Vibrio fetus endocarditis

Case reports

Vibrio Report

fetus

endocarditis

of 2 cases

Henry Loeb, M.D. Jerome L. Bettag, M.D. Nan Kit Yung, M.D. Sylvia King, M.S. David Bronsky, M.D.* Chicago, Ill.

V

ibrio fetus is an important cause of infectious abortion in cattle and sheep. Human infection with I/. fetus is uncommon but is being recognized with increasing frequency. We have observed 2 patients with subacute bacterial endocarditis due to 5’. fetus within 1 year. Only 3 other cases have been recorded previously in the medical literature.lJ Since infection with V. fetus responds readily to appropriate antibiotic therapy, it is important that this organism be considered in all cases of bacterial endocarditis. In this paper, we shall record the case histories of our 2 patients, review the epidemiology and clinical manifestations of the infection, and describe laboratory methods for the isolation and identification of V. fetus. Casa histories Case 1. A 67-year-old white man, a former boxer and construction laborer, was admitted to Cook County Hospital in November, 1963. He was mentally confused and unable to give an accurate history. He complained that he had had fever, chills, nausea, From

diarrhea, poor appetite, and loss of weight for 7 weeks, and a rash on his arms and legs for 2 weeks. In the past he had had hypertension, occasional ankle edema, paroxymal nocturnal dyspnea, and nocturia. Three years ago he was treated for pulmonary tuberculosis in a sanitarium. He drank alcohol liberally. Physical examination revealed a cachectic, dehydrated, pale white man who appeared to be both chronically and acutely ill. The blood pressure was 90/70 mm. Hg, pulse 88 per minute, respiration 24 per minute, and temperature 97°F. A confluent petechial and purpuric eruption was present on the hands, feet, and back. The mucous membranes were pale. There were no subungual hemorrhages or clubbing of the fingers. There were no conjunctival hemorrhages or icterus. The fundi appeared to be normal. The tongue was smooth and beefy red. The eyes, ears, nose, and throat were otherwise normal. The neck was supple. The thyroid gland was not palpable. There was moderate distention of the neck veins. There was no peripheral lymphadenopathy. The thorax was symmetrical, and the lung fields were hyperresonant to percussion. The breath sounds were diminished, but scattered rhonchi were audible in all areas. The heart size was normal to percussion, and the rhythm was regular. The heart sounds were distant and obscured by respiratory rhonchi. No murmurs were heard. The abdomen was slightly distended, and there was tenderness in the right upper quadrant, but no muscle

the Hektoen Institute for Medical Research, the Departments of Medicine and Bacteriology of the Cook County Hospital, and the Department of Medicine of the University of Illinois School of Medicine, Chiacgo, III. This study was supported by a grant from the Dr. Leonard 14. and Louis D. Weissman Medical Research Foundation. Received for publication March 11, 1965. *Address: Cook County Hospital, 1825 West Harrison St., Chicago, Ill., 60612.

