Journal of Infection (I983) 6, 75-80

CASE REPORT

C a r d i o b a c t e r i u m homin i s : a n e l u s i v e c a u s e o f e n d o c a r d i t i s

T imothy Lane, Rob Roy MacGregor, David Wright* and Joseph Hollander

University of Pennyslvania School of Medicine, Departments of Medicine and *Pathology, Philadelphia, Pennsylvania, U.S.A.

Summary Cardiobacterium hominis is a fastidious bacterium of the normal mouth flora. It has rarely been recognised in the past as a human pathogen and has been difficult to recover from the bloodstream. Mistaken diagnoses and delays in therapy have been common. We report a 29-year-old man with C. hominis endocarditis who was initially treated for a presumed collagen-vascular disorder with anti-flammatory drugs. The organism was eventually recovered in brain-heart infusion medium after prolonged incubation, and cure was accomplished with parenteral penicillin. Special blood culturing methods should be used if endocarditis caused by a fastidious organism is clinically suspected.

Introduction

Cardiobacterium hominis is a fastidious bacter ium of the normal oropharyngeal flora? In the rare instances when it has been implicated as a human pathogen, it has been associated with endocarditis. Twenty - s ix patients with C. hominis endocardit is have been repor ted previously. 2-2° These reports emphasise the difficulty in isolating the organism from blood cultures, the f requent initial diagnosis of cul ture-negat ive endocardit is , and the occasional confusion of the clinical presentat ion with a collagen-vascular disorder. Consequent ly , specific antibiotic therapy has often been delayed. W e describe a patient with C. hominis endocardit is that e luded early diagnosis who was treated initially with anti- inflammatory drugs for a suspected vasculitis. This case illustrates the clinical and bacteriological characteristics of this apparently unusual cause of infective endocardit is and emphasises the importance of appropriate blood culture methods in patients with apparent ly ' cu l ture-negat ive ' endocarditis.

Case report

A 29-year-old man had onset of a non-product ive cough, severe myalgia, and malaise in June x977. Over the next several weeks the myalgia worsened and he developed intermit tent rigors. In July he was admit ted to another hospital because of these symptoms. Past medical history was unremarkable except for a heart m u r m u r that was heard during a rout ine physical examination ten years before. H e had had no dental manipulat ions in the past three years. Physical

Address for reprints: Dr Timothy W. Lane, Internal Medicine Teaching Program, The University of North Carolina, The Moses H. Cone Memorial Hospital, I200 North Elm Street, Greensboro, N.C. 27420, U.S.A.

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76 T. L A N E E T AL.

findings included an oral temperature of 38 °C, a grade IV/VI pansystolic murmur, but absence of a palpable spleen, petechiae, and Roth spots. Laboratory data included: haemoglobin 12"3 g/dl, white blood cell count lO.2 × lO9/1 with a normal differential count, normal urine sediment, and a normal chest roentgenogram and ECG. The erythrocyte sedimentation rate (ESR) was not measured. The clinical impression was that of infective endocarditis, and five routine blood cultures in neopeptone broth were obtained during the first three days in hospital. The patient became afebrile, without therapy, after the second hospital day. He was discharged on the seventh day when his blood cultures remained sterile. These cultures were discarded according to laboratory routine after I o days with no bacterial growth evident. Symptoms persisted and he lost nine kg in weight over the next two months. In October of the same year he noted migratory arthralgia of the fingers and wrists and developed mild swelling of his phalangeal joints. In addition, he developed transient but recurring tender, raised lesions on several of his fingertips. Further tests revealed an ESR of 43 m m / h (Westergren) and an M mode echocardiogram demonstrated a prolapsing mitral valve but no vegeta- tions. These findings suggested a collagen-vascular disease, and an empirical trial of aspirin (16 300 mg tablets/day) and prednisone (2o mg/day) was begun in November. On this regimen his symptoms improved and he returned to work.

In January 1978, while still taking 20 mg of prednisone daily, he developed acute pain in the left upper quadrant of the abdomen that radiated to the left shoulder, and he was admitted to the Hospital of the University of Pennsylvania. Pertinent findings included a normal temperature, a grade IV/VI pansystolic murmur , mild left upper quadrant tenderness without a palpable spleen, and a tender, erythematous nodule on the tip of the right fourth finger. Hemoglobin was 12"5 g/dl ; urine analysis was normal, ESR 3o mm/h , normal Ca, C4, and CH~0 complement, and a negative ANA. An M mode echocardiogram again demonstrated a prolapsing mitral valve without vegetations. A spleen scan showed a filling defect compatible with an infarct.

