doi: 10.1111/1346-8138.

15257 Journal of Dermatology 2020; : 1–5

ORIGINAL ARTICLE
Prospective trial for the clinical efficacy of anogenital skin
care with miconazole nitrate-containing soap for diaper
candidiasis
Hidenori TAKAHASHI,1,2 Noritaka OYAMA,1 Masaya AMAMOTO,3 Tomoko TORII,3
Tomoko MATSUO, Minoru HASEGAWA1
3
1
Department of Dermatology, Division of Medicine, Faculty of Medical Sciences, University of Fukui Hospital, Departments of
2
Dermatology, 3Clinical Examination, JCHO Fukui Katsuyama General Hospital, Fukui, Japan

ABSTRACT
Anogenital skin care for the elderly remains an umbrella term concerning protective and non-interventional
regimens, particularly for ordinary diaper users. Our recent investigation has demonstrated the preventive effect
of daily anogenital washing with miconazole nitrate-containing soap to the development of diaper candidiasis.
We extended this work to cover our hypothesis as to whether the miconazole soap has a therapeutic benefit in
genital candidiasis. The study outline includes: (i) the enrollment of 21 bedridden inpatients (84  9 years; eight
men and 13 women) who were diagnosed clinically and mycologically with genital candidiasis, and who had
never received topical and/or systemic antifungal agents; (ii) administration of anogenital washing with 0.75%
miconazole-containing soap once daily for 4 weeks; and (iii) assessment of clinical symptoms and detection of
Candida materials by culture and microscopic examination. As assessed by clinical symptom scoring for incon-
tinence-associated dermatitis (IAD), the ratio of patients with severe to moderate symptoms dramatically
decreased by 2 weeks and 10 of 21 patients became symptom-free at 4 weeks. The IAD clinical severity score
was significantly decreased at 4 weeks. Compared with the baseline positivity, both microscopic and cultured
Candida-positive rates were significantly decreased at 4 weeks after washing. All culture-detected fungi were
Candida albicans. Severe adverse events did not occur in all participants. Individual medical and risk factors
had no significant correlation with clinical severity and duration of candidiasis on variance analysis. In conclu-
sion, topical washing with miconazole soap is a safe and reliable non-medical approach for soothing diaper-
associated genital candidiasis in bedridden inpatients in whom it is difficult to perform prompt medical
examination.
Key words: diaper candidiasis, genital candidiasis, incontinence-associated dermatitis, miconazole nitrate,
soap.

INTRODUCTION associated fungal infections. Of these, genital (vulvovaginal)

candidiasis is the most frequent complication. Candida spp.
A rapidly aging society has increased rates of diaper users, are part of normal flora in the gastrointestinal tract, in combina-
particularly in the bedridden elderly population. It is also widely tion with suitable temperature and moisture, allowing them to
known that diapers may weaken the potential anxiety regarding develop and persist to the diaper-covered skin site. The inevi-
abrupt excretion and cause the adverse skin condition of so- table sequalae considerably affects the morbidity of patients,
called incontinence-associated dermatitis (IAD). IAD represents particularly bedridden elderly inpatients and inmates in whom it
the skin inflammation caused by local barrier dysfunction due is difficult to perform dermatological examination. Routine
to excessive moisture stress and increased pH from inconti- microscopic examination using the lesional scales to detect
nence.1–3 In Japan, the prevalence of IAD is of growing social pseudohyphae and/or blastoconidia remains the mainstay for
impact and concern, estimated to occur in 5.9–17.0% of conclusive diagnosis of candidiasis, requiring therapeutic inter-
elderly subjects.4,5 Deterioration of anogenital hygiene is vention. In diverse clinical settings such as microscopically
responsible for the eventual alterations in the local microorgan- uncertain cases and chronically habitual cases with candidia-
ism flora,6 and carries an increased incidence of diaper- sis, a fungal culture for determining pathogenic significance

Correspondence: Noritaka Oyama, M.D., Ph.D., Department of Dermatology, University of Fukui Hospital, 23-3 Matsuoka Shimoaizuki,
Eiheiji-cho, Yoshida-gun, Fukui 910-1193, Japan. Email: norider@u-fukui.ac.jp
Received 1 September 2019; accepted 9 January 2020.

