CANDIDA KRUSEI AS A PATHOGEN

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CANDIDA

KRUSEI

AS

A

PATHOGEN

Case

Report

of

an

Unusual

Infection

of the

Tonsils

By

GEORGE

D.

ROOK,

M.D.,

ND DAwn BRAND,

M.D.

New York Cit

ANGENBECK,

reporting

a typical

case

of thrush

in

1839, was the first to describe a

Candida

infection.

Since

then,

many

cases

of Candidiasis,

with

involvement

of skin,

nails, mouth, vagina, bronchi, lungs, meninges, endocardium, bones and joints, have ap-peared in the literature.

Until fairly recently, there

was

chaos in the classification of this genus. The name Mo-nilia had originally been given to an entirely different group of fungi. Conant’ states that

there

are

172 synonyms in the literature for Candida albicans alone. Dodge’s Medical

My-cology,

published in

1935,2

lists one hundred species of Candida in the index. Opinions

have

varied

greatly

concerning

the

criteria

to be

used.

Much

of

the

disorder

may

be

at-tributed to the attempts, following the extensive studies of Castellani, to classify the spe-cies on the basis of slight differences in fermentation. It is now known that carbohydrate

fermentation may vary depending on the conditions under which the test is done.

Further-more,

it has been shown that the complex carbohydrates used by Castellani may in

them-selves vary from sample to sample. Langeron’ has also demonstrated that there may be

latent organisms which under certain conditions appear in apparently pure cultures. Finally,

to compound

the

confusion,

Candida

is frequently

found

in

the

upper

respiratory

tract,

vagina, stools, and on the skin of apparently normal individuals. These organisms cannot

be considered

as pathogenic

in any

particular

case,

unless

there

is some

pathologic

tissue

change and they are isolated repeatedly.

With

some

understanding

of

the

difficulties

in

diagnosis

and

classification

and

the

causes of past errors, mycologists today have reduced the number of species of Candida to

six:

albicans,

Krusei,

parakrusei,

tropicalis,

stellatoidea

and

Guilliermondi.

The

vast

majority

of

clinical

reports,

however,

have

described

cases

caused

by C.

albi-cans. In a thorough review of the literature, few cases definitely attributed to C. Krusei

could

be found.

Carter,4

while

studying

labial

and

vaginal

flora

of two

hundred

pregnant

women,

isolated

C. Krusei

four

times,

but

felt

that

this

species

was

of no clinical

signifi-cance, for the symptomatology and physical findings always associated with

C. albicans

and C. stellatoidea infections were absent. Hopkins’ cultured C. Krusei from a skin lesion

but

stated

that

it probably

was

not

the causative

agent.

Robinson

and

Moss6

reported

on

22

cases

of glossitis

and

perleche

and,

although

C. Krusei

was

isolated

from

the

lips

in one

case,

they

did

not

feel

it to be pathogenic,

for

C. albicans

was grown

from

finger

lesions

in

the same patient. Benham7 reported two cases of colitis and one of pruritis ani where

C.

Krusei was

isolated

from

the

stools.

She

felt

that

the

etiologic

relationship

was

doubtful.

Dodge2

mentioned

a case of purulent

urethritis,

described

by Castellani,

in which

C. Krusei

was cultured from the discharge. He also briefly made note of a patient with a severe

cough in which both C. Krusei and C. tropicalis were isolated from sputum. The final

From the Department of Pediatrics, New York Medical College, Flower and Fifth Avenue Hospi-tals, and the Ear, Nose and Throat Department, Metropolitan Hospital, New York City.

(Received for publication Feb. 10, 1950.)

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report in the literature which mentions C. Krusei is that by Catanei.8 This author described

a special form of glossitis from which he isolated the fungus. He studied 14 cases with

infection of the mouth and found nine were caused by C. albicans.

Conant,i in a personal communication, stated that he had cultured C. Krusei from no case except the one that the authors are now presenting.

CASE HISTORY

J- S., an 11 yr. old Puerto Rican male, was brought to the Outpatient Department because he had had frequent sore throats during the previous 2 mo. He had been seen 3 yr. previously for dermatophy-tosis of the left foot, palms and fingers of both hands. The foot lesion showed evidence of

super-FIG. 1

imposed pyogenic infection with inguinal adenopathy. All the lesions cleared rapidly when treated with magnesium sulphate fomentations and half-strength Whitfield’s ointment. Bacteriologic and

mycologic studies were not made. The year following this first admission he was seen in the Out-patient Department on 3 occasions, each time with what appeared to be a nonspecific hypertrophic

tonsillitis. The past history disclosed nothing else which might be considered as relevant.

