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BMJ Clinical Evidence Mar 2009Candida is present in the mouths of up to 60% of healthy people, but overt infection is associated with immunosuppression, diabetes, broad-spectrum antibiotics, and... (Review)
Review
INTRODUCTION
Candida is present in the mouths of up to 60% of healthy people, but overt infection is associated with immunosuppression, diabetes, broad-spectrum antibiotics, and corticosteroid use. In most people, untreated candidiasis persists for months or years unless associated risk factors are treated or eliminated. In neonates, spontaneous cure of oropharyngeal candidiasis usually occurs after 3-8 weeks.
METHODS AND OUTCOMES
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of interventions to prevent and treat oropharyngeal candidiasis in: adults having treatment causing immunosuppression; infants and children; people with diabetes; people with dentures; and people with HIV infection? Which treatments reduce the risk of acquiring resistance to antifungal drugs? We searched: Medline, Embase, The Cochrane Library, and other important databases up to September 2008 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
RESULTS
We found 46 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
CONCLUSIONS
In this systematic review we present information relating to the effectiveness and safety of the following interventions: antifungals (absorbed or partially absorbed, and topical absorbed/partially absorbed/non-absorbed [e.g. amphotericin B, fluconazole, itraconazole, miconazole, and nystatin]) used for intermittent or continuous prophylaxis or therapy, and denture hygiene.
Topics: Administration, Oral; Antifungal Agents; Candidiasis; Candidiasis, Oral; Fluconazole; HIV Infections; Humans; Oropharynx
PubMed: 19445752
DOI: No ID Found -
Veterinary Dermatology Feb 2009The aim of this systematic review was to evaluate the efficacy of antifungal treatments for Malassezia dermatitis in dogs and, when possible, to propose recommendation... (Review)
Review
The aim of this systematic review was to evaluate the efficacy of antifungal treatments for Malassezia dermatitis in dogs and, when possible, to propose recommendation for or against their use. Electronic searches were carried out using PubMed MEDLINE(R), CABDirect and CONSULTANT database. The volumes of Advances in Veterinary Dermatology, the proceedings of ESVD/ECVD and AAVD/ACVD congresses were hand-searched for studies relevant to this review. All articles and book chapters discussing treatment of Malassezia dermatitis were scanned for additional citations. Lastly, a request was sent to the Vetderm Listserv to share recent clinical trials. The analysis evaluated study design, methodology quality, subject enrolment quality, type of interventions and outcome measures. The searches identified 35 articles, and 14 trials that fulfilled the following selection criteria: (i) in vivo clinical trials, (ii) dogs showing clinical lesions of Malassezia dermatitis and (iii) enrolment of at least five dogs. Among these, only eight studies fulfilled the following additional criterion: (iv) prospective in vivo clinical trials reporting clinical and mycological outcome measures. A total number of 14 different treatment protocols included four blinded, randomized and controlled trials (quality of evidence grade A), four controlled studies lacking blinding and/or randomization (grade B), five open uncontrolled trials (grade C) and one descriptive study (grade D). This systematic review allowed us to recommend, with good evidence, the use of only one topical treatment of Malassezia dermatitis (2% miconazole nitrate +2% chlorhexidine, twice a week for 3 weeks) and with fair evidence the use of two systemic treatments with azole derivatives (ketoconazole, 10 mg kg(-1) day(-1) and itraconazole, 5 mg kg(-1) day(-1) for 3 weeks).
Topics: Animals; Antifungal Agents; Dermatomycoses; Dog Diseases; Dogs; Malassezia; Veterinary Medicine
PubMed: 19152584
DOI: 10.1111/j.1365-3164.2008.00721.x -
BMJ Clinical Evidence Jul 2009Around 15% to 25% of people are likely to have athlete's foot at any one time. The infection can spread to other parts of the body and to other people. (Review)
Review
INTRODUCTION
Around 15% to 25% of people are likely to have athlete's foot at any one time. The infection can spread to other parts of the body and to other people.
METHODS AND OUTCOMES
We conducted a systematic review and aimed to answer the following clinical question: What are the effects of topical treatments for athlete's foot? We searched: Medline, Embase, The Cochrane Library, and other important databases up to July 2008 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
RESULTS
We found 14 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
CONCLUSIONS
In this systematic review we present information relating to the effectiveness and safety of the following interventions: improved foot hygiene, including socks and hosiery; topical allylamines (naftifine and terbinafine); topical azoles (bifonazole, clotrimazole, econazole nitrate, miconazole nitrate, sulconazole nitrate, and tioconazole); and topical ciclopirox olamine.
