543

Bacteremia Due to Citrobacter Species: Significance of Primary IntraabdominalInfection

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

From the Section of Infectious Disease, Department of InternalMedicine and the Department ofLaboratory 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 forcitrobacter bacteremia at National Taiwan University Hospital (Taipei). All patients had at least oneunderlying disease. Citrobacter bacteremia most commonly occurred in patients with malignancies(48.9%) or hepatobiliary stones (22.2%). Intraabdominal tumors comprised the majority (59.1%) ofmalignancies. Bacteremia commonly originated from sites such as the abdominal cavity (51.1%), urinarytract (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 third-generation cephalosporin was significantly associated (P < .01) with the development of multidrugresistance among the isolates. The mortality associated with citrobacter bacteremia was 17.8%. Poorprognostic factors included pneumonia, altered mental status on presentation, hypothermia, oliguria,septic shock, deterioration in mental status, hyperbilirubinemia, azotemia, and thrombocytopenia. Com-bination therapy, as compared with other regimens, improved the outcome of citrobacter bacteremia.

Citrobacter species are aerobic, gram-negative bacilli com-monly found in water, soil, food, and the intestinal tracts ofanimals and humans [I]. These organisms cause a wide spec-trum 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 ofonly two reported series in the English-language literature[2, 3]. Therefore, little is known about citrobacter bacteremiain terms of incidence, associated underlying diseases, primarysites of infection, and outcome. Although differences betweenCitrobacter freundii and Citrobacter divers us in terms of anti-microbial susceptibility have been cited [3-6], that these differ-ences exist when these organisms are the cause of bacteremiais unclear. Citrobacter has been reported to be frequently asso-ciated with polymicrobial bacteremia [3], but there are no datathat explain this phenomenon.

After the the third-generation cephalosporins were intro-duced, multidrug resistant strains of Enterobacter emerged asa cause of bacteremia [7], but no data are available on Citro-bacter species. We review our experience with citrobacter bac-teremia over a B-year period and compare it with that pre-viously reported in the literature [2, 3].

Patients and MethodsWe 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 SouthRoad, 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 Uni-versity Hospital (Taipei), a major teaching hospital in Taiwan;this hospital had 1,200 beds before 1991 and 1,500 beds after1991. The blood culture medium used to grow Citrobacterhad been changed from trypticase soy broth containing sodiumpolyanetholesulfonate and modified Lombard-Dowell broth tothe Bactec 6A broth and the Bactec 7A broth (Becton Dickin-son, Sparks, MD) in 1987. Citrobacter species were identifiedaccording to standard laboratory methods. Antimicrobial sus-ceptibility tests were done by means of the Kirby-Bauer diskdiffusion method [8, 9]. Multidrug-resistance was defined asresistance in vitro to the extended-spectrum penicillins (ticarcil-lin, ticarcillinlclavulanate, and piperacillin) and the third-gener-ation cephalosporins (cefotaxime, ceftazidime, ceftizoxime,ceftriaxone, and cefoperazone) [7].

A patient was considered to have citrobacter bacteremiawhen this organism was isolated from blood cultures on at leastone occasion. The primary site of infection was determined onthe basis of a clinical picture that was consistent with thelaboratory data and/or by a culture of tissue that was positivefor a Citrobacter species. If none of these findings was present,the origin of the bacteremia was deemed unknown. Bacteremiawas defined as nosocomial if infections were acquired duringtreatment at the study hospital, at other hospitals before transferto the study hospital, or during out-patient clinic visits or emer-gency room visits. Otherwise, the bacteremia was consideredto be community acquired.

The empirical treatment was considered appropriate if allorganisms cultured were found to be susceptible to the drug(s)during in vitro susceptibility testing. Treatment was defined asdelayed if no appropriate treatment was begun within 48 hoursafter blood for cultures was drawn. Septic shock was definedas the septic syndrome, with a systolic blood pressure of 40 mmHg from the baseline, in the absence of other causes of hypoten-

544 Shih et al. em 1996;23 (September)

sion. Outcome was evaluated at discharge or 1 month aftertreatment was started. Death was considered bacteremia-relatedif patients died within 10 days of the report of positive cultureresults. Patients who died of other conditions and had obviousinitial clinical responses after receiving antibiotic treatmentwere excluded from the study.

Statistical analysis was performed with use of the X2 testand a two-tailed Fisher's exact test. The odds ratios and 95%confidence intervals were calculated at the same time. The logitestimators used a correction of 0.5 in every cell of those labelsthat contained a zero.

