Malani, Anurag N. MD*‡; Malani, Preeti N. MD*†‡§; Cinti, Sandro K. MD*‡
An estimated 2.4 million cases of campylobacter infection occur annually in the United States,1 with Campylobacter jejuni-associated gastroenteritis being the most common presentation. Campylobacter fetus subspecies fetus, a less common species, is primarily associated with bacteremia and extraintestinal infection.2 Previously called Vibrio fetus, this agent was first isolated in 1909 from sheep and cattle with septic abortions3 and has since been isolated from swine, poultry, and reptiles.3
Campylobacter fetus infection is generally acquired from contact with infected animals or ingestion of contaminated meats, dairy, or water. Outbreaks due to unpasteurized milk and consumption of raw calves' liver are described.4,5 Recent literature suggests that systemic C. fetus infection may be more frequent than previously estimated,6,7 and C. fetus has been labeled an emerging human pathogen.8 Many laboratories use antibiotic-containing blood agar and incubation at 42°C for the optimal isolation of C. jejuni. Paradoxically, these conditions inhibit the growth of C. fetus and may contribute to the underidentification of C. fetus infection.2 Optimal growth of this fastidious gram-negative bacillus occurs under microaerophilic (5%-10% oxygen) conditions on nonselective rich media, such as chocolate agar, with incubation at 25°C.3,8
Campylobacter fetus often causes a systemic febrile illness in patients with underlying medical conditions. Bacteremia is frequent and associated with a mortality rate of 17% to 43%, making proper diagnosis imperative.9 Other clinical manifestations of infection include meningitis, vascular infections, septic abortions, and cellulitis.7,10-12 Campylobacter fetus is a rare cause of septic arthritis.13 To our knowledge, there are at least 4 other cases of C. fetus prosthetic joint infection in the English-language literature.13-16 Each patient underwent surgical debridement, removal of infected prosthetic joints, or abscess drainage. We present a case of C. fetus prosthetic joint infection successfully treated with medical therapy alone. Also reviewed are the salient clinical and microbiological features of C. fetus prosthetic joint infection in the English-language literature.
A 61-year-old man with osteoarthritis secondary to trauma underwent a total right hip replacement in November 2003. In April 2005, he presented with a 10-day history of fevers, night sweats, headaches, right hip and back pain, and progressive difficulty with ambulation. Four days before admission, he was evaluated in the urgent care for fevers of 101°F, myalgias, and headache. Results of laboratory tests and physical examination were unremarkable, and he was discharged with a diagnosis of "viral illness." Blood cultures obtained during evaluation showed no growth.
On admission, physical examination result was remarkable for a temperature of 101°F, point tenderness at the lateral aspect of the right hip, and difficulty with hip abduction and adduction. Laboratory test results were remarkable for white blood cell (WBC) count of 7200 cells/mm3, hemoglobin level 12.8 g/dL, platelet count 315,000/mm3, and an elevated serum creatinine level of 1.6 mg/dL (baseline, 1.1 mg/dL). Westergren erythrocyte sedimentation rate (WESR) was 92 mm/h, and C-reactive protein was 36.4 mg/dL. Multiple sets of blood cultures were drawn. Radiographs of the right hip showed no effusions.
On hospital day 7, he underwent fluoroscopic-guided right hip aspiration that yielded 35 mL of cloudy fluid. Synovial fluid analysis demonstrated WBC count of 22,000 μL (81% neutrophils) and red blood cell (RBC) count of 30,000 μL, and Gram stain showed no organisms. Empirical antimicrobial therapy was started with intravenous piperacillin/tazobactam and vancomycin. A computed tomography (CT) scan of the abdomen and pelvis without contrast did not show any fluid collections or hip effusions. Serial blood cultures and synovial fluid cultures yielded no growth.
The patient's condition was evaluated by orthopedic surgery, and a bedside closed reduction was performed for a right hip dislocation. Multiple attempts at repeat hip aspiration failed to produce additional fluid. Although his fevers, headaches, and hip pain continued, antimicrobials were discontinued after 1 week because there was no clear microbiological evidence of prosthetic joint infection. Repeat WESR had risen to 145 mm/h. Workup for infectious and rheumatologic etiologies remained unrevealing.
By hospital day 16, fevers and hip pain had resolved, and the patient was ambulating. His renal function returned to baseline. Repeat CT scan demonstrated 2 enhancing fluid collections at the lateral and posterior aspect of the right femoral neck, the largest measuring 3 × 6 cm (Fig. 1). A technetium-labeled WBC scan showed uptake in the right hip and hemipelvis. An ultrasound-guided hip aspiration yielded 20 mL of cloudy fluid. Synovial fluid analysis showed WBC count of 28,250 μL (84% neutrophils) and RBC count of 20,000 μL, and Gram stain showed no organisms. On the third day of incubation, a tiny gram-negative bacillus was noted in the aerobic bottle. Growth of the fastidious organism occurred on both blood and chocolate agar plates. The organism was sent to the Michigan Department of Community Health state laboratory for further testing.