Topics: Administration, Oral; Administration, Topical; Clotrimazole; Drug Administration Schedule; Econazole; Evidence-Based Medicine; Humans; Hygiene; Miconazole; Tinea Pedis
PubMed: 21696646
DOI: No ID Found -
The Cochrane Database of Systematic... Jan 2008Fungal keratitis is common in agricultural tropical countries but relatively uncommon in developed countries. Although there are medications available, their... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Fungal keratitis is common in agricultural tropical countries but relatively uncommon in developed countries. Although there are medications available, their effectiveness is unclear.
OBJECTIVES
The purpose of the review was to examine the effect of different antifungal drugs in the management of fungal keratitis.
SEARCH STRATEGY
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Group Trials Register) in The Cochrane Library (Issue 4, 2006), MEDLINE (1966 to January 2007), EMBASE (1980 to January 2007), LILACS (Latin American and Caribbean Literature on Health Sciences), reference lists of primary reports, review articles and conference proceedings. We contacted investigators and experts in the field for details of published and unpublished reports.
SELECTION CRITERIA
We included all relevant randomised controlled trials on medical therapy for fungal keratitis.
DATA COLLECTION AND ANALYSIS
Two review authors extracted and assessed trial quality. Interventions were compared by the proportions of participants that did not heal after a specific time of therapy. No meta-analysis was performed because the trials studied different medications with different concentrations.
MAIN RESULTS
Six trials were identified which compared different antifungal drugs namely: 1% topical itraconazole versus 1% topical itraconazole and oral itraconazole, different concentrations of silver sulphadiazine versus 1% miconazole, 1% silver sulphadiazine ointment versus 1% miconazole ointment, 2% econazole versus 5% natamycin, different concentrations of topical chlorhexidine gluconate versus 5% natamycin, and 0.2% chlorhexidine gluconate versus 2.5% natamycin. A total of 370 participants were randomised. No single reference drug was used. All trials considered clinical cure as primary outcome. Comparing treatment effects of all the drug preparations studied, silver sulphadiazine ointment had the lowest proportion of participants with treatment failure followed by itraconazole, miconazole, chlorhexidine, econazole, and the drug with the most treatment failure was natamycin. These differences were not, however, statistically significant which might in part be due to low sample sizes.
AUTHORS' CONCLUSIONS
There is no evidence that the current available and investigational antifungal agents are effective. The review identified the need for large multicentre randomised trials.
Topics: Antifungal Agents; Eye Infections, Fungal; Humans; Keratitis; Randomized Controlled Trials as Topic
PubMed: 18254043
DOI: 10.1002/14651858.CD004241.pub2 -
The Cochrane Database of Systematic... Oct 2007Invasive fungal infection is an important cause of mortality and morbidity in very low birth weight infants. Early diagnosis is difficult, and treatment is often... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Invasive fungal infection is an important cause of mortality and morbidity in very low birth weight infants. Early diagnosis is difficult, and treatment is often delayed. The available data are insufficient to conclude that topical/oral prophylaxis (usually nystatin and/or miconazole) prevents invasive fungal infection or mortality in very low birth weight infants. Systemic antifungal agents (usually azoles) are increasingly used as prophylaxis against invasive fungal infection.
OBJECTIVES
To assess the effect of prophylactic systemic antifungal therapy on mortality and morbidity in very low birth weight infants.
SEARCH STRATEGY
The standard search strategy of the Cochrane Neonatal Review Group was used. This included searches of the Cochrane Controlled Trials Register (The Cochrane Library, Issue 2, 2007), MEDLINE (1966 - May 2007), EMBASE (1980 - May 2007), conference proceedings, and previous reviews.
SELECTION CRITERIA
Randomised controlled trials that compared the effect of prophylactic systemic antifungal therapy versus placebo, or no drug, or another antifungal agent or dose regimen, in very low birth weight infants.
DATA COLLECTION AND ANALYSIS
Data were extracted using the standard methods of the Cochrane Neonatal Review Group, with separate evaluation of trial quality and data extraction by each author, and synthesis of data using relative risk, risk difference, and weighted mean difference. The pre-specified outcomes were death prior to hospital discharge, long-term neurodevelopment, incidence of invasive fungal infection, emergence of antifungal resistance, and adverse drug reactions.
