We found that 5.5% of bacteraemic episodes were due to biliary tract infections. The most common infecting organisms were E coli and K pneumoniae, and there was a strong association with choledocholithiasis and malignancies. Almost half the malignancies were newly diagnosed and were carcinoma of the head of the pancreas, cholangiocarcinoma or liver metastases. The main cause of death was septic shock caused by “sensitive” Gram‐negative organisms or disseminated cancer in patients who were treated palliatively.
Our study showed a strong association with underlying abnormalities, in particular choledocholithiasis and malignancies that few other studies of patients with bacteraemia have detailed. Almost half the malignancies where newly diagnosed, and this demonstrates the importance of appropriate imaging in determining the nature of an underlying abnormality. We did not find the co‐existence of choledocholithiasis and malignancy that others have reported.12
The relative importance of host and bacterial virulence factors in ascending cholangitis was not addressed, although others have found that biliary tract obstruction was the most important factor for E coli
bacteraemia, not bacterial virulence.13
- Biliary tract infections that cause bacteraemia often occur in patients with an underlying structural abnormality, normally choledocholithiasis or malignancy.
- At the time of bacteraemia, the most common malignancies are carcinoma of the head of the pancreas, cholangiocarcinoma or liver metastases.
- After bacteraemia, appropriate imaging by endoscopic retrograde cholangiopancreatography (ERCP), CT or MRI of the abdomen can be useful for diagnosis of a new malignancy.
- Empirical treatment with a cephalosporin targeting Enterobacteriaceae should be given and, when the patient is hypotensive, an aminoglycoside active against ESBL‐producing coliforms should be used as adjuvant treatment.
- Biliary drainage, either by ERCP or percutaneous transhepatic cholangiography, is often required for successful clinical outcome.
The strength of this study was the analysis of over 1000 patient episodes of community‐acquired and hospital‐acquired bacteraemia, reliably allowing us to determine the proportion of bacteraemic episodes caused by biliary tract infection. A previous study of 875 bacteraemias reported 9.5% of episodes secondary to “acute cholangitis”,14
a proportion similar to ours. We are aware of only two other studies with larger numbers of bacteraemic patients with cholangitis. In a study of 78 patients,10
a single organism, most commonly E coli
or K pneumoniae
, was isolated from blood in 87% of cases, findings similar to ours. The authors, however, did not detail the presence of underlying structural abnormalities. In an Israeli study15
of 70 patients with 76 episodes of bacteraemia, 13/70 (19%) had an underlying malignancy compared with our finding of 18/49 (37%). Patients were classified into three groups: those with cholelithiasis without previous surgery; those with cholangitis after remote or recent cholecystectomy; those with pancreatic or biliary tract tumours. Dual pathology was not identified. It is unclear why fewer malignancies were identified in the Israeli study even though a similar proportion were new diagnoses following an episode of bacteraemia: 6/13 (46%) vs 8/18 (44%).
Our study had some limitations. We did not determine the prevalence of bacteraemia in acute cholecystitis, previously quoted at 7.65%.10
Bile obtained at ERCP was not routinely cultured. Although of interest, we do not believe that this was required for a correct diagnosis of ascending cholangitis. Some information from case notes was collected retrospectively, although most data were collected prospectively. Finally, although our results are applicable to other UK district general hospitals, they may be less generalisable to specialist units where liver transplant recipients are managed or where biliary drainage procedures are more common.
Symptoms, signs and laboratory tests enabled most clinicians to correctly diagnose the site of infection and start appropriate antibiotic treatment without prompting from a clinical microbiologist after blood culture results. This is in contrast with other conditions such as urinary tract infections.16
Therefore, the most important messages conveyed to the clinicians were to emphasise the association of underlying structural abnormalities, particularly choledocholithiasis or malignancy, and the importance of obtaining biliary drainage in patients with obstruction.
Enterobacteriaceae were the most common organisms isolated from the blood, in particular E coli
and K pneumoniae
, and, as in another study,14
we found a small number of polymicrobial infections. The isolation from blood of both E coli
and K pneumoniae
was similar to two previous studies,10,16
although detection of ESBL‐producing organisms that had multiple drug resistance was new and has only been recently described.17
In another study, enterococci were more often isolated from blood and bile in patients with acute cholecystitis.18
On the basis of these findings, many doctors favour the use of co‐amoxiclav or piperacillin/tazobactam as empirical treatment for biliary tract infection. E faecalis
is, however, a “low‐virulence” organism, and co‐amoxiclav and piperacillin/tazobactam are not reliable treatments for infections caused by ESBL‐producing Enterobacteriaceae.19,20
Our microbiological data suggest that cefuroxime (intravenous) and metronidazole (intravenous) are optimal first‐line treatments, although, in hypotensive patients, an aminoglycoside active against ESBL‐producing coliforms should be used as adjuvant therapy.
In addition to antibiotics, successful management of patients often requires biliary drainage, either transhepatically or by sphincterotomy and biliary stenting at ERCP. Many patients required ERCP for both diagnostic and therapeutic reasons. Most of these procedures were successful, comparing favourably with audits performed at other centres.21,22
We did not audit the proportion of patients with choledocholithiasis listed for elective cholecystectomy as is appropriate for patients who have suffered a life‐threatening complication.
Doctors and clinical microbiologists should be aware that bacteraemia caused by biliary tract infection often occurs in patients with an underlying biliary tract abnormality. Appropriate imaging can diagnose a new underlying malignancy, and we reported a significant minority of patients who presented with malignancy‐associated cholangitis in the absence of choledocholithiasis. Death following bacteraemia caused by biliary tract infection is uncommon. Treatment should target Enterobacteriaceae with a cephalosporin, and, when the patient is hypotensive, an aminoglycoside effective against ESBL‐producing E coli or K pneumoniae should also be administered. Biliary drainage, by ERCP or percutaneous transhepatic cholangiography, is often required for a successful clinical outcome.