Journal
of Hospital
Infection
(1992) 20, 43-50
Sepsis associated with transhepatic cholangiography A. Sacks-Berg, Infectious University
0. V. Calubiran,
H. Y. Epstein,
B. A. Cunha
Disease Division and the Department of Radiology, WinthropHospital, Mineola, New York, USA and S. U.N. Y. School of Medicine, Stony Brook, New York, USA Accepted for publication
24 October 1991
Summary: A retrospective study was carried out of 74 elderly patients with obstructive jaundice undergoing percutaneous transhepatic cholangiography (PTC) and/or percutaneous biliary drainage (PBD) in order to assess the effect of prophylactic antibiotics on the incidence of fever and sepsis complicating these procedures. Seventeen patients underwent PTC alone, while 57 had both PTC and PBD. Fifty-three patients had either primary or metastatic malignancy. In the other patients with benign disease, choledocholithiasis was the most common reason for undertaking these procedures. Prophylactic antibiotics were given in 80% of cholangiographies and 93 % of biliary drainage procedures. There was an overall incidence of sepsis of 13.5%. Enterobacter cloacae and Acinetobacter anitratus were the most common blood culture isolates in patients with malignant biliary obstruction. The incidence of fever was no different between patients who underwent PTC alone compared with those who had PTC and PBD. Of 24 patients who developed fever, two died secondary to sepsis. Although there was no difference in the rate of sepsis and febrile episodes between the two groups, the risk of septic episodes and mortality emphasizes the need for antibiotic prophylaxis and early therapy in elderly patients undergoing percutaneous biliary drainage procedures. Keywords: prophylactic
Transhepatic antibiotics.
cholangiography;
biliary
obstruction;
septicaemia;
Introduction Percutaneous biliary drainage (PBD) is used as a temporary procedure prior to operative surgery, or as a palliative measure for decompression in patients with a biliary obstruction secondary to malignancy or choledocholithiasis, to improve the patient’s condition. A percutaneous transhepatic cholangiogram (PTC) is perfformed in order to visualize and define the area of obstruction for emergent decompression with PBD or eventual planned surgery. Infectious complications, which include ascending cholangitis and biliary sepsis following the procedure, contribute significantly to morbidity Correspondence Hospital,
to: Mine&,
0195&6701/92/010043+08
Burke NY
A.
Cunha,
11501,
USA.
M.D.,
Chief,
Infectious
$03.00/O
Disease
Division,
Winthrop-University
0 1992 The Hospeal
43
Infection
Society
A. Sacks-Berg
44
et al.
and mortality with rates as high as 76% noted in previous studies.“-’ The risk of sepsis from obstructive jaundice may be due to several factors including the exogenous introduction of pathogens during percutaneous catheter insertion. Many elderly patients with an obstructed biliary tract will have bacteria in the bile before percutaneous biliary drainage is performed. Therefore, although the term antibiotic prophylaxis is generally used to signify drug administration before the procedure, the term prophylaxis in this setting really represents early empirical therapy. Febrile episodes, with or without bacteraemia, were reviewed in 74 patients who underwent PTC and/or PBD. Morbidity and mortality among patients with either malignant or benign disease were compared with respect to antibiotic prophylaxis. Patients
and methods
Seventy-four patients with obstructive jaundice underwent PTC and/or PBD at Winthrop-University Hospital between 23 January 1984 and 1 July 1987. There were 46 men and 28 women; the average age was 67 years. retrospectively for the (Table I). Medical records were examined development of fever (2 101” F), bacteraemia, antibiotic prophylaxis and mortality. Sepsis was defined as either (a) bacteraemia with more than two of three blood cultures positive with bacterial pathogens, or (b) the development of fever, chills and hypotension in the presence of positive blood cultures. Prophylactic antibiotics were administered at various times before the procedure. Most commonly, 2 g of cefoperazone was given 12-hourly or 2 g Table
I. Details
of patients
and antibiotic
All patients Number of patients Sex: Male Female Average age (years) Underlying diseases: Malignant Benign Number of radiological PTC PBD Total Prophylaxis given for: PTC PBD Total Mortality
prophylaxis
Patients
with sepsis
Patients
without sepsis
74 28 46 67
10 4 6 68
64 24 40 67
53 21
7 3
46 18
45 123 168
10 16 26
35 107 142
36 (80%) 115 (93%)
9 (90%) 16 (100%) 25 (96%) 2
27 (77%) 99 (93%) 127 (89%) 13
procedures:
15
Sepsis
of cefoxitin was given given intravenously.
and
transhepatic
S-hourly,
cholangiography
used
as single
45
agents.
