Adjunctive glucocorticoid therapy for Pneumocystis jirovecii pneumonia in solid organ transplant recipients: A multicenter cohort, 2015-2020.

Solid organ transplant recipients (SOTRs) frequently receive adjunctive glucocorticoid therapy (AGT) for Pneumocystis jirovecii pneumonia (PJP). This multicenter cohort of SOTRs with PJP admitted to 20 transplant centers in Canada, the United States, Europe, and Australia, was examined for whether AGT was associated with a lower rate of all-cause intensive care unit (ICU) admission, 90-day death, or a composite outcome (ICU admission or death). Of 172 SOTRs with PJP (median [IQR] age: 60 (51.5-67.0) years; 58 female [33.7%]), the ICU admission and death rates were 43.4%, and 20.8%, respectively. AGT was not associated with a reduced risk of ICU admission (adjusted odds ratio [aOR] [95% CI]: 0.49 [0.21-1.12]), death (aOR [95% CI]: 0.80 [0.30-2.17]), or the composite outcome (aOR [95% CI]: 0.97 [0.71-1.31]) in the propensity score-adjusted analysis. AGT was not significantly associated with at least 1 unit of the respiratory portion of the Sequential Organ Failure Assessment score improvement by day 5 (12/37 [32.4%] vs 39/111 [35.1%]; P = .78). We did not observe significant associations between AGT and ICU admission or death in SOTRs with PJP. Our findings should prompt a reevaluation of routine AGT administration in posttransplant PJP treatment and highlight the need for interventional studies.

Current and Emerging Therapies for COVID-19 in Lung Transplantation.

Purpose of Review: The landscape of the coronavirus disease 2019 (COVID-19) pandemic has rapidly changed over the past 3 years. Paralleling this evolution, the scientific and medical communities have reported many novel findings relating to the infection's epidemiology, transmission, diagnosis, and treatment. We review pertinent studies of COVID-19 therapeutics with an emphasis on their application to lung transplant recipients. Recent Findings: Agents that have been well-studied for treating COVID-19 include antivirals (remdesivir, nirmatrelvir/ritonavir, molnupiravir), monoclonal antibodies, and immunomodulators (for example, corticosteroids and tocilizumab). Summary: Remdesivir remains an essential therapy for managing mild-moderate COVID-19. Though highly efficacious for mild-moderate COVID-19 for outpatient therapy, ritonavir-boosted nirmatrelvir has limited use in lung transplant recipients due to significant drug-drug interactions. Monoclonal antibodies, though useful, are the most affected by the emergence of new viral variants.

Clostridioides difficile colonization and the frequency of subsequent treatment for C. difficile infection in critically ill patients.

OBJECTIVE: To determine risk factors for Clostridioides difficile colonization and C. difficile infection (CDI) among patients admitted to the intensive care unit (ICU). DESIGN: Retrospective observational cohort study. SETTING: Tertiary-care facility. PATIENTS: All adult patients admitted to an ICU from July 1, 2015, to November 6, 2019, who were tested for C. difficile colonization. Patients with CDI were excluded. METHODS: Information was collected on patient demographics, comorbidities, laboratory results, and prescriptions. We defined C. difficile colonization as a positive nucleic acid amplification test for C. difficile up to 48 hours before or 24 hours after intensive care unit (ICU) admission without evidence of active infection. We defined active infection as the receipt of an antibiotic whose only indication is the treatment of CDI. The primary outcome measure was the development of CDI up to 30 days after ICU admission. Logistic regression was used to model associations between clinical variables and the development of CDI. RESULTS: The overall C. difficile colonization rate was 4% and the overall CDI rate was 2%. Risk factors for the development of CDI included C. difficile colonization (aOR, 13.3; 95% CI, 8.3-21.3; P < .0001), increased ICU length of stay (aOR, 1.04; 95% CI, 1.03-1.05; P < .0001), and a history of inflammatory bowel disease (aOR, 3.8; 95% CI, 1.3-11.1; P = .02). Receipt of any antibiotic during the ICU stay was associated with a borderline increased odds of CDI (aOR, 1.9; 95% CI, 1.0-3.4; P = .05). CONCLUSION: C. difficile colonization is associated with the development of CDI among ICU patients.