Examination revealed, for the first time, whitish patches on both tonsils. There was no fever and lie appeared well. It was thought that he had a follicular tonsillitis. Smear and throat cultures were made and his parents were advised to return the next day.

The smear revealed structures resembling mycelia, many gram positive and negative bacilli, a few

gram positive cocci and a moderate number of spirilla and fusiform bacilli, No yeast-like bodies were seen. The culture grew out N. catarrhalis, alpha and beta streptococci and B. coli. He was not seen

again until 3 wk. later, when he was immediately admitted to the hospital.

Physical examination in the hospital disclosed no abnormality except the throat findings; these,

however, were unusual and striking. There were irregular, elevated, white patches covering most of both tonsils

(

Fig. 1

)

. These patches seemed to be formed by a piled up, creamy exudate. However,

every attempt to remove material for study by scraping with a tongue depressor was unsuccessful

because of the almost stony hardness of the masses, and it was necessary each time to break off small

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The lymph nodes were not enlarged. The liver and spleen were not palpable. The lungs were

clear. There was a short musical apical systolic murmur interpreted as functional.

The initial laboratory studies gave the following results : Throat smear and culture-revealed streptococci in long chains, fusiform bacilli and an unidentified fungus. Blood count-RBC, 5.3

million/cmm., Hgb., 12

gr./100

cc., WBC, 6.3 thousand/cmm. with 70% polymorphonuclears, 25% lymphocytes, 4% monocytes, 1% eosinophiles. Urine-negative. Serology-negative. Tuberculin patch

test-negative. Sheep heterophile test-negative

(

1/28

)

. Sickling-negative. Roentgenogram of the

heart and lungs was normal.

Because of the unusual appearance and long history, a fungus infection was suspected and, when confirmed by the initial culture, a portion of the whitish substance was broken off and mycologic studies were made. Cultures on dextrose, maltose and corn meal agars and dextrose broth showed the

fungus to have the morphologic and fermentative characteristics of C. Krusei. A flat dry growth was

TABLE 1

Penicillin-G crystalline

,

400,000 U. ql2h IM 400,000 U. ql2h IM 500,000 U. ql2h IM

4/7 to 4/14 6/14 to 6/17 7/23 to 8/12

Sodium bicarbonate

2% Aqueous gentlan violet

Mandi’s solution ,

10% Maphs in saline

. 1_ . .

10% Sodiuiernorate in glycerine

2% AueQ , tian violet

20% Bu r ‘Sodium caprylate

4

Strengih opronol

Full strength sopronol

Sat. sol. pot. iodide

Roentgen ray

Gargles 3 times/day

2 times/day locally 2 times/day locally

q2h locally

.

3 times/day locally

3 times/day locally 3 times/day locally

3 times/day locally

10 drops 3 times/day by mouth

100 R.U. to each side of neck once/wk.

4/14 to 4/22

4/24 to 5/10 5/10 to 5/28

5/29 to 6/10

6/11 to 6/17 6/25 to 7/5

7/6 to 8/10 8/11 to 8/12

8/13 to 9/13 9/7 to 9/19

10/19 to 12/17

obtained on Sabouraud’s dextrose agar while the dextrose broth produced a typical wide surface film which continued up the side of tube. The mycelium gave the impression of crossed sticks when grown

in the corn meal agar. On maltose agar there was no production of either acid or gas, both of which are always found when C. albicans grows in this media. A repetition of the tests with a second

specimen gave identical results. Because most texts and articles state that C. Krusei is nonpathogeni, a third specimen was taken from the tonsil and sent to Dr. Norman Conant of Duke University. He’

confirmed the findings of this laboratory.

Immediately after admission, penicillin therapy, 400,000 units every 12 hr., was started and un-tinued for 1 wk. until the initial culture studies were completed. The appearance of the throat was

not changed by this treatment. When a definite diagnosis of Candida infection had been made local applications of 2% aqueous gentian violet were instituted. There was no amelioration after 17

days of this therapy. During the next 2 mo. many drugs were tried which had previously been re-ported in the literature as giving good results when used against mycotic infections of the mucous

membranes ‘(table 1

)

. However at the end of this period the white patches appeared deeper and

more widespread.