MAIN RESULTS
Seven eligible trials enrolling a total of 638 participating infants were identified. Meta-analysis of data from four trials that compared prophylactic fluconazole versus placebo revealed a statistically significant reduction in the risk of invasive fungal infection in the infants who received prophylaxis [typical relative risk: 0.23 (95% confidence interval 0.11, 0.46); typical risk difference: -0.11 (95% confidence interval -0.16, -0.06); number needed to treat: 9 (95% confidence interval 6, 17)]. There was no statistically significant difference in the risk of death prior to hospital discharge [typical relative risk: 0.61 (95% confidence interval 0.37, 1.03); typical risk difference: -0.05 (95% confidence interval -0.11, -0.00)]. Only one trial reported long term neurodevelopmental outcomes. There were no statistically significant differences in the incidence of developmental delay, or motor or sensory neurological impairment in children assessed at a median age of 16 months. One small trial that compared systemic versus oral/topical prophylaxis did not detect a statistically significant effect on invasive fungal infection or mortality. Two trials compared different dosing regimens of prophylactic intravenous fluconazole. These did not detect any significant differences in infection rates or mortality.
AUTHORS' CONCLUSIONS
Prophylactic systemic antifungal therapy reduces the incidence of invasive fungal infection in very low birth weight infants. This finding should be interpreted cautiously. The incidence of invasive fungal infection was very high in the control groups of some of the included trials. Furthermore, the trials may have been affected by ascertainment bias since use of prophylactic fluconazole may reduce the sensitivity of microbiological culture for detecting fungi in blood, urine, or cerebrospinal fluid. Meta-analysis does not demonstrate a statistically significant effect on overall mortality rates, but the 95% confidence interval around this estimate of effect is wide. There are currently only limited data on the long-term neurodevelopmental consequences for infants exposed to this intervention. In addition, there is a need for further data on the effect of the intervention on the emergence of organisms with antifungal resistance.
Topics: Antifungal Agents; Developmental Disabilities; Fluconazole; Hospital Mortality; Humans; Infant, Newborn; Infant, Very Low Birth Weight; Mycoses; Randomized Controlled Trials as Topic
PubMed: 17943803
DOI: 10.1002/14651858.CD003850.pub3 -
The Cochrane Database of Systematic... 2004Systemic fungal infection has increased in prevalence in neonatal intensive care units (NICU) caring for very low birth weight infants. It is associated with a prolonged... (Review)
Review
BACKGROUND
Systemic fungal infection has increased in prevalence in neonatal intensive care units (NICU) caring for very low birth weight infants. It is associated with a prolonged stay and an increase in morbidity and mortality. An assessment of the use of oral prophylactic antifungals to prevent systemic infection is needed.
OBJECTIVES
To assess whether the prophylactic administration of oral antifungal agents to very preterm infants reduces the occurrence of systemic fungal infection.
SEARCH STRATEGY
The standard methods of the Cochrane Collaboration and its Neonatal Review Group were used. Searches were carried out up to July 2003 on the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library Issue 2, 2003), MEDLINE from 1966, EMBASE from 1980, CINAHL from 1992. Abstracts from SPR (1993 - 2003) and ESPR (1995 to 2002) were hand searched.
SELECTION CRITERIA
Randomized and quasi randomized controlled trials in very low birth weight or very preterm infants in which an oral antifungal agent was compared with placebo or no treatment or another oral antifungal agent
DATA COLLECTION AND ANALYSIS
Data were extracted using the standard methods of the Cochrane Neonatal Review Group, with separate evaluation of the trial quality and data extraction undertaken by each author. Results were reported using relative risk (RR) and risk difference (RD) and weighted mean difference (WMD). 95% confidence intervals were reported.
MAIN RESULTS
We identified three eligible trials, one comparing nystatin with no treatment (67 infants), one comparing miconazole with placebo (600 infants), and one comparing nystatin with fluconazole (21 infants). As the two trials comparing nystatin or miconazole with placebo or no treatment were clinically quite different, meta-analysis was not performed. In the trial of nystatin versus no treatment, systemic fungal infection was significantly reduced [RR 0.19 (0.04,0.78)] in the group treated with nystatin. In the study comparing miconazole with placebo there was no significant effect on systemic fungal infection [RR 1.32 (0.46,3.75)]. Neither study found a significant effect on mortality, and there was no significant difference in the mean number of days infants received ventilation or stayed in the neonatal intensive care unit. In the small trial comparing oral fluconazole with nystatin, no significant difference in systemic fungal infection [RR 0.17 (0.01, 2.84)] or mortality [RR 0.17 (0.01, 2.84)] was reported. Adverse drug reactions were not reported in any study.
