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Mycoses Sep 2023Isavuconazole is a novel triazole antifungal agent. However, the previous outcomes were highlighted by statistical heterogeneity. This meta-analysis aimed to validate... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Isavuconazole is a novel triazole antifungal agent. However, the previous outcomes were highlighted by statistical heterogeneity. This meta-analysis aimed to validate the efficacy and safety of isavuconazole for the treatment and prophylaxis of invasive fungal infections (IFIs) compared with other antifungal agents (amphotericin B, voriconazole and posaconazole).
METHODS
Scopus, EMBASE, PubMed, CINAHL and Ichushi databases were searched for relevant articles that met the inclusion criteria through February 2023. Mortality, IFI rate, discontinuation rate of antifungal therapy and incidence of abnormal hepatic function were evaluated. The discontinuation rate was defined as the percentage of therapy discontinuations due to adverse events. The control group included patients who received other antifungal agents.
RESULTS
Of the 1784 citations identified for screening, 10 studies with an overall total of 3037 patients enrolled. Isavuconazole was comparable with the control group in mortality and IFI rate in the treatment and prophylaxis of IFIs, respectively (mortality, odds rate (OR) 1.11, 95% confidential interval (CI) 0.82-1.51; IFI rate, OR 1.02, 95% CI 0.49-2.12). Isavuconazole significantly reduced the discontinuation rate in the treatment (OR 1.96, 95% CI 1.26-3.07) and incidence of hepatic function abnormalities in the treatment and prophylaxis, compared with the control group (treatment, OR 2.31, 95% CI 1.41-3.78; prophylaxis, OR 3.63, 95% CI 1.31-10.05).
CONCLUSIONS
Our meta-analysis revealed that isavuconazole was not inferior to other antifungal agents for the treatment and prophylaxis of IFIs, with substantially fewer drug-associated adverse events and discontinuations. Our findings support the use of isavuconazole as the primary treatment and prophylaxis for IFIs.
Topics: Humans; Antifungal Agents; Invasive Fungal Infections; Voriconazole; Triazoles
PubMed: 37300337
DOI: 10.1111/myc.13622 -
Pulmonary Pharmacology & Therapeutics Oct 2023Invasive fungal infections potentially result in fatal outcomes in immunocompromised hosts. Compared to intravenous administration, a nebulization therapy can achieve a...
PURPOSE
Invasive fungal infections potentially result in fatal outcomes in immunocompromised hosts. Compared to intravenous administration, a nebulization therapy can achieve a high concentration of drug delivered in the respiratory tract, without a systematic absorption. We herein summarized the study findings on the safety and clinical utility of nebulized liposomal amphotericin B therapy.
METHODS
According to the PRISMA Extension for Scoping Reviews, we performed a search on MEDLINE and EMBASE for articles with relevant keywords, including "inhaled liposomal amphotericin B″, "nebulized liposomal amphotericin B″, or "aerosolized liposomal amphotericin B″, from the inception of these databases to August 31, 2022.
RESULTS
Of the 172 articles found, 27 articles, including 13 case reports, 11 observational studies, and 3 clinical trials, were selected. Generally, findings showed that nebulized liposomal amphotericin B treatment appeared to be safe and without severe adverse effects. We found an accumulated evidence for the safety, tolerability, and effectiveness of nebulized liposomal amphotericin B prophylaxis among lung transplantation recipients; however, a randomized controlled study has yet to be reported. Data on hemato-oncological patients are relatively scarce; however, a randomized controlled study suggested the prophylactic effect of nebulized liposomal amphotericin B on invasive pulmonary aspergillosis. Observational and randomized controlled studies to evaluate therapeutic efficacy of the nebulized liposomal amphotericin B therapy have not been performed.
CONCLUSION
In conclusion, we found increasing evidence for the effectiveness of the inhalation therapy among patients after lung transplantation and with hemato-oncological diseases.