381

guarding. The liver \vas enlarged and estendetl 4 c-m. below the right costai margin. No other organs or masses were palpated. There was no evidence of thrombophlebitis. Slight pitting edema of the legs w-as present. ‘l‘he genitalia were normal. The neurological examin,~tion showed disorientation to time and place but was otherwise Ilormal. LAHOKATOKU INVRSTIGA'TIONS. The urinalysis showed specific gravity 1.010, protein 2+, white blood ceils S-10 per high-power tieid, erythrocytes S-10 per high-power field, and was otherwise normal. On admission, the hematocrit was 19 per cent and the ervthrocyte sedimentation rate was 80 mm. per hour. ‘The nest day the hemoglobin was 4.9 Gm. per 100 ml., red blood ceils 1,930,000, and white blood ceils 21,550 per cubic millimeter. The differential white ceil count showed segmented cells 56 per cent, bands 36 per cent, lymphocytes 4 per cent, monorvtes 2 per cent, and metamyeiocytes 2 per cent. ?‘he blood film showed a decrease ill platelets a11d 2+ anisorytosis, polychromatophiiia, and tosicity. .A platelet count showed 10,000 pfateets per cubic millimeter. The reticulocytes count wxs 2 per cent. Aspiration of the bone marron showed moderate hyperceiiuiarity. The megakaryocvtes were decreasecl in number. The nucleated RRC: li’i3C ratio \vas 1 :l. Erythropoiesis was normob&tic, and granulopoiesis was moderately loxit,. ‘l‘here was an increase in histiocytes alld reticular cells. Occasional giant band ceils were seen. Hiochemicai determinations showed a blood urea nitrogen of 89 and creatinine of 4.0 mg. per 100 ml. The total protcill was 5.3, albumin 2.9, globulin 2.4, and gamma globulin turbidity 2.02 Gn. per 100 ml. The ralciunl was 8.3, and phosphorus 5.6 mg. per 100 ml. The sodiuni was 123, chloride 80, potassium 3.0 and COY 16.0 mF:q. per liter. The total cholesterol was 98 mg. per 100 ml., with 56 per cent esters. The icteric. index was 9 units, thr alkaline phosphate was 3.6 Rodanski units, the cephnlin floculation was I?+, and thymol t[rrbidit;. \vas 6.7 MacI.agcn units. The glucose was 118 mg. per 100 ml. lioe~~tgenograms of the chest showed the heart to be of normal size and configuration. The aorta wab elongated and the arch wxs calcihed. ‘I‘he electroc~lrdiogranl showed low voltage, ;I sinus tachycardia, and nonspecifir flattening of the ‘I‘ waves in Leads I, Vi,+ The Kahn test was negative. :Z skin test with O.T., 1:lOOO dilution, was negative. Smear and culture of one collection of sputum \vas negatix-e for ;lfyi-uhnc-teriunl tuberc-ulosis. On admission the patient was given intro\-enous fluids and large doses of vitamin C and thiamilx. The day after admission he was semicomatose and appeared to be moribund. His blood pressure was 105/60 mm. Hg.. pulse 120 per minute, and temperature 101°F. He was given 1,000 ml. of whole blood, hydrocortisone, 300 mg. daily, and antituberculosis therapy with isoniazid, 300 mg. daily; and streptomycin, 1 Gm. daillr, was begun. On the third hospital day, six samples of blood for culturing were drawn and therapy with intravenous penicillin, 15 million units daily, was instituted. On the fifth da)-. many coarse Ales were heard throughout the chest. In thv afternoon he had a massive eplstaxis, whic.h was controlletl h\, :I posterior nas;11 pxk. Froln then on his c,oudi;iorl deteriorated. Ilis out-

of urine dec~roaseti. .i’hc IIIw~I ure;i uitrogcrt rose to 100 mg. pf’r 100 ml. and he I;rpsed into 2 coma. He died 8 days after adnlission to t hc ho+ pitai, having bee11 ill for appr~~simatei~ 8 weeks. Postmortem es,tmirlativll re~enied the following: marked c,lchesi;c h> pertroph!d t hc heart; an unruptured aneuqxnl of thr hinus of \‘;dsalv:t; verrucous endocarditis totally involving the left anterior xx-tic cuy and partially intiitrating the right anterior cusp; tiny Lerrltra on the mitr;li valves; severe massive hilatcral l)ro~~chopneumorli;l; and tracheobrotichitis. After the patient died, V’. f&s was cultured from all specimens of blood drawn during life. The identit, of the organism \vas verified by &Iiss Elizabeth 0. King, of the Conlmunicable Disease Center, Chambiec, Georgia. I’. fetusorganisms \vere not recovered from postmortem ~lfltures. COMMENTS. ‘The patient presented as a debilitated alcoholic lvith multiple vitamin deficiencies, severe anemla, thromboc.vtopenia, and sepsis. Therap? with large doses of penicillin and streptoml,cin was ineffective. ‘Thrornt)ocJ’topenia has not been reported previously in infection with V.fetu.s. Case 2. :\ Gyear-old unmarried Negro man, a cab driver, was admitted to Cook County Hospital in September, 1964, complaining of rhiils and fever. Four weeks prior to admission, after :t l-day episode of transient p,iin ill both flanks and a generalized musculx aching. the patient noted heat, pain, and tenderness ill (I small area WI the medial aspecl of his left thigh. A roentgenogram of the thigh made at another hospital showed no abnormality. Several days later hv developed shaking chills and fever. His tenlperature UYIS 103°F. He was given an oral medicxtirrn 13~ his physician, and the symptonrz abated tempor;n-il>, bcrt rccurrcd and pcraisted for 2 weeks beforc his admission to the hospital. He also c-omplained of anore=&, loss of weight of 20 pounds, frontal headxhc, and two recent episodes of vomitiug. There was ILO histor!, of cough, chest pain, hemoptyis, tlysp~~e,~, a11k1r cdcma, hematuria, upper respirator\, infection, or diarrhea. He had not llndcrgone ;my dental procedures rc’cently. He had no contact w-it h animals. He smoked a moderate llunlber of cigarettes daily ~IKI did not drink alcohol. \Vhcn he W\‘;LS12 years old, he had been told that he had ;L “heart conciition.” He was never told that he had rheumatic fever, and there was no history of congestive heart failure. IVhen the patient was 27 years old, he had beeu rejected for service with the ;u-med forcer heccltlse of a heal-t murmur. Physical exanlination re\,ealed a tvell-developed. well-nourished Negro man who did not appear to be chronically ill and was in no acute distress. The blood pressure was 100/40 mm. Hg, pulse 72 per minute and regular, respiration 24 per minute, and temperature 104°F. One suspicious conjulu-tivai petechia $vas obscr\,ed. The neck b,eins Lvere not distended. Examination of the head and neck revealed no other abnormalities. The thorax was symmetrical. The lung fields were clear to auscuitation and percussion. On percussion, the ~~tiiac apes was in the lifth illterc.oal;d SP;KV at IhP Icft xnterior ayilIarv line. Palpation sho\vctl ,111 active left \,elltric IIlar impulse. (III aus~.uitrllion. rherr \vas ‘1 soft 5~;. pill

