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Chronic Respiratory Disease 2008There are increasing reports describing invasive pulmonary aspergillosis (IPA) in patients with chronic obstructive pulmonary disease (COPD) without the classic risk... (Review)
Review
BACKGROUND
There are increasing reports describing invasive pulmonary aspergillosis (IPA) in patients with chronic obstructive pulmonary disease (COPD) without the classic risk factors for this severe infection. The available literature on this association is based on case reports or small case series. The aim of this review is to systematically review these cases and describe the clinical features, diagnostic studies and outcome.
METHODS
We identified all the cases of IPA and COPD reported in the literature and had enough clinical information. We also included five cases of IPA in patients with COPD identified by the authors. These cases were systematically reviewed for clinical features, diagnostic studies and outcome.
RESULTS
There were 60 cases of IPA in patients with COPD identified from the literature. The total number of cases reviewed was 65. The mean age was 65.1 years, the mean FEV1 was 39% of predicted (n = 17, range 19-56%). Forty-nine patients were documented to be on systemic corticosteroids. The mean dose was 24 mg/day (range 15-65 mg/day). Five patients were only on inhaled corticosteroids and in 11 patients there was no documentation of corticosteroid therapy. The clinical and radiological findings were nonspecific. Thirteen patients had documented evidence of disseminated IPA. Sputum examination was positive for Aspergillus in 76% and bronchoscopy with bronchoalveolar lavage that was positive in 70%. The diagnosis of IPA was definite in 43 patients and probable in 22 patients. Forty-six patients were treated with anti-fungal therapy. Fifty-nine patients (91%) died with IPA.
CONCLUSION
Invasive pulmonary aspergillosis is an emerging serious infection in patients with COPD. The majority of these patients have advanced COPD and/or on corticosteroid therapy. The clinical and radiological presentation is nonspecific. High index of suspicion is necessary for the timely treatment of these patients.
Topics: Aged; Aged, 80 and over; Amphotericin B; Aspergillosis; Comorbidity; Female; Humans; Itraconazole; Lung Diseases, Fungal; Male; Middle Aged; Pulmonary Disease, Chronic Obstructive; Risk Factors
PubMed: 18303098
DOI: 10.1177/1479972307085637 -
Italian Journal of Pediatrics Oct 2020To describe a case of thrombophlebitis associated with Candida infection and to analyze other published reports to define clinical characteristics, prognostic data,...
OBJECTIVE
To describe a case of thrombophlebitis associated with Candida infection and to analyze other published reports to define clinical characteristics, prognostic data, diagnostic and therapeutic strategies.
STUDY DESIGN
A computerized search was performed without language restriction using PubMed and Scopus databases. An article was considered eligible for inclusion if it reported cases with Candida thrombophlebitis. Our case was also included in the analysis.
RESULTS
A total of 16 articles reporting 27 cases of Candida thrombophlebitis were included in our review. The median age of patients was 4 years. In 10 cases there was a thrombophlebitis of peripheral veins; in the remaining cases the deep venous circle was interested. Candida albicans was the most frequently involved fungal species. The most recurrent risk factors were central venous catheter (19/28), broad spectrum antibiotics (17/28), intensive care unit (8/28), surgery (3/28), mechanical assisted ventilation (5/28), total parenteral nutrition (8/28), cancer (2/28), premature birth (6/28), cystic fibrosis (2/28). Fever was the most frequent clinical feature. All children with peripheral and deep thrombophlebitis were given antifungal therapy: amphotericin B was the most used, alone or in combination with other antifungal drugs. Heparin was most frequently used as anticoagulant therapy. Illness was fatal in two cases.
CONCLUSION
Candida thrombophlebitis is a rare but likely underdiagnosed infectious complication in pediatric critically ill patients. It is closely connected to risk factors such as central venous catheter, hospitalization in intensive care unit, prematurity, assisted ventilation, chronic inflammatory diseases. Antifungal therapy and anticoagulant drugs should be optimized for each patient and surgical resection is considered in the persistence of illness.
