Systemic Candidiasis in Very Low-Birth-Weight Infants ...

1984;73;138PediatricsDana E. Johnson, Theodore R. Thompson, Thomas P. Green and Patricia Ferrieri

Systemic Candidiasis in Very Low-Birth-Weight Infants (<1,500 Grams)

http://pediatrics.aappublications.org/content/73/2/138

the World Wide Web at: The online version of this article, along with updated information and services, is located on

ISSN: 0031-4005. Online ISSN: 1098-4275.PrintIllinois, 60007. Copyright © 1984 by the American Academy of Pediatrics. All rights reserved.

by the American Academy of Pediatrics, 141 Northwest Point Boulevard, Elk Grove Village,it has been published continuously since 1948. PEDIATRICS is owned, published, and trademarked PEDIATRICS is the official journal of the American Academy of Pediatrics. A monthly publication,

at University of Manchester Library on February 8, 2013pediatrics.aappublications.orgDownloaded from


http://pediatrics.aappublications.org/

138 PEDIATRICS Vol. 73 No. 2 February 1984

Systemic Candidiasis in Very Low-Birth-WeightInfants (<1,500 Grams)

Dana E. Johnson, MD, PhD, Theodore R. Thompson, MD,Thomas P. Green, MD, and Patricia Ferrieri, MD

From the Departments of Pediatrics and Laboratory Medicine and Pathology, University ofMinnesota Medical School, Minneapolis

ABSTRACT. Previous reports in the literature have doc-

umented that systemic infection with Candida albicans

in very premature infants is frequently fatal (54%) orassociated with significant morbidity in survivors (25%).Five patients with a mean birth weight of 829 g had adiagnosis of systemic candidiasis during their stay in anewborn intensive care unit. All infants survived withminimal sequelae following aggressive early treatmentwith amphotericin B and 5-flucytosine. A review of thesefive extremely premature infants and 26 previously re-ported patients suggests the following: (1) disseminatedcandidiasis is common in the absence ofpositive findingsin blood, CSF, and/or urine cultures; (2) transient can-didemia rarely resolves without therapy; (3) meningitisand osteoarthritis occur more frequently than in olderpatients with disseminated disease; and (4) premature

infants tolerate amphotericin B and 5-flucytosine well.Infants who are found to have systemic cultures positivefor candidiasis should be treated by (1) removing allfactors that predispose to systemic candidiasis (eg, in-dwelling catheters, broad-spectrum antibiotics); (2) earlyinitiation of systemic antifungal therapy with amphoter-icin B and 5-flucytosine; and (3) searching for additionalfoci of disease. After the disease is recognized and treat-ment is prompt and aggressive, outcome can be substan-

tially improved. Pediatrics 1984;73:138-143; Candida,

low-birth-weight infants, sepsis, meningitis.

Systemic candidiasis in very premature infants

(<1,500 g birth weight) is a serious infection asso-

ciated with high morbidity and mortality. Little

information is available, however, on the recogni-

tion and treatment of infants at risk for systemic

disease, as no one has detailed the successful treat-

ment of more than one infant. Therefore, it has

Received for publication Feb 22, 1983; accepted May 4, 1983.Reprint requests to (D.E.J.) Box 211, Mayo Memorial Building,University of Minnesota Hospitals, 420 Delaware St SE, Mm-neapolis, MN 55455.

PEDIATRICS (ISSN 0031 4005). Copyright © 1984 by the

American Academy of Pediatrics.

been difficult to develop diagnostic criteria and to

evaluate the type, duration, and complications of

drug therapy in these infants. This report details

the successful clinical management of five ex-

tremely premature infants with a mean birth weight

of 869 g (28 weeks’ gestation) who had a diagnosis

of systemic Candida albicans septicemia while inour newborn intensive care unit. Data from these

patients, plus a review of the literature,118 were

used to develop suggestions for diagnosis and treat-

ment of systemic candidiasis in very immature in-

fants.