Both
agents
were
Results
underwent 168 radiological procedures; 4.5 Seventy-four patients cholangiograms and 123 biliary drainage procedures. Seventeen patients underwent PTC alone, while the remaining 57 patients also underwent biliary drainage procedures at the same time as PTC. Twenty-seven of these 57 patients underwent more than one drainage procedure; the average was 2.16 drainages per patient (range l-8). Biliary obstruction was secondary to malignancy in the majority of our patients. Of the 53 patients with malignancy 28 had pancreatic carcinoma, seven had cholangiocarcinorna, six had carcinoma of the gallbladder, three had metastatic lung carcinoma, three had metastatic colon carcinoma, three had breast carcinoma with metastases, two had lymphomas and one had primary liver carcinoma (Figure 1). Twenty-one patients (28%) had a benign disease causing biliary obstruction. Choledocholithiasis was the most common underlying disease in this group: eight patients were found to have stones impacted in the common bile duct, five patients had chronic cholecystitis; one patient hald a duodenal polyp obstructing the ampulla of Vater and another patient had peptic ulcer disease. One patient had persistent jaundice after an episode of haemolytic anaemia, and one patient had post-operative stenosis of the common bile duct after a cholecystectomy. Twenty-nine patients experienced a total of 37 febrile events temporally related to biliary tract manipulations. Seven temperature elevations
Pancreatic Bile Duct Gall bladder
Breast Lung Lymphoma Hepatomo 0
5
15
IO
20
25
NO. of potients
Figure 1. Types of malignancy
in elderly
patients
undergoing
PTC/PBD.
A. Sacks-Berg
46
et al.
(2 101°F) developed within the first 24 h of the procedure and eight additional temperature elevations occurred within 24 to 72 h. Sepsis resulting from the procedure per se could not be directly implicated as the explanation of fever in the majority of cases. Fourteen temperature elevations (38%) occurred in patients prior to the radiological intervention, and the remaining eight febrile episodes occurred more than 72 h after the procedure (Table II), Ten of the 17 patients who underwent cholangiography alone had temperatures of more than 101°F. One of these patients had two cholangiograms and developed fever on both occasions. Of the 4.5 cholangiograms performed in this group, there were 11 febrile events (rate 24%). Nineteen of 57 patients who underwent insertion or revision of a biliary drain experienced a total of 26 febrile episodes. There were 123 PBD procedures performed in this group; the rate of fever development was 21%. There were no differences in the rate of fevers between the group that underwent PTC alone compared with the group that had PBD as well as PTC (24% and 21% respectively) (Table III). Eighteen of the 53 patients (34%) with underlying cancers, and 11 of the 21 cases (52%) with benign disease, developed fevers. However, of the 10 associated patients with sepsis, eight (80%) were febrile. Temperatures with biliary tract instrumentation and sepsis ranged between 102 and 105” F. Seven patients with malignancies (13%) and three patients with or were considered benign disease (14%) d eveloped proven bacteraemia septic on clinical grounds. Overall, sepsis occurred in 13.5% of patients. Blood cultures were obtained during 34 of 37 febrile episodes (92%) in the 29 patients. The bile was not cultured. Six sets of blood cultures demonstrated bacterial pathogens in at least two of three cultures. Two other sets of blood cultures yielded positive results, although only in one of two cultures. In both cases, Acinetobacter anitratus was isolated and the patients were considered septic as they developed chills, fever and hypotension coinciding with the positive blood cultures. The yield of positive blood cultures in the group of febrile patients was 24%. In bacteraemias associated with malignant biliary tract obstruction Enterobacter, Acinetobacter and Serratia were the most common organisms isolated. This may reflect the changes in flora due to age, prolonged hospitalization or previous antibiotic exposure. In patients with benign Table
II.
Time of onset of fever
(> 101°F) zn relation PTC
Before procedure After procedure: Within 24 h 2472 h >72 h PTC, Percutaneous
transhepatic
cholangiography;
to radiological
PTC
procedures
and PBD
Total
5
9
14
2 1 3
:
7 8 8
PBD, percutaneous
biliary drainage.