Because endocarditis was strongly suspected, multiple blood cultures were obtained over the first week in hospital; several were inoculated into biphasic agar and broth bottles of brain-heart infusion (BHI) medium designed primarily for isolation of fungi. The patient's abdominal pain and finger nodule resolved over several days, and he was discharged on the tenth hospital day to continue his regimen of anti-inflammatory drugs. The microbiology laboratory incubated the blood cultures beyond the usual IO days, and on the 2ISt day of incubation a BHI culture grew a small Gram-negative rod eventually identified as C. hominis. The patient was readmitted for therapy of infective endocarditis. A new finding was the presence of rheumatoid factor at the titre of 640, having been 40 two months previously. Further blood cultures from which C. hominis was later recovered were made before therapy was begun with daily administration of 12 million units of penicillin intra- venously. The minimum inhibitory concentration of penicillin to the isolate was found by a microtitre dilution technique to be I.O mg/l. The dose of penicillin was increased therefore, to 20 million units daily for the 2o remaining days of a 3o-days' course of therapy.

The patient felt generally improved within a few days and two blood cultures

C. Hominis endocarditis 77

in BHI medium with penicillinase that were drawn on the fourteenth day of therapy remained sterile after 30 days of incubation. He remained well six months after completion of therapy and with no evidence of active disease.

Discussion Bacteriology

Cardiobacterium hominis was first described in I962 by Tucker and colleagues 1 and was aptly named by Slotnick and Dougherty in I964 .2 The organism is an inhabitant of the upper respiratory tract of healthy human beings. 2 It is a facultatively anaerobic, non-motile, pleomorphic, Gram-negative bacillus that produces indole, is oxidase-positive and catalase-negative. It ferments glucose, maltose, and sucrose, but not lactose. The isolate from our patient was identified by these properties.

Clinical manifestations

The clinical manifestations of C. hominis endocarditis are similar in many respects to those of other causes ofsubacute bacterial endocarditis. The history is typified by an indolent course of low grade fever, myalgia, and nonspecific malaise as seen in our patient. Most patients also have a mild anaemia, an elevated ESR (a mean of 55 m m / h in I2 patients), and a heart murmur. 1-2° The types of predisposing valvular disease do not differ from those reported in large published series of endocarditis. 21 A prolapsing mitral valve was the probable predisposing lesion in our patient. The mean age of the reported patients is 5o years. The oropharynx is the presumed portal of blood stream invasion, but a history of prior dental procedures has been noted only occasionally.

The unusual features of our patient were the striking cutaneous and musculosketetal abnormalities that, in the context of negative blood cultures, were mistaken for an underlying collagen-vascular disorder. Geraci and. colleagues reported four patients with C. hominis endocarditis. Two had this type o f ' autoimmune' presentation, including immune complex glomerulone- phritis, and were treated with steroids for presumed vasculitis. 4 Arthritis, pleuritic pain, skin lesions, and urine sediments consistent with immune complex phenomena have been described in many of the cases of C. hominis infection. ~, ~. 5-7 For all forms of bacterial endocarditis, evidence continues to accumulate that many of these manifestations are immunologically mediated. Circulating immune complexes have been demonstrated in infective endocar- ditis and are thought to result from the chronic antigenic stimulus caused by the endovascular infection, z2 The concentration of circulating immune complexes correlates with the duration of infection. The prolonged and indolent course of untreated C. hominis infection may account for the findings that are misinterpreted as evidence of a primary immune complex disorder.

Antibiotic susceptibility and therapy

Antibiotic susceptibility testing was carried out for our patient's isolate by a modified microtitre dilution method using Schaedler's broth plus 5 % Fildes supplement incubated at 37 °C in Io per cent CO2 for 48 hours. 23 Minimum

78 T. L A N E E T AL.

Table I Summary of antimicrobial testing

Antibiotic tested MIC* (mg/l)

P e n i c i l l i n i "O

Ampicillin 0. 5 Vancomycin 32'o Gentamicin 2.0

* Minimum inhibitory concentration as determined in Schaedler's broth plus 5 per cent Fildes supplement at 37 °C for 48 hours in Io per cent CO 2.

