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Tropical Medicine and Infectious Disease Aug 2022A reliable estimate of antifungal susceptibility in candidemia patients is increasingly important to track the spread of bloodstream infections and define the true... (Review)
Review
A reliable estimate of antifungal susceptibility in candidemia patients is increasingly important to track the spread of bloodstream infections and define the true burden of the ongoing antifungal resistance. A systematic review and meta-analysis (SRMA) were conducted aiming to estimate the global prevalence and identify patterns of antifungal resistance. A systematic literature search of the PubMed, Scopus, ScienceDirect and Google Scholar electronic databases was conducted on published studies that employed antifungal susceptibility testing (AFST) on clinical isolates globally. Seventy-nine eligible studies were included. Using meta-analysis of proportions, the overall pooled prevalence of three most important antifungal drugs; Fluconazole, Amphotericin B and Voriconazole resistant were calculated as 15.2% (95% CI: 9.2-21.2), 1.3% (95% CI: 0.0-2.9) and 4.7% (95% CI: 2.2-7.3), respectively. Based on study enrolment time, country/continent and AFST method, subgroup analyses were conducted for the three studied antifungals to determine sources of heterogeneity. Timeline and regional differences in prevalence of antifungal resistance were identified with the same patterns among the three antifungal drugs. These findings highlight the need to conduct further studies to assess and monitor the growing burden of antifungal resistance, to revise treatment guidelines and to implement regional surveillance to prevent further increase in drug resistance emerging recently.
PubMed: 36006280
DOI: 10.3390/tropicalmed7080188 -
Ophthalmic Plastic and Reconstructive...Following COVID-19 infection a rising count of rhino-orbito-cerebral mucormycosis is observed, requiring orbital exenteration, a disabling lifetime affecting surgery....
PURPOSE
Following COVID-19 infection a rising count of rhino-orbito-cerebral mucormycosis is observed, requiring orbital exenteration, a disabling lifetime affecting surgery. One of the potential interventions for globe salvage in these patients is retrobulbar injections of amphotericin B. This study was conducted to review protocols, outcomes, and side effects of retrobulbar injection of amphotericin B in patients with COVID-19 associated rhino-orbito-cerebral mucormycosis (CAM).
METHODS
The PubMed, Scopus, Web of Science, and Embase databases were searched using a comprehensive string of relevant keywords. All English studies with the confirmed diagnosis of CAM infection were included. We excluded all studies in which retrobulbar injection of amphotericin B was not implemented in any of the patients or there was a lack of clarified and detailed data about this procedure among participants.
RESULTS
A total of 647 cases had a history of retrobulbar injection(s) of amphotericin B in 13 reviewed studies with 3,132 subjects of CAM. The most common protocol was the retrobulbar injection of 1 ml of 3.5 mg/ml liposomal amphotericin B for 3 doses daily or on alternate days. We discerned that the globe salvage rate was 95.0% in eyes with a history of retrobulbar injection(s). The total rate of orbital exenteration was 14.9%, regardless of the history of retrobulbar injection of the drug. Other outcomes of this intervention were vision salvage and reduced major ophthalmic complaints, including pain, swelling, chemosis, ptosis, and ophthalmoplegia. The side effects of this intervention were not serious, and most of them were transient. They included swelling at the injection site, restriction of ocular motilities, exacerbation of orbital inflammation, and even intensification of visual impairment in a few cases.
CONCLUSIONS
Retrobulbar injection of amphotericin B should be considered a nearly safe and protective intervention against orbital exenteration in patients with CAM. It may also be effective in saving vision. Since the effectiveness of orbital exenteration in the survival of patients is not ascertained, retrobulbar injections can be considered an alternative intervention.
Topics: Amphotericin B; Antifungal Agents; COVID-19; Eye Diseases; Eye Infections, Fungal; Humans; Mucormycosis; Orbital Diseases; Paranasal Sinus Diseases
PubMed: 35943425
DOI: 10.1097/IOP.0000000000002256 -
The Journal of Antimicrobial... Sep 2022Trichoderma spp. are filamentous fungi causing invasive fungal diseases in patients with haematological malignancies and in peritoneal dialysis patients.
BACKGROUND
Trichoderma spp. are filamentous fungi causing invasive fungal diseases in patients with haematological malignancies and in peritoneal dialysis patients.
OBJECTIVES
To analyse clinical presentation, predisposing factors, treatment and outcome of Trichoderma infections.
METHODS
A systematic literature review was conducted for published cases of invasive Trichoderma infection in PubMed until December 2021 and by reviewing the included studies' references. Cases from the FungiScope® registry were added to a combined analysis.
