-
The Cochrane Database of Systematic... Feb 2010Invasive fungal infections are associated with significant morbidity and mortality in children. Optimal treatment strategies are yet to be defined. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Invasive fungal infections are associated with significant morbidity and mortality in children. Optimal treatment strategies are yet to be defined.
OBJECTIVES
This review aims to systematically identify and summarise the effects of different antifungal therapies in children with proven, probable or suspected invasive fungal infections.
SEARCH STRATEGY
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2008, Issue 3), MEDLINE (1966 to September 2008), EMBASE (1980 to September 2008) and CINAHL (1988 to September 2008) without language restrictions. We also handsearched reference lists and abstracts of conference proceedings and scientific meetings, and contacted authors of included studies and pharmaceutical manufacturers.
SELECTION CRITERIA
We included randomised clinical trials (RCTs) comparing a systemic antifungal agent with a comparator (including placebo) in children (one month to 16 years) with proven, probable or suspected invasive fungal infection.
DATA COLLECTION AND ANALYSIS
Two review authors independently applied selection criteria, performed quality assessment, and extracted data using an intention-to-treat approach. We synthesised data using the random-effects model and expressed results as relative risks (RR) with 95% confidence intervals (CIs).
MAIN RESULTS
We included seven trials of antifungal agents in children with prolonged fever and neutropenia (suspected fungal infection) and candidaemia or invasive candidiasis (proven fungal infection). Four trials compared a lipid preparation of amphotericin B with conventional amphotericin B (395 participants), one trial compared an echinocandin with a lipid preparation of amphotericin B (82 participants) in suspected infection; one trial compared an echinocandin with a lipid preparation of amphotericin B in children with candidaemia or invasive candidiasis (109 participants) and one trial compared different azole antifungals in children with candidaemia (43 participants). No difference in all-cause mortality and other primary endpoints (mortality related to fungal infection or complete resolution of fungal infections) were observed. No difference in breakthrough fungal infection was observed in children with prolonged fever and neutropenia.When lipid preparations and conventional amphotericin B were compared in children with prolonged fever and neutropenia, nephrotoxicity was less frequently observed with a lipid preparation (RR 0.43, 95% CI 0.21 to 0.90, P = 0.02) however substantial heterogeneity was observed (I(2) = 59%, P = 0.06). Children receiving liposomal amphotericin B were less likely to develop infusion-related reactions compared with conventional amphotericin B (chills: RR 0.37, 95% CI 0.21 to 0.64, P = 0.0005). Children receiving a colloidal dispersion were more likely to develop such reactions than with liposomal amphotericin B (chills: RR 1.76, 95% CI 1.09 to 2.85, P = 0.02). The rate of other clinically significant adverse reactions attributed to the antifungal agent (total reactions; total reactions leading to treatment discontinuation, dose reduction or change in therapy; hypokalaemia and hepatotoxicity) were not significantly different. When echinocandins and lipid preparations were compared, the rate of clinically significant adverse reactions (total reactions; total reactions leading to treatment discontinuation, dose reduction or change in therapy) were not significantly different.
AUTHORS' CONCLUSIONS
Limited paediatric data are available comparing antifungal agents in children with proven, probable or suspected invasive fungal infection. No differences in mortality or treatment efficacy were observed when antifungal agents were compared. Children are less likely to develop nephrotoxicity with a lipid preparation of amphotericin B compared with conventional amphotericin B. Further comparative paediatric antifungal drug trials and epidemiological and pharmacological studies are required highlighting the differences between neonates, children and adults with invasive fungal infections.
