Bacteremia was rarely found in Campylobacteriosis, with C. jejuni and C. coli found to be the most common causes among the cases[5]. A previous study showed that up to 93% of the bacteremia cases are related to the recognized risk factors of immune function decline or immunosuppression, such as chronic liver disease, human immunodeficiency virus infection, malignant tumor and humoral immunodeficiency[6]. Though Campylobacter bacteremia might resolve without antibiotic treatment in a normal host[4], appropriate selection of empirical antibiotics from clinicians and definite confirmation from laboratories were of great importance to the outcome and prognosis of immunocompromised patients. In addition, the studies of bacteremia combined with spontaneous bacterial peritonitis (SBP) caused by Campylobacter were more rarely found in the database. Peritonitis generally occured in patients with ascites, and patients with liver disease were more likely to form ascites, which provided space and conditions for bacterial growth and reproduction. This report presented the case of C. jejuni bacteremia and SBP in a patient with liver cirrhosis. She suffered from fever and ascites, but recovered with the administration of empirical antibiotics and supportive care. It was worth noting that the leukocyte count of the patient were lower than the normal value on admission, so if other symptoms such as fever were not obvious, it was easy to ignore the bacterial infection in diagnosis. Besides, the common diarrhea symptoms caused by C. jejuni were not found in this patient, which meant that clinicians should be alert to non-diarrhea symptoms of C. jejuni infection to avoid delaying treatment.
Rare relevant publications about liver cirrhosis with Campylobacter infection since 2010 were selected using PUBMED, excluding non English article, as shown in Table 2. Among them, 4 cases were Campylobacter infection patients combined with bacteremia and SBP, and the patients all got a good recovery fortunately. A study hypothesised the hepatic immune response fails to inhibit the haematogenous spread of the infection when the bacteria gain access to the portal circulation in immunocompromised patients[7], which would also lead to the formation of ascites. Besides, it was worth noting that diarrhea didn’t always appear as a common first symptom in these cases, which was different from the common Campylobacter infection. The special culture environment led to the difficulty in the growth of Campylobacter, hence, the accuracy of the choice for agar should be emphasized. Brain heart infusion agar plates incubated at 25°C and 42°C[8], Schaedler and Columbia agar used in this report were able to culture the Campylobacter, and 5% sheep blood agar and chocolate agar were used to subculture the bacteria for further analysis[9]. However, chocolate agar failed to culture the C. jejuni in this report, which might due to the culture conditions and operation technology. Other molecular methods, including MALDI-TOF MS and the 16S rRNA gen analysis, were also useful for rapid identification of strains[8]. Due to the lack of bacteria for further molecular analysis, only MALDI-TOF MS was used in this study to provide faster and more sensitive identifying process in strain typing, epidemiological studies, antibiotic resistance, etc[10]. Besides, biomedical tests were also performed for auxiliary identification in this report, but were uncommon in other reports because these tests were more commonly used in testing known results rather than identifying specific bacterial species from unknown positive results. In the process of culturing C. jejuni in the laboratory, positive alarm was generally given in 24–48 hours after acterial culture and transformation. At this time, clinicians could take the lead in empirical medication. C. jejuni would show different growth rates according to the temperature difference of the culture environment in 24–72 hours after the blood culture alarm. The culture temperature after bacterial transformation was 42–43 ℃ or 37 ℃, which was suitable for the growth of C. jejuni. Although inappropriate or delayed appropriate antimicrobial treatment does not seem to be associated with the recovery of patient[11], timely blood or body fluid culture would benefit the prognosis of patients and reduce the incidence of sequelae.
Table 2
Reported Campylobacter infection cases in liver cirrhosis patients since 2010.
