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The Cochrane Database of Systematic... May 2015Seborrhoeic dermatitis is a chronic inflammatory skin condition that is distributed worldwide. It commonly affects the scalp, face and flexures of the body. Treatment... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Seborrhoeic dermatitis is a chronic inflammatory skin condition that is distributed worldwide. It commonly affects the scalp, face and flexures of the body. Treatment options include antifungal drugs, steroids, calcineurin inhibitors, keratolytic agents and phototherapy.
OBJECTIVES
To assess the effects of antifungal agents for seborrhoeic dermatitis of the face and scalp in adolescents and adults.A secondary objective is to assess whether the same interventions are effective in the management of seborrhoeic dermatitis in patients with HIV/AIDS.
SEARCH METHODS
We searched the following databases up to December 2014: the Cochrane Skin Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL) (2014, Issue 11), MEDLINE (from 1946), EMBASE (from 1974) and Latin American Caribbean Health Sciences Literature (LILACS) (from 1982). We also searched trials registries and checked the bibliographies of published studies for further trials.
SELECTION CRITERIA
Randomised controlled trials of topical antifungals used for treatment of seborrhoeic dermatitis in adolescents and adults, with primary outcome measures of complete clearance of symptoms and improved quality of life.
DATA COLLECTION AND ANALYSIS
Review author pairs independently assessed eligibility for inclusion, extracted study data and assessed risk of bias of included studies. We performed fixed-effect meta-analysis for studies with low statistical heterogeneity and used a random-effects model when heterogeneity was high.
MAIN RESULTS
We included 51 studies with 9052 participants. Of these, 45 trials assessed treatment outcomes at five weeks or less after commencement of treatment, and six trials assessed outcomes over a longer time frame. We believe that 24 trials had some form of conflict of interest, such as funding by pharmaceutical companies.Among the included studies were 12 ketoconazole trials (N = 3253), 11 ciclopirox trials (N = 3029), two lithium trials (N = 141), two bifonazole trials (N = 136) and one clotrimazole trial (N = 126) that compared the effectiveness of these treatments versus placebo or vehicle. Nine ketoconazole trials (N = 632) and one miconazole trial (N = 47) compared these treatments versus steroids. Fourteen studies (N = 1541) compared one antifungal versus another or compared different doses or schedules of administration of the same agent versus one another. KetoconazoleTopical ketoconazole 2% treatment showed a 31% lower risk of failed clearance of rashes compared with placebo (risk ratio (RR) 0.69, 95% confidence interval (CI) 0.59 to 0.81, eight studies, low-quality evidence) at four weeks of follow-up, but the effect on side effects was uncertain because evidence was of very low quality (RR 0.97, 95% CI 0.58 to 1.64, six studies); heterogeneity between studies was substantial (I² = 74%). The median proportion of those who did not have clearance in the placebo groups was 69%.Ketoconazole treatment resulted in a remission rate similar to that of steroids (RR 1.17, 95% CI 0.95 to 1.44, six studies, low-quality evidence), but occurrence of side effects was 44% lower in the ketoconazole group than in the steroid group (RR 0.56, 95% CI 0.32 to 0.96, eight studies, moderate-quality evidence).Ketoconozale yielded a similar remission failure rate as ciclopirox (RR 1.09, 95% CI 0.95 to 1.26, three studies, low-quality evidence). Most comparisons between ketoconazole and other antifungals were based on single studies that showed comparability of treatment effects. CiclopiroxCiclopirox 1% led to a lower failed remission rate than placebo at four weeks of follow-up (RR 0.79, 95% CI 0.67 to 0.94, eight studies, moderate-quality evidence) with similar rates of side effects (RR 0.9, 95% CI 0.72 to 1.11, four studies, moderate-quality evidence). Other antifungalsClotrimazole and miconazole efficacies were comparable with those of steroids on short-term assessment in single studies.Treatment effects on individual symptoms were less clear and were inconsistent, possibly because of difficulties encountered in measuring these symptoms.Evidence was insufficient to conclude that dose or mode of delivery influenced treatment outcome. Only one study reported on treatment compliance. No study assessed quality of life. One study assessed the maximum rash-free period but provided insufficient data for analysis. One small study in patients with HIV compared the effect of lithium versus placebo on seborrhoeic dermatitis of the face, but treatment outcomes were similar.
