Antifungal
agents for common paediatric infections
Infectious Diseases and Immunization Committee, Canadian Paediatric Society (CPS)
Paediatrics & Child Health 2007; 12(10): 875-878
Revision in progress February 2011
Index of position statements from the Infectious Diseases and Immunization Committee
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The most common fungal infections in infants and children are mucocutaneous candidiasis, pityriasis versicolor, tinea corporis, tinea pedis and tinea capitis (1). The objective of the present update is to inform clinicians on options for treatment of these symptomatic fungal infections, due to a variety of over-the-counter (Table 1) and prescription (Table 2) drugs available. It replaces the previous position statement published in 2000 (2).
MUCOCUTANEOUS CANDIDIASIS
Candida albicans colonization can occur as early as the first week of life.
Symptomatic infections such as thrush and Candida diaper dermatitis (CDD) may
develop at any age thereafter, particularly following broad-spectrum antibiotic
treatment. Systemic candidiasis is rare, but is a particular risk for premature
infants (3,4).
Although mucocutaneous candidiasis is common, only a few high-quality randomized control studies of drug therapy have been published. In fact, one recent review (5) of oral candidiasis in patients with cancer found only eight studies that met the inclusion criteria. Control trials for diaper dermatitis are also rare, making it difficult to derive recommendations for optimal therapy.
Oropharyngeal candidiasis (thrush)
Oropharyngeal candidiasis (thrush) may start as early as seven days after birth,
with an incidence in infants of 5% to 10% depending on the population studied
(6-7). Response to antifungal agents is usually good in neonates with no major
underlying condition, but a prolonged course may be required and recurrences are
common. Use of an infant soother increases the incidence of thrush and may make
treatment less effective, unless the soother is carefully washed after use (8).
Topical gentian violet, the oldest therapeutic agent, is moderately effective against thrush but prolonged use can cause irritation and even ulceration (9). Gentian violet stains tissue and clothing and, thus, is not well accepted by parents; it also interferes with clinical assessment.
Nystatin suspension has been used since the 1950s (10). It is well tolerated and remains the most frequently prescribed agent for thrush. The usual dosage of 200,000 units four times daily is highly effective, curing 50% of newborns after one week and 80% of newborns after two weeks of treatment (11). It should be administered after feeds.
First-generation imidazoles, such as
miconazole and clotrimazole, are more effective than nystatin (12). However,
miconazole gel and oral preparation of clotrimazole are not licensed in
Second-generation imidazoles, such as fluconazole and itraconazole or other new oral antifungals, may be considered if conventional topical treatments fail, particularly among immunocompromised patients. Although these drugs are effective, they are not recommended as first-line management of thrush in normal children because of limited paediatric data, potentially significant adverse effects and high costs.
CDD
CDD is common during the second to fourth months of life in healthy infants
(7,8). Candida albicans is present in the feces of 90% of such infants (13,16).
Treatment should include decreasing maceration of the skin by eliminating
impervious diaper covers, changing diapers frequently and leaving diapers off
for long periods of time. Topical antifungal therapy is also necessary. In one
randomized, double-blind, controlled trial (17) comparing miconazole ointment
with zinc oxide petroleum base, miconazole was safe and more effective,
particularly in moderate to severe cases. Ointments, creams and powders of
nystatin, miconazole and clotrimazole are available (Table 1). It is still not
clear whether concomitant oral and topical antifungals should be recommended. In
two studies (18,19), no difference in the initial clinical responses was found.
In another study (18), relapses were decreased (although not significantly) when
an oral supplement of nonabsorbable nystatin was added to the topical ointment
of nystatin (16% versus 33%).
There are no well-designed trials to assess the efficacy of adding a topical anti-inflammatory agent in treatment of CDD. Potent anti-inflamatory preparations, such as those with high concentrations of steroids, may impair the response to antifungal agents and should be avoided. The place for low concentrations of steroids (eg, 1% hydrocortisone) is unclear. Although some experts never use steroids with antifungal agents, others advocate them in CDD.
PITYRIASIS VERSICOLOR (TINEA
VERSICOLOR)
Pityriasis versicolor is a mild or chronic condition characterized by scaly
hypo- or hyperpigmented lesions on the trunk. Infection often occurs in
adolescents when the sebaceous glands are active. Malassezia, an organism
restricted to invading the stratum corneum (20), causes the infection (21).
Antifungal preparations can be effective, but recurrences are common (22).
Topical ketoconazole, selenium sulfide and clotrimazole are the most common treatments (23). Treatment usually consists of applying shampoo preparations, such as ketoconazole 2% or selenium sulfide as a 2.5% lotion or 1% shampoo, to the affected area for 15 min to 30 min nightly for one to two weeks, and then once a month for three months to avoid recurrences (24). In one randomized trial (25) using ketoconazole shampoo for three days or one day compared with placebo, the response was 73%, 69% and 5%, respectively.
TINEA CORPORIS
Tinea corporis (ringworm) is a superficial infection of the skin that is not
covered by hair. It can occur at any age. Lesions are circular (thus the name
ringworm). Common causes in
TINEA PEDIS
Tinea pedis (athlete’s foot) is a common superficial fungal infection of the
foot. Causes include T rubrum, T mentagrophytes and E floccosum. Although tinea
pedis often spreads among household members, it is uncommon in young children
(26,27).
