Galactomannan detection in bronchoalveolar lavage (BAL) fluid samples (GM test) is currently considered the gold standard test for diagnosing invasive pulmonary aspergillosis (IPA). The limitations, ...however, are the various turnaround times and availability of testing. We compared the performance of GM testing with that of conventional culture, an Aspergillus lateral-flow-device (LFD) test, a beta-d-glucan (BDG) test, and an Aspergillus PCR assay by using BAL fluid samples from immunocompromised patients. A total of 78 BAL fluid samples from 78 patients at risk for IPA (74 samples from Graz and 4 from Mannheim) collected between December 2012 and May 2013 at two university hospitals in Austria and Germany were included. Three patients had proven IPA, 14 probable IPA, and 17 possible IPA, and 44 patients had no IPA. The diagnostic accuracies of the different methods for probable/proven IPA were evaluated. The diagnostic odds ratios were the highest for the GM, PCR, and LFD tests. The sensitivities for the four methods (except culture) were between 70 and 88%. The combination of the GM (cutoff optical density index ODI, >1.0) and LFD tests increased the sensitivity to 94%, while the combination of the GM test (>1.0) and PCR resulted in 100% sensitivity (specificity for probable/proven IPA, 95 to 98%). The performance of conventional culture was limited by low sensitivity, while that of the BDG test was limited by low specificity. We evaluated established and novel diagnostic methods for IPA and found that the Aspergillus PCR, LFD, and GM tests were the most useful methods for diagnosing the disease by using BAL fluid samples. In particular, the combination of the GM test and PCR or, if PCR is not available, the LFD test, allows for sensitive and specific diagnosis of IPA.
The airborne fungus Aspergillus fumigatus poses a serious health threat to humans by causing numerous invasive infections and a notable mortality in humans, especially in immunocompromised patients. ...Mould-active azoles are the frontline therapeutics employed to treat aspergillosis. The global emergence of azole-resistant A. fumigatus isolates in clinic and environment, however, notoriously limits the therapeutic options of mould-active antifungals and potentially can be attributed to a mortality rate reaching up to 100 %. Although specific mutations in CYP51A are the main cause of azole resistance, there is a new wave of azole-resistant isolates with wild-type CYP51A genotype challenging the efficacy of the current diagnostic tools. Therefore, applications of whole-genome sequencing are increasingly gaining popularity to overcome such challenges. Prominent echinocandin tolerance, as well as liver and kidney toxicity posed by amphotericin B, necessitate a continuous quest for novel antifungal drugs to combat emerging azole-resistant A. fumigatus isolates. Animal models and the tools used for genetic engineering require further refinement to facilitate a better understanding about the resistance mechanisms, virulence, and immune reactions orchestrated against A. fumigatus. This review paper comprehensively discusses the current clinical challenges caused by A. fumigatus and provides insights on how to address them.
Liposomal amphotericin B—the future Hoenigl, M; Lewis, R; van de Veerdonk, F L ...
Journal of antimicrobial chemotherapy,
11/2022, Letnik:
77, Številka:
Supplement_2
Journal Article
Recenzirano
Odprti dostop
Abstract
Advances in medicine have led to a growing number of people with compromised or suppressed immune systems who are susceptible to invasive fungal infections. In particular, severe fungal ...infections are becoming increasingly common in ICUs, affecting people within and outside of traditional risk groups alike. This is exemplified by the emergence of severe viral pneumonia as a significant risk factor for invasive pulmonary aspergillosis, and the recognition of influenza-associated pulmonary aspergillosis and, more recently, COVID-19-associated pulmonary aspergillosis.
The treatment landscape for haematological malignancies has changed considerably in recent years, and some recently introduced targeted agents, such as ibrutinib, are increasing the risk of invasive fungal infections. Consideration must also be given to the risk of drug–drug interactions between mould-active azoles and small-molecule kinase inhibitors.
At the same time, infections caused by rare moulds and yeasts are increasing, and diagnosis continues to be challenging. There is growing concern about azole resistance among both moulds and yeasts, mandating continuous surveillance and personalized treatment strategies.
It is anticipated that the epidemiology of fungal infections will continue to change and that new populations will be at risk. Early diagnosis and appropriate treatment remain the most important predictors of survival, and broad-spectrum antifungal agents will become increasingly important. Liposomal amphotericin B will remain an essential therapeutic agent in the armamentarium needed to manage future challenges, given its broad antifungal spectrum, low level of acquired resistance and limited potential for drug–drug interactions.
Lomentospora prolificans is an emerging cause of serious invasive fungal infections. Optimal treatment of these infections is unknown, although voriconazole-containing treatment regimens are ...considered the treatment of choice. The objective of this study was to evaluate the role of combination antifungal therapy for L. prolificans infections.
We performed a retrospective review of medical records of patients with invasive L. prolificans infection diagnosed between 1 January 2008 and 9 September 2019 that were documented in the FungiScope® registry of rare invasive fungal infections. We compared clinical outcomes between antifungal treatment strategies.
Over the study period, 41 individuals with invasive L. prolificans infection from eight different countries were documented in the FungiScope® registry. Overall, 17/40 (43%) had treatment response/stable disease and 21/40 (53%) had a fatal outcome attributed to invasive fungal infection. Combination antifungal therapy was associated with increased 28-day survival (15/24 survived versus 4/16 receiving monotherapy; p 0.027) and the combination voriconazole plus terbinafine trended to be associated with higher rates of treatment success (10/16, 63%, 95% CI 35%–85%) compared with other antifungal treatment regimens (7/24, 29%, 95% CI 13%–51%, p 0.053). In Kaplan–Meier survival analysis there was a higher survival probability in individuals receiving the voriconazole/terbinafine combination compared with other antifungal regimens (median survival 150 days versus 17 days).