Topics: Amphotericin B; Anticoagulants; Antifungal Agents; Candidiasis; Child; Child, Preschool; Cross Infection; Humans; Prognosis; Risk Factors; Thrombophlebitis
PubMed: 33023609
DOI: 10.1186/s13052-020-00913-5 -
Medical Mycology Jun 2024In response to the growing global burden of fungal infections with uncertain impact, the World Health Organization (WHO) established an Expert Group to identify priority...
In response to the growing global burden of fungal infections with uncertain impact, the World Health Organization (WHO) established an Expert Group to identify priority fungal pathogens and establish the WHO Fungal Priority Pathogens List for future research. This systematic review aimed to evaluate the features and global impact of invasive candidiasis caused by Candida tropicalis. PubMed and Web of Science were searched for studies reporting on criteria of mortality, morbidity (defined as hospitalization and disability), drug resistance, preventability, yearly incidence, diagnostics, treatability, and distribution/emergence from 2011 to 2021. Thirty studies, encompassing 436 patients from 25 countries were included in the analysis. All-cause mortality due to invasive C. tropicalis infections was 55%-60%. Resistance rates to fluconazole, itraconazole, voriconazole and posaconazole up to 40%-80% were observed but C. tropicalis isolates showed low resistance rates to the echinocandins (0%-1%), amphotericin B (0%), and flucytosine (0%-4%). Leukaemia (odds ratio (OR) = 4.77) and chronic lung disease (OR = 2.62) were identified as risk factors for invasive infections. Incidence rates highlight the geographic variability and provide valuable context for understanding the global burden of C. tropicalis infections. C. tropicalis candidiasis is associated with high mortality rates and high rates of resistance to triazoles. To address this emerging threat, concerted efforts are needed to develop novel antifungal agents and therapeutic approaches tailored to C. tropicalis infections. Global surveillance studies could better inform the annual incidence rates, distribution and trends and allow informed evaluation of the global impact of C. tropicalis infections.
Topics: Candida tropicalis; Humans; Antifungal Agents; World Health Organization; Drug Resistance, Fungal; Candidiasis, Invasive; Incidence; Global Health; Risk Factors
PubMed: 38935905
DOI: 10.1093/mmy/myae040 -
Medical Mycology Jun 2024The World Health Organization (WHO) in 2022 developed a fungal priority pathogen list. Candida auris was ultimately ranked as a critical priority pathogen. PubMed and...
The World Health Organization (WHO) in 2022 developed a fungal priority pathogen list. Candida auris was ultimately ranked as a critical priority pathogen. PubMed and Web of Science were used to find studies published from 1 January 2011 to 18 February 2021, reporting on predefined criteria including: mortality, morbidity (i.e., hospitalization and disability), drug resistance, preventability, yearly incidence, and distribution/emergence. Thirty-seven studies were included in the final analysis. The overall and 30-day mortality rates associated with C. auris candidaemia ranged from 29% to 62% and 23% to 67%, respectively. The median length of hospital stay was 46-68 days, ranging up to 140 days. Late-onset complications of C. auris candidaemia included metastatic septic complications. Resistance rates to fluconazole were as high as 87%-100%. Susceptibility to isavuconazole, itraconazole, and posaconazole varied with MIC90 values of 0.06-1.0 mg/l. Resistance rates to voriconazole ranged widely from 28% to 98%. Resistance rates ranged between 8% and 35% for amphotericin B and 0%-8% for echinocandins. Over the last ten years, outbreaks due to C. auris have been reported in in all WHO regions. Given the outbreak potential of C. auris, the emergence and spread of MDR strains, and the challenges associated with its identification, and eradication of its environmental sources in healthcare settings, prevention and control measures based on the identified risk factors should be evaluated for their effectiveness and feasibility. Global surveillance studies could better inform the incidence rates and distribution patterns to evaluate the global burden of C. auris infections.
