543

Bacteremia Due to Citrobacter Species: Significance of Primary Intraabdominal

Infection
Chiang-Ching Shih, * Yee-Chun Chen,
Shan-Chwen Chang, Kwen-Tay Luh,
and Wei-Chuan Hsieh

From the Section of Infectious Disease, Department of Internal

Medicine and the Department of Laboratory Medicine, National Taiwan
University Hospital, Taipei, Taiwan. Republic of China

From 1982 to 1994, 45 patients (1.22 episodes per 10,000 discharged patients) were treated for
citrobacter bacteremia at National Taiwan University Hospital (Taipei). All patients had at least one
underlying disease. Citrobacter bacteremia most commonly occurred in patients with malignancies
(48.9%) or hepatobiliary stones (22.2%). Intraabdominal tumors comprised the majority (59.1%) of
malignancies. Bacteremia commonly originated from sites such as the abdominal cavity (51.1%), urinary
tract (20%), and lung (11.1%). Polymicrobial bacteremia was diagnosed in 15 patients (33.3%);for nine
(60%) of these patients, the source of the infection was intraabdominal. Prior treatment with a thirdgeneration cephalosporin was significantly associated (P < .01) with the development of multidrug
resistance among the isolates. The mortality associated with citrobacter bacteremia was 17.8%. Poor
prognostic factors included pneumonia, altered mental status on presentation, hypothermia, oliguria,
septic shock, deterioration in mental status, hyperbilirubinemia, azotemia, and thrombocytopenia. Combination therapy, as compared with other regimens, improved the outcome of citrobacter bacteremia.

Citrobacter species are aerobic, gram-negative bacilli commonly found in water, soil, food, and the intestinal tracts of
animals and humans [I]. These organisms cause a wide spectrum of infections in the urinary tract, respiratory tract, wounds,
bone, peritoneum, endocardium, meninges, and intestines [1].
Citrobacter bacteremia is a rare infection; we are aware of
only two reported series in the English-language literature
[2, 3]. Therefore, little is known about citrobacter bacteremia
in terms of incidence, associated underlying diseases, primary
sites of infection, and outcome. Although differences between
Citrobacter freundii and Citrobacter divers us in terms of antimicrobial susceptibility have been cited [3-6], that these differences exist when these organisms are the cause of bacteremia
is unclear. Citrobacter has been reported to be frequently associated with polymicrobial bacteremia [3], but there are no data
that explain this phenomenon.
After the the third-generation cephalosporins were introduced, multidrug resistant strains of Enterobacter emerged as
a cause of bacteremia [7], but no data are available on Citrobacter species. We review our experience with citrobacter bacteremia over a B-year period and compare it with that previously reported in the literature [2, 3].

Patients and Methods

We reviewed the hospital records from 1 January 1982
through 31 December 1994 for all patients whose blood cul-

Received 18 January 1996; revised 26 March 1996.

* Current address: Koo Foundation Sun Yat-Sen Cancer Center, Taipei,
Taiwan, Republic of China.
Reprints or correspondence: Dr. Shan-Chwen Chang, Department ofIntemal
Medicine, National Taiwan University Hospital, No.7, Chung-Shan South
Road, Taipei, Taiwan, Republic of China.
Clinical Infectious Diseases

1996; 23:543-9

1996 by The University of Chicago. All rights reserved.

