The heterogeneity of Streptococcus viridans: therapeutic considerations in infective endocarditis J. Fisher, md; D.L. Levene,

md

A 24-year-old woman with syndrome and mitral regurgitation had clinical features suggestive of infective endocarditis. The causative organism was Streptococcus viridans. Initial therapy with penicillin G, in a dose that

Summary: Marfan's

should have been bactericidal and hence curative according to the results of the initial quantitative antimicrobial studies, became inadequate. The strain of 5. viridans displayed considerable variation in both growth properties and antimicrobial sensitivity during the course of therapy. In addition, a different strain of S. viridans was cultured 1 month after treatment had begun. It is therefore important to repeat cultures and antimicrobial sensitivity testing during treatment of infective endocarditis.

Resume: L'h6t6rog4neit6 du Streptococcus viridans: quelques aspects therapeutiques dans I'endocardite

infectieuse

Most

infectieuse. L'organisme pathogene 6tait le Streptococcus viridans. Le traitement initial a la penicilline G, a

une posologie qui aurait du etre bactericide et partant, curative d'apres les resultats des essais de sensibilite antimicrobienne quantitatifs pretherapeutiques, devint rapidement insuffisant. En cours de traitement la souche de 5. viridans montra des variations considerables et de ses

propri6tes de pousse et de sa sensibilite antimicrobienne. D'autre part, une souche differente de S. viridans a et6 isolee dans les cultures 1 mois apres le debut du traitement. II importe done de rep6ter les cultures et les essais de sensibilite antimicrobienne tout au long du traitement de I'endocardite infectieuse.

From the division of cardiology, University of Toronto Clinic, Sunnybrook Medical Centre, Toronto Reprint requests to: Dr. Donald L. Levene, University of Toronto Clinic, Medical Centre, 2075 Bayview Sunnybrook Ave., Toronto, Ont. M4N 3M5

of endocarditis due to

successfully treated with penicillin G. A decrease in temperature and an improvement in the general well-being of the patient are commonly interpreted as signs of successful therapy. Some authors do not stress repeating cultures and antimicrobial sensiti¬ vity studies during the treatment of infectious endocarditis,1 even when the infecting organism is penicillin-resistant S. viridans;2 others recommend repeating cultures during3 and after4 therapy. The importance of repeating cultures during therapy is demonstrated by this case report. The patient seemed to be infected with a strain of S. viridans that had considerable capacity for vari¬ ation, both in growth properties and in antimicrobial sensitivity. In addition, and possibly less important, a different are

strain of S. viridans was cultured from the blood about 1 month after treat¬ ment was begun. The advisability of repeating cultures and quantitative anti¬ microbial sensitivity studies throughout the period of treatment must therefore be

Une femme de 24 ans souffrant du syndrome de Marfan et de regurgitation mitrale avait des signes cliniques qui suggeraient une endocardite

cases

Streptococcus viridans

emphasized.

Case report A

24-year-old white woman presented department with an erythematous papular rash of 1 week's duration on both lower extremities, which had been preceded by vague arthralgias involving both knees and ankles. She also had noted increased sweating at night for several weeks. Her pulse rate was 110 beats/min and her temperature was 38.2°C. She was tall and had features suggestive of Marfan's syndrome: her face was long, her palate was high and arched, her teeth protruded and she had kyphoscoliosis. One petechial hemorrhage was noted on the buccal mu¬ cosa. There was no evidence of lenticular dislocation. A double apical impulse and a systolic thrill were palpable on examina¬ to the emergency

tion of the heart. The mitral component of the first heart sound was diminished at the apex and was followed by a grade 5/6 pansystolic murmur. A soft third sound gallop was audible. There were no other abnormal physical findings and, in particular, no peripheral signs of infective endocarditis. Her hemoglobin value was 10.8 g/dl and the erythrocyte sedimentation rate was 43 mm/h. The erythrocytes were normochromic and the leukocyte count and re¬ sults of urinalysis were normal. After drawing a blood sample for cul¬ ture her family physician strongly advised

