Cervicofacial Actinomyces viscosus infection

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Table I. Age distribution of patients with Shigella enteritis

Age Patients

12yrlJyr14yrl yr1612 r

O-lmol2-Jmole-rmol7mo-lyr[13-23mo

Total No. (948) Fatalities (254)

17 9

52 25

98 41

196 72

199 58

109 28

71 7

50 6

47 4

109 4

Table II. Clinical and bacteriologic features of patients with Shigella septicemia

Age l 2 yr 3 wk 20 mo 1 yr 1 mo 15 mo 2 yr 18 mo 5 mo 1 yr 6 mo

Nutrition Kwashiorkor Marasmus Marasmus Marasmus Marasmus Kwashiorkor Marasmus Satisfactory Kwashiorkor Satisfactory Marasmus

Other ihfections

[

Bronchopneumonia Bronchopneumonia Bronchopneumonia Bronchopneumonia Viral pneumonia, salmonellosis Bronchopneumonia, salmonellosis Bronchopneumonia

Shigellosis in adults is usually a relatively innocuous disease with low mortality. However, fatalities and complications such as septicemia or intussusception may occur in malnourished or debilitated children.

REFERENCES 1. Faucon R, and Ducloux M: Septicemies a Shigella, M~d Trop 24:537, 1964. 2. Henson M: Bacillary dysentery with bacteremia, Am J Med Technol 22:179, 1956. 3. Tatham P, Pearse Williams T, and Stewart GT: Bacillaemia due to Shigella sonnei. Report of a case, Lancet 1:997, 1951. 4. Winter BV, and Harding HB: Shigella sonnei bacteremia, JAMA 180:927, 1962. 5. Johnston RB, and Sell SH: Septicemia in infants and children, Pediatrics 34:473, 1964. 6. Whitfield C, and Humphries JM: Meningitis and septice-

7.

8. 9. 10. l l. 12.

Blood culture

Stool culture

S. flexneri S. flexneri S. dysenteriae S. sonnet S. flexneri S. flexneri S. flexneri S. flexneri S. flexneri S. flexneri S. sonnet

S. flexneri S. flexneri S. dysenteriae -

S. flexneri S, flexneri S. flexneri S. flexneri S. sonnei

Outcome . Recovered Died Died Recovered Died Died Recovered Recovered Died Recovered Recovered

mia due to Shigellae in a newborn infant, J PEDIATR71:805, 1967. Kraybill EN, and Controni G: Septicemia and enterocolitis due to Shigella sonnei in a newborn infant, Pediatrics 42:529, 1968. Moore EEM: Shigella sonnei septicaemia in a neonate, Br Med J 1:22, 1974. Spiers ASD: Shigella sonnei septicaemia in a child with acute monocytic leukaemia, Br Med J 1:456, 1974. Barrett-Connor E, and Connor JD: Shigella boydii bacteremia, J PEDIATR75:298, 1969. Levin SE: Shigella septicemia in the newborn infant, J PEDIATR71:917, 1967. Smythe PM, Schonland M, Brereton-Stiles GG, Coovadia HM, Grace HJ, Loening WEK, Mafoyane A, and Vos GH: Thymolymphatic deficiency and depression of cellmediated immunity in protein-calorie malnutrition, Lancet 2:939, 1971.

Cervicofacial Actinomyces viscosus infection John Larsen, M.D., Edward J. Bottone, Ph.D.,* Steven Dikman, M.D., and Richard Saphir, M.D.,

New York, N. Y.

From the Departments of Pediatrics, Microbiology, and Pathology, Mount Sinai School of Medicine and the Mount Sinai Hospital *Reprint address: Department of Microbiology, Mount Sinai Hospital New York, NY 10029.

0022-3476/78/110797 + 05500.50/0 © 1978 The C. V. Mosby Co.

ACTINOMYCOSIS is an u n c o m m o n chronic bacterial infection characterized by abscesses and sinus tract formation which involve the cervicofacial, thoracic, or abdominal regions. Actinomyces israelii is the most

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Brief clinical and laboratory observations

