Previous Article | Next Article 
Antimicrobial Agents and Chemotherapy, August 1999, p. 1955-1960, Vol. 43, No. 8
0066-4804/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
Safety and Tolerability of Fluconazole in
Children
Vas
Novelli1 and
Helen
Holzel2
Infectious Diseases
Unit1 and Department of Medical
Microbiology,2 Great Ormond Street Hospital
for Children NHS Trust, London, United Kingdom
Received 14 January 1998/Returned for modification 19 April
1998/Accepted 26 May 1999
 |
ABSTRACT |
The safety profile of fluconazole was assessed for 562 children
(ages, 0 to 17 years) comprising 323 males and 239 females. The data
are derived from 12 clinical studies of fluconazole as prophylaxis or
treatment for a variety of fungal infections in predominantly
immunocompromised patients. Most children received multiple doses of
fluconazole in the range of 1 to 12 mg/kg of body weight; a few
received single doses. Administration was mainly by oral suspension or
intravenous injection. Overall, 58 (10.3%) children reported 80 treatment-related side effects. The most common side effects were
associated with the gastrointestinal tract (7.7%) or skin (1.2%).
Self-limiting, treatment-related side effects affecting the liver and
biliary system were reported in three patients (0.5%). Overall, 18 patients (3.2%) discontinued treatment due to side effects, mainly
gastrointestinal symptoms. Dose and age did not appear to influence the
incidence and pattern of side effects. Treatment-related laboratory
abnormalities were uncommon, the most frequent being transient elevated
alanine aminotransferase (4.9%), aspartate aminotransferase (2.7%),
and alkaline phosphatase (2.3%) levels. Although 98.6% of patients
were taking concomitant medications, no clinical or laboratory
interactions were observed. The safety profile of fluconazole was
compared with those of other antifungal agents, mostly oral polyenes,
by using a subset of data from five controlled studies. Side effects
were reported by more patients treated with fluconazole (45 of 382;
11.8%) than by those patients treated with comparable agents (25 of
381; 6.6%); vomiting and diarrhea were the most common events in both
groups. The incidence and type of treatment-related laboratory
abnormalities were similar for the two groups. In conclusion,
fluconazole was well tolerated by the pediatric population, many of
whom were suffering from severe underlying disease and were taking a
variety of concurrent medications. The safety profile of fluconazole in children mirrors the excellent safety profile seen in adults.
| |
INTRODUCTION |
Fluconazole, an orally active
synthetic bis-triazole, is established worldwide as a leading
antifungal agent (13). It has an important role in the
treatment and prophylaxis of fungal infections in immunocompromised
adults (12).
Fluconazole is well tolerated in adult patients, including those who
are seriously ill (21). The safety profile of the drug has
been defined by data from clinical trials involving more than 4,000 adult patients, of whom approximately one-third had AIDS (21a). All patients received fluconazole therapy for at
least 7 days. Overall, 16% experienced treatment-related side effects, most commonly gastrointestinal effects (nausea, 3.7%; abdominal pain,
1.7%; vomiting, 1.7%; diarrhea, 1.5%), headache (1.9%), and skin
rash (1.8%). Side effects did not appear to be correlated with dosage
over a range of 50 to 400 mg daily. Few patients were withdrawn from
the study due to treatment-related side effects or laboratory
abnormalities (1.5 and 1.2%, respectively). Fluconazole had no
consistent effect on patients' biochemical parameters. Although
isolated instances of clinically overt hepatic dysfunction have been
reported in patients with AIDS, fluconazole appears to have less
hepatotoxic potential than other azoles (10, 19). Data from
a prescription-event monitoring study involving more than 15,000 adult
patients have confirmed that fluconazole is well tolerated and is
associated with very few side effects (15, 16).
Opportunistic fungal infections are also an important cause of
morbidity and mortality in immunocompromised children (22, 27). Neutropenia induced by chemotherapy places the pediatric patient at risk of serious fungal infection, most commonly with Candida spp. (22). Mucosal candidiasis is the
most frequent opportunistic infection affecting children with human
immunodeficiency virus (HIV) infection (11).