Vibrio fetus endocardifis

tolic ejection murmur and a long diastolic blow at the third intercostal space just to the left of the sternum. Examination of the abdomen showed a sharp edge to the liver one fingerbreadth below the right costal margin. No other organs or masses were palpated. Recta1 examination showed a small prostate gland. The stool benzidine test was negative. Examination of the extremities showed a palpable thrill and audible bruit over the lower media1 aspect of the left thigh. The blood pressure of the right leg was 170/50 mm. Hg, and that of the left leg was lOO/SO mm. Hg. Compression of the aneurysm caused no change in pulse rate or peripheral blood pressure. The peripheral arterial pulses were bilaterally equal. There were no signs of inflammation. There was no tenderness of the calves, and Homan’s sign was negative. There was no edema. Examination of the genitalia showed that the testicles were of normal size and consistency. The neurological examination was normal. The urinalysis LABORATORY INVESTIGATIONS. showed specific gravity 1.017, pH 5.0, a trace of urobilinogen, 6 white blood cells per high-power field, and was otherwise normal. Cultures of the urine revealed no growth. The hemogram showed a hemoglobin of 11.8 Gm. per 100 ml., erythrocytes 4,120,OOO and white blood cells 15,100 per cubic millimeter. The differential white cell count was: segmented cells 78 per cent, bands 5 per cent, lymphocytes 13 per cent, and monocytes 4 per cent. The blood film showed I+ anisocytosis, rouleaux formation, 2+ toxicity, and normal platelets. Biochemical studies showed a blood urea nitrogen of 19, glucose 70, and uric acid 8.3 mg. per 100 ml. The total protein was 7.8, and gamma globulin turbidity was 2.68 Gm. per 100 ml. The alkaline phosphatase was 3.4 Bodansky units, thymol turbidity 6.3 MacLagen units, and a cephalin flocculation test was 3+. The antistreptolysin-0 titer was less than 150. The “C” reactive protein reaction was 3+. The Kahn test was negative. Roentgenograms of the chest showed a moderate increase in the transverse diameter of the heart, with prominence of the left ventricle and the aorta. An electrocardiogram showed left ventricular hypertrophy. The initial therapy of tetracycline, 2 Gm., was discontinued after 1 dav. Five samoles of blood for culturing were drawn within 48 hours after admission. On the second hospital day, therapy with penicillin, 20,000,OOO units daily, intravenously, streptomycin, 2 Gm. daily, intramuscularly, and probenecid, 2 Cm. daily, was begun. On the sixth hospital day a purpuric eruption was observed on both supraclavicular fossae and the left thigh, which persisted 2 days. All five blood cultures grew V. fetus, which was sensitive to penicillin, chloramphenicol, tetracycline, erythromycin, and methicillin using the disk method. One of the cultures also grew hemolytic Staphylococcus aweus which was coagulase positive. The identity of the V. fetus was subsequently veritied by Miss Elizabeth 0. King. On the seventh hospital day, therefore, therapy with tetracycline, 2 Gm. a day, was reinstituted in addition to penicillin. A low-grade fever which had persisted for a week now subsided, and the patient became asymptomatic. A sample of blood drawn for culture on the

