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ScienceDirect www.sciencedirect.com Médecine et maladies infectieuses 44 (2014) 167–173
Original article
Campylobacter fetus infections Infections à Campylobacter fetus A. Cypierre a,∗ , E. Denes a , O. Barraud b , Y. Jamilloux a , J. Jacques c , H. Durox a , P. Pinet a , P. Weinbreck a a
Service de maladies infectieuses et tropicales, CHU Dupuytren, 2, avenue Martin-Luther-King, 87042 Limoges, France Service de bactériologie, virologie, hygiène, CHU Dupuytren, 2, avenue Martin-Luther-King, 87042 Limoges, France c Service d’hépato-gastro-entérologie, CHU Dupuytren, 2, avenue Martin-Luther-King, 87042 Limoges, France
b
Available online 14 March 2014
Abstract Background. – Campylobacter fetus infections usually occur in immunodepressed patients or patients presenting with diabetes mellitus or cancer. They rarely cause diarrhea but frequently cause bacteremia or vascular diseases. The therapeutic management is not well codified and fluoroquinolone resistance is continuously increasing. Methods. – We conducted a retrospective study of C. fetus infections from January 2007 to August 2013 at the Limoges teaching hospital. The infections were defined by at least 1 bacteriological sample positive for C. fetus. Results. – Twenty patients were included (15 men), with an average age of 73 years (43–91). Sixteen presented with cancer, 12 with solid cancer including 9 of the urinary tract, and 9 patients with hematologic diseases. Five patients presented with diabetes mellitus, 9 with isolated bacteremia, 3 with cellulitis, and 3 with septic arthritis. The diagnosis was made by blood cultures for 17 patients. Twenty percent of the isolates were resistant to amoxicillin and 30% to fluoroquinolones. The therapeutic regimens and the treatment duration were quite different. The outcome was unfavorable for 3 patients whose implanted port had not been removed and 1 with subdural hematoma infection. 1 patient died. Conclusions. – C. fetus infection occurs in case of underlying diseases, most frequently promoting urinary tract cancer. Fluoroquinolones must not be used without susceptibility testing and catheters should be removed. © 2014 Elsevier Masson SAS. All rights reserved. Keywords: Cancer; Campylobacter fetus; Catheter; Diabetes mellitus
Résumé Introduction. – Les infections à Campylobacter fetus surviennent généralement chez des patients immunodéprimés ou avec des antécédents de diabète ou de néoplasie. Les diarrhées sont rares et l’on constate essentiellement des bactériémies isolées ou des atteintes vasculaires. Le traitement est mal codifié et les résistances acquises aux fluoroquinolones sont en augmentation constante. Méthode. – Étude rétrospective au CHU de Limoges, entre janvier 2007 et août 2013 portant sur les infections à C. fetus, définies par la présence d’au moins un prélèvement bactériologique positif à C. fetus. Résultats. – Vingt patients ont été inclus (15 hommes), avec un âge moyen de 73 ans (43–91). Seize patients étaient porteurs d’une néoplasie : 12 présentaient un cancer solide dont 9 d’origine urinaire et 9 des pathologies hématologiques. Cinq étaient diabétiques. Neuf patients présentaient une bactériémie isolée, 3 une dermo-hypodermite et 3 une arthrite septique. Le diagnostic était réalisé sur les hémocultures chez 17 patients. On notait 20 % de résistance à l’amoxicilline et 30 % de résistance aux fluoroquinolones. Les schémas thérapeutiques étaient très variés, de même que les durées de traitement. L’évolution était défavorable chez les 3 patients chez qui le site implantable n’avait pas été retiré et chez une patiente avec une infection d’hématome sous-dural. Un patient était décédé.
∗
Corresponding author. E-mail addresses: [email protected] (A. Cypierre), [email protected] (E. Denes), [email protected] (O. Barraud), [email protected] (Y. Jamilloux), [email protected] (J. Jacques), [email protected] (H. Durox), [email protected] (P. Pinet), [email protected] (P. Weinbreck). 0399-077X/$ – see front matter © 2014 Elsevier Masson SAS. All rights reserved. http://dx.doi.org/10.1016/j.medmal.2014.02.001
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Conclusion. – Les infections à C. fetus surviennent en présence de pathologies sous-jacentes favorisantes essentiellement des néoplasies à point de départ urinaires. Les fluoroquinolones ne doivent pas être utilisées avant obtention d’un antibiogramme et les cathéters doivent être retirés pour améliorer le pourcentage de guérison. © 2014 Elsevier Masson SAS. Tous droits réservés. Mots clés : Cancer ; Campylobacter fetus ; Cathéter ; Diabète
1. Introduction
2.3. Laboratory data
Campylobacter are Gram-negative bacilli, transmitted to humans by contaminated food, frequently causing diarrheas [1]. The species Campylobacter fetus is different in several ways. C. fetus infections usually occur patients presenting with underlying cancer, diabetes, or an immunosuppressive treatment [2–5]. They rarely cause diarrheas but are responsible for bacteremia which may be associated or not to secondary localizations, most frequently vascular (aneurysms, vascular prosthesis infections) [3,6], or cutaneous [7]. The diagnosis is made by identifying Campylobacter in biological samples, usually in hemocultures. These bacteria present as curved or spiraled rods, with a typical mobility in “gnat cloud”. The culture is made on a specific medium, in micro-aerophilic conditions at 37 ◦ C. There is no consensus for the treatment of these infections but bitherapy is accepted for bacteremia. The first-line antibiotherapy is the amoxicillin + clavulanic acid combination and gentamycin or imipenem for severe infections. Fluoroquinolones and macrolides are good alternatives but should be used after susceptibility testing because of increasing acquired resistance. We conducted a 6-year retrospective study at the Limoges teaching hospital (TH) so as to improve our knowledge on promoting factors, clinical presentations, and therapy for C. fetus infections.
The samples were sent to and analyzed by the Limoges TH bacteriology laboratory. The BacT/ALERT® 3D (bioMerieux® ) system was used for hemocultures. Each hemoculture was made in 2 vials (1 aerobic and 1 anaerobic), incubated for 5 days at 37 ◦ C. Samples positive for curved or spiraled Gram-negative bacilli, were seeded on blood agar in micro-aerophilic conditions at 37 ◦ C. The identification was made with the identification galleries (Api Campy® ) or with the MALDI-TOF Vitek® MS (bioMerieux® ) system. Susceptibility testing was performed for each sample according to recommendations of the Antibiogram Committee of the French Microbiology Society (CA-SFM).