Topics: Adolescent; Amphotericin B; Antifungal Agents; Candidiasis; Child; Child, Preschool; Echinocandins; Fever; Humans; Infant; Mycoses; Neutropenia; Randomized Controlled Trials as Topic
PubMed: 20166083
DOI: 10.1002/14651858.CD006343.pub2 -
The Cochrane Database of Systematic... Sep 2018This review adds to a series of reviews looking at primary medical management options for patients with chronic rhinosinusitis.Chronic rhinosinusitis is common and... (Review)
Review
BACKGROUND
This review adds to a series of reviews looking at primary medical management options for patients with chronic rhinosinusitis.Chronic rhinosinusitis is common and characterised by inflammation of the lining of the nose and paranasal sinuses leading to nasal blockage, nasal discharge, facial pressure/pain and loss of sense of smell. The condition can occur with or without nasal polyps. Antifungals have been suggested as a treatment for chronic rhinosinusitis.
OBJECTIVES
To assess the effects of systemic and topical antifungal agents in patients with chronic rhinosinusitis, including those with allergic fungal rhinosinusitis (AFRS) and, if possible, AFRS exclusively.
SEARCH METHODS
The Cochrane ENT Information Specialist searched the Cochrane ENT Trials Register; Cochrane Central Register of Controlled Trials (CENTRAL); Ovid MEDLINE; Ovid Embase; CINAHL; Web of Science; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished trials. The date of the search was 17 November 2017.
SELECTION CRITERIA
Randomised controlled trials (RCTs) with at least a two-week follow-up period comparing topical or systemic antifungals with (a) placebo, (b) no treatment, (c) other pharmacological interventions or (d) a different antifungal agent. We did not include post-surgical antifungal use.
DATA COLLECTION AND ANALYSIS
We used the standard Cochrane methodological procedures. Our primary outcomes were disease-specific health-related quality of life (HRQL), patient-reported disease severity and the significant adverse effects of hepatic toxicity (systemic antifungals). Secondary outcomes included general HRQL, endoscopic nasal polyp score, computerised tomography (CT) scan score and the adverse effects of gastrointestinal disturbance (systemic antifungals) and epistaxis, headache or local discomfort (topical antifungals). We used GRADE to assess the quality of the evidence for each outcome; this is indicated in italics.
MAIN RESULTS
We included eight studies (490 adult participants). The presence of nasal polyps on examination was an inclusion criterion in three studies, an exclusion criterion in one study and the remaining studies included a mixed population. No studies specifically investigated the effect of antifungals in patients with AFRS.Topical antifungal treatment versus placebo or no interventionWe included seven studies (437 participants) that used amphotericin B (six studies; 383 participants) and one that used fluconazole (54 participants). Different delivery methods, volumes and concentrations were used.Four studies reported disease-specific health-related quality of life using a range of instruments. We did not meta-analyse the results due to differences in the instruments used, and measurement and reporting methods. At the end of treatment (one to six months) none of the studies reported statistically significant differences between the groups (low-quality evidence - we are uncertain about the result).Two studies reported disease severity using patient-reported symptom scores. Meta-analysis was not possible. At the end of treatment (8 to 13 weeks) one study showed no difference and the second found that patients in the placebo group had less severe symptoms (very low-quality evidence - we are very uncertain about the result).In terms of adverse effects, topical antifungals may lead to more local irritation compared with placebo (risk ratio (RR) 2.29, 95% confidence interval (CI) 0.61 to 8.62; 312 participants; 5 studies; low-quality evidence) but little or no difference in epistaxis (RR 0.97, 95% CI 0.14 to 6.63; 225 participants; 4 studies, low-quality evidence) or headache (RR 1.26, 95% CI 0.60 to 2.63; 195 participants; 3 studies; very low-quality evidence).None of the studies found a difference in generic health-related quality of life (one study) or endoscopic score (five studies) between the treatment groups. Three studies investigated CT scan; two found no difference between the groups and one found a significant decrease in the mean percentage of air space occluded, favouring the antifungal group.Systemic antifungal treatment versus placebo or no treatmentOne study (53 participants) comparing terbinafine tablets against placebo reported that there may be little or no difference between the groups in disease-specific health-related quality of life or disease severity score (both low-quality evidence). Systemic antifungals may lead to more hepatic toxicity events (RR 3.35, 95% CI 0.14 to 78.60) but fewer gastrointestinal disturbances (RR 0.37, 95% CI 0.04 to 3.36), compared to placebo, although the evidence was of low quality.This study did not find a difference in CT scan score between the groups. Generic health-related quality of life and endoscopic score were not measured.Other comparisonsWe found no studies that compared antifungal agents against other treatments for chronic rhinosinusitis.
