scholarly journals DAS181 Treatment of Severe Lower Respiratory Tract Parainfluenza Virus Infection in Immunocompromised Patients: A Phase 2 Randomized, Placebo-Controlled Study

2021 ◽  
Author(s):  
Roy F Chemaly ◽  
Francisco M Marty ◽  
Cameron R Wolfe ◽  
Steven J Lawrence ◽  
Sanjeet Dadwal ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
Respiratory Tract ◽  
Primary Endpoint ◽  
Lower Respiratory Tract ◽  
Parainfluenza Virus ◽  
Controlled Study ◽  
Solid Organ ◽  
Immunocompromised Patients ◽  
Post Hoc Analysis ◽  
Post Hoc

Abstract Background There are no antiviral therapies for parainfluenza virus (PIV) infections. DAS181, a sialidase fusion protein, has demonstrated activity in in vitro and in animal models of PIV. Methods Adult immunocompromised patients diagnosed with PIV lower respiratory tract infection (LRTI) who required oxygen supplementation were randomized 2:1 to nebulized DAS181 (4.5 mg/day) or matching placebo for up to 10 days. Randomization was stratified by need for mechanical ventilation (MV) or supplemental oxygen (SO). The primary endpoint was the proportion of patients reaching clinical stability survival (CSS) defined as returning to room air (RTRA), normalization of vital signs for at least 24 hours, and survival up to day 45 from enrollment. Results A total of 111 patients were randomized to DAS181 (n = 74) or placebo (n = 37). CSS was achieved by 45.0% DAS181-treated patients in the SO stratum compared with 31.0% for placebo (P = .15), whereas patients on MV had no benefit from DAS181. The proportion of patients achieving RTRA was numerically higher for SO stratum DAS181 patients (51.7%) compared with placebo (34.5%) at day 28 (P = .17). In a post hoc analysis of solid organ transplant, hematopoietic cell transplantation within 1 year, or chemotherapy within 1 year, more SO stratum patients achieved RTRA on DAS181 (51.8%) compared with placebo (15.8%) by day 28 (P = .012). Conclusions The primary endpoint was not met, but post hoc analysis of the RTRA component suggests DAS181 may have clinical activity in improving oxygenation in select severely immunocompromised patients with PIV LRTI who are not on mechanical ventilation. Clinical Trials Registration. NCT01644877.

scholarly journals The Use of Aerosolized Ribavirin in Respiratory Syncytial Virus Lower Respiratory Tract Infections in Adult Immunocompromised Patients: A Systematic Review

2019 ◽  
Vol 55 (4) ◽  
pp. 224-235
Author(s):  
Lisa Avery ◽  
Charles Hoffmann ◽  
Karen M. Whalen
Keyword(s):  
Systematic Review ◽  
Mechanical Ventilation ◽  
Respiratory Syncytial Virus ◽  
Tract Infection ◽  
Respiratory Tract ◽  
Respiratory Tract Infection ◽  
Lower Respiratory Tract ◽  
Adverse Reactions ◽  
Immunocompromised Patients ◽  
Syncytial Virus

Introduction: Respiratory syncytial virus (RSV)–associated lower respiratory tract infection (LRTI) is a concern in immunocompromised patients. Aerosolized ribavirin (RBV AER) is used for treatment of RSV LRTI; however, adverse events and rising drug costs remain a challenge for patient management. The purpose of this systematic review is to summarize the efficacy and adverse event profile of RBV AER for the treatment of hospitalized RSV LRTI in immunocompromised adult patients. Methods: A Medline/PubMed, Embase, Google Scholar, Clinicaltrials.gov, and Cochrane Library database search was conducted from 1966 to January 2019 for the use of RBV AER. Search strategy: [(ribavirin OR ICN1229) AND (“administration, oral” OR “oral” OR “administration, inhalation” OR “inhalation)] AND (“respiratory tract infection” OR “pneumonia”). Studies were reviewed if adult patients were hospitalized, immunocompromised, had RSV LRTI, received RBV AER, and included the outcome of mortality and/or adverse reactions. Methodological quality was assessed using the Cochrane Collaboration GRADE approach. Results: A total of 1787 records were identified and 15 articles met inclusion criteria: hematopoietic stem cell transplant (HSCT)/bone marrow transplant (n = 8), other malignancy/neutropenic (n = 2), solid organ transplant (n = 5). All of the trials are observational with a low quality rating; therefore, a meta-analysis was not performed. The 30-day mortality in studies that contain >10 patients with HSCT, malignancy, and transplant range from 0 to 15.4%, 6.3%, and 0 to 27%, respectively. Improved mortality was cited in 4 studies when RBV AER started before mechanical ventilation or within 2 weeks of symptom onset. Only 3 studies had comparative mortality data with RBV AER and RBV PO. Adverse reactions were reported in 5 studies and included psychiatric manifestations (anxiety, depression, feeling of isolation; n = 14), wheezing/bronchospasm (n = 6), snowflakes/hail blowing in face (n = 6), and precipitation in ventilator tubing (n = 5). Conclusion: There is a lack of high quality, comparative trials on the use of RBV AER for the treatment of RSV LRTI in adult hospitalized immunocompromised patients. There may be a mortality benefit when RBV AER is initiated early after diagnosis or prior to mechanical ventilation, but requires further study. Patient isolation and psychological effects must be weighed against the benefit of therapy.