her to be admitted for investigation. She elected to go home but returned several days later because of persistence of symp¬ toms. An organism resembling S. viridans had been cultured. She agreed to be ad¬ mitted and six further blood samples were drawn for culture over several hours. Therapy with penicillin G, 24 million units/d intravenously, was then started. Within 24 hours her temperature returned to normal and it thereafter remained with¬ in normal limits. The minimal inhibitory concentration (MIC) of penicillin for the S. viridans strain isolated from the initial blood cul¬ ture was 0.08 U/ml and the minimal bac¬ tericidal concentration (MBC) was 0.16 U/ml. Therefore the initial therapy was assumed to be adequate. But 12 days after penicillin therapy was begun the labora¬ tory reported culturing a second strain of S. viridans, more slow growing than the first isolated and somewhat different in colonial morphology. The MIC of peni¬ cillin for this strain was 0.16 U/ml and the MBC more than 10 U/ml. Genta¬ micin, 120 mg/d intravenously in divided doses, was added to the therapeutic regi¬ men, and the dosage was subsequently in¬ creased to 160 mg/d. Two days later the laboratory reported that gentamicin and penicillin G was a more synergistic com¬ bination for this organism than penicillin and streptomycin. This regimen was con¬ tinued for 2 months. Penicillin MICs were determined by adding an inoculum of 0.02 ml containing 105 bacteria to a series of tubes with 1 ml of trypticase soy broth (Baltimore Biological Laboratories) containing twofold dilutions of penicillin, from 0.01 to 10.24 U/ml. Tubes were incubated at 37 °C for 18 hours, then end points were read by the presence or absence of visible growth. MBCs were measured by subculturing to solid media 0.02-ml aliquots from the tubes showing no visible growth; end points were read by the presence or ab-sence of growth after 18 hours' incubation at 37°C. Synergistic bactericidal effects were measured by performing the same test with a constant amount of either 10 fxg/ml of streptomycin or 4 jjig/ml of gentamicin in each of the tubes containing the range of penicillin dilutions. The two isolates of S. viridans were initially believed to be different strains because of differences in colonial mor¬ phology and growth rate; hence antibiotic tests were performed on each separately. Later it was found that a clone of one colony type could give rise to both colo¬ nial forms. Both were of Lancefield group H and gave identical reactions in 20 bio¬ chemical and growth tests used to dif¬ ferentiate subtypes of S. viridans. There¬ fore there appeared to be only one type of bacterium in the initial series of blood cultures, but it gave rise to cells showing

CMA JOURNAL/MAY 17, 1975/VOL. 112 1217

SURMONTIL trim ipram me Dosage-Oral route: ambulatory patients: 50 to 150 mg daily in 2 or 3 doses. Treatment to be initiated at lowest dosage, increased in a few days, then adjusted to lowest level required when response has been obtained. When insomnia is present, a larger portion of the dosage may be given at night. Hospitalized patients: 100 to 300 mg daily in 2 or 3 doses: occasionally up to 400 mg. Contraindications: glaucoma, prostatic hypertrophy, drug-induced CNS depression. Should not be associated with MAO inhibitors: a two-week delay is recommended before using the drug in patients having received an MAO inhibitor. Warnings: warn against engaging in activities requiring alertness until response is established. May potentiate alcohol and CNS depressants. Safety in pregnancy has not yet been established. Precautions: in elderly patients, in patients with cardiovascular problems or In those with a history of convulsive disorders: start treatment by the oral route with low doses, progressively increased - in ambulatory psychotic patients, if the drug aggravates psychotic manifestations or induces manic episodes: reduce dosage or discontinue therapy-in seriously depressed patients, because of the possibility of suicide at the beginning of treatment, close supervision should be exercised. Adverse reactions: the following have been reported: excitement, confusion, drowsiness (during initial therapy), Insomnia, tremor, dystonia, epileptic seizures, dry mouth, blurred vision, urinary retention, constipation, nausea and vomiting, palpitations, orthostatic hypotension, qulnidine-like reactions, changes in libido, weight gain, sidn rash, obstructive jaundice. Supply: tablets: 12.5, 25, 50 and 100 mg, bottles of 50 and 500. References: 1. KRISTOF, F. E., et at.: Systematic studiea with trimtpramine-a new antidepressive drug. Can. Psychtat. Assoc. J. 12:517-520, (Oct.) 1967. 2. DuNLEAvY, D. L. F., at at.: Changes during weeks in effects of tricyctic drugs on the human steeping brain. Brit. J. Psychiat. 120:683672, 1972. 3. MARSHALL, B.: The treatment of depression in general practice by a stngte-dose schedute. Practitioner, 206, 806-810, June 1971. 4. HUSSAtN, M. Z. and CHAUDHRY, Z. A.: Singte versus divided daity dose of trimipramine in the treatment of depressive titnesa. Amer. J. Psychiat., 130, (10), 1142-44, Oct. 1973.