Fluconazole has recently been approved for pediatric use and shows
promise in the treatment and prophylaxis of fungal infections in
immunocompromised children (4, 5, 9, 14, 18, 20, 26). This
review summarizes pediatric safety data obtained during phase II and
III clinical studies of fluconazole (1, 9, 14, 17, 20, 23,
24).
| |
MATERIALS AND METHODS |
Data were obtained from six pharmacokinetic studies and six
therapeutic studies carried out in Europe, the United States, and
Canada (1, 9, 14, 17, 20, 23, 24). A subset of these data
from five controlled studies was used to compare the safety profile of
fluconazole with those of other antifungal agents (9, 14,
20). Fluconazole was evaluated as prophylaxis or treatment for a
variety of fungal infections, including oropharyngeal candidiasis,
candidemia, and disseminated candidiasis. Many of the patients who were
recruited were immunocompromised, primarily due to chemotherapy,
radiotherapy, HIV infection, or transplantation. Ethics committee
approval and written informed consent of the parents or legal guardians
of the children were obtained. Study details are summarized in Tables
1 and 2.
Side effects were recorded at each clinical assessment
if they were reported spontaneously by the patient or a parent or
guardian of the patient or if they were observed by the investigator.
The relationship to treatment was assessed by the investigator.
Laboratory data were collected at the baseline and were monitored
throughout the study period. In the multiple-dose studies, laboratory
tests were generally repeated at weekly intervals. Since many of the children were seriously ill, the underlying disorder and effects of
concomitant therapy were taken into consideration in the assessment of
the relationship of laboratory abnormalities to treatment.
Fluconazole was evaluated at dosages ranging from 1 to 12 mg/kg of body
weight once daily (Table 3). The majority
of children (66%) received 3 mg/kg (prophylactic dose), equivalent to
an adult dose of 100 mg, while 33% received 6 to 12 mg/kg (treatment
dose), equivalent to 200 to 400 mg in an adult. Most children (88%)
were given multiple doses over several days; the remainder received a
single dose. The mean duration of therapy at a dose of 3 mg/kg was 3 weeks. Fluconazole was administered predominantly as an oral suspension
(81%) or an intravenous injection (18%).
| |
RESULTS |
Data for 562 children treated with fluconazole are presented. More
male than female patients were recruited; their ages ranged from
premature neonatal age to age 17 years (Table
4).
Side effects.
Overall, 58 (10.3%) fluconazole-treated
patients reported 80 treatment-related side effects (Table
5). The most common side effects were
associated with the gastrointestinal tract (7.7% of children), with
vomiting (24 patients), diarrhea (12 patients), abdominal pain (10 patients), and nausea (4 patients) being the most frequent symptoms.
The only other system with a greater than 1.0% incidence of side
effects was the skin (1.2% of children). Three patients had an
unspecified rash, two had an erythematous rash, one had pruritus, and
one had a maculopapular rash. Side effects involving the special senses
comprised taste perversion (four patients) and deafness (one patient).
One case of purpura was reported.
View this table:
[in this window]
[in a new window]
|
TABLE 5.
Nature and incidence of treatment-related side effects in
children treated with fluconazole, by age group
|
|
Three treatment-related side effects associated with the liver and
biliary system were reported. All occurred in children
with leukemia
who received fluconazole at 3 mg/kg as prophylaxis
during
chemotherapy-induced neutropenia. The first patient, a
2-year-old boy,
showed transient elevations in aspartate aminotransferase
(AST) and
alanine aminotransferase (ALT) levels during fluconazole
therapy. The
second patient, a 9-year-old girl, developed hepatomegaly
with moderate
but sustained increases in AST and ALT levels; the
condition resolved
during follow-up. Jaundice and a small increase
in serum bilirubin
levels in the third patient, a boy aged 2 1/2
years, returned to normal
during continued treatment. In all three
patients, chemotherapy was
also implicated as a possible cause
of
hepatotoxicity.
A total of 59 deaths occurred either during treatment or within 11 days
of the cessation of treatment with fluconazole. None
of the deaths was
attributable to fluconazole
therapy.
Almost all (98.6%) of the patients who were treated with fluconazole
also received concurrent additional therapy. These most
frequently
consisted of other antimicrobial agents, corticosteroids,
chemotherapeutic agents, immunosuppressants, and agents to relieve
nausea and vertigo. No clinical or laboratory evidence of drug
interaction with fluconazole was evident in these
trials.
