LitCovid-sentences  

PMC:7306567 / 6566-19217 JSONTXT 13 Projects

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Id Subject Object Predicate Lexical cue
T44 0-13 Sentence denotes Expert review
T45 15-56 Sentence denotes Global epidemiology of influenza and IAPA
T46 57-262 Sentence denotes Although figures vary depending on geographic region, season and vaccination rates, approximately 0.1% of influenza patients require hospital admission with 5–10% of these requiring ICU admission [13, 14].
T47 263-363 Sentence denotes The mortality in patients admitted for influenza is 4% and 20–25% for those admitted to ICU [14–16].
T48 364-497 Sentence denotes Bacterial superinfection is common, affecting 10–35% of cases, typically with Streptococcus pneumoniae or Staphylococcus aureus [16].
T49 498-740 Sentence denotes However, a recent Dutch–Belgian multicenter study over seven influenza seasons in seven institutes demonstrated influenza as an independent risk factor of IPA (adjusted odds ratio 5.19, 95% confidence interval (CI) 2.63–10.26, p < 0.001) [9].
T50 741-939 Sentence denotes Results also showed that the 90-day mortality rate for ICU patients with IAPA was almost double that of ICU influenza patients without IAPA (51% vs. 28%, adjusted odds ratio 1.87, 95% CI 1.05–3.32).
T51 940-1125 Sentence denotes IAPA was initially thought to be associated with influenza A/H1N1pdm09 only [7, 17], but it became clear that IAPA is also associated with other influenza A and influenza B viruses [9].
T52 1126-1227 Sentence denotes The median time between influenza diagnosis and IAPA was short, often in the first 5 days [7, 8, 18].
T53 1228-1469 Sentence denotes Studies have shown considerable variation in rates of IAPA in different countries, with high rates in the Netherlands, Belgium and Taiwan, but lower rates in other countries [19], and in some we do not know the incidence (e.g., USA) [20–22].
T54 1470-1790 Sentence denotes Potential reasons for these regional differences are related to the underlying conditions, concomitant exposure to corticosteroids, environmental factors, including exposure to Aspergillus, use of non-culture-based diagnostic tests for Aspergillus (e.g., galactomannan (GM)) and differences in awareness of IAPA [23–25].
T55 1791-1889 Sentence denotes Autopsy rates are very low, which results in a considerable underdiagnosis in many countries [26].
T56 1890-2144 Sentence denotes Other factors that might contribute to regional differences in IAPA rates include influenza vaccination rates, with different policies in different countries, and differences in influenza antiviral treatment strategies with oseltamivir or zanamivir [27].
T57 2145-2354 Sentence denotes Annual vaccination reduces influenza-associated complications (hospitalization, ICU admission, severity of illness, superinfection) and improves the outcome in transplant recipients and COPD patients [28, 29].
T58 2356-2376 Sentence denotes Pathogenesis of IAPA
T59 2377-2699 Sentence denotes In pending studies that explore the pathogenesis of IAPA and host immune defects, it is likely that damage to the epithelium by influenza and defective fungal host responses in the lung due to influenza and/or inflammatory conditions predispose to Aspergillus disease, similar as what is seen in bacterial superinfections.
T60 2700-2860 Sentence denotes Furthermore, autopsy studies have shown the presence of sporulating heads of Aspergillus inside the bronchi with invasive growth occurring into the lung tissue.
T61 2861-3034 Sentence denotes Sporulation could contribute to a high fungal burden and spread of the disease within the lung, thus contributing to the rapid disease progression and extensive lung damage.
T62 3035-3179 Sentence denotes Other factors that have been implicated in IAPA include the use of corticosteroids and of neuraminidase inhibitors, such as oseltamivir [7, 30].
T63 3180-3343 Sentence denotes Ultimately, these insights may aid in identifying patients at risk of IAPA and to design effective antifungal and adjunctive immunomodulatory treatment strategies.
T64 3345-3388 Sentence denotes Clinical presentation and diagnosis of IAPA
T65 3389-3539 Sentence denotes A retrospective Belgian study of influenza patients admitted to ICU between September 2009 and March 2011 showed that 9 of 40 (23%) patients had IAPA.
T66 3540-3661 Sentence denotes Four cases (44%) were proven despite not being immunocompromised according to the EORTC/MSGERC consensus definitions [7].
T67 3662-3743 Sentence denotes The median time between influenza diagnosis and IAPA was 2 days (range 0–4 days).
T68 3744-3844 Sentence denotes All IAPA patients had positive BAL GM, and 78% had positive serum GM, despite not being neutropenic.
T69 3845-4086 Sentence denotes Eighty-nine percent of patients had Aspergillus growth in BAL culture (almost exclusively Aspergillus fumigatus), and 55% of patients had endobronchial lesions observed during bronchoscopy, possibly indicating invasive tracheobronchitis [7].
T70 4087-4194 Sentence denotes Similar performance characteristics of BAL GM and culture were reported in two other cohort studies [8, 9].