Topics: Humans; Antifungal Agents; Amphotericin B; Infusions, Intravenous; Randomized Controlled Trials as Topic
PubMed: 37414132
DOI: 10.1016/j.pupt.2023.102233 -
Journal of Oncology Pharmacy Practice :... Jul 2024This systematic review and meta-analysis aimed to determine the safety of liposomal amphotericin B (L-AMB) compared to other antifungal agents for secondary prophylaxis. (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
This systematic review and meta-analysis aimed to determine the safety of liposomal amphotericin B (L-AMB) compared to other antifungal agents for secondary prophylaxis.
METHOD
We conducted a comprehensive search across international databases and reference lists of articles to compile all relevant published evidence evaluating the efficacy and safety of L-AMB versus other antifungals (NLAMB) for secondary prophylaxis against invasive fungal infections. Pooled estimates were calculated after data transformation to evaluate mortality, breakthrough infections, and the frequency of adverse effects, including hypokalemia and nephrotoxicity. Comparisons of breakthrough fungal infection and mortality between the L-AMB and NLAMB groups were performed.
RESULT
We identified 10 studies. The cumulative frequency of patients using L-AMB was 148, compared to 341 patients in the NLAMB group. The mortality rates in the L-AMB and NLAMB groups were 10% and 0%, respectively. However, based on the odds ratio, the mortality in the L-AMB group was lower than that in the NLAMB group. No significant difference was observed in breakthrough invasive fungal infections between the L-AMB and NLAMB groups. The frequencies of nephropathy and hypokalemia in the L-AMB group were 36% and 18%, respectively.
CONCLUSION
Our findings indicate a lower incidence of mortality in the L-AMB group compared to the NLAMB group. No statistically significant difference was observed in the incidence of breakthrough infection between the two groups. L-AMB administration is associated with nephropathy and hypokalemia. However, the refusal to continue treatment due to adverse effects is not significantly high.
Topics: Amphotericin B; Humans; Antifungal Agents; Invasive Fungal Infections; Mycoses; Secondary Prevention; Hypokalemia
PubMed: 38720564
DOI: 10.1177/10781552241241317 -
American Journal of Rhinology & Allergy May 2024Orbital involvement of invasive fungal sinusitis (IFS) is an ominous prognostic marker that should prompt rapid intervention. Transcutaneous retrobulbar administration... (Review)
Review
BACKGROUND
Orbital involvement of invasive fungal sinusitis (IFS) is an ominous prognostic marker that should prompt rapid intervention. Transcutaneous retrobulbar administration of amphotericin B (TRAMB) is an off-label adjunctive treatment that can increase drug penetrance into diseased orbital tissue. To date, there is a lack of consensus regarding the use of TRAMB for treatment of IFS with orbital involvement.
OBJECTIVE
This systematic review aims to synthesize the indications, efficacy, and potential complications of TRAMB.
METHODS
PubMed, EMBASE, and Web of Science databases were probed for systematic review. Article search was conducted through June 2023 using the keywords "invasive fungal sinusitis," "invasive fungal rhinosinusitis," "rhino-orbital mucormycosis," "rhinosinusitis," "orbital," "retrobulbar," and "amphotericin."
RESULTS
In suitable cases as determined by radiologic and clinical evaluation, TRAMB administration has the potential to improve orbital salvage rates and improve versus stabilize visual acuity. Treatment complications are more likely with deoxycholate than with liposomal amphotericin formulations. The existing literature describing use of TRAMB is limited due to its retrospective nature, but the increase in IFS cases since 2020 due to the COVID pandemic has broadened the literature.
CONCLUSIONS
TRAMB is an effective adjunctive treatment in IFS with mild-to-moderate orbital involvement when used in combination with standard of care debridement, systemic antifungal therapy, and immunosuppression reversal. Prospective longitudinal studies and multi-institutional randomized trials are necessary to determine the definitive utility of TRAMB.
