Campylobacter coli bacteraemia: how common is it?

Abstract

Campylobacter species are known to cause enteritis. However, over the past 40–50 years, there have been reports of varying presentations, such as cellulitis, spondylodiscitis and bacteraemia. Of the Campylobacter species, Campylobacter jejuni is the most common culprit for causing bacteraemia, however, Campylobacter coli bacteraemia is becoming more prevalent. Here, we discuss an unusual case of C. coli bacteraemia in a patient with decompensated liver cirrhosis.

Background

Campylobacter infections are notorious for causing enteritis. It is also well known that Campylobacter jejuni, specifically, may cause Guillain-Barre syndrome. Over the last 40–50 years, alternative presentations have been proposed to be caused by Campylobacter species. These infections include cellulitis, bacteraemia and spondylodiscitis.^{1 2}

The Campylobacter genus consists of gram negative, non-spore forming, microaerofili, oxidase-producing, ‘thermotolerant’ species, the majority of which have a polar flagellum that allows their motility.³ Of the Campylobacter species, C. jejuni is the most common culprit for causing bacteraemia; however, C. coli bacteraemia is becoming more prevalent. Here, we discuss a case of C. coli bacteraemia and the possible factors contributing to its increased prevalence.

Case presentation

The patient discussed in this case is a 59-year-old man with a history of hepatitis C (status postantiviral treatment in 2014) and liver cirrhosis a result of alcohol abuse complicated by oesophageal varices who presented to the ER in Kansas City, Missouri, in November 2018, having nine episodes of black, watery stools in the previous 1 week with concurrent scrotal swelling.

At initial presentation in the ER, vital signs were stable with temperature of 36.4°C, heart rate 84 bpm, respiratory rate 16, blood pressure 117/72 and oxygen saturation 99% on room air. Physical examination was remarkable for voluntary guarding, right upper quadrant tenderness, positive abdominal fluid shift and erythematous, edematous, tender scrotum with extension to the perineum (table 1).

Table 1.

Laboratory results

Laboratory results	Result	Reference range/ normal
White cell count	2.3x109/L	4.3–10.8x109/L
Haemoglobin	99 g/L	140–180 g/L
Sodium level	123 mmol/L	136–144 mmol/L
Potassium level	2.5 mmol/L	3.6–5.1 mmol/L
Magnesium level	1.2 mg/dL	1.8–2.5 mg/dL
Phosphorus level	2.2 mg/dL	2.4–4.7 mg/dL
Alkaline phosphatase	132 IU/L	40–129 IU/L
Aspartate aminotransaminase	65 U/L	15–41U/L
Alanine aminotransaminase	26 U/L	7–35 U/L
Lactic acid level	5.0 mmol/L	0.5–2.2 mmol/L
Hepatitis C RNA PCR	Not detected	Not detected

CT abdomen/pelvis with contrast showed infectious versus inflammatory colitis. Ultrasound of the scrotum showed possible scrotal cellulitis. The patient was empirically started on vancomycin intravenous 1250 mg every 12 hours and piperacillin/tazobactam intravenous 3.375 g every 8 hours before transfer to the inpatient unit.

Appropriate electrolyte replacement and fluid resuscitation was provided for patient’s lactic acidosis and electrolyte derangements. Urology was consulted and deemed patient’s urological symptoms could be managed non-surgically without concern for Fournier’s gangrene. Scrotal ultrasound did not reveal any signs of epididymo-orchitis. Urology deemed the scrotal changes to be cellulitis. It could have been an atypical presentation of Campylobacter species but one that could not have been confirmed. Unfortunately, no fluid could be drained to further analyse the scrotal infection. Further investigation of stools revealed faecal occult blood to be negative and Clostridium difficile to be negative. Stool culture returned positive for C. jejuni/coli antigen, for which doxycycline 100 mg every 12 hours was initiated.