Topics: Humans; Antifungal Agents; Drug Resistance, Fungal; World Health Organization; Candidiasis; Candida auris; Microbial Sensitivity Tests; Candidemia; Disease Outbreaks; Candida; Incidence
PubMed: 38935900
DOI: 10.1093/mmy/myae042 -
Open Forum Infectious Diseases Jun 2024Mucormycosis is an emerging disease primarily affecting the immunocompromised host, but scarce evidence is available for solid organ transplant recipients (SOTRs). We... (Review)
Review
Mucormycosis is an emerging disease primarily affecting the immunocompromised host, but scarce evidence is available for solid organ transplant recipients (SOTRs). We systematically reviewed 183 cases occurring in SOTRs, exploring epidemiology, clinical characteristics, causative pathogens, therapeutic approaches, and outcomes. Kidney transplants accounted for half of the cases, followed by heart (18.6%), liver (16.9%), and lung (10.4%). Diagnosis showed a dichotomous distribution, with 63.7% of cases reported within 100 days of transplantation and 20.6% occurring at least 1 year after transplant. The 90-day and 1-year mortality rates were 36.3% and 63.4%, respectively. Disseminated disease had the highest mortality at both time points (75% and 93%). Treatment with >3 immunosuppressive drugs showed a significant impact on 90-day mortality (odds ratio [OR], 2.33; 95% CI, 1.02-5.66; = .0493), as did a disseminated disease manifestation (OR, 8.23; 95% CI, 2.20-36.71; = .0027) and the presence of diabetes (OR, 2.35; 95% CI, 1.01-5.65; = .0497). Notably, prophylaxis was administered to 12 cases with amphotericin B. Further investigations are needed to validate these findings and to evaluate the potential implementation of prophylactic regimens in SOTRs at high risk.
PubMed: 38887489
DOI: 10.1093/ofid/ofae043 -
Medical Mycology Jun 2024The World Health Organization, in response to the growing burden of fungal disease, established a process to develop a fungal priority pathogens list (FPPL). This...
The World Health Organization, in response to the growing burden of fungal disease, established a process to develop a fungal priority pathogens list (FPPL). This systematic review aimed to evaluate the epidemiology and impact of invasive fungal disease due to Mucorales. PubMed and Web of Science were searched to identify studies published between January 1, 2011 and February 23, 2021. Studies reporting on mortality, inpatient care, complications and sequelae, antifungal susceptibility, risk factors, preventability, annual incidence, global distribution, and emergence during the study time frames were selected. Overall, 24 studies were included. Mortality rates of up to 80% were reported. Antifungal susceptibility varied across agents and species, with the minimum inhibitory concentrations lowest for amphotericin B and posaconazole. Diabetes mellitus was a common risk factor, detected in 65%-85% of patients with mucormycosis, particularly in those with rhino-orbital disease (86.9%). Break-through infection was detected in 13.6%-100% on azole or echinocandin antifungal prophylaxis. The reported prevalence rates were variable, with some studies reporting stable rates in the USA of 0.094-0.117/10 000 discharges between 2011 and 2014, whereas others reported an increase in Iran from 16.8% to 24% between 2011 and 2015. Carefully designed global surveillance studies, linking laboratory and clinical data, are required to develop clinical breakpoints to guide antifungal therapy and determine accurate estimates of complications and sequelae, annual incidence, trends, and global distribution. These data will provide robust estimates of disease burden to refine interventions and better inform future FPPL.
Topics: Humans; Mucorales; Antifungal Agents; Mucormycosis; World Health Organization; Risk Factors; Invasive Fungal Infections; Microbial Sensitivity Tests; Prevalence; Drug Resistance, Fungal; Incidence; Global Health
PubMed: 38935901
DOI: 10.1093/mmy/myad130 -
Annals of Clinical Microbiology and... Jun 2021Aspergillosis of Central Nervous System (CNS) is a highly lethal infection in patients with leukemia and Stem Cell Transplantation (SCT). (Review)
Review
BACKGROUND
Aspergillosis of Central Nervous System (CNS) is a highly lethal infection in patients with leukemia and Stem Cell Transplantation (SCT).