inhibitory concentrations (MICs) were determined for penicillin, ampicillin, vancomycin and gentamicin and are summarised in Table I. Our isolate was relatively sensitive to penicillin and ampicillin. A uniform method of determining MICs has not been adopted because of the problems in growing C. hominis, and this difficulty probably accounts for the variability of penicillin MICs reported by others. 4 Although penicillin or ampicillin administered for three to four weeks has generally resulted in bacteriological cure of C. hominis endocarditis, three possible antibiotic failures have been reported. TM is, ~ In one of these instances of antibiotic failure, Rahal and coworkers described a penicillin-resistant isolate and suggested that susceptibility to penicillin should not be assumed. It should also be noted that our isolate was resistant to vancomycin (MIC -- 32 mg/1). Prior and colleagues have shown similar resis- tance to vancomycin (MIC 25 mg/l) for a strain of C. hominis. TM Vancomycin may not be appropriate empirical therapy for the penicillin allergic patient with C. hominis endocarditis unless susceptibility is demonstrated in vitro. Four deaths have followed the complications of valvular destruction or rupture of a mycotic aneurysm. ~

Diagnoses The isolation of C. hominis from blood cultures is difficult because of its slow growth and apparent fastidious nature. C. hominis was recovered from our patient in six blood cultures and only in those bottles containing a biphasic liquid and solid BHI medium (BBL) intended primarily for fungal isolation. There was no growth in multiple blood culture flasks containing Columbia broth or thioglycollate broth after 30 days of incubation. C. hominis has been recovered by others in a variety of media including BHI and casein digest broth. ~ These particular media differ from standard blood culture media primarily by their protein enrichment. Optimum growth conditions also include an increase of CO2 in the atmosphere and Io0 per cent humidity. Improvement and standardization of blood culture methods may account for the fact that half of the cases of C. hominis infections have been reported since 1975.

The percentage of cases of endocarditis that are culture-negative has been fairly constant over the past fifty years. ~1 Recent observations of the growth requirements of fungi and certain bacteria may reduce this percentage if special culturing methods are used. ~4 In retrospect, our patient's findings including

C. H o m i n i s endocardi t is 79

ini t ia l ly nega t ive b l o o d cu l tu res m a d e an exce l len t case for ' c u l t u r e - n e g a t i v e ' endoca rd i t i s and an empi r i ca l tr ial o f ant ib io t ics . T h e even tua l bac te r io logica l d iagnosis was s e r e n d i p i t o u s ; in fact , the c o m m o n l y e m p l o y e d empi r ica l r e g i m e n o f penic i l l in and an aminog lyco s id e w o u l d a lmos t ce r ta in ly have b e e n cu ra t ive w i t h o u t ou r d e t e r m i n i n g the causat ive o rgan i sm. B H I m e d i u m was inocu la t ed because it enhances the i sola t ion o f fungi f r o m the b lo o d s t r eam . 25 F r o m o u r e xpe r i ence and tha t o f o the r s , we r e c o m m e n d the use o f B H I m e d i u m and p r o l o n g e d i n c u b a t i o n in s imilar clinical s i tua t ions so as to i m p r o v e the r e c ove r y o f fas t id ious o rgan isms .

O t h e r po ten t i a l causes o f endoca rd i t i s t ha t r eq u i r e special b l o o d cu l tu re m e d i a inc lude the s t rep tococc i . M c C a r t h y and B o t t o n e have e n c o u n t e r e d several s t r ep tococca l isolates f r o m pa t ien ts wi th endocard i t i s tha t g row on s u b c u l t u r e on ly in the p r e sence o f cys te ine or t h i o g l y c o l l a t e ) 6 R o b e r t s r ecen t ly d e s c r i b e d s t ra ins o f Strep tococcus v i r idans i sola ted f r o m pa t i en t s w i th e n d o c a r - dit is tha t r e q u i r e d p y r i d o x a l h y d r o c h l o r i d e (Vi tamin B6) for g r o w t h in v i t r o ) 7

T h e inc idence o f these nu t r i t i ona l ly va r ian t bac te r ia as causes o f endocard i t i s is u n k n o w n . T h e y and o the r fas t id ious o rgan i sms m a y be m o r e c o m m o n th an is genera l ly be l i eved because a p p r o p r i a t e t e c h n i q u e s o f cu l t u r ing are n o t sys temat ica l ly e m p l o y e d .

(We acknowledge Ms Patricia Kuglin for determining antibiotic susceptibilities and Ms Patricia Pardue and Ms Paula McDaniel for secretarial assistance.)

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