© 2020 Japanese Dermatological Association 1

H. Takahashi et al.

may be helpful, although it sometimes accounts for confusing conditions. The primary exclusion criteria included: (i) previous
results due to the potential difficulty of excluding possible con- use of systemic/local antifungal agents; (ii) suspicious hypersen-
tamination and non-pathogenic colonization. sitivity or allergic responses to miconazole or any soap compo-
We have recently conducted a double-blind, placebo-con- nents; (iii) use of any investigational drugs; and (iv) unplanned or
trolled study demonstrating that daily anogenital skin care emergency use of antifungal agents due to worsening of symp-
using miconazole nitrate-containing soap for prophylactic pur- toms. Patients who were withdrawn from this study included: (i)
poses successfully inhibits the development and progression those with severe adverse effects; and (ii) discharged earlier
of diaper candidiasis in hospitalized, bedridden patients.7 than the 4 weeks of study. In cases in which miconazole soap
Miconazole, an imidazole derivative, is a potent bacteriostatic washing worsened symptoms or at least caused unsatisfactory
agent against a wide variety of fungal spp. through inhibiting clinical confidence, their study was disclosed at the timing of the
the cytochrome P450-dependent biosynthesis of ergosterol, a judgement and immediately replaced with approved antifungal
critical component of the fungal cell membrane.8 Substantial treatment.
efficacies of miconazole have been stated for the treatment of
superficial fungal infections, such as dermatomycosis, ony-
Materials
chomycosis and vulvovaginal mycoses.9–11 The drug is appli-
cable topically to any of the mucocutaneous sites affected by Diapers
fungal infections. Another advantage of miconazole includes The diapers used in this study were all commercially available,
non-specific antibacterial action in impetigo and ecthyma, sug- disposable, comfortably breathable standard materials for the
gesting the additional therapeutic benefit of this drug not only incontinence excrement care of adults, as described previ-
for fungal clearance, but also for disruption of bacterial–fungal ously.7 No participants overlaid any particular materials that
biofilm formation.12–14 This concept can be traced to the clini- would cause an excess of moisture within the diapers.
cal settings of IAD because of a higher frequency of the com-
bined infection with fungi and bacteria in the anogenital skin.15 Soaps
Considering this sociomedical background for diaper users We used 0.75% miconazole nitrate containing soap that was
and simple administration of miconazole soap, an attractive kindly provided by Mochida Healthcare (Tokyo, Japan).
strategy emerges from our current hypothesis concerning
whether the antifungal soap has an efficacy comparable with Cleaning procedure of the skin
the commercially available antifungal drugs or at least inhibit At every washing, the practitioner extended the foamy soap to
further progression of the disease. Apart from the established the diaper-covered skin area, rubbed softly with gloved fingers
drugs, there has been to date no trials or recommendations and then rinsed with lukewarm water so that no foam
regarding the therapeutic efficacy of a non-medical approach remained.
to diaper candidiasis. Therefore, this study aimed to conduct a
prospective trial to evaluate the clinical and mycological effects Detection of fungal materials
of daily anogenital care with miconazole nitrate-containing For fungal culture, the sample was taken by single brief swab-
soap for diaper candidiasis in elderly subjects under long-term bing with sterilized cotton, applied directly onto 9-cm mycosel
inpatient care. agar medium, and incubated at 37°C for at least 48 h. After
that, bacterial species were identified with standard chromo
agar Candida medium. Sample collection was carried out from
METHODS
at least three different skin sites of the anogenital region, fol-
Patients lowed by identification of Candida materials on microscopy
In this study, we primarily enrolled 23 elderly inpatients at JCHO with a standard 10% KOH preparation under 9100–400 magni-
Fukui Katsuyama General Hospital who wore diapers all day at fication and combination of adequate agar plate and medium.
least over the study course (4 weeks) and who had been diag-
nosed as having genital candidiasis by direct microscopic exam- Study design
ination and fungal culture. All participants who agreed with the This study was undertaken from September 2017 to December
institutional review board and provided informed consent were 2018 at JCHO Fukui Katsuyama General Hospital (Fukui,
assigned to receive the following procedure for daily anogenital Japan) on the basis of the updated amendments of the Decla-
washing with miconazole nitrate-containing soap. The consent ration of Helsinki and good clinical practice guidelines.16 The
form stated all of the clinically assumed disadvantages that ethics committee of JCHO Fukui Katsuyama General Hospital
might affect the participants who did not primarily receive any of approved the study protocol. After obtaining approval from the
the approved antifungal treatments. The diaper products used institutional review board, patients were assigned into this
are detailed below. At the beginning of the study, we carefully study. The planned duration of the study was 4 consecutive
revisited and checked the previous and ongoing medical histo- weeks. At the time of daily diaper changing, the diaper-cov-
ries of each participant; patients requiring an unrelated systemic ered skin was gently washed with the soap and lukewarm
medication over the 4-week study period were included. Other- water to remove urine or fecal contamination. Subsequently,
wise, the introduction of new medications was not permitted at we performed microscopic examination and fungal culture from
any time points during the study, except under emergency the scales of the suspicious anogenital skin sites to confirm

