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ORIGINAL ARTICLE
Bacterial infections are a serious complication of end-stage liver disease (ESLD) that occurs in 20% to 60% of patients. We
retrospectively reviewed medical records of patients with ESLD who were identied by our microbiology laboratory as having
Streptococcus salivarius bacteremia. Of 592 patients listed for transplantation between January 1998 and January 2006, 9
(1.5%) had 10 episodes of S salivarius bacteremia. Of 2 patients already receiving quinolone prophylaxis for spontaneous
bacterial peritonitis (SBP), 1 later presented with a second episode. The male-to-female ratio was 1:1.2. Medians for age,
Model for End-Stage Liver Disease score, and Child-Turcotte-Pugh score were 50 years, 17, and 10, respectively. Presenting
symptoms and signs in 10 episodes of infection were ascites (in 8 episodes), elevated temperature (6), abdominal pain (5), and
encephalopathy (4). Median laboratory values included: white blood cell count, 15.1 109/L; creatinine, 0.9 mg/dL; albumin,
3.1 gm/dL; aspartate aminotransferase, 64 U/L; alanine aminotransferase, 52.5 U/L; ammonia, 67 g/dL; and prothrombin
time, 17.3 seconds. Ascitic uid in patients with peritonitis showed a median white blood cell count of 466 cells/mm3 (range,
250-12,822 cells/mm3), with 66% polymorphs, protein of 0.9 gm/dL, and albumin of 0.4 gm/dL. S salivarius may cause primary
bacteremia and SBP in liver transplantation candidates despite quinolone prophylaxis. Liver Transpl 13:1582-1588, 2007.
2007 AASLD.
Received April 5, 2007; accepted June 24, 2007.
Bacterial infections are a common and serious complication of end-stage liver disease (ESLD). Their prevalence has been reported to range from 20 to 60%.1,2
They are associated with increased morbidity and overall in-hospital mortality.1,2 Proposed mechanisms for
increased risk of infection are changes in humoral immunity with a decreased synthesis in the complement
system,3 a decrease in the phagocytosis capability of
the hepatic reticuloendothelial system,4 an alteration
in the function of neutrophils,5,6 and a reduction in
opsonic activity of ascitic uid.7 In addition, rupture of
natural barriers induced by invasive diagnostic or therapeutic procedures may be involved in the pathogenesis of infections.
Commonly observed infections in cirrhotic patients
are pneumonia, urinary tract infection, spontaneous
bacterial peritonitis (SBP), and bacteremia. Most of
Abbreviations: ESLD, end-stage liver disease; SBP, spontaneous bacterial peritonitis; VGS, viridans group streptococci.
Address reprint requests to Shimon Kusne, MD, Division of Infectious Diseases, Mayo Clinic, 13400 East Shea Boulevard, Scottsdale, AZ 85259.
Telephone: 480-342-0115; FAX: 480-342-2324; E-mail: kuse.shimon@mayo.edu
DOI 10.1002/lt.21277
Published online in Wiley InterScience (www.interscience.wiley.com).
Age (yr)
Gender
CTP score
MELD score
Prior SBP
54
52
30
60
35
47
66
50
39
M
F
M
M
F
F
F
M
F
9
10
10
9
11
10
6
NA
NA
13
13
17
20
21
17
22
NA
NA
No
No
No
No
Yes
No
No
No
No
CTP, Child-Turcotte-Pugh; F, female; M, male; MELD, Model for End-Stage Liver Disease; NA, not available; NASH,
nonalcoholic steatohepatitis; PSC, primary sclerosing cholangitis.
RESULTS
Of 592 patients with ESLD listed for liver transplantation between January 1998 and January 2006, 9 (1.5%;
4 men and 5 women) were identied as having 10 episodes of symptomatic S salivarius infection. The demographic features of these 9 patients are summarized in
Table 1. The median age of the group was 50 years
(range, 33-66 yr). Eight patients had underlying
Laboratory Data
The median white blood cell count for the group of 9
patients was 15.1 109/L (range, 0.6-21.2 109/L).