1058--4838/96/2303 -0020$02.00

tures yielded Citrobacter species at the National Taiwan University Hospital (Taipei), a major teaching hospital in Taiwan;
this hospital had 1,200 beds before 1991 and 1,500 beds after
1991. The blood culture medium used to grow Citrobacter
had been changed from trypticase soy broth containing sodium
polyanetholesulfonate and modified Lombard-Dowell broth to
the Bactec 6A broth and the Bactec 7A broth (Becton Dickinson, Sparks, MD) in 1987. Citrobacter species were identified
according to standard laboratory methods. Antimicrobial susceptibility tests were done by means of the Kirby-Bauer disk
diffusion method [8, 9]. Multidrug-resistance was defined as
resistance in vitro to the extended-spectrum penicillins (ticarcillin, ticarcillinlclavulanate, and piperacillin) and the third-generation cephalosporins (cefotaxime, ceftazidime, ceftizoxime,
ceftriaxone, and cefoperazone) [7].
A patient was considered to have citrobacter bacteremia
when this organism was isolated from blood cultures on at least
one occasion. The primary site of infection was determined on
the basis of a clinical picture that was consistent with the
laboratory data and/or by a culture of tissue that was positive
for a Citrobacter species. If none of these findings was present,
the origin of the bacteremia was deemed unknown. Bacteremia
was defined as nosocomial if infections were acquired during
treatment at the study hospital, at other hospitals before transfer
to the study hospital, or during out-patient clinic visits or emergency room visits. Otherwise, the bacteremia was considered
to be community acquired.
The empirical treatment was considered appropriate if all
organisms cultured were found to be susceptible to the drug(s)
during in vitro susceptibility testing. Treatment was defined as
delayed if no appropriate treatment was begun within 48 hours
after blood for cultures was drawn. Septic shock was defined
as the septic syndrome, with a systolic blood pressure of <90
mm Hg or a drop in the mean arterial pressure of >40 mm
Hg from the baseline, in the absence of other causes of hypoten-

544

Shih et al.

sion. Outcome was evaluated at discharge or 1 month after

treatment was started. Death was considered bacteremia-related
if patients died within 10 days of the report of positive culture
results. Patients who died of other conditions and had obvious
initial clinical responses after receiving antibiotic treatment
were excluded from the study.
Statistical analysis was performed with use of the X2 test
and a two-tailed Fisher's exact test. The odds ratios and 95%
confidence intervals were calculated at the same time. The logit
estimators used a correction of 0.5 in every cell of those labels
that contained a zero.
Results

From 1982 through 1994, 56 blood cultures for 45 patients

yielded Citrobacter species, and these isolates accounted for
0.55% of the 10,263 blood isolates recovered at our hospital
during this period. Twenty-two patients (48.9%) were male,
and 23 patients (51.1%) were female. The ages ranged from 2
days to 86 years (median age, 60 years). Eight patients (17.8%)
were < 18 years of age.
Of the 45 episodes of bacteremia, 21 occurred during the
first 6.5 years of the study period (1.28 episodes per 10,000
patients discharged) and the remaining 24 episodes occurred
in the second period (1.18 episodes per 10,000 patients discharged). No significant change in the incidence of citrobacter
bacteremia was found during this 13-year period. Throughout
the entire study period, recovery of Citrobacter isolates from
blood appeared to be random, since the isolates were not clustered by season or in outbreaks. Twenty-three episodes (51.1%)
were community acquired, and 22 (48.9%) were nosocomial.
Underlying diseases. The patients' underlying diseases are
listed in table 1. Of those who had a malignancy, five had
leukemia, and 16 had solid tumors (including 13 of intraabdominal origin). The number of cases of citrobacter bacteremia per
10,000 newly registered cancer patients in our hospital was
49.5 for those with acute leukemia, 37.8 for those with chronic
leukemia, 6.3 for those with solid tumors, and 19.9 for those
with intraabdominal tumors (table 1). Eight patients had received chemotherapy, and five of them were neutropenic (neutrophil count, <500/mm3 ) when citrobacter bacteremia developed.
Primary sites of infection. The primary sites of infection
and the numbers of patients who presented with each are listed
in table 1. Intraabdominal infections (23 patients) included
hepatobiliary tree infections (19, including three with liver abscesses), peritonitis (three), and perianal abscess (one). Ofthese
23 patients, 20 (87%) had underlying intraabdominal lesions
including hepatobiliary stones (10 patients), malignancy with
biliary obstruction (nine), and pancreatitis (one). Citrobacter
bacteremia of intraabdominal origin was often associated with
underlying intraabdominal pathology.
Eight (88.9%) of nine patients with urinary tract infections had
urinary tract abnormalities. These abnormalities included neurogenic bladder, retroperitonealfibrosis and hydronephrosis, chronic