2. Patients and methods
2.4. Statistical analysis The descriptive data were analyzed for all patients. The results for quantitative variables are presented as means, maximum, and minimum. The results for qualitative variables are expressed as percentages. 3. Results Twenty patients had at least 1 biological sample positive for C. fetus between January 2007 and August 2013. There was no difference according to the years studied. The average age was 73 years; 15 patients were men. The age, sex, the underlying diseases, the clinical signs, the septic sites, the treatments, and the outcome are listed in Table 1 and the average data in Table 2.
2.1. Type of study 3.1. Underlying diseases We conducted a retrospective study at the Limoges TH between January 2007 and August 2013. All the patients hospitalized in our institution with at least 1 sample tested positive for C. fetus at the bacteriology laboratory were included.
2.2. Patients and data The patients were identified from the data database. The epidemiological data (sex, age, history, and risk factors of immunodepression), clinical data (symptoms, localizations), biological data (inflammatory proteins, CBC), bacteriological data (type of sampling, identification, and antibiogram), treatment, and outcome were collected from the patient’s health records.
Five patients (25%) presented with diabetes, 9 patients (35%) with a hematological disease, and 12 patients (60%) with a history of solid cancer including 7 progressive diseases. Among the solid cancers, 11 were urinary tract tumors (5 prostate, 4 bladder, and 2 renal cancers), 1 was vesicular, 1 breast, 1 melanoma, 1 colon, 1 pancreatic, and 1 gastric. 3 patients had a history of 2 cancers, and 1 patient of 3 cancers. Among the hematological diseases there were 4 CLL (chronic lymphoid leukemia), 1 CML (chronic myeloid leukemia), 1 lymphoma, 1 AML (acute myeloblastic leukemia), 1 resistant anemia, and 1 IPT (idiopathic thrombocytopenic purpura). 4 patients did not have any history of cancers. 8 patients had received immunosuppressing treatment including 7 with ongoing chemotherapy and 3 with corticosteroid therapy. 2 patients were chronic alcohol abuser including 1 presenting with cirrhosis. Only 1 patient had no risk factor.
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Table 1 Clinical data for the 20 patients with Campylobacter fetus infections. Résumé des données cliniques des 20 patients porteurs d’une infection à Campylobacter fetus. Age
Sex
Underlying diseases
Clinical signs
Septic localization
Treatment and duration
Outcome
1
91
M
Amox/clav + Azithro 5d
Favorable
87 66
M F
AGS, thoracic pain Fever Fever
Pneumonia
2 3
Bacteremia Bacteremia
83
F
Amox + Cipro 14d Amox/clav + Cipro 2d then Piper/Tazo + Cipro 14d Amox/clav 11d
Favorable Favorable
4
Resistant anemia, prostate cancer Renal cancer CLL, corticotherapy, chemotherapy Vesicular cancer
5
83
F
Diabetes
Favorable
6
61
M
CLL, chemotherapy
Acute dermohypodermitis
Ceftriaxone 18d + Ofloxacine 21d Pristinamicine 15d
7
85
F
Acute dermohypodermitis
Amox 10d + Ofloxacine 5d
Favorable
8
73
M
Fever, chills
Bacteremia
Amox/clav 7d
Favorable
9 10
86 75
F M
CLM, breast cancer, corticotherapy, chemotherapy Gastric, prostate, pancreas cancers chemotherapy Diabetes Renal and vesical cancer
Fall, confusion Fever, pyuria
Bacteremia Renal abscess
Unfavorable Favorable
11
79
M
AGS, dyspnea
Pneumonia
Ofloxacine 10d Ceftriaxone + Cipro 7d then Amox 28d Amox/Clav 14d
12
87
M
AGS, cough
Pneumonia
Amox/Clav 10d
Favorable
13
73
M
Abdominal pain
Cipro 6 sem
Unfavorable
14
43
M
peritoneal dialysis fluid infection Acute dermohypodermitis
Amox/clav 8d + Genta 3d
Favorable
15 16 17 18 19
49 90 43 59 75
M M M M M
Unfavorable Favorable Favorable Favorable Favorable
20
47
M
Pristinamicine Amox/Clav + Genta 15d + 2d None Amox/Clav Vibramycin + Ciprofloxacine 6 sem + Genta 7d Amox/Clav + Genta 15d + 3d
Diabetes, prostate cancer, CLL Diabetes, prostate cancer, CLL Diabetes, vesical cancer Lymphoma, chemotherapy AML, chemotherapy Prostate, vesical cancer Chronic alcohol abuse None ITP, corticotherapy, melanoma Chemotherapy, cirrhosis, alcohol abuse colon and urothelial cancer
Abdominal pain, Fever Fever, fall, coxal pain Fever, leg erythema Fever, gonalgia, thoracic pain
Fever, calf pain Fever Fever Acute pancreatitis Fever, headaches Fever, shoulder pain Fever, fall
Peritonitis Bacteremia
Pneumonia Bacteremia Bacteremia Bacteremia Septic arthritis Bacteremia
Favorable
Favorable
Favorable
Unfavorable
CLL: chronic lymphoid leukemia; CLM: chronic myeloid leukemia; AML: acute myeloblastic leukemia; ITP: idiopathic thrombocytopenic purpura; AGS: alteration of global status; Amox/clav: amoxicillin + clavulanic acid; cipro: ciprofloxacin; oflox: ofloxacin; amox: amoxicillin; genta: gentamycin; azithro: azithromycin; piper/tazo: piperacillin + tazobactam.
