reduced, enriched Brucella blood agar (EBBA) plates composed of Brucella agar (BBl), 4.3%; sheep rbc's, 0.5%; cysteine hydrochloride, 0.05%; hemin, 0.00001 %; menadione, 0.00005%; sodium carbonate, 0.042%; and dibasic potassium phosphate, 0.25%. Each dilution was spread evenly over the entire surface by gentle tilting of the plate. The plates were allowed to stand, cover up, until all liquid was absorbed into the agar. One plate was incubated anaerobically for 7 days to ensure sufficient development of colonies. The second plate was removed from the chamber and aerobically incubated at 37°C for 48 hours. Organism Identification. Anaerobic bacteria were identified accordi ng to the scheme outl ined by Holdeman and Moore. 13 Cram-stain reaction and gas chromatographic analysis placed the unknown isolate into a genus category, whereas biochemical characteristics were used to speciate the 34
Procedures with bade rial isolation
o
1
15
I 30
(post procedure)
T lme in minutes
Figure 1. Frequency of bacterial isolations according to the time during colonoscopy. isolate. Biochemical characteristics were determined with the Minitek system (BBl). The facultative bacteria were identified according to the procedure outlined by Edwards and Ewing. 14 RESULTS Bacteremia was not detected in any patient in schedule A. There were 14 patients with a total of 63 cultures. The findings in the 134 cultures of schedule B were significantly different with bacterial isolations in 6 of 22 (27%) colonoscopies in the second schedule (p<0.04). All positive isolations were obtained during the procedure, with a preponderance of positives occuring during the first 5 minutes of the colonoscopy (Figure 1). Organisms isolated were all anaerobic with the exception of 1 isolation of Enterobacter aerogenes, a facultative anaerobic organism (Table II). Colony counts ranged from 2 colony forming units (CFU)/ml (Bacteroides fragilis) to 40 CFU/ml (Enterobacter aerogenes). Eight of 14 patients underwent polypectomy or biopsy in schedule A without detection of bacteremia. Polypectomy was performed in only 1 of the 6 positive isolations in schedule B. The isolation was from a sample taken 5 minutes after insertion ofthe colonoscope, well before polypectomy. There were a total of 4 polypectomies or biopsies in the negative patients of schedule B. Positive isolations occurred randomly throughout the 6 month period of study in schedule B. Two patients developed fever and chills after the procedure and had positive cultures during the procedure. DISCUSSION The occurrence of bacteremia duringcolonoscopy in patients without inflammatory bowel disease or diseases compromising host defenses has not been reported. Sampling frequency may have contributed to previous negative reports during colonoscopy. The sampling frequency during sigmoidoscopy by LeFrock et al. 3 differed markedly from that of Buchman and Unterman.' LeFrock and his associates found a significant incidence of bacteremia by sampling blood at the conclusion of sigmoidoscopy and at 1, 5, 10, and 15 minutes thereafter. Most positive cultures were obtained at the 1 and 5 minute intervals. Investigators studying the possible occurrence of bacteremia during colonoscopy did not use this sampling frequency. According to schedule A Table II
Bacteriology of isolations during colonoscopy organism number of isolations concentrations' Peptostreptococcus species 2 3.8 Bacteroides fragilis 1 8 40 Enterobacter aerogenes 1 Clostridium innocuum 2 4.6 ·colony forming units/ml blood
GASTROINTESTINAL ENDOSCOPY
of our study, the sampling frequency was similar to that which has been reported as yielding negative results during colonoscopy. With the publication of the report by LeFrock et al. on bacteremia during barium enema" we altered our sampling schedule. It is clear that the detection of bacteremia in this study is related to the time the culture is obtained. The appearance of bacteremia in the first few minutes of the procedure occurs during the traverse of the rectum and lower sigmoid colon. This area is drained by the inferior hemorrhoidal veins into the systemic circulation. The remainder of the procedure, including the effect of pressures generated by air insufflation, involves those segments of the colon drained by the portal circulation. The reticuloendothelial system of the liver is a significant barrier preventing entry of enteric bacteria into the systemic circulation.'6 The role played by intraluminal pressure in the genesis of the bacteremia may be significant. In a companion studY,17 utilizing the same sampling frequency as in this investigation, we have demonstrated bacteremia during barium enema. Bacteremia occurred much later in the barium enema study when maximal pressures were developed at complete filling of the colon. Pressures generated during colonoscopy have been cited as a significant hazard for perforation.'8 Pressures in the range of 440 to 570 mm Hg were reported with Olympus equipment; pressures under 150 mm Hg were reported with ACMI equipment. Positive bacterial cultures were obtained during the use of both types of colonoscopes in this study.