METHODS
Case reports of CNS aspergillosis in patients with leukemia and SCT published between 1990 and August 2020 were gathered using a structured search through PubMed/Medline.
RESULTS
Sixty-seven cases were identified over the searches of the PubMed bibliographic database and then, 59 cases were included in the final analysis. Europe had the largest share of cases at 57.6% (34 reports), followed by Americas and Asia. Affected patients were predominantly males (58.6%) and the mean age of the patients was 36.1 years, while 62.7% of the patients were under the age of 50 years. The most common leukemia types include Acute Lymphoblastic Leukemia (ALL), Chronic Lymphocytic Leukemia (CLL), and Acute Myeloid Leukemia (AML) at 43.4%, 27.4%, and 23.5%, respectively. Furthermore, stem cell transplantation was reported in 11 cases. The overall mortality was 33%; however, the attributable mortality rate of CNS aspergillosis was 24.5%. Altered mental status, hemiparesis, cranial nerve palsies, and seizures were the clearest manifestations of infection and lung involvement reported in 57% of the patients. Histopathologic examination led to the diagnosis of infection in 57% of the patients followed by culture (23.7%), galactomannan assay (8.5%), and molecular method (3.3%). Amphotericin B and voriconazole were the most frequently used drugs for infection treatment. Good results were not obtained in one-third of the patients treated by voriconazole. Finally, neurosurgical intervention was used for 23 patients (39%).
CONCLUSION
CNS aspergillosis is a rapidly progressive infection in leukemic patients. Thus, these patients should be followed up more carefully. Furthermore, management of induction chemotherapy, use of different diagnostic methods, and use of appropriate antifungal can lead to infection control.
Topics: Antifungal Agents; Asia; Aspergillosis; Central Nervous System; Databases, Factual; Europe; Female; Humans; Leukemia; Male; Stem Cell Transplantation; Voriconazole
PubMed: 34130699
DOI: 10.1186/s12941-021-00452-9 -
The Cochrane Database of Systematic... Nov 2010Oral candidiasis (OC) associated with human immunodeficiency virus (HIV) infection occurs commonly and recurs frequently, often presenting as an initial manifestation of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Oral candidiasis (OC) associated with human immunodeficiency virus (HIV) infection occurs commonly and recurs frequently, often presenting as an initial manifestation of the disease. Left untreated, these lesions contribute considerably to the morbidity associated with HIV infection. Interventions aimed at preventing and treating HIV-associated oral candidal lesions form an integral component of maintaining the quality of life for affected individuals.
OBJECTIVES
To determine the effects of any intervention in preventing or treating OC in children and adults with HIV infection.
SEARCH STRATEGY
The search strategy was based on that of the Cochrane HIV/AIDS Review Group. The following electronic databases were searched for randomised controlled trials for the years 1982 to 2005: Medline, AIDSearch, EMBASE and CINAHL. The Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effectiveness, and the Cochrane Central Register of Controlled Trials (CENTRAL) were also searched through May 2005. The abstracts of relevant conferences, including the International Conferences on AIDS and the Conference on Retroviruses and Opportunistic Infections, as indexed by AIDSLINE, were also reviewed. The strategy was iterative, in that references of included studies were searched for additional references. All languages were included.The updated database search was done for the period 2005 up to 2009. The following databases were searched: Medline, EMBASE, the Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effectiveness and the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library. AIDSearch was not searched for the updated search as it ceased publication during 2008.
SELECTION CRITERIA
Randomised controlled trials (RCTs) of palliative, preventative or curative therapy were considered, irrespective of whether the control group received a placebo. Participants were HIV positive adults and children.
DATA COLLECTION AND ANALYSIS
Two authors independently assessed the methodological quality of the trials and extracted data. Study authors were contacted for additional data where necessary.
