Efficacy of nystatin for the treatment of oral candidiasis: a systematic review and meta-analysis

Figures & data

Figure 1 Trial flow and study selection.

Abbreviation: SCI, Science Citation Index.

Table 1 Characteristics of the included studies

Author	Year	Region	Risk factor	Nystatin group			Control group			Nystatin group				Control group
				Age (mean)	Sex ratio (F:M)	N	Age (mean)	Sex ratio (F:M)	N	Formulation	Dose	Frequency (times/day)	Duration (days)	Medication	Formulation	Duration
Mima et al^Citation26	2012	Brazil	Denture	62.45 y	3:1	20	61.25 y	13:7	20	Suspension	100,000 IU	4	15	Photodynamic therapy	–	15 d
Johnson et al^Citation27	1989	USA	Denture	–	–	8 8	–	–	8	Pastille	200,000 IU 400,000 IU	5	14	Placebo	Pastille	14 d
Nairn^Citation28	1975	England	Denture	–	–	13	–	–	18 15	Pastille	500,000 IU	4	30	Amphotericin B placebo	Tablet	1 month
Goins et al^Citation29	2002	USA	Infants	1–12 mo	–	28	1–12 mo	–	17	Suspension	100,000 IU	4	10	Fluconazole	Suspension	7 d
Hoppe^Citation20	1997	Germany	Infants	130.8 d	57.6:42.4	107	132.0 d	48:52	105	Suspension	100,000 IU	4	12	Miconazole	Gel	12 d
Flynn et al^Citation30	1995	USA	Infants Children	6 mo to 13 y	–	88	6 mo to 13 y	–	94	Suspension	400,000 IU	4	14	Fluconazole	Suspension	14 d
Moshi et al^Citation31	1998	Tanzania	AIDS	15–59 y	–	91	15–59 y	–	91	Suspension	100,000 IU	3	14	Sodium benzoate	Solution	14 d
Pons et al^Citation32	1997	USA	HIV AIDS	38 y	1:7	84	38 y	1:7	83	Suspension	500,000 IU	4	14	Fluconazole	Suspension	14 d
Nyst et al^Citation33	1992	Zairian	AIDS	35.4 y	25:22	47	34.5 y	27:22 23:22	49 45	Suspension	200,000 IU	4	14	Gentian violet ketoconazole	Suspension troche	14 d
Meunier et al^Citation34	1990	Belgium	Cancer patients	–	–	24	–	–	18	Suspension + pastille	1,000,000 IU 100,000 IU	3	10–12	Ketoconazole	Tablet	10–12 d
Blomgren et al^Citation35	1998	Sweden	Multigroup patients	60.7 y	16:14	33	58.4 y	18:12	34	Solution	100,000 IU	4	21	Fluconazole	Capsule	7 d

Abbreviations: d, days; mo, months; y, years; F, female, M, male.

Figure 2 Risk of bias graph: the overall risk of each bias is presented as a percentage representing the risk in all the included studies.

Figure 3 Risk of bias summary: the risk of each bias in each of the included studies is shown separately.

Note: +, ?, − indicate the low bias, uncertain, and high bias, respectively.

Table 2 Clinical and mycological efficacy of nystatin and the control treatments

Author	Risk factor	Clinical cure rate			Mycological cure rate
		Nystatin (%)	Control (%)	OR (95% CI)	Nystatin (%)	Control (%)	OR (95% CI)
Mima et al^Citation26	Denture	53	45	1.22 (0.35–4.24)	–	–	–
Johnson et al^Citation27	Denture	28.6	0	7.73 (0.31–193.44)	57.1	0	21.86 (0.91–523.42)
		14.3	0	3.92 (0.14–112.90)	71.4	0	37.40 (1.49–936.27)
Nairn^Citation28	Denture	76.9	88.8	0.42 (0.06–2.95)	40	6.25	10.00 (0.92–108.82)
		76.9	40	5.00 (0.96–26.11)	40	20	2.67 (0.36–19.71)
Goins et al^Citation29	Infants	28.6	100	0.01 (0.00–0.26)	5.6	73.3	0.07 (0.01–0.64)
Hoppe^Citation20	Infants	54.1	99	0.01 (0.00–0.09)	8.2	54.1	0.08 (0.03–0.18)
Flynn et al^Citation30	Infants and children	51	91	0.11 (0.04–0.25)	11	76	0.04 (0.01–0.11)
Moshi et al^Citation31	AIDS	63.5	55.6	1.24 (0.65–2.37)	–	–	–
Pons et al^Citation32	HIV/AIDS	52	87	0.16 (0.07–0.38)	6	60	0.04 (0.01–0.13)
Nyst et al^Citation33	AIDS	9	42	0.13 (0.03–0.67)	13	62	0.09 (0.02–0.40)
		9	43	0.12 (0.02–0.66)	13	57	0.12 (0.03–0.50)
Meunier et al^Citation34	Cancer patients	87.5	72.2	2.69 (0.55–13.20)	66	61	1.27 (0.36–4.54)
Blomgren et al^Citation35	Multigroup patients	16.7	30	0.47 (0.14–1.61)	–	–	–

Abbreviations: CI, confidence interval; OR, odds ratio.