REVIEWER'S CONCLUSIONS
There is insufficient evidence to support the use of prophylactic oral antifungal agents in very low birth weight infants in the neonatal intensive care unit. Randomised controlled trials in current neonatal practice settings are needed, comparing oral antifungal agents with placebo and with each other and including an assessment of side effects, in order to determine whether oral antifungal agents have a role in preventing systemic fungal infections in preterm infants.
Topics: Administration, Oral; Antifungal Agents; Candidiasis; Candidiasis, Chronic Mucocutaneous; Fluconazole; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Infant, Very Low Birth Weight; Miconazole; Nystatin; Randomized Controlled Trials as Topic
PubMed: 14974017
DOI: 10.1002/14651858.CD003478.pub2 -
The Cochrane Database of Systematic... 2002Systemic fungal infection is considered to be an important cause of morbidity and mortality in cancer patients, particularly those with neutropenia. Antifungal drugs are... (Review)
Review
BACKGROUND
Systemic fungal infection is considered to be an important cause of morbidity and mortality in cancer patients, particularly those with neutropenia. Antifungal drugs are often given prophylactically, or to patients with persistent fever.
OBJECTIVES
The objective of this review was to assess the effect of antifungal drugs in cancer patients with neutropenia.
SEARCH STRATEGY
We searched the Cochrane Controlled Trials Register and MEDLINE (November 2001) and the reference lists of articles. We searched the proceedings of the ICAAC (from 1990 to 2001, General Meeting of the ASM (from 1990 to 2001), and the European Congress of Clinical Microbiology and Infectious Diseases (1995 to 2001) and contacted researchers in the field.
SELECTION CRITERIA
Randomised trials of amphotericin B, fluconazole, ketoconazole, miconazole, or itraconazole compared with placebo or no treatment in cancer patients with neutropenia.
DATA COLLECTION AND ANALYSIS
Two reviewers independently assessed trial eligibility, methodological quality and abstracted data.
MAIN RESULTS
Thirty trials involving 4094 patients were included. Prophylactic or empirical treatment with antifungals as a group had no statistically significant effect on mortality (relative risk 0.95, 95% confidence interval 0.82 to 1.11). The relative risk was smallest for amphotericin B, 0.73 (0.52 to 1.03) (P=0.08). In another review, three trials compared intravenous lipid soluble amphotericin B (AmBisome) with smaller doses of standard intravenous amphotericin B; the relative risk was 0.74 (0.52 to 1.07). Taken together, these results indicate that intravenous amphotericin B might decrease mortality. In contrast, trials with fluconazole, ketoconazole, miconazole and itraconazole failed to find an effect on mortality. The incidence of invasive fungal infection decreased significantly with administration of amphotericin B (relative risk 0.39, 95% CI 0.20 to 0.76), fluconazole (0.39, 0.27 to 0.57) and itraconazole (0.51, 0.27 to 0.96), but not with miconazole or ketoconazole.
REVIEWER'S CONCLUSIONS
Intravenous amphotericin B is the only antifungal agent for which there is evidence suggesting that it might reduce mortality. It should therefore be preferred when prophylactic or empirical antifungal therapy in cancer patients with neutropenia is considered indicated.
Topics: Antifungal Agents; Humans; Immunocompromised Host; Mycoses; Neoplasms; Neutropenia; Opportunistic Infections; Randomized Controlled Trials as Topic
PubMed: 12076377
DOI: 10.1002/14651858.CD000026 -
The Cochrane Database of Systematic... 2000Systemic fungal infection is considered to be an important cause of morbidity and mortality in cancer patients, particularly those with neutropenia. Antifungal drugs are... (Review)
Review
BACKGROUND
Systemic fungal infection is considered to be an important cause of morbidity and mortality in cancer patients, particularly those with neutropenia. Antifungal drugs are often given prophylactically, or to patients with persistent fever.
OBJECTIVES
The objective of this review was to assess the effect of antifungal drugs in cancer patients with neutropenia.
SEARCH STRATEGY
We searched the Cochrane Controlled Trials Register and MEDLINE (November 1999) and the reference lists of articles. We searched the proceedings of the ICAAC, General Meeting of the ASM (from 1990 to 1999), and the 7th European Congress of Clinical Microbiology and Infectious Diseases (1995 to 1999) and contacted researchers in the field.