em 1996;23 (September)

cystitis, cervical cancer and hydronephrosis, rectal cancer and

hydronephrosis, rectal cancer with a uroanal fistula, transitional
cell carcinoma, and benign prostate hypertrophy with urethral
stricture. The bacteremias that originated from the urinary tract
were also frequently associated with local lesions.
Five patients had pneumonia, which was associated (in order
of frequency) with prematurity, congestive heart failure,
lymphoma, colon cancer, and congenital heart disease with
asplenism.
Of three patients who had soft tissue infections and/or wound
infections, one had cellulitis at the irradiated site of nasopharyngeal carcinoma, and one had a skin ulcer caused by extravasation with vincristine. The other patient had chronic lymphocytic leukemia with cellulitis of the leg but no obvious
cutaneous breakdown.
One patient had citrobacter bacteremia secondary to gouty
arthritis, and one premature neonate had citrobacter meningitis.
Nineteen of 42 patients with identified origins of infection
had Citrobacter species isolated from the primary sites of infection. The specimens included bile (four patients), liver abscess
(two), gall bladder pus (two), discharge from peritoneal cavity
(one), perianal abscess (one), urine (five), lung tissue (one),
sputum (one), CSF (one), and wound discharge (one) (table 1).
Three (6.7%) of the 45 patients presented with signs of
citrobacter sepsis that had no identifiable origin. Two of these
patients were children; one had acute lymphocytic leukemia,
and the other had chemotherapy-induced leukopenia. The third
patient, a 56-year-old male, had idiopathic segmental axial
dystonia and underwent intermittent urinary catheterization;
however, the results of his urinalysis were normal.
Fifteen patients for whom a hepatobiliary origin of infection
was documented had community-acquired bacteremia. Six of
nine patients with urinary tract infections acquired the infections in the community; the other three had nosocomial infections, and all of them had undergone urinary tract manipulation
in the hospital.
Initial clinical manifestations ofbacteremia. Fever was the
most common initial manifestion of bacteremia in these patients.
Thirty-nine (86.7%) of the 45 patients had fever, two had hypothermia, and four had normal temperatures. Thirty-five febrile
patients (77.8%) had chills. Fifteen patients (33.3%) were hypotensive. Eight (18.2%) of 44 patients had altered mental status,
and 13 (32.5%) of 40 had oliguria. Five (12.5%) of 40 had
cough, and 26 (61.9%) of 42 had abdominal pain, ileus, and/
or gastrointestinal bleeding; of these patients, 12 had jaundice.
Twenty-eight (65.1%) of 43 patients had leukocytosis (WBC
count, > 1O,000/mm3) , and five (11.4%) of 44 had neutropenia
(neutrophil count, <500/mm3) due to prior chemotherapy for
cancer.
Complications. Among the 45 patients, the most frequent
complication was septic shock, which was present in 15
(33.3%) of the patients. Liver dysfunction was present in 15
(33.3%) of the patients; respiratory failure, in 13 (28.9%); deteriorated mental status, in 12 (26.7%); renal dysfunction, in 11
(24.4%); and thrombocytopenia, in 7 (15.6%).

em

1996;23 (September)

545

Citrobacter Bacteremia

Table 1. Summary of data from 45 cases of citrobacter bacteremia in Taiwan.