RESULTS
We identified 50 invasive infections due to Trichoderma species, including 11 in the FungiScope® registry. The main underlying conditions were haematological malignancies in 19 and continuous ambulatory peritoneal dialysis (CAPD) in 10 cases. The most prevalent infection sites were lung (42%) and peritoneum (22%). Systemic antifungal therapy was administered in 42 cases (84%), mostly amphotericin B (n = 27, lipid-based formulation 13/27) and voriconazole in 15 cases (30%). Surgical interventions were performed in 13 cases (26%). Overall mortality was 48% (n = 24) and highest for allogeneic HSCT and solid organ transplantation (SOT) recipients [80% (4/5) and 77% (7/9), respectively]. In patients treated with amphotericin B, voriconazole and caspofungin, mortality was 55% (15/27), 46% (7/15) and 28% (2/7), respectively. Three out of four patients treated with a combination therapy of voriconazole and caspofungin survived.
CONCLUSIONS
Despite treatment with antifungal therapies and surgery, invasive Trichoderma infections are life-threatening complications in immunocompromised patients, especially after HSCT and SOT. In addition, Trichoderma spp. mainly affect the lungs in patients with haematological malignancies and the peritoneum in CAPD patients.
Topics: Amphotericin B; Antifungal Agents; Caspofungin; Hematologic Neoplasms; Humans; Registries; Trichoderma; Voriconazole
PubMed: 35929089
DOI: 10.1093/jac/dkac235 -
Medical Mycology Aug 2022Aspergillus spp. osteoarticular infections are destructive opportunistic infections, while there is no clear consensus on their management. The purpose of this review is...
UNLABELLED
Aspergillus spp. osteoarticular infections are destructive opportunistic infections, while there is no clear consensus on their management. The purpose of this review is to investigate the current literature regarding Aspergillus spp. osteoarticular infections. An electronic search of the PubMed and Scopus databases was conducted considering studies that assessed osteoarticular infections from Aspergillus spp. We included only studies with biopsy proven documentation of positive cultures or histological findings for Aspergillus spp., and those with essential information for each case such as the anatomical location of the infection, the type of treatment (conservative, surgical, combination), the antifungal therapy, and the outcome. Overall, 148 studies from 1965 to 2021 including 186 patients were included in the review. One hundred and seven (57.5%) patients underwent surgical debridement in addition to antifungal therapy, while 79 (42.7%) patients were treated only conservatively. Complete infection resolution was reported in 107 (57.5%) patients, while partial resolution in 29 (15.5%) patients. Surgical debridement resulted in higher complete infection resolution rate compared to only antifungal therapy (70.0% vs. 40.5%, P < 0.001), while complete resolution rate was similar for antifungal monotherapy and combination/sequential therapy (58.3% vs. 54.5%; P = 0.76). Last, complete resolution rate was also similar for monotherapy with amphotericin B (58.1%) and voriconazole (58.6%; P = 0.95). The results of this study indicate that antifungal monotherapy has similar efficacy with combination/sequential therapy, while voriconazole has similar efficacy with amphotericin B. Moreover, surgical debridement of the infected focus results in better outcomes in terms of infection eradication compared to conservative treatment.
LAY SUMMARY
Antifungal monotherapy has similar efficacy with combination/sequential therapy, and voriconazole has similar efficacy with amphotericin B for the treatment of Aspergillus spp. osteoarticular infections, while surgical debridement of the infected focus improves the infection eradication rate.
Topics: Animals; Amphotericin B; Antifungal Agents; Aspergillosis; Aspergillus; Microbial Sensitivity Tests; Treatment Outcome; Voriconazole
PubMed: 35867975
DOI: 10.1093/mmy/myac052 -
British Journal of Clinical Pharmacology Sep 2022This systematic literature review and meta-analysis aimed to evaluate the risk factors for vancomycin-associated acute kidney injury (AKI) incidence. (Meta-Analysis)
Meta-Analysis Review
AIMS
This systematic literature review and meta-analysis aimed to evaluate the risk factors for vancomycin-associated acute kidney injury (AKI) incidence.
METHODS
This study assessed risk factors for vancomycin-associated AKI in adult patients by searching studies from PubMed, the Cochrane Library and Embase. Random effect models were used to calculate odds ratios (ORs) and 95% confidence intervals (CIs).