The entire course during these 1st 2 mo. of hospitalization had been uneventful, except for a

complaint of right submandibular pain the 54th hospital day. This lasted for only 24 hr., but ex-amination at that time disclosed 2 pea-sized tender lymph nodes in the right submandibular region and 1 nontender node on the left. They had not been present on admission.

However, 1 mo. later, the patient, for the first time since admission, complained of a sore throat,

and his temperature rose to 38.8#{176}C. Penicillin, 400,000 u. every 12 hr., by intramuscular inlection,

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of the throat. It may be noted here that this was the only febrile period during the long

hospitaliza-tion, except for a few hours on the day following the first roentgen treatment.

The entire gamut of older antimycotic drugs having been used with no success, but rather with

some progression of the lesions, it was decided to try one of the new fatty acid preparations. A 20%

buffered solution of sodium caprylate had been used by Keeney’#{176} against resistant C. albicans infec-tions with excellent results. Starting 3#{189}mo. after admission, this preparation was applied to the tonsils and pharyngeal mucosa with cotton applicators 3 times daily. This was the first type of treat-ment to have any effect on the pathologic process, causing a slight retrogression of the lesions.

However, after more than a month of this therapy, it was obvious that there was again slow hut progressive encroachment on the remaining apparently still normal areas of tonsillar tissue.

Following this, a mixture of sodium propionate and sodium caprylate (Sopronol-Wyeth) was

applied in a similar manner with even less success. After a month of this treatment, the major part of the tonsillar tissue had been destroyed by the fungus.

After a short course of potassium iodide by mouth, which had no effect, it was decided to try roentgen therapy.” The patient was given 100 RU to each side of the neck and this was repeated

weekly for 8 wk. After 16 days of roentgen therapy, there was marked improvement, and after the 38th day of treatment, the lesions had almost disappeared. However, on the 45th day of roentgen therapy, a new patch appeared on the tonsil and in the next 10 days grew appreciably.

Therefore, the entire medical therapeutic armamentarium having been exhausted, the boy having been hospitalized for many months, but the growth still as vigorous as ever, a tonsillectomy, which had been rejected on admission, was finally performed. Two days later, after 9 mo. of hospitalization,

the patient was discharged to the follow-up clinic. For these last 2 days and for 2 days prior to the operation, he had been receiving sulfadiazine prophylactically.

The tissue removed at operation was sent to the laboratory, but through an oversight, no culture was made, and only hematoxylineosin stain was used. This technic probably explains why the pathologic

re-port stated that only granulomatous tissue was seen.

Throughout the months of hospitalization, the patient’s general condition had remained good. He

was always up and about, ate well, and took part in all activities. His weight, which had been 6.7 kg. on admission, had increased to 39.5 kg. at the time of discharge.

The patient was last seen in the Outpatient Department approximately 1 yr. after operation.

There had been no recurrence of the fungus infection. He looked very well and had gained 4.1 kg. since discharge from the hospital.

COMMENT

The great preponderance of cases reported due to C. albicans is not the only reason for the widespread belief that this species alone is pathogenic. Attempts to correlate animal ex-periments with clinical infection have also been misleading. C. albicans is the only

or-ganism in this genus which will kill a rabbit when injected intravenously. Recently Meyer

and Ordall2 studied the pathogenicity of Candida for chick embryos. They showed that

C.

albicans and C. stellatoidea killed 100% of the embryos, C. tropicalis caused lesions in 100% but only killed 50%, while C. Krusei and C. parakrusei did not pr’oduce lesions.

However,

of

the

five

cases

of

mycotic

endocarditis,

all

in

drug

addicts,

reported

up

to

date, four have been caused by C. parakrusei.13

That the presented case is a true C. Krusei infection cannot be doubted. Twice, from separate specimens, the laboratory obtained the characteristic growths in Sabouraud’s dex-trose agar and broth, and the ‘

‘crossed

stick’

‘ mycelia on corn meal agar ; twice, attempts

at acid or gas production by fermentation of maltose failed. These characteristics definitely

identified

the

causative agent as C. Krusei and not

C. albicans.

However,

because

of the

frequency of the statement in the medical literature that C. albicans is the only pathogenic

species, this in spite of the authentic reports on steflatoidea and parakrusei infections, an-other part of the specimen was sent to Dr. Norman Conant’s laboratory. Again it was

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Another

common

misconception

is that

Candida

infections,

except

during

the

newborn

period,

are seen

only

in the seriously

ill or debilitated.