5
Sepsis
and transhepatic
cholangiography
47
biliary obstruction, bacteraemia was due to the usual biliary pathogens except for Bacteroides fragih. Blood cultures were also obtained from 35 afebrile patients. Two sets of blood cultures demonstrated significant growth of microorganisms. An enterococcus was isolated from all three sets of blood cultures from case no. 6. Polymicrobial bacteraemia was demonstrated in case no. 7. The patient and all three blood cultures grew an was afebrile but hypotensive, Serratia marcescens and a viridans Klebsiella pneumoniae, enterococcus, streptococcus. The patient died of sepsis 10 days after the demonstration of bacteraemia. The yield of positive blood cultures in the afebrile patient group was 6%. Antibiotic prophylaxis was administered before 90% of the radiological procedures. Prophylactic antibiotics were given in only 36 of 45 cholangiograms (SO%), whereas in 115 of the 123 biliary drainage procedures (93%) antimicrosbial agents were given prior to the procedure. There was no difference between the septic and non-septic groups with regard to the prophylactic antibiotic regimen. Ninety-six per cent of radiological interventions in the group that developed sepsis received prophylactic antibiotics, whereas 89% of the procedures performed in the who did not become septic groups were preceded by antibiotic administration. Cefoperazone and cefoxitin were the most frequently prescribed antibiotics (83%) for prophylaxis. Fifteen of the 74 patients died during their hospitalization, giving an overall mortality rate of 20%. Sepsis resulted in death in two patients. One patient died of congestive heart failure, and one patient haemorrhaged after a PBD procedure. The other patients died of their underlying diseases; two of these patients had cirrhosis and the remaining nine patients had metastatic carcinomas.
Discussion
Cholangitis and septic complications following PTC and PBD occur primarily among elderly patients with obstructive jaundice due to malignancy or choledocholithiasis. Previous studies of TC have shown that cholangitis occurs in 47-54% of patients with 53% of these having bacteraemia.2r3’5 Inadequate biliary drainage, biliary stasis, obstruction to bile flow, increased ductal pressures, bacterial reflux, bile leakage and procedure-related complications of catheter occlusion or dislodgement and prolonged catheter manipulation are all factors predisposing to bacteraemia.6-9 Studies have also shown lower postoperative infection rates in patients who receive antibiotic prophylaxis, before undergoing biliary procedures and studies by Cohan et al. have shown an increased incidence of infectious complications among patients with malignancies compared with those with benign disease;3 patients with underlying heart valve disease and
48
A. Sacks-Berg
et al. Table
Patient
no.
Age
III.
Procedure PTC* PTC + PBDt alone
Underlying disease
Factors associated with Antibiotic prophylaxis
b-s)
Sex
Malignancy group 1
68
F
Carcinoma of breast with metastases to porta hepatis
1
4
Cefoxitin for all five procedures
2
71
F
Pancreatic CLLS
0
1
Ampicillin, amikacin + clindamycin
3
73
M
Cholangiocarcinoma
0
1
Cefoperazone
4
67
F
Carcinoma of breast with metastases to liver
0
1
1 .PBD-cefoperazone + amikacin
5
6.5
F
Pancreatic alcoholism
carcinoma,
0
1
Cefoperazone
6
75
F
Carcinoma gall-bladder
of
4
1
Cefoxitin for first three PTC; None for fourth PTC; Cefoperazone + amikacin for PBD
7
71
M
Colon carcinoma with hepatic metastases
0
5
Cefoxitin-first three PBDs; cefoperazone last two PBDs
8
54
M
Ascending cholangitis; acute cholecystitis; diabetes mellitus
0
1
Cefoxitin
9
70
F
Chronic COPD$
3
0
Cefoperazone three PTCs
for all
10
67
M
Acute
2
0
Cefoperazone PTCs
for both
Benign group
carcinoma;
disease
cholecystitis; cholecystitis
* PTC, Percutaneous transhepatic cholangiography. t PBD, Percutaneous biliary drainage. $ COPD, Chronic obstructive pulmonary disease. 0 CLL, Chronic lymphatic leukaemia.
immunosuppressed patients were considered at high risk for bacteraemia and antibiotic prophylaxis was recommended. For patients with neither of antibiotic recommendations remain these risk factors, prophylactic controversial.’ However, in another study, patients who were undergoing endoscopic retrograde cholangiopancreatography (ERCP) for obstructive jaundice and who received antibiotic prophylaxis, showed no septicaemic episodes, while 4-3 % of patients without prophylaxis developed infectious complications.” In our study, there were 74 patients with obstructive jaundice who
Sepsis and transhepatic sepsis in transhepatic
Blood cultures
cholangiography
49
cholangiography
Fever 101-F
onset fever
of
onset of bacteraemia
Outcome
Enterobacter
cloacae
Yes
Within 24 h of third PBDl
Within 24 h of third PBD
Expired 14 days after last procedure--was not septic
Enterobacter
cloacae
Yes
5 days b&ore
1 day before
Survived-discharged home
to
Survived-discharged home
to
Survived-discharged home
to
17 days after PBD
Survived-discharged home
to to
Acinetobacter
anitratus
Yes
Within PBD
Acinetobacter
anitratus
Yes
2 days before PBD
PBD
24 h of
Within PBD
first
24 h of
PBD
24 h of
2 days after PBD
first
Enterococcus
sp.