Results

From 1982 through 1994, 56 blood cultures for 45 patientsyielded Citrobacter species, and these isolates accounted for0.55% of the 10,263 blood isolates recovered at our hospitalduring this period. Twenty-two patients (48.9%) were male,and 23 patients (51.1%) were female. The ages ranged from 2days 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 thefirst 6.5 years of the study period (1.28 episodes per 10,000patients discharged) and the remaining 24 episodes occurredin the second period (1.18 episodes per 10,000 patients dis-charged). No significant change in the incidence of citrobacterbacteremia was found during this 13-year period. Throughoutthe entire study period, recovery of Citrobacter isolates fromblood appeared to be random, since the isolates were not clus-tered 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 arelisted in table 1. Of those who had a malignancy, five hadleukemia, and 16 had solid tumors (including 13 of intraabdom-inal origin). The number of cases of citrobacter bacteremia per10,000 newly registered cancer patients in our hospital was49.5 for those with acute leukemia, 37.8 for those with chronicleukemia, 6.3 for those with solid tumors, and 19.9 for thosewith intraabdominal tumors (table 1). Eight patients had re-ceived chemotherapy, and five of them were neutropenic (neu-trophil count, 1O,000/mm3) , and five (11.4%) of 44 had neutropenia(neutrophil count,

em 1996;23 (September) Citrobacter Bacteremia 545

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

No. of patients with indicated primary site of infection

LowerIntraabdominal Urinary respiratory Total no. of cases per 10,000

Variable tissues tract tract Others* Unknown Total newly registered patients

Underlying diseaseMalignancy 10 2 3 2 22 5.27

Solid tumor 9 5 I I a \6 6.3Intraabdominal tumor 9 3 1 a 0 13 19.9

Hematological tumor I 0 1 2 2 6 26.3Acute leukemia I a 0 I 2 4 49.5Chronic leukemia 0 0 0 I 0 I 37.S

Hepatobiliary stone 10 0 0 0 0 10Heart disease 2 I 2 0 1 6Diabetes mellitus 1 4 0 0 0 S

Plaee of acquisitionCommunity 1St 6 I I 0 23Hospital 8 3 4 4 3 22

Etiologic organismC. jreundii 11 3 1 2 1RC. diversus 2 3 0 1 7Citrobacter species plus other organisms 9 2 3 0 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; lowerrespiratory 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. Ofthe 45 episodes ofcitrobacter bacteremia,18 (40%) were due to Cifrcundii, and seven (15.6%) were dueto C diversus. The Citrobacter isolates were not identified tothe species level in the remaining cases. C freundii was amore frequent cause ofbacteremia than was C diversus amongpatients 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 anintraabdominal origin of infection (nine patients), a community-acquired infection (nine), or a malignancy (eight, including sixwith intraabdominal malignancies).

Antimicrobial susceptibilities. Antimicrobial susceptibilitypatterns were analyzed for 44 strains (these data were not avail-able for one strain). Resistance to ampicillin, cefazolin, andcefamandole was common. However, almost all of the strainstested were susceptible to gentamicin (table 2).

The percentage of C freundii isolates that were resistant toampicillin, cefazolin, cefamandole, and cefotaxime was higherthan the percentage of C diversus isolates that were resistantto these drugs.

Treatment with first- or second-generation cephalosporins be-fore the onset of bacteremia resulted in an increase in the rate ofresistance to ampicillin, cefazolin, and cefamandole but not to

cefotaxime. On the other hand, pretreatment with third-generationcephalosporins resulted in an increase in the rate of resistance tocefotaxime. Multidrug resistance was found in five strains andwas associated significantly (P < .01) with pretreatment withthird-generation cephalosporins. All four multidrug-resistantstrains that were tested were susceptible to ciprofloxacin.

Treatment. Thirty-five patients received appropriate antibi-otic treatment. Four patients did not receive appropriate treat-ment within 48 hours of the onset of bacteremia, and five didnot receive any effective medical treatment. Two of these ninepatients died of bacteremia. The appropriateness of the treat-ment one patient received could not be judged because thedrug susceptibilities of his isolates were not determined.

The 45 patients received one or more of the following anti-biotics: penicillins (two patients [4.4%]); first- or second-generation cephalosporins (25 [55.6%]); third-generation ceph-alosporins (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 amino-glycoside and a ,B-lactam. Of the 18 patients who receivedcombination therapy, only one (5.6%) died, whereas five(45.5%) of II patients who received monotherapy with a third-generation cephalosporin died; thus combination therapy wassignificantly superior to monotherapy with a third-generationcephalosporin (OR = 0.07; 95% CI = 0.01-0.73; P = .018).When compared with all other single-agent regimens, combina-tion therapy was found to be more protective, although thisdifference was not significant (P = .11) (table 3).