Many topical antifungals are effective against tinea pedis. Drying agents, such as Burow’s solution, may be a useful adjunct for macerated or vesicular lesions. Recurrence of the infection can be prevented with good foot hygiene. Oral antifungals are indicated for infections involving the toenails. Clinical studies in children are limited, but suggest that fluconazole, itraconazole and terbinafine are effective (28,29).
TINEA CAPITIS AND SEBORRHEIC
DERMATITIS
Tinea capitis (fungal infection of the scalp) is the most common paediatric
superficial dermatophyte infection. The causative species vary geographically; M
canis predominates in
Seborrheic dermatitis and pityriasis capitis (cradle cap) are common, but usually mild, scalp infections caused by Malassezia species (eg, Malassezia furfur). The condition often resolves with mild soap application. Shampoos containing selenium sulfide or an azole are useful in severe forms.
ORAL ANTIFUNGAL AGENTS ABSORBED SYSTEMICALLY
Fluconazole
Fluconazole is a triazole with activity against Candida species, some
dermatophytes and many systemic mycoses. The drug is hydrophilic and, thus,
present mainly in bodily fluids rather than in keratin or lipids (30). It is,
therefore, not useful for routine treatment of most superficial fungal
infections (31,32).
Griseofulvin
Griseofulvin is no longer available in
Itraconazole
Itraconazole is an azole with activity against many dermatophytes, Candida
species, M furfur and some moulds. It has a long half-life in the skin and
nails, an affinity for both lipids and keratin, and reaches the skin primarily
through sebum. The drug may be excreted in sebum for one month after therapy has
been discontinued. Itraconazole is available in tablet and liquid formats.
Clinical trials and case series using itraconazole to treat tinea capitis have
shown it to be effective (approximately 90% of the time) for infections caused
by either Trichophyton and Microsporum species (33-37). Few side effects were
seen in most studies using 3 mg/kg/day to 5 mg/kg/day for four to six weeks.
Although more studies on safety are needed, itraconazole may become a good
first-line agent for tinea capitis.
Ketoconazole
Ketoconazole was the first azole evaluated for efficacy in the treatment of
resistant superficial fungal infections such as tinea capitis. Ketoconazole was
found to be equivalent to griseofulvin for such cases in these clinical trials
(38-41).
Terbinafine
Terbinafine is a lipophilic and keratinophilic fungicidal agent, active in
vitro against dermatophytes and some moulds. It diffuses to keratinocytes from
the blood stream to reach the stratum corneum and hair follicles (42). Because
it is not metabolized through cytochrome P-450, many of the drug interactions
seen with the azoles do not occur. Terbinafine is well tolerated, with
gastrointestinal and skin reactions in only 2% to 7% of patients. Loss of the
sense of taste has been reported, but resolves after therapy has ended.
Oral terbinafine is effective in the
treatment of relatively resistant superficial dermatophyte infections including
tinea unguium (onychomycosis), tinea pedis and tinea corporis or tinea cruris,
achieving mycological cure in over 80% of adult patients (43). It is effective
for children with tinea capitis at a dose of 62.5 mg/day to 250 mg/day for four
weeks (44-48). Topical terbinafine 1% formulations have been effective when
applied once or twice daily for two weeks. Gupta et al (49) concluded that
terbinafine may be the drug of choice for superficial fungal infections in
children. Terbinafine is available in
Drug interactions
The extent to which an antifungal agent interacts with the hepatic P-450
enzyme system has implications on its potential to cause significant drug
interactions (50). Azoles are metabolized by cytochrome P-450 3A (CYP 3A) and
may inhibit the elimination of other drugs metabolized by this enzyme such as
antiarrhythmics, cortisol, cyclosporin, estradiol and tacrolimus. Terbinafine is
not an azole; it does not affect CYP 3A and it has few drug interactions.
For further details on the use of
antifungal agents for common paediatric infections, the reader is referred to
recent review articles (1,49,51).
INFECTIOUS DISEASES AND IMMUNIZATION
COMMITTEE
Members: Drs Robert Bortolussi, IWK Health Centre, Halifax, Nova Scotia
(chair); Dorothy L Moore, The Montreal Children’s Hospital, Montreal, Quebec;
Joan Louise Robinson, Edmonton, Alberta; Élisabeth Rousseau-Harsany,
Sainte-Justine UHC, Montreal, Quebec (board representative); Lindy Michelle
Samson, Children’s Hospital of Eastern Ontario, Ottawa, Ontario
Consultant: Dr Noni E MacDonald, IWK Health Centre,
Liaisons: Drs Upton Dilworth Allen, The Hospital for Sick Children,
Toronto, Ontario (Canadian Pediatric AIDS Research Group); Scott Alan Halperin,
IWK Health Centre, Halifax, Nova Scotia (Immunization Program, ACTive); Charles
PS Hui, Children’s Hospital of Eastern Ontario, Ottawa, Ontario (Health
Canada, Committee to Advise on Tropical Medicine and Travel); Larry Pickering,
Elk Grove, Illinois, USA (American Academy of Pediatrics, Red Book Editor and
ex-officio member of the Committee on Infectious Diseases); Marina Ines
Salvadori, Children’s Hospital of Western Ontario, Ottawa, Ontario (Health
Canada, National Advisory Committee on Immunization)
Principal author: Dr Robert Bortolussi, IWK Health Centre,
Posted: December 2007
| Disclaimer: The recommendations in this position statement do not indicate an exclusive course of treatment or procedure to be followed. Variations, taking into account individual circumstances, may be appropriate. Internet addresses are current at time of publication. |