Clinical characteristics of hospitalized patients with false-negative severe acute respiratory coronavirus virus 2 (SARS-CoV-2) test results.

OBJECTIVE: To determine clinical characteristics associated with false-negative severe acute respiratory coronavirus virus 2 (SARS-CoV-2) test results to help inform coronavirus disease 2019 (COVID-19) testing practices in the inpatient setting. DESIGN: A retrospective observational cohort study. SETTING: Tertiary-care facility. PATIENTS: All patients 2 years of age and older tested for SARS-CoV-2 between March 14, 2020, and April 30, 2020, who had at least 2 SARS-CoV-2 reverse-transcriptase polymerase chain reaction tests within 7 days. METHODS: The primary outcome measure was a false-negative testing episode, which we defined as an initial negative test followed by a positive test within the subsequent 7 days. Data collected included symptoms, demographics, comorbidities, vital signs, labs, and imaging studies. Logistic regression was used to model associations between clinical variables and false-negative SARS-CoV-2 test results. RESULTS: Of the 1,009 SARS-CoV-2 test results included in the analysis, 4.0% were false-negative results. In multivariable regression analysis, compared with true-negative test results, false-negative test results were associated with anosmia or ageusia (adjusted odds ratio [aOR], 8.4; 95% confidence interval [CI], 1.4-50.5; P = .02), having had a COVID-19-positive contact (aOR, 10.5; 95% CI, 4.3-25.4; P < .0001), and having an elevated lactate dehydrogenase level (aOR, 3.3; 95% CI, 1.2-9.3; P = .03). Demographics, symptom duration, other laboratory values, and abnormal chest imaging were not significantly associated with false-negative test results in our multivariable analysis. CONCLUSIONS: Clinical features can help predict which patients are more likely to have false-negative SARS-CoV-2 test results.

Bacterial infections in lung transplantation.

Lung transplantation has lower survival rates compared to other than other solid organ transplants (SOT) due to higher rates of infection and rejection-related complications, and bacterial infections (BI) are the most frequent infectious complications. Excess morbidity and mortality are not only a direct consequence of these BI, but so are subsequent loss of allograft tolerance, rejection, and chronic lung allograft dysfunction due to bronchiolitis obliterans syndrome (BOS). A wide variety of pathogens can cause infections in lung transplant recipients (LTRs), including a number of nosocomial pathogens and other multidrug-resistant (MDR) pathogens. Although pneumonia and intrathoracic infections predominate, LTRs are at risk of a number of types of infections. Risk factors include altered anatomy and function of airways, impaired immunity, the microbial flora of the donor and recipient, underlying medical conditions, and genetic factors. Further work on immune monitoring has the potential to improve outcomes. The infecting agents can be derived from the donor lung, pre-existing recipient flora, or acquired from the environment over time. Certain infections may preclude lung transplantation, but this varies from center to center, and more recent studies suggest fewer patients should be disqualified. New molecular methods allow microbiome studies of the lung, gut, and other sites that may further our knowledge of how airway colonization can result in infection and allograft loss. Surveillance, early diagnosis, and aggressive antimicrobial therapy of BI is critical in LTRs. Antibiotic resistance is a major barrier to successful management of these infections. The availability of new agents for MDR Gram-negatives may improve outcomes. Other new therapies, such as bacteriophage therapy, show promise for the future. Finally, it is important to prevent infections through peri-transplant prophylaxis, vaccination, and infection control measures.

Obesity is Associated with Increased Risk for Mortality Among Hospitalized Patients with COVID-19.

