Publications by authors named "Patricia Muñoz"

400 Publications

Different dynamics of mean SARS-CoV-2 RT-PCR Ct values between the first and second COVID-19 waves in the Madrid population.

Transbound Emerg Dis 2021 Feb 23. Epub 2021 Feb 23.

Servicio de Microbiología Clínica y Enfermedades Infecciosas, Hospital General Universitario Gregorio Marañón, Madrid, Spain.

SARS-CoV2-RT-PCR cycle-threshold values from 18,803 cases (2 March-4 October) in Madrid define three stages: i) initial ten weeks with sustained reduction of viral load (Ct: 23.4-32.3), ii) stability with low-viral loads (Ct:31.9-35.5) in the next nine weeks, and iii) sudden increase with progressive higher viral loads until reaching stability at high levels in the next twelve weeks, coinciding with an increased percentage of positive cases and reduced median age. These data indicate differential virological/epidemiological patterns between the first and second COVID-19 waves in Madrid.
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http://dx.doi.org/10.1111/tbed.14045DOI Listing
February 2021

Multicenter evaluation of the Panbio™ COVID-19 rapid antigen-detection test for the diagnosis of SARS-CoV-2 infection.

Clin Microbiol Infect 2021 Feb 16. Epub 2021 Feb 16.

Osakidetza Basque Health Service, Hospital Universitario Donostia, Clinical Management Unit of Gipuzkoa Laboratories, San Sebastián, Spain; National Centre for Microbiology, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain. Electronic address:

Objectives: The standard RT-PCR assay for coronavirus disease 2019 (COVID-19) is laborious and time-consuming, limiting testing availability. Rapid antigen-detection tests are faster and less expensive; however, the reliability of these tests must be validated before they can be used widely. The objective of this study was to determine the performance of the Panbio™ COVID-19 Ag Rapid Test Device (PanbioRT) (Abbott) in detecting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in nasopharyngeal swab specimens.

Methods: This prospective multicentre study was carried out in ten Spanish university hospitals and included individuals with clinical symptoms or epidemiological criteria of COVID-19. Only individuals with ≤7 days from the onset of symptoms or from exposure to a confirmed case of COVID-19 were included. Two nasopharyngeal samples were taken to perform the PanbioRT as a point-of-care test and a diagnostic RT-PCR test.

Results: Among the 958 patients studied, 325 (90.5%) had true-positive results. The overall sensitivity and specificity for the PanbioRT were 90.5% (95%CI 87.5-93.6) and 98.8% (95%CI 98-99.7), respectively. Sensitivity in participants who had a threshold cycle (C) < 25 for the RT-PCR test was 99.5% (95%CI 98.4-100), and in participants with ≤5 days of the clinical course it was 91.8% (95%CI 88.8-94.8). Agreement between techniques was 95.7% (κ score 0.90; 95%CI 0.88-0.93).

Conclusions: The PanbioRT performs well clinically, with even more reliable results for patients with a shorter clinical course of the disease or a higher viral load. The results must be interpreted based on the local epidemiological context.
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http://dx.doi.org/10.1016/j.cmi.2021.02.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7884234PMC
February 2021

In vitro activity of ibrexafungerp and comparators against Candida albicans genotypes from vaginal samples and blood cultures.

Clin Microbiol Infect 2021 Feb 15. Epub 2021 Feb 15.

Clinical Microbiology and Infectious Diseases Department, Hospital General Universitario Gregorio Marañón, Madrid, Spain; Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain.

Objectives: Emergence of azole resistance may contribute to recurrences of vulvovaginal candidiasis. Thus, new drugs are needed to improve the therapeutic options. We studied the in vitro activity of ibrexafungerp and comparators against Candida albicans isolates from vaginal samples and blood cultures. Furthermore, isolates were genotyped to study compartmentalization of genotypes and the relationship between genotype and antifungal susceptibility.

Methods: Candida albicans unique-patient isolates (n=144) from patients with clinical suspicion of vulvovaginal candidiasis (n=72 isolates) and from patients with candidemia (n=72) were studied. Antifungal susceptibility to amphotericin B, fluconazole, voriconazole, posaconazole, isavuconazole, clotrimazole, miconazole, micafungin, anidulafungin, and ibrexafungerp was tested (EUCAST 7.3.2). Mutations in the erg11 gene were analysed and isolates genotyped.

Results: Ibrexafungerp showed high activity (MICs from 0.03 mg/L to 0.25 mg/L) against the isolates, including those with reduced azole susceptibility, and regardless their clinical source. Fluconazole resistance rate was 7% (n=5/72) and 1.4% (n=1/72) in vaginal and blood isolates, respectively. Some amino acid substitutions in the Erg11 protein were observed exclusively in phenotypically fluconazole non-wild type. Population structure analysis suggested two genotype populations, one mostly involving isolates from blood samples (66.3%) and another mostly from vaginal samples (69.8%). The latter group hosted all fluconazole non-wild type isolates.

Conclusions: Ibrexafungerp shows good in vitro activity against Candida albicans from vaginal samples including phenotypically fluconazole non-wild type isolates. Furthermore, we found a certain population structure where some genotypes show reduced susceptibility to fluconazole.
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http://dx.doi.org/10.1016/j.cmi.2021.02.006DOI Listing
February 2021

Sample pooling is efficient in PCR testing of SARS-CoV-2: a study in 7400 healthcare professionals.

Diagn Microbiol Infect Dis 2021 Jan 30;100(1):115330. Epub 2021 Jan 30.