Eleven patients presented with arterial hypertension, 5 with auricular fibrillation, and 5 had a history of acute coronary syndrome. Five patients (20%) carried a joint prosthesis (4 hip prostheses and 2 knee prostheses). 3.1.1. Clinical data On admission, 70% of patients (14/20) presented with fever, 25% (5/20) with abdominal pain at the diagnosis, but none with diarrhea. The most frequent secondary septic sites were the lungs in 4 cases (20%), a joint in 3 cases (15%), and the skin in 3 cases (15%). 9 patients (45%) presented with bacteremia without any secondary septic site. Four patients (20%) carried of an implantable port. 3.1.2. Biological data The average CRP level was 142 mg/L (8–289 mg/L) and the average leukocyte count was 13,955/mL (3380–40,000/mL). 14
patients (70%) presented with hyperleukocytosis (>10,000/mL) at the diagnosis. Campylobacter were identified in the hemocultures of 17 patients. Two of the patients with negative blood samples presented with peritonitis, and 1 with a renal abscess and the peroperative local samples were positive. Coprocultures that had been performed for 2 patients were negative. Four of the identified bacteria were resistant to amoxicillin (20%), 6 to ciprofloxacin (30%), and 2 isolates were of intermediate susceptibility to tetracycline (10%). No isolate was resistant to amoxicillin–clavulanic acid, to gentamycin, or to erythromycin. 3.1.3. Treatment Only 1 of the 20 patients did not receive any antibiotherapy. The average duration of treatment was 19 days (5 to 51 days). The antibiotic schemes were varied with mono or bitherapy, parenteral or oral treatment, relying on penicillins, macrolides,
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Table 2 Demographic characteristics, underlying conditions, clinical features, bacterial samples, biological data, treatments, and outcome of patients with Campylobacter fetus infection. Caractéristiques démographiques, antécédents, données cliniques, types de prélèvements, données biologiques, traitements et évolution des patients de notre cohorte. Data
Results
Mean age Sex Male Female
15/20 (75%) 5/20 (25%)
Samples Hemocultures Others
17/20 (85%) 3/20 (15%)
Underlying disease Alcohol abuse Cirrhosis Diabetes Solid cancer Urinary Hematological disease Vascular device
2/20 (10%) 1/20 (5%) 5/20 (25%) 12/20 (60%) 9/12 (75%) 9/20 (45%) 5/20 (25%)
Immunosuppressive treatment Chemotherapy Corticotherapy Clinical signs Fever Diarrhea Abdominal pain Weight loss Skin infection Joint infection Pneumonia Biological assessment CRP (mg/L) Leukocytes (/mm3)
73 (43–91)
8/20 (40%) 7/8 (87.5%) 3/8 (37.5%) 14/20 (70%) 0/20 (0%) 5/20 (25%) 3/20 (15%) 3/20 (15%) 3/20 (15%) 4/20 (20%) 142 (8–289) 13,955 (3380–40,000)
Resistance (I OR R) Amoxicillin Amoxicillin–clavulanic ac. Erythromycin Gentamycin Ciprofloxacin
4/20 (20%) 0/20 (0%) 0/20 (0%) 0/20 (0%) 6/20 (30%)
Unfavorable outcome Death
4/20 (20%) 1/20 (5%)
fluoroquinolones, aminosides, but also 3GC and imidazoles. The various treatments used are listed in Table 3. 3.1.4. Outcome The outcome was unfavorable for 4 patients. One female patient presented with recurrence of fever again after 10 days of ofloxacine treatment and alteration of her neurological status. Hemocultures were positive for C. fetus resistant to fluoroquinolones and she presented with a subdural collection requiring surgical drainage. The PCR genic amplification, using specific primers, of collection samples proved the presence of C. fetus. A new antibiotherapy, with amoxicillin and
Table 3 Antibiotics used. Schémas thérapeutiques des patients traités. Therapeutic schemes
Number of patient (n = 19)
Amox or Amox/clav ac alone Amox or Amox/clav ac + aminosides Amox or Amox/clav ac + FQ FQ seules Amox or Amox/clav ac + macrolides Amox or Amox/clav ac + aminosides + FQ Pristinamycin FQ + aminosides FQ + macrolides + aminosides
3 3 3 2 2 2 2 1 1
Amox: amoxicillin; amox/clav: amoxicillin + clavulanic acid; FQ: fluoroquinolones.
clindamycin, combined with the surgical treatment chirurgical, led to complete cure. Three other patients presented recurrence of fever after stopping the treatment. They carried medical devices (2 implantable ports and 1 peritoneal dialysis catheter) that had not been removed during the first episode and 1 patient had been given an antibiotic lock. The hemocultures were also positives for C. fetus. When hypothermia recurred, antibiotherapy was reintroduced, the medical devices were removed, and the outcome was favorable for 2 patients. The 3rd patient died when hypothermia recurred; he had presented with resistant AML. 4. Discussion We included 20 patients presenting with a C. fetus infection. Pacanowski in 2008 reported 94 patients [2], and Gazaigne 21 patients in 2007 [3]. As in the 2 previously mentioned studies, there was a majority of male (75% in our series, 70% for Pacanowski, 86% for Gazaigne) and aged patients (average 73 years of age). Similar results were reported recently by National Reference Center in Bordeaux with 875 C. fetus strains and a mean age of 68.4 years [8]. The published data prove a strong association between C. fetus infections and an underlying risk factor, contrary to other types of Campylobacter [9,10]. The most frequently reported diseases are cancers, especially digestives or hematological tumors, diabetes, with cirrhosis or liver failure, a history of organ transplantation, or chronic alcohol abuse [2–5,11–13]. The immunosuppression due to some therapies (corticosteroid therapy, chemotherapy, immunosuppressive or immunomodulating drugs: methotrexate, leflunomide, cyclophosphamide, rituximab) is also a well-known risk factor. 80% of patients in our study had presented with recent or old cancer, including 70% (14/20) with progressive diseases. Sixty percent of the patients presented with solid cancers and 45% of these with a hematological disease; this was a higher rate than usually reported: Pacanowski had mentioned only 38% of patients with cancer [2]. The cancers were urinary tract lesions for 15 patients in our study contrary to others reported series in which cancers most frequently of digestive origin. We cannot explain this difference.
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Diabetes was reported as a frequent comorbidity, as in our study, in this type of infection for close to 20% of patients [2,3,7,14]. Some authors suggested that old age could be by itself a risk factor. The mean age was high in our study (73 years) and correlated to main published studies. The presence of vascular devices was also reported as a risk factor, and 5 of our patients carrier an implantable port or a vascular catheter [3]. Cardiovascular diseases were also reported as a risk factor for C. fetus infection but they were mostly related to vascular prostheses or valvular diseases [3]. Thirteen of our patients (65%) had a history of cardiac disease but only 2 presented with a valvular disease. Only 1 patient did not present with any underlying immunodepression, which compares to Pigrau’s data but is one of the lowest rates reported [5]. The patient was younger (59 years) with only a history of arterial hypertension. C. fetus are rarely isolated in stools, like other Campylobacter strains, but they are most frequently identified in hemocultures [15]. No coproculture was positive in our study and only 3 patients had negative hemocultures. Contrary to Campylobacter jejuni, C. fetus rarely cause diarrhea or enteritis, but they are known to cause isolated bacteremia or vascular infections with endocarditis and mycotic aneurysms [2,3,6,7,14–16]. Indeed this bacterium has specific adherence to injured vascular endothelium as well as for prosthetic material, related to a surface receptor with a strong affinity for the vascular endothelium, and to the secretion of a local pro-coagulant factor which promotes the formation of thrombi [17]. Physicians should systematically screen for the presence of an embolus or of a secondary vascular localization in patients presenting with C. fetus bacteremia. But many other infections have been reported: enteritis, peritonitis, pneumonia, meningitis, meningoencephalitis, pericarditis, thrombophlebitis, empyema, UTIs, spondylodiscitis, arthritis [3,4,13,18], as well as cerebral [19], colic, gluteal muscle [20], and pulmonary abscesses [21]. Acute cellulitis is frequently associated with C. fetus bacteremia, with higher rates of complications and mortality than with other bacteria [15]. Fifteen percent of patients in our study presented with a skin infection. Twenty percent of our patients presented with pneumonia, diagnosed because of dyspnea, cough, and fever; this was much higher than reported rates and unusual in this type of infection. Nevertheless, the diagnosis of pneumonia was made in the emergency unit, for patients presenting with severe sepsis or cardiac failure. Thus it could have been a complication of sepsis and not a pulmonary infection. There is no consensus for treatment. C. fetus bacteremia may be transitory in immunocompetent patients and the outcome may be favorable without any antibiotic treatment [2,13]. But the contribution of antibiotherapy was demonstrated for immunodepressed or geriatric patients, with a higher death rate in patients not having received appropriate antibiotic treatment [2]. Only 1 of our patients was not given any antibiotherapy. He was a young patient, without any risk factor or medical history except for chronic alcohol abuse, hospitalized for acute pancreatitis and presenting with isolated bacteremia. The outcome was spontaneously favorable. The treatment for these infections is not well codified, as demonstrated by the great variety of therapeutic schemes used
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in our study. This type of infection is rare which accounts for the absence of any clinical trial; only isolated cases or small series have been reported. Third generation cephalosporins are often used as firstline empirical treatment for community acquired infections in immunodepressed patients, or as an alternative to fluoroquinolones in cases of enteroinvasive diarrheas. The authors of a Quebec study on 111 C. fetus strains reported that 13% of isolates were resistant to cefotaxime [16]. The results do not correlated with the usually reported rates, especially in France where the rate of cefotaxime resistant strains is much higher [3]. Only 1 strain was resistant to cefotaxime in our study, but these results are sometimes interpreted by microbiologists (given as resistant whereas they are susceptible in vitro), because of the weak effectiveness and of reported therapeutic failures [4]. Some cases of resistance to penicillins have been reported, related to the secretion of beta-lactamase, usually inhibited by clavulanic acid, but not by sulbactam or tazobactam [2,22]. This is why most C. fetus strains are susceptible to the amoxicillin- clavulanic acid combination. Carbapenems, with imipenem, seemed to be the first-line therapy for the treatment of severe C. fetus infections or vascular infections, without any reported resistance so far. Gazaigne reported in his 2008 study, that the outcome had been favorable for all his patients treated by imipenem [3]. Furthermore, no resistance has been demonstrated yet. Tremblay, in the Quebec study, reported that all strains were susceptible to ampicillin, gentamycin, imipenem, and meropenem [16]. This antibiotherapy was not used in our study. Fluoroquinolones, usually first-line treatment for Campylobacter enteritis, are associated to higher death rate when they are used as empirical treatment for C. fetus infections [2]. Indeed some cases of resistance to this antibiotic have been reported [23] and it is contra-indicated to use them before obtaining antibiogram results. We observed, as in Pacanowski’s study, 30% of resistance to fluoroquinolones, 10% more than in the NRC 2011 data, but this rate has been continuously increasing [24]. Gentamycin is the most frequently used aminoside for this type of infection. It is a good first-line antibiotic because of a very low MIC, the absence of reported resistance, and its quick bactericidal activity for bacteremia or vascular infections when combined with a beta-lactam [2,16,25]. Delayed initiation of antibiotherapy or inadequate antibiotic treatment is a risk factor for death in Campylobacter infections [2]. Nevertheless initiating an adequate first-line therapy for this bacterium is difficult for the clinician for several raisons: it is a rare infection, with an unspecific clinical presentation, and resistance is possible with 3GC and fluoroquinolones, the 2 firstline treatments usually given to immunodepressed and febrile patients. The minimum duration of treatment has not been determined yet. In our study it was 19 days on average (5 to 51 days). The treatment duration usually depends on the infectious localizations but seems longer than for the same infections due to other bacteria. Cellulitis is usually treated for 21 days, arthritis and spondylodiscitis from 6 weeks to 3 months [5,11], joint prosthesis infections for 3 months. A prolonged parenteral treatment is
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recommended in case of vascular infection, for at least 3 to 4 weeks [3,5,15], and up to 12 weeks in cases of prosthetic valve endocarditis [6]. Another crucial point of the treatment is the removal of infected implantable material. Several authors have already reported this [26–28] for vascular but also for joint prostheses. Five of our patients carried catheters (4 implantable ports and 1 peritoneal dialysis catheter). The 3 patients whose material had not been removed relapsed when the antibiotic treatment was stopped. Removing the catheters and reinitiating an adequate antibiotherapy led to cure. Only 1 of our patients died: he was carrying an implantable port, which had not been removed, and presented with bacteremia treated by pristinamycin. Our study was retrospective, including a small number of patients; but it raised several interesting points. It confirmed that C. fetus infections occur most frequently in immunodepressed patients with a history of diabetes or cancer, especially urinary. It did not allow making recommendations for the antibiotic treatment or its duration but stressed the contribution of an adapted antibiotherapy and the need to remove infected medical material, especially for catheter-related infections. 5. Conclusion C. fetus infections occur most frequently in men, geriatric patients, and patients presenting with immunodepression, diabetes, or cancer. C. fetus diarrhea is rare and the main clinical presentations are isolated bacteremias, cutaneous, and vascular infections. The treatment is not codified but amoxicillin/clavulanic acid and gentamycin seem to be the best therapy because of their pharmacodynamic properties and of the weak rate of resistance. Fluoroquinolones and macrolides must not be used in first intention. Removal of the medical material and especially of catheters is mandatory to achieve therapeutic success. Disclosure of interest The authors declare that they have no conflicts of interest concerning this article. References [1] Denis F, Ploy MC, Martin C, Bingen E, Quentin R. Bactériologie médicale, techniques usuelles. Masson 2007:389–92. [2] Pacanowski J, Lalande V, Lacombe K, Boudraa C, Lesprit P, Legrand P, et al. Campylobacter bacteremia: clinical features and factors associated with fatal outcome. Clin Infect Dis 2008;47(6):790–6. [3] Gazaigne L, Legrand P, Renaud B, Bourra B, Taillandier E, Brun-Buisson C, et al. Campylobacter fetus bloodstream infection: risk factors and clinical features. Eur J Clin Microbiol Infect Dis 2008;27(3):185–9. [4] Francioli P, Herzstein J, Grob JP, Vallotton JJ, Mombelli G, Glauser MP. Campylobacter fetus subspecies fetus bacteremia. Arch Intern Med 1985;145(2):289–92. [5] Pigrau C, Bartolome R, Almirante B, Planes AM, Gavalda J, Pahissa A. Bacteremia due to Campylobacter species: clinical findings and antimicrobial susceptibility patterns. Clin Infect Dis 1997;25(6):1414–20.
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caused by Campylobacter fetus after tooth extraction. Intern Med 2005;44(10):1055–9. [28] Rutherford EJ, Eakins JW, Maxwell JG, Tackett AD. Abdominal aortic aneurysm infected with Campylobacter fetus subspecies fetus. J Vasc Surg 1989;10(2):193–7.