T71 4195-4335 Sentence denotes BAL sampling is thus an important diagnostic procedure as serum GM can be negative and sputum/tracheal aspirate cultures can remain sterile.
T72 4336-4492 Sentence denotes Lesions that are suggestive of invasive mold disease on imaging in neutropenic patients, such as the halo sign, are often absent in critically ill patients.
T73 4493-4626 Sentence denotes However, in some IAPA patients with autopsy-confirmed Aspergillus tracheobronchitis, chest CT demonstrated peribronchial infiltrates.
T74 4627-4836 Sentence denotes The main diagnostic clue for airway-invasive Aspergillus tracheobronchitis is epithelial plaques, pseudomembranes or ulcers that can be visualized via bronchoscopy, as radiological features may be subtle [31].
T75 4837-5070 Sentence denotes Worsening of radiographic pulmonary infiltrates in patients with influenza is often attributed to progression of ARDS or bacterial infection, leading to a change of antimicrobial therapy without performing diagnostic procedures [32].
T76 5071-5345 Sentence denotes Patients who survived IAPA received antifungal therapy much earlier than those who did not (2 days after diagnosis of influenza among survivors versus 9 days among non-survivors) [8], suggesting that early diagnosis and administration of antifungal therapy may be important.
T77 5346-5554 Sentence denotes Lateral flow tests have recently become available as an alternative for diagnosing IPA (AspLFD, OLM Diagnostics and the sōna Aspergillus GM, IMMY) showing overall good performance in hematology patients [33].
T78 5555-5717 Sentence denotes The very quick assessment, with results available within 30–45 min, makes this type of test very attractive for the management of IAPA and use in clinical trials.
T79 5718-5796 Sentence denotes However, lateral flow tests have not yet been validated in the ICU population.
T80 5797-5988 Sentence denotes IAPA needs to be considered in patients admitted to the ICU with influenza and where indicated these patients should undergo early BAL for Aspergillus antigen testing, culture and microscopy.
T81 5989-6218 Sentence denotes Patients who test positive require anti-Aspergillus therapy, and the BAL fluid sample should be fast-tracked for azole resistance testing by PCR (and culture when positive) in regions with high (> 5%) azole resistance rates [34].
T82 6219-6337 Sentence denotes This would enable diagnostic assessment and initiation of adequate antifungal therapy within 24–48 h of ICU admission.
T83 6338-6517 Sentence denotes Diagnostic workup for IAPA may be repeated in patients deteriorating while on antivirals and/or appropriate antibiotics or when initiating corticosteroid treatment is unavoidable.
T84 6519-6576 Sentence denotes Discussion on clinical presentation and diagnosis of IAPA
T85 6577-6753 Sentence denotes If a patient is admitted to the ICU and has influenza with pulmonary infiltrates, the diagnosis of IAPA should be considered and further investigation performed as appropriate.
T86 6754-7006 Sentence denotes Ideally, this would include in order of invasiveness, serum GM testing, fungal cultures of sputum and/or tracheal aspirate, pulmonary CT, bronchoscopy to visualize the large airways and obtain BAL fluid for GM testing and fungal and bacterial cultures.
T87 7007-7150 Sentence denotes Testing is most appropriate in patients who are on mechanical ventilation, but the diagnostic strategy is less clear in patients not intubated.
T88 7151-7315 Sentence denotes As up to 50% of patients may present with tracheobronchitis, the presence of plaques and ulceration might be considered for inclusion in the definition of IPA [35].
T89 7316-7469 Sentence denotes Policies for taking biopsies of lesions seen on bronchoscopy may vary, mainly because of concerns about the risk of bleeding with biopsy in ICU patients.
T90 7470-7543 Sentence denotes The use of a flexible brush may also be sufficient to make the diagnosis.
T91 7544-7666 Sentence denotes Although a positive serum GM is highly indicative of IA, BAL GM can be positive in patients with Aspergillus colonization.
T92 7667-7755 Sentence denotes It therefore does not absolutely discriminate between colonization and invasive disease.
T93 7756-7838 Sentence denotes However, it clearly makes it more likely that an invasive disease is present [36].
T94 7840-7862 Sentence denotes Use of corticosteroids
T95 7863-7991 Sentence denotes Corticosteroids should not be given to influenza patients as their use may be associated with increased risk of IAPA [7, 37–39].
T96 7992-8141 Sentence denotes A recent Cochrane review on this topic concluded that the use of corticosteroids in patients with influenza was associated with a worse outcome [40].
T97 8142-8201 Sentence denotes However, the evidence was almost exclusively observational.
T98 8202-8389 Sentence denotes Furthermore, patients are often given steroids in the first few days preceding or after ICU admission for a variety of reasons including COPD exacerbation or complications such as sepsis.
T99 8390-8576 Sentence denotes With surveys suggesting that approximately half of the physicians are not aware of IAPA [24], many physicians may additionally not be aware of the potential drawbacks of corticosteroids.
