-
PloS One 2020Chronic pulmonary aspergillosis (CPA) requires prolonged treatment with itraconazole or voriconazole. However, adverse events (AEs) are common with the use of these... (Comparative Study)
Comparative Study Meta-Analysis
BACKGROUND
Chronic pulmonary aspergillosis (CPA) requires prolonged treatment with itraconazole or voriconazole. However, adverse events (AEs) are common with the use of these agents, with the need to discontinue the offending drug in a significant proportion of the patients. The aim of this study was to evaluate the frequency of adverse events of itraconazole and voriconazole for the treatment of CPA.
METHODS
We searched Embase and Medline to select clinical studies providing information on AEs to itraconazole or voriconazole for the treatment of CPA from inception to May 2020. Reviews, single case reports, and case series reporting less than 10 patients were excluded. Random effect meta-analysis was performed using STATA 16.0.
RESULTS
We included 9 eligible studies with an overall total of 534 CPA patients enrolled. Of these, 69% (n = 366) were treated with voriconazole and 31% (n = 168) with itraconazole. The median daily dose of both itraconazole and voriconazole used was 400mg. In a pooled analysis, AEs were observed in 36% (95% CI: 20-52%, N = 366) of patients on voriconazole and 25% (95% CI: 18 to 31%, N = 168) in those treated with itraconazole. Discontinuation rate due to AEs was the same for both drugs; 35% (47/366) and 35% (15/168) for voriconazole and itraconazole, respectively. There were 70 AEs reported with itraconazole use, the commonest being cardiotoxicity (29%). Skin AEs (28%) were the most frequent among the 204 AEs reported with voriconazole use. None of the studies compared the tolerability of itraconazole head-to-head with voriconazole.
CONCLUSIONS
AEs due itraconazole and voriconazole are common and may lead to discontinuation of treatment in a significant proportion of patients. This information can be used to educate patients prior to commencement of these antifungal therapies.
PROSPERO REGISTRATION NUMBER
CRD42020191627.
Topics: Humans; Administration, Oral; Antifungal Agents; Cardiotoxicity; Itraconazole; Pulmonary Aspergillosis; Treatment Outcome; Voriconazole
PubMed: 33052954
DOI: 10.1371/journal.pone.0240374 -
International Dental Journal Oct 2022Studies reviewing orofacial mycoses in coronavirus disease-2019 (COVID-19) caused by severe acute respiratory syndrome 2 (SARS-CoV-2) infection are sparse. Here we...
OBJECTIVES
Studies reviewing orofacial mycoses in coronavirus disease-2019 (COVID-19) caused by severe acute respiratory syndrome 2 (SARS-CoV-2) infection are sparse. Here we review the major oral and maxillofacial mycoses of COVID-19, the associated comorbidities, and the probable precipitating factors.
METHODS
English-language manuscripts published between March 2020 and October 2021 were searched using PubMed, OVID, SCOPUS, and Web of Science databases, using appropriate keywords.
RESULTS
We identified 30 articles across 14 countries, which met the inclusion criteria of PRISMA guidelines. These yielded a total of 292 patients with laboratory-confirmed COVID-19, 51.4% (n = 150) of whom presented with oral and maxillofacial fungal infections, mainly comprising candidosis, mucormycosis, and aspergillosis. Candida infections were the most prevalent, present in 64% (n = 96), followed by mucormycosis, and only a single case of aspergillosis was noted. Oral and maxillofacial mycoses were predominantly seen in those with comorbidities, especially in those with diabetes (52.4%). Oral mucormycosis was noted in 8.6% (n = 13) and mainly manifested on the hard palate. An overall event rate of oral/maxillofacial mucormycosis manifestation in patients with COVID-19 with diabetes mellitus type 1/2 was about 94% (49/52; 95% confidence interval, 0.73%-0.89%), implying a very high association between diabetes mellitus and the latter condition. All fungal infections appeared either concurrently with COVID-19 symptoms or during the immediate recovery period.