SELECTION CRITERIA
Randomised trials of amphotericin B, AmBisome, fluconazole, ketoconazole, miconazole, or itraconazole compared with placebo or no treatment in cancer patients with neutropenia.
DATA COLLECTION AND ANALYSIS
Two reviewers independently assessed trial eligibility, methodological quality and abstracted data.
MAIN RESULTS
Twenty-nine trials involving 3875 patients were included. Intravenous amphotericin B reduced total mortality (relative risk 0.72, 95% confidence interval 0.51 to 1.02, P=0.06) based on 8 trials. This borderline result was confirmed by three trials which compared lipid soluble amphotericin B (AmBisome) with smaller doses of standard amphotericin B; the trials demonstrated an effect of AmBisome on mortality, relative risk 0.70 (95% CI 0.50 to 0.99). The risk difference for the two estimates combined is 0.040 (95% CI 0.012 to 0.068) which means that 25 patients (95% CI 15 to 83) would need to be treated with intravenous amphotericin B to avoid one death. In contrast, fluconazole, ketoconazole, miconazole and itraconazole had no effect on mortality. The incidence of invasive fungal infection decreased with administration of amphotericin B (relative risk 0.39, 95% CI 0.20 to 0.76), fluconazole (relative risk 0.39, 95% CI 0.27 to 0.57) and itraconazole (relative risk 0.45, 95% CI 0.20 to 0.99), but not with miconazole or ketoconazole.
REVIEWER'S CONCLUSIONS
Intravenous amphotericin B is the only antifungal agent which has a documented effect on mortality, and there is not sufficient evidence to judge the relative merits of other antifungal agents. This drug should therefore be preferred for prophylactic or empirical antifungal therapy in cancer patients with neutropenia.
Topics: Antifungal Agents; Humans; Immunocompromised Host; Mycoses; Neoplasms; Neutropenia; Opportunistic Infections; Randomized Controlled Trials as Topic
PubMed: 11034669
DOI: 10.1002/14651858.CD000026 -
The Cochrane Database of Systematic... 2000Systemic fungal infection is considered to be an important cause of morbidity and mortality in cancer patients, particularly those with neutropenia. Antifungal drugs are... (Review)
Review
BACKGROUND
Systemic fungal infection is considered to be an important cause of morbidity and mortality in cancer patients, particularly those with neutropenia. Antifungal drugs are often given prophylactically, or to patients with persistent fever.
OBJECTIVES
The objective of this review was to assess the effect of antifungal drugs in cancer patients with neutropenia.
SEARCH STRATEGY
We searched the Cochrane Controlled Trials Register (October 1997), MEDLINE (to September 1997) and the reference lists of articles. We searched the proceedings of the ICAAC, General Meeting of the ASM (from 1990 to 1995), and the 7th European Congress of Clinical Microbiology and Infectious Diseases (1995) and contacted researchers in the field.
SELECTION CRITERIA
Randomised trials of amphotericin B, AmBisome, fluconazole, ketoconazole, miconazole, or itraconazole compared with placebo or no treatment in cancer patients with neutropenia.
DATA COLLECTION AND ANALYSIS
Two reviewers independently assessed trial eligibility, methodological quality and abstracted data.
MAIN RESULTS
Twenty-five trials involving 2912 patients were included. In 19 trials, prophylactic or later treatment with antifungal drugs had no effect on mortality (odds ratio 0.92, 95% confidence interval 0.75 to 1.14). Only amphotericin showed a significant benefit (odds ratio 0.58, 95% confidence interval 0.37 to 0.93) based on seven trials, but the studies were small and the difference in number of deaths was only 15. Overall it would be necessary to treat 59 patients (95% confidence interval 37 to 131) with an antifungal drug to prevent one case of fungal invasion in surviving patients, although only amphotericin and fluconazole showed a clear beneficial effect. Antifungal treatment decreased fungal colonisation and the need for additional antifungal therapy, but there was heterogeneity across the trials.
REVIEWER'S CONCLUSIONS
Routine prophylactic or later therapy with antifungal drugs in cancer patients with neutropenia does not appear to have a beneficial effect on mortality and only a modest effect on fungal invasion.
Topics: Antifungal Agents; Humans; Mycoses; Neoplasms; Neutropenia; Opportunistic Infections
PubMed: 10796687
DOI: 10.1002/14651858.CD000026