PubMed: 38772559
DOI: 10.1177/19458924241254422 -
Pulmonary Pharmacology & Therapeutics Aug 2023Allergic bronchopulmonary aspergillosis (ABPA) is complicated by exacerbations in more than one-third of the subjects. Whether nebulized amphotericin B (NAB) therapy... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Allergic bronchopulmonary aspergillosis (ABPA) is complicated by exacerbations in more than one-third of the subjects. Whether nebulized amphotericin B (NAB) therapy prevents ABPA exacerbations remains unclear.
OBJECTIVES
The primary objective of this systematic review and meta-analysis was to determine the frequency of subjects remaining exacerbation-free, one year after initiating NAB. The key secondary objectives were the time to first exacerbation and the safety of NAB therapy.
METHODS
We searched the PubMed and Embase databases for studies evaluating ≥5 subjects of ABPA managed with NAB. We report the pooled proportion of ABPA subjects remaining exacerbation free after one year. For the randomized controlled trials (RCTs), we estimate the pooled risk difference (RD) of exacerbation-free status at one year with NAB versus the control arm.
RESULTS
We included five studies for our analysis; three were observational (n = 28) and two RCTs (n = 160). The pooled proportion (95% confidence interval [CI]) of subjects remaining exacerbation free with NAB at one year was 76% (62-88). The pooled RD (95% CI) of an exacerbation-free status at one year was 0.33 (-0.12 to 0.78) and was not significantly different between the NAB and control arms. The time to first exacerbation was longer with NAB than with the standard therapy. No serious adverse events were reported with NAB.
CONCLUSION
NAB does not improve exacerbation-free status at one year; however, weak evidence suggests it delays ABPA exacerbations. More research using different dosing regimens is required.
Topics: Humans; Amphotericin B; Antifungal Agents; Aspergillosis, Allergic Bronchopulmonary; Databases, Factual; Observational Studies as Topic
PubMed: 37230237
DOI: 10.1016/j.pupt.2023.102226 -
Open Forum Infectious Diseases Jan 2024Mucormycosis is a potentially lethal mycosis. We reviewed peer-reviewed publications on mucormycosis to assess therapeutic outcomes. (Review)
Review
BACKGROUND
Mucormycosis is a potentially lethal mycosis. We reviewed peer-reviewed publications on mucormycosis to assess therapeutic outcomes.
METHODS
A systematic literature search using the Ovid MEDLINE and EMBASE databases identified manuscripts describing human mucormycosis diagnosed according to European Organization for Research and Treatment of Cancer and the Mycoses Study Group criteria with therapeutic outcomes published from 2000 to 2022.
RESULTS
In 126 articles, 10 335 patients were described, most from Asia (n = 6632, 66%). Diabetes was the most frequent underlying disease (n = 6188, 60%); 222 (2.1%) patients had no underlying diseases. The dominant clinical form was rhino-orbitocerebral (n = 7159, 69.3%), followed by pulmonary (n = 1062, 10.3%). Of 5364 patients with outcome data, amphotericin B monotherapy (n = 3749, mortality 31.5%) was most frequent, followed by amphotericin B + azole (n = 843, mortality 6.6%; < .0001), amphotericin B followed by azole (n = 357, mortality 13.7%; < .0001), posaconazole only (n = 250, mortality 17.2%; < .0001), and isavuconazole only (n = 65, mortality 24.6%; = .24). Duration and dose of antifungals varied widely. Documented outcomes from surgical resections in 149 patients found that 47 of 125 died (37.6%), compared with 16 of 24 (66.7%) patients who did not undergo surgery ( = .008).
CONCLUSIONS
Mucormycosis is more frequently reported in Asia than in Europe and is often linked to diabetes. Antifungal therapy, usually with surgery, is frequently effective for mucormycosis.