scholarly journals Lower Respiratory Tract Infection and Short-Term Outcome in Patients With Acute Respiratory Distress Syndrome

2018 ◽  
Vol 35 (6) ◽  
pp. 588-594 ◽  
Author(s):  
Fernando G. Zampieri ◽  
Pedro Póvoa ◽  
Jorge I. Salluh ◽  
Alejandro Rodriguez ◽  
Sandrine Valade ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
Acute Respiratory Distress Syndrome ◽  
Random Forest ◽  
Respiratory Tract ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Lower Respiratory Tract ◽  
Distress Syndrome ◽  
Icu Mortality ◽  
Mortality Model

Objective: To assess whether ventilator-associated lower respiratory tract infections (VA-LRTIs) are associated with mortality in critically ill patients with acute respiratory distress syndrome (ARDS). Materials and Methods: Post hoc analysis of prospective cohort study including mechanically ventilated patients from a multicenter prospective observational study (TAVeM study); VA-LRTI was defined as either ventilator-associated tracheobronchitis (VAT) or ventilator-associated pneumonia (VAP) based on clinical criteria and microbiological confirmation. Association between intensive care unit (ICU) mortality in patients having ARDS with and without VA-LRTI was assessed through logistic regression controlling for relevant confounders. Association between VA-LRTI and duration of mechanical ventilation and ICU stay was assessed through competing risk analysis. Contribution of VA-LRTI to a mortality model over time was assessed through sequential random forest models. Results: The cohort included 2960 patients of which 524 fulfilled criteria for ARDS; 21% had VA-LRTI (VAT = 10.3% and VAP = 10.7%). After controlling for illness severity and baseline health status, we could not find an association between VA-LRTI and ICU mortality (odds ratio: 1.07; 95% confidence interval: 0.62-1.83; P = .796); VA-LRTI was also not associated with prolonged ICU length of stay or duration of mechanical ventilation. The relative contribution of VA-LRTI to the random forest mortality model remained constant during time. The attributable VA-LRTI mortality for ARDS was higher than the attributable mortality for VA-LRTI alone. Conclusion: After controlling for relevant confounders, we could not find an association between occurrence of VA-LRTI and ICU mortality in patients with ARDS.

scholarly journals 1704. Geotrichum spp. Invasive Infection: Experience From a Third-Level Referral Center in Mexico

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S624-S624
Author(s):  
Sandra Rajme-López ◽  
María F Gonzalez-Lara ◽  
Andrea Rangel-Cordero ◽  
Alfredo Ponce de Leon
Keyword(s):  
Tract Infection ◽  
Respiratory Tract ◽  
Respiratory Tract Infection ◽  
Lower Respiratory Tract Infection ◽  
Antifungal Therapy ◽  
Lower Respiratory Tract ◽  
Common Finding ◽  
Clinical Samples ◽  
Invasive Infection ◽  
Solid Organ

Abstract Background Geotrichum spp has been recognized as an emergent pathogen that causes invasive infection in immunosuppressed hosts. There is no data in Latin America about invasive Geotrichum spp. infections. Our objective was to describe the epidemiology, clinical characteristics, and outcomes of patients with this infection. Methods We conducted a retrospective survey from 2001 to 2018, of all the Geotrichum spp. isolated from clinical samples at our institution. Data on demographic, clinical, laboratory findings, and imaging studies were obtained from medical records. All cases classified as proven or probable invasive fungal infections (IFI) according to the EORTC/MSG criteria were included. Isolates with unavailable clinical information were excluded. Descriptive analysis was made. Results We found 18 patients with a proven/probable Geotrichum spp. IFI. The mean age was 48.5 years and 55.5% were male. The most common predisposing condition was hematological malignancy (55.5%), autoimmune diseases (22.2%) and HIV, chronic granulomatous disease, and solid-organ malignancy in 1 case, respectively. Fifteen (83.3%) received immunosuppressors (cancer chemotherapy or steroids); 27.7% had neutropenia at the time of diagnosis. The most common clinical syndromes were lower respiratory tract infection and persistent fever (83.3%). Chest abnormalities were present in 15/16 CT scans, pulmonary nodules were the most common finding (62.5%). Geotrichum spp. was isolated from bronchoalveolar lavage, 77.7%; blood culture, 22.2%; and peritoneal dyalisis fluid, 5.6%. Seven patients were coinfected with other pathogens: 4 Aspergillus spp., 1 H. parainfluenzae, 1 P. aeruginosa, and 1 E. coli. Fifteen patients received antifungal treatment: 7 amphotericin B, 8 voriconazole, and 1 itraconazole. Among survivors (11), 72.7% received antifungal therapy at discharge: 4 voriconazole and 4 itraconazole. Three patients did not receive any antifungal: 1 was diagnosed postmortem and 2 were considered colonization (both were alive at 30 days). Overall mortality was 38.8%. Conclusion Eighteen cases of Geotrichum spp. were found. The majority had lower respiratory tract infection. Despite antifungal therapy 38.8% died. Geotrichum spp. should be recognized as an emerging pathogen in immunosuppressed hosts. Disclosures All authors: No reported disclosures.

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