Helicobacter ciVia^i-associated Bacteremia and Cellulitis
in Immunocompromised Patients
Julia A. Kiehlbauch, PhD; Robert V. Tauxe, MD; Carolyn N. Baker, BS; and I. Kaye Wachsmuth, PhD
• Objective: To define the clinical spectrum of illness
associated with Helicobacter cinaedi infection in the
United States and to determine associated epidemio-
logic risk factors and optimal laboratory methods for
recovery of H. cinaedi.
• Design: A retrospective epidemiologic study of 23
patients with H. c/naed/'-associated illness.
• Patients: 23 patients with H. cinaedi infection
identified between January 1982 and August 1990.
Most isolates (22 of 23) were from blood; one was from
stool.
• Results: Ages ranged from 24 to 84 years (mean, 44
years). Eighty-three percent of patients were men; 17%
were women. Clinical and laboratory data were ob-
tained from 21 patients. Eighteen patients were febrile
(15 required hospitalization); cellulitis was reported in 9
patients. Sixty percent were immunocompromised;
45% were reported to be seropositive for human im-
munodeficiency virus (HIV). For bacteremic patients,
positive blood cultures were detected by a slightly
elevated growth index in an automated blood culture
system; many hospital laboratories had difficulty isolat-
ing the organism.
• Conclusions: Helicobacter cinaedi appears • to
cause recurrent cellulitis with fever and bacteremia in
immunocompromised hosts. Blood cultures from im-
munocompromised patients with these symptoms may
need special handling to isolate H. cinaedi.
Ann Intern Med. 1994;121:90-93.
From the Centers for Disease Control and Prevention, Atlanta,
Georgia. For current author addresses, see end of text.
Although initially associated with gastroenteritis in ho-
mosexual men (1-4), Helicobacter cinaedi was also iso-
lated from asymptomatic (1, 3, 4) and bacteremic (5-7)
homosexual men. These organisms are also associated
with illness outside the homosexual population; Van-
damme and colleagues (8) described three bacteremic
patients and two children with fecal isolates.
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. ci-
naedi isolates received at the Centers for Disease Control
and Prevention (CDC) between January 1982 and August
1990.
90 15 July 1994 • Annals of Internal Medicine • Volume 121 • Number 2
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Case Report
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 cepha-
lexin, 500 mg four times a day, for sinusitis; he noted that
the rash worsened. Three weeks before he was hospital-
ized, 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 admis-
sion. The patient stated that the rash first appeared ap-
proximately 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 un-
treated surface water. He traveled within the United
States and Europe and reported having homosexual con-
tact in the month before onset of illness.
After positive blood cultures were identified, the pa-
tient 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
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 1 shows the clinical features of 21 Table 1. Antimicrobial Susceptibility of 22 Strains of
patients (information on 5 patients was provided after a Helicobacter cinaedi Associated with Human Clinical Ill-
review of medical records by the local health depart- ness*
ment). Most patients had a sudden onset of fever (range,
37.8 to 40.0 °C; mean, 38.9 °C). Nine bacteremic patients Antimicrobial Minimum Inhibitory Concentration
Agent Range MIC50 MIC^ Mode
(41%) had both fever and a distinctive cellulitis that was
described as atypical, appearing red-brown or copper - jLtg/mL -
without noticeable warmth. Underlying immunosuppres-
sive illness was reported for 14 of 21 patients; other Ampicillin 2.0 to 16.0 16.0 16.0 16.0
Cefazolin <1.0tol6.0 4.0 16.0 4.0
underlying conditions, previously associated with systemic Ceftriaxone <0.12 to >8.0 8.0 8.0 8.0
Campylobacter infections, were reported infrequently. Cephalothin 16.0 to > 128.0 64.0 128.0 64.0
Information regarding potential exposures in the 4 Chloramphenicol 0.12 to 4.0 1.0 2.0 1.0
weeks before onset was available for 15 patients. The Ciprofloxacin 0.12 to >8.0 0.25 1.0 0.25
most frequent exposures of interest were contact with or Clindamycin <0.06 to > 128.0 8.0 16.0 8.0
Doxycycline <0.06 to 1.0 0.25 1.0 0.25
consumption of untreated surface water (three patients) Erythromycin <0.06 to > 128.0 128.0 >128.0 >128.0
and contact with animals (nine patients). Four patients Gentamicin 0.12 to 4.0 0.25 0.5 0.25
reported out-of-state travel in the 4 weeks before onset: Kanamycin <1.0tol6.0 <1.0 <1.0 <1.0
one to Mexico, one to Europe, one to Hawaii, and one to Sulfamethoxazole- 0.5/9.5 to 4/76 2/38 2/38 2/38