383

ninth hospital day, while he was receiving antibiotic therapy, showed no growth. On the seventeenth hospital day the patient left the hospital and discontinued all therapy against medical advice. One month later the patient was observed at the outpatient clinic in response to a letter. He was short of breath on exertion and occasionally noted a rapid beating of the heart, but was otherwise well. He had not returned to work. On physical examination, the aneurysm of the left thigh was no longer demonstrable. The cardiac findings were unchanged. A blood culture showed no growth. Agglutinating antibodies in the patient’s serum were detected against V. fetus organisms isolated from the patient in titers of 1:lO and 1:20 on the ninth and fifteenth hospital day and were negative 1 month later. A higher titer may have been reached during the period that the patient was lost from observation. COMMEKTS. The patient’s underlying heart lesion was rheumatic aortic valvular disease. Upon this was superimposed an endocarditis due to V. fetus. The initial manifestation of the infection was a mycotic aneurysm of the femoral artery. Although V. fetus was sensitive to penicillin in the test tube, penicillin was clinically ineffective and the patient did not respond to therapy until tetracycline was administered.

Previously reported fetus infection

aspects

of Vibrio

Epidemiology. The epidemiology of V. fetus infection in animals has been reviewed by King.’ In cattle, the infection is a venereal disease. In the bull, the organism is found on the prepuce and in the semen. It is apparently maintained indefinitely in the testes. In the cow, there are minor lesions in the vagina. The major lesion is in the placenta, causing interference with the circulation and a resulting abortion. In sheep, ewes are probably infected by the ingestion of contaminated food or water, and although venereal transmission may occur, it is relatively uncommon. The guinea pig and hamster can be infected experimentally with V. fetus, after which the disease is spread to other members of the colony by sexual contact. The epidemiology of human infection with V. fetus is not clear. Twenty-seven cases have been recorded in the literature.1-20Whether transmission is by coitus, contact with infected animals, or ingestion of contaminated food and water has not been definitely determined. Hood and Todd3 have reported an abortion due to V. fetus infection, in which case the organism was isolated from the brain of the fetus and the placenta, and antibodies to

17.~~1~s were demonstrated in the blood of both parents. This strongly suggests that venereal transmission of the infection had occurred. A similar mode of transmission may have been involved in 3 patients in whom the infection XVRS associated \vith problems of pregnancy,4x5 and in one report of V. fetzls meningitis in a newborn child.” However, virtually all other instances of infection with I,‘. f&us have occurred in adult men. The occupation of some of these men could have brought them into contact with infected animals, but man). had no contact with animals at all. Although yetto be documented, it seems to be likely that the infection in these patients was by the ingestion of contaminated food and water. The onset of the diseaseafter dental procedures in 2 patients supports the concept that infection may occur by the oral route. The direct transmission of the infection from laboratory culture to skin has also been reported.’ Bacteriology. The bacteriologic isolation and identification of V. fetus is not difficult if the bacteriologist is aware that this organism is pathogenic for man. The organism is microaerophilic and gro\vs well in tryptone soy broth and tryptone soy blood agar plates under increased carbon-dioxide tension. Primary isolation may require 4 to 5 days of incubation. Morphologically, I’. fete is a motile, comma-shaped rod w’ith a single polar flagellum which can be demonstrated b> Leifson’s flagella stain. Often, several or more organisms will form a strand resembling a spirillum.8 Biochemically, the organism is oxidase positive, catalase positive, and does not produce indol. It does not ferment any of the carbohydrates. Serologic identification of the organism is currently being performed at the Communicable Disease Center in Chamblee, Georgia. Problems of isolation and identification of the organism have been discussed by KingIs and by Jackson and associates.‘” Clinical manifestations. The clinical manifestations of V. fetus infection in human beings are markedly varied. The infection has been reported in 5 women, 2 newborn babies, and 20 men. The average age of the men was 52 years, and ranged from 31 to 74 years. The most common manifestn-