The median values of liver function tests were as fol-
LIVER TRANSPLANTATION.DOI 10.1002/lt. Published on behalf of the American Association for the Study of Liver Diseases
TABLE 2. Clinical and Laboratory Features of 9 Patients With Streptococcus salivarius Infection
Patient #
Clinical
diagnosis
Laboratory data
Microbiology
Blood culture
grew S
salivarius (2 of
2 bottles)
Primary
bacteremia
Temperature 38.6C;
encephalopathy and
ascites; no prior SBP
prophylaxis
Temperature 39.4C;
abdominal pain and
ascites; no prior SBP
prophylaxis
Temperature 38.4C
and ascites; no prior
SBP prophylaxis
Presented with
abdominal pain,
nausea, vomiting,
cough,
encephalopathy,
ascites, and rightsided hydrothorax;
prior treatment of SBP
of unclear etiology
followed by
ciprooxacin
prophylaxis
Temperature 38.4C;
abdominal pain,
nausea, vomiting,
SOB, cough, and
ascites; no prior SBP
prophylaxis
Blood culture
grew S
salivarius (1
bottle each in
2 sets); ascitic
uid was
sterile
Blood culture
grew S
salivarius (1 of
3 bottles);
ascitic uid
culture was
sterile
Blood culture
grew S
salivarius (3 of
3 bottles);
ascitic uid
culture grew S
salivarius
Blood culture
grew S
salivarius (1 of
2 bottles);
ascitic uid
culture was
sterile
Primary
bacteremia
Blood culture
grew S
salivarius (2 of
2 bottles);
ascitic uid
culture grew S
salivarius
Blood culture
grew S
salivarius (2 of
2 bottles);
ascitic uid
culture grew S
salivarius
Blood culture
grew S
salivarius (3
of 4 bottles);
ascitic uid
culture
grew S
salivarius
Blood culture
grew S
salivarius (3
of 3 bottles);
no ascites
Blood culture
grew S
salivarius (1
of 3 bottles);
no ascites
6a
6b
Presented 1 month
after initial episode
with temperature
40.4C, nausea,
abdominal pain,
ascites, and
encephalopathy
Temperature 38.1C;
abdominal pain,
nausea, vomiting,
hypotension, and
ascites; no prior
SBP prophylaxis
Temperature 38.8C
with neutropenia
after therapy for
NHL; no prior SBP
prophylaxis
Temperature 37.8C
and
encephalopathy; no
prior SBP
prophylaxis
Treatment
Outcome
Vancomycin HCl
and piperacillin
sodium/
tazobactam
sodium (14
days)
Cefotaxime
sodium, then
oral
metronidazole (7
days)
Responded;
underwent DDLT
11 months later
Responded;
underwent DDLT
2 months later
SBP
Ceftriaxone
sodium, then
oral amoxicillin
Responded;
underwent LDLT
3 months later
SBP
Ceftriaxone
sodium (5 days)
Responded; later
lost to follow-up
SBP
Cefotaxime
sodium, then
ceftriaxone
sodium (15
days)
Responded;
underwent LDLT
3 weeks later
SBP
Cefotaxime
sodium (5 days),
then started on
weekly
prophylaxis dose
of ciprooxacin
HCl
Ceftriaxone
sodium (14
days)
SBP
Responded;
underwent LDLT
4 months later
SBP
Vancomycin HCl
and
piperacillin
sodium/
tazobactam
sodium (21
days)
Responded;
underwent
DDLT 2
months later
Presumptive
endocarditis
Ceftriaxone
sodium (28
days)
Responded;
awaiting liver
transplantation
Primary
bacteremia
Ceftriaxone
sodium
Abbreviations: ALP, alkaline phosphatase; ALT, alanine aminotransferase; AST, aspartate aminotransferase; DDLT, deceased
donor liver transplantation; GI, gastrointestinal; LDLT, living donor, liver transplantation; NHL, non-Hodgkin lymphoma;
SOB, shortness of breath; WBC, white blood cell count.
lows: aspartate aminotransferase, 64 U/L (range, 31590 U/L); alanine aminotransferase, 52.5 U/L (range,
32-1,750 U/L); and alkaline phosphatase, 204.5 U/L
LIVER TRANSPLANTATION.DOI 10.1002/lt. Published on behalf of the American Association for the Study of Liver Diseases
total protein, 5.2 gm/dL (range, 4.0-7.5 gm/dL); albumin, 3.1 gm/dL (range, 1.7-3.7 gm/dL); bilirubin, 2.5
gm/dL (range, 0.5-31.6 gm/dL); prothrombin time,
17.3 seconds (range, 13.7-150 seconds); international
normalized ratio, 1.38 (range, 1.0-2.58); and ammonia,
67 g/dL (range, 31-619 g/dL). All blood cultures
from the group grew S salivarius. Paracentesis was performed in all but 1 patient (no. 1). Ascitic uid showed:
466 nucleated white blood cells/mm3 (range,
250-12,822 nucleated white blood cells/mm3); 66%
polymorphs (range, 1%-95%); total protein, 0.9 gm/dL
(range, 0.8-1.0 gm/dL); and albumin, and 0.4 gm/dL
(range, 0.2-0.6 gm/dL). Ascitic uid culture from 3 patients (nos. 4, 6, and 7) grew S salivarius, which was
sensitive to penicillin, vancomycin hydrochloride, levooxacin, and ceftriaxone sodium, and resistant to
erythromycin. Five patients were diagnosed with 6 episodes (including 1 relapse) of SBP on the basis of our
denition as detailed in the Patients and Methods section.