Clinical Microbiology and Infectious Diseases, Hospital General Universitario Gregorio Marañón (HGUGM), Madrid, Spain; Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain; CIBER Enfermedades Respiratorias-CIBERES, Madrid, Spain. Electronic address:

SARS-CoV-2 pandemic shows the importance of having efficient virus diagnosis, especially in groups of particular relevance such as health care professionals, without involving a large economic expense. This is a prevalence study carried out in 7400 health care professionals in a 1350-bed hospital in Madrid, Spain. Pools of 10 samples were performed, using the Xpert® Xpress SARS-CoV-2 test for the diagnosis from clinical samples of nasopharyngeal exudate. A previous study was performed to evaluate the effect of the dilution in terms of sensitivity. The estimated sensitivity was over 95%. A total of 740 pools were performed, with a final result of 218 health care professionals being positive. Using the pooling system, the reagent cost reduction to the institution was 75.3%. It can be concluded that the described sample pooling system is a useful and efficient tool in the diagnosis of SARS-CoV-2 in certain groups, assuming a cost reduction without reducing the sensitivity.
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http://dx.doi.org/10.1016/j.diagmicrobio.2021.115330DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7846879PMC
January 2021

Development of a Risk Prediction Model for Carbapenem-Resistant Enterobacteriaceae Infection after Liver Transplantation: A Multinational Cohort Study.

Clin Infect Dis 2021 Feb 10. Epub 2021 Feb 10.

Infectious Diseases Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Policlinico di Sant'Orsola, Bologna, Italy.

Background: Patients colonized with carbapenem resistant Enterobacteriaceae (CRE) are at higher risk of developing CRE infection after liver transplantation (LT) with associated high morbidity and mortality. Prediction model for CRE infection after LT among carriers could be useful to target preventive strategies.

Methods: Multinational multicenter cohort study of consecutive adult patients underwent LT and colonized with CRE before or after LT, from January 2010 to December 2017. Risk factors for CRE infection were analyzed by univariate analysis and by Fine-Gray sub-distribution hazard model, with death as competing event. A nomogram to predict 30- and 60-day CRE infection risk was created.

Results: 840 LT recipients found to be colonized with CRE before (n=203) or after (n=637) LT were enrolled. CRE infection was diagnosed in 250 (29.7%) patients within 19 (IQR 9-42) days after LT. Pre-and post-LT colonization, multisite post-LT colonization, prolonged mechanical ventilation, acute renal injury, and surgical re-intervention were retained in the prediction model. Median 30 and 60-day predicted risk was 15% (IQR 11-24%) and 21% (IQR 15-33%), respectively. Discrimination and prediction accuracy for CRE infection was acceptable on derivation (AUC 74.6, Brier index 16.3) and bootstrapped validation dataset (AUC 73.9, Brier index 16.6). Decision-curve analysis suggested net benefit of model-directed intervention over default strategies (treat all, treat none) when CRE infection probability exceeded 10%. The risk prediction model is freely available as mobile application at https://idbologna.shinyapps.io/CREPostOLTPredictionModel/.

Conclusions: Our clinical prediction tool could enable better targeting interventions for CRE infection after transplant.
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http://dx.doi.org/10.1093/cid/ciab109DOI Listing
February 2021

Characteristics and outcome of acute heart failure in infective endocarditis: focus on cardiogenic shock.

Clin Infect Dis 2021 Feb 9. Epub 2021 Feb 9.

Infectious Diseases Service. Hospital Clinic-IDIBAPS. University of Barcelona, Barcelona, Spain.

Background: Studies investigating the impact of cardiogenic shock (CS) on endocarditis are lacking. We aimed to investigate the characteristics and outcomes of endocarditis patients presenting with acute heart failure (AHF), particularly of those developing CS.

Methods: Prospectively collected cohort from 35 Spanish centers (2008-2018). Logistic regression analyses were performed to identify risk factors for developing CS and predictors of mortality.

Results: Amongst 4,856 endocarditis patients, 1,652 (34%) had AHF and 244 (5%) CS. Compared to patients without AHF and AHF but no CS, patients with CS presented higher rates of surgery (40.5%, 52.5% and 68%,p<.001) and in-hospital mortality (16.3%,39.1%, and 52.5%). Compared to patients with septic shock, CS patients presented higher rates of surgery (42.5% vs. 68%, p<.001), and lower rates of in-hospital and 1-year mortality (62.3% vs. 52.5%,p.008;and 65.3% vs. 57.4%,p.030). Severe aortic and mitral regurgitation (OR 2.47, 95%CI 1.82-3.35 and OR 3.03, 95%CI 2.26-4.07, both p<.001), left-ventricle ejection fraction<60% (OR 1.72, 95%CI 1.22-2.40, p.002), heart block (OR 2.22, 95%CI 1.41-3.47, p.001), tachyarrhythmias (OR 5.07,95%CI 3.13-8.19, p<.001) and acute kidney failure (OR 2.29, 95%CI 1.73-3.03,p<.001) were associated to a higher likelihood of developing CS. Prosthetic endocarditis (OR 2.03, 95%CI 1.06-3.88, p.032), S. aureus (OR 3.10, 95%CI 1.16-8.30, p.024), tachyarrhythmias (OR 3.09,95%CI 1.50-10.13, p.005), and not performing cardiac surgery (OR 11.40, 95%CI 4.83-26.90, p<.001) were associated to a higher risk of mortality.

Conclusions: Acute heart failure is common among patients with endocarditis. Cardiogenic shock is associated to very high mortality and should be promptly identified and assessed for cardiac surgery.
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http://dx.doi.org/10.1093/cid/ciab098DOI Listing
February 2021

Cellular Trafficking of Glutathione Transferase M2-2 Between U373MG and SHSY-S7 Cells is Mediated by Exosomes.

Neurotox Res 2021 Feb 8. Epub 2021 Feb 8.

Molecular and Clinical Pharmacology ICBM Faculty of Medicine, University of Chile, Santiago, Chile.

The enzyme glutathione transferase M2-2, expressed in human astrocytes, increases its expression in the presence of aminochrome and catalyzes the conjugation of aminochrome, preventing its toxic effects. Secretion of the enzyme glutathione transferase M2-2 from U373MG cells, used as a cellular model for astrocytes, has been reported, and the enzyme is taken up by neuroblastoma SYSH-S7 cells and provide protection against aminochrome. The present study provides evidence that glutathione transferase M2-2 is released in exosomes from U373MG cells, thereby providing a means for intercellular transport of the enzyme. With particular relevance to Parkinson disease and other degenerative conditions, we propose a new mechanism by which astrocytes may protect dopaminergic neurons against the endogenous neurotoxin aminochrome.
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http://dx.doi.org/10.1007/s12640-020-00327-5DOI Listing
February 2021

Endotracheal tubes coated with a broad-spectrum antibacterial ceragenin reduce bacterial biofilm in an in vitro bench top model.