546 Shih et al. em 1996; 23 (September)

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

No. of indicated species No. of resistant isolates/no.tested/no. of resistant strains of isolates from patients

(%) pretreated with a first- orNo. of resistant strains/no. second-generation

Antimicrobial agent of strains tested (%) C.freundii C. diversus OR* 95% CI* cephalosporin (%)

Ampicillin 33/43 (76.7) 16/18 (88.9) 5/7 (71.1) 3.2 0.35-28.95 10/10 (100)Cefazolin 26/44 (59.1) 13/18 (72.2) 1/7 (l4.3)t 15.6 1.48-164.38 7110 (70)Cefamandole 8/33 (24.4) 8118 (44.4) 1/7 (14.3) 4.48 0.48-48.46 5/7 (71.4)Cefotaxime 7/41 (17.1) 5/17 (29.2) 0/7 6.58 0.32-142.86 2/10 (20)Ciprofloxacin 0117Imipenem 0/13Gentamicin 2/43 (4.7) 0117 0/7 0/9Multiple agents 5/41 (12.1) 3117 (17.7) 0/7 3.62 0.16-76.92 2/10 (20)

* 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 pa-tients.

Outcome. Fifteen (33.3%) of the 45 patients died. Six ofthese 15 patients died of causes other than bacteremia, althoughthey responded well to treatment of bacteremia. One otherpatient died of hepatic failure that was associated with gastriccancer, and the bacteremia probably contributed to his death.Eight (17.8%) of the 45 patients died of bacteremia. Table 3lists potential risk factors for death due to citrobacter bacter-emia. The initial manifestations that were significant risk fac-tors included pneumonia, altered mental status, hypothermia,and oliguria, and complications during the course of the illnessthat were significant included septic shock, further deteriorationin mental status, hyperbilirubinemia, hypercreatinemia, andthrombocytopenia. Polymicrobial bacteremia and alcoholismwere also associated with an increase in mortality, but thisincrease was not significant statistically.

Factors such as old age, cold weather, place of acquisition,the primary site and/or manifestation of the infection (exceptpneumonia), antibiotic resistance, the initial presence of hypo-tension, the leukocyte count, chemotherapy, previous invasiveprocedure, pretreatment, delayed treatment, or no treatmentdid not have significant influence on mortality. Appropriatetreatment did not result in lower mortality. Although infectionthat originated in the urinary tract was associated with lowermortality, the difference was not significant. Surgical interven-tion and combination therapy were associated with a protectiveeffect.

Discussion

Citrobacter species have been reported as a cause of manykinds of human infections [1, 6, 10-13], but bacteremia dueto these organisms remains uncommon. The incidence of Citro-

bacter bacteremia among our patients was similar to that re-ported by Drelichman and Band [3].

The urinary tract was the leading site of citrobacter infectionin many previous reports [1-3, 14], including the two thatdescribed citrobacter bacteremia [2, 3]. However, in our series,intraabdominal tissues (mainly in hepatobiliary system) werethe most common primary sites of infection in bacteremic pa-tients. The reason that such sites predominated in our serieswas that a large portion of our patients had hepatobiliary stones(22.2%) and intraabdominal malignancies (28.8%). Hepatobili-ary infection was the most frequent (82.6% ofpatients) intraab-dominal infection due to Citrobacter species, which is consis-tent with the findings of Lew et al. [15]. We emphasize thatenterococci, E. coli, and anaerobes still predominate amongpatients with the pancreatic and hepatobiliary cancer and in-traabdominal abscesses [16], and antimicrobial coverage forthese organisms should be considered first.

According to previous reports [1-3, 14], most citrobacterinfections have been hospital acquired. In our study, about one-half of the cases (51.1%) were community acquired, a findingthat may be due to the predominance of cases hepatobiliaryinfection (19) in our study. One large-scale study [17] showedthat hospital-acquired cases ofbacteremia predominated amongpatients with infections that originated from any site other thanthe biliary tree and reproductive tract. Fifteen (78.9%) of the19 patients with hepatobiliary infection in our study had com-munity-acquired bacteremia.