Yes
Within PBD
Enterococcus
sp.
NO
N/A
8 days after fourth PTC
Survived-discharged home
Enterococcus sp. Klebsiella pneumoniae, Serratia marcescens, viridans streptococcus
NO
N/A
1 day before PBD
Died 10 days after last procedure-septic
Streptococcus constellatus, Klebsiella pneumoniae
Yes
13 days before
PBD
13 days before
Bacteroides
fragilis
Yes
12 days before PTC
first
Escherichia
coli
Yes
2 days before PTC
first
fifth
PBD
Survived-discharged home
to
49 days after first PTC
Survived-discharged home
to
2 days before PTC
Survived-discharged home
to
first
underwent either PTC or PTC plus PBD. Seven of 53 (13%) with malignancy had septic episodes as did three of 21 (14%) with benign disease. In patients undergoing cholangiogram and PBD who received prophylactic antibiotics there was no difference in the incidence of sepsis between those with malignant and benign diseases. These results contrast infectious complications and with studies done by Cohan et al. in which mortality were higher in patients with malignancies compared to patients with benign disease.3 The use of antibiotics did not prevent febrile and septic episodes from occurring and 24% of febrile patients had significant
50
A. Sacks-Berg
et al.
bacterial isolates from blood cultures, with a resultant septic mortality of 13.5%. Fever occurring prior to radiological intervention was most likely due to cholangitis secondary to the underlying obstructive process whether benign or malignant, whereas febrile episodes that occurred in the 24 h after the procedure were related to bacteraemia secondary to manipulation during procedures despite prophylactic antibiotics. (In the presence of biliary obstruction antibiotic concentrations in the biliary tract are often suboptimal.) Fever occurring between 24 and 72 h after PTC or biliary decompression was more likely to be due to prolonged manipulation, biliary leakage or catheter occlusion/dislodgement. The overall mortality rate of 13.5% secondary to sepsis is comparable to that of other studies, but lower than the 17% reported by Kadir et aZ.’ and much lower than the 50-70% reported in patients with cholangitis.‘-‘a’ This difference may be due to the fact that our patients were elderly. This study emphasizes the importance of prophylactic antibiotics to prevent episodes of cholangitis or sepsis in elderly patients undergoing PTC and/or PBD with an underlying biliary obstruction. However, this study also suggests that despite antibiotic prophylaxis, infectious complications remain a common problem following percutaneous biliary decompression. In the patients studied, there was no difference in bacteraemia rates between malignant and benign conditions. Bacteraemias in elderly patients undergoing PTC/PBD are related to pre-existing biliary obstruction or septic complications and are not significantly reduced by antibiotic prophylaxis. We wish to thank data retrieval.
Ms. Angela
Mitrani,
R.N.
and Ms. Andrea
Yanelli
for their
assistance
in
References 1. Bedikian AY, Valdivieso M, De La Cruz A, Martin R, Luna M, Guinee VF, Bodey GP. Cancer of the extrahepatic bile ducts. Med Pediutr Oncol 1989; 8: 53-61. 2. Carrasco CH, Zornoza J, Bechtel WJ. Malignant biliary obstruction: complications of percutaneous biliary drainage. Radiology 1984; 152: 343-346. 3. Cohan RH, Illescas, FF, Safed M, Perimutt LM, Braun SD, Newman GE, Dunnick NR. Infectious complications of percutaneous biliary drainage. Invest Radio1 1986; 21; 705-709. 4. Ferrucci JT Jr, Mueller PR, Harbin WP. Percutaneous transhepatic biliary drainage. Radiology 1980; 135: 1-13. 5. Low DE, Shoenut JP, Durhahn G, Morrow IM, Harding GK, Kennedy JK, Lautatzis M. Bacteremia associated with percutaneous extraction of biliary tract stones. J Infect Dis 1989; 159, 986988. 6. Harbin WP, Mueller PR, Ferrucci JT Jr. Transhepatic cholangiography: complications and use patterns of the fine-needle technique. Diagn Radio1 1980; 135: 15-22. 7. Kadir S, Baassiri A, Barth KH, Kaufman SL, Cameron JL, White RI Jr. Percutaneous biliary drainage in the management of biliary sepsis. Am J Radio2 1982; 138: 25-29. E, Ferrucci JT Jr. Percutaneous biliary drainage: technical 8. Mueller PR, van Sonnenberg and catheter-related problems in 200 procedures. AmY Radio1 1982; 138: 17-23. RL. Percutaneous biliary GR, Bender CE, Williams HJ Jr, MacCarty 9. May decompression. Sem Interven Radio1 1985: 2: 31-30. Y, Spinrad S, Rattan J. Septic complications following endoscopic 10. Siegman-Igra retrograde cholangiopancreatography: the experience in Tel Aviv Medical Center. r. Hasp Infect 1988; 12: 7-12.