AUTHORS' CONCLUSIONS
Due to the very low quality of the evidence, it is uncertain whether or not the use of topical or systemic antifungals has an impact on patient outcomes in adults with chronic rhinosinusitis compared with placebo or no treatment. Studies including specific subgroups (i.e. AFRS) are lacking.
Topics: Administration, Topical; Adult; Amphotericin B; Antifungal Agents; Chronic Disease; Fluconazole; Humans; Quality of Life; Randomized Controlled Trials as Topic; Rhinitis; Sinusitis
PubMed: 30199594
DOI: 10.1002/14651858.CD012453.pub2 -
International Dental Journal Jun 2024Mucormycosis is a rare human infection associated with Mucorales, a group of filamentous moulds found in different environmental niches. Its oral manifestations may...
AIM
Mucormycosis is a rare human infection associated with Mucorales, a group of filamentous moulds found in different environmental niches. Its oral manifestations may occur in the mandible and tongue despite being rare. We aimed to systematically review the data on clinical manifestations, risk factors, diagnostic approaches, treatment options, and outcomes of mandibular and tongue mucormycosis.
METHODS
An electronic search of articles published between January 1975 and November 2022 in PubMed, Web of Science, and EMBASE databases was performed. A total of 22 articles met the inclusion criteria and reported 27 cases of oral mucormycosis in total.
RESULTS
Fourteen patients had mandibular mucormycosis signs unrelated to COVID-19 infection, 6 had SARS-CoV-2-related mandibular mucormycosis, and 6 had manifestations in the tongue. All published case reports during the COVID-19 pandemic were from India. Patient ages ranged from 4 months old to 82 years, and most patients had important comorbidities, such as blood dyscrasias related to immune deficiency and uncontrolled type 2 diabetes mellitus. The signs and symptoms of mandibular and tongue mucormycosis varied from dental pain, loose teeth, and nonhealing sockets to dysphagia and paraesthesia of the lip. Some patients also reported trismus, draining sinus tract, and facial pain. The diagnosis of oral mucormycosis was based on a combination of clinical, radiographic, and histopathologic findings by demonstrating fungal hyphae in tissue specimens. In most cases, mucormycosis was managed with systemic amphotericin B, strict glycaemic control, and aggressive surgical debridement of infected tissue, minimising the progression of the fungal infection and thus improving the survival rate. In some cases, combined antifungal therapy, antibiotic therapy, and chlorhexidine mouthwashes were used successfully.
CONCLUSIONS
Recognition of the signs and symptoms by oral care providers is pertinent for the early diagnosis and treatment of tongue and mandibular mucormycosis, and providers should be aware of the possibility of this opportunistic fungal infection in patients with COVID-19. A multidisciplinary approach is recommended for the management of this lethal infection.
Topics: Humans; Mucormycosis; Tongue Diseases; COVID-19; Antifungal Agents; Mandibular Diseases; Aged; Middle Aged; Mandible; Risk Factors; Adult; Aged, 80 and over; Adolescent
PubMed: 38143163
DOI: 10.1016/j.identj.2023.11.011 -
Open Forum Infectious Diseases Jun 2024is a World Health Organization critical priority fungal pathogen. We conducted a systematic review to describe its epidemiology in Africa. PubMed and Google scholar... (Review)
Review
is a World Health Organization critical priority fungal pathogen. We conducted a systematic review to describe its epidemiology in Africa. PubMed and Google scholar databases were searched between January 2009 and September 2023 for clinical studies on cases and/or isolates from Africa. Reviews were excluded. We included 19 studies, involving at least 2529 cases from 6 African countries with the most, 2372 (93.8%), reported from South Africa. Whole-genome sequencing of 127 isolates identified 100 (78.7%) as clade III. Among 527 isolates, 481 (91.3%) were resistant to fluconazole, 108 (20.5%) to amphotericin B, and 9 (1.7%) to micafungin. Ninety of 211 (42.7%) patients with clinical outcomes died. is associated with high mortality and antifungal resistance, yet this critical pathogen remains underreported in Africa. Collaborative surveillance, fungal diagnostics, antifungals, and sustainable infection control practices are urgently needed for containment.
