790 • CID 2008:47 (15 September) • Pacanowski et al.

M A J O R A R T I C L E

Campylobacter Bacteremia: Clinical Featuresand Factors Associated with Fatal Outcome

Jerome Pacanowski,1 Valerie Lalande,2 Karine Lacombe,1,6,8 Cherif Boudraa,1 Philippe Lesprit,10 Patrick Legrand,11

David Trystram,3 Najiby Kassis,12 Guillaume Arlet,4,6 Jean-Luc Mainardi,5,7 Florence Doucet-Populaire,9,7,13

Pierre-Marie Girard,1,6,8 and Jean-Luc Meynard,1 for the CAMPYL Study Groupa

1Service des Maladies Infectieuses et Tropicales and 2Laboratoire de Microbiologie, Hopital Saint-Antoine, 3Laboratoire de Bacteriologie, HopitalLa Pitie-Salpetriere, 4Laboratoire de Bacteriologie, Hopital Tenon, 5Service de Microbiologie, Unite Mobile de Microbiologie Clinique, HopitalEuropeen Georges Pompidou, 6Universite Paris VI Pierre et Marie Curie, 7Universite Paris V Rene Descartes, 8INSERM UMR-S707, and 9Unite EA4065, Paris, 10Unite Controle Epidemiologie et Prevention de l’Infection and 11Laboratoire de Microbiologie, Hopital Henri Mondor, Creteil,12Laboratoire de Microbiologie, Hopital Paul Brousse, Villejuif, and 13Laboratoire de Microbiologie, Hopital de Versailles, Le Chesnay, France

Background. Campylobacter bacteremia is uncommon. The influence of underlying conditions and of theimpact of antibiotics on infection outcome are not known.

Methods. From January 2000 through December 2004, 183 episodes of Campylobacter bacteremia were iden-tified in 23 hospitals in the Paris, France, area. The medical records were reviewed. Characteristics of bacteremiadue to Campylobacter fetus and to other Campylobacter species were compared. Logistic regression analysis wasperformed to identify risk factors for fatal outcome within 30 days.

Results. Most affected patients were elderly or immunocompromised. C. fetus was the most commonly iden-tified species (in 53% of patients). The main underlying conditions were liver disease (39%) and cancer (38%).The main clinical manifestations were diarrhea (33%) and skin infection (16%). Twenty-seven patients (15%) diedwithin 30 days. Compared with patients with bacteremia due to other Campylobacter species, patients with C. fetusbacteremia were older (mean age, 69.5 years vs. 55.6 years; ) and were more likely to have cellulitis (19%P ! .001vs. 7%; ), endovascular infection (13% vs. 1%; ), or infection associated with a medical deviceP p .03 P p .007(7% vs. 0%; ). Independent risk factors for death were cancer (odds ratio [OR], 5.1; 95% confidenceP p .02interval [CI], 1.2–20.8) and asymptomatic infection (OR, 6.7; 95% CI, 1.5–29.4) for C. fetus bacteremia, the absenceof prescription of appropriate antibiotics (OR, 12.2; 95% CI, 0.9–157.5), and prescription of third-generationcephalosporins (OR, 10.2; 95% CI, 1.9–53.7) for bacteremia caused by other species.

Conclusions. Campylobacter bacteremia occurs mainly in immunocompromised patients. Clinical features andrisk factors of death differ by infection species.

Campylobacter jejuni subsp. jejuni is the main bacterial

cause of enteroinvasive diarrhea [1–4]. As compared

with Salmonella infections, C. jejuni infection is rarely

complicated by bacteremia or extraintestinal localiza-

tion [2, 5]. In contrast to C. jejuni, Campylobacter fetus

subsp. fetus is usually isolated from blood samples and

is less frequently associated with enteritis [5, 6]. The

clinical features of Campylobacter bacteremia were re-

Received 29 January 2008; accepted 21 May 2008; electronically published 12August 2008.

a Other members of the study group are listed at the end of the text.Reprints or correspondence: Dr. Jerome Pacanowski, Service des Maladies

Infectieuses et Tropicales, Hopital Saint-Antoine, 184 rue du Faubourg Saint-Antoine, 75012 Paris, France (jerome.pacanowski@sat.aphp.fr).