Diagnoses
Of 10 episodes, 8 were community-acquired, 1 was
hospital-acquired, and 1 was a relapse within 1 month
of prior S salivarius peritonitis. Six episodes were diagnosed as secondary to SBP. One patient (no. 8) had
signs indicative of possible vegetations on the aortic
valve on a transthoracic echocardiogram and was
treated for a presumptive diagnosis of endocarditis. He
was not known to have any preexisting valvular disease. The source of infection was not clear in the remaining patients and hence was labeled as primary
bacteremia. All patients were treated with appropriate
antibiotics for a median of 14 days (range, 5-28 days).
Outcomes
Follow-up blood culture and paracentesis were conducted before patients were discharged from the hospital. All but 1 patient was cured after treatment. One
patient (no. 6) had a relapse of S salivarius bacterial
peritonitis 1 month after the initial episode while taking
ciprooxacin prophylaxis. She was initially treated with
intravenous cefotaxime sodium for 5 days. She then
was continued on 750 mg ciprooxacin every week for
prophylaxis. However, the organism responsible for the
second episode was susceptible to quinolones. During
the second episode, this patient was treated with intravenous ceftriaxone for 14 days and had a good response
to therapy. The patient who was admitted for fulminant
hepatic failure died 8 days after admission due to multiple organ failure. There were no mortalities related to
S salivarius bacterial infection. One patient (no. 4) was
lost to follow-up within 3 months. Of the other 7 patients with chronic liver disease still on the liver transplant list, 6 had undergone liver transplantation (3 deceased donor and 3 living donor) at follow-up. One
patient (no. 8) was awaiting liver transplantation as of
this writing.
DISCUSSION
The management of complications from cirrhosis has
been revolutionized in the past decade. With the extension of liver transplant programs, more invasive diagnostic procedures are being performed more frequently.
These may have predisposed the patients to infections
with more common and usually nonpathogenic inhabitants of skin, oropharyngeal areas, and the gastrointestinal tract. Another problem is emergence of resistant infections in patients who are on long-term
selective intestinal decontamination.10
S salivarius is a gram-positive organism that belongs
to viridans group streptococci (VGS).11 It is a relatively
nonvirulent bacterium that is part of the normal oral
ora.12 It is rarely isolated from blood and is usually
considered a contaminant. In 1 study, 68% of the isolates were considered either contaminants or of unclear
signicance.13 There are case reports of S salivarius
infection involving the eyes,14 the endocardium,15 the
bloodstream in neutropenic patients,16,17 and the central nervous system in patients with neoplasia or iatrogenia.18,19
There are few reports of S salivarius SBP in patients
with underlying liver disease. Peterson20 reported a
case of S salivarius SBP in a 50-yr-old male patient with
ESLD due to chronic hepatitis C. The patient was
treated with ciprooxacin hydrochloride for 3 days, followed by levooxacin for 7 days (10 days of total treatment), with the intention of maintaining him on prophylactic noroxacin. There was no reported
information on cure. A second case report was of a
61-yr-old male patient with alcohol-related ESLD who
was diagnosed with S salivarius SBP.21 He was treated
with intravenous third-generation cephalosporin and
oral amoxicillin. He responded to treatment and was
maintained on noroxacin prophylaxis.
We identied 10 episodes of symptomatic S salivarius
infection in 9 (1.5%) of 592 patients with ESLD who
were managed in our institution. Six episodes were due
to SBP. In the other 3 patients, the source of bacteremia
was unclear. One patient had a diagnostic upper gastrointestinal endoscopy without any intervention before
the onset of the symptoms. Bacteremia after an upper
gastrointestinal endoscopy is not rare. Carley22 reported a case of S salivarius bacteremia after upper
gastrointestinal endoscopy and cauterization for gastric bleeding. Meningitis later developed in this patient.
S sanguis bacteremia and peritonitis have been reported after sclerotherapy.23 One patient in our series
had S salivarius bacteremia 1 week after endoscopic
variceal ligation. Endoscopic variceal ligation has been
associated with asymptomatic bacteremia in 16% of
patients.24 The isolated organisms in that series were
gram-positive oral or skin commensals. However, no
case of peritonitis was reported by those authors. Dental evaluation was conducted as part of the pretransplantation workup. None of our patients had any dental
procedure before the onset of S salivarius infection.
Kiddy et al.25 reported 4 cases of VGS peritonitis in
patients receiving continuous ambulatory peritoneal
LIVER TRANSPLANTATION.DOI 10.1002/lt. Published on behalf of the American Association for the Study of Liver Diseases
CONCLUSIONS
S salivarius, a nonpathogenic and commensal organism, may cause symptomatic infection in patients with
ESLD. This streptococcal infection may be associated
with increased morbidity. We did not observe any mortality among our patients. A high proportion of patients
with liver failure who present with S salivarius bacteremia may have SBP. Prophylaxis with quinolones may
not be adequate to prevent future episodes of S salivarius peritonitis.
LIVER TRANSPLANTATION.DOI 10.1002/lt. Published on behalf of the American Association for the Study of Liver Diseases
ACKNOWLEDGMENT
Editing, proofreading, and reference verication were
provided by the Section of Scientic Publications, Mayo
Clinic.
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