ScienceDirect www.sciencedirect.com Médecine et maladies infectieuses 44 (2014) 167–173
Original article
Campylobacter fetus infections Infections à Campylobacter fetus A. Cypierre a,∗ , E. Denes a , O. Barraud b , Y. Jamilloux a , J. Jacques c , H. Durox a , P. Pinet a , P. Weinbreck a a
Service de maladies infectieuses et tropicales, CHU Dupuytren, 2, avenue Martin-Luther-King, 87042 Limoges, France Service de bactériologie, virologie, hygiène, CHU Dupuytren, 2, avenue Martin-Luther-King, 87042 Limoges, France c Service d’hépato-gastro-entérologie, CHU Dupuytren, 2, avenue Martin-Luther-King, 87042 Limoges, France
b
Available online 14 March 2014
Abstract Background. – Campylobacter fetus infections usually occur in immunodepressed patients or patients presenting with diabetes mellitus or cancer. They rarely cause diarrhea but frequently cause bacteremia or vascular diseases. The therapeutic management is not well codified and fluoroquinolone resistance is continuously increasing. Methods. – We conducted a retrospective study of C. fetus infections from January 2007 to August 2013 at the Limoges teaching hospital. The infections were defined by at least 1 bacteriological sample positive for C. fetus. Results. – Twenty patients were included (15 men), with an average age of 73 years (43–91). Sixteen presented with cancer, 12 with solid cancer including 9 of the urinary tract, and 9 patients with hematologic diseases. Five patients presented with diabetes mellitus, 9 with isolated bacteremia, 3 with cellulitis, and 3 with septic arthritis. The diagnosis was made by blood cultures for 17 patients. Twenty percent of the isolates were resistant to amoxicillin and 30% to fluoroquinolones. The therapeutic regimens and the treatment duration were quite different. The outcome was unfavorable for 3 patients whose implanted port had not been removed and 1 with subdural hematoma infection. 1 patient died. Conclusions. – C. fetus infection occurs in case of underlying diseases, most frequently promoting urinary tract cancer. Fluoroquinolones must not be used without susceptibility testing and catheters should be removed. © 2014 Elsevier Masson SAS. All rights reserved. Keywords: Cancer; Campylobacter fetus; Catheter; Diabetes mellitus
Résumé Introduction. – Les infections à Campylobacter fetus surviennent généralement chez des patients immunodéprimés ou avec des antécédents de diabète ou de néoplasie. Les diarrhées sont rares et l’on constate essentiellement des bactériémies isolées ou des atteintes vasculaires. Le traitement est mal codifié et les résistances acquises aux fluoroquinolones sont en augmentation constante. Méthode. – Étude rétrospective au CHU de Limoges, entre janvier 2007 et août 2013 portant sur les infections à C. fetus, définies par la présence d’au moins un prélèvement bactériologique positif à C. fetus. Résultats. – Vingt patients ont été inclus (15 hommes), avec un âge moyen de 73 ans (43–91). Seize patients étaient porteurs d’une néoplasie : 12 présentaient un cancer solide dont 9 d’origine urinaire et 9 des pathologies hématologiques. Cinq étaient diabétiques. Neuf patients présentaient une bactériémie isolée, 3 une dermo-hypodermite et 3 une arthrite septique. Le diagnostic était réalisé sur les hémocultures chez 17 patients. On notait 20 % de résistance à l’amoxicilline et 30 % de résistance aux fluoroquinolones. Les schémas thérapeutiques étaient très variés, de même que les durées de traitement. L’évolution était défavorable chez les 3 patients chez qui le site implantable n’avait pas été retiré et chez une patiente avec une infection d’hématome sous-dural. Un patient était décédé.
∗
Corresponding author. E-mail addresses: [email protected] (A. Cypierre), [email protected] (E. Denes), [email protected] (O. Barraud), [email protected] (Y. Jamilloux), [email protected] (J. Jacques), [email protected] (H. Durox), [email protected] (P. Pinet), [email protected] (P. Weinbreck). 0399-077X/$ – see front matter © 2014 Elsevier Masson SAS. All rights reserved. http://dx.doi.org/10.1016/j.medmal.2014.02.001
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Conclusion. – Les infections à C. fetus surviennent en présence de pathologies sous-jacentes favorisantes essentiellement des néoplasies à point de départ urinaires. Les fluoroquinolones ne doivent pas être utilisées avant obtention d’un antibiogramme et les cathéters doivent être retirés pour améliorer le pourcentage de guérison. © 2014 Elsevier Masson SAS. Tous droits réservés. Mots clés : Cancer ; Campylobacter fetus ; Cathéter ; Diabète
1. Introduction
2.3. Laboratory data
Campylobacter are Gram-negative bacilli, transmitted to humans by contaminated food, frequently causing diarrheas [1]. The species Campylobacter fetus is different in several ways. C. fetus infections usually occur patients presenting with underlying cancer, diabetes, or an immunosuppressive treatment [2–5]. They rarely cause diarrheas but are responsible for bacteremia which may be associated or not to secondary localizations, most frequently vascular (aneurysms, vascular prosthesis infections) [3,6], or cutaneous [7]. The diagnosis is made by identifying Campylobacter in biological samples, usually in hemocultures. These bacteria present as curved or spiraled rods, with a typical mobility in “gnat cloud”. The culture is made on a specific medium, in micro-aerophilic conditions at 37 ◦ C. There is no consensus for the treatment of these infections but bitherapy is accepted for bacteremia. The first-line antibiotherapy is the amoxicillin + clavulanic acid combination and gentamycin or imipenem for severe infections. Fluoroquinolones and macrolides are good alternatives but should be used after susceptibility testing because of increasing acquired resistance. We conducted a 6-year retrospective study at the Limoges teaching hospital (TH) so as to improve our knowledge on promoting factors, clinical presentations, and therapy for C. fetus infections.
The samples were sent to and analyzed by the Limoges TH bacteriology laboratory. The BacT/ALERT® 3D (bioMerieux® ) system was used for hemocultures. Each hemoculture was made in 2 vials (1 aerobic and 1 anaerobic), incubated for 5 days at 37 ◦ C. Samples positive for curved or spiraled Gram-negative bacilli, were seeded on blood agar in micro-aerophilic conditions at 37 ◦ C. The identification was made with the identification galleries (Api Campy® ) or with the MALDI-TOF Vitek® MS (bioMerieux® ) system. Susceptibility testing was performed for each sample according to recommendations of the Antibiogram Committee of the French Microbiology Society (CA-SFM).