No. of patients with indicated primary site of infection

Variable
Underlying disease
Malignancy
Solid tumor
Intraabdominal tumor
Hematological tumor
Acute leukemia
Chronic leukemia
Hepatobiliary stone
Heart disease
Diabetes mellitus
Plaee of acquisition
Community
Hospital
Etiologic organism
C. jreundii
C. diversus

Citrobacter species plus other organisms

Intraabdominal
tissues

Urinary
tract

10

9
9
I

5
3
0

Lower
respiratory
tract

Total no. of cases per 10,000

Others*

Unknown

Total

22
\6

2
I
1

3
I

13

2
I
I

0
2
2
0

4
I

49.5
37.S

a
0

1
0
0

10
2

0
I
4

0
2
0

0
0
0

0
1
0

10

1St

I
4

23

I
4

22

11
2

3
3
2

1
0

2
1

1R

5.27
6.3
19.9
26.3

I
0

newly registered patients

7
15

NOTE. The number of patients with culture-proven primary sites of infection were as follows: intraabdominal tissues, 10 of 23; urinary tract,S of 9; lower
respiratory tract, 2 of 5; others, 2 of 5; and unknown, 0 of 3.
* Includes bone and joint infection (n = 1), CNS infection (1), and wound and soft-tissue infection (3).
I All IS patients' infections originated in the hepatobiliary tract.

Bacteriology. Of the 45 episodes of citrobacter bacteremia,

18 (40%) were due to Cifrcundii, and seven (15.6%) were due
to C diversus. The Citrobacter isolates were not identified to
the species level in the remaining cases. C freundii was a
more frequent cause of bacteremia than was C diversus among
patients with infections of intraabdominal origin (table 1).
Citrobacter was isolated in association with other bacteria
(most frequently gram-negative bacilli) from 15 of the 45 patients.
Other concomitantly isolated bacteria included Escherichia coli
(six patients), Klebsiella pneumoniae (four), Bacteroides species
(three), Enterococcus species (three), Aeromonas hydrophila
(two), Morganella morganii (two), and Proteus vulgaris (one).
Polymicrobial infection was more frequent in patients with an
intraabdominal origin of infection (nine patients), a communityacquired infection (nine), or a malignancy (eight, including six
with intraabdominal malignancies).
Antimicrobial susceptibilities. Antimicrobial susceptibility
patterns were analyzed for 44 strains (these data were not available for one strain). Resistance to ampicillin, cefazolin, and
cefamandole was common. However, almost all of the strains
tested were susceptible to gentamicin (table 2).
The percentage of C freundii isolates that were resistant to
ampicillin, cefazolin, cefamandole, and cefotaxime was higher
than the percentage of C diversus isolates that were resistant
to these drugs.
Treatment with first- or second-generation cephalosporins before the onset of bacteremia resulted in an increase in the rate of
resistance to ampicillin, cefazolin, and cefamandole but not to

cefotaxime. On the other hand, pretreatment with third-generation

cephalosporins resulted in an increase in the rate of resistance to
cefotaxime. Multidrug resistance was found in five strains and
was associated significantly (P < .01) with pretreatment with
third-generation cephalosporins. All four multidrug-resistant
strains that were tested were susceptible to ciprofloxacin.
Treatment. Thirty-five patients received appropriate antibiotic treatment. Four patients did not receive appropriate treatment within 48 hours of the onset of bacteremia, and five did
not receive any effective medical treatment. Two of these nine
patients died of bacteremia. The appropriateness of the treatment one patient received could not be judged because the
drug susceptibilities of his isolates were not determined.
The 45 patients received one or more of the following antibiotics: penicillins (two patients [4.4%]); first- or secondgeneration cephalosporins (25 [55.6%]); third-generation cephalosporins (17 [37.8%]); fluoroquinolones (two [4.4%]);
nitrofurantoin (one [2.2% J); and aminoglycosides (20 [44.4% D.
Eighteen patients received combination therapy with an aminoglycoside and a ,B-lactam. Of the 18 patients who received
combination therapy, only one (5.6%) died, whereas five
(45.5%) of II patients who received monotherapy with a thirdgeneration cephalosporin died; thus combination therapy was
significantly superior to monotherapy with a third-generation
cephalosporin (OR = 0.07; 95% CI = 0.01-0.73; P = .018).
When compared with all other single-agent regimens, combination therapy was found to be more protective, although this
difference was not significant (P = .11) (table 3).

em 1996; 23 (September)

Shih et al.