PubMed: 38887473
DOI: 10.1093/ofid/ofad681 -
Infection Apr 2007Non-neoformans cryptococci have been generally regarded as saprophytes and rarely reported as human pathogens. However, the incidence of infection due to these organisms... (Review)
Review
Non-neoformans cryptococci have been generally regarded as saprophytes and rarely reported as human pathogens. However, the incidence of infection due to these organisms has increased over the past 40 years, with Cryptococcus laurentii and Cryptococcus albidus, together, responsible for 80% of reported cases. Conditions associated with impaired cell-mediated immunity are important risks for non-neoformans cryptococcal infections and prior azole prophylaxis has been associated with antifungal resistance. The presence of invasive devices was a significant risk factor for Cryptococcus laurentii infection (adjusted OR = 8.7; 95% CI = 1.48-82.9; p = 0.003), while predictors for mortality included age > or =45 years (aOR = 8.4; 95% CI = 1.18-78.82; p = 0.004) and meningeal presentation (aOR = 7.0; 95% CI = 1.85-60.5; p= 0.04). Because clinical manifestations of non-neoformans cryptococcal infections are most often indistinguishable from Cryptococcus neoformans, a high index of suspicion remains important to facilitate early diagnosis and prompt treatment for such infections.
Topics: Amphotericin B; Cryptococcosis; Drug Resistance, Fungal; Humans; Risk Factors
PubMed: 17401707
DOI: 10.1007/s15010-007-6142-8 -
PLoS Neglected Tropical Diseases Mar 2016Leishmania aethiopica is the etiological agent of cutaneous leishmaniasis (CL) in Ethiopia and can cause severe and complicated cases such as diffuse CL (DCL),... (Review)
Review
Leishmania aethiopica is the etiological agent of cutaneous leishmaniasis (CL) in Ethiopia and can cause severe and complicated cases such as diffuse CL (DCL), mucocutaneous leishmaniasis or extensive CL, requiring systemic treatment. Despite the substantial burden, evidence-based treatment guidelines are lacking. We conducted a systematic review of clinical studies reporting on treatment outcomes of CL due to L aethiopica in order to help identify potentially efficacious medications on CL that can be taken forward for clinical trials. We identified a total of 24 records reporting on 506 treatment episodes of CL presumably due to L aethiopica. The most commonly used drugs were antimonials (n = 201), pentamidine (n = 150) and cryotherapy (n = 103). There were 20 case reports/series, with an overall poor study quality. We only identified two small and/or poor quality randomized controlled trials conducted a long time ago. There were two prospective non-randomized studies reporting on cryotherapy, antimonials and pentamidine. With cryotherapy, cure rates were 60-80%, and 69-85% with antimonials. Pentamidine appeared effective against complicated CL, also in cases non-responsive to antimonials. However, all studies suffered from methodological limitations. Data on miltefosine, paromomycin and liposomal amphotericin B are extremely scarce. Only a few studies are available on DCL. The only potentially effective treatment options for DCL seem to be antimonials with paromomycin in combination or pentamidine, but none have been properly evaluated. In conclusion, the evidence-base for treatment of complicated CL due to L aethiopica is extremely limited. While antimonials remain the most available CL treatment in Ethiopia, their efficacy and safety in CL should be better defined. Most importantly, alternative first line treatments (such as miltefosine or paromomycin) should be explored. High quality trials on CL due to L aethiopica are urgently needed, exploring group sequential methods to evaluate several options in parallel.
