First Case Report of Fatal Sepsis Due to Campylobacter upsaliensis

Abstract

We encountered a rare case of severe fatal infection in a 70-year-old woman due to Campylobacter upsaliensis, identified by PCR amplification and sequencing analysis of the 16S rRNA gene using DNA extracted from the isolates. To our knowledge, fatal sepsis due to this organism has never been described to date.

CASE REPORT

A 70-year-old woman was admitted to the emergency department complaining of loss of consciousness. On admission, her vital signs showed lethargy, hypothermia (35.1°C), hypotension (systolic blood pressure of 80 mm Hg), and tachycardia (pulse rate of 160 per minute). She did not have any recent episodes of diarrhea or enterocolitis, as assessed at her periodic visits to our hospital. Prolonged hypoglycemia with treatment resistance was also observed, and glucose was administered more than once. She had a history of left ureteral cancer, thyroid cancer, ectopic Cushing's syndrome, hypertension, and atrial fibrillation. Laboratory examination showed a normal white blood cell count, thrombocytopenia, a high serum transaminase level, and acute kidney injury (estimated glomerular filtration rate of 15.4 ml/min/liter). Severe metabolic acidosis and lactic acidosis were also observed. Enhanced computed tomography imaging led to a diagnosis of Stanford type A dissecting aortic aneurysm with cardiac tamponade. Enteritis and abscesses were not observed. Although pericardiocentesis was performed for the cardiac tamponade caused by the dissecting aortic aneurysm, the patient chose not to have artificial blood vessel replacement performed. Large amounts of vasopressors (noradrenaline and dopamine) and glucose were administered while the patient was in the intensive care unit. Cefazolin (2 g per day) was administered to prevent surgical site infection following pericardiocentesis rather than as a treatment for the original infection. However, severe hypotension, hypoglycemia, and liver failure worsened without improvement. The patient died due to multiorgan failure 2 days after admission.

Bacterial isolates from the blood of the patient, which was taken at admission for the evaluation of hypertension, were positive in Bactec aerobic bottles alone (BD, Franklin Lakes, NJ, USA). Subculture of the positive blood culture bottle yielded growth after 72 h of microaerobic incubation at 37°C (2 days after the patient's death). Bacterial identification using API Campy (Sysmex-bioMérieux, Tokyo, Japan) did not yield a definitive identification. Therefore, PCR amplification and sequencing were performed to analyze the 16S rRNA gene using DNA extracted from the isolates. Genomic DNA from all strains grown were extracted by physical extraction using zirconia beads (Mora extraction kit; AMR Co., Gifu, Japan), according to the manufacturer's instructions. The universal primers 8UA (5′-AGAGTTTGATCMTGGCTCAG-3′) and 1485B (5′-ACGGGCGGTGTGTRC-3′) were used as described previously (1). We performed sequencing analysis using a GenBank BLAST search and EzTaxon (http://www.ezbiocloud.net/eztaxon/). The sequence of the 16S rRNA gene (GenBank accession no. AB980278) was 99.1% identical (1,437 bp over the entire 1,450 bp fragment) with that of Campylobacter upsaliensis strain DSM5365 (accession number L14628). Based on the sequencing results, we identified the isolate as C. upsaliensis. Antimicrobial susceptibility testing was performed according to the Clinical and Laboratory Standards Institute (CLSI) standards for Campylobacter jejuni and Campylobacter coli (2). The MICs of the antibiotic agents were determined by the broth microdilution method using MicroScan (Siemens, Tokyo, Japan), except for azithromycin (AZM), for which Etest (bioMérieux, France) was used. The MICs of antibiotics against the C. upsaliensis strain are shown in Table 1. Antibiotic agents like penicillins, cephalosporins, and macrolides, including AZM, showed low MICs, consistent with previous reports (3–5). On the other hand, the MIC of fluoroquinolone (levofloxacin) was >8 μg/ml, indicating resistance to fluoroquinolone, as seen in a previous report (4).

TABLE 1.

MICs of antibiotics against C. upsaliensis isolated from the patient's blood culture

Antimicrobial agent	MIC (μg/ml)a
Penicillin G	0.5
Ampicillin	≤0.06
Ampicillin-sulbactam	≤0.25/0.125
Cefotiam	1.0
Ceftriaxone	1.0
Meropenem	≤0.12
Erythromycin	≤0.12
Azithromycin	1.25
Levofloxacin	>8
Sulfamethoxazole-trimethoprim	≤0.5/9.5

^aThe MIC of each antibiotic was determined by broth microdilution performed according to the CLSI standards, except for azithromycin, whose MIC was determined using Etest.

C. upsaliensis is known as a catalase-negative or weakly positive thermotolerant Campylobacter species (3). This organism's characteristics include the absence of H₂S production on triple sugar iron agar and susceptibility to nalidixic acid and cephalosporin. Therefore, C. upsaliensis was reported as being intolerant to the culture conditions optimized for C. jejuni and C. coli (6). Because routine laboratory procedures also overlooked this organism in our case, cases of C. upsaliensis infection might still be underdiagnosed.