T100 8577-8761 Sentence denotes Whenever the use of corticosteroids is unavoidable, more efforts (bronchoscopy with GM detection in BAL fluid or serum β-D-glucan test) should be made to exclude or diagnose IAPA [41].
T101 8763-8808 Sentence denotes Rationale for antifungal prophylaxis for IAPA
T102 8809-9005 Sentence denotes In settings with high IAPA rates in ICU patients with influenza pneumonia, an antifungal prophylaxis strategy might be appropriate, particularly as IAPA typically occurs early after ICU admission.
T103 9006-9113 Sentence denotes However, there is currently no mold-active antifungal agent licensed for prophylaxis of IA in ICU patients.
T104 9114-9268 Sentence denotes Posaconazole (POS) prophylaxis reduces the prevalence of IA in neutropenic AML patients and those with graft-versus-host disease following alloHCT [2, 3].
T105 9269-9392 Sentence denotes Based on this proof-of-principle, it has been hypothesized that POS prophylaxis can reduce IAPA prevalence in ICU patients.
T106 9393-9568 Sentence denotes Intravenous (IV) administration of POS prophylaxis in the ICU is favored in patients on mechanical ventilation or with a high likelihood of malabsorption of oral formulations.
T107 9569-9671 Sentence denotes POS IV formulation should be administered through a central catheter due to its acidity (pH 3.2) [42].
T108 9673-9725 Sentence denotes Treatment options and challenges for IAPA in the ICU
T109 9726-9811 Sentence denotes First-line treatment options for IPA include voriconazole and isavuconazole [35, 43].
T110 9812-10054 Sentence denotes Other options include echinocandins in combination with anti-mold azoles, and liposomal amphotericin B (L-AmB) in regions with high rates of azole-resistant A. fumigatus, although clinical data with L-AmB in ICU patients are limited [43, 44].
T111 10055-10185 Sentence denotes Achieving adequate drug exposure is challenging in ICU patients with multiple factors contributing to pharmacokinetic variability.
T112 10186-10372 Sentence denotes Unlike L-AmB and the echinocandins, drug interactions are clinically relevant for the azoles and pharmacogenetic factors are important in inter-individual drug exposure variability [45].
T113 10373-10509 Sentence denotes The impact of therapeutic drug monitoring (TDM) for voriconazole shows a clear relation between exposure and both efficacy and toxicity.
T114 10510-10755 Sentence denotes Target plasma trough voriconazole concentrations of ≥ 1.5–2 mg/L are associated with near-maximal clinical response in treatment of IA with a wild-type phenotype [46–51], with higher exposures (> 5.5 mg/L) increasing the risk of (neuro)toxicity.
T115 10756-10883 Sentence denotes Higher trough concentrations (> 2 mg/L) are recommended for treatment of pathogens with elevated MICs (e.g., > 0.25 mg/L) [52].
T116 10884-11075 Sentence denotes For isavuconazole, there is no robust target plasma concentration, and the population average exposure of participants that demonstrated a favorable response (2–4 mg/L) is commonly used [43].
T117 11077-11154 Sentence denotes Discussion on antifungal treatment options and challenges for IAPA in the ICU
T118 11155-11491 Sentence denotes A specific drug–drug interaction is relevant for patients with IAPA given the fact that co-infections with S. aureus are frequently observed; undetectable voriconazole levels have been observed in 11 of 20 patients, who were concomitantly treated with flucloxacillin [53], but the mechanisms of interaction are not yet fully understood.
T119 11492-11550 Sentence denotes Similar interactions have not been seen with other azoles.
T120 11551-11652 Sentence denotes Many other drug interactions with azoles and drugs commonly deployed in the ICU can be expected [45].
T121 11653-11859 Sentence denotes Aerosolized antifungal treatment may be a useful adjunctive therapy to systemic antifungal therapy for patients with confirmed Aspergillus tracheobronchitis, to achieve good endobronchial exposure [35, 54].
T122 11860-12042 Sentence denotes However, dense lipophilic plaques in the trachea may be difficult to penetrate and more research is needed into when and how to use aerosolized antifungals as well as their efficacy.
T123 12043-12276 Sentence denotes The ECCMID/ECMM/ERS Aspergillus guideline reviewed the teratogenic and mutagenic potential of antifungals in early pregnancy and recommends that azoles should be avoided, with polyenes being considered the preferred therapy [43, 55].
T124 12277-12386 Sentence denotes Thus, for pregnant patients at risk of IAPA a diagnostic approach was preferred above antifungal prophylaxis.
T125 12387-12467 Sentence denotes There is little evidence on the impact of ECMO on antifungal drug exposure [56].
T126 12468-12525 Sentence denotes For the echinocandins, an impact of ECMO is not expected.
T127 12526-12651 Sentence denotes Experts felt that, given these uncertainties, TDM of any antifungal used would be advised to ensure sufficient drug exposure.