Bacteremia due to Helicobacter cinaedi in two patients with human immunodeficiency virus infection

Helicobacter cinaedi (formerly Campylobacter cinaedi) has been associated with enteric disease in homosexual men. The authors report two cases of H cinaedi bacteremia occurring in patients with human immunodeficiency virus (HIV) infection. These cases illustrate that H cinaedi may act as an opportunistic pathogen in patients with HN infection or the acquired immune deficiency syndrome.

C AMPYLOBACTER SPECIES ARE FREQUENTLY ISOLATED from homosexual men and have been recovered from patients with the acquired immune deficiency syndrome (AJDS) (1)(2)(3).Most patients have symptoms of enterocolitis, although occasionally systemic illness with bacteremia has also been reported.The majority of these infections have been due to either Campylobacter jejuni or Campylobacter fetus subspecies fetus.1\vo newly recognized and related bacterial species, H elicobacter cinaedi and Helicobacter fennelliae (formerly Campylobacter cinaedi and Campylobacter fennelliae) (4).have recently been associated with enteric disease in homosexual men (5,6).
The a uthors report two cases of bacteremia due to H cinaedi occurring in patients with human immunodeficiency virus (HIV) infection .These cases provide further information regarding tl1e spectrum of illness associated with this organism and serve to illustrate that H cinaedi may act as an opportunistic pathogen in patients with HIV infection.

CASE PRESENTATIONS Case 1:
A 38-year-old homosexual male ,vi.thAJDS was admitted to hospital in June 1990 for investigation of fever , cough and dyspnea.The patient had first been found to be HN antibody positive in 1988 when he developed Kaposi's sarcoma and Pneumocystis carinii pneumonia.Subsequently, he developed pulmonary involvement with Kaposi's sarcoma and was started on chemotherapy witl1 adriamycin.bleomycin and vinblastine.Other medications were zidovudine, acyclovir and ketoconazole .Ten days prior to admission the patient developed fever, chills, increasing cough and shortness of breath.He also had mild diarrhea but no abdominal pain .
On examination, the patient was cachectic, febrile, tachycardic and dyspneic.Blood and stool cultures obtained on admission yielded no significant growtl1.No opportunistic pulmonary infections were identified and the respiratory failure was attributed to progressive pulmonary Ka posi's sarcoma.A colonoscopy revealed edematous mucosa involving the transverse colon.Histopathological examination of a colonic biopsy revealed cytomegalovirus inclusions identified by in situ DNA hybridization.Treatment with ganciclovir was started and continued for three weeks.The diarrhea resolved , but the patient remained febrile.Repeat blood cultures.obtained two months following admission to hospital , yielded H cinaedi after five days of incubation .During treatment with eryfuromycin the patient became afebrile and was subsequently discharged from hospital.Three months later, the patient died of respiratory failure ; there was no evidence of recurrent bacteremia.Cas e 2: A 35-year-old homosexual male presented to the emergency department in July 1990 with a one day history of fever.chills, myalgias and arthralgias.In tl1e previous two weeks.the patient had also noted mild diarrhea and a cough productive of scanty amounts of sputum.The patient had first been found to be HN antibody positive in 1987.In the following year, he was hospitalized with bacteremic pneumococcal pneumonia.The patient had had oral candidiasis for several years , but no other opportunistic infections had been identified.Medications included zidovudine, acyclovir and ketoconazole.
On examination in the emergency department.the patient was afebrile and did not appear to be acutely ill.There was oropharyngeal candidiasis, but no other focus of infection was apparent.Cardiopulmonary and a bdominal examinations were normal.A chest x-ray was also normal.Blood and urine specimens were obtained for culture and the patient was discharged home from the emergency department with no specific treatment.He continued to complain of intermittent fever, myalgias and diarrhea.Empiric treatment with ciprofloxacin was started and the patient became afebrile with resolution of the diarrhea 48 h later.After five days of incubation.the blood cultures grew H cinaedi. Treatment with ciprofloxacin was continued for 140 10 days , and there has been no recurrence of symptoms after four months of follow-up.
Isolation of H cinaedi from the present two patients occurred approximately one month apart.The patients were not sexual partners and had no other known common contacts.Neitl1er of them had a significant history of animal contact or travel.Their isolates were identified as H cinaedi-like organisms by accepted criteria (4 ,5); the identities were confirmed by the National Laboratory for Ente1ic Patl1ogens (Laboratory Centre for Disease Control, Ottawa, Ontario).