of Hospital
Infection
(1992) 20, 43-50
Sepsis associated with transhepatic cholangiography A. Sacks-Berg, Infectious University
0. V. Calubiran,
H. Y. Epstein,
B. A. Cunha
Disease Division and the Department of Radiology, WinthropHospital, Mineola, New York, USA and S. U.N. Y. School of Medicine, Stony Brook, New York, USA Accepted for publication
24 October 1991
Summary: A retrospective study was carried out of 74 elderly patients with obstructive jaundice undergoing percutaneous transhepatic cholangiography (PTC) and/or percutaneous biliary drainage (PBD) in order to assess the effect of prophylactic antibiotics on the incidence of fever and sepsis complicating these procedures. Seventeen patients underwent PTC alone, while 57 had both PTC and PBD. Fifty-three patients had either primary or metastatic malignancy. In the other patients with benign disease, choledocholithiasis was the most common reason for undertaking these procedures. Prophylactic antibiotics were given in 80% of cholangiographies and 93 % of biliary drainage procedures. There was an overall incidence of sepsis of 13.5%. Enterobacter cloacae and Acinetobacter anitratus were the most common blood culture isolates in patients with malignant biliary obstruction. The incidence of fever was no different between patients who underwent PTC alone compared with those who had PTC and PBD. Of 24 patients who developed fever, two died secondary to sepsis. Although there was no difference in the rate of sepsis and febrile episodes between the two groups, the risk of septic episodes and mortality emphasizes the need for antibiotic prophylaxis and early therapy in elderly patients undergoing percutaneous biliary drainage procedures. Keywords: prophylactic
Transhepatic antibiotics.
cholangiography;
biliary
obstruction;
septicaemia;
Introduction Percutaneous biliary drainage (PBD) is used as a temporary procedure prior to operative surgery, or as a palliative measure for decompression in patients with a biliary obstruction secondary to malignancy or choledocholithiasis, to improve the patient’s condition. A percutaneous transhepatic cholangiogram (PTC) is perfformed in order to visualize and define the area of obstruction for emergent decompression with PBD or eventual planned surgery. Infectious complications, which include ascending cholangitis and biliary sepsis following the procedure, contribute significantly to morbidity Correspondence Hospital,
to: Mine&,
0195&6701/92/010043+08
Burke NY
A.
Cunha,
11501,
USA.
M.D.,
Chief,
Infectious
$03.00/O
Disease
Division,
Winthrop-University
0 1992 The Hospeal
43
Infection
Society
A. Sacks-Berg
44
et al.