In one previous report of citrobacter bacteremia in patientswith cancer [2], those with acute leukemia accounted for thehighest number with bacteremia due to Citrobacter speciesalone (this number was 20 times higher than the number ofpatients with solid tumors and citrobacter bacteremia). Al-though patients with acute leukemia still had the highest rateof citrobacter bacteremia in our study, those with tumors of

cm 1996;23 (September) Citrobacter Bacteremia 547

Table 2. (Continued)

No. of resistant isolates/no.of isolates from patients No. of resistant isolates/no. No. of resistant isolates/no.

without pretreatment with of isolates from patients of isolates from patientsa first- or second- pretreated with a third- without pretreatment with

generation cephalosporin generation cephalosporin a third-generation(%) OR* 95% CI* (%) cephalosporin (%) OR* 95% CI*

23/33 (69.7); 9.35 0.5-166.67 6/6 (l00) 27/37 (73.0) 4.98 0.26-1019/34 (35.9) 1.84 0.41-8.36 6/6 (l00) 20/38 (52.6)t 11.76 0.62-2507/26 (26.9)t 6.79 1.06-43.36 4/5 (80) 8/28 (28.6); 10 0.96-103.785/31 (l6.1) 1.3 0.21-8.03 4/6 (66.7) 3/35 (8.6) 21.33 2.69-168.94

2/34 (5.9) 0.68 0.03-45.51 0/6 2/37 (5.4) 1.09 0.05-25.483/31 (9.7) 2.06 0.33-16.47 3/6 (50) 2/35 (5.7); 16.5 1.93-140.85

the abdominal cavity were also found to have a high incidence(10.7 cases per 10,000 newly registered patients) of the infec-tion. Furthermore, the incidence among such patients was evenhigher ifcases of polymicrobial bacteremia were included (19.9cases per 10,000 newly registered patients). We emphasize theimportance of underlying intraabdominal tumors in the devel-opment of Citrobacter bacteremia among our patients, sincethis observation has not been made previously.

The incidence (33.3%) of bacteremia due to Citrobacter,in combination with other organisms, in our hospital is similarto 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 amixed infection in the abdominal cavity was unexpectedlycommon (nine patients) in our study. These cases presumablyrepresented the introduction of Citrobacter species that werealready present in the patients' gastrointestinal tracts; thisphenomenon has been mentioned in previous reports [1, 3].

One other important finding in our study was that administra-tion of a third-generation cephalosporin within 14 days beforethe onset of citrobacter bacteremia had a significant influenceon the selection of cefotaxime-resistant strains (P = .005) andmultidrug-resistant strains (P = .017). This finding confirmedthe fact that multidrug-resistant organisms may emerge morerapidly when the third-generation cephalosporins are used rou-tinely, as has been predicted by other investigators [7]. Thedifference between C. freundii and C. diversus in terms ofsusceptibility to the cephalosporins has been noted since the1970s [2, 4-6] and has been confirmed again in this study ofstrains that cause bacteremia.

Combination therapy had a protective effect in our study.This benefit of combination therapy has been proposed by otherauthors [2, 7]. Samonis et al. [24] reported that imipenem,

amikacin, and the new fluoroquinolones had good activityagainst Citrobacter species. Our results are compatible withtheir findings. Because the data are limited, we suggest theuse of combination therapy for initial empirical treatment ofcitrobacter bacteremia, and the fluoroquinolones can be usedfor the treatment of episodes due to multidrug-resistant strains.However, further studies are needed to support this recommen-dation.

The overall mortality associated with citrobacter bacter-emia was 33.3% in our series; this percentage is lower thanthat (48.3%) reported by Drelichman et al. in 1985 [3]. Themortality associated with citrobacter bacteremia is similar tothat 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, pneumo-nia, sources of bacteremia other than the urinary tract, alco-holism, diabetes mellitus, congestive heart failure, infectionwith a multidrug-resistant strain, inappropriate treatment,respiratory tract infection, polymicrobial bacteremia, nosoco-mial infection, chemotherapy-induced neutropenia, leu-kocytosis, septic shock, azotemia, hyperbilirubinemia, andthrombocytopenia have all been significantly associated withdeath due to gram-negative bacteremia. In our series pneumo-nia, altered mental status, oliguria, septic shock, deteriorationin mental status, azotemia, hyperbilirubinemia, and thrombo-cytopenia were found to have a significant influence on mor-tality. The fact that other factors were not significant wasprobably due to the smaller number of cases in our study.

In conclusion, citrobacter bacteremia is uncommon andusually develops in patients with underlying diseases.In our series, about one-half of cases were community

548 Shih et al. em 1996;23 (September)

Table 3. Risk factors for death due to citrobacter bacteremia.