AUTHORS' CONCLUSIONS
Ketoconazole and ciclopirox are more effective than placebo, but limited evidence suggests that either of these agents is more effective than any other agent within the same class. Very few studies have assessed symptom clearance for longer periods than four weeks. Ketoconazole produced findings similar to those of steroids, but side effects were fewer. Treatment effect on overall quality of life remains unknown. Better outcome measures, studies of better quality and better reporting are all needed to improve the evidence base for antifungals for seborrhoeic dermatitis.
Topics: Adolescent; Adult; Antifungal Agents; Ciclopirox; Clotrimazole; Dermatitis, Seborrheic; Facial Dermatoses; Humans; Ketoconazole; Lithium Compounds; Miconazole; Pyridones; Randomized Controlled Trials as Topic; Scalp Dermatoses; Solanum; Steroids
PubMed: 25933684
DOI: 10.1002/14651858.CD008138.pub3 -
The Cochrane Database of Systematic... Apr 2015Fungal keratitis is a fungal infection of the cornea. It is common in lower income countries, particularly in agricultural areas but relatively uncommon in higher income... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Fungal keratitis is a fungal infection of the cornea. It is common in lower income countries, particularly in agricultural areas but relatively uncommon in higher income countries. Although there are medications available, their effectiveness is unclear.
OBJECTIVES
To assess the effects of different antifungal drugs in the management of fungal keratitis.
SEARCH METHODS
We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (2015, Issue 2), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to March 2015), EMBASE (January 1980 to March 2015), Latin American and Caribbean Health Sciences Literature Database (LILACS) (January 1982 to March 2015), the ISRCTN registry (www.isrctn.com/editAdvancedSearch), ClinicalTrials.gov (www.clinicaltrials.gov) and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 16 March 2015.
SELECTION CRITERIA
We included randomised controlled trials of medical therapy for fungal keratitis.
DATA COLLECTION AND ANALYSIS
Two review authors selected studies for inclusion in the review, assessed trials for risk of bias and extracted data. The primary outcome was clinical cure at two to three months. Secondary outcomes included best-corrected visual acuity, time to clinical cure, compliance with treatment, adverse outcomes and quality of life.
MAIN RESULTS
We included 12 trials in this review; 10 trials were conducted in India, one in Bangladesh and one in Egypt. Seven of these trials were at high risk of bias in one or more domains, two of these studies were at low risk of bias in all domains. Participants were randomised to the following comparisons: topical 5% natamycin compared to topical 1% voriconazole; topical 5% natamycin compared to topical 2% econazole; topical 5% natamycin compared to topical chlorhexidine gluconate (0.05%, 0.1% and 0.2%); topical 1% voriconazole compared to intrastromal voriconazole 50 g/0.1 mL (both treatments combined with topical 5% natamycin); topical 1% voriconazole combined with oral voriconazole compared to both oral voriconazole and oral itraconazole (both combined with topical 5% natamycin); topical 1% itraconazole compared to topical 1% itraconazole combined with oral itraconazole; topical amphotericin B compared to topical amphotericin B combined with subconjunctival injection of fluconazole; intracameral injection of amphotericin B with conventional treatment compared to conventional treatment alone (severe fungal ulcers); topical 0.5% and 1% silver sulphadiazine compared to topical 1% miconazole. Overall the results were inconclusive because for most comparisons only one small trial was available. The exception was the comparison of topical natamycin and topical voriconazole for which three trials were available. In one of these trials clinical cure (healed ulcer) was reported in all 15 people allocated to natamycin and in 14/15 people allocated to voriconazole (risk ratio (RR) 1.07; 95% confidence interval (CI) 0.89 to 1.28, low quality evidence). In one trial people randomised to natamycin were more likely to have a microbiological cure at six days (RR 1.64; 95% CI 1.38 to 1.94, 299 participants). On average, people randomised to natamycin had better spectacle-corrected visual acuity at two to three months compared to people randomised to voriconazole but the estimate was uncertain and the 95% confidence intervals included 0 (no difference) (mean difference -0.12 logMAR, 95% CI -0.31 to 0.06, 434 participants; 3 studies, low quality evidence) and a decreased risk of corneal perforation or therapeutic penetrating keratoplasty, or both (RR 0.61; 95% CI 0.40 to 0.94, 434 participants, high quality evidence). There was inconclusive evidence on time to clinical cure. Compliance with treatment and quality of life were not reported. One trial comparing natamycin and voriconazole found the effect of treatment greater in Fusarium species, but this subgroup analysis was not prespecified by this review.