PATIENT POPULATION

The five patients (all female) included in the

study were hospitalized in the Newborn Intensive

Care Unit (NICU) at the University of MinnesotaHospitals during the time period from Oct 1, 1980,

through April 1, 1982. Four of the five infants were

cared for in our NICU during their entire postnatal

course. Patient 4 was transferred to our NICU at

138 days of age with right-sided cardiac failure

secondary to a right ventricular fungal mass. Dur-

ing this period of time, 166 infants with a birth

weight <1,500 g were admitted to our NICU. Thefive patients represent a 3% incidence of systemic

candidiasis in infants weighing <1,500 g at birth.The clinical course, positive cultures for Candida

albicans, and treatment for all five of our patients

are shown in Table 1. The infants had severe apneic

spells at the time of their original positive cultures.

All infants had been treated with broad-spectrumantibiotics and had indwelling catheters in place

for central parenteral nutrition prior to the docu-

mentation of Candida infection. Patients 2, 4, and

5 had additional factors that have been associated

with systemic invasion by the organism. Patient 2,whose body surfaces were colonized with C albicans

at birth, had an iatrogenic esophageal perforation



and she is the only known survivor of this entitywith a birth weight <1,500 g.’6 She had numerousnegative systemic cultures (blood, CSF, and urine)documented prior to the onset of her septicemia at therapy.

ARTICLES 139

TABLE 1. Clinical Data*

Patient Birth Gesta- Neonatal Problems Antibiotics Umbilical LinesNo. Weight (g) tional -

A e Drug Day Arte- Venous(wk) rial(d) (d)

- 1 680 26 Pulmonary insufficiency of prematurity, apneic and A 1-7bradycardic episodes, retrolental fibroplasia G 1-7 1-7 1-7

(mild)

2 1,137 28 Hyaline membrane disease, esophageal perforation, A 1-15periventricular hemorrhage, retrolental fibropla- G 1-15 1-15 1-15sia (mild)

3 730 29 Transient tachypnea, apneic and bradycardic spells, A 1-3periventricular hemorrhage G 1-3 . . . 1-12

4 920 30 Transient tachypnea, jejunal atresia, intraventricu- A 2-5,lar hemorrhage, posthemorrhagic hydrocephalus, 20-30,developmental delay 92-95,

100-110 . . . 1-20G 2-5,

20-30,92-95

5 880 26 Congenital cutaneous candidiasis, hyaline mem- A 1-14,brane disease, enterococcal sepsis, periventricular 27-33hemorrhage, retrolental fibroplasia (moderate) G 1-14,

27-33 1-17 1-30

* Abbreviations used are: A, ampicillin sodium; G, gentamicin sulfate.

TABLE 2. Positive Cultures, Drug Sensitivities, and Treatment of Patients

Patient Cultures Positive for Candida aibicans Minimal Inhibi- Oral Nysta- TreatmentNo. (Day of Life) tory Concentra- tin (d)

tions (�tg/mL)

Skin Blood Catheter CSF Urine Eye Ampho- 5-Flucy-ten- tosine

cm B

1 5, 7 6, 7 0.15 0.05 1-67 Amphotericin B, 13 mg/kg, days 6-33;5-flucytosine, 125 mg/kg/d, days 6-

47

2 3 13-18 . . . . . . 15, 16 . . . 0.33 0.20 1-65 Amphotericin B, 13 mg/kg, days 14-31; 5-flucytosine, 50 mg/kg/d, days14-49

3 . . . 12 12 13* 0.15 0.1 1-44 Amphotericin B, 14 mg/kg, days 13-43; 5-flucytosine, 100 mg/kg/d, days13-55

4t . . . 20, 92 . . . 0.15 0.8 137-178 Amphotericin B, 38 mg/kg, days 137-232; 5-flucytosine, 125-150 mg/kg/d, days 137-232

5:1: 1 30-33 30 . . . 30 60 0.25 0.12 1-101 Amphotericin B, 34 mg/kg, days 31-101; 5-flucytosine, 100-125 mg/kg/d, days 31-101

* Culture negative, but increased CSF protein, decreased glucose, elevated WBC count.

1� Fungal mass removed from right side of heart on day 140 was positive for C albicans.