PubMed: 38288347
DOI: 10.1093/ofid/ofad704 -
Nanotoxicology Apr 2024Amphotericin B (AmB) is a broad-spectrum therapeutic and effective drug, but it has serious side effects of toxicity and solubility. Therefore, reducing its toxicity... (Review)
Review
Amphotericin B (AmB) is a broad-spectrum therapeutic and effective drug, but it has serious side effects of toxicity and solubility. Therefore, reducing its toxicity should be considered in therapeutic applications. Nanotechnology has paved the way to improve drug delivery systems and reduce toxicity. The present study, for the first time, comprehensively reviews the studies from 2011 to 2023 on reducing the toxicity of AmB. The findings showed that loading AmB with micellar structures, nanostructured lipid carriers, liposomes, emulsions, poly lactide-co-glycolide acid, chitosan, dendrimers, and other polymeric nanoparticles increases the biocompatibility and efficacy of the drug and significantly reduces toxicity. In addition, modified carbon nanoparticles (including graphene, carbon nanotubes, and carbon dots) with positively charged amine groups, PEI, and other components showed favorable drug delivery properties. Uncoated and coated magnetic nanoparticles and silver NPs-AmB composites had less cytotoxicity and more antifungal activity than free AmB. Citrate-reduced GNPs and lipoic acid-functionalized GNPs were also effective nanocarriers to reduce AmB cytotoxicity and improve anti-leishmania efficacy. In addition, zinc oxide-NPs and PEGylated zinc oxide-NPs showed favorable antifungal activity and negligible toxicity. According to a review study, carbon-based nanoparticles, metal nanoparticles, and especially polymer nanoparticles caused some reduction in the toxicity and improved solubility of AmB in water. Overall, considering the discussed nanocarriers, further research on the application of nanotechnology as a cost-effective candidate to improve the efficiency and reduce the cytotoxicity of AmB is recommended.
PubMed: 38646931
DOI: 10.1080/17435390.2024.2340467 -
Mycoses Oct 2023Sporotrichosis is a subcutaneous mycosis caused by a dimorphic fungus belonging to the genus Sporothrix. This fungal infection can affect both humans and domestic... (Review)
Review
Sporotrichosis is a subcutaneous mycosis caused by a dimorphic fungus belonging to the genus Sporothrix. This fungal infection can affect both humans and domestic animals, and in recent years, an increase in the geographic spread and prevalence of sporotrichosis has been observed globally. This systematic review aimed to examine the clinical-epidemiological and therapeutic aspects related to sporotrichosis co-infection with human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS). An extensive electronic search was conducted on databases including PubMed, Web of Science, Lilacs, Medline, Embase, Scopus and SciELO was performed to identify clinical cases of people living with HIV (PLWH) with sporotrichosis published until May 2023. As a result, we found that most co-infected patients were male, representing 71.76% (94/131) of cases. The most prevalent age group was 41-50 years, with a mean age of 36.98 years. The countries with the highest number of cases were Brazil (75.57%, 99/131) and the United States (16.03%, 21/131). The most frequent clinical presentation was systemic dissemination, accounting for 69.47% (91/131) of the cases, followed by cutaneous dissemination with 13% (17/131). The mean CD4 cell count was 154.07 cells/μL, and most patients used amphotericin B with at least one azole, which represented 47.33% (62/131) of cases, followed by azole monotherapy in 17.56% (23/131) of cases. As for the outcome, 51.15% (67/131) of the patients remained alive, and 37.4% (49/131) died. Therefore, it was concluded that sporotrichosis in PLWH is a disease with a high prevalence in Brazil and may be associated with systemic clinical manifestations requiring longer periods of systemic antifungal therapy.
Topics: Animals; Humans; Male; Adult; Middle Aged; Female; Sporotrichosis; Acquired Immunodeficiency Syndrome; HIV; Coinfection; Antifungal Agents; Sporothrix; Azoles; Brazil
PubMed: 37376902
DOI: 10.1111/myc.13627 -
International Journal of Antimicrobial... Feb 2024The use of extracorporeal membrane oxygenation (ECMO) as a cardiocirculatory or respiratory support has tremendously increased in critically ill patients. In the setting...