J Antimicrob Chemother 2021 Feb 5. Epub 2021 Feb 5.

Department of Clinical Microbiology and Infectious Diseases, Hospital General Universitario Gregorio Marañón, Madrid, Spain.

Background: Ventilator-associated pneumonia is one of the most common nosocomial infections, caused mainly by bacterial/fungal biofilm. Therefore, it is necessary to develop preventive strategies to avoid biofilm formation based on new compounds.

Objectives: We performed an in vitro study to compare the efficacy of endotracheal tubes (ETTs) coated with the ceragenin CSA-131 and that of uncoated ETTs against the biofilm of clinical strains of Pseudomonas aeruginosa (PA), Escherichia coli (EC) and Staphylococcus aureus (SA).

Methods: We applied an in vitro bench top model using coated and uncoated ETTs that were treated with three different clinical strains of PA, EC and SA for 5 days. After exposure to biofilm, ETTs were analysed for cfu count by culture of sonicate and total number of cells by confocal laser scanning microscopy.

Results: The median (IQR) cfu/mL counts of PA, EC and SA in coated and uncoated ETTs were, respectively, as follows: 1.00 × 101 (0.0-3.3 × 102) versus 3.32 × 109 (6.6 × 108-3.8 × 109), P < 0.001; 0.0 (0.0-5.4 × 103) versus 1.32 × 106 (2.3 × 103-5.0 × 107), P < 0.001; and 8.1 × 105 (8.5 × 101-1.4 × 109) versus 2.7 × 108 (8.6 × 106-1.6 × 1011), P = 0.058. The median (IQR) total number of cells of PA, EC and SA in coated and non-coated ETTs were, respectively, as follows: 11.0 [5.5-not applicable (NA)] versus 87.9 (60.5-NA), P = 0.05; 9.1 (6.7-NA) versus 62.6 (42.0-NA), P = 0.05; and 97.7 (94.6-NA) versus 187.3 (43.9-NA), P = 0.827.

Conclusions: We demonstrated significantly reduced biofilm formation in coated ETTs. However, the difference for SA was not statistically significant. Future clinical studies are needed to support our findings.
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http://dx.doi.org/10.1093/jac/dkab019DOI Listing
February 2021

Disseminated lomentosporiosis in a heart transplant recipient: Case report and review of the literature.

Transpl Infect Dis 2021 Feb 1:e13574. Epub 2021 Feb 1.

Clinical Microbiology and Infectious Diseases Department, Hospital General Universitario Gregorio Marañón, Madrid, Spain.

Background: Lomentospora prolificans (formerly S prolificans) is a saprophyte fungi that causes opportunistic infections in solid organ transplant (SOT) recipients. Resulting disseminated infections are difficult to treat and have a high mortality. Indications for antifungal prophylaxis after heart transplantation (HT) include CMV disease, reoperation, renal replacement therapy, extracorporeal membrane oxygenation (ECMO), and high environmental exposure to Aspergillus spores. However, the risk of breakthrough infections, such as Lomentosporiosis, remains a cause of concern.

Methods: We report the clinical findings, microbiology, treatment and outcome of a disseminated Lomentosporiosis in a heart transplant recipient with ECMO and antifungal prophylaxis.

Results: A 25-year-old male with complex grown-up congenital heart disease (GUCHD) was admitted for HT. He presented severe post-surgical complications including acute kidney injury and right heart and respiratory failure requiring venoarterial-ECMO, continuous renal replacement therapy (CCRT) and later on (+14) a ventricular assist device (VAD). Ganciclovir, cotrimoxazole, and antifungal prophylaxis with anidulafungin at standard doses had been started on day + 3 post HT. The patient presented seizures (+4), pancytopenia with mild neutropenia (days + 6 to + 11), influenza B (+7), and bacteremic Pseudomonas aeruginosa ventilator associated pneumonia (VAP) (+10). On days + 14 to + 16 Lomentospora prolificans was recovered from blood cultures, broncho aspirate, catheter tip, and skin biopsy. Despite treatment with L-AMB, voriconazole and terbinafine the patients died on day 17 after HT. Necropsy revealed disseminated infection with fungal invasion in central nervous system, heart, lung, cutaneous, and subcutaneous tissue. Broth microdilution tests demonstrated resistance to all antifungals.

Conclusions: Lomentosporiosis is a rare complication that may emerge as a breakthrough invasive fungal infection in heart transplant recipients on ECMO despite antifungal prophylaxis.
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http://dx.doi.org/10.1111/tid.13574DOI Listing
February 2021

Clinical course of severe patients with COVID-19 treated with tocilizumab: report from a cohort study in Spain.

Expert Rev Clin Pharmacol 2021 Jan 26:1-12. Epub 2021 Jan 26.

Pharmacy Department. Hospital General Universitario Gregorio Marañón , Madrid, Spain.

: We report the long-term outcomes, changes in laboratory parameters, the incidence of secondary nosocomial infections and treatment cost of a Spanish cohort of patients with severe COVID-19 that received tocilizumab (TCZ). : Retrospective cohort of PCR confirmed adult patients who received TCZ from March 1 to 24, 2020 in a tertiary hospital was analyzed. Patients were followed up until 10 May 2020. : We included 162 patients (median age 64 years; 70.4% male). At time of TCZ administration, 48.1% of patients were on invasive mechanical ventilation (IMV). Over a median follow-up of 53 days, 46.9% of patients were discharge in good conditions and 19.8% were still hospitalized. The overall mortality was 33.3%, being higher in patients on IMV than those who did not (46.2% vs 26.7%, P < 0.001). A significant improvement in the lymphocyte count, C-reactive protein, lactate dehydrogenase, and D-dimer was observed. Overall, 43.2% patients presented nosocomial infections, causing death in 8%. Infections were more prevalent in ICU units (63.0% vs 17.1%, P < 0.001). The total cost of TCZ was €371,784. : Among the patients who used TCZ, one third died, regardless the improvement in some inflammatory biomarkers. The incidence of secondary nosocomial infections was high.
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http://dx.doi.org/10.1080/17512433.2021.1875819DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7852278PMC
January 2021

Utility of 1,3 β-d-Glucan Assay for Guidance in Antifungal Stewardship Programs for Oncologic Patients and Solid Organ Transplant Recipients.