C. upsaliensis has been reported mainly as an organism causing diarrhea not only in dogs (7) but in humans (8). The presumed transmission of this organism from dogs and cats to humans has been reported (7, 9). Water or food contaminated with the feces of pets, such as dogs or cats, might be routes of transmission. On the other hand, the majority of human-infecting strains are genetically separate from the canine-infecting strains, indicating that dogs may not be the main source of human infection (10). In addition, there is only 1 report to date on human-to-human transmission (11). Although C. upsaliensis is an emerging diarrhea-causing pathogen that is thought to be transmitted from household pets (7, 9), the patient had no history of owning pets. She also did not have contact with any other person with diarrhea or colitis; therefore, her infection route is unclear.

C. upsaliensis has most frequently been reported as the causative organism in cases of enteritis and bacteremia (Table 2). In addition, C. upsaliensis was also isolated from patients with extraintestinal infections. These previous reports are summarized in Table 2. However, to our knowledge, a severe fatal case due to this organism has never been described to date, and the clinical spectrum of this organism in humans is not fully understood.

TABLE 2.

Thirty-four cases of C. upsaliensis infection from previous reports^a

Age (yrs or as indicated)	Sex	Underlying disease	Clinical presentation	Reference
—	—	—	Hemolytic uremic syndrome	16
4	—	—	Guillain-Barré syndrome	17
64	M	—	Guillain-Barré syndrome	18
83	M	CHF, CRF, COPD	Bacteremia	14
10 (mo)	M	None	Bacteremia	14
20	M	None	Enteritis	14
72	M	CRF	Peritonitis	14
35	F	AML	Enteritis	14
6 (mo)	M	None	URI, erythematous tympanic membranes	14
38	M	AIDS	Bacteremia	14
1	M	URI	Enteritis	14
80	F	Glioblastoma	Bacteremia	14
25	F	REP	Bacteremia	14
64	M	LC	Bacteremia	14
11	F	None	Enteritis	12
36	M	Alcohol syndrome	Pneumonia	12
30	F	None	Burn	12
4	F	None	Enteritis	12
6	M	Anorexia	Enteritis	12
9	M	Kwashiorkor	Bacteremia	12
13	F	None	Enteritis	12
9	M	Anemia	Pneumonia	12
7	F	Myocarditis	Bacteremia	12
6	M	None	Enteritis	12
18	M	Kwashiorkor	Bacteremia	12
27	M	Kwashiorkor	Enteritis	12
10	F	Underweight for age	Enteritis	12
12	M	None	Enteritis	12
2	F	Kwashiorkor	Enteritis	12
18	F	Kwashiorkor	Bacteremia	12
46	F	None	Breast abscess	19
26	F	None	Abortion	9
24	M	Knee arthroplasty	Prosthetic knee infection	15
83	M	IBS	Persistent bloody diarrhea	5
70	M	UC, TC, CS	Severe sepsis	This report

^a—: unknown; M, male; F, female; CHF, congestive heart failure; CRF, chronic renal insufficiency; COPD, chronic obstructive pulmonary disease; AML, acute myeloid leukemia; URI, upper respiratory illness; REP, ruptured ectopic pregnancy; LC, liver cirrhosis; IBS, irritable bowel syndrome; UC, ureteral cancer; TC, thyroid cancer; CS, Cushing's syndrome.

We concluded that the patient's severe hypotension, severe acute liver failure, acute kidney injury, lactic acidosis, and hypoglycemia were all caused by the sepsis, because no other cause of these symptoms could be identified. In addition, enteritis was not observed in the patient. Infections due to C. upsaliensis have been reported to be associated with an underlying disease or immunocompromised state, including human immunodeficiency virus infection (12–14). This patient also had a history of cancer and endocrine disease.

To our knowledge, a severe fatal case of C. upsaliensis infection resulting in multiorgan failure, such as this case, has never been reported to date. Dissecting aortic aneurysms are usually induced by aortic sclerosis. The causal association between C. upsaliensis bacteremia and the aneurysm in this case is unclear, because an infected aneurysm is usually of the saccular type, and C. upsaliensis was detected only in the blood culture (the patient's aortic tissue was not obtained).

In previous reports, erythromycin resistance of C. upsaliensis infections ranged from 10% to 15% (6, 14), and ciprofloxacin resistance was approximately 5% (4). C. upsaliensis isolated from our patient showed a high MIC only for fluoroquinolone, in addition to macrolides, similar to a previous report (15). For the selection of antibiotic treatments, further data on the antibiograms of C. upsaliensis strains from different countries are required. In addition, there was a significant time lag until the identification of this organism in our case. Because C. upsaliensis infection is rare in clinical settings, if a patient has underlying disease, as in our case, treatment assuming C. upsaliensis infection is unlikely to be performed.

This case report is thought to be valuable since it highlights a severe and rare case due to C. upsaliensis, an emerging pathogen. It is important to clarify the conditions and medium required to culture this organism. The clinical spectrum of C. upsaliensis infection remains unclear, and further studies are required to establish appropriate treatments.