No. of patients who died! No. of patients who died!no. of patients with risk no. of patients without

Risk factor factor (%) risk factor (%) aRt CIt P value

Enrollment during first 6.5 years of study* 6/21 (28.6) 2/24 (8.3) 4.40 0.78-24.81 NSOccurrence of bacteremia during months

of November-February 3/14 (21.4) 5/31 (16.1) 1.42 0.29-6.99 NSAge ;0.65 years 2/15 (13.3) 6/30 (20) 0.62 0.11-3.50 NSMale sex 5/22 (22.7) 3/23 (13.0) 1.96 0.41-9.43 NSPresence of underlying condition

Malignancy 3/22 (13.6) 5/23 (21.7) 0.57 0.12-2.73 NSHematologic tumor 1/6 (16.7) 2/16 (12.5) 1.4 0.10-19.01 NS

Other conditionsIntraabdominal lesions 2/11 (18.2) 6/34 (17.6) 1.04 0.18-6.07 NSDiabetes mellitus 0/5 8/40 (20) 0.35 0.02-6.94 NSHeart disease 1/6 (16.7) 7/39 (17.9) 0.91 0.09-9.10 NSDelayed admission 1/11 (9.1) 7/34 (20.6) 0.39 0.04-3.54 NSChemotherapy 0/8 8/37 (21.6) 0.2 0.01-3.91 NSSteroid therapy 2/7 (28.6) 6/38 (15.8) 2.13 0.33-13.67 NSAlcoholism 2/3 (66.7) 6/42 (14.3) 12.33 0.96-158.08 NSInvasive procedure 1/15 (6.7) 7/30 (23.3) 0.23 0.03-2.11 NSPrior antibiotic treatment 3/17 (17.6) 5/28 (17.9) 0.99 0.20-4.78 NS

Polymicrobial bacteremia 4/15 (26.7) 4/30 (13.3) 2.36 0.50-11.19 NSNosocomial acquisition of bacteremia 4/22 (18.1) 4/23 (17.4) 1.05 0.21-4.76 NSPrimary site of bacteremia

Lung 3/5 (60) 5/40 (12.5) 10.5 1.39-79.13 .03Intraabdomina1 site 4/23 (17.4) 4/22 (18.2) 0.95 0.21-4.37 NSUrinary tract 0/9 8/36 (22.2) 0.18 0.01-3.36 NS

Multidrug resistance 1/5 (20) 7/40 (17.5) 1.18 0.11-12.21 NSInitial clinical manifestation

Hypotension 4/15 (26.7) 4/30 (13.3) 2.36 0.50-11.19 NSAltered mental status 4/8 (50) 4/36 (11.1) 8 1.41-45.23 .03Body temperature

38SC 6/39 (15.4) 2/4 (50) 0.18 0.02-1.55 NS

Oliguria 4/13 (30.8) 1/27 (3.7) 11.56 1.14-117.44 .03Jaundice 4/12 (33.3) 4/33 (12.1) 3.63 0.74-17.81 NSLeukocytosis (WBC count, > 10,000/mm3) 6/28 (21.4) 2/15 (13.3) 1.77 0.31-10.11 NSNeutropenia (neutrophil count, 1 mg/dL 6/15 (40) 1/29 (3.4) 18.67 1.97-176.45 .003Increase in creatinine level of more than twofold 7/11 (63.6) 1/34 (2.9) 57.75 5.57-598.44 .00005Platelet count, < 100,000/nun3 5/7 (71.4) 1/36 (2.8) 87.5 6.65-1151.19 .00013

TreatmentNone or delayed 2/9 (22.2) 5/35 (14.3) 1.71 0.27-10.74 NSDelayed 1/4 (25) 5/35 (14.3) 2 0.17-23.25 NSSurgical/invasive procedure 1/10 (10) 7/35 (20) 0.44 0.05-4.12 NSCombination therapy 1/18 (5.6) 7/27 (25.9) 0.17 0.02-1.51 .11

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 urinarytract, was the leading primary site of citrobacter infection.Malignancy, especially in the intraabdominal organs, andhepatobiliary stones were the two most predominant under-lying diseases.

Citrobacter species were more often isolated in our cases ofpolymicrobial bacteremia than were other gram-negative bacilli

because of the predominance of primary infections at contami-nated sites, especially the abdominal cavity. When a patientpresents with citrobacter bacteremia, a thorough search for anintraabdominal lesion should be made. Multidrug resistanceamong Citrobacter species was found to be associated withadministration of a third-generation cephalosporin before theonset of bacteremia.

cm 1996;23 (September) Citrobacter Bacteremia 549

Because the data are limited, we suggest that ciprofloxacinbe considered the drug of choice for bacteremia due to thesestrains. Combination therapy with a ,B-Iactarn and an aminogly-coside are suggested as the initial empirical treatment becausethis combination was associated with a lower mortality rate inour study. Septic shock with organ failure was the most im-portant poor prognostic factor, and the need for good supportivecare for patients with this complication cannot be overempha-sized.

Acknowledgment

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

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