Multiple sets of blood cultures were obtained. A fourth aspiration yielded 10 mL of cloudy synovial fluid, WBC count of 21,750 μL (88% neutrophils), and RBC count of 190,000 μL, and the Gram stain showed no organisms. The cultures yielded no growth. Given the patient's history of cerebrovascular accident, partial aortic graft placement, and severe hypertension, orthopedic surgery felt the risks of surgical intervention outweighed potential benefit, and it was decided to treat him medically. He was treated with ceftriaxone 2 g IV daily.
Ten days after hospital discharge and 7 weeks after his initial presentation, the Michigan Department of Community Health laboratory identified the pathogen as C. fetus. Given that the patient continued to demonstrate clinical improvement, ceftriaxone was continued for 6 weeks. After 3 months, repeat WESR had decreased to 8 mm/h, and follow-up CT scan performed showed resolution of the earlier fluid collections (Fig. 2). Therapy was changed to oral suppressive therapy with levofloxacin 750 mg daily for 4 months, followed by indefinite doxycycline suppressive therapy 100 mg BID. The patient remains well more than 1 year later.
Prosthetic joint infection secondary to C. fetus appears to have a favorable prognosis despite limited surgical intervention. Among the 5 cases described in Table 1, 2 patients underwent surgical debridement, 1 had removal of infected prosthetic joints, and 1 had an abscess contiguous with the hip prosthesis drained. Our patient was treated successfully with medical therapy alone. Two of the 5 cases, including the present case, required chronic oral suppressive therapy.
Earlier reviews of C. fetus infection have noted that about 75% of patients have underlying medical illnesses, including malignancy, hypogammaglobulinemia, alcoholism, diabetes mellitus, or the need for immunosuppressive medications.9,10,17 Our review is consistent with these studies as 3 of the 5 patients were immunocompromised; the patients had chronic lymphocytic leukemia (1), chronic myelogenous leukemia (1), and rheumatoid arthritis (1); and 2 were receiving oral steroids.
Campylobacter fetus infection shows a predilection for older adults. In a study of C. fetus infections during a 17-year period, 53% of infected patients were 70 years or older.18 About 70% of their isolates were identified from blood with only 20% identified from stool. Among the patients with prosthetic joint infection, ages ranged from 61 to 75 years.
Despite the propensity for C. fetus to cause bacteremia, only 1 case of C. fetus prosthetic joint infection noted isolation of the organism from blood.15 In contrast to C. jejuni, C. fetus is less likely to cause intestinal infection with only 2 cases reporting an antecedent gastroenteritis and 1 having the organism isolated from stool.15
Isolation of C. fetus has occurred from sheep, cattle, swine, poultry, and reptiles.3 Campylobacter fetus infection in sheep and cattle can present as a septic abortion.3 One case of C. fetus prosthetic joint infection had significant contact with cattle, including exposure to an aborted calf in the weeks preceding his infection.13 Our patient denied any animal exposure.
The 5 patients received different antimicrobial regimens of varying lengths (Table 1). Clinical outcomes were generally good. As of yet, there are no standard treatment guidelines or established antibiotic susceptibility breakpoints for C. fetus infection. In this case, susceptibility data would have been useful because resistance to extended-spectrum cephalosporins, quinolones, and tetracycline has been described.6,18,19 Nearly all C. fetus isolates are susceptible to imipenem, meropenem, gentamicin, and ampicillin,18 and these antibiotics can be used as empirical therapy, with definitive treatment based on antibiotic susceptibility testing.8,18
Our case was a challenging diagnostic dilemma. Seven weeks were needed to make a diagnosis of C. fetus septic arthritis requiring 3 hip aspirations. Numerous blood cultures yielded no growth, and repeated Gram stains from synovial fluid showed no organisms. Three (75%) of the 4 cases of C. fetus prosthetic joint infection were reported to have Gram stains from infected tissue or fluid that showed no organisms (Table 1). Because of its fastidious and slow-growing nature, recommendations are to hold blood cultures longer than 7 days to increase the yield of C. fetus.6,17
In the past year, our case is the third report of C. fetus prosthetic joint infection,13,15 perhaps indicating the emerging nature of this fastidious pathogen.6-8 Campylobacter fetus prosthetic joint infection may become more common given the increasing number of prosthetic joint placements, the growing elderly population, the increasing intensity of immunosuppressive therapies, and changes in food consumption.8 Campylobacter fetus prosthetic joint infection has a favorable prognosis, generally requiring a combination of medical and surgical therapy. Clinicians should be aware of this infection in debilitated and immunocompromised hosts, especially those with relevant animal exposure or tendency to eat undercooked foods and meats.
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