546

Table 2. Rates of antimicrobial resistance and significance of factors influencing the antimicrobial susceptibilities of Citrobacter species
causing bacteremia in patients in Taiwan.

No. of indicated species

tested/no. of resistant strains
(%)
Antimicrobial agent
Ampicillin

Cefazolin
Cefamandole
Cefotaxime
Ciprofloxacin
Imipenem
Gentamicin
Multiple agents

No. of resistant strains/no.

of strains tested (%)
33/43 (76.7)
26/44 (59.1)
8/33 (24.4)
7/41 (17.1)
0117
0/13
2/43 (4.7)
5/41 (12.1)

C. freundii
16/18 (88.9)
13/18 (72.2)
8118 (44.4)
5/17 (29.2)

0117
3117 (17.7)

C. diversus

OR*

95% CI*

No. of resistant isolates/no.

of isolates from patients
pretreated with a first- or
second-generation
cephalosporin (%)

5/7 (71.1)
1/7 (l4.3)t

3.2
15.6
4.48
6.58

0.35-28.95
1.48-164.38
0.48-48.46
0.32-142.86

10/10 (100)
7110 (70)
5/7 (71.4)
2/10 (20)

3.62

0.16-76.92

0/9
2/10 (20)

1/7 (14.3)
0/7

0/7
0/7

* Determined by means of the X2 test and two-tailed Fisher's exact test.

t p = .01-.05.
t P = .05-0.1.
P = .001-.01.

Surgical procedures or drainage were performed in 10 patients.

Outcome. Fifteen (33.3%) of the 45 patients died. Six of
these 15 patients died of causes other than bacteremia, although
they responded well to treatment of bacteremia. One other
patient died of hepatic failure that was associated with gastric
cancer, and the bacteremia probably contributed to his death.
Eight (17.8%) of the 45 patients died of bacteremia. Table 3
lists potential risk factors for death due to citrobacter bacteremia. The initial manifestations that were significant risk factors included pneumonia, altered mental status, hypothermia,
and oliguria, and complications during the course of the illness
that were significant included septic shock, further deterioration
in mental status, hyperbilirubinemia, hypercreatinemia, and
thrombocytopenia. Polymicrobial bacteremia and alcoholism
were also associated with an increase in mortality, but this
increase was not significant statistically.
Factors such as old age, cold weather, place of acquisition,
the primary site and/or manifestation of the infection (except
pneumonia), antibiotic resistance, the initial presence of hypotension, the leukocyte count, chemotherapy, previous invasive
procedure, pretreatment, delayed treatment, or no treatment
did not have significant influence on mortality. Appropriate
treatment did not result in lower mortality. Although infection
that originated in the urinary tract was associated with lower
mortality, the difference was not significant. Surgical intervention and combination therapy were associated with a protective
effect.
Discussion
Citrobacter species have been reported as a cause of many
kinds of human infections [1, 6, 10-13], but bacteremia due
to these organisms remains uncommon. The incidence of Citro-