AUTHORS' CONCLUSIONS
The trials included in this review were of variable quality and were generally underpowered. There is evidence that natamycin is more effective than voriconazole in the treatment of fungal ulcers. Future research should evaluate treatment effects according to fungus species.
Topics: Antifungal Agents; Eye Infections, Fungal; Humans; Keratitis; Natamycin; Randomized Controlled Trials as Topic; Voriconazole
PubMed: 25855311
DOI: 10.1002/14651858.CD004241.pub4 -
The Cochrane Database of Systematic... Sep 2014Systemic fungal infection is considered to be an important cause of morbidity and mortality in cancer patients, particularly those with neutropenia. Antifungal drugs are... (Meta-Analysis)
Meta-Analysis 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 empirically to patients with persistent fever.
OBJECTIVES
To assess whether commonly used antifungal drugs decrease mortality in cancer patients with neutropenia.
SEARCH METHODS
We searched PubMed from 1966 to 7 July 2014 and the reference lists of identified articles.
SELECTION CRITERIA
Randomised clinical trials of amphotericin B, fluconazole, ketoconazole, miconazole, itraconazole or voriconazole compared with placebo or no treatment in cancer patients with neutropenia.
DATA COLLECTION AND ANALYSIS
The two review authors independently assessed trial eligibility and risk of bias, and abstracted data.
MAIN RESULTS
Thirty-two trials involving 4287 patients were included. Prophylactic or empirical treatment with amphotericin B significantly decreased total mortality (relative risk (RR) 0.69, 95% confidence interval (CI) 0.50 to 0.96), whereas the estimated RRs for fluconazole, ketoconazole, miconazole, and itraconazole were close to 1.00. No eligible trials were found with voriconazole. Amphotericin B and fluconazole decreased mortality ascribed to fungal infection (RR 0.45, 95% CI 0.26 to 0.76 and RR 0.42, 95% CI 0.24 to 0.73, respectively). The incidence of invasive fungal infection decreased significantly with administration of amphotericin B (RR 0.41, 95% CI 0.24 to 0.73), fluconazole (RR 0.39, 95% CI 0.27 to 0.57) and itraconazole (RR 0.53, 95% CI 0.29 to 0.97), but not with ketoconazole or miconazole. Effect estimates were similar for those 13 trials that had adequate allocation concealment and were blinded. The reporting of harms was far too variable from trial to trial to allow a meaningful overview. For the 2011 and 2014 updates no additional trials were identified for inclusion.
AUTHORS' CONCLUSIONS
Intravenous amphotericin B was the only antifungal agent that reduced total mortality. It should therefore be preferred when prophylactic or empirical antifungal therapy is introduced in cancer patients with neutropenia.
Topics: Antifungal Agents; Humans; Immunocompromised Host; Mycoses; Neoplasms; Neutropenia; Opportunistic Infections; Randomized Controlled Trials as Topic
PubMed: 25188768
DOI: 10.1002/14651858.CD000026.pub2 -
Asia-Pacific Journal of Ophthalmology... 2014Fungal keratitis (FK) typically requires intensive therapy with topical antifungal agents. To date, evidence from clinical trials has been conflicting with respect to...