Clinical Infectious Diseases 2008; 47:790–6� 2008 by the Infectious Diseases Society of America. All rights reserved.1058-4838/2008/4706-0009$15.00DOI: 10.1086/591530

ported in several series published during 1993–1998 [7–

11], and a retrospective study of C. fetus antimicrobial

susceptibility was reported in 2003 [12]. The number

of cases reported in published series was quite small,

even though the study periods were long. None of these

reports examined factors associated with fatal outcome.

In the past decade, several factors may have led to an

increased incidence of Campylobacter extraintestinal lo-

calization like bacteremia, and Campylobacter suscep-

tibility may have been affected by misuse of antibiotics,

especially fluoroquinolones, in both veterinary and hu-

man medicine.

Therefore, we conducted a retrospective study of

Campylobacter bacteremia diagnosed in 23 hospitals in

the Paris, France, area, from January 2000 through De-

cember 2004, to increase our knowledge about the clin-

ical, bacteriological, and therapeutic characteristics of

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Campylobacter Bacteremia • CID 2008:47 (15 September) • 791

the affected patients and to identify risk factors for death within

30 days after infection onset.

PATIENTS AND METHODS

Definition of cases. Cases of Campylobacter bacteremia oc-

curring in patients treated in 23 hospitals in the Paris area

between 1 January 2000 and 31 December 2004 were collected

from the relevant microbiology laboratories.

Patients and data collection. The medical records of the

affected patients were reviewed. The following data were sys-

tematically extracted: demographic characteristics, clinical

manifestations associated with bacteremia, underlying condi-

tions, whether there was fatal outcome within 30 days, and

microbiological data (i.e., identification to the species level,

results of concomitant stool culture, and susceptibility to amox-

icillin, amoxicillin–clavulanic acid, erythromycin, gentamicin,

and fluoroquinolones). We also extracted the start and end

dates of treatment with individual antibiotics. The nature of

the empirical regimen and switches that were based on the

results of culture of blood samples and susceptibility testing

were recorded. The antibiotic treatment was considered to have

been appropriate if the strain was susceptible to at least 1 of

the drugs prescribed. C. fetus isolates were assumed to be sus-

ceptible to cefotaxime and ceftriaxone, whereas C. jejuni, Cam-

pylobacter coli, and Campylobacter lari isolates were assumed

to be resistant to all third-generation cephalosporins [12–15].

All isolates were assumed to be resistant to ticarcillin and pi-

peracillin [13, 15, 16], and treatment with these antibiotics was

considered to be inappropriate.

Laboratory methods. All laboratories used continually

monitored noninvasive blood culture systems—namely, BacT/

Alert (Organon Technika), Bactec (Becton Dickinson) or Vital

(bioMerieux). Each blood culture set included an aerobic and

an anaerobic bottle that were incubated for 5 days at 37�C.

Curved or spiral-shaped gram-negative rods were identified as

Campylobacter species and were speciated with conventional

phenotypic methods (i.e., biochemical tests, growth at 25�C

and 42�C, and susceptibility to nalidixic acid and cephalotin).

Susceptibility testing was based on the disk-diffusion method,

as recommended by the Antibiogram Committee of the French

Society of Microbiology. The species identification of some iso-

lates was not reported by the laboratories, but the cephalotin

and nalidixic acid susceptibility results were used to tentatively

identify these isolates as C. fetus or as members of the group

comprising C. jejuni, C. coli, and C. lari.

Statistical analysis. Descriptive statistics were expressed as

percentages for categorical variables and as mean � SD and

median and interquartile range for continuous variables, as

appropriate. Demographic and clinical characteristics (table 1)

were compared between patients with bacteremia due to C.

fetus and patients with bacteremia due to other Campylobacter

species, by use of the x2 test for categorical variables or the

Mann-Whitney U test for continuous variables, after exclusion

of patients whose isolates were not speciated. Associations be-

tween fatal outcome within 30 days and candidate variables

were assessed as ORs and 95% CIs. The tested variables are

listed in table 2. ORs determined by univariate analysis were

calculated by means of simple regression analysis. A multiple

logistic regression model (Hosmer and Lemeschow backward

procedure) was constructed using variables that were statisti-

cally significantly associated with fatal outcome within 30 days

( ) in univariate analyses, to calculate adjusted ORs. AllP ! .10

results with P values !.05 were considered to be statistically

significant. Data on patients who had died 130 days after pre-

sentation of an unknown cause were consequently removed

from the analysis, because the impossibility of excluding an

association between their death and the presence of factors

related to bacteremia might have biased the identification of

risk factors for fatal outcome. The SPSS software package, ver-

sion 11 (SPSS), was used for statistical analysis.

