Recurrent Septicemia Due to Campylobacter fetus and ... - Springer Link

Infection

Case Report

Recurrent Septicemia Due to Campylobacter fetus and Campylobacter lari in an Immunocompetent Patient R. Krause, S. Ramschak-Schwarzer, G. Gorkiewicz, W. J. Schnedl, G. Feierl, C. Wenisch, E. C. Reisinger

Abstract We describe a severe and recurrent septicemia due to Campylobacter in a 75-year-old immunocompetent patient. Two Campylobacter strains were detected in several blood cultures. Campylobacter fetus and Campylobacter lari were identified with PCR tests based on species-specific nucleotide sequences for the 16S rRNA gene.

Key Words Campylobacter · Recurrent septicemia · Immunocompetent patient Infection 2002; 30: 171–174 DOI 10.1007/s15010-002-2115-0

Introduction Campylobacter species are microaerophilic and capnophilic curved gram-negative bacteria found worldwide in various animals, in water and in humans. They are among the most common causes of diarrhea and have also been reported to cause arthritis, cellulitis, osteomyelitis, prosthetic hip joint infection, peritonitis, meningitis, native and prosthetic valve endocarditis, sepsis, septic abortion and empyema and are associated with the Guillain-Barré syndrome [1–3]. The usual sources of infection are improperly handled or cooked food and raw milk, but human-to-human transmission also occurs. Campylobacter jejuni and Campylobacter coli are common causes of gastrointestinal infections in humans but they rarely (in less than 1% of cases) cause septicemia [4]. Campylobacter fetus rarely causes gastroenteritis in humans and infrequently systemic illness (e.g. endocarditis, meningitis, arthritis, peritonitis and sepsis) in immunocompromised hosts [5]. 17 cases of gastroenteritis due to Campylobacter lari and eight cases of systemic infections in immunocompetent and immunosuppressed patients have been described [1, 6–12]. We report the first case of a previously healthy immunocompetent patient with severe and recurrent septicemia due to mixed infection with C. fetus and C. lari.

Case Report A 75-year-old white male presented with undulating fever up to 40 °C and a spontaneously drained apical abscess in his upper jaw. Four weeks before admission he had returned from Poland, where he had done volunteer relief work after a disastrous flood and had frequently consumed smoked cheese made from unpasteurized sheep milk. During this stay he developed diarrhea, which resolved within 2 days after treatment with sulfaguanidine. Four weeks later, back in Austria, he developed undulating fever up to 40 °C and was admitted to our department after 1 week of fever. Physical examination revealed two defective teeth. Radiographic examination of the jaws showed two abscessed teeth, which were extracted. The bacteria responsible for the abscessed teeth could not be identified.Abnormal laboratory parameters included C-reactive protein 58 mg/l (normal < 5 mg/l), fibrinogen 667 mg/dl (170–400 mg/dl), gamma-glutamyl transpeptidase 76 U/l (< 28 U/l) and creatinin 1.6 mg/dl (0.6–1.3 mg/dl). Peripheral blood counts showed leukocytosis of 14.4 granulocytes/l (4.0–10.0 granulocytes/l) with neutrophil counts of 87.7% (50–75) and basophil counts of 5.3% (< 1%). CD4 lymphocyte counts, CD4/CD8-ratio and all other routine laboratory parameters were within normal ranges. HIV and Brucella antibodies in the serum and cultures from blood, urine and stool were repeatedly negative. Ultrasound examination and computed tomography of the abdomen showed moderate splenomegaly. Echocardiography showed an apical aneurysm and an ejection fraction of 35% after a myocardial infarction 5 years earlier. Transesophageal echocardiography showed no valve alterations or signs of endocarditis. Chest X-ray and granulocyte scintigraphy were both normal. Intravenous amoxicillin/clavulanic acid was administered for 3 days but the fever continued. Intravenous imipenem 1g tid plus vancomycin 1g bid were started and the body temperature reR. Krause (corresponding author), S. Ramschak-Schwarzer, W. J. Schnedl, C. Wenisch Division of Infectious Diseases, Dept. of Internal Medicine, Karl-Franzens University School of Medicine, Auenbruggerplatz 15, A-8036 Graz, Austria; Phone: (+43/31) 6385-3150, Fax: -3062, e-mail: [email protected] G. Gorkiewicz Institute of Molecular Biology, Biochemistry and Microbiology, KarlFranzens University, Graz, Austria G. Feierl Institute of Hygiene, Karl-Franzens University, Graz, Austria E.C. Reisinger Dept. of Internal Medicine, University of Rostock, Germany Received: August 10, 2001 • Revision accepted: December 27, 2001