The

general

condition

of the patient

reported here was always good. Tumulty and Michael’4 described 18 cases of Candidiasis,

all in well

nourished

soldiers,

otherwise

in good

health.

Lehndorff,15

in his article

“Paral-lergy,”

discussed

the

frequency

of C. albicans

infection

following

serum

sickness

or other

allergic

manifestations.

In

differential

diagnosis

of throat

infections,

Candidiasis

must

also

be considered

along

with

the

more

commonly

seen

conditions,

such

as diphtheria,

hemolytic

streptococcus

and

Vincent’s

infections,

infectious

mononucleosis

and

occasionally

secondary

lues.

lt should

be emphasized

that

the

lesions

presented

themselves

in this

case

as stony

hard,

irregular, grey-white patches. When confronted with pathology of this type, a fungus is

to be suspected, but the exact final diagnosis can only be made by cultures.

Early

surgical

extirpation

is recommended

when

the

lesions

are

localized

to the

tonsils

and

there

is not

an immediate

favorable

response

to antimycotic

therapy.

SuMMARY

A case

of

an

infection

of

the

tonsils

due

to C. Krusei

is presented.

A review

of

the

literature reveals this type of infection as extremely rare.

Almost

all

the

reported

successful

medical

remedies

for

the

treatment

of

Candidiasis

were

tried

without

results.

Permanent

cure

was

obtained

finally

by surgery.

ACKNOWLEDGM ENT

The

authors

are

indebted

to

Dr.

Norman

Conant

of

Duke

University

for

his

kind

assistance

in

confirming

the

identity

of

the

causative

organism

and

to Dr.

H. Marks

of

Goldwater

Memorial

Hospital

for

his

cooperation

in planning

and

carrying

out

the

roent-gen

therapy.

. REFERENCES

I. Conant, N., and others, Manual of Clinical Mycology, Philadelphia, W. B. Saunders Company,

1944.

2. Dodge, C. W., Medical Mycology, St. Louis, C. V. Mosby Company, 1935.

3. Langeron, M., and Guerra, P., Nouvelles recherches de zymologie m#{233}dicale, Ann. de parasitol.

16:429, 1938.

4. Carter, A., Jones, C. P., Ross, R. A., and Thomas, W. L., Vulvovaginal mycosis in pregnancy with relation of symptoms to genera and species of fungi, Am. J. Obst.

&

Gynec. 39:213,

1940.

5. Hopkins, J G., Moniliasis and monilids, Arch. Dermat. & Syph. 25699, 1932.

6. Robinson, L. B., and Moss, M. C., Superficial glossitis and perleche due to monilia albicans, Arch

Dermat. & Syph. 25:644, 1932.

7. Benham, Rhoda W., Certain monilias parasitic on man, J. Infect. Dis. 49: 183, 1931. 8. Catanei, A., Morphologic and biologic characteristics of monilias isolated from humans in Algeria,

Arch. Inst. Pasteur d’Alg#{233}rie23:45,1945.

9.

Conant,

N., Personal communication to the authors.

10. Keeney, L., Sodium caprylate: New and effective treatment for moniliasis of skin and mucous

membrane, Bull. Johns Hopkins Hosp. 78:533, 1946.

I 1. Eloy, L., Mycotic infection of tonsil cleared with x-ray, Monde med., Paris 55: 134, 1945. 12. Meyer, E., and Ordal, Z.

J.,

Pathogenicity of candida species for chick embryo, J. Bact. 52:615,

1946.

-1 3. Cassels, D., and Steiner, P., Mycotic endocarditis, Am. J. Dis. Child. 67: 128, 1944.

14. Tumulty, P., and Michael, M., Jr., Monilia pharyngitis, War Med. 8:167, 1945.

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SPANISH ABSTRACT

La Patogenicidad

de

la Candida

Krusei

Reporte

de

un

Caso

con

una

Infeccion

en

las

Amigdalas

Se reporta un caso de infeccion de las amigdalas causada por Ia Candida Krusei. t’n estudio de Ia literatura medica revel#{243}que este tipo de infeccion es extremadamente raro. Practicamente, todos los

remedios reportados como satisfactorios contra Ia candidiasis fueron tratados en este caso sin resultado

alguno. Finalmente una cura permanente fu#{233}obtenida mediante Ia extirpacion quirurgica de las

amigdalas.

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1950;6;638

Pediatrics

GEORGE D. ROOK and DAVID BRAND

Tonsils

CANDIDA KRUSEI AS A PATHOGEN: Case Report of an Unusual Infection of the

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