MAIN RESULTS
For the first publication of the review in 2006, forty studies were retrieved. Twenty eight trials (n=3225) met inclusion criteria. During the update search for the review a, further six studies were identified. Of these, five met the inclusion criteria and were included in the review. The review now includes 33 studies (n=3445): 22 assessing treatment and 11 assessing prevention of oropharyngeal candidiasis. Six studies were done in developing countries, 16 in the United States of America and the remainder in Europe.Treatment Treatment was assessed in the majority of trials looking at both clinical and mycological cures. In the majority of comparisons there was only one trial. Compared to nystatin, fluconazole favoured clinical cure in adults (1 RCT; n=167; RR 1.69; 95% CI 1.27 to 2.23). There was no difference with regard to clinical cure between fluconazole compared to ketoconazole (2 RCTs; n=83; RR 1.27; 95% CI 0.97 to 1.66), itraconazole (2 RCTs; n=434; RR 1.05; 95% CI 0.94 to 1.16), clotrimazole (2 RCTs; n=358; RR 1.14; 95% CI 0.92 to 1.42) or posaconazole (1 RCT; n=366; RR1.32; 95% CI 0.36 to 4.83). Two trials compared different dosages of fluconazole with no difference in clinical cure. When compared with clotrimazole, both fluconazole (2 RCTs; n=358; RR 1.47; 95% CI 1.16 to 1.87) and itraconazole (1 RCT; n=123; RR 2.20; 95% CI 1.43 to3.39) proved to be better for mycological cure. Both gentian violet (1 RCT; n=96; RR 5.28; 95% CI 1.23 to 22.55) and ketoconazole (1 RCT; n=92; RR 5.22; 95% CI 1.21 to 22.53) were superior to nystatin in bringing about clinical cure. A single trial compared gentian violet with lemon juice and lemon grass with no significant difference in clinical cure between the groups. Prevention Successful prevention was defined as the prevention of a relapse while receiving prophylaxis. Fluconazole was compared with placebo in five studies (5 RCTs; n=599; RR 0.61; 95% CI 0.5 to 0.74) and with no treatment in another (1 RCT; n=65; RR 0.16; 95% CI 0.08 to 0.34). In both instances the prevention of clinical episodes was favoured by fluconazole. Comparing continuous fluconazole treatment with intermittent treatment (2 RCTs; n=891; RR 0.65; 95% CI 0.23 to 1.83), there was no significant difference between the two treatment arms. Chlorhexidine was compared with normal saline in a single study with no significant difference between the treatment arms.
AUTHORS' CONCLUSIONS
Five new studies were added to the review, but their results do not alter the final conclusion of the review.Implications for practice Due to there being only one study in children, it is not possible to make recommendations for treatment or prevention of OC in children. Amongst adults, there were few studies per comparison. Due to insufficient evidence, no conclusion could be made about the effectiveness of clotrimazole, nystatin, amphotericin B, itraconazole or ketoconazole with regard to OC prophylaxis. In comparison to placebo, fluconazole is an effective preventative intervention. However, the potential for resistant Candida organisms to develop, as well as the cost of prophylaxis, might impact the feasibility of implementation. No studies were found comparing fluconazole with other interventions. The direction of findings suggests that ketoconazole, fluconazole, itraconazole and clotrimazole improved the treatment outcomes.Implications for research It is encouraging that low-cost alternatives are being tested, but more research needs to be on in this area and on interventions like gentian violet and other less expensive anti-fungal drugs to treat OC. More well-designed treatment trials with larger samples are needed to allow for sufficient power to detect differences in not only clinical, but also mycological, response and relapse rates. There is also a strong need for more research to be done on the treatment and prevention of OC in children as it is reported that OC is the most frequent fungal infection in children and adolescents who are HIV positive. More research on the effectiveness of less expensive interventions also needs to be done in resource-poor settings. Currently few trials report outcomes related to quality of life, nutrition, or survival. Future researchers should consider measuring these when planning trials. Development of resistance remains under-studied and more work must be done in this area. It is recommended that trials be more standardised and conform more closely to CONSORT.
