A retrospective epidemiologic study was done to define the clinical spectrum of illness and epidemiologic risk factors associated with H. cinaedi infection in the United States. We also looked at laboratory methods used to recover H. cinaedi. Patients were identified from H. cinaedi isolates received at the Centers for Disease Control and Prevention (CDC) between January 1982 and August 1990.

Case Report

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A 32-year-old man developed red-copper-colored blotches on his left ankle 6 weeks before admission; these spread to his right ankle, up the legs, to the arms, chest, and face. At the time of onset, the patient reported fever but no gastrointestinal symptoms. He was given cephalexin, 500 mg four times a day, for sinusitis; he noted that the rash worsened. Three weeks before he was hospitalized, the patient received oral ciprofloxacin for 2 weeks; the rash resolved. The rash reappeared, and the patient presented with chills and fever (a temperature of 39.4 °C), nausea, arthralgias, and the maculopapular skin eruption. At admission, blood cultures were done, and he was treated empirically with cefotaxime and tobramycin. His leukocyte count at admission was 7.8 x 10⁹/L, with a differential of 73 segmented neutrophils, 18 lymphocytes, and 8 monocytes. Platelets were noted as adequate.

His medical history included seropositivity to human immunodeficiency virus (HIV) and transient immune thrombocytopenia (platelet count, 35 x 10⁹/L); a platelet count of 192 x 10⁹/L was noted 4 months before admission. The patient stated that the rash first appeared approximately 24 hours after using a whirlpool spa. He did not recall eating raw dairy products, eggs, seafood, or other meats. The patient reported recreational exposure to sea and lake water but did not recall drinking untreated surface water. He traveled within the United States and Europe and reported having homosexual contact in the month before onset of illness.

After positive blood cultures were identified, the patient was given empiric ciprofloxacin, 250 mg twice a day for 14 days. The cellulitis cleared, and the patient was discharged. The cellulitis recurred 11 weeks later; the patient was rehospitalized and treated with cefotaxime and ciprofloxacin. Two blood cultures obtained at the time of the second admission again yielded H. cinaedi. The patient's leukocyte count was now 6.8 x 10⁹/L. The rash again cleared. The patient reported three additional recurrences. After zidovudine therapy was initiated, no further recurrence of cellulitis was noted.

Results

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Patients with H. cinaedi infection ranged in age from 24 to 84 years (mean, 44 years); 83% were men. Patients resided in 14 different states (1, Arizona; 1, Colorado; 6, California; 1, Georgia; 1, Illinois; 1, Kansas; 1, Michigan; 2, Missouri; 2, Nebraska; 1, New Mexico; 2, Ohio; 1, Tennessee; 3, Texas; and 1, Wisconsin). Isolation of the organism occurred from 1982 to 1990 (2 in 1982, 2 in 1984, 3 in 1985, 2 in 1986, 3 in 1987, 5 in 1988, 2 in 1989, and 4 in 1990) without seasonal clustering. No one died of this infection.

Appendix Table 2 shows the clinical features of 21 patients (information on 5 patients was provided after a review of medical records by the local health department). Most patients had a sudden onset of fever (range, 37.8 to 40.0 °C; mean, 38.9 °C). Nine bacteremic patients (41%) had both fever and a distinctive cellulitis that was described as atypical, appearing red-brown or copper without noticeable warmth. Underlying immunosuppressive illness was reported for 14 of 21 patients; other underlying conditions, previously associated with systemic Campylobacter infections, were reported infrequently.

Information regarding potential exposures in the 4 weeks before onset was available for 15 patients. The most frequent exposures of interest were contact with or consumption of untreated surface water (three patients) and contact with animals (nine patients). Four patients reported out-of-state travel in the 4 weeks before onset: one to Mexico, one to Europe, one to Hawaii, and one to Colorado on a camping trip.

All blood isolates of H. cinaedi were recovered after detection by an automated blood culture instrument; 21 of 22 isolates were recovered from the aerobic bottle; 1 isolate was also detected in the anaerobic bottle, and 1 isolate was detected solely in the anaerobic bottle. Most isolates were detected after 5 or more days of incubation by slightly elevated growth indexes (generally between 40 and 80; mean, 57). In general, organisms were not seen on initial Gram staining of the blood culture material but were detected by dark-field or acridine orange staining. Only 9 (41%) of 22 blood isolates were recovered by the primary hospital laboratory; all other isolates were cultured by reference laboratories.

In contrast to Campylobacter jejuni, H. cinaedi is not susceptible to erythromycin in vitro (Table 1). In general, tetracyclines and aminoglycosides seem most effective in vitro.

Discussion

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Our findings indicate that H. cinaedi is associated with a new syndrome, consisting of fever, bacteremia, and recurrent cellulitis. Most patients had signs of systemic infection, including leukocytosis, and were often thrombocytopenic. Although H. cinaedi isolates were recovered primarily from immunocompromised patients and from those with chronic alcoholism, we also documented infections in three nonimmunocompromised men and in women (both with and without HIV infection). Thus, the patient group affected by H. cinaedi is larger than originally thought.

We did not find distinctive risk factors for acquisition of H. cinaedi by interviewing a subset of patients; however, our review may have been hampered by the time between illness and interview. Our data suggest that contact with animals or exposure to untreated surface water are possible sources of infection. Currently, H. cinaedi has been isolated only from humans and gerbils [9], but no patients reported having contact with gerbils.

Many antimicrobial therapies were used to treat patients with H. cinaedi infection. From our series, it appears that treatment with a penicillin, tetracycline, or aminoglycoside may be more effective than treatment with cephalosporins, erythromycin, or ciprofloxacin. In addition, prolonged therapies (2 to 6 weeks) may be more effective than short-term therapies ( 10 days; data not shown). The apparent effectiveness of tetracycline or aminoglycosides agrees with in vitro antimicrobial susceptibility data. Although two reports suggest treating H. cinaedi with ciprofloxacin [10, 11], infection reappeared in two patients treated with this agent, and our in vitro data indicate that their isolates and two additional isolates were resistant (minimal inhibitory concentration > 8 µg/mL). This finding suggests that ciprofloxacin should be used with caution. However, we were unable to obtain isolates before and after treatment, so we cannot determine whether resistance to ciprofloxacin developed as a result of therapy or existed before therapy was begun. Our susceptibility data agree with previously published data [12], with one exception: Fifty percent of our strains were resistant to cephalothin.

Laboratory diagnosis of H. cinaedi infection is unlikely using blood culture procedures that rely on visual detection because it grows slowly and the growth is difficult to see; all blood isolates were recovered using an automated system. We therefore suggest examining blood cultures that develop slightly elevated growth indexes in an automated system using acridine orange staining, Giemsa staining, or dark-field examination before discarding a specimen as negative. In general, specialized culture techniques and prolonged incubation (7 days) must be used to isolate these organisms: Growth is enhanced by the presence of hydrogen gas in a microaerobic atmosphere and incubation on rich, nonselective media (blood or chocolate agar) at 37 °C. Techniques that would probably isolate H. cinaedi from stool specimens include filtration onto nonselective media or inoculation of appropriate selective media and incubation at 37 °C in a hydrogen-containing atmosphere for 3 to 4 days.

A retrospective review of patients with H. cinaedi infection suggests a syndrome of recurrent febrile bacteremia, which may be accompanied by cellulitis in immunocompromised patients. Helicobacter cinaedi infection should be considered in an immunocompromised or thrombocytopenic patient with fever and cellulitis. Specific antimicrobial therapy may be needed to prevent recurrence. The slow growth and fastidious culture requirements of this organism indicate that it may be currently under-recognized.