Defining COVID-19-associated pulmonary aspergillosis: systematic review and meta-analysis.

BACKGROUND: Pulmonary aspergillosis may complicate coronavirus disease 2019 (COVID-19) and contribute to excess mortality in intensive care unit (ICU) patients. The disease is poorly understood, in part due to discordant definitions across studies. OBJECTIVES: We sought to review the prevalence, diagnosis, treatment, and outcomes of COVID-19-associated pulmonary aspergillosis (CAPA) and compare research definitions. DATA SOURCES: PubMed, Embase, Web of Science, and MedRxiv were searched from inception to October 12, 2021. STUDY ELIGIBILITY CRITERIA: ICU cohort studies and CAPA case series including ≥3 patients were included. PARTICIPANTS: Adult patients in ICUs with COVID-19. INTERVENTIONS: Patients were reclassified according to four research definitions. We assessed risk of bias with an adaptation of the Joanna Briggs Institute cohort checklist tool for systematic reviews. METHODS: We calculated CAPA prevalence using the Freeman-Tukey random effects method. Correlations between definitions were assessed with Spearman's rank test. Associations between antifungals and outcome were assessed with random effects meta-analysis. RESULTS: Fifty-one studies were included. Among 3297 COVID-19 patients in ICU cohort studies, 313 were diagnosed with CAPA (prevalence 10%; 95% CI 8%-13%). Two hundred seventy-seven patients had patient-level data allowing reclassification. Definitions had limited correlation with one another (ρ = 0.268-0.447; p < 0.001), with the exception of Koehler and Verweij (ρ = 0.893; p < 0.001); 33.9% of patients reported to have CAPA did not fulfill any research definitions. Patients were diagnosed after a median of 8 days (interquartile range 5-14) in ICUs. Tracheobronchitis occurred in 3% of patients examined with bronchoscopy. The mortality rate was high (59.2%). Applying CAPA research definitions did not strengthen the association between mould-active antifungals and survival. CONCLUSIONS: The reported prevalence of CAPA is significant but may be exaggerated by nonstandard definitions.

Invasive mould disease in fatal COVID-19: a systematic review of autopsies.

Invasive mould disease (IMD) might affect up to a third of critically ill patients with COVID-19. COVID-19-associated pulmonary aspergillosis (CAPA) is typically diagnosed on the basis of a combination of non-specific clinical, radiographical, and mycological findings, but whether most cases represent invasive disease is unresolved. We systematically reviewed autopsy series of three or more decedents with COVID-19 for evidence of IMD. We searched PubMed, Web of Science, OVID (Embase), and medRxiv for studies in English or French published from Jan 1, 2019, to Sept 26, 2020. We identified 1070 references, of which 50 studies met the criteria. These studies described autopsies from 677 decedents, with individual-level data for 443 decedents. The median age was 70·0 years (IQR 57·0-79·0). Of decedents with individual-level data, 133 (30%) had diabetes, 97 (22%) had pre-existing lung disease, and 27 (6%) had immunocompromising conditions. Of 548 decedents with such data, 320 (58%) received invasive mechanical ventilation; among 140 decedents for whom this was known, ventilation was for a median of 9·0 days (IQR 5·0-20·0). Treatment included immunomodulation in 60 decedents and antifungals in 50 decedents. Autopsy-proven IMD occurred in 11 (2%) of 677 decedents, including eight CAPA, two unspecified IMD, and one disseminated mucormycosis. Among 320 decedents who received mechanical ventilation, six (2%) had IMD. We conclude that IMD, including CAPA, is an uncommon autopsy finding in COVID-19.

Pseudomonas aeruginosa infection in intensive care: Epidemiology, outcomes, and antimicrobial susceptibilities.