Vancomycin was discontinued on hospital day 2 as blood cultures remained negative. However, on hospital day 3, blood cultures resulted with gram negative rods. The patient continued having black stools and noted chills and sweats. Repeat blood culture was collected on hospital day 3, which continued to grow gram negative rods while patient was on Piperacillin/tazobactam. Infectious disease was consulted and recommended broadening coverage with imipenem–cilastatin intravenous 500–500 mg for every 6 hours for Campylobacter species and continuing coverage with doxycycline for Helicobacter species. Faecal occult blood was positive at this time. Gastroenterology was consulted and completed a bedside paracentesis that drained 3500 mL of fluid. Fluid analysis did not indicate a bacterial peritonitis. Repeat blood cultures collected on hospital day 4 and 5 were negative for any growth. Doxycycline was discontinued. Imipenem was continued until the day of discharge (hospital day 14). Patient’s hospitalisation was complicated by an upper GI bleed for which he underwent EGD and variceal ligation. Unfortunately, the patient left the hospital against medical advice and was sent home with ciprofloxacin 500 mg every 12 hours to complete a total antibiotic course of 2 weeks after last negative blood culture.

Outcome and follow up

The patient was seen at his primary care physician’s office 4 days after leaving the hospital and reported complete resolution of his symptoms.

Discussion

Although our patient’s hospital course was complicated by the decompensation of his other comorbidities, this case highlights the recurring characteristics of a rare Campylobacter coli bacteraemia. Here, we will mainly focus on a review of the pathophysiology, comorbidities, manifestations, diagnosis and outcomes of developing C. coli bacteraemia.

The literature included in table 2 was selected from searching for ‘C. coli and bacteraemia’ in PubMed. Articles were excluded if they solely discussed Campylobacter infections in the setting of pregnancy, if they involved animal models, if the articles were non-English, if they focused on the optimal laboratory/microbiological detection methods, if they characterised methods of immunity against Campylobacter species, if the cases did not include bacteraemia, if the articles only outlined the molecular/genetic characteristics of Campylobacter species, and if the articles mainly discussed odontology.

Table 2.

Summary table of literature outlining clinical management and outcomes of patients infected with Campylobacter species