tions are chills. fravcbr,hp:ldarhe, and ma. laise, with periods of remission and exacerbation. This form of the infection mimics brucellosis. Thrombophiebitis occurs often and may be superfi&l or deep, ma)- involve any extremit),. tnay be nligratory, and may develop at the sit.e of a venipuncture. The infection has a tendency- to occur in the debilitated patient \vith a chronic underlJ,ing illness. rIpparent-ly. an>’ body system may show primary involvement. Infection of the gastrointestinal tract causes diarrhea.“,‘” Infection of the central nervous system may produce a meningitis6v’3-15or multiple brain abscesses.6Jaundice, pneumania , and septic arthritis have been described.‘,% The infection responds readilq to therapy \\-ith the usual doses of tetracycline or chloramphenicol. Penicillin alone, even in massive doses, is usually ineffertive. Endocarditis. I’ibrio jetus endocarditis has been reported in 3 patients.‘z2 Two patients have been reported on briefly by King’ in a table in her paper. The first patlent was a .50-year-old male painter with an “athlete’s heart.” He had had chills, fever, and an enlarged liver for 2 months. I/. ,[t?t~s \~as c.ultured from the blood. Treatment and results \\‘ere not recorded. The second patient was a 47year-old male janitor with cirrhosis of the liver. IIe was jaundiced and had a fever. Ije died of cirrhosis and bleeding. ci. fefrls ~-as cultured from the blood. The case of Auquier and associates” has been reported in detaif. X 45year-old maIe storekeeper developed chills, fever, severe headache, and a transient scarlxtiniform eruption 5 days after extraction of a tooth for an apical abscess. On physical examnation, the sole abnormal finding was elevation of the temperature. The initial laboratory studies were normal. After 20 days of persistent fever, :t diastolic murmur was heard in the third intercostal space t.o the left of the sternum. Two samples of blood dra\\:n for culturing grcm: gramnegative motile rods that were not further identified. 1)uring the course of illness a thrombophlebitis developed at the site of a venipuncture. Therapy included, in succession, penicillin, initially 500,000 units, then 10,000,000 units daily, streptom>rcin, 1 (,m. dall)., tetrac>rlmc. 1..5 Gm. daily,

Volwne

71

Number

3

and erythromycin, 1.2 Gm. daily, without clinical effect. Finally, 31 days after the onset of illness, chloramphenicol, 2 Gm. daily, was administered. This was followed by rapid defervescence, and the blood cultures became negative. After the patient had recovered from his illness, the organism isolated from the blood was identified as V. fetus. Blood antibody titers to the organism, 1 and 2 months after recovery, were 1:640 and 1:2500, respectively. The patient, on follow up, presented the manifestations of aortic insufficiency. Comments

The predilection of V. fetus for involvement of the endothelium of the vascular tree has been remarked upon frequently. To this we may now add that it has a tendency to occupy the aortic valves, particularly when there is a pre-existing valvular deformity. The tendency for the infection to occur in debilitated, chronically ill patients is demonstrated again in Case 1. King’ has suggested that the source of infection in such patients is the testes, for if V. fetus is maintained in the testes, as it is in the bull, then when natural body defenses weaken, dissemination may occur. The thrombocytopenia observed in this patient was probably the result of sepsis. However, in the absence of an adequate history, the possibility of a druginduced thrombocytopenia cannot be discarded. The therapeutic response of the second patient to tetracycline is consistent with previous reports. For this reason, infection with V. fetus should be considered in all cases of bacterial endocarditis, particularly when there is involvement of the aortic valves or when there are peripheral vascular disturbances, such as a mycotic aneurysm or thrombophlebitis.