The Journal of Pediatrics November 1978

Fig. 1. Actinomycotic sulfur granule in resected tissue surrounded by acute inflammation. (Original magnification x 800.) prevalent etiologic agent, with occasional instances of human disease attributed to other species. Cervicofacial actinomycosis, the most c o m m o n clinical form of infection, is seldom encountered in pediatric patients. 1 We describe a patient with cervical infection that was unusual because of retropharyngeal and possible thyroid involvement, and because the species isolated, Actinomyces viscosus, is a seldom encountered etiologic agent of h u m a n actinomycosis. CASE R E P O R T Patient P.K., an 8-year-old white boy, presented with fever and a cervical mass. One week prior to admission, he developed a sore throat and fever to 102°F. A physician noted slight swelling of the neck; pharyngitis was diagnosed and the patient was treated with ampicillin. Neck swelling progressed and the patient developed head tilt to the left. There was no history of recent trauma or dental work. A thyroid scan showed decreased uptake and posterior displacement of the left upper pole; it could not be determined whether the process was intra- or extrathyroid. On 12/28/76, the patient was admitted to The Mount Sinai Hospital where a 4 x 6 cm, firm, smooth, warm, nontender mass was found in the left anterior cervical triangle. The remainder of

the physical examination was normal. The erythrocyte sedimentation rate was 55 mm/hour; the hemoglobin was 12.6 gm/dl, the white blood cell count was 6,400/mm 3 with 52% segmented forms, 2% bands, 44% lymphocytes, and 2% monocytes. Thyroxine by radioimmunoassay was 13.2 btg/dl (nl 4.5-13.5 #g/d 0 and tri-iodothyronine uptake was 0.93 (hi 0.85-1.15). Antistreptolysin 0 titer was 400 Todd units and C-reactive protein was recorded as 1 +. A lateral radiograph of the neck disclosed a retropharyngeal mass but an esophagram was normal. Culture of the nasopharynx and throat showed Staphylococcus aureus and a viridans streptococcus, respectively. Blood cultures were sterile. Acute suppurative thyroiditis with cervical adenitis was diagnosed, and the patient was treated for two weeks with oxacillin 200 mg/kg/24 hours and ampicillin 200 mg/kg/24 hours intravenously. There was a good clinical response with shrinkage of the mass and return of the sedimentation rate to normal. He was discharged and subsequently treated with a several week course of ampicillin and oxacillin orally. Three months following admission, the thyroid was normal. The patient was well until 7/5/77 when a nontender mass was detected in the lateral aspect of the midthird of the left lobe of the thyroid. The patient was asymptomatic and afebrile. The white blood cell count and urinalysis were normal. Surgical exploration of the neck showed an indurated area which involved the

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Fig. 2. Brown and Brenn stain of sulfur granule showing gram-positive filamentous branching organisms. sternomastoid and strap muscles. The thyroid gland appeared to be uninvolved. The resected specimen consisted of a 1.8 x 1.4 x 1.5 cm fragment of rubbery, irregular, brown to gray-tan tissue with a soft central yellow area of necrosis. Microscopic examination revealed fibrous tissue, fat, and skeletal muscle, showing extensive acute and chronic inflammation. A confluent area of suppuration contained a large colony of tangled, branching, filamentous organisms with an irregular, fuzzy eosinophilic periphery (Fig. 1). Brown and Brenn stain revealed masses of gram-positive filamentous forms (Fig. 2). The organism failed to stain by the acid-fast method. A diagnosis of actinomycosis was made and the patient was treated orally with phenoxymethyl penicillin, one gram daily for a total of six months. He has remained clinically well without recurrence of the neck mass. BACTERIOLOGY Gram-stained touch prints prepared from the surgically removed mass showed very few gram-positive filaments with terminal bifurcations and, occasionally, swollen ends. Branching and intertwining filaments typical of Actinomyces were rare. The excised mass was inoculated onto duplicate sets of 5% sheep blood, trypticase soy, and chocolate agars by

placing a section of the tissue onto the medium and dragging it across the agar surface. The specimen was then placed into thioglycolate broth supplemented with menadione and hemin. One set of Petri dishes was incubated at 37°C in an anaerobic environment containing COs (GasPak, BBL); the second was maintained at 37°C in an atmosphere of 10% COs. Four days after inoculation, two white, smooth, slightly raised colonies were observed on blood agar incubated anaerobically. Examination of these colonies under 100 x magnification did not reveal the "spider" morphology frequently noted with Actinomyces israelii. Instead, the colonies were composed of fragmented, diphtheroid-like organisms and filamentous forms. Gram-stained smears prepared from these colonies showed gram-positive filamentous branching bacilli. Subculture of these colonies to blood and trypticase soy agars produced, after three days incubation at 37°C, scant growth under aerobic conditions, good growth in 10% COs, and less abundant growth anaerobically with COs. In thioglycolate broth, growth occurred in the form of discrete granules about I cm beneath the liquid surface, and extended downward for approximately 2 cm. Direct

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The Journal of Pediatrics November 1978