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turned to normal within 9 days. Two weeks after initiation of this intravenous regimen the patient was discharged in good condition. 10 days later he was readmitted with undulating fever up to 40 °C. This time he was started on cefoperazone plus gentamicin. In three aerobic blood cultures obtained prior to administration of these antibiotics, bacterial growth was detected on day 3 and the isolate was presumed to be a Campylobacter species (for microbiological characteristics see below). Cefoperazone plus gentamicin did not affect the fever within 3 days and the antibiotic regimen was switched to intravenous clarithromycin, which some authors consider the drug of choice in Campylobacter infections [13]. After 5 days of clarithromycin, however, the fever remained unchanged. Intravenous imipenem (1 g tid) was started but the fever responded only slowly. When the patient was still subfebrile on day 22 with imipenem, intravenous amoxicillin/clavulanic acid (2.2 g tid) was added. After another 9 days the patient was finally afebrile. Treatment was then switched to oral amoxicillin/clavulanic acid (1 g tid) plus doxycycline (200 mg once daily) for another 5 days and the patient was discharged in good condition.The patient was well at 3-year follow-up. The isolate from positive blood cultures was a microaerophilic, gram-negative, curved and spiral organism that grew at 25 °C, 35 °C and 42 °C. It was oxidase and catalase positive, reduced nitrate to nitrite, but did not hydrolyze hippurate and indoxyl acetate. In vitro MIC testing by E-test [10, 14, 15] showed susceptibility to cephalothin (8 µg/ml), ampicillin (0.25 µg/ml), amoxicillin/clavulanic acid (0.125 µg/ml), cefotaxime (8 µg/ml), imipenem (0.064 µg/ml), meropenem (0.016 µg/ml), gentamicin (0.125 µg/ml), tetracycline (0.5 µg/ml), erythromycin (0.5 µg/ml), lincomycin (0.25 µg/ml) and clarithromycin 0.25 µg/ml) and resistance to nalidixic acid (disk test), piperacillin (> 256 µg/ml), piperacillin/tazobactam (> 256 µg/ml), cefuroxime (64 µg/ml), cefoxitin (> 256 µg/ml), ceftazidime (64 µg/ml), ciprofloxacin (> 32 µg/ml), norfloxacin (> 32 µg/ml) and trovafloxacin (> 32 µg/ml). As reported in a previous case [16], a cephalothin MIC of 8 µg/ml would explain the growth of the Campylobacter isolate on Campylobacter selective agar. Phenotypical identification of C. lari is based on growth on selective agar at 37 °C and 42 °C and resistance to nalidixic acid and cephalothin. C. fetus subsp. fetus grows at 25 °C and 37 °C on selective agar and is susceptible to cephalothin but resistant to nalidixic acid. Both C. lari and C. fetus have positive catalase, positive cytochrome oxidase and negative urease reactions, but hippurate and indoxyl acetate hydrolyzation are negative. Nalidixic acid-sensitive and urease-positive C. lari variants have been described [17,18]. These criteria, however, did not suffice for an unequivocal identification of our isolate. The isolate was sent to reference laboratories for further identification (Dept. of Microbiology, University of Freiburg, Germany; Campylobacter and Helicobacter Reference Laboratory, CDC, Atlanta, GA, USA). Analysis of cellular fatty acids (CFA) and demonstration of DNA relatedness by PCR of the isolate to Campylobacter reference strains were performed by previously described techniques [19–21]. In the German laboratory single isolates of the original culture revealed C. fetus by analysis of CFA and were positive in the C. fetus PCR. A C. lari PCR was not performed. In the analysis performed at CDC a sample from the center of the agar plate with total plate growth was positive in both the C. fetus and C. lari PCRs. To confirm these results the PCR assays were repeated from the total plate growth and on three single isolates of the original culture. All three single isolates were only positive in the C. fetus PCR. The sample from total plate growth was again positive in both the C. fetus and C. lari PCRs, in-

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dicating that the culture was mixed.As described in reference [20], the C. lari-specific primers generated a 561-bp amplicon from C. lari, while C. fetus-specific primers generated a 997-bp amplicon from C. fetus but from no other Campylobacter, Helicobacter and Arcobacter species tested.