J Fungi (Basel) 2021 Jan 17;7(1). Epub 2021 Jan 17.

Clinical Microbiology and Infectious Diseases Department, Hospital General Universitario Gregorio Marañón, 28007 Madrid, Spain.

The implementation of 1,3 β-d-glucan (BDG) has been proposed as a diagnostic tool in antifungal stewardship programs (ASPs). We aimed to analyze the influence of serum BDG in an ASP for oncologic patients and solid organ transplant (SOT) recipients. We conducted a pre-post study. In the initial period (PRE), the ASP was based on bedside advice, and this was complemented with BDG in the post-period (POST). Performance parameters of the BDG assay were determined. Antifungal (AF) use adequacy was evaluated using a point score. Clinical outcomes and AF costs were also compared before and after the intervention. Overall, 85 patients were included in the PRE-period and 112 in the POST-period. Probable or proven fungal infections were similar in both groups (54.1% vs. 57.1%; = 0.67). The determination of BDG contributed to improved management in 75 of 112 patients (66.9%). The AF adequacy score improved in the POST-period (mean 7.75 vs. 9.29; < 0.001). Median days of empiric AF treatment was reduced in the POST-period (9 vs. 5 days, = 0.04). All-cause mortality (44.7% vs. 34.8%; = 0.16) was similar in both periods. The cost of AF treatments was reduced in the POST-period with a difference of 779.6 €/patient. Our data suggest that the use of BDG was a cost-effective strategy that contributed to safely improving the results of an ASP for SOT and oncologic patients.
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http://dx.doi.org/10.3390/jof7010059DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7830184PMC
January 2021

Monitoring the epidemiology and antifungal resistance of yeasts causing fungaemia in a tertiary care hospital in Madrid, Spain. Any relevant changes in the last 13 years?

Antimicrob Agents Chemother 2021 Jan 19. Epub 2021 Jan 19.

Clinical Microbiology and Infectious Diseases, Hospital General Universitario Gregorio Marañón, Universidad Complutense de Madrid, Madrid, Spain

Updated analysis on yeast isolates causing fungaemia in patients admitted to a tertiary hospital in Madrid, Spain, over a 13-year period.We studied 896 isolates associated to 872 episodes of fungaemia in 857 hospitalized patients between January 2007 and December 2019. Antifungal susceptibility was assessed by EUCAST EDef 7.3.2. Mutations conferring azole and echinocandin resistance were further studied, and genotyping of resistant clones performed with species-specific microsatellite markers. (45.8%) was the most frequently identified species, followed by the complex (26.4%), (12.3%), (7.3%), (2.3%), other spp. (3.1%), and non-Candida yeasts (2.8%). Rate of fluconazole resistance in spp. was 4.7%, ranging from 0% () to 9.1% (). The overall rate of echinocandin resistance was 3.1%. Resistance was highly influenced by the presence of intrinsically resistant species. Although the number of isolates between 2007 and 2013 was almost two-fold higher than that of the 2014-2019 period (566 330), fluconazole resistance in spp. was greater in the second period (3.5% 6.8%; < 0.05), while overall resistance to echinocandins remained stable (3.5% 2.4%; > 0.05). Resistant clones were collected from different wards and/or time points, suggesting no epidemiological links.The number of fungaemia episodes has been decreasing over the last 13 years, with a slight increase in the rate of fluconazole resistance and stable echinocandin resistance. Antifungal resistance is not the cause of the spread of resistant clones.
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http://dx.doi.org/10.1128/AAC.01827-20DOI Listing
January 2021

Valganciclovir-Ganciclovir Use and Systematic Therapeutic Drug Monitoring. An Invitation to Antiviral Stewardship.

Antibiotics (Basel) 2021 Jan 15;10(1). Epub 2021 Jan 15.

Clinical Microbiology and Infectious Diseases Department, Hospital General Universitario Gregorio Marañón, Doctor Esquerdo 46, 28007 Madrid, Spain.

Valganciclovir (VGCV) and ganciclovir (GCV) doses must be adjusted according to indication, renal function and weight. No specific therapeutic exposure values have been established. We aimed to evaluate the adequacy of VGCV/GCV doses, to assess the interpatient variability in GCV serum levels, to identify predictive factors for this variability and to assess the clinical impact. This is a prospective study at a tertiary institution including hospitalized patients receiving VGCV/GCV prophylaxis or treatment. Adequacy of the antiviral dose was defined according to cytomegalovirus guidelines. Serum levels were determined using High-Performance Liquid Chromatography. Blood samples were drawn at least 3 days after antiviral initiation. Outcome was considered favorable if there was no evidence of cytomegalovirus infection during prophylaxis or when a clinical and microbiological resolution was attained within 21 days of treatment and no need for drug discontinuation due to toxicity. Seventy consecutive patients [74.3% male/median age: 59.2 years] were included. VGCV was used in 25 patients (35.7%) and GCV in 45 (64.3%). VGCV/GCV initial dosage was deemed adequate in 47/70 cases (67.1%), lower than recommended in 7/70 (10%) and higher in 16/70 (22.9%). Large inter-individual variability of serum levels was observed, with median trough levels of 2.3 mg/L and median peak levels of 7.8 mg/L. Inadequate dosing of VGCV/GCV and peak levels lower than 8.37 or greater than 11.86 mg/L were related to poor outcome. Further studies must be performed to confirm these results and to conclusively establish if VGCV/GCV therapeutic drug monitoring could be useful to improve outcomes in specific clinical situations.
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http://dx.doi.org/10.3390/antibiotics10010077DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7831032PMC
January 2021

Prevalence of Colorectal Neoplasms Among Patients With Enterococcus faecalis Endocarditis in the GAMES Cohort (2008-2017).