Fungal keratitis (FK) typically requires intensive therapy with topical antifungal agents. To date, evidence from clinical trials has been conflicting with respect to the most effective topical antifungal drug in the treatment of FK. Therefore, a systematic review and meta-analysis of randomized controlled trials (RCTS) using the Cochrane methodology was undertaken to evaluate the effectiveness of topical antifungals in management of FK. Outcomes included time to cure, treatment failure, complications of infection, visual acuity and adverse effects. A comprehensive search for studies was undertaken resulting in inclusion of 8 RCTs, predominantly from India, involving a total of 793 participants, the majority of whom were infected with filamentous fungi. Topical voriconazole was more likely to result in therapeutic keratoplasty compared with natamycin [relative risk (RR) 1.89 95% CI: 1.14, 3.12] with a number needed to treat of 13 (95% CI: 7, 50). Final visual acuity was significantly better with natamycin compared with voriconazole [weighted mean difference (WMD) 0.13, 95% CI 0.00, 0.27]. There was no difference in risk of treatment failure across all topical antifungal treatments studied (chlorhexidine gluconate, econazole, miconazole, natamycin, silver sulphadiazine and voriconazole). This study suggests treatment failure was comparable among antifungal treatments reviewed. However, natamycin resulted in better visual acuity following acute infection, compared with voriconazole. Voriconazole had a significantly greater risk of therapeutic keratoplasty compared with natamycin in the populations studied.
PubMed: 26107307
DOI: 10.1097/APO.0b013e3182a618dd -
BMJ Clinical Evidence Nov 2013Candida is a fungus present in the mouths of up to 60% of healthy people, but overt infection is associated with immunosuppression, diabetes, broad-spectrum antibiotics,... (Review)
Review
INTRODUCTION
Candida is a fungus 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 to 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 undergoing treatments that cause immunosuppression; infants and children; people with dentures; and people with HIV infection? Which antifungal treatments reduce the risk of acquiring resistance to antifungal drugs? We searched: Medline, Embase, The Cochrane Library, and other important databases up to July 2013 (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), the European Medicines Agency (EMA), and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
RESULTS
We found 47 RCTs or systematic reviews of RCTs 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, partially or topically absorbed, or non-absorbed; for example, imidazole [ketoconazole, clotrimazole, toiconazole, miconazole], polyene [amphotericin B, nystatin], triazole [fluconazole, itraconazole], melaleuca and posaconazole), intermittent or continuous prophylaxis, or treatment, and denture hygiene.
Topics: Administration, Oral; Antifungal Agents; Candidiasis, Oral; HIV Infections; Humans; Miconazole; Oropharynx
PubMed: 24209593
DOI: No ID Found -
The Cochrane Database of Systematic... Mar 2013Invasive fungal infection is an important cause of mortality and morbidity in very preterm or very low birth weight infants. Uncertainty exists about the effect of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Invasive fungal infection is an important cause of mortality and morbidity in very preterm or very low birth weight infants. Uncertainty exists about the effect of prophylactic oral/topical non-absorbed antifungals to reduce mucocutaneous colonisation and so limit the risk of invasive fungal infection in this population.
OBJECTIVES
To assess the effect of prophylactic oral/topical non-absorbed antifungal therapy on the incidence of invasive fungal infection, mortality and morbidity in very preterm or very low birth weight infants.
SEARCH METHODS
We used the standard search strategy of the Cochrane Neonatal Review Group. This included searches of the Cochrane Central Register of Controlled Trials (CENTRAL: The Cochrane Library, 2012, Issue 3), MEDLINE, EMBASE, and CINAHL (to August 2012), conference proceedings, and previous reviews.
SELECTION CRITERIA
Randomised controlled trials or quasi-randomised controlled trials that compared the effect of prophylactic oral/topical non-absorbed antifungal therapy versus placebo or no drug or another antifungal agent or dose regimen in very preterm or very low birth weight infants.
DATA COLLECTION AND ANALYSIS
We extracted data using the standard methods of the Cochrane Neonatal Review Group with separate evaluation of trial quality and data extraction by two review authors.
MAIN RESULTS
Four trials, in which a total of 1800 infants participated, compared oral/topical non-absorbed antifungal prophylaxis (nystatin or miconazole) with placebo or no drug. These trials had various methodological weaknesses including quasi-randomisation, lack of allocation concealment, and lack of blinding of intervention and outcomes assessment. The incidence of invasive fungal infection was very high in the control groups of three of these trials. Meta-analysis found a statistically significant reduction in the incidence of invasive fungal infection [typical risk ratio 0.20 (95% confidence interval 0.14 to 0.27); risk difference -0.18 (-0.21 to -0.16)] but substantial statistical heterogeneity was present. We did not find a statistically significant effect on mortality [typical risk ratio 0.87 (0.72 to 1.05); risk difference -0.03 (-0.06 to 0.01)]. None of the trials assessed posthospital discharge outcomes.Two trials (N = 265) assessed the effect of oral/topical non-absorbed versus systemic antifungal prophylaxis. Meta-analyses did not find any statistically significant differences in the incidences of invasive fungal infection or all-cause mortality.
