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Infection and Drug Resistance 2024Azole resistance in poses a significant challenge in the management of invasive aspergillosis. This study aimed to investigate the antifungal susceptibility and...
PURPOSE
Azole resistance in poses a significant challenge in the management of invasive aspergillosis. This study aimed to investigate the antifungal susceptibility and mutation profiles of isolates in Malaysia.
PATIENTS AND METHODS
Sixty clinical isolates were collected and subjected to antifungal susceptibility testing (AFST) and molecular analysis. The antifungal susceptibility testing was performed according to CLSI M38 guideline. The geometric mean (GM) minimum inhibitory concentration (MIC), MIC/MIC for voriconazole, itraconazole, posaconazole, amphotericin B, and isavuconazole against in non-invasive cases and invasive cases were calculated. In addition, the presence of mutations was also identified.
RESULTS
The present study revealed an overall resistance rate of 6.7% among the isolates. In non-invasive cases, isavuconazole and posaconazole demonstrated the lowest GM MIC of 0.08 µg/mL. Following them were itraconazole, voriconazole, and amphotericin B with concentrations of 0.15µg/mL, 0.16µg/mL and 0.90µg/mL, respectively. Similarly, in invasive cases, isavuconazole and posaconazole exhibited the lowest GM MIC of 0.09µg/mL. Following them were itraconazole, voriconazole, and amphotericin B with concentrations of 0.14µg/mL, 0.17µg/mL and 0.80µg/mL, respectively. Genotypic analysis revealed various mutations, including F46Y, M172V, N248K, R34L, V244A, V244S, and E427K. However, not all mutations corresponded to antifungal resistance.
CONCLUSION
The majority of clinical isolates demonstrated susceptibility to the antifungal agents tested, with isavuconazole and posaconazole demonstrating the lowest MIC values. However, mutations were discovered without a consistent correlation to antifungal resistance, emphasising the need for additional research.
PubMed: 38828376
DOI: 10.2147/IDR.S452619 -
Journal of Family Medicine and Primary... Apr 2024To analyze the potential predisposing factors and clinical presentation of mucormycosis in patients with COVID-19.
AIM
To analyze the potential predisposing factors and clinical presentation of mucormycosis in patients with COVID-19.
MATERIAL AND METHODS
Medical records of 141 patients with COVID-19-associated mucormycosis (CAM) treated at a tertiary care center in Bihar were reviewed. The predisposing factors, clinical features, and imaging findings of mucormycosis were analyzed.
RESULTS
The median age was 48 years (IQR, 43-60). A total of 58 patients developed concurrent CAM and 83 post-CAM. The median interval between COVID-19 and onset of CAM symptoms was 15 days (IQR, 9-16). A total of 80 patients received at-home treatment for COVID-19, and 73 had mild-to-moderate disease. While 61 patients received in-hospital treatment, 57 had severe disease. At presentation, 131 patients had hyperglycemia: 64 type 2 diabetes mellitus (DM) and 67 new-onset DM. The history of glucocorticoid use for COVID-19 was present in 125 patients; 47% were administered at home without monitoring plasma glucose. The common presenting features were toothache, periocular or facial pain, and edema. Rhino-orbital mucormycosis was the most common. Imaging revealed rhinosinusitis in all patients, including pansinusitis (68%), pterygopalatine fossa involvement (21%), cavernous sinus thrombosis (38%), brain abscess (8%), and infarct (4%). All patients received intravenous liposomal amphotericin B, and surgical debridement was performed in 113.
CONCLUSION
COVID-19 patients with hyperglycemia are at risk of developing CAM, irrespective of the severity. Timely recognition of symptoms and prompt initiation of therapy by primary healthcare physicians are imperative for enhancing outcomes. Additionally, glucocorticoid overuse should be avoided, and close monitoring for hyperglycemia development is warranted.
PubMed: 38827672
DOI: 10.4103/jfmpc.jfmpc_1259_23 -
Journal of Family Medicine and Primary... Apr 2024SARS-COV virus operates as a significant risk factor for invasive fungal aspergillosis and mucormycosis. Successful management of this fulminant infection requires early...
BACKGROUND
SARS-COV virus operates as a significant risk factor for invasive fungal aspergillosis and mucormycosis. Successful management of this fulminant infection requires early recognition of the disease and aggressive medical or surgical interventions to prevent the high morbidity and mortality associated with the disease process.
AIMS AND OBJECTIVE OF THE STUDY
1. To isolate and identify different species of fungi among acute rhinosinusitis patients. 2. To assess the association of risk factors causing fungal rhinosinusitis. 3. To assess the changing trend in fungal rhinosinusitis during the COVID era.