RESULTS

During the 5-year study period, 183 episodes of Campylobacter

bacteremia were diagnosed in 178 patients (5 patients presented

with recurrent episodes of bacteremia) in the 23 participating

hospitals. Clinical characteristics and rates of resistance by spe-

cies are listed in table 1. C. fetus was the most commonly

identified species (94 [53%] of 178 patients). Among the 77

remaining non–C. fetus isolates (43%), precise identification to

the species level was made as follows: 54 C. jejuni isolates, 16

C. coli isolates, and 2 C. lari isolates. Most cases involved male

patients and elderly patients. Only 37 patients (21%) were not

immunocompromised. Cancer (67 patients [38%]) and liver

disease (69 patients [39%]) were the leading underlying con-

ditions. Gastrointestinal tract (66 patients [37%]) and skin (28

patients [16%]) infections were the most frequent manifesta-

tions, but there was no symptom other than fever in 74 patients

(42%). The rate of resistance to fluoroquinolones was 32%,

whereas none of the isolates was resistant to imipenem, 1%

were resistant to amoxicillin–clavulanic acid, and 3% were re-

sistant to gentamicin.

Compared with patients with bacteremia due to other Cam-

pylobacter species, patients with C. fetus bacteremia were older,

were more likely to be male, and were more likely to have both

implanted medical devices and no identified cause of immu-

nosuppression; they were more likely to have received a di-

agnosis of skin, endovascular, or medical device infection than

were patients with bacteremia due to other Campylobacter spe-

cies. C. fetus bacteremia tended to be less frequently associated

with febrile diarrhea. Resistance to amoxicillin and to eryth-

romycin was less frequent in C. fetus than in other species.

Three patients died 130 days after presentation. Twenty-

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792

Table 1. Demographic characteristics, underlying conditions, and clinical features of patientswith Campylobacter bacteremia due to Campylobacter fetus and to other identified isolates.

CharacteristicsAll patients(n p 178)

Patients withC. fetus infection

(n p 94)

Patients with otherCampylobacter infection

(n p 77) P

Age

Mean years (range) 64 (6–97) 69.5 55.6 !.001

180 years 41 (23) 27 (29) 13 (17) …

!15 years 7 (4) 0 (0) 7 (9) …

Male sex 124 (70) 71 (76) 49 (64) NS

Underlying condition

Cancer 67 (38) 31 (33) 34 (44) NS

Hematologic malignancya 21 (12) 6 (6) 15 (19) NS

Digestive malignancy(ies)b 24 (13) 10 (11) 13 (17) NS

Otherc 22 (12) 15 (16) 6 (8) NS

Chemotherapy 43 (24) 18 (19) 24 (31) NS

Neutropenia 13 (7) 5 (5) 8 (10) NS

Liver disease

All 69 (39) 32 (34) 34 (44) NS

Alcohol abuse 50 (28) 25 (27) 24 (31) NS

HCV infection 19 (11) 6 (6) 11 (14) NS

HBV infection 10 (6) 5 (5) 5 (6) NS

Cirrhosis 45 (25) 19 (20) 23 (30) NS

HIV infection 17 (10) 9 (10) 7 (9) NS

Steroid therapy 32 (18) 18 (19) 11 (14) NS

Diabetes

All 31 (17) 20 (21) 10 (13) NS

Insulin therapy 17 (10) 9 (10) 7 (9) NS

Oral therapy 14 (8) 11 (12) 3 (4) NS

Splenectomy 4 (2) 3 (3) 0 (0) NS

Organ transplantation 6 (3) 1 (1) 4 (5) NS

Autoimmune disorder 9 (5) 5 (5) 3 (4) NS

No underlying immunodepressiond 37 (21) 24 (26) 11 (14) .08

Medical device 35 (20) 27 (29) 8 (10) .004

Clinical feature

Fever with no clinical signse 74 (42) 39 (41) 35 (45) NS

Diarrhea 58 (33) 25 (27) 31 (40) .07

Other digestive infectionsf 7 (4) 3 (3) 4 (5) NS

Skin or soft-tissue infection 28 (16) 18 (19) 5 (6) .03

Endovascular infectiong 13 (7) 12 (13) 1 (1) .007

Bone or joint infectionh 5 (3) 3 (3) 1 (1) NS

Infection associated with a medical devicei 7 (4) 7 (7) 0 (0) .02

Positive stool culture 13/61 (21) 2/25 (8) 11/33 (33) .03

Death within 30 days 27 (15) 13 (14) 13 (17) NS

Antimicrobial susceptibility (intermediate and resistant)