AUTHORS' CONCLUSIONS
The finding of a reduction in risk of invasive fungal infection in very low birth weight infants treated with oral/topical non-absorbed antifungal prophylaxis should be interpreted cautiously because of methodological weaknesses in the included trials. Further large randomised controlled trials in current neonatal practice settings are needed to resolve this uncertainty. These trials might compare oral/topical non-absorbed antifungal agents with placebo, with each other, or with systemic antifungal agents and should include an assessment of effect on long-term neurodevelopmental outcomes.
Topics: Administration, Oral; Administration, Topical; Antifungal Agents; Fluconazole; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Infant, Very Low Birth Weight; Miconazole; Mycoses; Nystatin; Randomized Controlled Trials as Topic
PubMed: 23543519
DOI: 10.1002/14651858.CD003478.pub4 -
American Journal of Rhinology & Allergy 2012Chronic rhinosinusitis (CRS) is an inflammatory disorder of the nose and sinuses. Because fungi were postulated as a potential cause of CRS in the late 1990s,... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Chronic rhinosinusitis (CRS) is an inflammatory disorder of the nose and sinuses. Because fungi were postulated as a potential cause of CRS in the late 1990s, contrasting articles have advocated and refuted the use of antifungal agents in its management. Although good research shows an interaction of the immune system with fungus in CRS, e.g., allergic fungal sinusitis (AFS), this does not imply that fungi are the cause of CRS or that antifungals will be effective in management. This study was designed to assess the potential advantage of either topical or systemic antifungal therapy in the symptomatic treatment of CRS to aid physicians in making informed decisions about treating patients with CRS.
METHODS
A systematic review of the literature was performed with meta-analysis. All studies obtained from searches were reviewed and trials meeting the eligibility criteria were selected. CRS was defined using either the European Position Paper on Rhinosinusitis and Nasal Polyps or American Academy of Otolaryngology-Head and Neck Surgery criteria. Authors were contacted and original data were used for data analysis.
RESULTS
Five studies investigating topical antifungals and one investigating systemic antifungals met the inclusion criteria. All trials were double blinded and randomized. Pooled meta-analysis showed no statistically significant benefit of topical or systemic antifungals over placebo. Symptoms scores statistically favored the placebo group for this outcome. Adverse event reporting was higher in the antifungal group.
CONCLUSION
Reported side-effects of antifungal therapies may outweigh any potential benefits of treatment based on this meta-analysis and the authors therefore do not advocate the use antifungal treatment in the management of CRS.
Topics: Antifungal Agents; Chronic Disease; Disease Management; Humans; Miconazole; Mycoses; Randomized Controlled Trials as Topic; Rhinitis; Sinusitis; Treatment Outcome
PubMed: 22487292
DOI: 10.2500/ajra.2012.26.3710 -
BMJ Clinical Evidence Feb 2012Candida is a fungus present in the mouths of up to 60% of healthy people, but overt infection is associated with immunosuppression, diabetes, broad-spectrum antibiotics,... (Review)
Review
INTRODUCTION
Candida is a fungus 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 to 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 August 2011 (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 51 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, clotrimazole, fluconazole, itraconazole, ketoconazole, miconazole, nystatin, posaconazole) used for intermittent or continuous prophylaxis or treatment, and denture hygiene.
Topics: Administration, Oral; Antifungal Agents; Candidiasis, Oral; Fluconazole; HIV Infections; Humans; Oropharynx
PubMed: 22348417
DOI: No ID Found -
The Cochrane Database of Systematic... Feb 2012Fungal keratitis is a fungal infection of the cornea. It is common in agricultural tropical countries but relatively uncommon in developed countries. Although there are... (Review)
Review
BACKGROUND
Fungal keratitis is a fungal infection of the cornea. It is common in agricultural tropical countries but relatively uncommon in developed countries. Although there are medications available, their effectiveness is unclear.
OBJECTIVES
To examine the effect of different antifungal drugs in the management of fungal keratitis.