Vibrio fetus endocarditis

tetracycline and does not respond to penicillin alone. Vi’brio fetus, therefore, should always be considered as a possible cause of bacterial endocarditis. Addendum

Case2. It was later learned that several days after this patient’s last visit to the clinic, he awakened during the night acutely short of breath. A pulmotor squad administered oxygen, but the patient was dead on arrival at a local hospital. Death was attributed to acute pulmonary edema. An autopsy was not performed. A soluble flagellar antigen was subsequently prepared from the organism that was isolated from this patient. With this we demonstrated precipitin bands in agar gel from three samples of sera obtained 5, 8, and 30 days after the first positive blood culture. These bands were identical to precipitin bands produced from rabbit sera which were immunized with the same organism. We Truman script.

are indebted 0. Anderson

to Dr. Rolf Gunnar and Dr. for their review of this manu-

REFERENCES 1. King, E. 0.: Human infections fetus and a closely related vibrio,

101:119, 1957. 2. Auquier, L., Chretien, 3. 4.

Summary

The case histories of 2 patients with Vibrio fetus endocarditis have been recorded. The organism apparently has a predilection for the aortic valve, particularly when there is a pre-existing abnormality of this valve. Peripheral vascular manifestations, such as a mycotic aneurysm or thrombophlebitis, have been observed. The infection responds readily to the usual therapeutic doses of chloramphenicol or

385

9.

10.

11.

with Vibrio J. Infect. Dis.

J., and Hodara, M.: Septic&me avec endocardite B “Vibrio foetus,” Bull Sot. Med. HSp. Paris 72:580,1956. Hood, M., and Todd, J. M.: Vibrio fetus-A cause of human abortion, Am. J. Obst. & Gynec. 80:506, 1960. Vinzent, R., Dumas, J., and Picard, N.: Septicemie grave au tours de la grossesse, due h un vibrion, Avortement consecutif, Bull. Acad. Nat. Med. 131:90, 1947. Vinzent. R.: L’infection humaine a Vibrio foetus, Nourrisson 38:96, 1950. Eden, A. N.: Vibrio fetus meningitis in a newborn infant, J. Pediat. 61:33, 1962. Ward, B. Q.: Apparent involvement of Vibrio fetus in infection of man, J. Bact. 55:113, 1948. King, S., and Bronsky, D.: Vibrio fetus isolated from a patient with localized septic arthritis, J.A.M.A. 175:1045, 1961. King, E. 0.: The laboratory recognition of Vibrio fetus and a closely related vibrio isolated from cases of human vibriosis, Ann. New York Acad. SC. 98:700. 1962. Jackson, J. F., Hinton; P., and Allison, F., Jr.: Human vibriosis: Report of patient with relapsing febrile illness due to vibrio fetus, Am. J. Med. 28:986, 1960. Mandel, A. D., and Ellison, R. C.: Acute dysen-

12.

13.

14.

15.

tary syndrome caused by \Ybrio fetus, J.l\.Al.-~. 185536, 1963 \Vheeler, W. E., and Borrhcrs. J.: Vilkonicenteritis in infants, .\.M.A. J. 1% Child. 101:60, 1961. Rurgert, \fr., jr., and Hagstrom, J. \V. C.: \?brio fetus meningoencephalitis, Arch. Keurtrl. 10:196, 1964. Collins, H. S., Blevins, :I., and Benter, E.: Protracted bacteremia and meningitis due to \Ybrio fetus, Arch. Int. Med. 113:361, 1964. Robin, L. A., Duprey, G., Jouannot, J. F., Paris, I’., Magard, H., Mignard, J., and BerA4 propos de trois cas de vibriose teal, P.: humaine (\Ybrio foetus) dont une meningite, Press. M&l. 70:321, 1962.

18.

19. 20.

‘fhibault, Chatelain, Nat. bled. SpinI;, \\‘. Vibrio fetus, Kahlcr, I<. infection in 1218, 19t10.

I’., G~illartl, 1.. Sec~nrd, I.., and Ii.: “librio foctus.” Bull. Acacl. 1.19:9.5, 1955. \V.: tluman vibriosis caused h> J..\.\I.:\. 16.7:180, 1957. I... and Sheldon, 11.: \ibrio fetus i1nm, \j c’u England J. hletl. 262:-