Reference
|
Country
|
Clinical Manifestation
|
Comorbidities
|
Diagnosis
|
Leukocyte
(×109/L)
|
Antibiotics Used
|
Antibiotic Susceptibility Test
|
Outcome
|
Sensitive
|
Resistant
|
[4]
|
Korea
|
[Drowsiness]
[Fever]
|
[Cryptogenic liver cirrhosis]
|
[Bacteremia]
|
5.7
|
[Cefotaxime]
[Azithromycin]
|
[Erythromycin]
|
[Ciprofloxacin]
[Tetracycline]
|
Recover
|
[12]
|
USA
|
[Positive abdominal fluid shift]
[Erythematous]
[Edematous]
|
[Hepatitis C cirrhosis]
|
[Bacteremia]
[SBP]
|
2.3
|
[Vancomycin]
[Doxycycline]
[Imipenem]
[Cilastatin]
[Ciprofloxacin]
[Piperacillin/tazobactam]
|
NM
|
Recover
|
[13]
|
USA
|
[Ascites fluid]
[Fever]
|
[Polycythemia vera with splenomegaly]
[Alcoholic liver cirrhosis]
|
[Bacteremia]
[SBP]
|
4.67
|
[Ceftriaxone]
[Meropenem]
|
[Erythromycin]
[Ciprofloxacin]
|
NM
|
Recover
|
[14]
|
Thaiwan
|
[Fever]
[Abdominal pain]
[Abdominal swelling]
|
[Alcoholic liver cirrhosis]
[Type 2 diabetes]
|
[Bacteremia]
[SBP]
|
8.5
|
[Ciprofloxacin]
|
NM
|
Recover
|
[9]
|
Japan
|
[Fatigue]
[Abdominal pain]
[Slight diarrhoea]
|
[Alcoholic liver
cirrhosis]
[Oesophageal varices]
|
[Bacteremia]
[SBP]
|
13.1
|
[Cefotaxime]
[Ampicillin]
|
[Ampicillin]
[Ceftriaxone]
[Erythromycin]
[Ciprofloxacin]
[Gentamicin]
[Imipenem]
|
[Minocycline]
|
Recover
|
It was found that cephalosporins were mainly used in patients with Campylobacter infection in liver cirrhosis, while macrolides and quinolones were mainly used in patients with other diseases such as cancer and HIV infection. In fact, the guidelines suggested the third-generation cephalosporin (such as cefotaxime) for empiric treatment of SBP[6]. Hence, cephalosporins were often used as empirical drugs in the treatment of peritonitis in the absence of blood culture results, and the cirrhotica patients with peritonitis and bacteremia caused by Campylobacter treated with this kind of drugs had achieved good outcomes. However, the therapeutic effect of cephalosporins in other cases remained to be studied, and carbapenems (such as imipenem) are generally considered to be a good choice for radical cure of Campylobacter infection[9]. Besides, fluoroquinolones and macrolides are considered as first-line agents for the treatment of Campylobacter infections. Nevertheless, high resistance to the above antibacterials were also found in many cases, and might vary in different regions[15]. In addition, clinicians should also take note of the situation that the patients who repeatedly infected with Campylobacter were sensitive to one drug at the beginning, but later developed resistance. Hence, the observation to the dynamic changes of antibiotic sensitivity and appropriate combination therapy were of great importance for the improvement of treatment efficiency.
Due to the particularity of the leukocyte level in this report, the reports of Campylobacter bacteremia since 2011 have also been searched for comparison. Reports that did not give leukocyte data were excluded, and the leukocyte counts of the remaining reports were summarized, as shown in Fig. 4. Four cases had leukopenia among the enrolled reports, but only one of four patients had cirrhosis with bacteremia and peritonitis, like the present case. Patients with leukocyte count less than 1.0×109/L had serious primary diseases, including acute lymphoblastic leukemia (ALL), chronic non indolent Hodgkin's lymphoma and immunosuppressive therapy due to kidney transplantation, while leucopenia was rarely found in patients with cirrhosis. It is not surprising that leukopenia occurs in patients with acute lymphoblastic leukemia and Hodgkin's lymphoma due to decreased hematopoietic system function and bone marrow suppression. However, leukopenia was rarely found in patients with cirrhosis. Surprisingly, the leukocyte level in this report showed similar trend with the case of hepatitis C cirrhosis with C. jejuni infection. Declination of immune function might be the leading reason to this phenomenon even in bacterial infection. However, other patients with cirrhosis showed the opposite trend of leukocyte level, which illustrated that leukopenia was not a common feature of bacterial infection in patients with impaired immune function. Even so, the above-mentioned reports warned that the bacterial infection concealed by leukopenia should be considered as a special character in the clinical treatment of immunocompromised patients, so as to avoid the adverse consequences caused by the aggravation of infection.
In conclusion, this is the first report of C. jejuni bacteremia and SBP characterized by leucopenia in a patient with hepatitis B cirrhosis in Asia. Careful consideration of bacterial infection and corresponding laboratory examination are needed when the patients with leukopenia and immunosuppression have fever and other suspected infection symptoms. The use of antibiotics should be carefully considered for patients with peritonitis and bacteremia, and the combination of drugs can be used when necessary.