:1:Right atrial fungal mass documented by ultrasound on day 33; removed on day 58.

shortly after birth. Patient 4 had jejunal atresiarequiring corrective surgery at 5 days of age. Patient5 was born with congenital cutaneous candidiasis,

1 month of age. Two infants (patients 4 and 5)

developed right-sided intracardiac fungal masses,an unusual complication of systemic candidiasis,which we have previously reported’9 in another

infant. Both patients were treated by surgical re-moval of the masses, as well as systemic antifungal



140 CANDIDIASIS IN PRFMATURE INFANTS

A tabulation of positive cultures, drug sensitivi-ties, and antifungal drug treatment protocols is

given in Table 2. In patients 1, 2, 3, and 5, ampho-

tericin B (0.1 mg/kg/d, intravenously [IV]) and 5-

flucytosine (50 to 150 mg/kg/d, orally) were begun

within 24 hours of the first positive blood culture.

In patient 4, blood cultures grew C albicans on day

20 and day 92 of life. Because these cultures were

felt to be contaminants, treatment was withheld.

On day 136, the recognition of congestive heartfailure prompted echocardiographic examination,

which revealed a fungal mass in the right ventric-

ular outflow tract. On the basis ofprevious cultures,

antifungal therapy was begun, and patient 4 was

transferred to our hospital. In all five patients,amphotericin B therapy was continued to a total

dose of 13 to 38 mg/kg, during a period ranging

from 17 to 95 days. All infants continued to betreated with 5-flucytosine during amphotericin B

therapy. Decreased urine output, azotemia, leuko-

penia, thrombocytopenia, and elevated levels ofliver enzyme were not observed. Hypokalemia and

acidemia were observed in patient 3, but resolvedwith a 24-hour decrease ofthe amphotericin B dose.

Serum 5-flucytosine assays were performed dur-ing treatment of patients 2 (n = 1) and 5 (n = 9).

When doses were normalized to 25 mg/kg per dose

for comparison, mean levels at a steady state were

57 ± 10 �g/ml. No statistically significant differ-

ence existed among levels drawn at 1 (n = 3), 2 (n

= 4), and 3 (n = 3) hours. No � data could be

extracted. Drug clearance based on average steady-state levels was calculated to be 1.2 mL/kg/min. In

patient 3, one CSF level of 43 1�g/mL was obtained

three hours following a 25-mg/kg oral dose. Noserum drug concentration monitoring for ampho-

tericin B was performed.

All five patients recovered and have been fol-lowed sequentially for periods ranging from 4months to 2 years. They appear to have no sequelae

directly related to their infection, with the excep-tion of patient 5, who h�s severe scarring of the

anterior chamber of her left eye.

DISCUSSION

Over the past 20 years, 26 cases of postnatallyacquired systemic candidiacis have been reportedin infants with birth weight <1,500 g.’’5 Only 12

of these infants (46%) have survived23’6’#{176}”2’13”5”7;

at least three (25%) ofthese survivors2-7-8 had either

severe mental retardation or hydrocephalus. Whenan additional 14 infants in this birth-weight cate-

gory with congenital candidiasis are included, all of

whom died,16 the mortality for systemic candidiasisin very low-birth-weight infants is 70%.

Numerous factors either predispose to, or are

associated with, systemic candidiasis. Neither an

infant’s microbial defenses nor normal anatomic

barriers (eg, skin, gastrointestinal mucosa) may be

adequate to localize and protect an extremely pre-mature infant from fungal invasion.2#{176}24 Compro-

mise of the gastrointestinal mucosa, from asphyxia,

necrotizing enterocolitis, or surgical proceduresmay allow the systemic invasion of the orga-

nism.23’24 In addition, several common practices innewborn intensive care units, such as insertion ofindwelling catheters, provision of parenteral nutri-

tion, and administration of broad-spectrum anti-

biotics, are associated with an increased risk of

systemic disease.20’22 When all factors are taken

into account, it is understandable that systemic

candidiasis can be a common infection in premature

infants, occurring with an incidence of 3% in our

study and 4% in the study of Baley et al,15 among

infants with birth weight <1,500 g.

