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Therapeutic Advances in Urology 2023Aspergillosis localized to the kidneys and the urinary tract is uncommon. We conducted a comprehensive systematic review to evaluate risk factors and clinical outcomes... (Review)
Review
BACKGROUND
Aspergillosis localized to the kidneys and the urinary tract is uncommon. We conducted a comprehensive systematic review to evaluate risk factors and clinical outcomes of patients with isolated renal and genito-urinary tract aspergillosis.
METHODS
We systematically searched Medline, CINAHL, Embase, African Journal Online, Google Scholar, and the Cochrane Library, covering the period from inception to August 2023 using the key terms 'renal' OR 'kidney*' OR 'prostate' OR 'urinary bladder' OR 'urinary tract*AND 'aspergillosis' OR 'aspergillus' OR 'aspergilloma' OR 'mycetoma'. We included single case reports or case series. Review articles, guidelines, meta-analyses, animal studies, protocols, and cases of genitourinary and /or renal aspergillosis occurring as a part of disseminated disease were excluded.
RESULTS
We identified 91 renal and urinary aspergillosis cases extracted from 76 publications spanning 1925-2023. Among the participants, 79 (86.8%) were male, with a median age of 46 years. Predominantly, presentations consisted of isolated renal infections (74 instances, 81.3%), followed by prostate (5 cases, 5.5%), and bladder (7 cases, 7.7%) involvement. (42.9%), (9.9%), and (1.1% each) were isolated. Underlying risk factors included diabetes mellitus (29.7%), HIV (12.1%), haematological malignancies (11%), and liver cirrhosis (8.8%), while common symptoms encompassed flank pain (36.3%), fever (33%), and lower urinary tract symptoms (20.9%). An autopsy was conducted in 8.8% of cases. Diagnostic work-up involved histopathology (70.5%), renal CT scans and urine microscopy and culture (52.6% each), and abdominal ultrasound (17.9%). Treatments included amphotericin B (34 cases, 37.4%) and azole-based regimens (29 cases, 31.9%). Nephrectomy was performed in 16 of 78 renal cases (20.5%). All-cause mortality was 24.4% (19 cases). No significant mortality rate difference was observed among antifungal regimens ( = 0.739) or nephrectomy status ( = 0.8).
CONCLUSION
Renal and urinary aspergillosis is an important cause of morbidity and mortality, particularly in immunocompromised and people with diabetes mellitus. While varied treatment strategies were observed, mortality rates showed no significant differences based on treatments or nephrectomy status. Further research is needed to refine diagnostics, optimize treatments, and enhance awareness among clinicians for early detection and management.
PROSPERO REGISTRATION NUMBER
CRD42023430959.
PubMed: 38130371
DOI: 10.1177/17562872231218621 -
Journal de Mycologie Medicale Aug 2022Mucormycosis is a rare but life-threatening disease with high morbidity and mortality and is difficult to diagnose. Mucormycosis, is a severe but rare fungal infection... (Review)
Review
Mucormycosis is a rare but life-threatening disease with high morbidity and mortality and is difficult to diagnose. Mucormycosis, is a severe but rare fungal infection caused by a group of molds called mucormycetes. Diabetes, use of corticosteroids, metabolic/diabetic acidosis and Covid-19 mediated immunosuppression are reported in more than 70% of cases in mucormycosis patients. Coexisting mucormycosis, Covid-19 along with diabetes mellitus increase the likelihood of mortality. Despite its occurrence since the beginning of the pandemic, there are still unanswered concerns regarding the origin of this fungal infection and mortality rate and/or relation with diabetic patients. In this review, we describe the detailed view of causative pathogens responsible for mucormycosis, diabetes mellitus and Covid-19 association along with the morbidity cases during the latest Covid-19 crisis. In the case of mucormycosis diagnosis, imaging, histopathological confirmation, fungal culture and molecular identification methods should be considered. Once mucormycosis is diagnosed, a combined treating method consisting of antifungals administration like amphotericin B, surgical intervention is needed for the reversal of the underlying condition. Early detection of this potentially life-threatening infection and timely care is needed in lowering mortality rates.