CONCLUSIONS
SARS-CoV-2 infection-related immunosuppression, steroid therapy, as well as comorbidities such as diabetic hyperglycemia appear to be the major predisposing factors for the onset of oral and maxillofacial mycoses in patients with COVID-19 across all age groups.
Topics: COVID-19; Comorbidity; Humans; Mycoses; SARS-CoV-2; Steroids
PubMed: 35367044
DOI: 10.1016/j.identj.2022.02.010 -
Current Opinion in Critical Care Feb 2022We conducted a systematic literature review to summarize the available evidence regarding the incidence, risk factors, and clinical characteristics of...
PURPOSE OF REVIEW
We conducted a systematic literature review to summarize the available evidence regarding the incidence, risk factors, and clinical characteristics of ventilator-associated pneumonia (VAP) in patients undergoing mechanical ventilation because of acute respiratory distress syndrome secondary to SARS-CoV-2 infection (C-ARDS).
RECENT FINDINGS
Sixteen studies (6484 patients) were identified. Bacterial coinfection was uncommon at baseline (<15%) but a high proportion of patients developed positive bacterial cultures thereafter leading to a VAP diagnosis (range 21-64%, weighted average 50%). Diagnostic criteria varied between studies but most signs of VAP have substantial overlap with the signs of C-ARDS making it difficult to differentiate between bacterial colonization versus superinfection. Most episodes of VAP were associated with Gram-negative bacteria. Occasional cases were also attributed to herpes virus reactivations and pulmonary aspergillosis. Potential factors driving high VAP incidence rates include immunoparalysis, prolonged ventilation, exposure to immunosuppressants, understaffing, lapses in prevention processes, and overdiagnosis.
SUMMARY
Covid-19 patients who require mechanical ventilation for ARDS have a high risk (>50%) of developing VAP, most commonly because of Gram-negative bacteria. Further work is needed to elucidate the disease-specific risk factors for VAP, strategies for prevention, and how best to differentiate between bacterial colonization versus superinfection.
Topics: COVID-19; Humans; Overdiagnosis; Pneumonia, Ventilator-Associated; Respiration, Artificial; Respiratory Distress Syndrome; SARS-CoV-2
PubMed: 34932525
DOI: 10.1097/MCC.0000000000000908 -
Journal of Thoracic Disease Feb 2014The effectiveness of the combination therapy of triazole and echinocandin in treatment of invasive aspergillosis (IA) remains controversial. The objective of this...
OBJECTIVE
The effectiveness of the combination therapy of triazole and echinocandin in treatment of invasive aspergillosis (IA) remains controversial. The objective of this systematic review was to assess the efficacy of combination therapy of triazole and echinocandin in treatment of IA.
METHODS
Relevant articles on the combination therapy of triazole and echinocandin in IA, including the animal studies and clinical studies from January 1966 to October 2013, were searched on Web of Science, PubMed and Cochrane Library. The prolongation of survival of the combination therapy of triazole and echinocandin in IA was performed as risk ratio (RR) with 95% confidence interval (95% CI).
RESULTS
Nine animal studies with a total of 1,582 animals and five clinical trials totaling 872 patients were included. The survival of the included animal studies with combination therapy was significantly prolonged compared with echinocandin alone [RR =2.26, (95% CI, 1.79-2.87; P<0.00001)], but no statistical difference compared with monotherapy of triazole [RR =1.19, (95% CI, 0.98-1.44; P=0.08)]. Of the four human cohort studies, two studies observed that the combination therapy of triazole and echinocandin was associated with a significant reduction in mortality compared with other treatments, and one study might be considered as a preferable therapy [HR =0.58, (95% CI, 0.3-1.14; P=0.117)]. While another study revealed that there was no significant difference among the combination therapy of triazole and echinocandin and either of the monotherapy. In the randomized clinical trial (RCT), of the 135 patients who received the combination therapy, 39 died, while 55 died out of 142 patients who received monotherapy (P=0.08, 95% CI, -21.4, 1.09) by week 12.