Amoxicillin … 2/87 (2) 16/70 (23) .001

Amoxicillin–clavulanic acid … 0/89 (0) 1/72 (1) NS

Imipenem … 0/37 (0) 0/36 (0) NS

Erythromycin … 3/86 (3) 9/70 (13) .04

Gentamicin … 3/84 (4) 1/63 (2) NS

Ofloxacin-ciprofloxacin … 29/88 (33) 21/69 (30) NS

NOTE. All data are no. or proportion (%) of patients, unless otherwise indicated. HBV, hepatitis B virus; HCV,hepatitis C virus; NS, not significant ( ).P 1 .1

a Acute and chronic leukemia (6 patients), lymphoma (8), myeloma (6), polycythemia vera (1).b Primitive hepatocarcinoma (10 patients), pancreas (3), biliary ducts (1), esophagus (1), cardia (2), stomach (2),

bowel (2), rectum (3), and peritoneal carcinosis (1).c Lung (7 patients), prostate (5), ovary (3), breast (2), Kaposi sarcoma (2), brain (1), larynx (1), and skin (1).d Attributable to cancer, neutropenia, chemotherapy, liver disease, HIV infection, steroid therapy, diabetes,

splenectomy, organ transplantation, or autoimmune disorder.e No identified portal of entry, systemic sign (except fever), or diagnosed secondary localization of infection.f Primitive peritonitis (6 patients) and angiocholitis (1).g Endocarditis (6 patients), infection of Port-a-Cath (2), infection of an aneurysm or of a vascular bypass (2),

purulent pericarditis (1), septic thrombophlebitis (1), or multiple mycotic aneurysms (1).h Septic arthritis (4 patients) or vertebral osteomyelitis (1).i Infection associated with a joint prosthesis (2 patients), Port-a-Cath (2), pacemaker (1), vascular bypass (1),

or aortic graft (1).

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Table 2. Risk factors of death within 30 days after bacteremia diagnosis, by Campylobacter species.

VariableDeath within

30 days P a

OR (95% CI)

Crudeb Adjustedc

Patients with Campylobacter fetus bacteremia (n p 92d)

Underlying conditionse

Neoplasia

No 5 (8) 1 1

Yes 8 (27) .02 4.1 (1.2–14.1) 5.1 (1.2–20.8)

Splenectomy

No 11 (12) 1

Yes 2 (67) .06 14.2 (1.2–169.7) …

Clinical manifestations of bacteremiaf

Diarrhea

Yes 0 (0)

No 13 (19) .02 … …

Fever without other clinical symptoms

No 3 (6) 1 1

Yes 10 (27) .005 6.4 (1.6–25.3) 6.7 (1.5–29.4)

Treatment characteristicsg

Treatment containing fluoroquinolones before blood cultures

No 7 (10) 1 …

Yes 6 (30) .05 3.7 (1.002–13.6)

Treatment associating third-generation cephalosporins andfluoroquinolones before blood cultures

No 9 (11) 1 …

Yes 4 (31) .09 3.5 (0.9–13.6)

No. of appropriate antibiotics prescribed before Campylobacter identification

�1 11 (14)

0 1 (100) .1 … …

Patients with other Campylobacter bacteremia (n p 76h)

Third-generation cephalosporin monotherapy before blood culture

No 9 (15) 1

Yes 3 (50) .07 5.8 (1.002–33.2) …

Treatment associating third-generation cephalosporin and fluoroquinolones before bloodcultures

No 9 (14) 1

Yes 4 (40) .06 4.2 (1.00–17.9) …

Treatment associating third-generation cephalosporin and macrolides before blood cultures

No 10 (14) 1

Yes 3 (50) .06 6.0 (1.1–34.0) …

Third-generation cephalosporin -containing treatment prescribed after blood cultures

No 8 (62) 1 1

Yes 4 (7) .1 20.0 (4.4–90.7) 10.2 (1.9–53.7)

No. of appropriate antibiotics prescribed before Campylobacter identification

�1 7 (12) 1 1

0 5 (83) .001 36.4 (3.7–358.9) 12.2 (0.9–157.5)