trimethoprim
Colorado on a camping trip. Tetracycline <0.06 to 4.0 1.0 4.0 1.0
All blood isolates of H. cinaedi were recovered after Trimethoprim >128.0 > 128.0 >128.0 >128.0
detection by an automated blood culture instrument; 21
of 22 isolates were recovered from the aerobic bottle; 1 * Results were not available for one blood isolate.
isolate was also detected in the anaerobic bottle, and 1
isolate was detected solely in the anaerobic bottle. Most effective than short-term therapies (<10 days; data not
isolates were detected after 5 or more days of incubation shown). The apparent effectiveness of tetracycline or ami-
by slightly elevated growth indexes (generally between 40 noglycosides agrees with in vitro antimicrobial susceptibil-
and 80; mean, 57). In general, organisms were not seen ity data. Although two reports suggest treating H. cinaedi
on initial Gram staining of the blood culture material but with ciprofloxacin (10, 11), infection reappeared in two
were detected by dark-field or acridine orange staining. patients treated with this agent, and our in vitro data
Only 9 (41%) of 22 blood isolates were recovered by the indicate that their isolates and two additional isolates
primary hospital laboratory; all other isolates were cul- were resistant (minimal inhibitory concentration > 8 /utg/
tured by reference laboratories. mL). This finding suggests that ciprofloxacin should be
In contrast to Campylobacter jejuni, H. cinaedi is not sus- used with caution. However, we were unable to obtain
ceptible to erythromycin in vitro (Table 1). In general, tet- isolates before and after treatment, so we cannot deter-
racyclines and aminoglycosides seem most effective in vitro. mine whether resistance to ciprofloxacin developed as a
result of therapy or existed before therapy was begun.
Discussion Our susceptibility data agree with previously published
data (12), with one exception: Fifty percent of our strains
Our findings indicate that H. cinaedi is associated with were resistant to cephalothin.
a new syndrome, consisting of fever, bacteremia, and re- Laboratory diagnosis of H cinaedi infection is unlikely
current cellulitis. Most patients had signs of systemic in- using blood culture procedures that rely on visual detec-
fection, including leukocytosis, and were often thrombo- tion because it grows slowly and the growth is difficult to
cytopenic. Although H cinaedi isolates were recovered see; all blood isolates were recovered using an automated
primarily from immunocompromised patients and from system. We therefore suggest examining blood cultures
those with chronic alcoholism, we also documented infec- that develop slightly elevated growth indexes in an auto-
tions in three nonimmunocompromised men and in mated system using acridine orange staining, Giemsa
women (both with and without HIV infection). Thus, the staining, or dark-field examination before discarding a
patient group affected by H. cinaedi is larger than origi- specimen as negative. In general, specialized culture tech-
nally thought. niques and prolonged incubation (7 days) must be used to
We did not find distinctive risk factors for acquisition isolate these organisms: Growth is enhanced by the pres-
of H cinaedi by interviewing a subset of patients; how- ence of hydrogen gas in a microaerobic atmosphere and
ever, our review may have been hampered by the time incubation on rich, nonselective media (blood or choco-
between illness and interview. Our data suggest that con- late agar) at 37 °C. Techniques that would probably iso-
tact with animals or exposure to untreated surface water late H. cinaedi from stool specimens include filtration
are possible sources of infection. Currently, H. cinaedi has onto nonselective media or inoculation of appropriate
been isolated only from humans and gerbils (9), but no selective media and incubation at 37 °C in a hydrogen-
patients reported having contact with gerbils. containing atmosphere for 3 to 4 days.
Many antimicrobial therapies were used to treat pa- A retrospective review of patients with H. cinaedi in-
tients with H. cinaedi infection. From our series, it ap- fection suggests a syndrome of recurrent febrile bactere-
pears that treatment with a penicillin, tetracycline, or mia, which may be accompanied by cellulitis in immuno-
aminoglycoside may be more effective than treatment with compromised patients. Helicobacter cinaedi infection
cephalosporins, erythromycin, or ciprofloxacin. In addi- should be considered in an immunocompromised or
tion, prolonged therapies (2 to 6 weeks) may be more thrombocytopenic patient with fever and cellulitis. Spe-