Brief clinical and laboratory observations

phase contrast microscopic examination (400x) of a crushed granule showed intense filamentation and branching with clubbed ends radiating from a dense central core. This morphology bore a strong resemblance to that of the "sulfur granule" noted histologically. The isolate was indole negative but produced catalase, reduced nitrate to nitrites, and fermented glucose, maltose, sucrose, trehalose, lactose, and raffinose. Acidification of the latter two substrates was particularly useful in distinguishing the isolate from the morphologically similar Rothia dentocariosa and Propionibacterium aches. Salicin and mannitol were not fermented. Based on the observed morphologic, cultural, and biochemical characteristics, the isolate was identified as Actinomyces viscosus and confirmed by M. Weisburd of the New York City Department of Health Laboratories. In vitro susceptibility studies performed by the twotube broth dilution method s showed the isolate to be inhibited by ampicillin (5 Fg/ml), cephalothin (7.5 Fg/ ml), chloramphenicol (7.5 Fg/ml), clindamycin (1 Fg/ml), erythromycin (1 #g/ml, oxacillin (5/~g/ml), penicillin (1 unit/ml), tetracycline (2 Fg/ml), and vancomycin (5 Fg/ml), and resistant to gentamicin (10 ~tg/ml), kanamycin (10 /~g/ml), and sulfadiazine (I00 Fg/ml). By the disc-agar infusion method, the isolate was resistant to a combination (1:19) of trimethoprim-sulfamethoxazole. DISCUSSION Members of the genus A ctinomyces are characterized as gram-positive, branching, filamentous, anaerobic-tomicroaerophilic microorganisms. These species contain cell wall constituents (i.e. muramic acid), found in bacterial cell walls and are susceptible to a variety of antibiotics. They are therefore considered bacteria rather than fungi. Human infections associated with A. viscosus have been reported on three previous occasions. In one instance, recovery was from a chest wall mass in a 35-year-old patient with concomitant pulmonary tuberculosis~; the second was an infected branchial cleft cyst in a 19year-old male,' and the third was a patient with endocarditis and a dental abscess. 5 A probable fourth patient was a 24-year-old woman who had actinomycotic involvement of the thyroid gland. 9 In this last instance, the filamentous organism recovered from culture of surgically drained purulent exudate was identified as A. naeslundii. However, the isolate was catalase positive, a property which today would have identified the organism as A. viscoSldS. r

The filamentous branched isolate from the present patient also produced catalase. As this feature is not encountered among other more commonly occurring

Actinomyces species, it is seldom appreciated as a diagnostic characteristic for A. viscosus. In our patient, because of catalase activity, initial identification tended toward either Propionibacteriurn aches ("anaerobic diphtheroid"), or possibly Rothia dentocariosa. With either of these possibilities, the isolate could have been judged a contaminant introduced from skin (P. aches) or the oropharynx (R. dentocariosa) at the time of surgery, and discarded. The possibility also existed that the catalase-positive isolate could have been a Nocardia species. However, lack of "acid-fastness" or aerobic growth, as well as absence of growth on Sabouraud medium, pigmentation, and aerial hyphae, precluded such an identification. Thyroid involvement is rare in cervicofacial actinomycosis. In our patient, physical examination and thyroid scan suggested thyroid involvement but, at surgery, the gland appeared to be uninvolved. The recovery of what was probably A. viscosus from a patient with suppurative thyroiditis ~ may indicate a propensity of A. viscosus to invade the thyroid. Actinomyces viscosus is part of the human periodontal plaque flora 8 and it is reasonable to assume that A. viscosus infections extend from an oral focus. Such a conclusion is strengthened by the report of a patient with A. viscosus endocarditis and a concomitant dental abscess due to the same species. A. viscosus has been shown to be pathogenic for laboratory animals and to induce, in vivo, cell-mediated 9 and acute inflammatory responses. TM Actinornyces induce an acute and chronic inflammatory response associated with extensive fibrosis, within which the organism coalesces into dense, tangled colonies ("sulphur granules"). This sequestered characteristic mandates the approach to chemotherapy, which is intense and prolonged. Our patient might have relapsed, because an abscess had formed and prevented adequate penetration of antibiotics to the site of infection; surgical removal of the abscess, in conjunction with prolonged pencillin therapy, has apparently eradicated the infection. Penicillin is the recommended antimicrobial agent against the various species of Actinomyces, including A. viscosus, as judged from the present and previously reported instances? This case illustrates the potential difficulties in therapy when the causative organism of a cervical adenitis or suppurative thyroiditis is not identified by needle aspiration or surgical biopsy: REFERENCES

1. Drake DP, and Holt RJ: Childhood actinomycosis-report of three recent cases, Arch Dis Child 51:979, 1976. 2. Schneierson SS, and Amsterdam D: A simplified tube procedure for the routine determination of bacterial sensitivity to antibiotics, Am J Clin Pathol 31:81, 1959.