SEARCH METHODS
We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2011, Issue 8), MEDLINE (January 1950 to August 2011), EMBASE (January 1980 to August 2011), Latin American and Caribbean Literature on Health Sciences (LILACS) (January 1982 to August 2011), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com) and ClinicalTrials.gov (www.clinicaltrials.gov). There were no date or language restrictions in the electronic searches for trials. The electronic databases were last searched on 29 August 2011.
SELECTION CRITERIA
We included all relevant randomised controlled trials (RCTs) on medical therapy for fungal keratitis.
DATA COLLECTION AND ANALYSIS
Two review authors selected studies for inclusion into the review, assessed trials for risk of bias and extracted data. 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
We included nine trials in this review; seven conducted in India, one in Bangladesh and one in Egypt. A total of 568 participants were randomised to the following comparisons: 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, 0.2% chlorhexidine gluconate versus 2.5% natamycin and voriconazole 1% versus natamycin 5%. The included trials were small and of variable quality. Differences between different regimens were not statistically different, which may reflect the low sample sizes.
AUTHORS' CONCLUSIONS
Based on the trials included in this review, there is no evidence to date that any particular drug, or combination of drugs, is more effective in the management of fungal keratitis. The trials included in this review were of variable quality and were generally underpowered.
Topics: Antifungal Agents; Eye Infections, Fungal; Humans; Keratitis; Randomized Controlled Trials as Topic
PubMed: 22336802
DOI: 10.1002/14651858.CD004241.pub3 -
The Cochrane Database of Systematic... Oct 2009Invasive fungal infection is an important cause of mortality and morbidity in very preterm (< 32 weeks gestation) or very low birth weight (VLBW) infants. Clinical... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Invasive fungal infection is an important cause of mortality and morbidity in very preterm (< 32 weeks gestation) or very low birth weight (VLBW) infants. Clinical uncertainly exists about the effect of prophylactic oral/topical non-absorbed antifungals to reduce mucocutaneous colonisation and so limit the risk of invasive fungal infection in this population.
OBJECTIVES
To assess the effect of prophylactic oral/topical non-absorbed antifungal therapy on the incidence of invasive fungal infection, mortality and morbidity in VLBW 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, 2009), MEDLINE (1966 - May 2009), EMBASE (1980 - May 2009), conference proceedings, and previous reviews.
SELECTION CRITERIA
Randomised controlled trials that compared the effect of prophylactic oral/topical non-absorbed antifungal therapy versus placebo or no drug or another antifungal agent or dose regimen in very preterm or VLBW 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 review author and synthesis of data using relative risk (RR) and risk difference (RD) and weighted mean difference (WMD).
MAIN RESULTS
Three trials, in which a total of 1625 infants participated, have compared oral/topical non-absorbed antifungal prophylaxis (nystatin or miconazole) with placebo or no drug. These trials had various methodological weaknesses including quasi-randomisation, lack of allocation concealment, and lack of blinding of intervention and outcomes assessment. The incidence of invasive fungal infection was very high in the control groups of two of the included trials. Meta-analysis found a statistically significant reduction in the incidence of invasive fungal infection [typical RR 0.19 (95% confidence interval (CI) 0.14, 0.27); typical RD -0.19 (95% CI -0.22,-0.16)] but substantial statistical heterogeneity was detected. A statistically significant effect on mortality was not found [typical RR 0.88 (95% CI 0.72, 1.06); typical RD -0.02 (95% CI -0.06, 0.01)]. Long-term outcomes were not assessed by any of the trials.One small trial (N = 21) that assessed the effect of oral/topical non-absorbed antifungal prophylaxis (nystatin) compared with systemic antifungal (fluconazole) prophylaxis was underpowered to exclude important clinical effects.
AUTHORS' CONCLUSIONS
The finding of a reduction in risk of invasive fungal infection in infants treated with oral/topical non-absorbed antifungal prophylaxis should be interpreted cautiously because of methodological weaknesses in the included trials. Further large randomised controlled trials in current neonatal practice settings are needed to resolve this uncertainty. These trials might compare oral/topical non-absorbed antifungal agents with placebo, with each other, or with systemic antifungal agents and should include an assessment of effect on long-term neurodevelopmental outcomes.
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: 19821309
DOI: 10.1002/14651858.CD003478.pub3