Topics: Amphotericin B; COVID-19; Diabetes Mellitus; Diabetic Ketoacidosis; Humans; Mucormycosis
PubMed: 35219907
DOI: 10.1016/j.mycmed.2022.101257 -
Journal de Mycologie Medicale May 2023Systemic candidiasis is caused by Candida invading the bloodstream. The efficacy and safety of echinocandins in monotherapy and combination therapy regimes have not been... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Systemic candidiasis is caused by Candida invading the bloodstream. The efficacy and safety of echinocandins in monotherapy and combination therapy regimes have not been adequately compared in immunocompromised patients with Candidiasis, and thus this systematic review aims to do so.
METHODS
A protocol was prepared a priori. PubMed, Embase and Cochrane Library databases were searched systematically (from inception of each database to September 2022) to identify randomized controlled trials. Two reviewers performed screening, quality assessment of trials, and extracted data independently. Pairwise meta-analysis was performed using random-effects model to compare echinocandin monotherapy versus other antifungals. The primary outcomes of interest were treatment success and treatment-related adverse events.
RESULTS
547 records (PubMed=310, EMBASE=210 and Cochrane Library=27) were reviewed. Following our screening criteria, six trials involving 177 patients were included. Risk of bias of four included studies had some concerns due to lack of a pre-specified analysis plan. Meta-analysis shows that echinocandin monotherapy does not have significantly higher rates of "treatment success" compared to other classes of antifungals (RR 1.12, 95%CI 0.80-1.56). However, echinocandins appeared to be significantly safer than other forms of antifungal therapy (RR 0.79, 95%CI 0.73-0.86).
CONCLUSION
Our findings have shown that echinocandin monotherapy (micafungin, caspofungin) given intravenously are just as effective as other antifungals (amphotericin B, itraconazole) in the treatment of systemic candidiasis in immunocompromised patients. There appears to be similar benefits when using echinocandins compared to amphotericin B which has also been used as a broad-spectrum antifungal, while avoiding the severe adverse effects that amphotericin B causes, such as nephrotoxicity.
Topics: Humans; Antifungal Agents; Echinocandins; Amphotericin B; Candidiasis; Immunocompromised Host; Lipopeptides
PubMed: 36867970
DOI: 10.1016/j.mycmed.2023.101362 -
Scientific Reports Aug 2023The purpose of this study is to evaluate the efficacy of prophylactic use amphotericin B in patients with hematologic disorders complicated by neutropenia. We searched... (Meta-Analysis)
Meta-Analysis
The purpose of this study is to evaluate the efficacy of prophylactic use amphotericin B in patients with hematologic disorders complicated by neutropenia. We searched the PubMed, EMBASE, The Cochrane Library, CBM, CNKI, VIP and WanFang Data database and the China Clinical Trials Registry ( www.chictr.org.cn ) to collect randomized controlled trials (RCTs) of amphotericin B for patients with hematologic disorders complicated by neutropenia from inception to May 2023. The Cochrane risk-of-bias tool for RCTs was used to assess the bias risk of the included studies. The meta-analysis was performed using RevMan 5.3 software. A total of 6 studies with a total of 1019 patients were included. The results of the meta-analysis showed that the treatment group was superior to the control group in terms of the fungal infection rate, and the differences were statistically significant [RR = 0.47, 95% CI (0.32, 0.69), P < 0.0001]. There was no significant difference between the two groups in terms of the mortality [RR = 0.87, 95% CI (0.61, 1.23), P = 0.43] and the incidence of colonization [OR = 0.51, 95% CI (0.25, 1.03), P = 0.06]. The evidence shows that amphotericin B prophylactic use for patients with hematologic disorders complicated by neutropenia can decrease the fungal infection rate. However, there was no significant difference in reducing mortality or the incidence of colonization. Due to the limited quality and quantity of the included studies, more high-quality studies are needed to verify the above conclusion.
Topics: Humans; Amphotericin B; Neutropenia; Hematologic Diseases; China; Databases, Factual
PubMed: 37635176
DOI: 10.1038/s41598-023-41268-1 -
HIV Medicine Apr 2023The purpose of this systematic review is to provide updated evidence on the preferred induction therapy for the treatment of HIV-associated cryptococcal meningitis...