RESULTS
Fifty-three studies were included in our meta-analysis. For patient factors, black race (OR 1.47, 95% CI: 1.16-1.87), Caucasian (OR 0.72, 95% CI: 0.58-0.90) and obesity (OR 1.46, 95% CI: 1.12-1.90) were associated with an increase in vancomycin-associated AKIs. In terms of vancomycin-related factors, longer treatment duration (>14 d; OR 1.73, 95% CI: 1.06-2.83), serum vancomycin trough level >15 μg/mL (OR 2.10, 95% CI: 1.43-3.07) and vancomycin trough level >20 μg/mL (OR 2.84, 95% CI: 1.48-5.44) increased the risks of vancomycin-associated AKI. For comorbidities and clinical factors, renal disease (OR 2.19, 95% CI: 1.51-3.17) showed the highest odds of vancomycin-associated AKI, followed by hepatic disease, intensive care unit admission, heart failure, sepsis, coronary heart disease and diabetes mellitus. For concomitant nephrotoxic drugs, amphotericin B (OR 5.21, 95% CI: 3.44-7.87) showed the highest odds of vancomycin-associated AKI, followed by acyclovir (OR 3.22, 95% CI: 1.39-7.46), vasopressors, loop diuretics, piperacillin-tazobactam and aminoglycoside. The use of any concomitant nephrotoxic agent (OR 1.74, 95% CI: 1.17-2.58) increased the odds of vancomycin-associated AKI.
CONCLUSION
Our results may help predict the risk of vancomycin-associated AKI in the clinical setting.
Topics: Acute Kidney Injury; Adult; Anti-Bacterial Agents; Drug Therapy, Combination; Humans; Retrospective Studies; Risk Factors; Vancomycin
PubMed: 35665530
DOI: 10.1111/bcp.15429 -
Iranian Journal of Pathology 2022Cerebral mucormycosis (CM) is a life-threatening manifestation of mucormycosis, an angioinvasive fungal infection caused by Mucorales. We sought to systematically review... (Review)
Review
Cerebral mucormycosis (CM) is a life-threatening manifestation of mucormycosis, an angioinvasive fungal infection caused by Mucorales. We sought to systematically review all available case reports to describe epidemiologic features, clinical manifestations, predisposing factors, and diagnostic and treatment strategies of CM. A systematic search was conducted using a combination of the following keywords: "Mucor", "Zygomycetes", "mucormycosis", "cereb*", "brain", "central nervous system", and "intracranial", separately and in combination until December 31 2018. Data sources included PubMed, Scopus, EMBASE, Web of Science, Science Direct, and Proquest without limiting the time of publication. We included 287 articles corresponding to 345 cases of CM. Out of the 345 cases, 206 (60%) were male with a median age of 44 years; 130 (38%) were reported from North America; 87 (25%) from Asia; and 84 (24%) from Europe. The median time from onset of symptoms to presentation was 3-7 days (65/345, 65%). The highest mortality was observed among patients with diabetes mellitus (=0.003). Debridement of infected brain tissue was associated with improved survival in CM cases (OR 1.5; 95% CI 01.3-1.8; <0.0001). The use of liposomal amphotericin B (L-AMB) was significantly associated with patients' recovery (OR 2.09; 95% CI 1.2-3.4; =0.003). The combination of L-AMB and posaconazole (12.5%) was more effective than the monotherapy treatment of CM cases (=0.009). Clinicians should consider DM as an important risk factor for CM. Moreover, surgical debridement and antifungal combination therapy could be an effective approach in the management of CM patients.
PubMed: 35463720
DOI: 10.30699/IJP.2022.538690.2721 -
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 -
Pathogens (Basel, Switzerland) Feb 2022Recommendations for managing patients with cerebral cryptococcomas are scarce across multiple clinical guidelines. Due to the deficiency of high-quality data coupled... (Review)
Review
BACKGROUND
Recommendations for managing patients with cerebral cryptococcomas are scarce across multiple clinical guidelines. Due to the deficiency of high-quality data coupled with an increasing number of at-risk patients, the purpose of this review is to describe the demographic characteristics, causative pathogen, intracranial imaging, surgical and/or pharmacological interventions, as well as outcomes of patients with cerebral cryptococcomas to improve recognition and management.
METHODS
We conducted a scoping review in accordance with the PRISMA guidelines using PubMed and Web of Science. Reports were included if the following details were presented: (1) site of infection; (2) treatment details which at least include the specific antifungal therapy administered, if applicable; and (3) patient outcome.
RESULTS
A total of 40 records representing 47 individual patients were included, of which the median age was 48.5 years, 75% were male, and 60% reported a significant past medical, surgical, or social history. . was isolated more often than . (74% vs. 26%, respectively). Patients most often presented with headache, altered mental status and/or confusion, and vomiting occurring over a median of 30 days; though few were noted to have significant findings on physical examination. More than 50% of patients had a single cerebral cryptococcoma lesion, whereas perilesional edema was present in 73% of cases. Surgical intervention occurred in 49% of patients. An amphotericin B-based formulation was administered as "induction" therapy to 91% of patients, but combined with flucytosine or fluconazole in only 58%, for an overall median of 42 days. Fifty two percent of patients received "maintenance" therapy for a median of 126 days, in which fluconazole was most often used. Corticosteroids were administered to approximately 30% of patients for a median of 31.5 days. Overall, mortality was 34%.
