Spontaneous bacterial peritonitis due to Helicobacter pylori in a cirrhotic patient with human immunodeficiency virus and hepatitis C virus coinfection

We present the case of a 46-year-old man with a history of parenteral drug use as well as co-infection with hepatitis C virus [HCV] (genotype 1b) and human immunodeficiency virus [HIV] (stage A3) who was admitted due to abdominal pain and ascites. One year earlier, the patient had suffered from an initial episode of ascitic oedematous decompensation with spontaneous bacterial peritonitis, for which he was taking norfloxacin as secondary prophylaxis. At the time of admission, the patient was not on antiretroviral treatment and had a CD4 count of 199 cells/μl, an HIV RNA viral load of 21,000 copies/ml and an HCV RNA viral load of 1,070,000 IU/ml. Liver elastography one month prior to admission had shown 35 kPa and found fibrosis stage 4 and Child–Pugh class B (bilirubin 0.5 mg/dl, INR 1.7, ALT 147 IU/l, creatinine 0.72 mg/dl, haemoglobin 10.5 g/dl, platelets 57,000 and leukocytes 3100/mm³). One year earlier, he had suffered from an initial episode of ascitic oedematous decompensation with spontaneous bacterial peritonitis, for which he was taking norfloxacin as secondary prophylaxis. A paracentesis on admission showed an inflammatory fluid (laboratory values: leukocytes 800, mononuclear cells 93%, glucose 103 mg/dl and proteins 1.1 g/dl). Treatment was started with ceftriaxone and albumin. After 84 h of incubation of the ascitic fluid in blood culture bottles (BacT/ALERT^® FAN, BioMérieux, Marcy l’Étoile, France), curved Gram-negative bacilli with a tendency to cluster were seen to grow. After 4 days of subculture, small; transparent; catalase-, oxidase- and urease-positive colonies grew in pure culture on chocolate agar plates. Analysis using MALDI-TOF^® (bioMérieux) yielded no conclusive profiles for identification of this strain. The microorganism was definitively identified using sequencing of the 16S rRNA gene by PCR. This yielded a concordance of 99.9% with sequences of Helicobacter pylori (H. pylori) (GenBank number 382S94E7014). A day earlier, the patient had requested voluntary discharge. Antimicrobial sensitivity was determined using Etest^® (bioMérieux), according to EUCAST criteria, and showed sensitivity to tetracycline, clarithromycin and amoxicillin and resistance to metronidazole and levofloxacin. A genotypic study showed 2 critical mutations in the gyrA gene (C261 A/C and A272 A/G) as well as the absence of the cagA virulence factor and the s2m2 variant allele of the vacA gene.

When the microbiological results were known, the patient was contacted. As he refused to be readmitted, he was prescribed outpatient treatment with amoxicillin, clarithromycin and omeprazole for 14 days.

One month later, the patient was readmitted with abdominal pain, ascites and ascitic fluid with a predominance of mononuclear cells. Both bacterial culture and detection of the microorganism through PCR of the 16S rRNA gene were negative. The patient was empirically treated with ceftriaxone, and his condition resolved. As the patient had mononuclear chronic peritonitis, magnetic resonance imaging and exploratory laparoscopy were performed. Neither yielded conclusive findings on a peritoneal level. Mycobacterial cultures of ascitic fluids from both stays were negative. During his first stay, he underwent endoscopy to screen for oesophageal varices. This showed portal hypertensive gastropathy and grade I varices. As this test was performed before the microorganism was known to grow in ascitic fluid, no biopsies or other tests intended to detect H. pylori were done.

To date, very few cases have been documented in humans in whom H. pylori was isolated from ordinarily sterile samples,^1–3 including series of spontaneous bacterial peritonitis with negative culture and analysis using PCR and sequencing of the 16S rRNA gene.⁴ While most cases of spontaneous bacterial peritonitis are due to bacterial translocation and haematogenous seeding, we could not explain how the microorganism reached the ascitic fluid in this case as no blood was drawn for culture on admission. However, it is well known that other species of Helicobacter spp. (H. fennelliae and H. cinaedi) cause bacteraemia in cirrhotic and immunosuppressed patients and grow in ordinary liquid media.⁵ In our case, mass spectrometry (MALDI-TOF^®) did not prove a useful tool for identifying H. pylori.⁶ It is interesting to note that study of the vacA and cagA virulence factors (linked to colonisation of the stomach mucosa) of our strain showed a profile that differed significantly from the profile of strains that usually colonise the stomach and duodenum.⁷ We do not know whether these differences, along with others, would be those responsible for a hypothetical invasive profile in this case. In addition, it was interesting to see how using norfloxacin selected a resistant strain in this patient, sample contamination being an implausible explanation for our case. Although there is not much information on the sensitivity of H. pylori to third-generation cephalosporins, the evidence published supports the hypothesis that they would have been effective in this case, given the patient's good clinical course.⁸

This strange case raised a number of questions that we were unable to answer. Should H. pylori be included among the causes of mononuclear chronic peritonitis in cirrhotic patients? Could H. pylori be analogous to Neisseria gonorrhoeae in that it has strains with an “invasive profile” capable of causing remote disease? Can H. pylori cause bacteraemia like other species from the genus Helicobacter spp.?

In summary, we have reported a decidedly unusual case that we were unable to classify as a rare isolated case or an underdiagnosed disease.