CONCLUSIONS
The combination therapy of triazole and echinocandin in treating IA results in a trend towards improved overall survival in animals' studies and clinical studies. Well-designed RCTs and further improved clinical trials are necessary to study the effectiveness of the combination therapy.
PubMed: 24605223
DOI: 10.3978/j.issn.2072-1439.2014.01.18 -
Diagnostics (Basel, Switzerland) Oct 2020In this systematic review, we investigate the epidemiology, pathogenesis, risk factors, clinical manifestations, diagnosis and treatment of COVID-19-associated pulmonary... (Review)
Review
In this systematic review, we investigate the epidemiology, pathogenesis, risk factors, clinical manifestations, diagnosis and treatment of COVID-19-associated pulmonary aspergillosis (CAPA). We identified 85 cases from 22 studies. The frequency of CAPA is currently unknown but ranges between <5% to >30% in different case series; the possibility of colonization rather than invasive disease is the most important confounder. The vast majority of patients with CAPA did not have any of the classic host risk factors, such as immunosuppression from organ transplant or neutropenia, although a significant proportion (46%) had received corticosteroids. Age, pulmonary comorbidities and male sex were associated with higher mortality. Patients treated with voriconazole had numerically lower case-fatality rate. Clinical vigilance for CAPA is advisable in critically ill patients with COVID-19 who are not improving, even those who do not meet classic host criteria for invasive mycoses, especially if they are receiving corticosteroids. A thorough, multi-faceted diagnostic work-up and early initiation of a mold-active triazole may be lifesaving. Further research studies using standardized, uniform definitions of invasive disease and colonization are urgently needed.
PubMed: 33050499
DOI: 10.3390/diagnostics10100807 -
BMC Infectious Diseases Mar 2015Antifungal prophylaxis is a promising strategy for reducing invasive fungal infections (IFIs) in allogeneic hematopoietic cell transplant (alloHCT) recipients, but the... (Meta-Analysis)
Meta-Analysis Review
Systematic review and mixed treatment comparison meta-analysis of randomized clinical trials of primary oral antifungal prophylaxis in allogeneic hematopoietic cell transplant recipients.
BACKGROUND
Antifungal prophylaxis is a promising strategy for reducing invasive fungal infections (IFIs) in allogeneic hematopoietic cell transplant (alloHCT) recipients, but the optimum prophylactic agent is unknown. We used mixed treatment comparison (MTC) meta-analysis to compare clinical trials examining the use of oral antifungals for prophylaxis in alloHCT recipients, with the goal of informing medical decision-making.
METHODS
Randomized controlled trials (RCTs) of fluconazole, itraconazole, posaconazole, and voriconazole for primary antifungal prophylaxis were identified through a systematic literature review. Outcomes of interest (incidence of IFI/invasive aspergillosis/invasive candidiasis, all-cause mortality, and use of other antifungals) were extracted from eligible RCTs and incorporated into a Bayesian hierarchical random-effects MTC.
RESULTS
Five eligible RCTs, randomizing 2147 patients in total, were included. Relative to fluconazole, prophylaxis with itraconazole (odds ratio [OR]: 0.52; interquartile range [IQR]: 0.35-0.76), posaconazole (OR: 0.56; IQR: 0.32-0.99), and voriconazole (OR: 0.46; IQR: 0.28-0.73) reduced incidence of overall proven/probable IFI. Posaconazole (OR: 0.31; IQR: 0.17-0.58) and voriconazole (OR: 0.33; IQR: 0.17-0.58) prophylaxis reduced proven/probable invasive aspergillosis more than itraconazole (OR: 0.68; IQR: 0.42-1.12). All-cause mortality was similar across all mould-active agents.