Table 3 Meta-analysis of the efficacy of nystatin compared with that of the placebo and fluconazole

Risk factor	Control	Study number	Patient number	Clinical cure rate			Mycological cure rate
				OR (95% CI)	P-value	I^2 (%)	OR (95% CI)	P-value	I^2 (%)
Denture	Placebo	3*	52	5.24 (1.37–20.08)	0.957	0.0	8.50 (2.14–33.84)	0.295	18.1
Infants, children HIV/AIDS	Fluconazole	3	394	0.11 (0.06–0.20)	0.253	27.2	0.04 (0.02–0.09)	0.908	0.0

Note:

* One study was divided into two investigations and included in the meta-analysis.

Abbreviations: CI, confidence interval; OR, odds ratio.

Figure 4 Forest plots evaluating the efficacy of nystatin (fixed-effect model).

Notes: (A) The overall clinical efficacy of nystatin was significantly superior to the placebo in treating denture stomatitis; (B) the overall mycological efficacy of nystatin was significantly superior to the placebo in treating denture stomatitis; (C) the overall clinical efficacy of nystatin was significantly inferior to fluconazole for treating oral or oropharyngeal candidiasis in infants, children, and HIV/AIDS patients; and (D) the overall mycological efficacy of nystatin was significantly inferior to fluconazole for treating oral or oropharyngeal candidiasis in infants, children, and HIV/AIDS patients.
Abbreviations: CI, confidence interval; OR, odds ratio.

Table 4 Summary of the usage and efficacy of nystatin

Risk factor	Formulation	Dose	Frequency (times/day)	Duration (days)	Clinical cure rate (%)	Mycological cure rate (%)
Denture	Suspension	100,000 IU	4	15	53	–
	Pastille	200,000/400,000 IU	5	14	28.6/14.3	57.1/71.4
	Pastille	500,000 IU	4	30	76.9	40
Young age (in infants and children)	Suspension	100,000–400,000 IU	4	10–14	28.6–54.1	5.6–11
HIV/AIDS	Suspension	100,000–500,000 IU	3–4	14	9–63.5	6–13
Cancer	Suspension + pastille	1,000,000+100,000 IU	3	10–12	87.5	66
Multiple	Suspension	100,000 IU	4	21	16.7	–

Table 5 Adverse effects of nystatin and the control treatments

Author	Risk factor	Adverse effects of nystatin	Adverse effects of the control treatment
Mima et al^Citation26	Denture	–	–
Johnson et al^Citation27	Denture	–	–
Nairn^Citation28	Denture	Unpleasant taste in eight patients	Unpleasant taste in five patients
Goins et al^Citation29	Infants	None	None
Hoppe^Citation20	Infants	Ten adverse events in six patients (vomiting, diarrhea)	Seven events in six patients (vomiting, diarrhea)
Flynn et al^Citation30	Young age (infants and children)	Three patients (vomiting, nausea, diarrhea, anorexia, abdominal pain), one patient (rash, headache)	Six patients (vomiting, nausea, diarrhea, anorexia, abdominal pain), one patient (rash, headache)
Moshi et al^Citation31	AIDS	Ten patients	14 patients
Pons et al^Citation32	HIV	Vomiting in one patient	Nausea in one patient, and elevated liver enzyme concentrations in two patients
Nyst et al^Citation33	AIDS	None	Irritation and small superficial oral ulcers in two patients
Meunier et al^Citation34	Cancer	–	–
Blomgren et al^Citation35	Multiple	Nausea in one patient	None

Table S1 Risk of bias and quality assessment of the included studies

Author	Random sequence generation	Allocation concealment	Blinding of participants and personnel	Blinding of outcome assessment	Incomplete outcome data	Selective reporting	Other bias
Mima et al^Citation26	Low bias	Uncertain	High bias	Low bias	Low bias	High bias	Low bias
Johnson et al^Citation27	Uncertain	Uncertain	Low bias	Low bias	High bias	Low bias	Low bias
Nairn^Citation28	Uncertain	Uncertain	Low bias	Low bias	Low bias	Low bias	Uncertain
Goins et al^Citation29	Low bias	Uncertain	High bias	High bias	High bias	Uncertain	Uncertain
Hoppe^Citation20	Low bias	Uncertain	High bias	Uncertain	High bias	Low bias	High bias
Flynn et al^Citation30	Low bias	Low bias	High bias	Low bias	Low bias	Low bias	High bias
Moshi et al^Citation31	Low bias	Uncertain	Uncertain	Low bias	High bias	Uncertain	Uncertain
Pons et al^Citation32	Uncertain	Uncertain	High bias	Low bias	High bias	Uncertain	Uncertain
Nyst et al^Citation33	Low bias	Low bias	Uncertain	Uncertain	High bias	Uncertain	High bias
Meunier et al^Citation34	Low bias	Low bias	High bias	Uncertain	Uncertain	Low bias	Uncertain
Blomgren et al^Citation35	High bias	Uncertain	High bias	Low bias	High bias	Uncertain	High bias

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