BACKGROUND AND OBJECTIVE
The use of extracorporeal membrane oxygenation (ECMO) as a cardiocirculatory or respiratory support has tremendously increased in critically ill patients. In the setting of ECMO support, invasive fungal infections are a severe cause of morbidity and mortality. This vulnerable population is at risk of suboptimal antifungal exposure due to an increased volume of distribution (Vd), drug sequestration and decreased clearance. Here, we aimed to summarize ex-vivo and clinical studies on the potential impact of ECMO on the pharmacokinetics (PK) of antifungal agents and dosing requirements.
METHODS
A systematic search of the literature within electronic databases PubMed and EMBASE was conducted from database inception to 30 April 2023. Inclusion criteria were as follows: critically ill patients receiving ECMO regardless of age and reporting at least one PK parameter.
RESULTS
Thirty-six studies met inclusion criteria, including seven ex-vivo experiments and 29 clinical studies evaluating three classes of antifungals: polyenes, triazoles and echinocandins. Based on the available ex-vivo PK data, we found a significant sequestration of highly lipophilic and protein-bound antifungals within the ECMO circuit such as voriconazole, posaconazole and micafungin but the PK of several antifungals remains to be addressed such as amphotericin B, isavuconazole and anidulafungin. Most clinical studies have shown increased Vd of some antifungals like fluconazole and micafungin, particularly in the pediatric population. Conflicting data exist about caspofungin exposure.
CONCLUSIONS
The available literature on the antifungal PK changes in ECMO setting is scarce. Whenever possible, therapeutic drug monitoring is highly advised to personalize antifungal therapy.
Topics: Humans; Antifungal Agents; Caspofungin; Critical Illness; Extracorporeal Membrane Oxygenation; Micafungin
PubMed: 38161046
DOI: 10.1016/j.ijantimicag.2023.107078 -
Open Forum Infectious Diseases Jul 2023Tegumentary leishmaniasis is often subject to limited funding, underpowered studies, and a paucity of high-quality interventional studies. Intravenous liposomal...
BACKGROUND
Tegumentary leishmaniasis is often subject to limited funding, underpowered studies, and a paucity of high-quality interventional studies. Intravenous liposomal amphotericin B (L-AmB) has been increasingly used to treat cutaneous and mucosal leishmaniasis (CL and ML, respectively) despite the lack of well-conducted interventional studies. We conducted a systematic review to consolidate the descriptive evidence on the efficacy and safety of L-AmB in treating CL and ML.
METHODS
Several online databases and the reference lists of included studies were searched to extract data from 132 studies comprising both case reports and case series. The population, intervention, comparison, outcome, and study design strategy and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were used.
RESULTS
Of 132 studies included, 92 were case reports and 40 were case series. Of the 92 cases, 65 (82.3%) were considered cured after receiving L-AmB as part of their treatment regimen. Twenty-one of the 92 (22.8%) cases reported adverse reactions to L-AmB. A pooled cure rate of 87.0% (95% CI, 79.0%-92.0%) was reported for the 38 case series that reported on treatment efficacy; 40.7% of the cases were associated with an adverse reaction.
CONCLUSIONS
Observational data on cure rates using L-AmB suggest efficacy between 80% and 90%, similar to rates reported for other antileishmanial drugs. The highest efficacy rates were observed when a single cycle of L-AmB was administered to patients with mild-moderate CL and ML. The limitations of this study include the heterogeneity observed among the included studies and the increased likelihood of publication bias associated with the inclusion of case reports and case series. This systematic review further illustrates the need for high-quality comparative trials of intravenous L-AmB for the treatment of tegumentary leishmaniasis.
PubMed: 37520422
DOI: 10.1093/ofid/ofad348