2 © 2020 Japanese Dermatological Association

 Washing diaper area with miconazole soap

the presence or absence of Candida pseudohyphae and/or 47.6%). There were no patients with severe to moderate
blastoconidia. Sample collection was carried out on at least disease at 4 weeks. No exacerbation and flare up of the skin
three different skin sites of the groin and gluteal region by a lesions were experienced throughout the study. In addition, the
consultant dermatologist (H. T.), and detection of Candida time-course of IADS value for clinical severity in all patients
materials was confirmed by a consultant dermatologist (H. T.), (n = 21) was significantly decreased from the onset to 4 weeks
as described above. Patients were evaluated clinically and (22.7  7.2 vs 9.5  3.0, P < 0.0003; Fig. 2).
mycologically on day 1 (onset) and once per 2 weeks for
4 weeks up to the final evaluation. Clinical symptoms were Topical washing with miconazole soap decreased
assessed by the three-stage IAD scale,17 categorized as: (i) Candida materials and colonies that were
none (no signs of IAD); (ii) mild (erythema with or without detectable on microscopy and fungal culture,
edema); and (iii) severe to moderate (mild disease with vesi- respectively
cles, blisters or erosions, and/or occasional infection). On the Patients with microscopically detected Candida materials, such
other hand, the clinical severity was scored objectively by as pseudohyphae and/or blastoconidia, did not differ in
using the IAD and its severity (IADS) scale, consisting of four
visible characteristics: location, redness, skin loss and rash.18
Table 1. Clinical features of patients at the onset (n = 21)
After study completion, all participants were treated with keto-
conazole cream. Age (years) 84.0  9.4
Sex
Male 8 (38.1%)
Statistical analyses
Female 13 (61.9%)
Statistical analyses were performed using EZR software (http://
Factors that may affect the study
www.jichi.ac.jp/ saitama-sct/SaitamaHP.files/statmed.html).18 Body mass index 20.7  3.2
Data were expressed as mean  standard deviation or number Bathing times (/week) 0.75  0.58
(%). Categorical variables were compared using the v2-test or Immunosuppressive therapy 1 (4.8%)
Fisher’s exact test between groups. P < 0.05 was considered Diarrhea 3 (14.3%)
indicative of statistical significance. Every explanatory variable Defecation control 4 (19.0%)
was analyzed using multivariable analysis (logistic regression). Underlying diseases
Cerebrovascular disorder 13 (61.9%)
Diabetes mellitus 5 (23.8%)
RESULTS Pneumonia 11 (52.4%)
Dementia 14 (66.7%)
Clinical efficacy of topical daily washing with
Parkinsonism 2 (9.5%)
miconazole soap for diaper candidiasis Chronic kidney diseases 3 (14.3%)
Twenty-three patients who were diagnosed microscopically Heart failure 6 (28.6%)
and mycologically as having genital candidiasis were enrolled Cancer 1 (4.8%)
in this study. Of these, two were withdrawn because of early
discharge, and no patients received unplanned, emergency
use of antifungal agents. Finally, 21 patients completed the 4- Severe to moderate
week study (84  9 years; eight men and 13 women). Details (n) 25
Mild
None
of their clinical features and medical backgrounds are shown in
Table 1. On multiple variance analysis, individual medical risk 20
factors showed no significant correlation with clinical severity
and persisted duration of candidiasis (data not shown). Stan- 15

dard fungal culture using the lesional skin swabbing exhibited

10
a high detection rate of fungal spp. at the study onset (20/21,
95.2%), all of which were Candida albicans. 5