Overall, 18 of 562 patients (3.2%) treated with fluconazole
discontinued treatment due to side effects. Fourteen of these
withdrawals were considered to be related to
therapy.
Higher doses of fluconazole did not appear to be associated with a
higher incidence of treatment-related side effects (Table
6). One case of vomiting was the only
reported treatment-related
side effect among 20 children who received
fluconazole at 12 mg/kg.
View this table:
[in this window]
[in a new window]
|
TABLE 6.
Incidence of treatment-related vomiting and diarrhea in
children treated with fluconazole, by dose group
|
|
Analysis of side effect data by age group was performed for the
following age categories: <6 months, 6 months to 2 years,
2 to 5 years, 5 to 14 years, and
14 years (Table
5). None of
the 42 infants
who were younger than 6 months old developed any
side effects. For
children who were older than 6 months, there
were no apparent
differences in the incidence or pattern of reported
side effects with
age.
Laboratory tests.
Laboratory assessments included a complete
blood count and tests of hepatic and renal function. Although
clinically significant laboratory abnormalities were common, the vast
majority were considered to be related to underlying diseases,
concomitant medications, or intercurrent illnesses. The number and
percentage of patients with abnormal laboratory test results that were
considered to be possibly related to fluconazole therapy are shown in
Table 7. Fluconazole did not have a
clinically significant or consistent effect on any of the laboratory
parameters. The most frequently reported (i.e., 2%)
treatment-related laboratory test abnormalities were elevated ALT
(4.9%), AST (2.7%), and alkaline phosphatase (2.3%) levels. Liver
function abnormalities were usually transient, with the test results
generally returning to normal values during therapy or after completion
of the study.
Two children (0.4%) discontinued fluconazole treatment because of
laboratory parameter abnormalities; both patients had elevated
levels
of AST and ALT. One of these patients was a 9-year-old
girl with
lymphoblastic leukemia who received fluconazole at a
dose of 2 mg/kg
for 5 days. The other patient, a 10-year-old boy
with a diagnosis of
alveolar rhabdomyosarcoma, received a dose
of 8 mg/kg for 6 days. In
both patients, liver function test results
were returning toward normal
at the final
assessment.
Comparative studies.
The safety profile of fluconazole was
compared with those of other antifungal agents by using data from five
controlled studies (9, 14, 20). Three hundred eighty-two
children received fluconazole. Of the 381 patients in a comparable
group, most were treated with the oral polyenes amphotericin B and
nystatin (n = 352; 92.4%), and a few received
ketoconazole (n = 29; 7.6%). The age distributions and
dosing durations for the fluconazole-treated and the comparison groups
were well matched. In both groups, the majority of patients were ages 5 to 14 years (fluconazole-treated group, 46.6%; comparison group,
48.0%) or 2 to 5 years (fluconazole-treated group, 28.3%; comparison
group, 30.7%). About two-thirds of the patients received therapy for
at least 7 days and less than 28 days (fluconazole-treated group,
65.7%; comparison group, 64.6%). The maximum durations of treatment
were 129 days for the fluconazole-treated group and 134 days for the
comparison group.
Side effects were reported by more patients who received fluconazole
than by patients who received the other agents (11.8
versus 6.6%;
Table
8). The types of side effects
reported were
similar to those who received fluconazole and those who
received
other drugs; vomiting and diarrhea were the most common
symptoms
in both groups. Withdrawal due to side effects was reported
for
15 of 382 patients (3.9%) who received fluconazole, 4 of 352 patients
(1.1%) who received oral polyenes, and 1 of 29 patients
(3.4%)
who received ketoconazole. Withdrawal was considered to be drug
related in 12 patients who received fluconazole and 3 treated
with oral
polyenes.
In general, the incidence of treatment-related laboratory abnormalities
was similar in both groups (Table
9).