Topics: Adolescent; Adult; Antifungal Agents; Candidiasis, Oral; Child; HIV Infections; Humans; Oropharynx; Pharyngeal Diseases; Randomized Controlled Trials as Topic; Secondary Prevention
PubMed: 21069679
DOI: 10.1002/14651858.CD003940.pub3 -
Scientific Reports Apr 2021Cryptococcal meningitis (CM) is the most fatal adult meningitis in patients with human immunodeficiency virus (HIV). There is no conclusive evidence for the superiority... (Meta-Analysis)
Meta-Analysis
Cryptococcal meningitis (CM) is the most fatal adult meningitis in patients with human immunodeficiency virus (HIV). There is no conclusive evidence for the superiority of 1-week amphotericin B deoxycholate (AmphB) + flucytosine (5-FC) regimen over other antifungals in the management of HIV patients with CM (HIV-CM patients). We aimed to evaluate the differences in efficacy and tolerability of different antifungal agents in HIV-CM patients by conducting a current network meta-analysis NMA. Overall, 19 randomized controlled trials were included with 2642 participants. A regimen indicated a possibly lower early mortality rate, namely, AmphB + 5-FC + Azole (OR = 1.1E-12, 95% CIs = 1.3E-41 to 0.06) comparing to AmphB + 5-FC. The current NMA provides evidence that AmphB + 5-FC + Azole are superior to all the investigated treatments for induction regimen in HIV-CM patients.
Topics: AIDS-Related Opportunistic Infections; Amphotericin B; Antifungal Agents; Deoxycholic Acid; Drug Combinations; Flucytosine; Humans; Induction Chemotherapy; Meningitis, Cryptococcal; Treatment Outcome
PubMed: 33883566
DOI: 10.1038/s41598-021-87726-6 -
Frontiers in Pharmacology 2020Precision dosing for many antifungal drugs is now recommended. Saliva sampling is considered as a non-invasive alternative to plasma sampling for therapeutic drug...
Precision dosing for many antifungal drugs is now recommended. Saliva sampling is considered as a non-invasive alternative to plasma sampling for therapeutic drug monitoring (TDM). However, there are currently no clinically validated saliva models available. The aim of this study is firstly, to conduct a systematic review to evaluate the evidence supporting saliva-based TDM for azoles, echinocandins, amphotericin B, and flucytosine. The second aim is to develop a saliva population pharmacokinetic (PK) model for eligible drugs, based on the evidence. Databases were searched up to July 2019 on PubMed and Embase, and 14 studies were included in the systematic review for fluconazole, voriconazole, itraconazole, and ketoconazole. No studies were identified for isavuconazole, posaconazole, flucytosine, amphotericin B, caspofungin, micafungin, or anidulafungin. Fluconazole and voriconazole demonstrated a good saliva penetration with an average S/P ratio of 1.21 (± 0.31) for fluconazole and 0.56 (± 0.18) for voriconazole, both with strong correlation (r = 0.89-0.98). Based on the evidence for TDM and available data, population PK analysis was performed on voriconazole using Nonlinear Mixed Effects Modeling (NONMEM 7.4). 137 voriconazole plasma and saliva concentrations from 11 patients (10 adults, 1 child) were obtained from the authors of the included study. Voriconazole pharmacokinetics was best described by one-compartment PK model with first-order absorption, parameterized by clearance of 4.56 L/h (36.9% CV), volume of distribution of 60.7 L, absorption rate constant of 0.858 (fixed), and bioavailability of 0.849. Kinetics of the voriconazole distribution from plasma to saliva was identical to the plasma kinetics, but the extent of distribution was lower, modeled by a scale factor of 0.5 (4% CV). A proportional error model best accounted for the residual variability. The visual and simulation-based model diagnostics confirmed a good predictive performance of the saliva model. The developed saliva model provides a promising framework to facilitate saliva-based precision dosing of voriconazole.
PubMed: 32595511
DOI: 10.3389/fphar.2020.00894