CONCLUSION
As expected, mould-active azoles prevented IFIs, particularly invasive aspergillosis, more effectively than fluconazole in alloHCT recipients. The paucity of comparative efficacy data suggests that other factors such as long-term tolerability, availability of intravenous formulations, local IFI epidemiology, and drug costs may need to form the basis for selection among the mould-active azoles.
Topics: Antifungal Agents; Bayes Theorem; Hematopoietic Stem Cell Transplantation; Humans; Mycoses; Randomized Controlled Trials as Topic; Transplant Recipients
PubMed: 25887385
DOI: 10.1186/s12879-015-0855-6 -
Lung India : Official Organ of Indian... 2023The prevalence of allergic bronchopulmonary aspergillosis (ABPA) in Indian asthmatic patients remains unknown. We systematically reviewed the literature for estimating...
BACKGROUND
The prevalence of allergic bronchopulmonary aspergillosis (ABPA) in Indian asthmatic patients remains unknown. We systematically reviewed the literature for estimating the prevalence of Aspergillus sensitization (AS) and ABPA in Indian subjects with bronchial asthma.
METHODS
We searched the PubMed and Embase databases for studies from India reporting the prevalence of AS or ABPA in at least 50 asthmatics. The primary outcome of our study was to assess the prevalence of ABPA. The secondary outcomes were to evaluate the prevalence of AS in asthma and ABPA in Aspergillus-sensitized asthma. We pooled the prevalence estimates using a random effects model and examined the factors influencing the prevalence using multivariate meta-regression.
RESULTS
Of the 8,383 records retrieved, 34 studies with 14,580 asthmatics met the inclusion criteria. All the studies were from tertiary centers. The pooled prevalence of ABPA in asthmatics (26 studies; 5,554 asthmatics) was 16.2% [95% confidence interval (CI), 12.5-20.4]. The pooled prevalence of AS in asthma (29 studies; 13,405 asthmatics) was 30.9% (95% CI, 25.3-36.6), while the prevalence of ABPA in AS (20 studies; 1,493 asthmatics) was 48.2% (95% CI, 39.6-56.8). Meta-regression identified studies published after 2009 (OR 1.14; 95% CI, 1.02-1.28) and studies with severe asthmatics (OR 1.12; 95% CI, 1.00-1.26) as the only factors associated with higher ABPA prevalence.
CONCLUSIONS
There is a high prevalence of ABPA in Indian asthmatic subjects at tertiary centers, underscoring the need for screening all asthmatic subjects in special asthma and chest clinics for ABPA.
PubMed: 37961961
DOI: 10.4103/lungindia.lungindia_69_23 -
Medical Mycology Oct 2017Osteomyelitis and arthritis caused by mucormycetes are rare diseases that rank among the most challenging complications in orthopedic and trauma surgery. The aim of this... (Review)
Review
Osteomyelitis and arthritis caused by mucormycetes are rare diseases that rank among the most challenging complications in orthopedic and trauma surgery. The aim of this work is to review the epidemiological, clinical, diagnostic, and therapeutic aspects of the osteoarticular mucormycosis with particular emphasis on high-risk patients. A systematic review of osteoarticular mucormycosis was performed using PUBMED and EMBASE databases from 1978 to 2014. Among 34 patients with median age 41 (0.5-73 years), 24 (71%) were males. While 12 (35%) were immunocompromised patients, 14 (41%) had prior surgery, and seven (21%) suffered trauma. Other underlying conditions included diabetes mellitus, hematological malignancies, transplantation, and corticosteroid therapy. The median diagnostic delay from onset of symptoms and signs was 60 (10-180) days. The principal mechanism of the infection was direct inoculation (n = 19; 56%), and in immunocompromised patients was usually hematogenous disseminated. The long bones were infected by trauma or surgery, while a wide variety of bones were involved by hematogenous dissemination. Combined surgery and amphotericin B treatment were implemented in 28 (82%) and eight (23%) had an unfavorable outcome. Osteoarticular mucormycosis occurs most frequently after trauma or surgical procedures. These infections are progressively destructive and more virulent in individuals with impaired immune systems. Early diagnosis, timely administration of amphotericin B, control of underlying conditions, and surgical debridement of infected tissue are critical for successful management of osteoarticular mucormycosis.