Mayo Clin Proc 2021 01;96(1):132-146

Hospital Clínic de Barcelona, IDIBAPS, Universitat de Barcelona, Barcelona, Spain. Electronic address:

Objective: To investigate the rate of colorectal neoplasms (CRNs) in patients who have Enterococcus faecalis infective endocarditis (EFIE) with available colonoscopies and to assess whether this is associated with the identification of a focus the infection.

Patients And Methods: Retrospective analysis of data from a prospective multicenter study involving 35 centers who are members of the Grupo de Apoyo para el Manejo de la Endocarditis en España [Support Group for the Management of Infective Endocarditis in Spain] cohort. A specific set of queries regarding information on colonoscopy and histopathology of colorectal diseases was sent to each participating center. Four-hundred sixty-seven patients with EFIE were included from January 1, 2008, to December 31, 2017, from whom data on colonoscopy performance and results were available in 411 patients.

Results: One hundred forty-two (34.5%) patients had a colonoscopy close to the EFIE episode. The overall rate of colorectal diseases was 70.4% (100 of 142), whereas the prevalence of CRN (advanced adenomas and colorectal carcinoma) was 14.8% (21 of 142), with no significant differences between the group of EFIE of unknown focus and that with an identified focus.

Conclusion: Our study adds to prior evidence suggesting a much higher rate of CRN among patients with EFIE than in the general population of the same age and sex. In addition, our findings suggest that this phenomenon might take place both in EFIE with an unknown and an identified source of infection.
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http://dx.doi.org/10.1016/j.mayocp.2020.06.056DOI Listing
January 2021

Recurrences of multidrug-resistant tuberculosis: Strains involved, within-host diversity, and fine-tuned allocation of reinfections.

Transbound Emerg Dis 2021 Jan 7. Epub 2021 Jan 7.

Hospital General Universitario Gregorio Marañón, Madrid, Spain.

Recurrent tuberculosis occurs due to exogenous reinfection or reactivation/persistence. We analysed 90 sequential MDR Mtb isolates obtained in Argentina from 27 patients with previously diagnosed MDR-TB that recurred in 2018 (1-10 years, 2-10 isolates per patient). Three long-term predominant strains were responsible for 63% of all MDR-TB recurrences. Most of the remaining patients were infected by strains different from each other. Reactivation/persistence of the same strain caused all but one recurrence, which was due to a reinfection with a predominant strain. One of the prevalent strains showed marked stability in the recurrences, while in another strain higher SNP-based diversity was observed. Comparisons of intra- versus inter-patient SNP distances identified two possible reinfections with closely related variants circulating in the community. Our results show a complex scenario of MDR-TB infections in settings with predominant MDR Mtb strains.
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http://dx.doi.org/10.1111/tbed.13982DOI Listing
January 2021

MixInYeast: A Multicenter Study on Mixed Yeast Infections.

J Fungi (Basel) 2020 Dec 29;7(1). Epub 2020 Dec 29.

Mycology Reference Laboratory, National Centre for Microbiology, Instituto de Salud Carlos III, 28220 Madrid, Spain.

Invasive candidiasis remains one of the most prevalent systemic mycoses, and several studies have documented the presence of mixed yeast (MY) infections. Here, we describe the epidemiology, clinical, and microbiological characteristics of MY infections causing invasive candidiasis in a multicenter prospective study. Thirty-four centers from 14 countries participated. Samples were collected in each center between April to September 2018, and they were sent to a reference center to confirm identification by sequencing methods and to perform antifungal susceptibility testing, according to the European Committee on Antimicrobial Susceptibility Testing (EUCAST). A total of 6895 yeast cultures were identified and MY occurred in 150 cases (2.2%). Europe accounted for the highest number of centers, with an overall MY rate of 4.2% (118 out of 2840 yeast cultures). Of 122 MY cases, the most frequent combinations were (42, 34.4%), (17, 14%), and (8, 6.5%). All Candida isolates were susceptible to amphotericin B, 6.4% were fluconazole-resistant, and two isolates (1.6%) were echinocandin-resistant. Accurate identification of the species involved in MY infections is essential to guide treatment decisions.
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http://dx.doi.org/10.3390/jof7010013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7823447PMC
December 2020

The classification of Staphylococcus aureus strains by biofilm production differs depending on the method used.

Enferm Infecc Microbiol Clin 2020 Dec 25. Epub 2020 Dec 25.

Department of Clinical Microbiology and Infectious Diseases, Hospital General Universitario Gregorio Marañon, Madrid, Spain; Instituto de Investigación Sanitaria Gregorio Marañon, Madrid, Spain. Electronic address:

Introduction: Strains can be classified in terms of biofilm production from quantitative absorbance values collectively by dividing strains into tertile ranks or individually by calculating the optical density for the negative control. However, these methods have not been compared in a large sample of Staphylococcus aureus strains. Therefore, our objective was to analyze the agreement between both methods in terms of biomass production and metabolic activity of their biofilm.

Methods: We classified 233 S. aureus strains by biomass production and metabolic activity using the crystal violet and XTT assays, respectively. Strains were classified as low, moderate, or high biofilm producers according to tertile or optical density.

Results: We found no agreement between both methods (p<0.001 and p=0.028, respectively).

Conclusions: We consider strains' biofilm classification by optical density to be a more reliable method, as it depends on the individual absorbance of each strain.
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http://dx.doi.org/10.1016/j.eimc.2020.11.002DOI Listing
December 2020

Angioimmunoblastic T-cell lymphoma after acute myeloid leukemia: Alleged common pathogenesis. A case report and literature review.