Authors	Location	Campylobacter subspecies (No)	Study date	Presenting sign/symptom*	Comorbidities†	Management	Outcome
Schønheyder et al9	Danish counties	Campylobacter coli (6) Campylobacter jejuni (6) Campylobacter fetus (2) Campylobacter spp (1)	1989–1994	Fever, diarrhoea, hypoglycaemic, coma, cellulitis	None (3) Immunodeficiency/ immunocompromise, endocrine disorders, malignancies, autoimmune disorders (12)	No antibiotic therapy (4) Penicillin/ampicillin+aminoglycoside (6) Penicillin (2) Ceftriaxone (1) Netilmicin (1) Beta-lactam, gentamicin, clindamycin, prosthetic valve replacement (1)	Resolved
Feodoroff et al26	Finland	C.coli (3) C. jejuni (73)	1998–2007	Fever, diarrhoea	None (53) HIV (1) Chronic pulmonary disease (5) CV disease, dementia, DM, or mild liver disease (4) Moderate-to-severe liver disease (3) Renal disease (1) Malignancies (5)	Appropriate (50) Inappropriate/no treatment (26)	Resolved (72) Death (2) Spondylodiscitis (1) GBS (1)
Ladrón de Guevara et al6	Madrid	C. coli (1) C. jejuni (5)	1991–1992	Fever, diarrhoea, haematochezia, abdominal pain	Jaundice (1) Chronic liver disease (1) Colonic adenocarcinoma (1) Enteric fistula (1) IVDU, HIV (2)	Erythromycin (3 gentamicin, clindamycin (1)	Resolved
Liao et al11	Taiwan	C. coli (15) C. jejuni (3) C. fetus (6)	1998–2008	Abdominal pain, nausea, diarrhoea, fever	Chronic renal insufficiency (10) Liver cirrhosis (9) Malignancy (8) Prior abdominal surgery (8) Steroid usage (7) DM, HF, Chronic lung disease, UC, hypogammaglobulinaemia (11)	Cephalosporin (13) Fluoroquinolones (5) Amoxicillin/clavulanate (3) Macrolides(2)	Resolved (21) Death (3)
Skirrow et al13	England and Wales	C.coli (23) C. jejuni (91) C. fetus (22) Campylobacter lari (2) Campylobacter spp (137) C. jejuni subspecies (114)	1981–1991	Diarrhoea	Malignancy (30) Renal disease (16) Liver disease (15) DM (11) HIV/AIDs (11) IBD (7) Hypogammaglobulinaemia (4) Miscellaneous (15)	Not reported	Not reported
Fernández-Cruz et al17	Madrid	C. coli (8) C. jejuni (45) C. fetus (13) Campylobacter spp (2)	1985–2007	Diarrhoea, vomiting, fever, abdominal pain, pneumonia, cellulitis	Liver disease (21) HIV (15) Malignancy (7) Solid organ transplantation (2) Hypogammaglobulinaemia (10) Others (18	Appropriate empirical therapy (25)–mainly administered ciprofloxacin or third generation cephalosporins	Resolved (44) Attributable death (10) Subsequent episodes (7) Death (11)) Unknown (6)
Cambier et al15	Belgium	C. coli (1)	2018	Fever, nausea, headache, diarrhoea	Polymyalgia rheumatic Steroid therapy (d/c 10 years ago) CAD s/p angioplasty Contact with sheep Ingestion of farm artisanal cheese	Meropenem	Resolved
Liu7	USA	C. coli/jejuni (1)—unable to differentiate in culture	2011	Generalised weakness, diarrhoea, fever	Stage IV gliosarcoma s/p radiation and chemotherapy on steroid taper and periodic bevacizumab therapy	Azithromycin	Resolved
Okada et al22	Japan	C. coli (1)—refractory to antibiotic therapy due to intestinal carriage	Not reported	Fever, cellulitis	XLA	Oral kanamycin and intravenous antibiotics	Resolved
Hagiya et al16	Japan	C. coli (1)	2015	Fever, cellulitis	XLA	Intravenous biapenem and oral minocycline	Resolved
Pigrau et al10	Spain	C. coli (1) C. jejuni (47) C. fetus (4) Campylobacter spp (6)	1979–1996	Fever, diarrhoea -most common	Liver cirrhosis (20) Neoplasia (8) Steroid therapy (13) Chemotherapy (10) HIV (7) Transplant (5) DM (4) Hypogammaglobulinaemia (4) Chronic renal failure (3) Pregnancy (3) SLE (2) Nephrotic syndrome (1) None (4) Hospitalisation (16)	Erythromycin Amoxicillin/clavulanate (3)	Resolved (39) Favourable outcome without treatment (11) Relapse (1) Death (6)