Topical washing with miconazole soap improved 0

clinical symptoms of diaper candidiasis Symptoms 0 week 2 weeks 4 weeks

Severe to moderate 20 (95.2%) 0 (0%) 0 (0%)
As assessed by the three-stage IAD scale for clinical symptoms,
Mild 1 (4.8%) 19 (90.5%) 11 (52.4%)
the vast majority of patients at the study onset had severe to
None 0 (0%) 2 (9.5%) 10 (47.6%)
moderate symptoms in the anogenital area (20/21, 95.2%), such
as intense erythema and scales (Fig. 1). Their clinical symptoms
Figure 1. Time-course of clinical severity in 21 patients with
turned into mild disease by at least 2 weeks of washing with
diaper candidiasis during topical genital washing with micona-
miconazole soap. Approximately one-tenth of patients became zole soap. Clinical symptoms were assessed by the three-
symptom free (2/21, 9.5%), one of whom had mild symptoms at stage incontinence-associated dermatitis (IAD) scale, catego-
the onset. The tendency became more apparent by 4 weeks of rized as: (i) none (no signs of IAD); (ii) mild (erythema with or
washing; approximately half of the patients had mild symptoms without edema); and (iii) severe to moderate (mild disease with
(11/21, 52.4%) and the remaining half had no symptoms (10/21, vesicles, blisters or erosions, and/or occasional infection).

© 2020 Japanese Dermatological Association 3

H. Takahashi et al.

35 P = 0.0003 Negative
(n) 25
Positive
30
20
25
15
IADS score

20
10
15
5
10
0
0 week 2 weeks 4 weeks
5
Positive 20 (95.2%) 15 (71.4%) 8 (38.1%)
Negative 1 6 13
0
IADS 0 week 4 weeks P value 0.038* <0.01*

