查看更多>>摘要：Abstract Cryptococcosis is a common opportunistic infection associated with HIV/AIDS. The present review systematically describes the clinical and biological aspects of cryptococcosis in the Democratic Republic of Congo (DRC) and estimates its 2020 burden in people living with HIV (PLHIV). Following PRISMA guidelines, we searched online databases for records of cryptococcosis/Cryptococcus spp. in the DRC. Meta‐analysis was then performed to estimate summary statistics and the corresponding 95% confidence intervals (CI). A total of 30 studies were included. These included 1,018 cryptococcosis patients, including 80.8% with neuromeningeal cryptococcosis (NMC) and predominantly immunocompromised due to HIV/AIDS (97.6%). The NMC mean prevalence was estimated at 9.63% (95% CI: 5.99–14.07). More than one in two patients (52.7%) under treatment died. Monotherapy with fluconazole was the main treatment administered (80.6%). Furthermore, we estimate that about 9,265 (95% CI: 5,763–13,537) PLHIV had cryptococcosis in 2020, in DRC; of which about 4,883 (95% CI: 3,037–7,134) would have died in the same year. Among isolates in all included studies, 74 strains have been characterised. Of these, 82.4% concerned Cryptococcus neoformans sensu lato (s.l) (exclusively of serotype A and mostly of molecular types VNI and VNII) and 17.6% concerned Cryptotoccus gattii s.l (belonging to serotype B/molecular type VGI). Cryptococcosis remains common with an unacceptably high mortality rate. A large number of PLHIV affected by and dying from cryptococcosis in 2020 demonstrates its heavy burden among the Congolese PLHIV. To mitigate this burden, it is important to improve the quality and accessibility of care for all PLHIV.
Alexander Maximilian AldejohannMiriam Wiese‐PosseltPetra GastmeierOliver Kurzai...
9页
查看更多>>摘要：Abstract Candida auris was first described as a yeast pathogen in 2009. Since then, the species has emerged worldwide. In contrast to most other Candida spp., C.?auris frequently exhibits multi‐drug resistance and is readily transmitted in hospital settings. While most detections so far are from colonised patients, C.?auris does cause superficial and life‐threatening invasive infections. During management of the first documented C.?auris transmission in a German hospital, experts from the National Reference Centers for Invasive Fungal Infections (NRZMyk) and the National Reference Center for Surveillance of Nosocomial Infections screened available literature and integrated available knowledge on infection prevention and C.?auris epidemiology and biology to enable optimal containment. Relevant recommendations developed during this process are summarised in this guidance document, intended to assist in management of C.?auris transmission and potential outbreak situations. Rapid and effective measures to contain C.?auris spread require a multi‐disciplinary approach that includes clinical specialists of the affected unit, nursing staff, hospital hygiene, diagnostic microbiology, cleaning staff, hospital management and experts in diagnostic mycology / fungal infections. Action should be initiated in a step‐wise process and relevant interventions differ between management of singular C.?auris colonised / infected patients and detection of potential C.?auris transmission or nosocomial outbreaks.
Matthias EggerMartin HoeniglGeorge R. ThompsonAgostinho Carvalho...
14页
查看更多>>摘要：Abstract Biological sex, which comprises differences in host sex hormone homeostasis and immune responses, can have a substantial impact on the epidemiology of infectious diseases. Comprehensive data on sex distributions in invasive fungal diseases (IFDs) are lacking. In this review, we performed a literature search of in vitro/animal studies, clinical studies, systematic reviews and meta‐analyses of invasive fungal infections. Females represented 51.2% of invasive candidiasis cases, mostly matching the proportions of females among the general population in the United States and Europe (>51%). In contrast, other IFDs were overrepresented in males, including invasive aspergillosis (51% males), mucormycosis (60%), cryptococcosis (74%), coccidioidomycosis (70%), histoplasmosis (61%) and blastomycosis (66%). Behavioural variations, as well as differences related to biological sex, may only in part explain these findings. Further investigations concerning the association between biological sex/gender and the pathogenesis of IFDs are warranted.