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 Appendix Table 1. Characteristics of Patients with Helicobacter cinaedi Infection
Patient Maximum Cellulitis Other Signs of Gastrointestinal Underlying
Number Temperature (Location) Systemic Infection* Symptomsf Illness^:

1 38.0 Left lower leg None None HIV infection

2 38.4 Left lower leg/penis None None HIV infection
3 37.7 Lower legs Headache Nausea Alcoholism and HIV
infection
4 39.4 Right lower leg None Nausea HIV infection

5 39.3 Shoulder None None Alcoholism

6 39.4 Prostate Joint pain in knees Diarrhea, bloody stools, None
and elbows abdominal pain, nau-
sea, vomiting
7 38.3 None None Chronic lymphocytic
leukemia, lung cancer
8 40.0 13.6-kg weight loss Diarrhea, abdominal HIV infection
pain
9 39.4 Abdominal pain Delivered child
10 39.4 None Congestive heart None None
failure (atrial
flutter)
11 39.4 None Night sweats, 11-kg None HIV infection
weight loss
12 Not febrile Right leg None None Colon cancer, conges-
tive heart failure,
alcoholism, peptic
ulcer disease
13 38.8 Both legs Splenomegaly None Chronic obstructive
pulmonary disease,
alcoholism, liver cir-
rhosis
14 38.9 Both ankles Headache Diarrhea, abdominal HIV infection
pain, nausea, vomiting
15 39.8 None Diarrhea, nausea HIV infection, central
nervous system lym-
phoma, steroid ther-
apy
16 Not febrile Both feet and legs Accumulation of None Diabetes
pericardial fluid
17 39.7 Chest pain Diarrhea Alcoholism
18 38.9 None Diarrhea, nausea, vomit- HIV infection, non-
ing Hodgkin lymphoma,
steroid therapy
19 Febrile, tempera- Endocarditis Respiratory symp- Diarrhea HIV infection
ture unknown toms
20 Not febrile Right forearm None None HIV infection
21 Not febrile Chest pain, arryth- None None
mia
22U Not febrile Diarrhea, abdominal Mononucleosis, Shigella
None
pain

* Includes headache, chills, and malaise.

t Includes diarrhea, bloody stools, abdominal pain, nausea, and vomiting.
$ Human immunodeficiency virus (HIV) infection noted if reported; not specifically solicited.
§ Leukocyte count, left shift (or normal) is indicated if noted in differential.
|| Questions asked included consumption of both cooked and raw or undercooked dairy products, seafood, or poultry, consumption or contact with
untreated surface water, travel history, contact with children in day care, and contact with ill and well pets.
11 Organism isolated from stool, not blood.

cific antimicrobial therapy may be needed to prevent re-
currence. The slow growth and fastidious culture require-
ments of this organism indicate that it may be currently
under-recognized.
Acknowledgments: The authors thank Gretchen Anderson, MPH, for sup-
plying information about patients included in this study and Fred Tenover,
PhD, for his advice.
Grant Support: This work was done while Dr. Kiehlbauch held a National
Research Council-Centers for Disease Control Research Associateship.
Requests for Reprints: Julia A. Kiehlbauch, PhD, Centers for Disease
Control and Prevention, Foodborne and Diarrheal Diseases Branch, Mail-
stop C 0 3 , Atlanta, GA 30333.
Current Author Addresses: Dr. Kiehlbauch: Medical College of Wisconsin,
Department of Pathology, 8700 West Wisconsin Avenue #152, Milwaukee,
WI 53226.
Drs. Tauxe and Wachsmuth, and Ms. Baker: Centers for Disease Control
and Prevention, 1600 Clifton Road, Atlanta, GA 30333.
References
1. Quinn TC, Goodell SE, Fennell C, Wang SP, Schuffler MD, Holmes
KK, et al. Infections with Campylobacter jejuni and Campylobacter-tike
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 Appendix Table 1. Continued

Duration of Antimicrobial Outcome Leukocyte Platelet Significant Epidemiologic

Hospitalization Therapy Count§ Count Exposure||

X109/L

4d Tetracycline Unknown 12.8, left shift 66 Unknown

21 d Erythromycin, rifampin Improved 12.5, left shift 184 Unknown
None Doxycycline, erythromycin Improved 3.1, left shift 35 Lake or river water, travel
to Mexico
None Cephalexin, ciprofloxacin Recurrences (X5) 7.8, left shift 35 Lake or river water, travel
within U.S. and Europe
None None Improved 7.3, left shift 65 None
21 d Trimethoprim-sulfameth- Improved 26.3, left shift 294 Raw eggs
oxazole, tobramycin

None Amoxicillin Improved 19.2, normal 130 Travel to Maui

10 d Erythromycin, tetracycline Improved Cats

4d Mefoxin Improved 9.2, left shift Well water, farm animals

6 wk Ampicillin Improved 11.7, left shift Dogs

6d Trimethoprim-sulfameth- Possible recurrence 6.3, left shift 323 Unknown

oxazole
5d Cefazolin Recurrence (XI) 12.8, left shift Unknown

7d Penicillin G Improved 13.6, left shift 89 None

2wk Oxacillin, dicloxacillin Recurrences (X3) 4.5 Dogs, cats, cows

3d Ceftazadime, tobramycin, Improved 4.1, left shift 124 Questionable water supply
ciprofloxacin

1 mo Tetracycline, vancomycin Recurrences (X4) Well water

Unknown Cefotaxime, ciprofloxacin Improved 9.0, left shift 180 Unknown

13 d Chloramphenicol, vanco- Improved 1.7, normal 97 Unknown
mycin, tobramycin

41 d Cefotaxime, chlorampheni- Recurrences (x2) 4.5, left shift 227 Unknown

col, gentamicin
Not hospitalized None Unknown 5.7, normal 36.9 Unknown
Not hospitalized Trimethoprim-sulfameth- Improved 9.7, left shift Lake water, cats, birds,
oxazole dogs
Not hospitalized Metronidazole Improved 13.6, abnormal Nonhuman primates

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