and mortality with rates as high as 76% noted in previous studies.“-’ The risk of sepsis from obstructive jaundice may be due to several factors including the exogenous introduction of pathogens during percutaneous catheter insertion. Many elderly patients with an obstructed biliary tract will have bacteria in the bile before percutaneous biliary drainage is performed. Therefore, although the term antibiotic prophylaxis is generally used to signify drug administration before the procedure, the term prophylaxis in this setting really represents early empirical therapy. Febrile episodes, with or without bacteraemia, were reviewed in 74 patients who underwent PTC and/or PBD. Morbidity and mortality among patients with either malignant or benign disease were compared with respect to antibiotic prophylaxis. Patients
and methods
Seventy-four patients with obstructive jaundice underwent PTC and/or PBD at Winthrop-University Hospital between 23 January 1984 and 1 July 1987. There were 46 men and 28 women; the average age was 67 years. retrospectively for the (Table I). Medical records were examined development of fever (2 101” F), bacteraemia, antibiotic prophylaxis and mortality. Sepsis was defined as either (a) bacteraemia with more than two of three blood cultures positive with bacterial pathogens, or (b) the development of fever, chills and hypotension in the presence of positive blood cultures. Prophylactic antibiotics were administered at various times before the procedure. Most commonly, 2 g of cefoperazone was given 12-hourly or 2 g Table
I. Details
of patients
and antibiotic
All patients Number of patients Sex: Male Female Average age (years) Underlying diseases: Malignant Benign Number of radiological PTC PBD Total Prophylaxis given for: PTC PBD Total Mortality
prophylaxis
Patients
with sepsis
Patients
without sepsis
74 28 46 67
10 4 6 68
64 24 40 67
53 21
7 3
46 18
45 123 168
10 16 26
35 107 142
36 (80%) 115 (93%)
9 (90%) 16 (100%) 25 (96%) 2
27 (77%) 99 (93%) 127 (89%) 13
procedures:
15
Sepsis
of cefoxitin was given given intravenously.
and
transhepatic
S-hourly,
cholangiography
used
as single
45
agents.
Both
agents
were
Results
underwent 168 radiological procedures; 4.5 Seventy-four patients cholangiograms and 123 biliary drainage procedures. Seventeen patients underwent PTC alone, while the remaining 57 patients also underwent biliary drainage procedures at the same time as PTC. Twenty-seven of these 57 patients underwent more than one drainage procedure; the average was 2.16 drainages per patient (range l-8). Biliary obstruction was secondary to malignancy in the majority of our patients. Of the 53 patients with malignancy 28 had pancreatic carcinoma, seven had cholangiocarcinorna, six had carcinoma of the gallbladder, three had metastatic lung carcinoma, three had metastatic colon carcinoma, three had breast carcinoma with metastases, two had lymphomas and one had primary liver carcinoma (Figure 1). Twenty-one patients (28%) had a benign disease causing biliary obstruction. Choledocholithiasis was the most common underlying disease in this group: eight patients were found to have stones impacted in the common bile duct, five patients had chronic cholecystitis; one patient hald a duodenal polyp obstructing the ampulla of Vater and another patient had peptic ulcer disease. One patient had persistent jaundice after an episode of haemolytic anaemia, and one patient had post-operative stenosis of the common bile duct after a cholecystectomy. Twenty-nine patients experienced a total of 37 febrile events temporally related to biliary tract manipulations. Seven temperature elevations
Pancreatic Bile Duct Gall bladder
Breast Lung Lymphoma Hepatomo 0
5
15
IO
20
25
NO. of potients
Figure 1. Types of malignancy
in elderly
patients
undergoing
PTC/PBD.
A. Sacks-Berg
46
et al.
(2 101°F) developed within the first 24 h of the procedure and eight additional temperature elevations occurred within 24 to 72 h. Sepsis resulting from the procedure per se could not be directly implicated as the explanation of fever in the majority of cases. Fourteen temperature elevations (38%) occurred in patients prior to the radiological intervention, and the remaining eight febrile episodes occurred more than 72 h after the procedure (Table II), Ten of the 17 patients who underwent cholangiography alone had temperatures of more than 101°F. One of these patients had two cholangiograms and developed fever on both occasions. Of the 4.5 cholangiograms performed in this group, there were 11 febrile events (rate 24%). Nineteen of 57 patients who underwent insertion or revision of a biliary drain experienced a total of 26 febrile episodes. There were 123 PBD procedures performed in this group; the rate of fever development was 21%. There were no differences in the rate of fevers between the group that underwent PTC alone compared with the group that had PBD as well as PTC (24% and 21% respectively) (Table III). Eighteen of the 53 patients (34%) with underlying cancers, and 11 of the 21 cases (52%) with benign disease, developed fevers. However, of the 10 associated patients with sepsis, eight (80%) were febrile. Temperatures with biliary tract instrumentation and sepsis ranged between 102 and 105” F. Seven patients with malignancies (13%) and three patients with or were considered benign disease (14%) d eveloped proven bacteraemia septic on clinical grounds. Overall, sepsis occurred in 13.5% of patients. Blood cultures were obtained during 34 of 37 febrile episodes (92%) in the 29 patients. The bile was not cultured. Six sets of blood cultures demonstrated bacterial pathogens in at least two of three cultures. Two other sets of blood cultures yielded positive results, although only in one of two cultures. In both cases, Acinetobacter anitratus was isolated and the patients were considered septic as they developed chills, fever and hypotension coinciding with the positive blood cultures. The yield of positive blood cultures in the group of febrile patients was 24%. In bacteraemias associated with malignant biliary tract obstruction Enterobacter, Acinetobacter and Serratia were the most common organisms isolated. This may reflect the changes in flora due to age, prolonged hospitalization or previous antibiotic exposure. In patients with benign Table
II.