Clin Case Rep 2020 Dec 3;8(12):3494-3497. Epub 2020 Nov 3.

Department of Hematology Universitary Hospital de La Princesa Madrid Spain.

The genomic landscape of AITL is characterized by mutation of epigenetic modifiers. This gene expression pattern resembles myeloid diseases and shows a potential role for hypomethylating agents as possible therapy for AITL.
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http://dx.doi.org/10.1002/ccr3.3430DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7752322PMC
December 2020

Oral decontamination with colistin plus neomycin in solid organ transplant recipients colonized by multidrug-resistant Enterobacterales: a multicentre, randomized, controlled, open-label, parallel-group clinical trial.

Clin Microbiol Infect 2020 Dec 24. Epub 2020 Dec 24.

Quality Unit, Hospital Universitario Marqués de Valdecilla, IDIVAL, Santander, Spain.

Objectives: To evaluate the efficacy of oral colistin-neomycin in preventing multidrug-resistant Enterobacterales (MDR-E) infections in solid organ transplant (SOT) recipients.

Methods: Multicentre, open-label, parallel-group, controlled trial with balanced (1:1) randomization in five transplant units. SOT recipients were screened for MDR-E intestinal colonization (extended-spectrum β-lactamase or carbapenemase producing) before transplantation and +7 and + 14 days after transplantation and assigned 1:1 to receive treatment with colistin sulfate plus neomycin sulfate for 14 days (decolonization treatment (DT) group) or no treatment (no decolonization treatment (NDT) group). The primary outcome was diagnosis of an MDR-E infection. Safety outcomes were appearance of adverse effects, mainly diarrhoea, rash, nausea and vomiting. Patients were monitored weekly until 30 days after treatment. Intention-to-treat analysis was performed.

Results: MDR-E rectal colonization was assessed in 768 SOT recipients; 105 colonized patients were included in the clinical trial, 53 receiving DT and 52 NDT. No significant decrease in the risk of infection by MDR-E was observed in the DT group (9.4%, 5/53) compared to the NDT group (13.5%, 7/52) (relative risk 0.70; 95% confidence interval 0.24-2.08; p 0.517). Four patients (5.6%), three (5.6%) in the DT group and one (1.9%) in the NDT group, developed colistin resistance. Twelve patients (22.7%) in the DT group had diarrhoea, eight related to treatment (15.0%); one patient (1.8%) developed skin rash and another (1.8%) nausea and vomiting. Two patients (3.8%) in the NDT group developed diarrhoea.

Conclusions: DT does not reduce MDR-E infections in SOT. Colistin resistance and adverse effects such as diarrhoea are a potential issue that must be taken seriously.
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http://dx.doi.org/10.1016/j.cmi.2020.12.016DOI Listing
December 2020

Lack of relationship between genotype and virulence in Candida species.

Rev Iberoam Micol 2020 Dec 21. Epub 2020 Dec 21.

Clinical Microbiology and Infectious Diseases, Hospital General Universitario Gregorio Marañón, Universidad Complutense de Madrid, Madrid, Spain; Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain.

Background: The virulence of isolates among different Candida species causing candidemia may play a role in the prognosis of the patients. Furthermore, the potential relationship between genotype and virulence is still unclear and need to be further studied.

Aims: We aim to assess the relationship between genotype and virulence in Candida species using a Galleria mellonella larvae infection model.

Methods: One hundred and ninety-four isolates from 68 clusters (Candida albicans, 114/41; Candida parapsilosis, 74/24; Candida tropicalis, 6/3) were compared against the same number of each species singleton genotypes in terms of survival of G. mellonella larvae.

Results: The median of survival and the IQR ranges of clusters and singleton were as follows: C. albicans (2 days, IQR 1.5-2 vs. 2 days, IQR 1-2.25), C. parapsilosis (2 days, IQR 1.5-2.6 vs. 2 days, IQR 2-3.3), and C. tropicalis (1 day, IQR 1-3.5 vs. 2 days, IQR 2-3.5; p<0.05). High intra-cluster variability in terms of median of survival was found regardless the species.

Conclusions: No relationship between genotype and virulence in Candida was observed with the G. mellonella model.
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http://dx.doi.org/10.1016/j.riam.2020.10.002DOI Listing
December 2020

Invasive Fusariosis in Nonneutropenic Patients, Spain, 2000-2015.

Emerg Infect Dis 2021 Jan;27(1)

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.
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http://dx.doi.org/10.3201/eid2701.190782DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7774531PMC
January 2021

Infective endocarditis in patients with heart transplantation.

Int J Cardiol 2021 Apr 10;328:158-162. Epub 2020 Dec 10.

Facultad de Medicina, Universidad Complutense de Madrid, Spain; Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain; Servicio de Microbiología Clínica y Enfermedades Infecciosas, Hospital General Universitario Gregorio Marañón, Madrid, Spain; CIBER Enfermedades Respiratorias-CIBERES (CB06/06/0058), Madrid, Spain.

Background: The incidence of nosocomial and health care-related infective endocarditis (IE) is increasing. Heart transplantation (HT) implies immunosuppression and frequent health care contact. Our aim was to describe the current profile and prognosis of IE in HT recipients.

Methods: Multicenter retrospective registry-based study in Spain and France that included cases between 2008 and 2019.

Results: During the study period, 8305 HT were performed in Spain and France. We identified 18 IE cases (rate 0.2%). Median age was 57 years; 12 were men (67%). Valve involvement did not have a predominant location and three patients (16.7%) had atrial or ventricular vegetations without valve involvement. The median age-adjusted Charlson index was 4 (interquartile range 3-5). Eleven IE cases (61%) were nosocomial/health care-related. Median time (range) between HT and development of IE was 43 months (interquartile range 6-104). The major pathogens were Staphylococcus sp. (n = 8, 44%), Enterococcus sp. (n = 4, 22%), and Aspergillus sp. (n = 3, 17%). Although eight patients (44%) had a surgical indication, it was only performed in three cases (17%). Three patients (17%) died during the first IE hospital admission.