REFERENCES 1. UNTERMAN D, MILBERG MB, KRANIO M: Evaluation of blood cultures after sigmoidoscopy. N Engl J Med 257:773, 'j 957 2. BUCHMAN E, BURGLAND EM: Bacteremia following sigmoidoscopy. Am Heart J 60:863, 1960 3. LEFROCK j, ELLIS C, TUBEHIK j, WEINSTEIN L: Transient bacteremia associated with sigmoidoscopy. N Engl J Med 289:467, 1973 4. SLADE N: Bacteremia and septicemia after urologic operations. Proc R Soc Med 51:331,1958 5. FELlxjE, ROSEN 5, App GR: Detection of bacteremia after the useof an oral irrigation device in subjects with peridontitis. J Peridonto/ogy 42:785-787,
1971 6. KORN NA, SCHAEFFER EM: A comparison of post-operative bacteremia induced following different periodontal procedures. J Peridonto/ogy
15:226, 1962 7. PAQUIN 0: Bacteremia following removal of diseased teeth. J Am Dent Assoc 28:879, 1941 8. SHULL Hj, GREENE BM, ALLEN SD, DUNN G D, SCHENKER 5: Bacteremia with upper gastrointestinal endoscopy. Ann Int Med 83:212, 1975 9. RAFOTH Rj, SORENSON RM, BOND jH: Bacteremia following colonoscopy. Gastrointestinal Endoscopy 22:32, 1975 10. DICKMAN MD, FARRELL R, HIGGS RH, WRIGHT LE, HUMPHRIES Tj, WOJCIK jD, CHAPPELKA R: Colonoscopy associated bacteremia. Surg Gynecol Obstet 142:173, 1976 11. NORFLEET RG, MULHOLLAND DD, MITCHEL PD, PHILO j, WALTERS EW: Does bacteremia follow colonoscopy? Gastroenterology 70:20, 1976 12. ARANKI A, FRETER R: Use of anaerobic glove boxes for the cultivation of strictly anaerobic bacteria. Am J Clin Nutr 25:1329,1972 13. HOLDEMAN LV, MOORE WEC: Anaerobe Laboratory Manual. Virginia Polytechnic Institute and State University, Blacksburg, Virginia, 1972 VOLUME 23, NO.1, 1976
Endoscopic equipment and dilators have been reported as sources of bacteremia.'·,20 Colonoscopes harbor a spectrum of bacterial species similar to that reported in this study.21 Coincident with this study, systematic bacteriologic monitoring of all endoscopic equipment during procedures was initiated in our laboratory. Between procedures, all equipment is carefully cleansed and then sterilized with 2% gluteraldehyde. At frequent intervals all endoscopes are gas sterilized with ethylene oxide. Bacteriologic monitoring revealed no contamination between procedures. It should be pointed out that all of the organisms isolated from the blood of our patients are present in human feces. 22 - 24 The organisms isolated in this study have potential pathogenetic significance. Ofthe species reported in anaerobic bacterial endocarditis/ s 75% were detected in the present study. We conclude that bacteremia does occur with significant frequency during colonoscopy as a transient, self-limited event. Venous drainage of the rectum and lower colon into the systemic circulation may facilitate the detection of bacteremia. Timing of the cultures significantly affects the rate of isolation of bacteria. Pressures developed in the colon during endoscopy may playa significant role in the pathogenesis of bacteremia. The consequence of transient bacteremia is probably insignificant in patients without valvular heart disease or compromised host defenses. In patients with these clinical problems, however, the implications of bacteremia during colonoscopy are more serious and are deserving of further systematic study.
14. EDWARDS PR, EWING WH: Identification of Enterobacteriaceae. Burgers Publishing Co., Minneapolis, Minn., 1962 15. LEFROCK j, ELLIS CA, KLAINER AS, WEINSTEIN L: Transient bacteremia associated with barium enema. Arch Int Med 135:835, 1975 16. BEESON PB, BRANNON ES, WARREN jV: Observation of sites of removal of bacteria from blood in patients with bacterial endocarditis. J Ex Med 81 :9, 1945 17. PELICAN G, HENTGES D, BUTT. j, HENSTORF H, HAAG T, ROLFE R: Bacteremia during barium enema. Presented at the meeting of the American Gastroenterological Association 27 May, 1976, Miami, Florida. 18. WILLIAMS CB, LANE RH, SAKAI Y, HANWELL AE: Colonoscopy: an air pressure hazard (letter). Lancet 2:729, 1973 19. GREENE WH, MAUDES M, HARELY R, EFFUEU E, AISNER j, YOUNG VM, NIERVIK PH: Esophagoscopy as a source of Pseudomonas aeruginosa sepsis in patients with acute leukemia: The need for sterilization of endoscopes. Gastroenterology 67:912,1974 20. RAINES DR, BRANCHE WC, ANDERSON DL, BOYCE HW: The occurrence of bacteremia after esophageal dilatation. Gastrointestinal Endoscopy
22:86,1975 21. CHANG F, SAKAI Y, ASHIZAWA 5: Bacterial pollution and disinfection of colonofiberscope I an investigation of traditional sterilization methods II ethylene oxide gas sterilization. Am J Dig Dis 18:946, 1973 22. FINEGOLD SM, ATTERBERY HR, SUTTER VL: Effect of diet on human fecal flora: comparison of Japanese and American diets. Am JC/in Nutr 27:1456,
1974 23. FINEGOLD SM, FLORA Dj, ATTEBERY H R, SUTTER VL: Fecal bacteriology of colonic polyp patients and control patients. Cancer Res 35:3407, 1975 24. HENTGES D: Unpublished data. 25. FELNER jM, DOWELL VE: Anaerobic bacterial endocarditis. N Engl J Med
283:1188,1970
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