Topics: Adolescent; Adult; Aged; Antifungal Agents; Arthritis; Child; Child, Preschool; Debridement; Early Diagnosis; Female; Humans; Infant; Male; Middle Aged; Mucorales; Mucormycosis; Osteomyelitis; Surgical Wound Infection; Wounds and Injuries; Young Adult
PubMed: 28053147
DOI: 10.1093/mmy/myw136 -
The Lancet. Microbe Aug 2021Invasive mould disease (IMD) might affect up to a third of critically ill patients with COVID-19. COVID-19-associated pulmonary aspergillosis (CAPA) is typically... (Review)
Review
Invasive mould disease (IMD) might affect up to a third of critically ill patients with COVID-19. COVID-19-associated pulmonary aspergillosis (CAPA) is typically diagnosed on the basis of a combination of non-specific clinical, radiographical, and mycological findings, but whether most cases represent invasive disease is unresolved. We systematically reviewed autopsy series of three or more decedents with COVID-19 for evidence of IMD. We searched PubMed, Web of Science, OVID (Embase), and medRxiv for studies in English or French published from Jan 1, 2019, to Sept 26, 2020. We identified 1070 references, of which 50 studies met the criteria. These studies described autopsies from 677 decedents, with individual-level data for 443 decedents. The median age was 70·0 years (IQR 57·0-79·0). Of decedents with individual-level data, 133 (30%) had diabetes, 97 (22%) had pre-existing lung disease, and 27 (6%) had immunocompromising conditions. Of 548 decedents with such data, 320 (58%) received invasive mechanical ventilation; among 140 decedents for whom this was known, ventilation was for a median of 9·0 days (IQR 5·0-20·0). Treatment included immunomodulation in 60 decedents and antifungals in 50 decedents. Autopsy-proven IMD occurred in 11 (2%) of 677 decedents, including eight CAPA, two unspecified IMD, and one disseminated mucormycosis. Among 320 decedents who received mechanical ventilation, six (2%) had IMD. We conclude that IMD, including CAPA, is an uncommon autopsy finding in COVID-19.
Topics: Aged; Autopsy; COVID-19; Humans; Pulmonary Aspergillosis; Respiration, Artificial; SARS-CoV-2
PubMed: 34189490
DOI: 10.1016/S2666-5247(21)00091-4 -
Emerging Infectious Diseases Sep 2020We conducted a systematic literature review to obtain risk population-based fungal disease incidence or prevalence data from China. Data were categorized by risk factors...
We conducted a systematic literature review to obtain risk population-based fungal disease incidence or prevalence data from China. Data were categorized by risk factors and extrapolated by using most recent demographic figures. A total of 71,316,101 cases (5.0% of the population) were attributed to 12 risk factors and 17 fungal diseases. Excluding recurrent Candida vaginitis (4,057/100,000 women) and onychomycosis (2,600/100,000 persons), aspergillosis (317/100,000 persons) was the most common problem; prevalence exceeded that in most other countries. Cryptococcal meningitis, an opportunistic infection, occurs in immunocompetent persons almost twice as often as AIDS. The pattern of fungal infections also varies geographically; Talaromyces marneffei is distributed mainly in the Pearl River Basin, and the Yangtze River bears the greatest histoplasmosis burden. New host populations, new endemic patterns, and high fungal burdens in China, which caused a huge impact on public health, underscore the urgent need for building diagnostic and therapeutic capacity.
Topics: China; Cost of Illness; Female; Humans; Mycoses; Prevalence; Talaromyces
PubMed: 32818410
DOI: 10.3201/eid2609.200016