Full information upon request.

Pouienc .

considerable variation in biologic properties. A third isolate of S. viridans was cultured I month after the patient's admission. It was of Lancefield group L and, unlike the other two isolates, grew on 40% bile agar and failed to ferment trehalose. This strain was tested in the same manner for its penicillin MIC and MBC, alone and in the presence of streptomycin or gentamicin. In addition, the bactericidal effects of 10 U of penicillin, 8 p.g of ampicillin, 10 .u.g of cephaloridine, 10 p.g of cephalothin and 10 .tg of vancomycin, each alone and in combination with (separately) 8 .ag of kanamycin, 10 1Lg of streptomycin and 4 .g of gentamicin, were determined. The broth used, the inoculum, the volume of samples and the incubation temperature were the same, but* samples were taken after 4 and 18 hours' incubation. The percentages of bacteria surviving were calculated. The penicillin-gentamicin combination was fully bactericidal and was therefore continued until the patient's discharge. Discussion Although there are reports of mitral valvular endocarditis in patients with Marfan's syndrome,5'6 and of infective endocarditis due to more than one organism (mixed infection),7 we have not found any report of a strain of S. yindans with such striking variation in both morphologic characteristics and penicillin sensitivity. We cannot tell whether the organism isolated 1 month after the patient's admission was involved in the infection, but the chances of it being a skin contaminant seem remote. The colonies of the first two isolates differed in growth rate, morphologic characteristics and sensitivity to penicillin G, showing the heterogeneity of this organism. It is possible that this case would have represented a treatment failure at the end of the course of penicillin had not further studies on the organism been performed throughout the period of treatment. Clearly it is essential to repeat cultures and antimicrobial sensitivity tests in treating patients with infective endocarditis. We thank Dr. I.B.R. Duncan for carrying out the bacteriologic investigation and for his advice on the interpretation of the results and in the preparation of this report. References 1. HARRisoN TR: Principles of Internal Medicine, seventh ed, New York, McGraw, 1974 2. KAYE D: Changes in the spectrum, diagnosis and management of bacterial and fungal endocarditis. Med Clin North Am 57: 941, 1973 3. CONN HE: Current Therapy. Toronto, Saunders, 1974 4. HURST 1W: The Heart, third ed. New York McGraw, 1974 5. WuNscsi CM, STEINMETZ EF, FsscH C: Marfan's syndrome and subacute bacterial endocarditis. Am I Cardiol 15: 102, 1965 6. BowEls D, LIM DW: Subacute bacterial endocarditis and Marfan's syndrome. Can Med Assoc 1 86: 455, 1962 7. FINLAND M, BARNES MW: Changing etiology of bacterial endocarditis in the antibacterial era. Experiences at Boston City Hospital 1933-1965. Ann Intern Med 72: 341, 1970