MATERIAL AND METHODS
This is a retrospective observational study conducted from May 2020 to October 2022, attending the ENT department and relevant data were collected from the medical records department of ABVIMS and Dr RML Hospital, New Delhi, a Tertiary Care Referral Centre in India. The major risk factors studied were age, gender, COVID-19 infection and underlying diseases (such as diabetes mellitus, ischaemic heart disease, hypertension, malignancies, chronic kidney DISEASES, etc.); details of corticosteroid use of all patients were recorded in the datasheet. The pandemic data was divided into three distinct time periods/waves/eras, i.e., first, second, and third waves, each of which included ten months, to examine the changing trend in fungal rhinosinusitis in the pandemic era of COVID-19.
RESULTS
A total of 412 patients out of which 236 patients were clinically diagnosed with fungal sinusitis based on revised EORTC criteria. The most common site involved was the orbit with paranasal sinus and eye 86/236 (36.4%), followed by involvement of nasal and paranasal sinus alone 68/236 (28.8%). The most prevalent age range affected was 40 to 50 years. The most commonly associated comorbidity was diabetes mellitus (DM) in 176 (74.5%), followed by head and neck malignancies in 22 (9.32%) patients. Thirty-eight (50.6%) species and 18 (24%) were the most common isolated fungal species on culture, followed by spp. 14 (18.6%) and 5 (6.6%) in the period. In the second wave of COVID, there was a surge in cases 36 (45%) and after the second wave, the cases increased by 14 (19%) during Jan-Oct 2022.
CONCLUSION
With the continuing coronavirus pandemic, there is an unprecedented and discernible rise in the prevalence of acute invasive fungal sinusitis certainly a spike in cases of Aspergillus infection was observed, probably due to unprecedented usage of Amphotericin B for the treatment of mucormycosis during the third wave This underlines the importance of the need to tailor our treatment protocol as per the etiological agents hence the right antifungal drugs combined with urgent surgical procedures on a case-to-case basis may certainly increase the chances of survival.
PubMed: 38827671
DOI: 10.4103/jfmpc.jfmpc_871_23 -
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 -
International Journal of Infectious... May 2024The ascomycete filamentous fungus Neurospora intermedia is commonly used in the food industry and considered nonpathogenic to humans. This study characterizes four N....
The ascomycete filamentous fungus Neurospora intermedia is commonly used in the food industry and considered nonpathogenic to humans. This study characterizes four N. intermedia isolates recovered from three patients. The first patient had a mediastinal germ cell tumor with multiple metastases. N. intermedia was recovered from his endotracheal aspirate and from the endobronchial mass obtained by bronchoscopic forceps biopsy. Histopathology of the biopsy tissue revealed necrotic tissue mixed with septate fungal hyphae with right-angle branching. An endobronchial mass caused by N. intermedia was thus diagnosed. Another two N. intermedia isolates were recovered from the endotracheal aspirates of two critically ill patients. In vitro, N. intermedia grows rapidly and forms orange, conidiating colonies composed of septate hyphae. Two isolates from the first patient belong to mating type a; the other two isolates belong to mating type A. Coculture of isolates of opposite mating types yielded dark ascomata containing ascospores, supporting that N. intermedia is a heterothallic fungus. N. intermedia isolates cross-reacted with the Aspergillus galactomannan antigen assay and were susceptible to amphotericin B and voriconazole. In conclusion, this report describes the first human infection (endobronchial mass) caused by N. intermedia, highlighting its potential to invade the human respiratory tract.
PubMed: 38821185
DOI: 10.1016/j.ijid.2024.107119 -
Transplantation Direct Jun 2024
PubMed: 38817629
DOI: 10.1097/TXD.0000000000001648 -
International Journal of Pharmaceutics May 2024Until relatively recently, the pediatric population has largely been ignored during the development of new drug products, which has led to a high level of "off-label"...
Development and in vitro evaluation of an infant friendly self-nanoemulsifying drug delivery system (SNEDDS) loaded with an amphotericin B-monoacyl phosphatidylcholine complex for oral delivery.
Until relatively recently, the pediatric population has largely been ignored during the development of new drug products, which has led to a high level of "off-label" use of drugs in this particular population. In this study, an infant friendly self-nanoemulsifying drug delivery system (SNEDDS) was developed for oral delivery of a commonly used "off-label" drug - amphotericin B (AmB). AmB was complexed with monoacyl-phosphatidylcholine (MAPC) by lyophilization, transforming crystalline AmB into its amorphous state in the AmB-MAPC complex (APC). The APC-loaded SNEDDS (APC-SNEDDS) showed excellent self-emulsifying properties; after dispersion of the APC-SNEDDS in purified water, nanoscale emulsion droplets were formed within 1 min with a z-average size of 179 ± 1 nm. In vitro pediatric gastrointestinal (GI) digestion and dissolution results showed that the APC-SNEDDS significantly increased the amount of AmB solubilized in aqueous phase and that the precipitated AmB from the APC-SNEDDS re-dissolved faster, compared with crystalline AmB in SNEDDS (AmB-SNEDDS), the complex without the SNEDDS (APC), the physical mixture of AmB and MAPC (AmB/MAPC PM), and crystalline AmB alone (AmB). Overall, the present in vitro results suggest that integrating the APC into an infant friendly SNEDDS is a promising approach for oral delivery of AmB to young pediatric patients.