CONCLUSION
Based on our findings, management should include antifungal therapy for a minimum of 6 months with considerations for concomitant corticosteroids in the setting of perilesional edema, as well as surgical intervention. Emphasis should be placed on providing well-documented treatment details in future case reports and series to allow for the development of more concise evidence-based recommendations.
PubMed: 35215148
DOI: 10.3390/pathogens11020205 -
Journal of Fungi (Basel, Switzerland) Feb 2022Cutaneous mucormycosis is the third most common clinical type of mucormycosis. The signs and symptoms vary widely, and it is important to make the diagnosis as early as... (Review)
Review
Cutaneous mucormycosis is the third most common clinical type of mucormycosis. The signs and symptoms vary widely, and it is important to make the diagnosis as early as possible in order to achieve a better outcome. We present a systematic review of its epidemiology, clinical presentation, diagnosis, and treatment, analyzing cases published from 1958 until 2021. The review was conducted according to the PRISMA guidelines and included 693 cases from 485 articles from 46 countries. Most publications were from North America (256 cases, 36.9%) and Asia (216 cases, 31.2%). The most common risk factors were diabetes mellitus (20%) and hematological malignancies (15.7%). However, a large proportion of published cases (275, 39.6%) had no identified underlying disease. The most common mode of transmission was trauma (54%), and 108 (15.6%) cases were healthcare-associated. In this review, 291 (42.5%) patients had localized infection, and 90 (13%) had disseminated mucormycosis. In Europe, N. America and S. America, the most common genus was spp., while in Asia it was spp. (34.7%). Treatment was performed with antifungals, mainly amphotericin B, and/or surgery. Mortality was significantly lower when both antifungals and surgery were applied (29.6%).
PubMed: 35205948
DOI: 10.3390/jof8020194 -
Indian Journal of Pharmacology 2021Till now, no meta-analysis is available to address the clinical profile, risk factors, different interventions, and outcomes among COVID-19-associated... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Till now, no meta-analysis is available to address the clinical profile, risk factors, different interventions, and outcomes among COVID-19-associated rhino-orbito-cerebral mucormycosis (C-ROCM) cases.
MATERIALS AND METHODS
Eight literature databases were screened using appropriate keywords from November 1, 2019, to June 30, 2021. The objectives were to analyze the clinical and microbiological profile, risk factor/comorbidity, intervention, and outcome. "R-metafor package" was used for analysis.
RESULTS
A total of 23 studies were included. The mean age of presentation of C-ROCM was 54.6 years. The most common presentation was ptosis (72.7%), lid edema (60.6%), proptosis (60.6%), ophthalmoplegia (57.3%), loss of vision (53.7%), facial edema (34.7%), and nasal-blockage (11.8%). Evidence of intracranial spread was seen in 42.8% of cases. Rhizopus was the most common fungus (57.1%) isolated in fungal culture. Among C-ROCM patients, diabetes was the commonest comorbid condition, and the use of corticosteroids related to COVID-19 treatment was the most common risk factor (85.75%). Compared to controlled diabetics, C-ROCM was significantly higher among uncontrolled diabetics (odds ratio [OR] 0.15, 95% confidence interval [C.I.] 0.041-0.544, P = 0.0010). However, no significant association was seen between C-ROCM and COVID-19 severity (OR 0.930, 95% C.I. 0.212-4.087, P = 0.923). For treatment, amphotericin-B was the most common antifungal drug used which was followed by surgical options. However, mortality was high (prevalence 0.344, 95% C.I. 0.205-0.403) despite treatment.
CONCLUSION
Although local rhino-orbito symptoms were the first to appear, rapid intracranial extension was seen in a significant number of C-ROCM cases. Uncontrolled diabetes and excessive use of corticosteroid were the most common risk factors present among the C-ROCM cases. High index clinical suspicion is imperative (specifically among COVID-19 patients with diabetes), and routine screening may be helpful.
Topics: Amphotericin B; Antifungal Agents; Brain Diseases; COVID-19; Humans; Mucormycosis; Nose Diseases; Orbital Diseases; Regression Analysis; Risk Factors; SARS-CoV-2
PubMed: 34975140
DOI: 10.4103/ijp.ijp_839_21