The diagnosis of systemic candidiasis in very

small infants can be difficult. In a retrospective

review of the 26 reported patients,”11’13”7 five in-fants (19%) had evidence of disseminated or focal

disease at autopsy, but negative systemic cultures

(urine, blood, and CSF) prior to death. A review of

79 cases revealed a similar statistic (21%) in pa-tients >1 year of age.22 In situations such as these,alternative means of diagnosis, such as gas-liquid

chromatography of the patient’s serum for fungal

components,25 may be a useful technique. However,

systemic disease can exist without this test being

positive.6 Serodiagnosis is not practical in most

situations due to an immature immune responseand the usual rapid progression of untreated diseasein extremely premature infants. Frequent micro-

scopic examination and/or culture of the urine,23 aswell as regular fundoscopic examination’5 in sus-

pect infants, may permit earlier diagnosis becauseofthe predilection for Candida involvement of thesesites.

The discrimination between systemic candidiasisand transient candidemia is important in older

patients, as removal of indwelling catheters and/or

discontinuing broad-spectrum antibodies or ste-

roids has resulted in the resolution of transient

infection in adults.22 This almost assuredly does

not happen in premature infants, who cannot lo-

calize and combat such infections. To our knowl-

edge, there is only one report of candidemia resolv-ing in a small premature infant without treat-

ment . �

Analysis of 31 cases of systemic candidiasis in

infants weighing <1,500 g’�18 (including patients 1

to 5) revealed that CSF (52%), urine (48%), and

blood (45%) are the sites from which positive cul-tures were most commonly obtained. Other sites of



TABLE 3. Course of Therapy for Systemic Candidiasis in 12 Infants with Birth Weight <1,500 Grams

Reference Foci of Infection Treatment

Blood CSF Urine Eye Joint Other Amphotericin B 5-Flucytosine

Total Dose Maxi- Length Dose (mg/ Length(/kg) mum of Time kg/d) of Time

Daily (d) (d)Dose

(mg/kg)

Baley et al’5 x x x x Abscess 15 mg ? ? 150 ?Palmer’2 x X X 10 mg 1.0 10 . . . ...

Svirsky-Fein et al’#{176} X x 40 mg 1.0 40 100 40

Rao and Myers9 x x x x 25 mgt 1.0 39 200 30

Chesney et al7 x x 19 mg 1.0 20 200 120Keller et al6 x x

x3.7 mg* 0.25 16

28mg 0.25 42100* 42100 120

DiLiberti and Hughes3x

x . . . . . .

?t ? 4250_150* 14

150 42This study,

patient No.1 x x 13 mg 0.5 27 125 412 x x 13 mg 0.5 17 50 35

3 x x 14 mg 0.5 30 100 424 x Cardiac 38 mg 1 95 125-150 955 x x x Cardiac 34 mg 0.5 70 100-125 70

* Treatment failure.

t Intrathecal or intraventricular therapy.

ARTICLES 141

involvement documented by culture or postmortemmorphology include bones/joints (26%), eye (23%),

lung (13%), skin abscesses (10%), heart (6%), and

peritoneum (3%). The high percentage of patientswith meningitis and osteoarthritis in infancy has

been noted previously, and is in contrast to findingsin older children and adults who have a 2.5% and

3.7% incidence of involvement at these sites, re-

spectively.22Review of 19 previous case reports on systemic

candidiasis, as well as the five infants in this study,indicate that, aside from the presence of Candida

in the blood, the organisms are commonly found in

more than one deep-seated focus. Sufficient datahave been obtained from these cases and our ownfive patients (a total of 28 cases) to analyze the foci

of infection. In these, 21/28 (75%) turned out to bemultifocal with Candida involvement of more thanone organ system, as listed above. The seven casesof unifocal infection include three cases of osteoar-

thritis,5”#{176} two with meningitis (patients 1, and 3),

two with brain abscess,” one with renal abscess,’3and one case of isolated pulmonary involvement.’

