Helicobacter cinaedi cellulitis and bacteremia in immunocompetent hosts after orthopedic surgery

Abstract

At various times after orthopedic operations (more than a few weeks, with an average of 29.9 days), 11 patients had a sudden onset of high temperature (average 38.9 degrees C) and local cellulitis at different sites on the operated sides. The wounds had completely healed, without complicated infections, when the cellulitis occurred. The clinical picture of cellulitis in all patients was atypical: diffuse salmon-pink skin color, local heat, swelling, spontaneous pain, and tenderness but no eruptions. No patient had any underlying immunocompromising conditions or had been given immunosuppressive agents. Gram-negative spiral bacteria were isolated from blood cultures and were identified as Helicobacter cinaedi on the basis of 16S rRNA gene sequencing and DNA-DNA hybridization using standard strains. By means of phylogenetic analysis, we divided these clinical isolates into two clones. The H. cinaedi strain isolated via fecal cultures from two patients without intestinal symptoms was the same clone as the blood isolate. All isolates were quite susceptible to various antibiotics, and clinical and inflammatory symptoms of bacteremia and cellulitis improved after treatment with penicillins and cephalosporins. A relatively high incidence of recurrence of the same disease was observed, however. Almost all patients responded immunologically to the infection, as evidenced by the production of serum antibody against H. cinaedi. We thus suggest that H. cinaedi should not be regarded as simply an opportunistic pathogen but that it may be a pathogen in immunocompetent hosts and may cause infections together with bacteremia and cellulitis.

FIG. 1.

A typical case of postoperative cellulitis caused by H. cinaedi (case 6). (A) A 58-year-old man with a left calcaneous fracture resulting from a traffic accident underwent orthopedic surgery in September 2004. Cellulitis occurred in the left lower leg. Note the salmon-pink color and swelling (arrows). (B) Magnetic resonance images of the left lower leg. Coronal and axial T2-weighted images showed a diffuse, widespread, high-intensity area, indicating inflammatory lesions in the subcutaneous tissues (arrows).

FIG. 2.

Genetic analysis of clinical isolates of H. cinaedi. 16S rRNA (A) and hsp60 (B) genes were analyzed by means of the FASTA search system. Phylogenetic relationships for these clinical isolates and representative members of the genus Helicobacter were analyzed on the basis of the 16S rRNA gene sequence (1,430-bp area) and hsp60 gene sequence (530-bp area) obtained from the DDBJ, GenBank, and EMBL databases. The accession numbers for the 16S rRNA and hsp60 gene sequences of each strain are shown in parentheses.

FIG. 3.

PFGE DNA fingerprints for H. cinaedi isolates digested with SpeI. PFGE patterns for the clinical strains differed from those for the type strains of H. cinaedi CCUG 18818^T (S1) and H. canis NCTC 12379^T (S2). Strains of clinical isolates were obtained from blood samples, except for sample 9′, which was isolated from a fecal sample. Case numbers are identical to those in Table 1.

FIG. 4.

RAPD analysis of the genome of H. cinaedi clinical isolates. Primers used in this analysis are indicated in the figure. See the text for details. Case numbers are identical to those in Table 1. S1, H. cinaedi CCUG 18818^T; S2, H. canis NCTC 12379^T.

FIG. 5.

Determination of antibody response to H. cinaedi infection by ELISA. Serum antibody levels against the H. cinaedi antigen of the H. cinaedi-infected patients were compared with those of control groups: H. pylori-infected subjects, age- and sex-matched controls without apparent H. cinaedi infection, and infants younger than 1 year of age. *, P < 0.05; **, P < 0.01.