bacter bacteremia among our patients was similar to that reported by Drelichman and Band [3].
The urinary tract was the leading site of citrobacter infection
in many previous reports [1-3, 14], including the two that
described citrobacter bacteremia [2, 3]. However, in our series,
intraabdominal tissues (mainly in hepatobiliary system) were
the most common primary sites of infection in bacteremic patients. The reason that such sites predominated in our series
was that a large portion of our patients had hepatobiliary stones
(22.2%) and intraabdominal malignancies (28.8%). Hepatobiliary infection was the most frequent (82.6% of patients) intraabdominal infection due to Citrobacter species, which is consistent with the findings of Lew et al. [15]. We emphasize that
enterococci, E. coli, and anaerobes still predominate among
patients with the pancreatic and hepatobiliary cancer and intraabdominal abscesses [16], and antimicrobial coverage for
these organisms should be considered first.
According to previous reports [1-3, 14], most citrobacter
infections have been hospital acquired. In our study, about onehalf of the cases (51.1%) were community acquired, a finding
that may be due to the predominance of cases hepatobiliary
infection (19) in our study. One large-scale study [17] showed
that hospital-acquired cases of bacteremia predominated among
patients with infections that originated from any site other than
the biliary tree and reproductive tract. Fifteen (78.9%) of the
19 patients with hepatobiliary infection in our study had community-acquired bacteremia.
In one previous report of citrobacter bacteremia in patients
with cancer [2], those with acute leukemia accounted for the
highest number with bacteremia due to Citrobacter species
alone (this number was 20 times higher than the number of
patients with solid tumors and citrobacter bacteremia). Although patients with acute leukemia still had the highest rate
of citrobacter bacteremia in our study, those with tumors of

cm

1996;23 (September)

Table 2.

(Continued)

No. of resistant isolates/no.

of isolates from patients
without pretreatment with
a first- or secondgeneration cephalosporin
(%)
23/33
19/34
7/26
5/31

547

Citrobacter Bacteremia

(69.7);
(35.9)
(26.9)t
(l6.1)

2/34 (5.9)
3/31 (9.7)

No. of resistant isolates/no.

of isolates from patients
pretreated with a thirdgeneration cephalosporin
(%)

OR*

95% CI*

9.35
1.84
6.79
1.3

0.5-166.67
0.41-8.36
1.06-43.36
0.21-8.03

6/6
6/6
4/5
4/6

0.68
2.06

0.03-45.51
0.33-16.47

0/6
3/6 (50)

the abdominal cavity were also found to have a high incidence

(10.7 cases per 10,000 newly registered patients) of the infection. Furthermore, the incidence among such patients was even
higher if cases of polymicrobial bacteremia were included (19.9
cases per 10,000 newly registered patients). We emphasize the
importance of underlying intraabdominal tumors in the development of Citrobacter bacteremia among our patients, since
this observation has not been made previously.
The incidence (33.3%) of bacteremia due to Citrobacter,
in combination with other organisms, in our hospital is similar
to that (35%-46.1 %) observed by other investigators [3, 15]
and is higher than that for bacteremias due to all organisms
(6%-17.8%) or bacteremias due to gram-negative organisms
(4%-25%) [17-23]. Isolation of Citrobacter as a part of a
mixed infection in the abdominal cavity was unexpectedly
common (nine patients) in our study. These cases presumably
represented the introduction of Citrobacter species that were
already present in the patients' gastrointestinal tracts; this
phenomenon has been mentioned in previous reports [1, 3].
One other important finding in our study was that administration of a third-generation cephalosporin within 14 days before
the onset of citrobacter bacteremia had a significant influence
on the selection of cefotaxime-resistant strains (P = .005) and
multidrug-resistant strains (P = .017). This finding confirmed
the fact that multidrug-resistant organisms may emerge more
rapidly when the third-generation cephalosporins are used routinely, as has been predicted by other investigators [7]. The
difference between C. freundii and C. diversus in terms of
susceptibility to the cephalosporins has been noted since the
1970s [2, 4-6] and has been confirmed again in this study of
strains that cause bacteremia.
Combination therapy had a protective effect in our study.
This benefit of combination therapy has been proposed by other
authors [2, 7]. Samonis et al. [24] reported that imipenem,

(l00)
(l00)
(80)
(66.7)

No. of resistant isolates/no.

of isolates from patients
without pretreatment with
a third-generation
cephalosporin (%)
27/37
20/38
8/28
3/35

(73.0)
(52.6)t
(28.6);
(8.6)

2/37 (5.4)
2/35 (5.7);