The most effective treatment for disseminated

candidiasis has been amphotericin B and 5-flucy-

tosine. The majority of successfully treated patients(10/12)2.3��b0�15 and all five of our infants weretreated with a combination of these drugs. Onepatient with isolated renal involvement was curedwith nephrectomy a1one.’� One infant was treated

systemically with miconazole,’7 and one infant wastreated with amphotericin B alone.’2 The combi-

nation of amphotericin B and 5-flucytosine appears

to be extremely effective. However, both have been

associated with serious side effects.22 The toxicity

of the drugs, particularly the renal side effects of

amphotericin B, may be one reason why definitivetherapy has often been delayed for premature in-fants with positive systemic cultures.

Although the side effects of amphotericin B area significant problem in older childen and adults,26

the drug has been well tolerated by premature in-

fants. None of 16 reported infants2’6 or our fiveinfants with birth weight <1,500 g who received

amphotericin B suffered any significant toxic ef-

fects. 5-Flucytosine has been reported to cause 5ev-

eral side effects, including blood dyscrasia and he-patic damage.26 These side effects, however, havenever been reported in premature infants receiving

dosages ranging from 50 to 200 mg/kg/d.The clinical data and treatment of 12 infants for

whom sufficient details were present to analyzeantifungal therapy are shown in Table 3. The ma-

jority of these infants were started at low doses (0.1

to 0.25 mg/kg/d) of amphotericin B and graduallyadvanced to a maximum dose of 0.5 to 1.0 mg/kg/

d. Although severe side effects have not as yet beenreported with a maximal daily dose of 1 mg/kg, a

dose of 0.25 to 0.5 mg/kg/d appears to be equallyas effective6 (patients 1, 2, 3, and 5) and may be

better tolerated by extremely ill patients.

Neither the total dosage of amphotericin B nor

the length of time required for successful treatmentof systemic candidiasis in very premature infants



142 CANDIDIASIS IN PREMATURE INFANTS

is known. In evaluating these treatment data, two

groups of infants can be identified. The first group

had evidence of CNS, renal, or ocular involvement,and the second group had evidence of bone, joint,

or cardiac involvement. Although the second groupwas treated with a higher total dose (33 ± 6 mg/kg

V 14 ± 3 mg/kg) for a longer period of time (51 ±

27 days v 21 ± 8 days), these data cannot be easily

translated into recommendations for treatment, be-cause a lower dose of the drug for a shorter period

of time might have been adequate treatment forthese infections.

The intrathecal,5’9 intraventricular,3 intraarticu-lar,5 and intraocular27 injection of amphotericin B

has been reported as adjunctive treatment to sys-

temic administration of the drug.26 However, infec-

tions of the CNS7’5 (patients 1 and 3), skele-

ton,36’9”#{176}and the eye’2”5 (patient 5) can resolvewithout the use of local amphotericin B injection.This is particularly important in the CNS, as pa-resis and blindness have been reported as compli-

cations of intrathecal amphotericin B injection.25Despite the fact that 5-flucytosine has been used

as the only treatment in a number of systemic

fungal infections,26 it perhaps is best used in con-junction with amphotericin B in this age group.

Two infants treated primarily with 5-flucytosine(Table 3) eventually required amphotericin B in

order to eradicate the infections completely.3’6 Al-though the drug has often been continued after the

discontinuation of amphotericin B6’7”#{176}(patient 1),

secondary resistance has developed in patients re-

ceiving 5-flucytosine alone.26’27As with amphotericin B, the optimum daily dose,

total dosage, and length of time of treatment with

5-flucytosine are unknown in this group of infants.The length of treatment has ranged from 30 to 120days, and the daily dosage has ranged from 50 to

200 mg/kg/d (Table 3). Although the pharmacoki-

netic data obtained from our patients are based onan extremely limited population, they point out thattreatment with 100 mg/kg/d given in four equallydivided doses can result in generally adequate ther-

apeutic levels which are well below the level (80 zg/mL) associated with bone marrow and hepatic tox-

icity.26

The primary goal in the management of systemiccandidiasis in very premature infants should beprevention. The use of oral prophylactic nystatin

has been reported as a means oflimiting overgrowthof yeast in the gut, thus preventing systemic inva-sion.23’24’28 Although antifungal prophylaxis has

been effective in a variety of patients at risk forsystemic candidiasis,� four of our five patients had

received oral nystatin from birth, but still developedsystemic disease. As neither toxicity nor primary

and secondary resistance to nystatin has been re-ported in infants,28 its use may be justified; how-ever, its efficacy remains to be demonstrated.