Walder et al18	Sweden	C. jejuni/coli (5)	1977–1979	Fever, diarrhoea, abdominal pain, headache, nausea, respiratory distress	None (2) Travel (1) Thymoma, hypoplastic anaemia, malabsorption (1) Chronic bronchitis, tobacco abuse (1) Ulcus, bronchopneumonia (1)	Ampicillin (2) None (1) Penicillin V (1) Penicillin G (1)	Resolved (5)
Hsueh et al24	Taiwan	C. coli (1)	Not reported	Fever, abdominal fullness	Hepatocellular carcinoma, liver cirrhosis, malfunctioning of peritoneal-caval shunt	Cefmetazole, surgical shunt manipulation Ciprofloxacin, netilmicin	Resolved
Tasaka et al25	Japan	C. coli (1) C. jejuni (8)	2000–2015	Fever, GI symptoms	Liver cirrhosis, malignancy (3) None (6)	None (1) Cefotaxime (2) Ceftriaxone (1) Imipenem/cilastatin (1) Ceftriaxone, levofloxacin (1)Cefmetazole (1) Ampicillin, Fosfomycin (2)	Resolved (7) Lost to follow-up (1) Death due to underlying disease (1)
Tasaka et al25–Summary of previously reported Campylobacter cases	Japan	C. coli (4) C. jejuni (10)	2000–2015	Vomiting, diarrhoea, abdominal pain	None (6) XLA (3) Malignancy (4) Liver cirrhosis (2) Chronic hepatitis (1)	Ampicillin, gentamicin (1) Ceftriaxone (1) Cefoperazone/sulbactam (1) Ceftazidime (1) Meropenem, ciprofloxacin (2) Ceftriaxone, levofloxacin (1) Meropenem (1) Azithromycin (1) Tosufloxacin (1) Amoxicillin/clavulanate (1) None (3)	Unknown (1) Resolved (8) Lost to follow-up (2) Relapse (3)
Vandewal12–Letter to the editor	Belgium	C. coli (1)	Not reported	Abdominal pain, diarrhoea	Pyelonephritis 3 months previously	Amikacin, ceftriaxone	Resolved
Brunel et al28	France	C. coli (1)	Not reported	‡	Chronic lymphoid leukaemia, Richter’s syndrome	Antimicrobial‡	Resolved
Arai et al23	Japan	C. coli	Not reported	Fever, pain/swelling of left ankle	XLA	1. Clarithromycin, prednisolone for arthralgia 2. Ceftazidime>minocycline 3. Cefepime 4. Cefepime 5. Cefepime, meropenem >minocycline	Multiple relapses, then resolved
Tokuda et al2	Japan	C. coli	1994−2000	Fever, cellulitis	XLA	1. Cefoperazone/sulbactam 2. Imipenem/cilastatin, amikacin 3. Panipenem/betamipron 4. Panipenem/betamipron, kanamycin	Multiple relapses, then resolved
Pulik et al27	France	C. coli (8) C. jejuni (10) Campylobacter spp (2)	1992–1995	Fever, diarrhoea	HIV/AIDS not on HAART	Antimicrobials	Resolved (9) Relapse (4) Bacteraemia (1)
Hussein et al14	Israel	C. coli (7) C. jejuni (33) C. fetus (5) Campylobacter upsaliensis (1) C. hypointestinal (1) Not Campylobacter (18)	2000–2015	Fever, diarrhoea, abdominal pain, nausea, vomiting, cough, chest pain, weakness, other, asymptomatic	Haematological malignancy (28) Solid tumour (4) Organ transplantation (1) Chronic liver disease (9) Chronic renal disease (7) DM (8) Cardiovascular disease (9) Bone marrow transplantation (13) On immunosuppressive therapy (37) None (10)	Cephalosporins and penicillin with penicillinase inhibitor OR Beta lactam and aminoglycoside/macrolide OR No antimicrobials	Relapse (3) Death (3)
Akiba et al19	Japan	C. coli (1)	2001	Fever, anorexia	None	1. Ceftriaxone, switched to 2. Cefcapene pivoxil	Resolved
Wang et al4	Taiwan	C. coli (24) C. jejuni (80)	2000–2006	Diarrhoea, abdominal pain, fever, vomiting	Haematological malignancy, solid organ transplantation, liver cirrhosis (15) None	Antimicrobials (not specified)	Not reported
Ben-Shimol et al8	Israel	C. coli (53.3%) C. jejuni (46.7%) C. laridis	1989–2010	Fever, diarrhoea, vomiting	None CVID, XLA, Leukaemia/lymphoma, Splenectomised (beta thalassaemia), prematurity of 28 weeks, or other chronic diseases (renal failure, biliary atresia with liver cirrhosis)	Not reported	No deaths
Lemaire et al1	France	C. coli (1)	2006	Lumbar pain	Myocardial injury, DLD, tobacco abuse	Bacteraemia/spondylodiscitis: 1. Cefotaxime plus gentamicin 2. Cefotaxime plus ciprofloxacin 3. Ciprofloxacin Ruptured AAA: endovascular prosthesis; drainage of periaortical haematoma	Resolution