2. Patients and methods
2.4. Statistical analysis The descriptive data were analyzed for all patients. The results for quantitative variables are presented as means, maximum, and minimum. The results for qualitative variables are expressed as percentages. 3. Results Twenty patients had at least 1 biological sample positive for C. fetus between January 2007 and August 2013. There was no difference according to the years studied. The average age was 73 years; 15 patients were men. The age, sex, the underlying diseases, the clinical signs, the septic sites, the treatments, and the outcome are listed in Table 1 and the average data in Table 2.
2.1. Type of study 3.1. Underlying diseases We conducted a retrospective study at the Limoges TH between January 2007 and August 2013. All the patients hospitalized in our institution with at least 1 sample tested positive for C. fetus at the bacteriology laboratory were included.
2.2. Patients and data The patients were identified from the data database. The epidemiological data (sex, age, history, and risk factors of immunodepression), clinical data (symptoms, localizations), biological data (inflammatory proteins, CBC), bacteriological data (type of sampling, identification, and antibiogram), treatment, and outcome were collected from the patient’s health records.
Five patients (25%) presented with diabetes, 9 patients (35%) with a hematological disease, and 12 patients (60%) with a history of solid cancer including 7 progressive diseases. Among the solid cancers, 11 were urinary tract tumors (5 prostate, 4 bladder, and 2 renal cancers), 1 was vesicular, 1 breast, 1 melanoma, 1 colon, 1 pancreatic, and 1 gastric. 3 patients had a history of 2 cancers, and 1 patient of 3 cancers. Among the hematological diseases there were 4 CLL (chronic lymphoid leukemia), 1 CML (chronic myeloid leukemia), 1 lymphoma, 1 AML (acute myeloblastic leukemia), 1 resistant anemia, and 1 IPT (idiopathic thrombocytopenic purpura). 4 patients did not have any history of cancers. 8 patients had received immunosuppressing treatment including 7 with ongoing chemotherapy and 3 with corticosteroid therapy. 2 patients were chronic alcohol abuser including 1 presenting with cirrhosis. Only 1 patient had no risk factor.
A. Cypierre et al. / Médecine et maladies infectieuses 44 (2014) 167–173
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Table 1 Clinical data for the 20 patients with Campylobacter fetus infections. Résumé des données cliniques des 20 patients porteurs d’une infection à Campylobacter fetus. Age
Sex
Underlying diseases
Clinical signs
Septic localization
Treatment and duration
Outcome
1
91
M
Amox/clav + Azithro 5d
Favorable
87 66
M F
AGS, thoracic pain Fever Fever
Pneumonia
2 3
Bacteremia Bacteremia
83
F
Amox + Cipro 14d Amox/clav + Cipro 2d then Piper/Tazo + Cipro 14d Amox/clav 11d
Favorable Favorable
4
Resistant anemia, prostate cancer Renal cancer CLL, corticotherapy, chemotherapy Vesicular cancer
5
83
F
Diabetes
Favorable
6
61
M
CLL, chemotherapy
Acute dermohypodermitis
Ceftriaxone 18d + Ofloxacine 21d Pristinamicine 15d
7
85
F
Acute dermohypodermitis
Amox 10d + Ofloxacine 5d
Favorable
8
73
M
Fever, chills
Bacteremia
Amox/clav 7d
Favorable
9 10
86 75
F M
CLM, breast cancer, corticotherapy, chemotherapy Gastric, prostate, pancreas cancers chemotherapy Diabetes Renal and vesical cancer
Fall, confusion Fever, pyuria
Bacteremia Renal abscess
Unfavorable Favorable
11
79
M
AGS, dyspnea
Pneumonia
Ofloxacine 10d Ceftriaxone + Cipro 7d then Amox 28d Amox/Clav 14d
12
87
M
AGS, cough
Pneumonia
Amox/Clav 10d
Favorable
13
73
M
Abdominal pain
Cipro 6 sem
Unfavorable
14
43
M
peritoneal dialysis fluid infection Acute dermohypodermitis
Amox/clav 8d + Genta 3d
Favorable
15 16 17 18 19
49 90 43 59 75
M M M M M
Unfavorable Favorable Favorable Favorable Favorable
20
47
M
Pristinamicine Amox/Clav + Genta 15d + 2d None Amox/Clav Vibramycin + Ciprofloxacine 6 sem + Genta 7d Amox/Clav + Genta 15d + 3d
Diabetes, prostate cancer, CLL Diabetes, prostate cancer, CLL Diabetes, vesical cancer Lymphoma, chemotherapy AML, chemotherapy Prostate, vesical cancer Chronic alcohol abuse None ITP, corticotherapy, melanoma Chemotherapy, cirrhosis, alcohol abuse colon and urothelial cancer
Abdominal pain, Fever Fever, fall, coxal pain Fever, leg erythema Fever, gonalgia, thoracic pain
Fever, calf pain Fever Fever Acute pancreatitis Fever, headaches Fever, shoulder pain Fever, fall
Peritonitis Bacteremia
Pneumonia Bacteremia Bacteremia Bacteremia Septic arthritis Bacteremia
Favorable
Favorable
Favorable
Unfavorable
CLL: chronic lymphoid leukemia; CLM: chronic myeloid leukemia; AML: acute myeloblastic leukemia; ITP: idiopathic thrombocytopenic purpura; AGS: alteration of global status; Amox/clav: amoxicillin + clavulanic acid; cipro: ciprofloxacin; oflox: ofloxacin; amox: amoxicillin; genta: gentamycin; azithro: azithromycin; piper/tazo: piperacillin + tazobactam.