Exposure to factors that predispose to systemic

candidiasis should be minimized. The use of broad-spectrum antibiotics should be limited to specificindications. Indwelling catheters should be usedonly as long as necessary and cared for with fastid-

ious sterile technique. In infants who develop Can-

dida septicemia, indwelling catheters should be re-moved immediately, as they can be a source of

ongoing candidemia. Use of antibiotics should prob-

ably be discontinued, unless there are specific in-dications for continuing therapy, as antibiotics have

been shown to enhance experimental Candida in-fection in laboratory animals.2#{176}

The most important aspect of treatment of fungalsepticemia in extremely premature infants is theearly initiation of systemic antifungal therapy. The

literature, as well as our patient population, dem-onstrates that systemic cultures positive for C al-

bicans must never be ignored. As amphotericin B

and 5-flucytosine are well tolerated when used care-

fully, there is no reason not to initiate therapy

while a comprehensive search is begun for foci ofinfection. Examination of the CSF and skeletal

system is necessary, because premature infants

have a high incidence of meningitis and osteoar-thritis. Infants who have had indwelling right atrial

catheters should have an echocardiogram per-

formed to determine whether a right-sided cardiacfungal mass is present. All of our patients did well,

although all isolates of C albicaris were extremelysensitive to both drugs. Initiation of aggressive

early therapy, combined with elimination of predis-

posing factors, may not guarantee fewer complica-

tions, but the outcome for our patients was sub-

stantially better than has been previously reported.

REFERENCES

1. Emanuel B, Lieberman AD, Goldin M, et al: Pulmonarycandidiasis in the neonatal period. J Pediatr 1962;61:44-52

2. Helmuth WV, Adam PAJ, Sweet AY: The effects of proteinhydrolysate-monosaccharide infusion on low-birth-weightinfants. J Pediatr 1972;81:129-136

3. DiLiberti JH, Hughes RA: Case report. Pediatrics

1975;55:897-8984. Bayer AS, Edwards JE Jr, Seidel JS, et a!: Candida menin-

gitis: Report of seven cases and review of the English liter-ature. Medicine 1976;55:477-486

5. Pittard WB III, Thullen JD, Fanaroff AA: Neonatal septicarthritis. J Pediatr 1976;88:621-624

6. Keller MA, Sellers BB Jr, Melish ME, et al: Systemiccandidiasis in infants. Am J Dis Child 1977;131:1260-1263

7. Chesney PJ, Justman RA, Bogdanowicz WM: Candida men-ingitis in newborn infants: A review and report of combinedamphotericin B-flucytosine therapy. Johns Hopkins Med J1978;142:155-160

8. Brill PW, Winchester P, Krauss AN, et al: Osteomyelitis in

a neonatal intensive care unit. Radiology 1979;131:83-87



ARTICLES 143

9. Rao, HKM, Myers GJ: Candida meningitis in the newborn.South Med J 1979;72:1468-1471

10. Svirsky-Fein 5, Langer L, Milbauer B, et al: Neonatal os-teomyelitis caused by Candida tropicalis: Report oftwo casesand review of the literature. J Bone Joint Surg 1979;61-A:455-459

11. Haruda F, Bergman MA, Headings D: Unrecognized Can-dida brain abscess in infancy: Two cases and a review of the

literature. Johns Hopkins Med J 1980;147:182-18512. Palmer EA: Endogenous Candida endophthalmitis in in-

fants. Am J Ophthalmol 1980;89:388-395

13. Patriquin H, Lebowitz R, Perreault G, et al: Neonatal can-didiasis: Renal and pulmonary manifestations. AJR1980;135:1205-1210

14. Speer ME, Hittner HM, Rudolph AJ: Candida endophthal-mitis: A manifestation of candidiasis in the neonate. SouthMed J 1980;73:1407-1409