OR*

95% CI*

4.98
11.76
10
21.33

0.26-10
0.62-250
0.96-103.78
2.69-168.94

1.09
16.5

0.05-25.48
1.93-140.85

amikacin, and the new fluoroquinolones had good activity

against Citrobacter species. Our results are compatible with
their findings. Because the data are limited, we suggest the
use of combination therapy for initial empirical treatment of
citrobacter bacteremia, and the fluoroquinolones can be used
for the treatment of episodes due to multidrug-resistant strains.
However, further studies are needed to support this recommendation.
The overall mortality associated with citrobacter bacteremia was 33.3% in our series; this percentage is lower than
that (48.3%) reported by Drelichman et al. in 1985 [3]. The
mortality associated with citrobacter bacteremia is similar to
that for bacteremia due to Klebsiella species (37%) [25],
Enterobacter species (20%) [7], Proteus mirabilis (29.0%)
[21], and bacteremias due to gram-negative organisms (25%)
[4] but higher than that associated with E. coli bacteremia
(10%) [22]. In previous reports [2, 7, 19,21-23,25-27],
many risk factors including the two extremes of age, pneumonia, sources of bacteremia other than the urinary tract, alcoholism, diabetes mellitus, congestive heart failure, infection
with a multidrug-resistant strain, inappropriate treatment,
respiratory tract infection, polymicrobial bacteremia, nosocomial infection, chemotherapy-induced neutropenia, leukocytosis, septic shock, azotemia, hyperbilirubinemia, and
thrombocytopenia have all been significantly associated with
death due to gram-negative bacteremia. In our series pneumonia, altered mental status, oliguria, septic shock, deterioration
in mental status, azotemia, hyperbilirubinemia, and thrombocytopenia were found to have a significant influence on mortality. The fact that other factors were not significant was
probably due to the smaller number of cases in our study.
In conclusion, citrobacter bacteremia is uncommon and
usually develops in patients with underlying diseases.
In our series, about one-half of cases were community

548

Table 3.

em

Shih et al.

1996;23 (September)

Risk factors for death due to citrobacter bacteremia.

Risk factor
Enrollment during first 6.5 years of study*
Occurrence of bacteremia during months
of November-February
Age ;0.65 years
Male sex
Presence of underlying condition
Malignancy
Hematologic tumor
Other conditions
Intraabdominal lesions
Diabetes mellitus
Heart disease
Delayed admission
Chemotherapy
Steroid therapy
Alcoholism
Invasive procedure
Prior antibiotic treatment
Polymicrobial bacteremia
Nosocomial acquisition of bacteremia
Primary site of bacteremia
Lung
Intraabdomina1 site
Urinary tract
Multidrug resistance
Initial clinical manifestation
Hypotension
Altered mental status
Body temperature
<37C
>38SC
Oliguria
Jaundice
Leukocytosis (WBC count, > 10,000/mm3)
Neutropenia (neutrophil count, <500/nun 3)
Complications
Septic shock
Deterioration in mental status
Bilirubin level > 1 mg/dL
Increase in creatinine level of more than twofold
Platelet count, < 100,000/nun 3
Treatment
None or delayed
Delayed
Surgical/invasive procedure
Combination therapy

No. of patients who died!

no. of patients with risk
factor (%)

No. of patients who died!

no. of patients without
risk factor (%)

aRt

CIt

P value

6/21 (28.6)

2/24 (8.3)

4.40

0.78-24.81

NS

3/14 (21.4)
2/15 (13.3)
5/22 (22.7)

5/31 (16.1)
6/30 (20)
3/23 (13.0)

1.42
0.62
1.96

0.29-6.99
0.11-3.50
0.41-9.43

NS
NS
NS

3/22 (13.6)
1/6 (16.7)

5/23 (21.7)
2/16 (12.5)

0.57
1.4

0.12-2.73
0.10-19.01

NS
NS

2/11 (18.2)
0/5
1/6 (16.7)
1/11 (9.1)
0/8
2/7 (28.6)
2/3 (66.7)
1/15 (6.7)
3/17 (17.6)
4/15 (26.7)
4/22 (18.1)