Liver function
abnormalities occurred at similar frequencies in groups
treated
with fluconazole and the oral polyenes. Although the incidence
of elevated AST and ALT levels appeared to be higher (approximately
double) for the ketoconazole-treated group than for the groups
treated
with fluconazole and the oral polyenes, the number of
patients who
received ketoconazole was small.
| |
DISCUSSION |
Fluconazole was well tolerated by the study population of 562 children, many of whom were suffering from severe underlying disease
such as HIV infection or hematological or oncological malignancies. The
predominant reported side effects were gastrointestinal symptoms. In
patients undergoing treatment for cancer, side effects such as nausea
and vomiting may have been associated with the administration of
chemotherapy or radiotherapy. The incidence and pattern of side effects
were similar in all age groups and did not appear to be related to dose
over the range studied. Both the most common dose of 3 mg/kg
(equivalent to 100 mg in a 70-kg adult) and the highest dose of 12 mg/kg (equivalent to 400 mg in a 70-kg adult) were well tolerated,
albeit by a small number of patients treated with the higher dose.
These data confirm the favorable tolerability and safety profile
observed in other published studies of fluconazole used in children
(4-8, 17, 18, 25, 26).
Dosage recommendations for fluconazole in pediatric patients have been
established on the basis of pharmacokinetic studies involving more than
100 children (1). The volume of distribution and elimination
rate in pediatric patients differed significantly from the values
reported for adults (2, 3). The volume of distribution
varied with age, being greatest in neonates and decreasing by young
adulthood to a value approaching that for adults. With the exception of
neonates, elimination was generally more rapid in children than in
adults, with a mean plasma elimination half-life of about 20 h for
all pediatric age groups. In neonates and premature babies, however,
fluconazole was eliminated slowly, with a mean elimination half-life of
88.6 h at birth, decreasing to 55.2 h at age 2 weeks.
Appropriate dosage recommendations for pediatric patients have been
developed to ensure that the concentrations attained in the plasma of
children are comparable to those seen in the plasma of adults receiving
currently recommended dosages.
Although fluconazole is not metabolized extensively by the liver,
hepatotoxicity is a potential concern, particularly in very young or
premature infants with suboptimal liver function. The results reported
here, however, provide no evidence of significant drug-induced
hepatotoxicity. Only three children (0.5%) had side effects related to
the liver, and in all patients the symptoms resolved during continued
treatment or follow-up. Transient increases in liver enzyme levels were
identified in fewer than 5% of patients.
The data obtained in studies with adult and pediatric populations are
not strictly comparable due to differences in the protocols, patient
populations, and dosage regimens. Nevertheless, these results suggest
that the pattern and incidence of side effects and laboratory
abnormalities seen in children treated with fluconazole are analogous
to those seen in adults. There were no indications of any unexpected
safety concerns specifically related to children.
In conclusion, fluconazole was well tolerated in the pediatric
population examined in this study. Many of the children were suffering
from severe underlying disease and were taking a variety of concomitant
medications. The safety profile of fluconazole in children mirrors the
excellent safety profile seen in adults.
| |
ACKNOWLEDGMENTS |
We thank the investigators and colleagues who participated in the
conduct and analysis of these studies: in the United States, M. Amantea, J. W. Lee, P. A. Pizzo, T. J. Walsh, and P. Whitcomb (Bethesda, Md.); D. Baker and P. M. Flynn (Memphis,