Conclusions: IE in HT recipients has specific characteristics. Valve involvement does not have a predominant location and non-valvular involvement is common. Three fifths have a nosocomial/health care-related origin. The major pathogens were staphylococci (44%), enterococci (22%), and Aspergillus (17%). In-hospital mortality was 17%.
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http://dx.doi.org/10.1016/j.ijcard.2020.12.018DOI Listing
April 2021

Correction to: Characterization of the virulence of Pseudomonas aeruginosa strains causing ventilator-associated pneumonia.

BMC Infect Dis 2020 Dec 11;20(1):951. Epub 2020 Dec 11.

Department of Clinical Microbiology and Infectious Diseases, Hospital General Universitario Gregorio Marañón, Madrid, Spain.

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http://dx.doi.org/10.1186/s12879-020-05691-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7731559PMC
December 2020

Pre-existing Hemagglutinin Stalk Antibodies Correlate with Protection of Lower Respiratory Symptoms in Flu-Infected Transplant Patients.

Cell Rep Med 2020 Nov 3;1(8):100130. Epub 2020 Nov 3.

Clinical Unit of Infectious Diseases, Microbiology and Preventive Medicine, Institute of Biomedicine of Seville, Virgen del Rocío University Hospital/CSIC/University of Seville, Seville, Spain.

Hemagglutination-inhibitory antibodies are usually highly strain specific with little effect on infection with drifted or shifted strains. The significance of broadly cross-reactive non-HAI anti-influenza antibodies against conserved domains of virus glycoproteins, such as the hemagglutinin (HA) stalk, is of great interest. We characterize a cohort of 40 H1N1pmd09 influenza-infected patients and identify lower respiratory symptoms (LRSs) as a predictor for development of pneumonia. A binomial logistic regression of log10 pre-existing antibody values shows that the probability of LRS occurrence decreased with increased anti-HA full-length and stalk antibody ELISA titers. However, a multilevel logistic regression model adjusted by other potential serocorrelates demonstrates that only antibodies directed against the stalk of HA correlate with protection from lower respiratory infection, limiting disease progression. Our predictive model indicates that a threshold of protective immunity based on broadly cross-reactive HA stalk antibodies could be feasible.
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http://dx.doi.org/10.1016/j.xcrm.2020.100130DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7691380PMC
November 2020

Implementation of MALDI-TOF Mass Spectrometry and Peak Analysis: Application to the Discrimination of Species Complex and Their Interspecies Hybrids.

J Fungi (Basel) 2020 Dec 2;6(4). Epub 2020 Dec 2.

Clinical Microbiology and Infectious Diseases Department, Hospital General Universitario Gregorio Marañón, Doctor Esquerdo, 46, 28007 Madrid, Spain.

Matrix-assisted laser desorption-ionization/time of flight mass spectrometry (MALDI-TOF MS) has been widely implemented for the rapid identification of microorganisms. Although most bacteria, yeasts and filamentous fungi can be accurately identified with this method, some closely related species still represent a challenge for MALDI-TOF MS. In this study, two MALDI-TOF-based approaches were applied for discrimination at the species-level of isolates belonging to the complex, previously characterized by Amplified Fragment Length Polymorphism (AFLP) and sequencing of the ITS1-5.8S-ITS2 region: (i) an expanded database was built with 26 isolates from the main species found in our setting (, and AFLP3 interspecies hybrids) and (ii) peak analysis and data modeling were applied to the protein spectra of the analyzed isolates. The implementation of the in-house database did not allow for the discrimination of the interspecies hybrids. However, the performance of peak analysis with the application of supervised classifiers (partial least squares-discriminant analysis and support vector machine) in a two-step analysis allowed for the 96.95% and 96.55% correct discrimination of from the interspecies hybrids, respectively. In addition, PCA analysis prior to support vector machine (SVM) provided 98.45% correct discrimination of the three analyzed species in a one-step analysis. This novel method is cost-efficient, rapid and user-friendly. The procedure can also be automatized for an optimized implementation in the laboratory routine.
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http://dx.doi.org/10.3390/jof6040330DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7711916PMC
December 2020

Characterization of the virulence of Pseudomonas aeruginosa strains causing ventilator-associated pneumonia.

BMC Infect Dis 2020 Dec 1;20(1):909. Epub 2020 Dec 1.

Department of Clinical Microbiology and Infectious Diseases, Hospital General Universitario Gregorio Marañón, Madrid, Spain.

Background: The objective of this study was to evaluate the virulence of P. aeruginosa ventilator-associated pneumonia (VAP) strains (cases) in terms of biofilm production and other phenotypic and genotypic virulence factors compared to P. aeruginosa strains isolated from other infections (controls).

Methods: Biofilm production was tested to assess biomass production and metabolic activity using crystal violet binding assay and XTT assay, respectively. Pigment production (pyocyanin and pyoverdine) was evaluated using cetrimide agar. Virulence genes were detected by conventional multiplex PCR and virulence was tested in an in vivo model in Galleria mellonella larvae.

Results: We did not find statistically significant differences between VAP and no-VAP strains (p > 0.05) regarding biofilm production. VAP strains had no production of pyocyanin after 24 h of incubation (p = 0.023). The distribution of virulence genes between both groups were similar (p > 0.05). VAP strains were less virulent than non-VAP strains in an in vivo model of G. mellonella (p < 0.001).

Conclusion: The virulence of VAP-Pseudomonas aeruginosa does not depend on biofilm formation, production of pyoverdine or the presence of some virulence genes compared to P. aeruginosa isolated from non-invasive locations. However, VAP strains showed attenuated virulence compared to non-VAP strains in an in vivo model of G. mellonella.
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http://dx.doi.org/10.1186/s12879-020-05534-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7706020PMC
December 2020

COVID-19 in hospitalised patients in Spain: a cohort study in Madrid.

Int J Antimicrob Agents 2021 Feb 28;57(2):106249. Epub 2020 Nov 28.