6/34
8/40
7/39
7/34
8/37
6/38
6/42
7/30
5/28
4/30
4/23

(17.6)
(20)
(17.9)
(20.6)
(21.6)
(15.8)
(14.3)
(23.3)
(17.9)
(13.3)
(17.4)

1.04
0.35
0.91
0.39
0.2
2.13
12.33
0.23
0.99
2.36
1.05

0.18-6.07
0.02-6.94
0.09-9.10
0.04-3.54
0.01-3.91
0.33-13.67
0.96-158.08
0.03-2.11
0.20-4.78
0.50-11.19
0.21-4.76

NS
NS
NS
NS
NS
NS
NS
NS
NS
NS
NS

3/5 (60)
4/23 (17.4)
0/9
1/5 (20)

5/40
4/22
8/36
7/40

(12.5)
(18.2)
(22.2)
(17.5)

10.5
0.95
0.18
1.18

1.39-79.13
0.21-4.37
0.01-3.36
0.11-12.21

.03
NS
NS
NS

4/15 (26.7)
4/8 (50)

4/30 (13.3)
4/36 (11.1)

2.36
8

0.50-11.19
1.41-45.23

NS
.03

2/2 (100)
6/39 (15.4)
4/13 (30.8)
4/12 (33.3)
6/28 (21.4)
0/5

6/43 (14)
2/4 (50)
1/27 (3.7)
4/33 (12.1)
2/15 (13.3)
8/39 (20.5)

28.85
0.18
11.56
3.63
1.77
0.34

1.24-672.13
0.02-1.55
1.14-117.44
0.74-17.81
0.31-10.11
0.02-6.71

.03
NS
.03

7/15 (46.7)
7/12 (58.3)
6/15 (40)
7/11 (63.6)
5/7 (71.4)

1/30 (3.3)
1/33 (3.0)
1/29 (3.4)
1/34 (2.9)
1/36 (2.8)

25.38
44.8
18.67
57.75
87.5

2.71-237.58
4.50-445.75
1.97-176.45
5.57-598.44
6.65-1151.19

.0009
.0001
.003
.00005
.00013

2/9 (22.2)
1/4 (25)
1/10 (10)
1/18 (5.6)

5/35
5/35
7/35
7/27

0.27-10.74
0.17-23.25
0.05-4.12
0.02-1.51

NS
NS
NS
.11

(14.3)
(14.3)
(20)
(25.9)

1.71
2
0.44
0.17

NS
NS
NS

NOTE. NS = not significant.

* Twenty-one of 45 episodes of citrobacter bacteremia occurred during this period.
t Statistical analysis by means of the X2 test with two-tailed Fisher's exact test.

acquired. An intraabdominal site, rather than the urinary

tract, was the leading primary site of citrobacter infection.
Malignancy, especially in the intraabdominal organs, and
hepatobiliary stones were the two most predominant underlying diseases.
Citrobacter species were more often isolated in our cases of
polymicrobial bacteremia than were other gram-negative bacilli

because of the predominance of primary infections at contaminated sites, especially the abdominal cavity. When a patient
presents with citrobacter bacteremia, a thorough search for an
intraabdominal lesion should be made. Multidrug resistance
among Citrobacter species was found to be associated with
administration of a third-generation cephalosporin before the
onset of bacteremia.

cm

1996;23 (September)

Citrobacter Bacteremia

Because the data are limited, we suggest that ciprofloxacin

be considered the drug of choice for bacteremia due to these
strains. Combination therapy with a ,B-Iactarn and an aminoglycoside are suggested as the initial empirical treatment because
this combination was associated with a lower mortality rate in
our study. Septic shock with organ failure was the most important poor prognostic factor, and the need for good supportive
care for patients with this complication cannot be overemphasized.

Acknowledgment
The authors thank Professor Andrew T. F. Huang of Duke University (Durham, NC) for reviewing the manuscript.

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