Tenn.); G. Borowski, J. Malloy, and B. Norton (Montgomery, Ala.); Y. Bryson and A. Kovacs (Los Angeles, Calif.); N. Bunin (Philadelphia,
Pa.); F. E. Cox (Augusta, Ga.); J. Cullen and B. Greffe (Denver,
Colo.); C. K. Cunningham and L. Weiner (Syracuse, N.Y.); G. V. Dahl (Palo Alto, Calif.); A. Dajani (Detroit, Mich.); E. Farrington
(Indianapolis, Ind.); G. Gilbert, B. Kramer, K. Lown, G. Noel, V. B. Peters, A. Rubinstein, and R. Warford (New York, N.Y.); M. Gooch
(Salt Lake City, Utah); J. Harris, S. Pelton, and L. C. Wolfe
(Boston, Mass.); M. Holdsworth (Albuquerque, N.M.); T. Kerkering
(Richmond, Va.); J. Lukens (Nashville, Tenn.); H. Maurer, R. Yogev
(Chicago, Ill.); M. Nahata (Columbus, Ohio); B. Parks (Jackson, Miss.); S. Paryani and P. A. Pitel (Jacksonville, Fla.); A. Petru
(Oakland, Calif.); K. Powell, C. Schwartz (Rochester, N.Y.); M. Reed
(Charlottesville, Va.); Z. Rodriguez, A. R. San Jorge, and G. Scott (Miami, Fla.); V. San Joaquin (Oklahoma City, Okla.); N. L. Seibel (Washington, D.C.); B. Sullivan (Marshfield, Mass.); R. Van Dyke
and L. Yu (New Orleans, La.); E. Wald (Pittsburgh, Pa.); T. Yamauchi
(Little Rock, Ark.); and G. Yee (Gainesville, Fla.); in Canada, D. Moore and L. de Repentigny (Montreal, Quebec); in Europe, L. M. Ball (Liverpool, United Kingdom); M. Bernacer Borja, T. Contra, T. Hernández-Sampelayo, M. I. de Jose, J. Lopez Perez, and B. Perez-Gorricho (Madrid, Spain); F. Berthold and A. Heinemann (Cologne,
Germany); S. Blanche, E. Gluckman, C. Griscelli, and G. Leverger
(Paris, France); F. Cockburn, B. S. Gibson, M. Greig, and T. Turner (Glasgow, United Kingdom); J. Cubells, C. Fortuny-Guasch, A. Mur-Sierra, and J. Sánchez de Toledo (Barcelona, Spain); P. J. Darbyshire (Birmingham, United Kingdom); R. Dopfer (Tübingen,
Germany); H. Gadner and W. Graninger (Vienna, Austria); D. M. Gibb
and I. M. Hann (London, United Kingdom); J. B. Gouvon (Dijon,
France); A. Groll (Frankfurt, Germany); K. Hoppu, M. Pohjavuori, and H. Saxén (Helsinki, Finland); J. M. Indiano Arce (Bilbao,
Spain); J. Kohler and A. Pallett (Southampton, United Kingdom); G. Margueritte (Montpellier, France); S. Meller (Sutton, United Kingdom);
A. Navajas Guitierrez (Baracaldo, Spain); J. Ninane and E. Sariban (Brussels, Belgium); G. Paolucci (Bologna, Italy); N. Principi (Milan,
Italy); P. Reinert (Creteil, France); A. Robert (Toulouse, France);
H. J. Schmitt (Mainz, Germany); L. Sierra-Seumaga (Pamplona, Spain); R. F. Stevens (Manchester, United Kingdom); J. P. Vannier (Rouen, France); and C. Viscoli (Genova, Italy).
| |
FOOTNOTES |
*
Corresponding author. Mailing address: Infectious
Diseases Unit, Great Ormond Street Hospital for Children NHS Trust,
Great Ormond St., London WC1N 3JH, United Kingdom. Phone: (44) 171 405 9200. Fax: (44) 171 813 8266. E-mail:
vnovelli{at}compuserve.com.
| |
REFERENCES |
| 1.
|
Brammer, K. W., and P. E. Coates.
1994.
Pharmacokinetics of fluconazole in pediatric patients.
Eur. J. Clin. Microbiol. Infect. Dis.
13:325-329[Medline].
|
| 2.
|
Brammer, K. W.,
A. J. Coakley,
S. G. Jezequel, and M. H. Tarbit.
1991.
The disposition and metabolism of [14C]fluconazole in humans.
Drug. Metab. Dispos.
19:764-767[Abstract].
|
| 3.
|
Brammer, K. W.,
P. R. Farrow, and J. K. Faulkner.
1990.
Pharmacokinetics and tissue penetration of fluconazole in humans.
Rev. Infect. Dis.
12(Suppl. 3):318-326.
|
| 4.
|
Cáp, J.,
A. Mojzesova,
E. Kayserova,
E. Bubánska,
K. Hatiar,
J. Trupl, and V. Krcméry, Jr.
1993.
Fluconazole in children: first experience with prophylaxis in chemotherapy-induced neutropenia in pediatric patients with cancer.
Chemotherapy
39:438-442[Medline].
|
| 5.
|
Cáp, J.,
D. Sejnova,
L. Soltes, and V. Krcméry, Jr.
1991.
Fluconazole in the treatment of mycotic infection in children.
Int. J. Exp. Clin. Chemother.
4:219-223.
|
| 6.
|
Ehninger, G.,
H. K. Schuler, and E. Sarnow.
1996.
Fluconazole in the prophylaxis of fungal infection after bone marrow transplantation.