*A cumulative list of all signs/symptoms experienced by individual patients included in the article.

†All comorbidities listed were not seen in every patient. This is a cumulative list of comorbidities that patients with C. coli bacteraemia presented with.

‡Further information unavailable as article was written in foreign language and could not be translated to English.

AAA, Abdominal Aortic Anuerysm; CAD, Coronary Artery Disease; CVID, Common Variable Immune Deficiency; DM, Diabetes Mellitus; GBS, Guillain-Barre Syndrome; GI, Gastrointestinal; HAART, Highly active antiretroviral therapy; HF, Heart Failure; IVDU, Intravenous Drug use; SLE, Systemic Lupus Erythematosis; UC, Ulcerative Colitis; XLA, X-linked agammaglobulinaemia.

With these exclusions in place, a total of 24 articles reported ~118 cases of C. coli bacteraemia beginning in the late 1970s (in comparison, the same articles mention ~417 cases of C. jejuni infections). Though C. jejuni infections are more prevalent, C. coli infections tend to be more severe.⁴ Before discussing the general trends found, we must first understand the pathophysiology of developing C. coli bacteraemia. Campylobacter species are generally known for causing enteritis. Contracted by ingestion of contaminated meat, patients present with fever, diarrhoea, nausea or vomiting.⁵ The rarity of C. coli infections makes it difficult to understand how the bacteraemia may develop. However, we may infer that C. coli bacteraemia infections are developed similarly to that of C. jejuni bacteraemia or any other Campylobacter species.¹

In efforts to understand the pathophysiology of this infection, Blaser proposes that with the ingestion of contaminated meats, intestinal colonisation eventually leads to enteric mucosal changes^{5 6} that allow bacteria to enter the portal circulation. Liu echoes this theory with a case of a patient with a history of stage 4 gliosarcoma on periodic bevacizumab therapy (known to cause hypoxaemia and necrosis of the GI (Gastrointestinal) epithelium), who developed Campylobacter bacteraemia after initially presenting with fever and diarrhoea.⁷ Blaser hypothesises that once the bacteria gain access to the portal circulation, specifically in immunocompromised individuals, the hepatic immune response fails to inhibit the haematogenous spread of the infection, whereas immunocompetent individuals are better equipped to prevent the spread.⁵ Once the bacteria overcome the hepatic defence, systemic bacteraemia occurs. Ben-Shimol et al considers the impact of pathogen virulence on the individual, and the health status of that individual—immunocompromised versus immunocompetent.⁸

Of those that developed Campylobacter bacteraemia, being immunocompromised or having certain comorbidities has appeared to increase the risk of contracting this infection.^{9 10} Ben-Shimol et al noted that either young immunocompetent or older immunocompromised children developed the infection.⁸ In one study that looked at Campylobacter bacteraemia cases in Taiwan from 1998 to 2008, it was concluded that of the three species that were isolated—C. coli, C. jejuni and Campylobacter fetus—individuals with C.coli bacteraemia were more likely to have comorbidities.¹¹ Vandewal and Skirrow et al noted that in patients without comorbidities, C. coli bacteraemia was usually a transient complication.^{12 13}