Topics: Adolescent; Adult; Aged; Antiprotozoal Agents; Child; Child, Preschool; Cryotherapy; Ethiopia; Female; Humans; Leishmania; Leishmaniasis, Cutaneous; Male; Middle Aged; Prospective Studies; Treatment Outcome; Young Adult
PubMed: 26938448
DOI: 10.1371/journal.pntd.0004495 -
BMC Infectious Diseases Nov 2020Candida auris is a new pathogen called "superbug fungus" which caused panic worldwide. There are no large-scale epidemiology studies by now, therefore a systematic... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Candida auris is a new pathogen called "superbug fungus" which caused panic worldwide. There are no large-scale epidemiology studies by now, therefore a systematic review and meta-analysis was undertaken to determine the epidemic situation, drug resistance patterns and mortality of C. auris.
METHODS
We systematically searched studies on the clinical report of Candida auris in Pubmed, Embase and Cochrane databases until October 6, 2019. A standardized form was used for data collection, and then statics was performed with STATA11.0.
RESULTS
It showed that more than 4733 cases of C. auris were reported in over 33 countries, with more cases in South Africa, United States of America, India, Spain, United Kingdom, South Korea, Colombia and Pakistan. C. auirs exhibited a decrease in case count after 2016. Clade I and III were the most prevalent clades with more cases reported and wider geographical distribution. Blood stream infection was observed in 32% of the cases, which varied depending on the clades. Resistance to fluconazole, amphotericin B, caspofungin, micafungin and anidulafungin in C. auris were 91, 12, 12.1, 0.8 and 1.1%. The overall mortality of C. auris infection was 39%. Furthermore, subgroup analyses showed that mortality was higher in bloodstream infections (45%), and lower in Europe (20%).
CONCLUSIONS
Over 4000 cases of C. auris were reported in at least 33 countries, which showed high resistance to fluconazole, moderate resistance to amphotericin B and caspofungin, high sensitivity to micafungin and anidulafungin. The crude mortality for BSI of C. auris was 45% which was similar to some drug-resistant bacteria previously reported. In conclusion, C. auris displayed similar characteristics to some drug resistance organisms. This study depicts several issues of C. auris that are most concerned, and is of great significance for the clinical management.
Topics: Amphotericin B; Anidulafungin; Antifungal Agents; Candida; Candidiasis; Caspofungin; Drug Resistance, Multiple, Fungal; Fluconazole; Humans; Micafungin; Prevalence
PubMed: 33176724
DOI: 10.1186/s12879-020-05543-0 -
Oman Medical Journal Jan 2020Histoplasmosis is uncommon in many parts of the world, including Bangladesh, where, in recent years, cases are increasingly reported. We sought to describe the... (Review)
Review
Histoplasmosis is uncommon in many parts of the world, including Bangladesh, where, in recent years, cases are increasingly reported. We sought to describe the sociodemographic characteristics, clinical presentation, investigations, treatment, and outcome of histoplasmosis in Bangladesh. We conducted a retrospective data review of published literature from 1962 to 2017, containing information on histoplasmosis in and/or from Bangladesh. Unpublished, well-documented histoplasmosis cases were also included. A total of 26 male patients aged 8-75 years, with a diagnosis of histoplasmosis were included; nine were farmers, seven had diabetes, one was a renal transplant recipient, and four had HIV/AIDS. Fever (n = 20), weight loss (n = 17), anemia (n = 15), lymphadenopathy (n = 9), and hepatosplenomegaly (n = 7) were common. Eleven patients had bilateral adrenal enlargement. Diagnosis was confirmed by histo/cytopathology from skin (n = 1), oropharyngeal ulcers (n = 8), lymph nodes (n = 3), adrenal glands (n = 11), paravertebral soft tissue (n = 2), and bone marrow (n = 4). Cultures of representative samples and antibodies were detected in three and two cases, respectively. Twenty-two patients had disseminated histoplasmosis and four patients had localized oropharyngeal disease. Nine patients were prescribed anti-tuberculosis drugs empirically before establishing the diagnosis of histoplasmosis. Treatment consisted of amphotericin B and itraconazole. Six patients died in hospital, 14 patients recovered with relapse in two cases, and the outcome of the other patients could not be ascertained. Histoplasmosis is thought to be endemic in Bangladesh, but few cases are reported to date, which may be due to many asymptomatic, undiagnosed, misdiagnosed, or under-reported cases. Histoplasmosis should be considered as a differential in appropriate clinical scenarios.