Average 22.7 7.2 9.5 3.0

Figure 4. Time-course difference in numbers of patients with
P value 0.0003*
culture-positive Candida colonies during topical genital wash-
Figure 2. Time-course transit of averaged clinical severity ing with miconazole soap. *P < 0.05.
value during topical genital washing with miconazole soap in
all patients (n = 21) The clinical severity was scored by the
incontinence-associated dermatitis severity (IADS) scale, con- administrated to bedridden, ordinary, diapering elderly who
sisting of four visible characteristics: location, redness, skin developed anogenital candidiasis. Our study disclosed that
loss and rash. *Indicates the statistical significance. topical daily washing with miconazole soap exhibits a satisfac-
tory therapeutic effect in diaper candidiasis. Clinically, symptom
relief arose within at least 2 weeks of washing in one-tenth of
Negative patients (9.5%) and became more apparent at 4 weeks;
(n) 25
Positive approximately half of the patients (52.4%) had mild symptoms
20 and the other half (47.6%) became symptom free. The early
clinical improvement may vary depending on the clinico-
15 pharmacological settings; for example, washing with soap
provides a local miconazole concentration beyond the minimum
10
inhibitory concentration for Candida spp. (0.32–20 ng/cm2), suf-
5 ficient to inhibit the growth and expansion of Candida.13,20 In
addition, miconazole soap possesses a detergency and
0 antibacterial potency that efficiently remove a combined colo-
0 week 2 weeks 4 weeks
nization and biofilm formation with residential bacterial flora,12–
Positive 21 (100%) 20 (95.2%) 13 (61.9%) 14
enabling inhibition of the recolonization of latent Candida
Negative 0 1 8
spp. This conclusion is strengthened by our recent study
P value 0.31 <0.01*
demonstrating the plausible efficacy of miconazole soap in pro-
Figure 3. Time-course difference in numbers of patients with phylactic approaches to the similar cohort with diaper candidia-
microscopy-positive Candida materials during topical genital sis.7 On this basis, the daily topical washing with miconazole
washing with miconazole soap. *P < 0.05. soap is highly recommendable and useful for preventive and
curative subclinical intervention in diaper candidiasis in regular
diapering elderly, particularly those in a bedridden condition or
number between the onset and at 2 weeks of washing with with a low activity of daily living score, in whom prompt medical
miconazole soap (20/21, 95.2%), but were significantly examination is difficult. In addition, evidence for other topical
decreased at 4 consecutive weeks of washing (13/21, 61.9%, antifungals with equivalent clinical efficacy in diaper candidia-
P < 0.01; Fig. 3). On the other hand, patients with culture-de- sis, namely nystatin, clotrimazole, sertaconazole and ciclopirox,
tected Candida colonies were significantly decreased in num- may share a therapeutic advantage similar to miconazole.21–23
ber at 2 weeks after washing, compared with those at the Currently, IAD has been recognized as a concept to summa-
onset (15/21, 71.4%, P = 0.038; Fig. 4), and the tendency rize the overall skin troubles in diaper users, alerting to the
became more obvious at 4 weeks as the final assessment increased incidence of candidiasis in the diaper-covered skin
point (8/21, 38.1%, P < 0.01). (32%).24 Considering this along with the constant increase of
the diaper product market, diaper candidiasis may represent
part of a sociomedical model of physical disability and
DISCUSSION
impaired health in the near future, and occasionally require
This is the first prospective trial of the clinical and mycological multidirectional management including highly adaptable formu-
efficacy of daily anogenital care with miconazole soap lations of antifungal agents, like antifungal soap or shampoo.25

4 © 2020 Japanese Dermatological Association

 Washing diaper area with miconazole soap

Conclusively, the greatest advantages of miconazole soap miconazole nitrate ointment in neonates and infants with moderate
include: (i) it is a commercially available, non-medical product to severe diaper dermatitis complicated by cutaneous candidiasis.
Pedeiatr Dermatol 2013; 30: 717–724.
in Japan (Mochida Healthcare); (ii) it is practically simple to use
10 Concannon P, Gisoldi E, Phillips S. Diaper dermatitis: atherapeutic
without specific and sophisticated techniques; and (iii) has high dilemma.Results of a double-blind placebo controlled trial of
tolerability and safety even in inflamed and erosive skin caused miconazole nitrate 0.25%. Pediatr Dermatol 2001; 18: 149–155.
by Candida. Notwithstanding these benefits, our study includes 11 Pierard-Franchimont C, Letawe C. Tribological and mycological
consequences of the use of miconazole nitrate-containing paste for
the limitation that the current results presuppose the definite
the prevention of diaper dermatitis: an open pilot study. Eur J Pedi-
diagnosis, and do not allow us to ignore inconclusive genital atr 1996; 155: 756–758.
candidiasis. Further longitudinal and larger cohort studies may 12 Odds FC, Webster CE, Mayuranathan P, Simmons PD. Candida
update the potential utility of miconazole soap in all diaper concentrations in the vagina and their association with signs and
users. symptoms of vaginal candidosis. J Med Vet Mycol 1988; 26: 277–
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13 Egawa A, Yamaguchi H, Iwata K. Studies on in vitro antimicrobial
CONFLICT OF INTEREST: Miconazole nitrate-containing activity of miconazole. Jpn J Med Mycol 1977; 18: 65–72.
soaps used in this study were donated by Mochida Healthcare (Tokyo, 14 Arvanitis M, Mylonakis E. Fungal-bacterial interactions and their rel-
Japan). evance in health. Cell Microbiol 2015; 17: 1442–1446.
15 Venugopal S, Gopalan K, Devi A, Kavitha A. Epidemiology and clin-
ico-investigative study of organisms causing vaginal discharge.
Indian J Sex Transm Dis AIDS 2017; 38: 69–75.
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