Discussion The epithet “lari” is derived from the Greek “sea gull,” which represents one of the natural hosts of this Campylobacter species. C. lari is also found in dogs, pigs, cattle, sheep, poultry, mussels, oysters and shellfish [18]. C. lari infections have been attributed to consumption of some of these, but waterborne outbreaks of C. lari infections have also been described [22]. C. fetus is found in cattle, calves, sheep, pigs and poultry [16]. C. fetus infections are acquired from consumption of animal-derived food products (e.g. calf liver, undercooked pork meat) but the source of infection usually remains unknown. Our patient may have acquired his infection with both of these Campylobacter species either through the consumption of raw sheep cheese or contaminated drinking water in Poland. Systemic disease due to C. fetus usually occurs in patients with chronic underlying diseases or reduced immunity [16, 23]. Septicemia due to C. lari has rarely been described in patients without immunosuppression. One immunocompetent patient with a pacemaker infection and bacteremia due to C. lari has been reported [6]. Bacteremia has been described in an immunocompromised patient with fever and altered mental status [1], in a neonate with chronic diarrhea [7], in a 10-year-old girl with anaplastic lyphoma in the medical history and post-radiotherapy occipital cavernoma [8] and in a 90-year-old patient with erysipelas and poor general health [9]. One patient had purulent pleurisy with bacteremia [10] along with a history of alcoholism, which is known to reduce immunity [24]. In contrast to these reports, our patient was neither immunocompromised nor did he have implanted prosthetic devices. Diarrhea and severe crampy abdominal pain due to C. lari have been reported in 17 patients, all of whom made a full recovery with imipenem (one patient), erythromycin (two patients), erythromycin plus netilmicin (two patients) or without antibiotic treatment (12 patients) (Table 1). Bacteremic C. fetus infection can be treated successfully with imipenem and gentamicin or erythromycin and the mortality rate is low [25–27]. Bacteremic C. lari infection is nonetheless associated with relatively high mortality.Three of eight reported patients with C. lari blood isolates died. Two immunosuppressed patients with bacteremia due to C. lari were treated with vancomycin, gentamicin, moxalactam and penicillin G but died after 3 days [1, 11]. Another patient was treated with intravenous amoxicillin/clavulanic acid for 18 days but died of hepatocellular deficiency and bronchitic congestion 46 days after admission [10]. In a recent report, an immunocompetent woman with bacteremia after pacemaker infection was successfully treated with imipenem plus gentamicin for 4 weeks [6]. Initial treatment



Table 1 C. lari diseases reported in the literature.

Case reports

No. of patients

Signs/symptoms

Suspected source of infection

Source of isolate

Therapy

Broczyk A [22]

7

Water

Stool

NA

Bruneau B [10] Chiu C [7]

1 1

Diarrhea, abdominal pain, vomiting, nausea, fever Purulent pleurisy Diarrhea

Unknown Unknown

Blood Stool, blood

Evans TG [28]

1

Unknown

Stool

Recovered

Goudswaard J [29]

1

Salt water

Stool

Erythromycin

Recovered

Morris CN [6]

1

Abdominal pain, fever, nausea, vomiting Diarrhea, abdominal pain, reactive arthritis Fever, weight loss, night sweats, chills

Amoxicillin Erythromycin, netilmicin Imipenem

Unknown

Imipenem, gentamicin

Recovered

Nachamkin I [1]

1

Fever, change in mental status

Unknown

Blood, pacemaker pocket aspirate Blood

Simor AE [30] Söderstrom C [12] Tauxe RV [11]

1 1 1

Diarrhea, abdominal pain Chicken Diarrhea, abdominal pain, fever Shellfish Fever Chicken

Stool Blood Blood

Godreuil S [9]

3 1 1 1

Diarrhea, abdominal pain Abdominal pain Diarrhea Fever, erysipelas

Chicken, pets Eggs, pets Chicken, pets Fish

Stool Stool Stool Blood

Martinot M [8]

1

Fever

Unknown

Blood

This report

1

Fever, chills

Cheese, water

Blood

a

Vancomycin, gentamicin, moxalactam, penicillin G No treatment Erythromycin Vancomycin, gentamicin, moxalactam, penicillin G Erythromycin No treatment No treatment Cefotaxim, penicillin G Amoxicillin/ clavulanic acid, amikacin Imipenem, amoxicillin/ clavulanic acid

Clinical outcome NA Fatality Recovered

Fatality

Recovered Recovered Fatality

Recovered Recovered Recovered NA Recovered

Recovered

NA: data not available

with intravenous amoxicillin/clavulanic acid was insufficient for our patient. He subsequently responded well to empirical treatment with imipenem for 15 days plus vancomycin for the first 7 days but relapsed with high fever 10 days after discontinuation of antibiotic treatment. His condition improved with administration of imipenem plus amoxicillin/clavulanic acid. Our patient and the two fatal infections reported in the literature [1, 11] indicate that bacteremic C. lari infection may not respond to antibiotic monotherapy, even if the strain is susceptible in vitro. In systemic infections due to these Campylobacter species the combination of imipenem with a second bactericidal drug (e.g. gentamicin or amoxicillin/clavulanic acid), both in high doses, seems appropriate.

Acknowledgments The authors thank P. Fields (Campylobacter and Helicobacter Reference Laboratory, CDC, Atlanta, GA) and M. Kist (Department


of Microbiology, University of Freiburg, Germany) for help in the species identification.

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