PubMed: 32095275
DOI: 10.5001/omj.2020.09 -
Journal of Clinical Medicine Mar 2024(1) In recent years, a global epidemiological shift in candidemia has been observed, marked by the emergence of resistant non-albicans Candida species. , in particular,... (Review)
Review
(1) In recent years, a global epidemiological shift in candidemia has been observed, marked by the emergence of resistant non-albicans Candida species. , in particular, has become a significant global concern, causing infections in both pediatric and adult populations within healthcare settings. Despite its widespread impact, there is a limited understanding of the clinical course and transmission dynamics of neonatal systemic Candida auris infections, hindering effective prevention and management. This study focused on the epidemiologic data, the clinical presentation, risk factors, and outcome of infection in neonatal population. (2) : A systematic review of the literature using PubMed and Scopus databases until December 2023 was conducted. (3) : A total of 24 relevant studies were identified, encompassing 476 documented cases of infection in neonates. Prematurity emerged as a primary risk factor, alongside total parenteral nutrition, central line insertion, mechanical ventilation, and prior broad-spectrum antibiotic use. The mortality rate reached approximately 42%, with therapeutic details sparingly reported in 12% of cases. Treatment strategies varied, with amphotericin B predominantly used as monotherapy, while combination antifungal agents were used in 44% of cases. Notably, 97.4% of cases exhibited fluconazole resistance, and 67.1% showed resistance to amphotericin B. Limited data were available on resistance to other antifungal agents. (4) : Despite the rarity of neonatal infections, their global occurrence necessitates comprehensive preparedness in patient care. A deeper understanding of pathogenesis is crucial for developing effective strategies to control and prevent neonatal infections caused by this pathogen.
PubMed: 38541815
DOI: 10.3390/jcm13061586 -
Frontiers in Pharmacology 2021Invasive fungal infections (IFI) is an important contributing factor in morbidity and mortality of immunocompromised and critically ill patients. Although the... (Review)
Review
Invasive fungal infections (IFI) is an important contributing factor in morbidity and mortality of immunocompromised and critically ill patients. Although the therapeutic effects of these drugs on IFI have been well documented, the long-term use of antifungal agents has raised concerns about drug tolerability and treatment-related toxicity risks. We searched articles published before June 30, 2020 in four electronic databases: Web of Science, Cochrane Library, embase and PubMed. 66 trials were determined to meet our inclusion criteria, providing data on 18,230 participants. We sorted out 23 AEs by system organ classes and six laboratory AEs, 13 of these were used to construct 13 network meta-analyses. Compared with LAmB, anidulafungin, caspofungin, micafungin, fluconazole, and posaconazole had a significantly low incidence of discontinuation of therapy due to AEs (OR = 0.24 (0.09,0.65), 0.24 (0.13,0.43), 0.32 (0.19,0.52), 0.38 (0.23,0.62) and 0.35 (0.17,0.69), respectively). We found that echinocandins are the most tolerated antifungal agents with high safety. The AEs of triazole drugs are mainly concentrated on the increase in liver enzymes, nervous system disorders, especially visual disorders, gastrointestinal disorders, and cardiac diseases. LAmB is the least tolerated and has the most abundant AEs.
PubMed: 34776941
DOI: 10.3389/fphar.2021.697330