PubMed: 38815640
DOI: 10.1016/j.ijpharm.2024.124286 -
Journal of Investigative Medicine High... 2024Hemophagocytic lymphohistiocytosis (HLH) secondary to is rare, impacting <1% globally, with a mortality rate of up to 31%. Herein, we present a rare case of HLH... (Review)
Review
Hemophagocytic lymphohistiocytosis (HLH) secondary to is rare, impacting <1% globally, with a mortality rate of up to 31%. Herein, we present a rare case of HLH secondary to , affecting a 57-year-old female with rheumatoid arthritis. Extensive investigations were unrevealing and despite broad-spectrum antibiotics, her condition worsened, leading to respiratory failure requiring extracorporeal membrane oxygenation (ECMO) support, shock requiring multiple vasopressors, and acute kidney injury (AKI) requiring hemodialysis. Diagnosis confirmed disseminated histoplasmosis (DHP), prompting Amphotericin B and methylprednisolone treatment, resulting in significant improvement and discharge with posaconazole therapy. Secondary HLH, primarily arising from severe infections like DHP, is discussed. Limited research exists on this condition in human immunodeficiency virus (HIV)-seronegative individuals. Diagnosis involves HLH-2004 and HScore criteria. Managing histoplasmosis-associated HLH remains challenging due to multiorgan failure risks and treatment complexities and needs further research.
Topics: Humans; Lymphohistiocytosis, Hemophagocytic; Histoplasmosis; Female; Middle Aged; Antifungal Agents; Histoplasma; Amphotericin B
PubMed: 38813977
DOI: 10.1177/23247096241258074 -
JAC-antimicrobial Resistance Jun 2024In Germany, the growing incidence of invasive fungal infections (IFIs) is a significant health concern, particularly impacting individuals with compromised immune...
INTRODUCTION
In Germany, the growing incidence of invasive fungal infections (IFIs) is a significant health concern, particularly impacting individuals with compromised immune systems due to factors like increasing transplant recipients, an ageing population, and heightened use of immunosuppressive medications. Diagnosing IFI remains challenging, and the integration of biomarker assays into clinical practice is difficult. Antifungal resistance, exemplified by pan-antifungal-resistant cases, adds complexity to treatment. This study aims to provide a concise overview of the diagnostic and treatment landscape for IFI in Germany, identifying areas for improvement and paving the way for targeted interventions.
METHODS
Data were collected using an online electronic case report form from October 2021 to February 2023. The survey included questions about institutional practices related to fungal infection diagnosis and treatment, with invitations extended to researchers nationwide.
RESULTS
The study surveyed 58 hospitals across Germany. Notably, 77.6% managed high-risk patients for IFI. While 86% had onsite microbiology labs, a significant difference was noted for high-risk patients (93% in specialized hospitals versus 62% in others). Microscopy services had 96% coverage, while overall access to culture was 96%. Antigen tests had 96% coverage, and antibody access was reported at 98%. PCR testing was available at 98%. Imaging access showed no significant access differences. Variability existed in amphotericin B formulations based on patient profiles. Therapeutic drug monitoring was more common in high-risk patient institutions (89.5% versus 50.0%). All analysed institutions reported access to surgery (100%).
CONCLUSIONS
Addressing identified disparities in diagnostic and therapeutic resources for IFI is crucial to improving patient outcomes. The study calls for ongoing research and collaboration to optimize strategies for the prevention and treatment of IFI, emphasizing the importance of equitable access to resources, especially in high-risk patient populations.
PubMed: 38812581
DOI: 10.1093/jacamr/dlae083 -
Heliyon May 2024is a recently discovered and not widely documented ascomycetous yeast phylogenetically related to the outbreak-causing and multidrug-resistant . A middle-aged Japanese...
is a recently discovered and not widely documented ascomycetous yeast phylogenetically related to the outbreak-causing and multidrug-resistant . A middle-aged Japanese man with no discernible immunodeficiency was admitted to hospital with ileal diverticulitis. Following laparoscopic right hemicolectomy against abscess formation on postoperative day (POD) 7, continuous fungemia occurred due to identified using a conventional method by confirming the biochemical phenotype. Micafungin was initiated; however, the fungus was persistently isolated from blood cultures. Eventually, the antifungal agent was changed to a combination of liposomal amphotericin B (L-AMB) and caspofungin (CPFG), which cleared the infection, and no pathogens were detected in the blood cultures on POD 31. Contrast-enhanced computed tomography showed septic emboli in the lungs and spleen; however, no evidence of vasculitis was observed. Moreover, sequential echocardiography did not reveal any signs of infectious endocarditis. Finally, CPFG and L-AMB were administered to the patient for 7 and 9 weeks, respectively, during which the patient's symptoms did not relapse. The strain was later genetically identified as . This case report illustrates a clinical presentation of and provides the diagnostic approach and treatment methods for this pathogen.
PubMed: 38803887
DOI: 10.1016/j.heliyon.2024.e31464