DISCUSSION
There are now several Campylobacter and Helicobacter species known to be associated with human disease.Cjejuni and Campylobacter coli are important causes of infectious diarrhea, whereas Cfetus subspeciesjetus is recognized as a cause of bacteremia and sepsis in debilitated or irnmunocompromised hosts.Helicobacter pylori has been associated with chronic active gastritis (7) .although patients with AJDS appear to have lower than e:x.'})ected rates of infection with this organism (8).The name H cinaedi has been proposed to denote a new species within the genus Helicobacter based on phenotypic characteristics, biochemical tests and DNA homology studies (4).The organisms are fastidious and slow growing, typically requiring several days of incubation in a m icroaerophilic environment for growtl1 to be detected.The source and natural reservoir of H cinaedi are not known.although the organism has been recovered from the feces of healthy hamsters (9) .Whether colonized hamsters serve as a reservoir for human H cinaedi infection has not been determined.The organism a ppears to be transmitted sexually within male homosexual populations, and had initially been isolated only from homosexual or bisexual men; no isolates were recovered from 150 heterosexual men or women san1pled by Quinn and co -workers (1).More recently, however, Vandamme et al (10) reported tl1e isolation of H cinaedi from two female adults and three children.
The spectrum of illness associated with H cinaedi infection includes asymptomatic gastrointestinal carriage, proctitis , enterocolitis and bacteremia (1).The present report adds to the seven previously reported cases of H cinaedi bacteremia (10)(11)(12)(13).Six cases (including the two reported here) have occurred in homosexual or bisexual men, four of whom were known to be infected witl1 HN.The other two male patients presented with H cinaedi bacteremia prior to tl1e availability of HN serological testing (1) .Interestingly. they both had concurrent pulmonary tuberculosis.suggesting that tl1ey may also have had HN infection.H cinaedi bacteremia occurring in two adult women and one child were reported by Vandamme et al (10).but no other clinical information is provided.All six of the patients for whom clinical data are available presented with a nonspecific febrile illness; only two patients had preceding gastrointestinal symptoms .In each of the reports, blood cultures were processed using the Bactec system (Johnston Laboratories, Maryland) .The blood cultures were incubated for two to six days before bacterial growth was detected.Patients were trea ted with a variety of antimicrobial agents, including erythromycin, tetracycline, chloramphenicol, ciprofloxacin, gentamicin and antituberculous drugs.All of the patients survived their episode of bacteremia and there were no reported relapses, although one HIV-infected patient subsequently had bacteremia due to Hfennelliae (13).
Susceptibility testing of H cinaedi to a variety of antimicrobial agents suggests that isolates are generally susceptible to ampicillin, tetracycline, chloran1phenicol, anunoglycosides and quinolones, although 28% of 43 isolates were found to be resistant to 8 µg/ mL erythromycin (14).Susceptibility testing for these slowgrowing organisms has not been standardized, and optimal therapy for H cinaedi infection has not been determined.However, based on in vitro susceptibility test results, appropriate therapy for bacteremic infections may include tetracycline, ciprofloxacin or an aminoglycoside.
In HIV-infected patients, bacterial en teric pathogens such as salmonella, campylobacter and slugella m ay cau se chronic relapsing and/or bacteremic infection.Both humoral and cell-mediated immunity m ay be important in host defence against infection due to bacterial enteropathogens.Sera from HIV-infected subjects with persistent and severe C j ejuni infection had abnormally low campylobacter -specific antibody responses compared to otl1erwise healthy volunteers.and specific humoral in1munity was found to be important in preventing can1pylobacter bacteremia (2).Changes in mucosa!secretory antibody production have also been noted in HIV-infected patients.Kotler et al (15) found a reduction in the number of IgA-containing plasma cells in the intestinal lanuna propria of patients with AJDS.Not surprisingly, changes in mucosa!cell-mediated immunity have also been reported.Rodgers and coworkers ( 16) have documented abnormalities in the distribution of T-lymphocyte subsets in the intestinal mucosa of AJDS patients.The number of CD4 helper-inducer T cells in the lanuna propria was found to be reduced, paralleling the depletion of circulating lymphocytes.These defects have been related to direct infection of intestinal mucosa!cells by HIV.Combined local and systemic defects in cell-mediated and humoral in1munity may render the HIV-infected patient susceptible to enteric infections that subsequently becom e bacteremic or chronic and relapsing.
In summary, H cinaedi is a recently recognized enteric pathogen that may cause proctocolitis or bacteremia .Most cases h ave been reported in homosexual men , and the organism is believed to be transmitted sexually in these patients.Bacteremic illness is more likely to occur in patients with HIV infection, possibly because of intestinal mucosa!and systemic defects in humoral and cell-mediated in1munity.