Time of onset of fever
(> 101°F) zn relation PTC
Before procedure After procedure: Within 24 h 2472 h >72 h PTC, Percutaneous
transhepatic
cholangiography;
to radiological
PTC
procedures
and PBD
Total
5
9
14
2 1 3
:
7 8 8
PBD, percutaneous
biliary drainage.
5
Sepsis
and transhepatic
cholangiography
47
biliary obstruction, bacteraemia was due to the usual biliary pathogens except for Bacteroides fragih. Blood cultures were also obtained from 35 afebrile patients. Two sets of blood cultures demonstrated significant growth of microorganisms. An enterococcus was isolated from all three sets of blood cultures from case no. 6. Polymicrobial bacteraemia was demonstrated in case no. 7. The patient and all three blood cultures grew an was afebrile but hypotensive, Serratia marcescens and a viridans Klebsiella pneumoniae, enterococcus, streptococcus. The patient died of sepsis 10 days after the demonstration of bacteraemia. The yield of positive blood cultures in the afebrile patient group was 6%. Antibiotic prophylaxis was administered before 90% of the radiological procedures. Prophylactic antibiotics were given in only 36 of 45 cholangiograms (SO%), whereas in 115 of the 123 biliary drainage procedures (93%) antimicrosbial agents were given prior to the procedure. There was no difference between the septic and non-septic groups with regard to the prophylactic antibiotic regimen. Ninety-six per cent of radiological interventions in the group that developed sepsis received prophylactic antibiotics, whereas 89% of the procedures performed in the who did not become septic groups were preceded by antibiotic administration. Cefoperazone and cefoxitin were the most frequently prescribed antibiotics (83%) for prophylaxis. Fifteen of the 74 patients died during their hospitalization, giving an overall mortality rate of 20%. Sepsis resulted in death in two patients. One patient died of congestive heart failure, and one patient haemorrhaged after a PBD procedure. The other patients died of their underlying diseases; two of these patients had cirrhosis and the remaining nine patients had metastatic carcinomas.
Discussion
Cholangitis and septic complications following PTC and PBD occur primarily among elderly patients with obstructive jaundice due to malignancy or choledocholithiasis. Previous studies of TC have shown that cholangitis occurs in 47-54% of patients with 53% of these having bacteraemia.2r3’5 Inadequate biliary drainage, biliary stasis, obstruction to bile flow, increased ductal pressures, bacterial reflux, bile leakage and procedure-related complications of catheter occlusion or dislodgement and prolonged catheter manipulation are all factors predisposing to bacteraemia.6-9 Studies have also shown lower postoperative infection rates in patients who receive antibiotic prophylaxis, before undergoing biliary procedures and studies by Cohan et al. have shown an increased incidence of infectious complications among patients with malignancies compared with those with benign disease;3 patients with underlying heart valve disease and
48
A. Sacks-Berg
et al. Table
Patient
no.
Age
III.
Procedure PTC* PTC + PBDt alone
Underlying disease
Factors associated with Antibiotic prophylaxis
b-s)
Sex
Malignancy group 1
68
F
Carcinoma of breast with metastases to porta hepatis
1
4
Cefoxitin for all five procedures
2
71
F
Pancreatic CLLS
0
1
Ampicillin, amikacin + clindamycin
3
73
M
Cholangiocarcinoma
0
1
Cefoperazone
4
67
F
Carcinoma of breast with metastases to liver
0
1
1 .PBD-cefoperazone + amikacin
5
6.5
F
Pancreatic alcoholism
carcinoma,
0
1
Cefoperazone
6
75
F
Carcinoma gall-bladder
of
4
1
Cefoxitin for first three PTC; None for fourth PTC; Cefoperazone + amikacin for PBD
7
71
M
Colon carcinoma with hepatic metastases
0
5
Cefoxitin-first three PBDs; cefoperazone last two PBDs
8
54
M
Ascending cholangitis; acute cholecystitis; diabetes mellitus
0
1
Cefoxitin
9
70
F
Chronic COPD$
3
0
Cefoperazone three PTCs
for all
10
67
M
Acute
2
0
Cefoperazone PTCs
for both
Benign group
carcinoma;
disease
cholecystitis; cholecystitis
* PTC, Percutaneous transhepatic cholangiography. t PBD, Percutaneous biliary drainage. $ COPD, Chronic obstructive pulmonary disease. 0 CLL, Chronic lymphatic leukaemia.