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3. Lewis R, and Gorbach S: Actinomyces viscosus in man, Lancet 1:641, 1972. 4. Adeniyi-Jones C, Menielly JA, and Matthews WR: Actinomyces viscosus in a branchial cyst, J Clin Pathol 60:711, 1973. 5. Gutschik E: Endocarditis caused by Actinomyces viscosus, Scand J Infect Dis 8:271, 1976. 6. Leers WD, Dussault J, Mullens JE, and Volpe R: Suppurative thyroiditis: An unusual case caused by Actinomyces naeslundi, Can Med Assoc J 101:56, 1969. 7. Georg LK, Pine L, and Gerencser MA: Actinomyces visco-

80 1

sus, comb. nov., a catalase positive, facultative member of the genus Actinomyces, Int J Syst Bacteriol 19:291, 1969. 8. Gerencser MA, and Slacik JM: Identification Of human strains of Actinomyces viscosus, Appl Microbiol 18:80, 1969. 9. Turner OW, Robertson BS, and Langton RW: Cellmediated immune response to products of Actinomyces viscosus cultures, Infect Immun 14:372, 1976. 10. Engel D, VanEpps D, and Clagett J: In vivo and in vitro studies on possible pathogenic mechanism of Actinomyces viscosus, Infect Immun 14:548, 1976.

Intravenous infusion of diazoxide in the treatment of

chlorpropamide-inducedhypoglycemia Richard F. Jacobs, M.D.,* Richard A. Nix, M.D., Thomas E. Paulus, M.D., Ernest A. Kiel, M.D., and Robert H. Fiser, Jr., M.D., Little Rock, Ark.

CHLORPROPAMIDE OVERDOSE may cause prolonged and even fatal hypoglycemia with cardiac arrhythmias, seizures, and coma? Chlorpropamide produces the most prolonged hypoglycemia of the oral agents that stimulate insulin release. ~ The peak plasma concentration is observed at 39 hours, with a half-life of approximately 72 hours. Because of such a long half-life, close monitoring of blood glucose, electrolyte values, and cardiac function for a m i n i m u m of five days is suggested following ingestion of chlorpropamide? The intravenous use of glucose solution may not be sufficient to resolve symptoms and establish normal blood sugar concentrations. Other treatment may be needed to (1) block peripheral insulin effects on glucose utilization, (2) inhibit insulin secretion, or (3) increase endogenous glucose production. An optimal treatment would be to block pancreatic insulin secretion with an "insulin antagonist," the effect of which would not be overcome by glucose stimulation of a "sulfonylurea-primed pancreatic beta cell. ''~ Diazoxide is known to have hyperglycemic properties and has been used in children with insulin-secreting tumors? The pharmacologic effects are felt to be due to blockage of insulin secretion and possibly to an extrapancreatic metabolite that stimulates hyperglycemia. Because diazoxide has been reported to be of use in adults, 2 we From the Department of Pediatrics, University of Arkansas for Medical Sciences. *Reprint address: Department of Pediatrics, University of Arkansas for Medical Sciences, 4301 West Markham St., Little Rock, AR 72201.

0022-3476/78/110801 +03500.30/0 © 1978 The C. V. Mosby Co.

used it in the treatment of a child who had ingested chlorpropamide. CASE R E P O R T

A 9-year-old black boy was admitted to the University Hospital in a comatose state secondarY to chlorpropamide intoxication. Approximately 36 hours prior to admission he had ingested a total of 5 gm of chlorpropamide (Diabinese) and 5 gm of alphamethyldopa with 3 gm of chlorthiazide (Aldochlor). Twenty-four hours prior to admission he was found in a comatose state and was admitted to a local hospital. During the first 12 hours of that admission he would awaken and respond appropriately following intravenous administration of 50% dextrose in water (DsoW). Shortly after eating dinner that evening, the patient had a grand mal seizure and lapsed into a coma, from which he did not respond in spite of repeated doses of the glucose solution. He was then transferred to the University Hospital. The patient arrived at the University Hospital emergency room in a comatose state and was responsive only to painful stimuli (36 hours post-ingestion). On admission the blood glucose concentration was 30 mg/dl and serum potassium was 3.0 mEq/1. An initial intravenous dose of DsoW elevated the blood glucose level tO 156 mg/dl without improving the patient's sensorium. Arterial blood gas values, skull and chest radiographs were normal, as were serum electrolytes with the exception of potassium. An electrocardiogram revealed prominent U-waves without evidence of arrhythmias. Intravenous treatment was begun with 10% dextrose, 0.45% saline (D~o½NS)at 5 mg glucose/kg/minute via a Holter pump with KC1 supplement. Two hours after admission his serum potassium concentration was 2.9 mEq/1 and glucose was 20 mg/dl (Figure). Blood sugar levels were checked hourly (by Dextrostix), and plasma glucose, BUN, and electrolyte values were evaluated everY six hours. The blood glucose levels were very labile during