查看更多>>摘要：Abstract Background Candida auris is an emerging multidrug‐resistant pathogen in intensive care settings (ICU). During the coronavirus disease 19 (COVID‐19) pandemic, ICU admissions were overwhelmed, possibly contributing to the C.?auris outbreak in COVID‐19 patients. Objectives The present systematic review addresses the prevalence, underlying diseases, iatrogenic risk factors, treatment and outcome of C.?auris infections in COVID‐19 patients. Methods MEDLINE, Scopus, Embase, Web of Science and LitCovid databases were systematically searched with appropriate keywords from 1 January 2020 to 31 December 2021. Results A total of 97 cases of C.?auris were identified in COVID‐19 patients. The pooled prevalence of C.?auris infections (encompassing candidemia and non‐candidemia cases)?in COVID‐19 patients was 14%. The major underlying diseases were diabetes mellitus (42.7%), hypertension (32.9%) and obesity (14.6%), followed by the iatrogenic risk factors such as a central venous catheter (76.8%%), intensive care unit (ICU) stay (75.6%) and broad‐spectrum antibiotic usage (74.3%). There were no significant differences in underlying disease and iatrogenic risk factors among C.?auris non‐candidemia/colonisation and C.?auris candidemia cases. The mortality rate of the total cohort is 44.4%, whereas, in C.?auris candidemia patients, the mortality was 64.7%. Conclusion This study shows that the prevalence of C.?auris infections remains unchanged in the COVID‐19 pandemic. Hospital‐acquired risk factors may contribute to the clinical illness. Proper infection control practices and hospital surveillance may stop future hospital outbreaks during the pandemic.
William Kane OlwitCharles BatteClaudine MukashyakaEmmanuel Mande...
10页
查看更多>>摘要：Abstract Background The occurrence of chronic pulmonary aspergillosis (CPA) among drug sensitive pulmonary tuberculosis (PTB) patients on optimal therapy with persistent symptoms was investigated. Methods We consecutively enrolled participants with PTB with persistent pulmonary symptoms after 2?months of anti‐TB treatment at Mulago Hospital, Kampala, Uganda, between July 2020 and June 2021. CPA was defined as a positive Aspergillus‐specific IgG/IgM immunochromatographic test (ICT), a cavity with or without a fungal ball on chest X‐ray (CXR), and compatible symptoms >3?months. Results We enrolled 162 participants (median age 30?years; IQR: 25–40), 97 (59.9%) were male, 48 (29.6%) were HIV‐infected and 15 (9.3%) had prior PTB. Thirty‐eight (23.4%) sputum samples grew A.?niger and 13 (8.0%) A.?fumigatus species complexes. Six (3.7%) participants had intracavitary fungal balls and 52 (32.1%) had cavities. Overall, 32 (19.8%) participants had CPA. CPA was associated with prior PTB (adjusted odds ratio [aOR]: 6.61, 95% CI: 1.85–23.9, p?=?.004), and far advanced CXR changes (aOR: 4.26, 95% CI: 1.72–10.52, p?=?.002). The Aspergillus IgG/IgM ICT was positive in 10 (31.3%) participants with CPA. Conclusions Chronic pulmonary aspergillosis may cause persistent respiratory symptoms in up to one‐fifth of patients after intensive treatment for PTB. The Aspergillus IgG/IgM ICT positivity rate was very low and may not be used alone for the diagnosis of CPA in Uganda.
查看更多>>摘要：Abstract Background and Objective The diagnosis of pulmonary cryptococcosis depends on serum testing, histopathology and mycological culture; there are few studies on touch imprints of lung tissue biopsies for the diagnosis of pulmonary cryptococcosis in patients without HIV infection. The purpose of the current study was to investigate the accuracy and timeliness of on‐site touch imprint cytology in the diagnosis of pulmonary cryptococcosis during CT‐guided percutaneous lung biopsy. Methods We retrospectively analysed the diagnosis and treatment of 56 patients with final proof of pulmonary cryptococcosis through histopathology and culture or surgical resection from September 2015 to February 2021. Diagnostic methods and treatment and the turnaround time for diagnosis were analysed. Results The sensitivity of rapid on‐site evaluation was 89.3%, and the sensitivity of serology, histopathology and mycological culture was 53.6%, 91.1% and 61.5%, respectively, compared with the final diagnosis. The average turnaround time to diagnose pulmonary cryptococcosis by on‐site touch imprint cytology was 8.3?±?0.9?min, which was significantly faster than serum testing, histopathology and mycological culture. Conclusion On‐site touch imprint cytology showed good sensitivity and timeliness in the diagnosis of pulmonary cryptococcosis. In addition, it contributed to the triage of biopsies based on the preliminary diagnosis. On‐site touch imprint cytology should be applied and promoted in the diagnosis of pulmonary cryptococcosis during biopsy.