BACKGROUND
The purpose of this systematic review is to provide updated evidence on the preferred induction therapy for the treatment of HIV-associated cryptococcal meningitis considering the most recent evidence available in order to inform the need for updates to WHO guidelines.
METHODS
We searched Medline via PubMed, EMBASE, the Cochrane Library and clinicaltrials.gov for published or completed randomized clinical trials that evaluated induction treatment of first episode HIV-associated cryptococcal meningitis from 9 July 2018 (date of last search) to 1 September 2021.
RESULTS
One randomized clinical trial of 844 people with HIV-associated cryptococcal meningitis met the inclusion criteria. Participants were randomized to: (1) amphotericin deoxycholate for 7 days, with flucytosine and fluconazole (control); or (2) a single dose of liposomal amphotericin 10 mg/kg with flucytosine and fluconazole (intervention). In the intention-to-treat analysis, 10-week mortality was 24.8% [95% confidence interval (CI): 20.7-29.3%] in the single-dose liposomal amphotericin group compared with 28.7% (95% CI: 24.4-33.4%) in the control group. The absolute difference in 10-week mortality was -3.9% with an upper one-sided 95% CI of 1.2%, within the 10% pre-specified non-inferiority margin. Fewer participants had grade 3 and 4 adverse events in the intervention arm compared with the control arm (50.0% vs. 62.3%, p < 0.001).
CONCLUSIONS
In the single study included in this systematic review, single high-dose liposomal amphotericin B with flucytosine and fluconazole was non-inferior to the WHO-recommended standard of care induction therapy for HIV-associated cryptococcal meningitis, with significantly fewer adverse events.
Topics: Humans; Amphotericin B; Meningitis, Cryptococcal; Flucytosine; Fluconazole; Antifungal Agents; HIV Infections; Drug Therapy, Combination; Randomized Controlled Trials as Topic
PubMed: 36123803
DOI: 10.1111/hiv.13412 -
Journal of Fungi (Basel, Switzerland) Feb 2023Opportunistic and hospital-acquired infections are common among recipients of solid organ transplantation. New pathogens are increasingly reported in the intensive care... (Review)
Review
Opportunistic and hospital-acquired infections are common among recipients of solid organ transplantation. New pathogens are increasingly reported in the intensive care unit (ICU) population. We report a case of a patient who developed spp.-related pneumonia (TRP) after heart-lung transplantation. In the absence of antifungal susceptibility testing, TRP was confirmed by histological examination, and empirical therapy with voriconazole and caspofungin was swiftly initiated. Complete resolution of pneumonia was obtained after prolonged combination therapy. Given the lack of guidelines, we conducted a systematic review to elucidate the diagnostic and therapeutic strategies to apply during infection. After deduplication and selection of full texts, we found 42 articles eligible for the systematic review. Pneumonia seems to be the most common clinical manifestation (31.8%). The most used antifungal therapy was amphotericin B, while combination therapy was also reported (27.3%). All the patients were immunocompromised except for one case. Despite the rarity of spp. infection, the increase in invasive fungal infections is of growing importance in ICU, considering their impact on mortality and the emergence of antifungal resistance. In the absence of prospective and multicenter studies, a review can provide useful insight regarding the epidemiology, clinical manifestations, and management of these unexpected challenges.
PubMed: 36836310
DOI: 10.3390/jof9020195 -
PLoS Neglected Tropical Diseases Apr 2024Cutaneous leishmaniasis (CL) is characterized by potentially disfiguring skin ulcers carrying significant social stigma. To mitigate systemic drug exposure and reduce...
BACKGROUND
Cutaneous leishmaniasis (CL) is characterized by potentially disfiguring skin ulcers carrying significant social stigma. To mitigate systemic drug exposure and reduce the toxicity from available treatments, studies addressing new local therapeutic strategies using available medications are coming up. This review systematically compiles preclinical and clinical data on the efficacy of amphotericin B (AmB) administered locally for cutaneous leishmaniasis.
