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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 -
BMC Infectious Diseases May 2024Oral candidiasis (OC) is a prevalent opportunistic infection in patients with human immunodeficiency virus (HIV) infection. The increasing resistance to antifungal... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Oral candidiasis (OC) is a prevalent opportunistic infection in patients with human immunodeficiency virus (HIV) infection. The increasing resistance to antifungal agents in HIV-positive individuals suffering from OC raised concerns. Thus, this study aimed to investigate the prevalence of drug-resistant OC in HIV-positive patients.
METHODS
Pubmed, Web of Science, Scopus, and Embase databases were systematically searched for eligible articles up to November 30, 2023. Studies reporting resistance to antifungal agents in Candida species isolated from HIV-positive patients with OC were included. Baseline characteristics, clinical features, isolated Candida species, and antifungal resistance were independently extracted by two reviewers. The pooled prevalence with a 95% confidence interval (CI) was calculated using the random effect model or fixed effect model.
RESULTS
Out of the 1942 records, 25 studies consisting of 2564 Candida species entered the meta-analysis. The pooled prevalence of resistance to the antifungal agents was as follows: ketoconazole (25.5%, 95% CI: 15.1-35.8%), fluconazole (24.8%, 95% CI: 17.4-32.1%), 5-Flucytosine (22.9%, 95% CI: -13.7-59.6%), itraconazole (20.0%, 95% CI: 10.0-26.0%), voriconazole (20.0%, 95% CI: 1.9-38.0%), miconazole (15.0%, 95% CI: 5.1-26.0%), clotrimazole (13.4%, 95% CI: 2.3-24.5%), nystatin (4.9%, 95% CI: -0.05-10.3%), amphotericin B (2.9%, 95% CI: 0.5-5.3%), and caspofungin (0.1%, 95% CI: -0.3-0.6%). Furthermore, there were high heterogeneities among almost all included studies regarding the resistance to different antifungal agents (I > 50.00%, P < 0.01), except for caspofungin (I = 0.00%, P = 0.65).
CONCLUSIONS
Our research revealed that a significant number of Candida species found in HIV-positive patients with OC were resistant to azoles and 5-fluocytosine. However, most of the isolates were susceptible to nystatin, amphotericin B, and caspofungin. This suggests that initial treatments for OC, such as azoles, may not be effective. In such cases, healthcare providers may need to consider prescribing alternative treatments like polyenes and caspofungin.
REGISTRATION
The study protocol was registered in the International Prospective Register of Systematic Reviews as PROSPERO (Number: CRD42024497963).
Topics: Humans; Candidiasis, Oral; Antifungal Agents; HIV Infections; Drug Resistance, Fungal; Candida; Prevalence; Microbial Sensitivity Tests; AIDS-Related Opportunistic Infections; Fluconazole
PubMed: 38822256
DOI: 10.1186/s12879-024-09442-6 -
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 -
Journal Der Deutschen Dermatologischen... Jun 2024Mucocutaneous leishmaniasis is a severe infectious disease, predominantly endemic in Central and South America and is characterized by granulomatous, destructive mucosal... (Review)
Review
Mucocutaneous leishmaniasis is a severe infectious disease, predominantly endemic in Central and South America and is characterized by granulomatous, destructive mucosal lesions in the oral, nasal, and pharyngeal cavities. It is caused by protozoa of the genus Leishmania spp. transmitted to humans by sandflies. Mucocutaneous leishmaniasis occurs after untreated or inadequately treated cutaneous leishmaniasis and is more common in immunocompromised patients. The aim of this systematic review is to summarize all reported treatment options for mucocutaneous leishmaniasis. This review is based on all English, German, French, Spanish and Portuguese articles published in the databases "PubMed" and "Lilacs" from 1995 to 2020. Most of the medical literature is limited to case reports, small case series, retrospective studies, and a few randomized controlled trials. Various treatment options include pentavalent antimonates such as meglumine antimonate or sodium stibogluconate, amphotericin B (liposomal, deoxycholate, lipid complex, colloidal dispersion), miltefosine, and pentamidine. Other therapeutic options include itraconazole, fluconazole, ketoconazole, aminosidine sulfate, and azithromycin. The choice of drug depends primarily on its availability in the endemic area and the patient's comorbidities.