POSTGRADUATE COURSES continued from page 1214 ANTIHYPERTENSIVE DRUGS. Stratford, Ont. Aug. 13, 1975. Information: Ontario Medical Foundation. 242 St. George St., Toronto, Ont. M5R 2P4 SYMPOSIUM SUR LES PROGRES RECENTS EN RECHERCHE MORPHOLOGIOIA. Universite de Montr4al. Lea 17-22 ao0t 1975. Promoteur: Association panam.rIcaine danatomie. Renseignements: Dr Pierre Jean, D.partement danatomle, Universit. de Montreal, CP 6207, Succursale A, Montr6al, Ou.. H3C 3T7 CUSEC. University of Ottawa. Aug. 18-29, 1975. Sponsored by the bureau of epidemiology of Health and Welfare Canada and the department of epidemiology and community medicine, University of Ottawa. Information: Dr. J. W. Davies, Director, Bureau of epidemiology. Laboratory centre for disease control. 200 Isabella, Ottawa, Ont. KiA 1B7 INTRAOCULAR LENS IMPLANT COURSE. University of Manitoba. Oct. 31 and Nov. 1, 1975. For ophthalmic surgeons. Information: Dr. Gordon M. Krolman, Department of ophthalmology, University of Manitoba medical college, Winnipeg, Man. R3E 0W3 RECENT DEVELOPMENTS IN HYPERTENSION. Conference Hall, Mount St. Joseph's Hospital, Vancouver. Sept. 2, 1975. Sponsored by the College of Family Physicians of Canada. Information: Dr. F. Ho, 3140 Main St., Vancouver, BC V5T 3G7 LAKEHEAD SUMMER SCHOOL. Lakehead University. Sept. 3-6, 1975. Sponsored by Ontario Medical Association and Thunder Bay Medical Society. Information: Dr. D. R. Henderson, Department of radiology, McKeIlar General Hospital, Thunder Bay, Ont. P7E 1G6 SURGERY IN THE ELDERLY PATIENT. St. Joseph's Hospital, London. Sept. 10, 1975. Sponsored by department of surgery, St. Joseph's Hospital. Information: Dr. A. T. Hunter, Continuing medical education, Faculty of medicine, University of Western Ontario, London, Ont. N6A 3K7 MANAGEMENT OF BURNS. Peterorough, Ont. Sept. 10, 1975. InformatIon: Ontario Medical Foundation, 242 St. George St., Toronto, Ont. M5R 2P4 CLINICAL RESPIROLOGY. University of Calgary Health Sciences Centre, Sept. 10-12, 1975. Information: Division of Continuing Medical Education, University of Calgary, Calgary, Alta. T2N 1 N4 ANESTHESIA. Sir Charles Tupper Medical Building, Daihousie University, Halifax. Sept. 11-13, 1975. Sponsored y Daihousle University and the Nova Scotia division of the Canadian Ansesthetics Society. Information: Dr. M. R. Clark, Division of continuing medical education, Daihousie University, Halifax, NS PEDIATRICS. James Paton Memorial Hospital, Gander, Nf Id. Sept. 12-13, 1975. Information: Continuing medical education office, Memorial University of Newfoundland, St. John's, Nf Id. CENTENNIAL PEDIATRIC RADIOLOGY SEMINAR. The Hospital for Sick Children, Toronto. Sept. 1518, 1975. Information: Dr. B. J. Reilly, Department of radiology, The Hospital for Sick Children, 555 University Ave., Toronto, Ont. M5G 1X8 MANAGEMENT OF INFERTILITY. Conference Hall, Mount St. Joseph's Hospital, Vancouver. Sept. 16. 1975. Sponsored by the College of Family Physicians of Canada. Information: Dr. F. Ho, 3140 Main St., Vancouver, BC VST 3G7 CARDIOLOGY. Royal Victoria Hospital, Montr6al. Sept. 17-19, 1975. Information: Secretary, Postgraduate board, RVH, 687 Pine Ave. W, Montr6al, Ou.. H3A IAl

Errata We regret that owing to an oversight in the layout of the May 3, 1975 issue of the Journal the masthead page was omitted. We apologize for any inconvenience this error may have caused the readers. In the final stage of production of the April 19, 1975 issue of the Journal, Figs. 1 and 2 of the article "Emergency department use at two Hamilton hospitals" by Vayda, Gent and Hendershot were transposed; the legends therefore apply to the wrong maps.

CMA JOURNAL/MAY 17, 1975/VOL. 112 1219

The heterogeneity of Streptococcus viridans: therapeutic considerations in infective endocarditis.

A 24-year-old woman with Marfan's syndrome and mitral regurgitation had clinical features suggestive of infective endocarditis. The causative organism...
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