Eleven patients presented with arterial hypertension, 5 with auricular fibrillation, and 5 had a history of acute coronary syndrome. Five patients (20%) carried a joint prosthesis (4 hip prostheses and 2 knee prostheses). 3.1.1. Clinical data On admission, 70% of patients (14/20) presented with fever, 25% (5/20) with abdominal pain at the diagnosis, but none with diarrhea. The most frequent secondary septic sites were the lungs in 4 cases (20%), a joint in 3 cases (15%), and the skin in 3 cases (15%). 9 patients (45%) presented with bacteremia without any secondary septic site. Four patients (20%) carried of an implantable port. 3.1.2. Biological data The average CRP level was 142 mg/L (8–289 mg/L) and the average leukocyte count was 13,955/mL (3380–40,000/mL). 14
patients (70%) presented with hyperleukocytosis (>10,000/mL) at the diagnosis. Campylobacter were identified in the hemocultures of 17 patients. Two of the patients with negative blood samples presented with peritonitis, and 1 with a renal abscess and the peroperative local samples were positive. Coprocultures that had been performed for 2 patients were negative. Four of the identified bacteria were resistant to amoxicillin (20%), 6 to ciprofloxacin (30%), and 2 isolates were of intermediate susceptibility to tetracycline (10%). No isolate was resistant to amoxicillin–clavulanic acid, to gentamycin, or to erythromycin. 3.1.3. Treatment Only 1 of the 20 patients did not receive any antibiotherapy. The average duration of treatment was 19 days (5 to 51 days). The antibiotic schemes were varied with mono or bitherapy, parenteral or oral treatment, relying on penicillins, macrolides,
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Table 2 Demographic characteristics, underlying conditions, clinical features, bacterial samples, biological data, treatments, and outcome of patients with Campylobacter fetus infection. Caractéristiques démographiques, antécédents, données cliniques, types de prélèvements, données biologiques, traitements et évolution des patients de notre cohorte. Data
Results
Mean age Sex Male Female
15/20 (75%) 5/20 (25%)
Samples Hemocultures Others
17/20 (85%) 3/20 (15%)
Underlying disease Alcohol abuse Cirrhosis Diabetes Solid cancer Urinary Hematological disease Vascular device
2/20 (10%) 1/20 (5%) 5/20 (25%) 12/20 (60%) 9/12 (75%) 9/20 (45%) 5/20 (25%)
Immunosuppressive treatment Chemotherapy Corticotherapy Clinical signs Fever Diarrhea Abdominal pain Weight loss Skin infection Joint infection Pneumonia Biological assessment CRP (mg/L) Leukocytes (/mm3)
73 (43–91)
8/20 (40%) 7/8 (87.5%) 3/8 (37.5%) 14/20 (70%) 0/20 (0%) 5/20 (25%) 3/20 (15%) 3/20 (15%) 3/20 (15%) 4/20 (20%) 142 (8–289) 13,955 (3380–40,000)
Resistance (I OR R) Amoxicillin Amoxicillin–clavulanic ac. Erythromycin Gentamycin Ciprofloxacin
4/20 (20%) 0/20 (0%) 0/20 (0%) 0/20 (0%) 6/20 (30%)
Unfavorable outcome Death
4/20 (20%) 1/20 (5%)
fluoroquinolones, aminosides, but also 3GC and imidazoles. The various treatments used are listed in Table 3. 3.1.4. Outcome The outcome was unfavorable for 4 patients. One female patient presented with recurrence of fever again after 10 days of ofloxacine treatment and alteration of her neurological status. Hemocultures were positive for C. fetus resistant to fluoroquinolones and she presented with a subdural collection requiring surgical drainage. The PCR genic amplification, using specific primers, of collection samples proved the presence of C. fetus. A new antibiotherapy, with amoxicillin and
Table 3 Antibiotics used. Schémas thérapeutiques des patients traités. Therapeutic schemes
Number of patient (n = 19)
Amox or Amox/clav ac alone Amox or Amox/clav ac + aminosides Amox or Amox/clav ac + FQ FQ seules Amox or Amox/clav ac + macrolides Amox or Amox/clav ac + aminosides + FQ Pristinamycin FQ + aminosides FQ + macrolides + aminosides
3 3 3 2 2 2 2 1 1
Amox: amoxicillin; amox/clav: amoxicillin + clavulanic acid; FQ: fluoroquinolones.
clindamycin, combined with the surgical treatment chirurgical, led to complete cure. Three other patients presented recurrence of fever after stopping the treatment. They carried medical devices (2 implantable ports and 1 peritoneal dialysis catheter) that had not been removed during the first episode and 1 patient had been given an antibiotic lock. The hemocultures were also positives for C. fetus. When hypothermia recurred, antibiotherapy was reintroduced, the medical devices were removed, and the outcome was favorable for 2 patients. The 3rd patient died when hypothermia recurred; he had presented with resistant AML. 4. Discussion We included 20 patients presenting with a C. fetus infection. Pacanowski in 2008 reported 94 patients [2], and Gazaigne 21 patients in 2007 [3]. As in the 2 previously mentioned studies, there was a majority of male (75% in our series, 70% for Pacanowski, 86% for Gazaigne) and aged patients (average 73 years of age). Similar results were reported recently by National Reference Center in Bordeaux with 875 C. fetus strains and a mean age of 68.4 years [8]. The published data prove a strong association between C. fetus infections and an underlying risk factor, contrary to other types of Campylobacter [9,10]. The most frequently reported diseases are cancers, especially digestives or hematological tumors, diabetes, with cirrhosis or liver failure, a history of organ transplantation, or chronic alcohol abuse [2–5,11–13]. The immunosuppression due to some therapies (corticosteroid therapy, chemotherapy, immunosuppressive or immunomodulating drugs: methotrexate, leflunomide, cyclophosphamide, rituximab) is also a well-known risk factor. 80% of patients in our study had presented with recent or old cancer, including 70% (14/20) with progressive diseases. Sixty percent of the patients presented with solid cancers and 45% of these with a hematological disease; this was a higher rate than usually reported: Pacanowski had mentioned only 38% of patients with cancer [2]. The cancers were urinary tract lesions for 15 patients in our study contrary to others reported series in which cancers most frequently of digestive origin. We cannot explain this difference.