15. Baley JE, Annable WL, Kliegman RM: Candida endoph-thalmitis in the premature infant. J Pediatr 1981;98:458-

46116. Johnson DE, Thompson TR, Ferrieri P. Congenital candi-

diasis. Am J Dis Child 1981;135:273-27517. Tuck S: Neonatal systemic candidiasis treated with micon-

azole. Arch Dis Child 1980;55:903-90618. Noe HN, Tonkin ILD: Renal candidiasis in the neonate. J

Urol 1982;127:517-519

19. Johnson DE, Bass JL, Thompson TR, et al: Candida septi-cemia and right atrial mass secondary to umbilical veincatheterization. Am J Dis Child 1981;135:275-277

20. Odds FC: Factors that predispose the host to candidiasis, inCandida and Candidosis. Baltimore, University Park Press,1979, chap 7, pp 75-91

21. Xanthou M, Valassi-Adam E, Kintzonidou E, et al: Phago-cytosis and killing ability of Candida athkans by bloodleucocytes of healthy term and preterm babies. Arch DisChild 1975;50:72-75

22. Odds FC: Acute disseminated candidiasis (Candida septicae-mis), in Candida and Candidosi.s. Baltimore, UniversityPark Press, 1979, chap 22, pp 178-188

23. Stone HH, Kolb LD, Currie CA, et al: Candida sepsis:Pathogenesis and principles of treatment. Ann Surg1974;179:697-711

24. Stone HH, Koib LD, Hoover MB, et a!: ‘Candida’ sepsis:Portals for invasion, tissue filtration, and principles of treat-

ment. Bull Soc mt Chir 1975;34:193-195

25. Marier RL, Milligan E, Fan Y-D: Elevated mannose levelsdetected by gas-liquid chromatography in hydrolysates ofserum from rats and humans with candidiasis. J Clin Micro-biol 1982;16:123-128

26. Odds FC: Antifungal agents and their use, in Candida andCandidosis. Baltimore, University Park Press, 1979, chap

25, pp 228-24427. Hill HR, Mitchell TG, Matsen JM, et al: Recovery from

disseminated candidiasis in a premature neonate. Pediatrics1974;53:748

28. Odds FC: Candida and candidiasis: A prospective view, in

Candida and Candidosi.s. Baltimore, University Park Press,1979, chap 27, pp 247-251

DISTRICT VIII SECTION ON NEONATAL/PERINATAL MEDICINE

The AAP District VIII Section on Perinatal Pediatrics will sponsor the 9thAnnual Conference on Neonatal/Perinatal Medicine at The Lodge at Key-stone, Colorado, on May 25-28, 1984. Contact L. Joseph Butterfield, MD, The

Children’s Hospital, Denver, CO 80218. (303) 861-6509.



1984;73;138PediatricsDana E. Johnson, Theodore R. Thompson, Thomas P. Green and Patricia Ferrieri

Systemic Candidiasis in Very Low-Birth-Weight Infants (<1,500 Grams)

ServicesUpdated Information &

http://pediatrics.aappublications.org/content/73/2/138including high resolution figures, can be found at:

Citations http://pediatrics.aappublications.org/content/73/2/138#related-urls

This article has been cited by 10 HighWire-hosted articles:

Permissions & Licensing

http://pediatrics.aappublications.org/site/misc/Permissions.xhtmlor in its entirety can be found online at: Information about reproducing this article in parts (figures, tables)

Reprints http://pediatrics.aappublications.org/site/misc/reprints.xhtml

Information about ordering reprints can be found online:

Online ISSN: 1098-4275.Copyright © 1984 by the American Academy of Pediatrics. All rights reserved. Print ISSN: 0031-4005. American Academy of Pediatrics, 141 Northwest Point Boulevard, Elk Grove Village, Illinois, 60007.has been published continuously since 1948. PEDIATRICS is owned, published, and trademarked by the PEDIATRICS is the official journal of the American Academy of Pediatrics. A monthly publication, it



http://pediatrics.aappublications.org/content/73/2/138#related-urls

http://pediatrics.aappublications.org/site/misc/Permissions.xhtml

http://pediatrics.aappublications.org/site/misc/reprints.xhtml


Systemic Candidiasis in Very Low-Birth-Weight Infants ...

Documents

Transcript of Systemic Candidiasis in Very Low-Birth-Weight Infants ...