immunosuppressed patients were considered at high risk for bacteraemia and antibiotic prophylaxis was recommended. For patients with neither of antibiotic recommendations remain these risk factors, prophylactic controversial.’ However, in another study, patients who were undergoing endoscopic retrograde cholangiopancreatography (ERCP) for obstructive jaundice and who received antibiotic prophylaxis, showed no septicaemic episodes, while 4-3 % of patients without prophylaxis developed infectious complications.” In our study, there were 74 patients with obstructive jaundice who
Sepsis and transhepatic sepsis in transhepatic
Blood cultures
cholangiography
49
cholangiography
Fever 101-F
onset fever
of
onset of bacteraemia
Outcome
Enterobacter
cloacae
Yes
Within 24 h of third PBDl
Within 24 h of third PBD
Expired 14 days after last procedure--was not septic
Enterobacter
cloacae
Yes
5 days b&ore
1 day before
Survived-discharged home
to
Survived-discharged home
to
Survived-discharged home
to
17 days after PBD
Survived-discharged home
to to
Acinetobacter
anitratus
Yes
Within PBD
Acinetobacter
anitratus
Yes
2 days before PBD
PBD
24 h of
Within PBD
first
24 h of
PBD
24 h of
2 days after PBD
first
Enterococcus
sp.
Yes
Within PBD
Enterococcus
sp.
NO
N/A
8 days after fourth PTC
Survived-discharged home
Enterococcus sp. Klebsiella pneumoniae, Serratia marcescens, viridans streptococcus
NO
N/A
1 day before PBD
Died 10 days after last procedure-septic
Streptococcus constellatus, Klebsiella pneumoniae
Yes
13 days before
PBD
13 days before
Bacteroides
fragilis
Yes
12 days before PTC
first
Escherichia
coli
Yes
2 days before PTC
first
fifth
PBD
Survived-discharged home
to
49 days after first PTC
Survived-discharged home
to
2 days before PTC
Survived-discharged home
to
first
underwent either PTC or PTC plus PBD. Seven of 53 (13%) with malignancy had septic episodes as did three of 21 (14%) with benign disease. In patients undergoing cholangiogram and PBD who received prophylactic antibiotics there was no difference in the incidence of sepsis between those with malignant and benign diseases. These results contrast infectious complications and with studies done by Cohan et al. in which mortality were higher in patients with malignancies compared to patients with benign disease.3 The use of antibiotics did not prevent febrile and septic episodes from occurring and 24% of febrile patients had significant
50
A. Sacks-Berg
et al.
bacterial isolates from blood cultures, with a resultant septic mortality of 13.5%. Fever occurring prior to radiological intervention was most likely due to cholangitis secondary to the underlying obstructive process whether benign or malignant, whereas febrile episodes that occurred in the 24 h after the procedure were related to bacteraemia secondary to manipulation during procedures despite prophylactic antibiotics. (In the presence of biliary obstruction antibiotic concentrations in the biliary tract are often suboptimal.) Fever occurring between 24 and 72 h after PTC or biliary decompression was more likely to be due to prolonged manipulation, biliary leakage or catheter occlusion/dislodgement. The overall mortality rate of 13.5% secondary to sepsis is comparable to that of other studies, but lower than the 17% reported by Kadir et aZ.’ and much lower than the 50-70% reported in patients with cholangitis.‘-‘a’ This difference may be due to the fact that our patients were elderly. This study emphasizes the importance of prophylactic antibiotics to prevent episodes of cholangitis or sepsis in elderly patients undergoing PTC and/or PBD with an underlying biliary obstruction. However, this study also suggests that despite antibiotic prophylaxis, infectious complications remain a common problem following percutaneous biliary decompression. In the patients studied, there was no difference in bacteraemia rates between malignant and benign conditions. Bacteraemias in elderly patients undergoing PTC/PBD are related to pre-existing biliary obstruction or septic complications and are not significantly reduced by antibiotic prophylaxis. We wish to thank data retrieval.
Ms. Angela
Mitrani,
R.N.
and Ms. Andrea
Yanelli
for their
assistance
in
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