METHODOLOGY
Structured searches were conducted in major databases. Clinical studies reporting cure rates and preclinical studies presenting any efficacy outcome were included. Exclusion criteria comprised nonoriginal studies, in vitro investigations, studies with fewer than 10 treated patients, and those evaluating AmB in combination with other antileishmanial drug components.
PRINCIPAL FINDINGS
A total of 21 studies were identified, encompassing 16 preclinical and five clinical studies. Preclinical assessments generally involved the topical use of commercial AmB formulations, often in conjunction with carriers or controlled release systems. However, the variation in the treatment schedules hindered direct comparisons. In clinical studies, topical AmB achieved a pooled cure rate of 45.6% [CI: 27.5-64.8%; I2 = 79.7; p = 0.002), while intralesional (IL) administration resulted in a 69.8% cure rate [CI: 52.3-82.9%; I2 = 63.9; p = 0.06). In the direct comparison available, no significant difference was noted between AmB-IL and meglumine antimoniate-IL administration (OR:1.7; CI:0.34-9.15, I2 = 79.1; p = 0.00), however a very low certainty of evidence was verified.
CONCLUSIONS
Different AmB formulations and administration routes have been explored in preclinical and clinical studies. Developing therapeutic technologies is evident. Current findings might be interpreted as a favorable proof of concept for the local AmB administration which makes this intervention eligible to be explored in future well-designed studies towards less toxic treatments for leishmaniasis.
Topics: Leishmaniasis, Cutaneous; Amphotericin B; Humans; Antiprotozoal Agents; Administration, Topical; Treatment Outcome
PubMed: 38626196
DOI: 10.1371/journal.pntd.0012127 -
BMC Infectious Diseases Feb 2017The most optimal antifungal agent for empiric treatment of invasive fungal diseases (IFDs) in febrile neutropenia is controversial. Our objective was evaluate the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The most optimal antifungal agent for empiric treatment of invasive fungal diseases (IFDs) in febrile neutropenia is controversial. Our objective was evaluate the relative efficacy of antifungals for all-cause mortality, fungal infection-related mortality and treatment response in this population.
METHODS
Pubmed, Embase and Cochrane Library were searched to identify randomized controlled trials (RCTs). Two reviewers performed the quality assessment and extracted data independently. Pairwise meta-analysis and network meta-analysis were conducted to compare the antifungals.
RESULTS
Seventeen RCTs involving 4583 patients were included. Risk of bias of included studies was moderate. Pairwise meta-analysis indicated the treatment response rate of itraconazole was significantly better than conventional amphotericin B (RR = 1.33, 95%CI 1.10-1.61). Network meta-analysis showed that amphotericin B lipid complex, conventional amphotericin B, liposomal amphotericin B, itraconazole and voriconazole had a significantly lower rate of fungal infection-related mortality than no antifungal treatment. Other differences in outcomes among antifungals were not statistically significant. From the rank probability plot, caspofungin appeared to be the most effective agent for all-cause mortality and fungal infection-related mortality, whereas micafungin tended to be superior for treatment response. The results were stable after excluding RCTs with high risk of bias, whereas micafungin had the lowest fungal infection-related mortality.
CONCLUSIONS
Our results highlighted the necessity of empiric antifungal treatment and indicates that echinocandins appeared to be the most effective agents for empiric treatment of febrile neutropenic patients based on mortality and treatment response. However, more studies are needed to determine the best antifungal agent for empiric treatment. Our systematic review has been prospectively registered in PROSPERO and the registration number was CRD42015026629.
Topics: Antifungal Agents; Febrile Neutropenia; Humans; Invasive Fungal Infections; Models, Statistical; Network Meta-Analysis; Treatment Outcome
PubMed: 28219330
DOI: 10.1186/s12879-017-2263-6 -
Alternative Therapies in Health and... Nov 2023Although the level of medical care has been improved in recent years, the probability of patients contracting pathogens has increased greatly, with a rising incidence of...
BACKGROUND
Although the level of medical care has been improved in recent years, the probability of patients contracting pathogens has increased greatly, with a rising incidence of invasive fungal infections. Deep-seated fungi have become common pathogens of nosocomial infections.