NOTE. Data are no. (%) of patients, unless otherwise indicated. Percentages are calculated as the proportion of patients who diedamong the patients with the specified variable. No underlying conditions, demographic data, or clinical manifestations of bacteremia wereassociated with the outcome with a significance of , for patients with Campylobacter bacteremia other than C. fetus.P ! .1

a By x2 test, with Fisher’s exact test when there were !5 expected cells.b Variables associated with a fatal outcome within 30 days with a significance of are presented with crude ORs (univariate analysis).P ! .1c The multivariate model was adjusted for all variables associated with a fatal outcome within 30 days with a significance of inP ! .1

univariate analysis. Only results of adjusted ORs with are included in the table.P ! .05d Of these 92 patients, 13 died within 30 days.e Other tested underlying conditions were chemotherapy, neutropenia, liver disease, HIV infection, steroid therapy, diabetes, presence

of a medical device, and no underlying immunosuppression.f Tested clinical manifestations were skin, soft-tissue, endovascular, or other digestive infection and infection associated with a medical

device.g Other tested treatment characteristics were treatment containing clavulanic acid, aminoglycosides, or third-generation cephalosporins

before or after blood cultures; treatment associating aminoglycosides and fluoroquinolones, aminoglycosides and macrolides, third-generationcephalosporins and macrolides, fluoroquinolones and macrolides; and monotherapy with third-generation cephalosporins, fluoroquinolones,macrolides, or aminoglycosides.

h Of these 76 patients, 13 died within 30 days.

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seven (15%) of the remaining 175 patients died within 30 days

after the date the first culture-positive blood sample was ob-

tained. Death occurred after a mean (�SD) of days11.5 � 9

and in !72 h in 8 cases. The risk of death was higher among

patients who had received a smaller mean number of appro-

priate antibiotics (0.88 drugs for patients who died vs. 1.34

drugs for survivors; ) and among those with no ap-P ! .001

propriate antibiotic treatment (87.5% vs. 12%; ). NoneP ! .001

of the 12 patients who were treated with imipenem died within

30 days. Risk factors of death differed by Campylobacter species

(table 2). In patients with C. fetus bacteremia, death was as-

sociated with cancer, splenectomy, lack of any clinical mani-

festations of bacteremia other than fever (in particular, the

absence of diarrhea), and treatment with fluoroquinolones. In

patients with bacteremia due to other Campylobacter species,

the risk of death was higher among those who did not receive

any appropriate antibiotics and among those who were pre-

scribed a third-generation cephalosporin. Third-generation

cephalosporins were deleterious, either as a treatment given

after identification of Campylobacter infection or given alone

or in association with fluoroquinolones or macrolides, before

test results had confirmed the presence of Campylobacter spe-

cies. Among patients who received treatment with a third-gen-

eration cephalosporin, mortality tended to be lower among

those with C. fetus bacteremia than among those with bacter-

emia due to another Campylobacter species (18% vs. 62%; OR,

6.6; 95% CI, 0.84–87.72; ). In multivariate analysis,P p .08

factors that remained independently associated with death were

cancer and isolated fever for patients with C. fetus bacteremia,

the absence of treatment with appropriate antibiotics, and the

prescription of third-generation cephalosporins for bacteremia

due to other Campylobacter species (table 2).

DISCUSSION

The study of this large series of 178 patients (183 episodes)

emphasizes the differences between clinical presentation and

prognostic factors by Campylobacter species. Campylobacter

bacteremia occurred mainly in elderly and immunocompro-

mised patients. The overall mortality rate was high. Patients

with C. fetus bacteremia had more frequently received a di-

agnosis of skin, endovascular, or medical device infection, com-

pared with patients with other Campylobacter bacteremia. The

resistance rate to fluoroquinolone was 32%. Resistance to

amoxicillin and to erythromycin was less frequent with C. fetus

than with other Campylobacter species. Failure to administer

appropriate antibiotics was strongly associated with fatal out-

come. Independent risk factors for death were cancer and iso-

lated fever among patients with C. fetus bacteremia, whereas

risk factors were the absence of appropriate antibiotic treatment

and the prescription of third-generation cephalosporins among

patients with bacteremia due to other Campylobacter species.

Human Campylobacter infections are well documented [5].