Pharmacy Department, Hospital General Universitario Gregorio Marañón, Madrid, Spain; Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain.

Few large series describe the clinical characteristics, outcomes and costs of COVID-19 in Western countries. This cohort reports the first 1255 adult cases receiving anti-COVID-19 treatment at a Spanish hospital (1-24 March 2020). Treatment costs were calculated. A logistic regression model was used to explore risk factors on admission associated with ARDS. A bivariate Cox proportional hazard ratio (HR) model was employed to determine the HR between individual factors and death. We included 1255 patients (median age 65 years; 57.8% male), of which 92.3% required hospitalisation. The prevalence of hypertension, cardiovascular disease and diabetes mellitus (DM) was 45.1%, 31.4% and 19.9%, respectively. Lymphocytopenia (54.8%), elevated alanine aminotransferase (33.0%) and elevated lactate dehydrogenase (58.5%) were frequent. Overall, 36.7% of patients developed ARDS, 10.0% were admitted to an ICU and 21.3% died. The most frequent antiviral combinations were lopinavir/ritonavir plus hydroxychloroquine (44.2%), followed by triple therapy with interferon beta-1b (32.7%). Corticosteroids and tocilizumab were used in 25.3% and 12.9% of patients, respectively. Total cost of anti-COVID-19 agents was €511 825 (€408/patient). By multivariate analysis, risk factors associated with ARDS included older age, obesity, DM, severe hypoxaemia, lymphocytopenia, increased creatine kinase and increased C-reactive protein. In multivariate Cox model, older age (HR 1.07, 95% CI 1.06-1.09), cardiovascular disease (HR 1.34, 95% CI 1.01-1.79), DM (HR 1.45, 95% CI 1.09-1.92), severe hypoxaemia (HR 2.01, 95% CI 1.49-2.72), lymphocytopenia (HR 1.62, 95% CI 1.20-2.20) and increased C-reactive protein (HR 1.04, 95% CI 1.02-1.06) were risk factors for mortality.
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http://dx.doi.org/10.1016/j.ijantimicag.2020.106249DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7698681PMC
February 2021

Inference of Active Viral Replication in Cases with Sustained Positive Reverse Transcription-PCR Results for SARS-CoV-2.

J Clin Microbiol 2021 01 21;59(2). Epub 2021 Jan 21.

Servicio de Microbiología Clínica y Enfermedades Infecciosas, Hospital General Universitario Gregorio Marañón, Madrid, Spain

The purpose of this study was to detect coronavirus disease 2019 (COVID-19) cases with persistent positive reverse transcription-PCR (RT-PCR) results for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), for which viable virus can be inferred due to the presence of subgenomic (SG) viral RNA, which is expressed only in replicating viruses. RNA remnants purified from diagnostic nasopharyngeal specimens were used as the templates for RT-PCR-specific detection of SG E gene RNA. As controls, we also detected viral genomic RNA for the E gene and/or a human housekeeping gene (RNase P). We assessed the samples of 60 RT-PCR-positive cases with prolonged viral SARS-CoV-2 shedding (24 to 101 days) since the first diagnostic RT-PCR. SG viral RNA was detected in 12/60 (20%) of the persistent cases, 28 to 79 days after the onset of symptoms. The age range of the cases with prolonged viral shedding and the presence of SG RNA was quite wide (40 to 100 years), and the cases were equally distributed between males (42%) and females (58%). No case was HIV positive, although seven were immunosuppressed. According to the severities of the COVID-19 episodes, they were mild (40%), intermediate (20%), and severe (40%). In a percentage of persistent SARS-CoV-2 PCR-positive cases, the presence of actively replicating virus may be inferred, far beyond diagnosis. We should not assume a universal lack of infectiousness for COVID-19 cases with prolonged viral shedding.
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http://dx.doi.org/10.1128/JCM.02277-20DOI Listing
January 2021

Invasive pulmonary aspergillosis in the COVID-19 era: An expected new entity.

Mycoses 2021 Feb 29;64(2):132-143. Epub 2020 Nov 29.

Clinical Microbiology and Infectious Diseases Department, Hospital General Universitario Gregorio Marañón, Madrid, Spain.

Objectives: Information on the recently COVID-19-associated pulmonary aspergillosis (CAPA) entity is scarce. We describe eight CAPA patients, compare them to colonised ICU patients with coronavirus disease 2019 (COVID-19), and review the published literature from Western countries.

Methods: Prospective study (March to May, 2020) that included all COVID-19 patients admitted to a tertiary hospital. Modified AspICU and European Organization for Research and Treatment of Cancer/Mycoses Study Group (EORTC/MSG) criteria were used.

Results: COVID-19-associated pulmonary aspergillosis was diagnosed in eight patients (3.3% of 239 ICU patients), mostly affected non-immunocompromised patients (75%) with severe acute respiratory distress syndrome (ARDS) receiving corticosteroids. Diagnosis was established after a median of 15 days under mechanical ventilation. Bronchoalveolar lavage was performed in two patients with positive Aspergillus fumigatus cultures and galactomannan (GM) index. Serum GM was positive in 4/8 (50%). Thoracic CT scan findings fulfilled EORTC/MSG criteria in one case. Isavuconazole was used in 4/8 cases. CAPA-related mortality was 100% (8/8). Compared with colonised patients, CAPA subjects were administered tocilizumab more often (100% vs. 40%, p = .04), underwent longer courses of antibacterial therapy (13 vs. 5 days, p = .008), and had a higher all-cause mortality (100% vs. 40%, p = .04). We reviewed 96 similar cases from recent publications: 59 probable CAPA (also putative according modified AspICU), 56 putative cases and 13 colonisations according AspICU algorithm; according EORTC/MSG six proven and two probable. Overall, mortality in the reviewed series was 56.3%.

Conclusions: COVID-19-associated pulmonary aspergillosis must be considered a serious and potentially life-threatening complication in patients with severe COVID-19 receiving immunosuppressive treatment.
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http://dx.doi.org/10.1111/myc.13213DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7753705PMC
February 2021