Mycoses
39:259-263[Medline].
|
| 7.
|
Fasano, C.,
J. O'Keefe, and D. Gibbs.
1994.
Fluconazole treatment of children with severe fungal infections not treatable with conventional agents.
Eur. J. Clin. Microbiol. Infect. Dis.
13:344-347[Medline].
|
| 8.
|
Fasano, C.,
J. O'Keefe, and D. Gibbs.
1994.
Fluconazole treatment of neonates and infants with severe fungal infections not treatable with conventional agents.
Eur. J. Clin. Microbiol. Infect. Dis.
13:351-354[Medline].
|
| 9.
|
Flynn, P. M.,
C. K. Cunningham,
T. Kerkering,
A. R. San Jorge,
V. B. Peters,
P. A. Pitel,
J. Harris,
G. Gilbert,
L. Castagnaro,
P. Robinson, and the Multicenter Fluconazole Study Group.
1995.
Oropharyngeal candidiasis in immunocompromised children: a randomized, multicenter study of orally administered fluconazole suspension versus nystatin.
J. Pediatr.
127:322-328[Medline].
|
| 10.
|
Franklin, I. M.,
E. Elias, and C. Hirsch.
1990.
Fluconazole-induced jaundice.
Lancet
336:565[Medline].
|
| 11.
|
Gazzard, B. G., and D. Smith.
1990.
Oral candidosis in HIV-infected patients.
Br. J. Clin. Pract. Symp. Suppl.
71:103-108.
|
| 12.
|
Goa, K. L., and L. B. Barradell.
1995.
Fluconazole. An update of its pharmacodynamic and pharmacokinetic properties and therapeutic use in major superficial and systemic mycoses in immunocompromised patients.
Drugs
50:658-690[Medline].
|
| 13.
|
Grant, S. M., and S. P. Clissold.
1990.
Fluconazole: a review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential, in superficial and systemic mycoses.
Drugs
39:877-916[Medline].
|
| 14.
|
Hernández-Sampelayo, T., and a Multicentre Study Group.
1994.
Fluconazole versus ketoconazole in the treatment of oropharyngeal candidiasis in HIV-infected children.
Eur. J. Clin. Microbiol. Infect. Dis.
13:340-344[Medline].
|
| 15.
|
Inman, W.,
G. Pearce, and L. Wilton.
1994.
Safety of fluconazole in the treatment of vaginal candidiasis. A prescription-event monitoring study, with special reference to the outcome of pregnancy.
Eur. J. Clin. Pharmacol.
46:115-118[Medline].
|
| 16.
|
Inman, W.,
K. Kubota,
G. Pearce, and L. Wilton.
1993.
PEM Report Number 3. Fluconazole. Pharmacoepidemiol.
Drug Safety
2:321-340.
|
| 17.
|
Lee, J. W.,
N. L. Seibel,
M. Amantea,
P. Whitcomb,
P. A. Pizzo, and T. J. Walsh.
1992.
Safety and pharmacokinetics of fluconazole in children with neoplastic diseases.
J. Pediatr.
120:987-993[Medline].
|
| 18.
|
Marchisio, P., and N. Principi.
1994.
Treatment of oropharyngeal candidiasis in HIV-infected children with oral fluconazole.
Eur. J. Clin. Microbiol. Infect. Dis.
13:338-340[Medline].
|
| 19.
|
Munoz, P.,
S. Moreno,
J. Berenguer,
J. C. Bernaldo de Quiros, and E. Bouza.
1991.
Fluconazole-related hepatotoxicity in patients with acquired immunodeficiency syndrome.
Arch. Intern. Med.
151:1020-1021[Abstract/Free Full Text].
|
| 20.
|
Ninane, J., and a Multicentre Study Group.
1994.
A multicentre study of fluconazole versus oral polyenes in the prevention of fungal infection in children with haematological or oncological malignancies.
Eur. J. Clin. Microbiol. Infect. Dis.
13:330-337[Medline].
|
| 21.
|
Osterloh, I. H.
1992.
Safety, p. 40-60.
In
W. B. Powderly, and J. W. Van't Wout (ed.), The Anti-fungal agents. Fluconazole. Marius Press, Carnforth, United Kingdom.
|
| 21a.
| Pfizer, Inc. Data on file. Pfizer, Inc., New York,
N.Y.
|
| 22.
|
Pizzo, P. A., and T. J. Walsh.