OBJECTIVE
This study aims to systematically assess the effectiveness, mortality, survival rate, and adverse reactions (ARs) of high-dose (HD) liposomal amphotericin B (L-AMB) for human diseases.
METHODS
Ten articles (1661 patients) of randomized controlled trials (RCTs; whether randomized, single-blind, or double-blind) from January 1, 1960, to December 31, 2020, of HD-L-AMB treatment of diseases were retrieved from the PubMed, Embase, Scopus, Web of Science, and Cochrane Central Register of Controlled Trials databases. The primary outcome measure was the overall therapeutic effect, and the secondary outcome measures were mortality, ≥10-week survival, and ARs. Data were meta-analyzed using RevMan 5.3.
RESULTS
Ten RCTs involving 1661 patients were included. HD-L-AMB did not show a significant therapeutic advantage in anti-infection treatment. In addition, HD-L-AMB treatment of invasive Aspergillus infection led to high mortality and low survival (≥10 weeks, OR = 0.57, 95%CI 0.34-0.94, P = .03). According to subgroup analysis, the incidence of ARs and the incidence of renal dysfunction associated with invasive fungal infection treatment were higher with HD-L-AMB than with regular-dose L-AMB.
CONCLUSION
HD-L-AMB had no obvious advantage for the treatment of diseases and was accompanied by increased mortality, reduced long-term survival, and increased ARs (including renal insufficiency). Therefore, the use of HD-L-AMB to control infections is recommended with caution only when the preferred treatment is contraindicated.
PubMed: 37971463
DOI: No ID Found -
Frontiers in Medicine 2022Cryptococcal meningitis (CM) is a leading cause of adult meningitis in countries with a high burden of HIV. It has remained a significant cause of morbidity and...
Prevalence of cryptococcal meningitis among people living with human immuno-deficiency virus and predictors of mortality in adults on induction therapy in Africa: A systematic review and meta-analysis.
BACKGROUND
Cryptococcal meningitis (CM) is a leading cause of adult meningitis in countries with a high burden of HIV. It has remained a significant cause of morbidity and mortality in Africa despite the extensive rollout of HIV antiretroviral therapy (ART). This study aimed to systematically synthesize the evidence on the prevalence of CM among people living with HIV (PLWH) and its predictors of mortality among adults who are on induction antifungal therapy in Africa.
METHODS
PubMed/MEDLINE, Embase, and Google Scholar were searched for randomized clinical trials or observational studies published in Africa from 1995 to April 2021. Pooled prevalence of CM among PLWH was calculated using R-studio Version 1.4.1717 software and the data extracted from eligible studies were pooled as percentage with a 95% confidence interval (CI). Predictors of mortality among adults on induction antifungal therapy were synthesized narratively.
RESULTS
Out of 364 studies identified, 17 eligible articles were included in the analysis. The prevalence of CM among PLWH in Africa was 5.11% (95% CI 2.71-9.43%; participants = 10,813; studies = 9; = 97%). In the subgroup analysis, the prevalence was 12.9% (95% CI 4.883-30.0; participants = 533; studies = 3; = 63%) in the years 1995-2010 and 3.18% (95% CI 1.54-6.45; participants = 10,280; studies = 6; = 98%) in the years 2011-2021, with the prevalence significantly decreased by 51% ( = ). Predictors of mortality were fluconazole monotherapy, focal neurological signs, low Glasgow coma scale, and delayed diagnosis of CM at varied timepoint.
CONCLUSION
Prevalence of CM has significantly decreased from 1996-2010 to 2011-2021 among PLWH on induction therapy in Africa. Fluconazole monotherapy, focal neurological symptoms, diastolic blood pressure < 60 mmHg, and concurrent tuberculosis coinfection were significant predictors of mortality at 2- and 10-weeks timepoints. CM remains a major concern among PLWH despite increases in ART coverage. Improved access to effective antifungal therapies is needed in Africa for timely initiation of combination induction therapy and better treatment outcomes of PLWH.
SYSTEMATIC REVIEW REGISTRATION
[https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=254113], identifier [CRD42021254113].
PubMed: 36160163
DOI: 10.3389/fmed.2022.989265