C. jejuni is isolated mainly from fecal culture and causes acute

enteroinvasive diarrhea, whereas bacteremia occurs in !1% of

cases [5]. In contrast, C. fetus is isolated mainly by blood cul-

ture, but only rarely by stool culture [6, 12]. When stool spec-

imens were available for culture for our patients, the cultures

were less likely to isolate C. fetus than C. jejuni. However, this

finding should be cautiously interpreted, because many labo-

ratories do not routinely screen stool specimens for C. fetus.

The presence of C. fetus in fecal specimens is, therefore, rare

but probably also underestimated.

Most cases of Campylobacter bacteremia involved males and

patients with underlying conditions, in keeping with previous

reports [7–11, 17]. However, no cause of immunosuppression

could be found in 21% of our patients; therefore, age itself

could be a major risk factor.

C. fetus was the leading cause of bacteremia among the pa-

tients in our study, which represents the largest recent clinical

series of C. fetus bacteremia since previous reports [12, 17, 18].

This is consistent with some studies [19, 20], but it is in striking

contrast to the main recent clinical case reviews [7–11], in

which C. jejuni and C. coli infections were far more frequent

than they were among our patients. This difference could reflect

improvements in recovery of these fastidious organisms

through use of automated blood culture systems [21] since the

beginning of our study or a preponderance of C. fetus in this

population of elderly patients. The 30-day mortality rate as-

sociated with Campylobacter bacteremia was 15% in this series,

similar to that observed in previous reports [8–10, 18].

Cellulitis was the leading extraintestinal manifestation of bac-

teremia, especially in patients with C. fetus infection. Cases of

Campylobacter cellulitis have been reported elsewhere [9, 10,

17, 18, 22, 23]. Many of the patients with cellulitis received

successful treatment with amoxicillin–clavulanic acid and were

discharged from the hospital before culture results were avail-

able. The frequency of Campylobacter cellulitis could, therefore,

be underestimated [22, 23]. Like some strains of Salmonella

species, C. fetus has a predilection for the vascular endothelium

[20] and for the site of medical devices. C. fetus has been known

to infect prosthetic joints [24] and prosthetic heart valves [25].

In our series, all but 1 endovascular infection and all medical

device–related infections were due to C. fetus. The infection

rate was considered to be 20% among bacteremic patients with

a medical device; but infection at the site of a medical device

could have been underestimated and should therefore be care-

fully considered in patients with C. fetus bacteremia.

It is uncertain whether all episodes of Campylobacter bac-

teremia need to be treated: C. jejuni bacteremia might be tran-

sient in immunocompetent patients, and transient C. fetus bac-

teremia can resolve without antimicrobial chemotherapy [5,

17]. The present study clearly demonstrates the need for an

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appropriate antibiotic treatment in a population of elderly and

immunocompromised patients: 88% of our patients who re-

ceived no appropriate antibiotics died within 30 days after

presentation.

However, there is no consensus on the optimal antibiotic

regimen; to our knowledge, there have been no published con-

trolled clinical trials and only anecdotal cases and clinical case

reviews. Although our study was descriptive and not designed

to assess antibiotic efficacy, several results are of particular in-

terest with respect to treatment.

Third-generation cephalosporins are widely used for empir-

ical treatment of community-acquired infections in immuno-

compromised patients and are considered to be alternatives to

fluoroquinolones for enteroinvasive bacterial diarrhea. We ob-

served a strong association between fatal outcome and pre-

scription of a third-generation cephalosporin for patients with

Campylobacter bacteremia due to species other than C. fetus, a

potentially important finding. Disk-diffusion or Etest suscep-

tibility data for third-generation cephalosporins were not avail-

able in our series. Several studies of Campylobacter susceptibility

to cephalosporins have been reported over the past 30 years

[12–16, 26–31]. With use of the breakpoints of the National

Committee on Clinical Laboratory Standards, few strains of C.

jejuni and C. coli seem to be susceptible to cefotaxime [13, 15].

In contrast, recent reports [12, 14] state that most C. fetus

isolates were susceptible to cefotaxime. The bactericidal activity

of cefotaxime was nonetheless weaker than that of ampicillin,

gentamicin, and imipenem [30, 31]. These reports and our

findings do not support the use of such third-generation ceph-

alosporins for the treatment of bacteremia involving species

other than C. fetus.

Campylobacter isolates are not regularly susceptible to pen-

icillins [12–14, 16]. The b-lactamase enzyme commonly en-

countered in C. jejuni strains [13]—but rarely encountered in

C. fetus strains [12]—is inhibited by clavulanic acid but not by

tazobactam or sulbactam [13, 16]; this is why amoxicillin–

clavulanic acid remains effective against almost all strains [26].