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Diabetes was reported as a frequent comorbidity, as in our study, in this type of infection for close to 20% of patients [2,3,7,14]. Some authors suggested that old age could be by itself a risk factor. The mean age was high in our study (73 years) and correlated to main published studies. The presence of vascular devices was also reported as a risk factor, and 5 of our patients carrier an implantable port or a vascular catheter [3]. Cardiovascular diseases were also reported as a risk factor for C. fetus infection but they were mostly related to vascular prostheses or valvular diseases [3]. Thirteen of our patients (65%) had a history of cardiac disease but only 2 presented with a valvular disease. Only 1 patient did not present with any underlying immunodepression, which compares to Pigrau’s data but is one of the lowest rates reported [5]. The patient was younger (59 years) with only a history of arterial hypertension. C. fetus are rarely isolated in stools, like other Campylobacter strains, but they are most frequently identified in hemocultures [15]. No coproculture was positive in our study and only 3 patients had negative hemocultures. Contrary to Campylobacter jejuni, C. fetus rarely cause diarrhea or enteritis, but they are known to cause isolated bacteremia or vascular infections with endocarditis and mycotic aneurysms [2,3,6,7,14–16]. Indeed this bacterium has specific adherence to injured vascular endothelium as well as for prosthetic material, related to a surface receptor with a strong affinity for the vascular endothelium, and to the secretion of a local pro-coagulant factor which promotes the formation of thrombi [17]. Physicians should systematically screen for the presence of an embolus or of a secondary vascular localization in patients presenting with C. fetus bacteremia. But many other infections have been reported: enteritis, peritonitis, pneumonia, meningitis, meningoencephalitis, pericarditis, thrombophlebitis, empyema, UTIs, spondylodiscitis, arthritis [3,4,13,18], as well as cerebral [19], colic, gluteal muscle [20], and pulmonary abscesses [21]. Acute cellulitis is frequently associated with C. fetus bacteremia, with higher rates of complications and mortality than with other bacteria [15]. Fifteen percent of patients in our study presented with a skin infection. Twenty percent of our patients presented with pneumonia, diagnosed because of dyspnea, cough, and fever; this was much higher than reported rates and unusual in this type of infection. Nevertheless, the diagnosis of pneumonia was made in the emergency unit, for patients presenting with severe sepsis or cardiac failure. Thus it could have been a complication of sepsis and not a pulmonary infection. There is no consensus for treatment. C. fetus bacteremia may be transitory in immunocompetent patients and the outcome may be favorable without any antibiotic treatment [2,13]. But the contribution of antibiotherapy was demonstrated for immunodepressed or geriatric patients, with a higher death rate in patients not having received appropriate antibiotic treatment [2]. Only 1 of our patients was not given any antibiotherapy. He was a young patient, without any risk factor or medical history except for chronic alcohol abuse, hospitalized for acute pancreatitis and presenting with isolated bacteremia. The outcome was spontaneously favorable. The treatment for these infections is not well codified, as demonstrated by the great variety of therapeutic schemes used
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in our study. This type of infection is rare which accounts for the absence of any clinical trial; only isolated cases or small series have been reported. Third generation cephalosporins are often used as firstline empirical treatment for community acquired infections in immunodepressed patients, or as an alternative to fluoroquinolones in cases of enteroinvasive diarrheas. The authors of a Quebec study on 111 C. fetus strains reported that 13% of isolates were resistant to cefotaxime [16]. The results do not correlated with the usually reported rates, especially in France where the rate of cefotaxime resistant strains is much higher [3]. Only 1 strain was resistant to cefotaxime in our study, but these results are sometimes interpreted by microbiologists (given as resistant whereas they are susceptible in vitro), because of the weak effectiveness and of reported therapeutic failures [4]. Some cases of resistance to penicillins have been reported, related to the secretion of beta-lactamase, usually inhibited by clavulanic acid, but not by sulbactam or tazobactam [2,22]. This is why most C. fetus strains are susceptible to the amoxicillin- clavulanic acid combination. Carbapenems, with imipenem, seemed to be the first-line therapy for the treatment of severe C. fetus infections or vascular infections, without any reported resistance so far. Gazaigne reported in his 2008 study, that the outcome had been favorable for all his patients treated by imipenem [3]. Furthermore, no resistance has been demonstrated yet. Tremblay, in the Quebec study, reported that all strains were susceptible to ampicillin, gentamycin, imipenem, and meropenem [16]. This antibiotherapy was not used in our study. Fluoroquinolones, usually first-line treatment for Campylobacter enteritis, are associated to higher death rate when they are used as empirical treatment for C. fetus infections [2]. Indeed some cases of resistance to this antibiotic have been reported [23] and it is contra-indicated to use them before obtaining antibiogram results. We observed, as in Pacanowski’s study, 30% of resistance to fluoroquinolones, 10% more than in the NRC 2011 data, but this rate has been continuously increasing [24]. Gentamycin is the most frequently used aminoside for this type of infection. It is a good first-line antibiotic because of a very low MIC, the absence of reported resistance, and its quick bactericidal activity for bacteremia or vascular infections when combined with a beta-lactam [2,16,25]. Delayed initiation of antibiotherapy or inadequate antibiotic treatment is a risk factor for death in Campylobacter infections [2]. Nevertheless initiating an adequate first-line therapy for this bacterium is difficult for the clinician for several raisons: it is a rare infection, with an unspecific clinical presentation, and resistance is possible with 3GC and fluoroquinolones, the 2 firstline treatments usually given to immunodepressed and febrile patients. The minimum duration of treatment has not been determined yet. In our study it was 19 days on average (5 to 51 days). The treatment duration usually depends on the infectious localizations but seems longer than for the same infections due to other bacteria. Cellulitis is usually treated for 21 days, arthritis and spondylodiscitis from 6 weeks to 3 months [5,11], joint prosthesis infections for 3 months. A prolonged parenteral treatment is
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recommended in case of vascular infection, for at least 3 to 4 weeks [3,5,15], and up to 12 weeks in cases of prosthetic valve endocarditis [6]. Another crucial point of the treatment is the removal of infected implantable material. Several authors have already reported this [26–28] for vascular but also for joint prostheses. Five of our patients carried catheters (4 implantable ports and 1 peritoneal dialysis catheter). The 3 patients whose material had not been removed relapsed when the antibiotic treatment was stopped. Removing the catheters and reinitiating an adequate antibiotherapy led to cure. Only 1 of our patients died: he was carrying an implantable port, which had not been removed, and presented with bacteremia treated by pristinamycin. Our study was retrospective, including a small number of patients; but it raised several interesting points. It confirmed that C. fetus infections occur most frequently in immunodepressed patients with a history of diabetes or cancer, especially urinary. It did not allow making recommendations for the antibiotic treatment or its duration but stressed the contribution of an adapted antibiotherapy and the need to remove infected medical material, especially for catheter-related infections. 5. Conclusion C. fetus infections occur most frequently in men, geriatric patients, and patients presenting with immunodepression, diabetes, or cancer. C. fetus diarrhea is rare and the main clinical presentations are isolated bacteremias, cutaneous, and vascular infections. The treatment is not codified but amoxicillin/clavulanic acid and gentamycin seem to be the best therapy because of their pharmacodynamic properties and of the weak rate of resistance. Fluoroquinolones and macrolides must not be used in first intention. Removal of the medical material and especially of catheters is mandatory to achieve therapeutic success. Disclosure of interest The authors declare that they have no conflicts of interest concerning this article. References [1] Denis F, Ploy MC, Martin C, Bingen E, Quentin R. Bactériologie médicale, techniques usuelles. Masson 2007:389–92. [2] Pacanowski J, Lalande V, Lacombe K, Boudraa C, Lesprit P, Legrand P, et al. Campylobacter bacteremia: clinical features and factors associated with fatal outcome. Clin Infect Dis 2008;47(6):790–6. [3] Gazaigne L, Legrand P, Renaud B, Bourra B, Taillandier E, Brun-Buisson C, et al. Campylobacter fetus bloodstream infection: risk factors and clinical features. Eur J Clin Microbiol Infect Dis 2008;27(3):185–9. [4] Francioli P, Herzstein J, Grob JP, Vallotton JJ, Mombelli G, Glauser MP. Campylobacter fetus subspecies fetus bacteremia. Arch Intern Med 1985;145(2):289–92. [5] Pigrau C, Bartolome R, Almirante B, Planes AM, Gavalda J, Pahissa A. Bacteremia due to Campylobacter species: clinical findings and antimicrobial susceptibility patterns. Clin Infect Dis 1997;25(6):1414–20.
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