Topics: Humans; Leishmaniasis, Mucocutaneous; Antiprotozoal Agents
PubMed: 38769082
DOI: 10.1111/ddg.15424 -
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 -
Journal of Fungi (Basel, Switzerland) Apr 2024Extrapulmonary infections by spp., though rare, can occur via dissemination, affecting singular or multiple sites, including the skin and musculoskeletal system.... (Review)
Review
Extrapulmonary infections by spp., though rare, can occur via dissemination, affecting singular or multiple sites, including the skin and musculoskeletal system. Skeletal involvement often manifests as osteomyelitis, particularly in the axial skeleton. The present systematic review evaluates all documented cases of skeletal coccidioidomycosis to assess the diagnostic and treatment strategies alongside the outcomes, drawing insights from an analysis of 163 verified cases. A systematic review following PRISMA guidelines identified all studies reporting skeletal infections by spp. up to 2023 from the PubMed and Scopus databases. Eligible studies evaluated osteoarticular infections from spp. Data extraction included demographics, microbiological data, diagnostic methods, and treatment outcomes. Of the 501 initially identified records, a total of 163 patients from 69 studies met the inclusion criteria. Most cases were from the USA, predominantly males, while the median age of the population was 36 years. Diabetes mellitus was the common comorbidity (14.7%). was the most prevalent pathogen. The spine and hand were common sites of infection (17.5% and 15.1%, respectively). Osteomyelitis by spp. was diagnosed, in most cases, by positive cultures ( = 68; 41.7%), while, in 49 (30.9%), both the histological examination and cultures yielded the fungus. Surgical debridement was performed in 80.9% of cases. A total of 118 (72.3%) patients were treated with monotherapy, while combination therapy with two or more antifungal agents was reported in 45 (17.7%). Amphotericin B (either liposomal or deoxycholate) was the most commonly given agent as monotherapy in 51 (31.2%) patients, while 30 (18.4%) patients received itraconazole as monotherapy. The rate of infection's resolution was higher in patients undergoing surgical debridement (79.5%), compared to those treated only with antifungal agents (51.6%, = 0.003). Treatment outcomes showed complete resolution in 74.2% of patients, with a mortality rate of 9.2%. Coccidioidal osseous infections present diagnostic and therapeutic challenges. Surgical intervention is often necessary, complementing antifungal therapy. Vigilance for spp. infections, especially in regions with endemicity, is crucial, particularly when bacterial cultures yield negative results.
PubMed: 38667941
DOI: 10.3390/jof10040270 -
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 -
PLoS Neglected Tropical Diseases Apr 2024Post-kala-azar dermal leishmaniasis (PKDL) is a dermatosis which can occur after successful treatment of visceral leishmaniasis (VL) and is a public health problem in VL...
Post-kala-azar dermal leishmaniasis (PKDL) drug efficacy study landscape: A systematic scoping review of clinical trials and observational studies to assess the feasibility of establishing an individual participant-level data (IPD) platform.
BACKGROUND
Post-kala-azar dermal leishmaniasis (PKDL) is a dermatosis which can occur after successful treatment of visceral leishmaniasis (VL) and is a public health problem in VL endemic areas. We conducted a systematic scoping review to assess the characteristics of published PKDL clinical studies, understand the scope of research and explore the feasibility and value of developing a PKDL individual patient data (IPD) platform.
METHODS
A systematic review of published literature was conducted to identify PKDL clinical studies by searching the following databases: PubMed, Scopus, Ovid Embase, Web of Science Core Collection, WHO Global Index Medicus, PASCAL, Clinicaltrials.gov, Ovid Global Health, Cochrane Database and CENTRAL, and the WHO International Clinical Trials Registry Platform. Only prospective studies in humans with PKDL diagnosis, treatment, and follow-up measurements between January 1973 and March 2023 were included. Extracted data includes variables on patient characteristics, treatment regimens, diagnostic methods, geographical locations, efficacy endpoints, adverse events and statistical methodology.
RESULTS
A total of 3,418 records were screened, of which 56 unique studies (n = 2,486 patients) were included in this review. Out of the 56 studies, 36 (64.3%) were from India (1983-2022), 12 (21.4%) from Sudan (1992-2021), 6 (10.7%) were from Bangladesh (1991-2019), and 2 (3.6%) from Nepal (2001-2007). Five (8.9%) studies were published between 1981-1990 (n = 193 patients), 10 (17.9%) between 1991-2000 (n = 230 patients), 10 (17.9%) between 2001-2010 (n = 198 patients), and 31 (55.4%) from 2011 onwards (n = 1,865 patients). Eight (14.3%) were randomised clinical trials, and 48 (85.7%) were non-randomised studies. The median post-treatment follow-up duration was 365 days (range: 90-540 days) in 8 RCTs and 360 days (range: 28-2,373 days) in 48 non-randomised studies. Disease diagnosis was based on clinical criterion in 3 (5.4%) studies, a mixture of clinical and parasitological methods in 47 (83.9%) and was unclear in 6 (10.7%) studies. Major drugs used for treatment were miltefosine (n = 636 patients), liposomal amphotericin B (L-AmB) (n = 508 patients), and antinomy regimens (n = 454 patients). Ten other drug regimens were tested in 270 patients with less than 60 patients per regimen.
CONCLUSIONS
Our review identified studies with very limited sample size for the three major drugs (miltefosine, L-AmB, and pentavalent antimony), while the number of patients combined across studies suggest that the IPD platform would be valuable. With the support of relevant stakeholders, the global PKDL community and sufficient financing, a PKDL IPD platform can be realised. This will allow for exploration of different aspects of treatment safety and efficacy, which can potentially guide future healthcare decisions and clinical practices.
Topics: Humans; Leishmaniasis, Visceral; Leishmaniasis, Cutaneous; Antiprotozoal Agents; Observational Studies as Topic; Clinical Trials as Topic; Feasibility Studies; Treatment Outcome; India; Bangladesh
PubMed: 38626228
DOI: 10.1371/journal.pntd.0011635 -
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 -
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