While overall mortality was high, combination antifungal treatment, and in particular combination therapy with voriconazole plus terbinafine may be associated with improved treatment outcomes compared with other antifungal regimens for the treatment of invasive L. prolificans infections.
A multiplexed biomarker bundle consisting of nine different inflammation markers was evaluated regarding their diagnostic and prognostic performances in 159 adult systemic inflammatory response ...syndrome (SIRS) patients enrolled at the emergency department. Fibronectin, interleukin-8 (IL-8), biotin, and neutrophil gelatinase-associated lipocalin (NGAL) were the most robust markers but were not superior to the already established markers IL-6, C-reactive protein (CRP), procalcitonin (PCT), and soluble urokinase plasminogen activator receptor (suPAR).
In Germany, previous reports have demonstrated transmitted human immunodeficiency virus type 1 (HIV-1) drug-resistance mutations (DRM) in 11% of newly diagnosed individuals, highlighting the ...importance of drug-resistance screening before the initiation of antiretroviral therapy (ART). Here, we sought to understand the molecular epidemiology of HIV DRM transmission in the Cologne-Bonn region of Germany, given one of the highest rates of new HIV diagnoses in western Europe (13.7 per 100 000 habitants).
We analysed 714 HIV-1 ART-naive infected individuals diagnosed at the University Hospitals Cologne and Bonn between 2001 and 2016. Screening for DRM was performed according to the Stanford University Genotypic Resistance Interpretation. Shared DRM were defined as any DRM present in genetically linked individuals (<1.5% genetic distance). Phylogenetic and network analyses were performed to infer putative relationships and shared DRM.
The prevalence of any DRM at time of diagnosis was 17.2% (123/714 participants). Genetic transmission network analyses showed comparable frequencies of DRM in clustering versus non-clustering individuals (17.1% (85/497) versus 17.5% (38/217)). The observed rate of DRM in the region was higher than previous reports 10.8% (87/809) (p < 0.001), revealing the need to reduce onward transmission in this area. Genetically linked individuals harbouring shared DRM were more likely to live in suburban areas (24/38) than in central Cologne (1/38) (p < 0.001).
The rate of DRM was exceptionally high. Network analysis elucidated frequent cases of shared DRM among genetically linked individuals, revealing the potential spread of DRM and the need to prevent onward transmission of DRM in the Cologne-Bonn area.
Summary
Background
Procalcitonin (PCT) has previously been proposed as useful marker to rule out bloodstream‐infection (BSI). The objective of this study was to evaluate the sensitivity of different ...PCT cut‐offs for prediction of BSI in patients with community (CA)‐ and hospital‐acquired (HA)‐BSI.
Methods
A total of 898 patients fulfilling systemic‐inflammatory‐response‐syndrome (SIRS) criteria were enrolled in this prospective cohort study at the Medical University of Graz, Austria. Of those 666 patients had positive blood cultures (282 CA‐BSI, 384 HA‐BSI, enrolled between January 2011 and December 2012) and 232 negative blood cultures (enrolled between January 2011 and July 2011 at the emergency department). Blood samples for determination of laboratory infection markers (e.g. PCT) were collected simultaneously with blood cultures.
Results
Procalcitonin was significantly (p < 0.001) higher in SIRS patients with bacteremia/fungemia than in those without. Receiver operating characteristic curve analysis revealed an area under the curve (AUC) value of 0.675 for PCT (95% CI 0.636–0.714) for differentiating patients with BSI from those without. AUC for IL‐6 was 0.558 (95% CI 0.515–0.600). However, even at the lowest cut‐off evaluated (i.e. 0.1 ng/ml) PCT failed to predict BSI in 7% (n = 46) of patients. In the group of patients with SIRS and negative blood culture 79% (n = 185) had PCT levels > 0.1.
Conclusion
Procalcitonin was significantly higher in patients with BSI than in those without and superior to IL‐6 and CRP. The clinical importance of this is questionable, because a suitable PCT threshold for excluding BSI was not established. An approach where blood cultures are guided by PCT only can therefore not be recommended.
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Abstract A prospective, observational, multicentre study was performed to assess the incidence, diagnosis, epidemiology and outcome of invasive mould infections (IMIs) reported to the Nationwide ...Austrian Aspergillus Registry. In total, 186 cases were recorded, corresponding to an annual incidence of 42 cases/1000 patients at risk or 2.36 cases/100 000 inhabitants. Patients with acute myelogenous leukaemia (34%) and lung transplant recipients (17%) are currently at highest risk for IMI, followed by a mixed population with impaired immunity (14%). In total, 34%, 30% and 36% were proven, probable and possible cases of IMI. Predominant pathogens were Aspergillus spp. (67%), followed by the zygomycetes (28%). Voriconazole was the most frequently administered agent (38%), followed by caspofungin (20%) and posaconazole (19%). Eighty patients (43%) received antifungal prophylaxis for ≥7 days, 30% of whom (24 patients) suffered from a breakthrough infection. The overall crude 12-week mortality was 34%. Multivariate analysis showed that outcome and survival did not correlate with the status of fungal disease, breakthrough infection, fungal species or age ( P > 0.05). Aspergillosis remains the most commonly identified IMI amongst immunocompromised and/or immunosuppressed patients, but other moulds constitute a significant problem. Survival from IMIs appears to have improved and the main challenge is to overcome breakthrough fungal infections.
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