OBJECTIVE: Obesity has been identified as a risk factor for severe coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 virus. This study sought to determine whether obesity is a risk factor for mortality among patients with COVID-19. METHODS: The study was a retrospective cohort that included patients with COVID-19 between March 1 and April 18, 2020. RESULTS: A total of 238 patients were included; 218 patients (91.6%) were African American, 113 (47.5%) were male, and the mean age was 58.5 years. Of the included patients, 146 (61.3%) had obesity (BMI > 30 kg/m2 ), of which 63 (26.5%), 29 (12.2%), and 54 (22.7%) had class 1, 2, and 3 obesity, respectively. Obesity was identified as a predictor for mortality (odds ratio [OR] 1.7 [1.1-2.8], P = 0.016), as was male gender (OR 5.2 [1.6-16.5], P = 0.01) and older age (OR 3.6 [2.0-6.3], P < 0.0005). Obesity (OR 1.7 [1.3-2.1], P < 0.0005) and older age (OR 1.3 [1.0-1.6], P = 0.03) were also risk factors for hypoxemia. CONCLUSIONS: Obesity was found to be a significant predictor for mortality among inpatients with COVID-19 after adjusting for age, gender, and other comorbidities. Patients with obesity were also more likely to present with hypoxemia.

Impact of Vasoactive Medications on ICU-Acquired Weakness in Mechanically Ventilated Patients.

BACKGROUND: Vasoactive medications are commonly used in the treatment of critically ill patients, but their impact on the development of ICU-acquired weakness is not well described. The objective of this study is to evaluate the relationship between vasoactive medication use and the outcome of ICU-acquired weakness. METHODS: This is a secondary analysis of mechanically ventilated patients (N = 172) enrolled in a randomized clinical trial of early occupational and physical therapy vs conventional therapy, which evaluated the end point of ICU-acquired weakness on hospital discharge. Patients underwent bedside muscle strength testing by a therapist blinded to study allocation to evaluate for ICU-acquired weakness. The effects of vasoactive medication use on the incidence of ICU-acquired weakness in this population were assessed. RESULTS: On logistic regression analysis, the use of vasoactive medications increased the odds of developing ICU-acquired weakness (odds ratio [OR], 3.2; P = .01) independent of all other established risk factors for weakness. Duration of vasoactive medication use (in days) (OR, 1.35; P = .004) and cumulative norepinephrine dose (µg/kg/d) (OR, 1.01; P = .02) (but not vasopressin or phenylephrine) were also independently associated with the outcome of ICU-acquired weakness. CONCLUSIONS: In mechanically ventilated patients enrolled in a randomized clinical trial of early mobilization, the use of vasoactive medications was independently associated with the development of ICU-acquired weakness. Prospective trials to further evaluate this relationship are merited. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT01777035; URL: www.clinicaltrials.gov.

One-Year Outcomes in Patients With Acute Respiratory Distress Syndrome Enrolled in a Randomized Clinical Trial of Helmet Versus Facemask Noninvasive Ventilation.

OBJECTIVES: Many survivors of acute respiratory distress syndrome have poor long-term outcomes possibly due to supportive care practices during "invasive" mechanical ventilation. Helmet noninvasive ventilation in acute respiratory distress syndrome may reduce intubation rates; however, it is unknown if avoiding intubation with helmet noninvasive ventilation alters the consequences of surviving acute respiratory distress syndrome. DESIGN: Long-term follow-up data from a previously published randomized controlled trial. PATIENTS: Adults patients with acute respiratory distress syndrome enrolled in a previously published clinical trial. SETTING: Adult ICU. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: The primary outcome was functional independence at 1 year after hospital discharge defined as independence in activities of daily living and ambulation. At 1 year, patients were surveyed to assess for functional independence, survival, and number of institution-free days, defined as days alive spent living at home. The presence of ICU-acquired weakness and functional independence was also assessed by a blinded therapist on hospital discharge. On hospital discharge, there was a greater prevalence of ICU-acquired weakness (79.5% vs 38.6%; p = 0.0002) and less functional independence (15.4% vs 50%; p = 0.001) in the facemask group. One-year follow-up data were collected for 81 of 83 patients (97.6%). One-year mortality was higher in the facemask group (69.2% vs 43.2%; p = 0.017). At 1 year, patients in the helmet group were more likely to be functionally independent (40.9% vs 15.4%; p = 0.015) and had more institution-free days (median, 268.5 [0-354] vs 0 [0-323]; p = 0.017). CONCLUSIONS: Poor functional recovery after invasive mechanical ventilation for acute respiratory distress syndrome is common. Helmet noninvasive ventilation may be the first intervention that mitigates the long-term complications that plague survivors of acute respiratory distress syndrome managed with noninvasive ventilation.