Aspergillus spp. is the fungus most frequently producing ventilator-associated pneumonia (VAP), constituting 8% of them. This risk is significantly increased in onco-hematological patients: solid ...organ transplant recipients, chronic obstructive pulmonary disease (COPD), corticotherapy, cirrhosis, solid cancer, or viral pneumonias. The European Organization for Research and Treatment of Cancer Mycoses (EORT/MSG criteria) developed for onco-hematological patients with angioinvasive forms of aspergillosis have important limitations for broncho-pulmonary forms, such as aspergillosis cases in the ICU. In recent years, new diagnostic criteria were developed to have a greater role in broncho-alveolar lavage, especially GM and lateral flow assay (LFA). Voriconazole and isavuconazole are the first treatment option. However, drug-drug interaction, level requirements, toxicity, and QT-interval modification are limitations that may favor isavuconazole or liposomal amphotercin B in the ICU.
Tuberculosis continues to be a major public health problem. A priority objective is the implementation of early diagnosis, contact investigation and latent tuberculosis infection (LTBI) testing. ...World Health Organization (WHO) concludes that there is no gold standard for the diagnosis of LTBI; both the tuberculin test and IGRA (interferon gamma release assays) indirectly identify tuberculosis infection; both tests are considered acceptable but imperfect. WHO recommends that regimens that include rifamycins are equally effective but less toxic and more adherent than long regimens with isoniazid.
Objectives: In vitro studies have shown good activity of linezolid against Mycobacterium tuberculosis, including multidrug-resistant strains. However, clinical experience with linezolid in ...tuberculosis is scarce. Methods: We report our clinical experience with five consecutive patients with multidrug-resistant tuberculosis infection treated with combination regimens that included linezolid. Results: Two patients had multidrug-resistant Mycobacterium bovis infection, with resistance to 12 antituberculous agents (one of them with HIV co-infection and <50 CD4 cells/mm3). The other three patients were infected by multidrug-resistant M. tuberculosis strains, with resistance to all first-line drugs and other second-line drugs. All patients received linezolid in combination with thiacetazone, clofazimine or amoxicillin/clavulanate. Susceptibility tests showed linezolid MIC values ≤0.5 mg/L against all tuberculosis strains tested (standard proportion method, Middlebrook agar 7H10). In all cases, tuberculosis cultures from respiratory samples were sterile after 6 weeks of therapy. Three patients have clinical and microbiological cure of tuberculosis with a combination regimen with linezolid (range: 5–24 months). One patient was lost to follow-up at month 5. The remaining patient has completed 11 months of therapy and is still on treatment. Four patients developed anaemia and needed blood transfusions. In two of these patients, the linezolid daily-dose (600 mg twice a day) was successfully reduced to 50% (300 mg twice a day) to decrease toxicity while maintaining efficacy. Peripheral neuropathy (two patients) and pancreatitis (one patient) were other adverse events observed during linezolid treatment. Conclusions: In our experience, linezolid has been a valid alternative drug in the management of multidrug-resistant tuberculosis. The prolonged use of linezolid is frequently associated with toxicity, mainly anaemia and peripheral neuropathy, that requires special management.
Invasive fusariosis (IF) is associated with severe neutropenia in patients with concurrent hematologic conditions. We conducted a retrospective observational study to characterize the epidemiology of ...IF in 18 Spanish hospitals during 2000-2015. In that time, the frequency of IF in nonneutropenic patients increased from 0.08 cases per 100,000 admissions in 2000-2009 to 0.22 cases per 100,000 admissions in 2010-2015. Nonneutropenic IF patients often had nonhematologic conditions, such as chronic cardiac or lung disease, rheumatoid arthritis, history of solid organ transplantation, or localized fusariosis. The 90-day death rate among nonneutropenic patients (28.6%) and patients with resolved neutropenia (38.1%) was similar. However, the death rate among patients with persistent neutropenia (91.3%) was significantly higher. We used a multivariate Cox regression analysis to characterize risk factors for death: persistent neutropenia was the only risk factor for death, regardless of antifungal therapy.
The aim was to analyze the characteristics and predictors of unfavorable outcomes in solid organ transplant recipients (SOTRs) with COVID-19. We conducted a prospective observational cohort study of ...210 consecutive SOTRs hospitalized with COVID-19 in 12 Spanish centers from 21 February to 6 May 2020. Data pertaining to demographics, chronic underlying diseases, transplantation features, clinical, therapeutics, and complications were collected. The primary endpoint was a composite of intensive care unit (ICU) admission and/or death. Logistic regression analyses were performed to identify the factors associated with these unfavorable outcomes. Males accounted for 148 (70.5%) patients, the median age was 63 years, and 189 (90.0%) patients had pneumonia. Common symptoms were fever, cough, gastrointestinal disturbances, and dyspnea. The most used antiviral or host-targeted therapies included hydroxychloroquine 193/200 (96.5%), lopinavir/ritonavir 91/200 (45.5%), and tocilizumab 49/200 (24.5%). Thirty-seven (17.6%) patients required ICU admission, 12 (5.7%) suffered graft dysfunction, and 45 (21.4%) died. A shorter interval between transplantation and COVID-19 diagnosis had a negative impact on clinical prognosis. Four baseline features were identified as independent predictors of intensive care need or death: advanced age, high respiratory rate, lymphopenia, and elevated level of lactate dehydrogenase. In summary, this study presents comprehensive information on characteristics and complications of COVID-19 in hospitalized SOTRs and provides indicators available upon hospital admission for the identification of SOTRs at risk of critical disease or death, underlining the need for stringent preventative measures in the early post-transplant period.