In recent reports from Quebec, all strains of C. jejuni were

susceptible to amoxicillin–clavulanic acid, imipenem, and mer-

openem (MIC90, �0.06 mg/mL) [26], and all strains of C. fetus

were susceptible to imipenem (MIC90, �0.06 mg/mL) [12]. Im-

ipenem has been suggested for the treatment of Campylobacter

bacteremia [5, 6, 23]. Imipenem and amoxicillin–clavulanic

acid seem to be the preferential b-lactam agents for treatment

of Campylobacter infection. Of note, none of the patients treated

with imipenem in our study died.

Fluoroquinolones and macrolides remain the standard

choice for empirical treatment of Campylobacter enteritis [5].

However, 32% and 8% of our bloodstream isolates were resis-

tant to fluoroquinolones and erythromycin, respectively, in

keeping with the results of a recent international survey [3].

Empirical treatment of C. fetus bacteremia with fluoroquino-

lones was associated with fatal outcome. This, together with

the increasing frequency of resistance to this class of antibiotics

[32, 33], prompts us to discourage the use of fluoroquinolones

for empirical treatment of Campylobacter bacteremia.

Gentamicin has very low MICs for C. fetus [12, 14, 29–31],

C. jejuni, and C. coli [28]. No gentamicin-resistant C. fetus

strains were identified in a recent report from Quebec [12].

On the basis of clinical experience and microbiological data,

many experts advocate the use of a regimen that includes gen-

tamicin to treat severe Campylobacter bacteremia and endo-

vascular infection [5, 8, 20].

Failure to administer appropriate antibiotics is strongly as-

sociated with fatal outcome, but several features make it dif-

ficult for the clinician to give an appropriate and prompt treat-

ment at the time of presentation. First, Campylobacter remains

an uncommon cause of bloodstream infection and is a fastid-

ious bacterium. Second, clinical findings of Campylobacter bac-

teremia lack of specificity. Eventually, third-generation cepha-

losporins and fluoroquinolones, which are widely prescribed in

this particular population of immunocompromised patients

with fever, seem to be deleterious in treatment of Campylobacter

bacteremia. Empirical use of fluoroquinolones is hampered by

the high rate of resistance and by its association with an in-

creased risk of death among patients with C. fetus bacteremia;

conversely, the prescription of third-generation cephalosporins

is deleterious in bacteremia that is attributable to Campylobacter

species other than C. fetus. Therefore, we advocate that third-

generation cephalosporins and fluoroquinolones be avoided as

soon as Campylobacter species have been isolated from culture

of blood samples, pending precise species identification and

susceptibility pattern.

OTHER MEMBERS OF THE CAMPYL STUDYGROUP

Sophie Coignard (Laboratoire de Microbiologie, Hotel Dieu,

Paris), Yannick Costa (Laboratoire de Microbiologie, Hopital

de Lagny-Marne la Vallee, Lagny), Frederic Faibis (Laboratoire

de Microbiologie, Hopital de Meaux, Meaux), Agnes Ferroni

(Laboratoire de Microbiologie, Hopital Necker, Paris), Beate

Heym (Laboratoire de Bacteriologie, Hopital Ambroise Pare,

Boulogne), Patrick Honderlic (Laboratoire de Bacteriologie,

Hopital Foch, Suresnes), Francoise Jaureguy (Laboratoire de

Microbiologie, Hopital Avicenne, Bobigny), Lea Lebrun (La-

boratoire de Microbiologie, Hopital Antoine Beclere, Clamart),

Claudette Muller (Laboratoire de Microbiologie, Hopital Bi-

chat, Paris), Marie-Helene Nicolas-Chanoine (Laboratoire de

Microbiologie, Hopital Beaujon, Clichy), Isabelle Poilane (La-

boratoire de Microbiologie, Hopital Jean Verdier, Bondy),

Claire Poyart (Laboratoire de Bacteriologie, Hopital Cochin),

Laurent Raskine (Laboratoire de Microbiologie, Hopital Lari-

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796 • CID 2008:47 (15 September) • Pacanowski et al.

boisiere, Paris), and Hoang Vu Thien (Laboratoire de Micro-

biologie, Hopital Trousseau, Paris).

Acknowledgments

Potential conflicts of interest. All authors: no conflicts.

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