Carl HinrichsMiriam Wiese‐PosseltBarbara GrafChristine Geffers...
7页
查看更多>>摘要：Abstract Background Candida auris a frequently multidrug‐resistant yeast species that poses a global health threat due to its high potential for hospital outbreaks. While C.?auris has become endemic in parts of Asia and Africa, transmissions have so far rarely been reported in Western Europe except for Great Britain and Spain. We describe the first documented patient‐to‐patient transmission of C.?auris in Germany in a COVID‐19 intensive care unit (ICU) and infection control measures implemented to prevent further spread of the pathogen. Methods Identification of C.?auris was performed by MALDI‐TOF and confirmed by internal transcribed spacer (ITS) sequencing. Antifungal susceptibility testing was carried out. We conducted repeated cross‐sectional examinations for the presence of C.?auris in the patients of the affected ICU and investigated possible routes of transmission. Results The index patient had been transferred to Germany from a hospital in Northern Africa and was found to be colonised with C.?auris. The contact patient developed C.?auris sepsis. Infection prevention and control (IPC) measures included strict isolation of the two C.?auris patients and regular screening of non‐affected patients. No further case occurred during the subsequent weeks. Reusable blades used in video laryngoscope‐guided intubation were considered as the most likely vehicle of transmission. Conclusions In view of its high risk of transmission, vigilance regarding C.?auris colonisation in patients referred from endemic countries is crucial. Strict and immediate IPC measures may have the potential to prevent C.?auris outbreaks.
Bertrand NyuykongeWilson LimLukas van AmelsvoortAlexandro Bonifaz...
6页
查看更多>>摘要：Abstract Introduction Eumycetoma is a subcutaneous mutilating disease that can be caused by many different fungi. Current treatment consists of prolonged itraconazole administration in combination with surgery. In many centres, due to their slow growth rate, the treatment for eumycetoma is often started before the causative agent is identified. This harbours the risk that the causative fungus is not susceptible to the given empirical therapy. In the open‐source drug program MycetOS, ravuconazole and luliconazole were promising antifungal agents that were able to inhibit the growth of Madurella mycetomatis, the most common causative agent of mycetoma. However, it is currently not known whether these drugs inhibit the growth of other eumycetoma causative agents. Materials and methods Here, we determined the in vitro activity of luliconazole, lanoconazole and ravuconazole against commonly encountered eumycetoma causative agents. MICs were determined for lanoconazole, luliconazole and ravuconazole against 37 fungal isolates which included Madurella species, Falciformispora senegalensis, Medicopsis romeroi and Trematosphaeria grisea and compared to those of itraconazole. Results Ravuconazole, luliconazole and lanoconazole showed high activity against all eumycetoma causative agents tested with median minimal inhibitory concentrations (MICs) ranging from 0.008–2?μg/ml, 0.001–0.064?μg/ml and 0.001–0.064?μg/ml, respectively. Even Ma.?fahalii and Me.?romeroi, which are not inhibited in growth by itraconazole at a concentration of 4?μg/ml, were inhibited by these azoles. Conclusion The commonly encountered eumycetoma causative agents are inhibited by lanoconazole, luliconazole and ravuconazole. These drugs are promising candidates for further evaluation as potential treatment for eumycetoma.
Ruth Van DaeleJoost WautersErwin DreesenJerina Boelens...
5页
查看更多>>摘要：Abstract Background Data on posaconazole in the critically ill are scarce. In the POSA‐FLU study, we examined the prevention of influenza‐associated pulmonary aspergillosis with posaconazole in this population. Methods In this observational sub‐study, we performed a pharmacokinetic analysis, including protein binding and target attainment (TA). Blood samples were collected over a 24?h‐dosing interval on both an early (Day 2 or 3) and a later (≥Day 4) treatment day. Results Target attainment was shown for AUC0‐24 and Cmin prophylaxis but not for Cmin treatment. Moreover, a saturable protein binding with a significant, positive relationship between albumin concentrations and the maximum binding capacity was observed. Conclusions Our analysis indicates that posaconazole may be a suitable drug to further investigate for prophylaxis, as TA for prophylaxis was reached. Exposure targets for treatment were insufficiently attained in this population.
NSTL
Wiley