Of the 24 articles reviewed, only 10 articles mentioned patients with zero comorbidities that developed Campylobacter bacteraemia. Comorbidities mainly involved conditions that may suppress/weaken the immune response.¹⁴ For example, X-linked agammaglobulinaemia (XLA), malignancy undergoing chemotherapy, chronic liver disease and recent solid-organ transplantation on immunosuppressive therapy were few such comorbidities. Contact with animals is also considered a risk factor.¹⁵ A complete list can be found in table 2. Hagiya et al went as far as to say that XLA is a definite risk factor for developing systemic campylobacteriosis.¹⁶ Humoral and cellular immunodeficiency may contribute to the incidence of campylobacter bacteraemia as well.¹⁷

So why is it that C. jejuni bacteraemia cases are more prevalent? Skirrow et al hypothesised that perhaps C. jejuni may have strains that are more capable of causing bacteraemia.¹³ It is possible that to isolate C. jejuni or C. coli in the blood, collection of blood cultures must be done early in the disease course to have appropriate diagnosis.¹⁸ In our patient’s case, fortunately, a blood culture was collected early in his hospitalisation, but identifying C. coli as the culprit was not possible until much later in the hospitalisation. C. coli bacteraemia may be underdiagnosed because of infrequent collection of blood cultures¹ as the awareness of the possibility that a bacteraemia can develop in a patient with gastrointestinal symptoms is low.¹⁹ Underdiagnosis may also be a concern due to the delicate environment needed to culture Campylobacter species in vitro²⁰—usually requiring specific solutions for adequate gram stain.²¹

Contrary to popular belief, fever and gastrointestinal symptoms are not the preceding symptoms to a Campylobacter bacteraemia. Cases of meningitis,¹⁵ cellulitis,^{16 22} reactive arthritis²³ and catheter-related blood stream infection²⁴ have been reported. In the case of the patient presented, presentation symptoms included diarrhoea and scrotal swelling. Stool studies were positive for Campylobacter species; therefore, it can be assumed that the diarrhoea (possible from melanotic stools) was secondary to the Campylobacter infection. However, as the scrotal cellulitis could not be further microbiologically analysed, the aetiology cannot be definitive.

Regarding treatment, the general caution of preventing resistant strains is advised. Campylobacter species exhibit a high level of resistance to quinolones, and for this reason, these drugs should be avoided as empiric therapy.¹⁰ Repeated use of antibiotics can result in carbapenem-resistant Campylobacter strains as well.¹⁶ However, immunocompromised individuals may require combined antimicrobial therapy² for eradication of the infection. Those with humoral immunodeficiencies should be treated with parenteral antibiotics.²⁵ If the bacteraemia is refractory to therapy due to intestinal carriage, oral aminoglycoside therapy plus intravenous antibiotics may be necessary.²²

As a counterpoint, Feodoroff et al state that outcomes of the 76 Campylobacter bacteraemia cases he studied were unaffected by appropriate vs inappropriate treatment or empiric versus delayed treatment.²⁶ However, as risk of sepsis increases with bacteraemia, early detection and treatment is vital for survival. Close monitoring after treatment is also important especially with relapsing patients.^{23 25} Prevention of the infection has been noted with rifabutin therapy given for MAC prophylaxis in AIDs patients,²⁷ HAART therapy in HIV/AIDs patients¹⁷ and Ig-replacement therapy in XLA patients.¹⁶

In conclusion, no matter the presenting symptom (diarrhoea vs back pain vs rash) or the health status of an individual (immunocompetent vs immunocompromised), we must be aware of the possibility of a Campylobacter species bacteraemia and consider this organism when choosing empiric antibiotics. Additionally, once confirmed of a Campylobacter bacteraemia, we must be mindful of resistance and choose treatment wisely. To spread awareness and learn the various ways the bacteria can cause infection, it is imperative that more cases of Campylobacter coli are shared with the world.

Learning points.

• An infectious aetiology differential must include Campylobacter infection whether the patient is a child, adult, immunocompromised or immunocompetent.

• Be mindful of resistance when treating Campylobacter infections and consult Infectious Disease specialists to ensure appropriate treatment.

• Close follow-up is key to prevent or have early detection of relapsing infection.