Background: Pseudomonas aeruginosa (PA) infection in the intensive care unit (ICU) contributes to substantial mortality. In this study, we describe the epidemiology, antimicrobial susceptibilities, and outcomes of ICU patients with pseudomonal infection. Methods: ICU patients with PA were identified and classified as colonized or infected. Infected patients were reviewed for source, patient characteristics, antimicrobial susceptibilities, appropriateness of empiric antimicrobial therapy, and 30-day mortality. Independent predictors of mortality were identified using multivariable logistic regression. Results: One hundred forty (71%) patients with PA were infected. Mean patient age was 55 (SD 18) years; 62% were male. Admission categories included medical (71%), surgical (20%), and trauma or neurological (9%). Mean Acute Physiology and Chronic Health Evaluation (APACHE) II score was 19 (SD 10). One hundred twenty-six (90%) patients were mechanically ventilated, 102 (73%) required vasopressors, and 27 (19%) received renal replacement; 32 (23%) died within 30 days. Infection was nosocomial in 101 (72%) cases. Sources were respiratory (66%), skin-soft tissue (11%), urinary (10%), blood (5%), surgical (5%), gastrointestinal (2%), or unknown (1%). Twenty (14%) isolates were multi-drug resistant; 6 (4%) were extensively drug resistant. Empiric antimicrobial therapy was effective in 97 (69%) cases. Liver disease (adjusted OR [aOR] 6.2, 95% CI 1.5 to 25.7; p = 0.01), malignancy (aOR 5.0, 95% CI 1.5 to 17.3; p = 0.01), and higher APACHE II score (aOR 1.1, 95% CI 1.0 to 1.1; p = 0.02) were independently associated with 30-day mortality. Conclusions: PA infection in ICU is most commonly respiratory and associated with substantial mortality. Existing malignancy, liver disease, and higher APACHE II score were independently associated with mortality.

Historique: L'infection à Pseudomonas aeruginosa (PA) contribue à une mortalité importante en soins intensifs. Dans la présente étude, les chercheurs décrivent l'épidémiologie, les susceptibilités antimicrobiennes et les résultats cliniques des patients atteints d'une infection à Pseudomonas hospitalisés en soins intensifs. Méthodologie: Les chercheurs ont répertorié les patients en soins intensifs atteints d'un PA et les ont classés comme colonisés ou infectés. Ils ont revu les dossiers des patients infectés pour connaître la source de l'infection, les caractéristiques des patients, leurs susceptibilités antimicrobiennes, le bien-fondé d'un traitement antimicrobien empirique et la mortalité au bout de 30 jours. Ils ont déterminé les prédicteurs indépendants de la mortalité au moyen de la régression logistique multivariable. Résultats: Cent quarante patients atteints d'un PA (71 %) étaient infectés. Ils avaient un âge moyen de 55 ans (ÉT 18), et 62 % étaient de sexe masculin. Les hospitalisations étaient d'ordre médical (71 %), chirurgical (20 %) et traumatique-neurologique (9 %). Le score APACHE II (Acute Physiology and Chronic Health Evaluation ou évaluation de la physiologie aiguë et de la santé chronique) s'élevait à 19 (ÉT 10). Cent vingt-six patients (90 %) étaient sous ventilation mécanique, 102 (73 %) dépendaient des vasopresseurs, 27 (19 %) ont reçu une transplantation rénale et 32 (23 %) sont décédés dans les 30 jours. Dans 101 cas (72 %), l'infection était d'origine nosocomiale. L'infection était de source respiratoire (66 %), cutanée-tissus mous (11 %), urinaire (10 %), sanguine (5 %), chirurgicale (5 %), gastro-intestinale (2 %) ou inconnue (1 %). Vingt isolats (14 %) étaient multirésistants et six (4 %), ultrarésistants. Le traitement antimicrobien empirique a été efficace dans 97 cas (69 %). Une maladie hépatique (rapport de cotes corrigé [RCc] 6,2, IC À 95 %, 1,5 à 25,7; p = 0,01), une tumeur maligne (RCc 5,0, IC à 95 %, 1,5 à 17,3; p = 0,01) et un score APACHE II élevé (RCc 1,1, IC à 95 %, 1,0 à 1,1; p = 0,02) étaient liés de façon indépendante à la mortalité au bout de 30 jours. Conclusions: L'infection à PA en soins intensifs est surtout de source respiratoire et associée à une mortalité importante. La préexistence d'une tumeur maligne, d'une maladie hépatique et d'un score APACHE II élevé était liée de façon indépendante à la mortalité.