Abstract
Background
Regardless of the available antifungals, intraabdominal candidiasis (IAC) mortality continues to be high and represents a challenge for clinicians.
Main body
This opinion paper ...discusses alternative antifungal options for treating IAC. This clinical entity should be addressed separately from candidemia due to the peculiarity of the required penetration of antifungals into the peritoneal cavity. Intraabdominal concentrations may be further restricted in critically ill patients where pathophysiological facts alter normal drug distribution. Echinocandins are recommended as first-line treatment in guidelines for invasive candidiasis. However, considering published data, our pharmacodynamic analysis suggests the required increase of doses, postulated by some authors, to attain adequate pharmacokinetic (PK) levels in peritoneal fluid. Given the limited evidence in the literature on PK/PD-based treatments of IAC, an algorithm is proposed to guide antifungal treatment. Liposomal amphotericin B is advocated as first-line therapy in patients with sepsis/septic shock presenting candidemia or endophthalmitis, or with prior exposure to echinocandins and/or fluconazole, or with infections by
Candida glabrata
. Other situations and alternatives, such as new compounds or combination therapy, are also analysed.
Conclusion
There is a critical need for more robust clinical trials, studies examining patient heterogeneity and surveillance of antifungal resistance to enhance patient care and optimise treatment outcomes. Such evidence will help refine the existing guidelines and contribute to a more personalised and effective approach to treating this serious medical condition. Meanwhile, it is suggested to broaden the consideration of other options, such as liposomal amphotericin B, as first-line treatment until the results of the fungogram are available and antifungal stewardship could be implemented to prevent the development of resistance.
Our goal was to study whether influenza vaccination induced antibody mediated rejection in a large cohort of solid organ transplant recipients (SOTR).
Serum anti-Human Leukocyte Antigen (HLA) ...antibodies were determined using class I and class II antibody-coated latex beads (FlowPRA
Screening Test) by flow cytometry. Anti-HLA antibody specificity was determined using the single-antigen bead flow cytometry (SAFC) assay and assignation of donor specific antibodies (DSA) was performed by virtual-crossmatch.
We studied a cohort of 490 SOTR that received an influenza vaccination from 2009 to 2013: 110 (22.4%) received the pandemic adjuvanted vaccine, 59 (12%) within the first 6 months post-transplantation, 185 (37.7%) more than 6 months after transplantation and 136 (27.7%) received two vaccination doses. Overall, no differences of anti-HLA antibodies were found after immunization in patients that received the adjuvanted vaccine, within the first 6 months post-transplantation, or based on the type of organ transplanted. However, the second immunization dose increased the percentage of patients positive for anti-HLA class I significantly compared with patients with one dose (14.6% vs. 3.8%;
= 0.003). Patients with pre-existing antibodies before vaccination (15.7% for anti-HLA class I and 15.9% for class II) did not increase reactivity after immunization. A group of 75 (14.4%) patients developed
anti-HLA antibodies, however, only 5 (1.02%) of them were DSA, and none experienced allograft rejection. Only two (0.4%) patients were diagnosed with graft rejection with favorable outcomes and neither of them developed DSA.
Our results suggest that influenza vaccination is not associated with graft rejection in this cohort of SOTR.
We assessed the potential role of T2Candida MR (T2MR) and serological biomarkers β-d-glucan (BDG) or Candida albicans germ tube antibodies (CAGTA), alone or in combination with standard cultures, for ...identifying patients with suspected invasive candidiasis (IC), who may benefit from maintaining antifungal therapy.
Prospective observational multicentre study including all adult patients receiving empirical antifungal therapy for suspected IC, from January to June 2017. CAGTA, BDG and T2MR were determined at baseline and at +2 and +4 days after enrolment. Primary endpoint was the diagnostic value of CAGTA, BDG and T2MR, alone or in combination with standard culture, to predict diagnosis of IC and/or mortality in the first 7 days after starting antifungal therapy (poor outcome).
Overall, 14/49 patients (28.6%) had a poor outcome (7 died within the first 7 days of antifungal therapy, whereas 7 ended with a diagnosis of IC). CAGTA 3/14 (21.4%) versus 8/35 (22.9%), P = 1 and BDG 8/14 (57.1%) versus 17/35 (48.6%), P = 0.75 results were similar in poor- and good-outcome patients. Conversely, a positive T2MR was associated with a higher risk of poor outcome 5/14 (35.7%) versus 0/35 (0.0%) P = 0.0001. Specificity and positive predictive value of a positive T2MR for predicting poor outcome were both 100%, with a negative predictive value of 79.6%. After testing the combinations of biomarkers/standard cultures and T2MR/standard cultures, the combination of T2MR/standard cultures showed a high capacity to discriminate patients with poor outcome from those with good clinical evolution.
T2MR may be of significant utility to identify patients who may benefit from maintaining antifungal therapy.
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