1990.
Fungal infections in the pediatric cancer patient.
Semin. Oncol.
17(Suppl. 6):6-9[Medline].
|
| 23.
|
Presterl, E.,
W. Graninger, and a Multicentre Study Group.
1994.
Efficacy and safety of fluconazole in the treatment of systemic fungal infections in pediatric patients.
Eur. J. Clin. Microbiol. Infect. Dis.
13:347-351[Medline].
|
| 24.
|
Saxén, H.,
K. Hoppu, and M. Pohjavuori.
1993.
Pharmacokinetics of fluconazole in very low birth weight infants during the first two weeks of life.
Clin. Pharmacol. Ther.
54:269-277[Medline].
|
| 25.
|
Seay, R. E.,
T. A. Larson,
J. P. Toscano,
B. C. Bostrom,
M. C. O'Leary, and D. L. Uden.
1995.
Pharmacokinetics of fluconazole in immune-compromised children with leukemia or other hematological disease.
Pharmacotherapy
15:52-58[Medline].
|
| 26.
|
Viscoli, C.,
E. Castagnola,
F. Fioredda,
B. Ciravegna,
G. Barigione, and A. Terragna.
1991.
Fluconazole in the treatment of candidiasis in immunocompromised children.
Antimicrob. Agents Chemother.
35:365-367[Abstract/Free Full Text].
|
| 27.
|
Walsh, T. J.,
C. Gonzalez,
C. A. Lyman,
S. J. Chanock, and P. A. Pizzo.
1996.
Invasive fungal infections in children: recent advances in diagnosis and treatment.
Adv. Pediatr. Infect. Dis.
11:187-290[Medline].
|
Antimicrobial Agents and Chemotherapy, August 1999, p. 1955-1960, Vol. 43, No. 8
0066-4804/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
This article has been cited by other articles:
-
Thurey, J., Molyneux, E.
(2008). Evidence behind the WHO Guidelines: Hospital Care for Children: The Usefulness of Azole Prophylaxis against Cryptococcal Meningitis in HIV-positive children. J Trop Pediatr
54: 361-363
[Full Text]
-
(2007). Recurrent tinea versicolor: treatment with itraconazole or fluconazole?. Arch. Dis. Child.
92: 1040-1042
[Full Text]
-
Blyth, C. C., Palasanthiran, P., O'Brien, T. A.
(2007). Antifungal Therapy in Children With Invasive Fungal Infections: A Systematic Review. Pediatrics
119: 772-784
[Abstract]
[Full Text]
-
Krishna, G., Sansone-Parsons, A., Martinho, M., Kantesaria, B., Pedicone, L.
(2007). Posaconazole Plasma Concentrations in Juvenile Patients with Invasive Fungal Infection. Antimicrob. Agents Chemother.
51: 812-818
[Abstract]
[Full Text]
-
Uko, S., Soghier, L. M., Vega, M., Marsh, J., Reinersman, G. T., Herring, L., Dave, V. A., Nafday, S., Brion, L. P.
(2006). Targeted Short-Term Fluconazole Prophylaxis Among Very Low Birth Weight and Extremely Low Birth Weight Infants. Pediatrics
117: 1243-1252
[Abstract]
[Full Text]
-
Charlier, C., Hart, E., Lefort, A., Ribaud, P., Dromer, F., Denning, D. W., Lortholary, O.
(2006). Fluconazole for the management of invasive candidiasis: where do we stand after 15 years?. J Antimicrob Chemother
57: 384-410
[Abstract]
[Full Text]
-
Manzoni, P., Arisio, R., Mostert, M., Leonessa, M., Farina, D., Latino, M. A., Gomirato, G.
(2006). Prophylactic Fluconazole Is Effective in Preventing Fungal Colonization and Fungal Systemic Infections in Preterm Neonates: A Single-Center, 6-Year, Retrospective Cohort Study. Pediatrics
117: e22-e32
[Abstract]
[Full Text]
-
Chetwynd, E. M., Ives, T. J., Payne, P. M., Edens-Bartholomew, N.
(2002). Fluconazole for Postpartum Candidal Mastitis and Infant Thrush. J Hum Lact
18: 168-171
[Abstract]
Top
Abstract
Introduction
