OBJECTIVE: To identify pathogenic microorganisms and microbiological risk factors causing high morbidity and mortality in immunocompromised patients requiring invasive mechanical ventilation due to pneumonia.
METHODS: A retrospective single-center study was performed at the intensive care unit (ICU) of the Department of Internal Medicine at Heidelberg University Hospital (Germany) including 246 consecutive patients with hematological malignancies requiring invasive mechanical ventilation due to pneumonia from 08/2004 to 07/2016. Microbiological and radiological data were collected and statistically analyzed for risk factors for ICU and 1-year mortality.
RESULTS: ICU and 1-year mortality were 63.0% (155/246) and 81.0% (196/242), respectively. Pneumonia causing pathogens were identified in 143 (58.1%) patients, multimicrobial infections were present in 51 (20.7%) patients. Fungal, bacterial and viral pathogens were detected in 89 (36.2%), 55 (22.4%) and 41 (16.7%) patients, respectively. Human herpesviruses were concomitantly reactivated in 85 (34.6%) patients. As significant microbiological risk factors for ICU mortality probable invasive Aspergillus disease with positive serum-Galactomannan (odds ratio 3.1 (1.2-8.0), p = 0.021,) and pulmonary Cytomegalovirus reactivation at intubation (odds ratio 5.3 (1.1-26.8), p = 0.043,) were identified. 1-year mortality was not significantly associated with type of infection. Of interest, 19 patients had infections with various respiratory viruses and Aspergillus spp. superinfections and experienced high ICU and 1-year mortality of 78.9% (15/19) and 89.5% (17/19), respectively.
CONCLUSIONS: Patients with hematological malignancies requiring invasive mechanical ventilation due to pneumonia showed high ICU and 1-year mortality. Pulmonary Aspergillosis and pulmonary reactivation of Cytomegalovirus at intubation were significantly associated with negative outcome.

Diagnosing Pneumocystis jirovecii pneumonia (PJP) can be complex, particularly in cases of significant respiratory failure. The 1,3-β-D-glucan (BDG) serum assay has emerged as a promising non-invasive diagnostic tool for detecting fungal infections, including PJP. However, factors that can confound the interpretation of BDG levels by causing elevation in serum levels have been documented. Here, we present the case of 51-year-old woman with underlying autoimmune disorder, hematologic malignancy, and chronic steroid use, who was admitted for acute hypoxemic respiratory failure. Obtaining the BDG assay after the administration of intravenous immunoglobulin (IVIG) posed a diagnostic challenge, as the patient was unable to undergo bronchoscopy. This circumstance led to a debate regarding the possibility of a false-positive BDG due to IVIG use or the presence of PJP. Ultimately, the patient was empirically treated for PJP. This case underscores the importance of comprehending factors that may contaminate BDG results, particularly in immunocompromised individuals.

UNASSIGNED: Neutropenic sepsis frequently requires admission to an intensive care unit (ICU). Differences between subgroups of patients with neutropenic sepsis are not well characterized.
UNASSIGNED: To investigate clinical outcomes among patients with neutropenic sepsis and hematological malignancy, metastatic solid cancer, or no cancer diagnosis.
UNASSIGNED: Retrospective cohort study of all patients admitted to ICU in Australia or New Zealand between January 2000 and December 2022 with a primary admission diagnosis of sepsis and total white cell count <1.0 × 109 cells/L.
UNASSIGNED: We identified 8617 ICU admissions with neutropenic sepsis (hematological malignancy n = 4660; metastatic solid cancer n = 1034; no cancer n = 2800). Patients with hematological malignancy were younger (median, 61.5 years) with low rates of chronic comorbidities (4.7%) and were usually admitted to ICU from the ward (67.4%). Mechanical ventilation rates were 20.2% and in-hospital mortality was 30.6%. Patients with metastatic solid cancers were older (median, 66.3 years), with higher rates of chronic comorbidities (9.9%), and were usually admitted to the ICU from the emergency department (50.8%). Mechanical ventilation rates were 16.9% and in-hospital mortality was 42.4%. Patients with no documented cancer had highest rates of mechanical ventilation (41.7%) and mortality (46.3%). Neutropenia was independently associated with mortality among patients with solid cancers or no cancer but did not confer increased risk among patients with hematological malignancy (odds ratio, 0.98; 95% confidence interval, .90-1.06; P = .60).
UNASSIGNED: Patients with neutropenic sepsis and hematological malignancy, metastatic solid cancer, or no cancer diagnosis constitute 3 distinct clinical groups. Management approaches should be tailored accordingly.

BACKGROUND: Immunosuppression at intensive care unit (ICU) admission has been associated with a higher incidence of ICU-acquired infections, some of them related to opportunistic pathogens. However, the association of immunosuppression with the incidence, microbiology and outcomes of ICU-acquired bacterial bloodstream infections (BSI) has not been thoroughly investigated.
METHODS: Retrospective single-centered cohort study in France. All adult patients hospitalized in the ICU of Lille University-affiliated hospital for > 48 h between January 1st and December 31st, 2020, were included, regardless of their immune status. Immunosuppression was defined as active cancer or hematologic malignancy, neutropenia, hematopoietic stem cell and solid organ transplants, use of steroids or immunosuppressive drugs, human immunodeficiency virus infection and genetic immune deficiency. The primary objective was to compare the 28-day cumulative incidence of ICU-acquired bacterial BSI between immunocompromised and non-immunocompromised patients. Secondary objectives were to assess the microbiology and outcomes of ICU-acquired bacterial BSI in the two groups.
RESULTS: A total of 1313 patients (66.9% males, median age 62 years) were included. Among them, 271 (20.6%) were immunocompromised at ICU admission. Severity scores at admission, the use of invasive devices and antibiotic exposure during ICU stay were comparable between groups. Both prior to and after adjustment for pre-specified baseline confounders, the 28-day cumulative incidence of ICU-acquired bacterial BSI was not statistically different between immunocompromised and non-immunocompromised patients. The distribution of bacteria was comparable between groups, with a majority of Gram-negative bacilli (~ 64.1%). The proportion of multidrug-resistant bacteria was also similar between groups. Occurrence of ICU-acquired bacterial BSI was associated with a longer ICU length-of-stay and a longer duration of invasive mechanical ventilation, with no significant association with mortality. Immune status did not modify the association between occurrence of ICU-acquired bacterial BSI and these outcomes.
CONCLUSIONS: The 28-day cumulative incidence of ICU-acquired bacterial BSI was not statistically different between patients with and without immunosuppression at ICU admission.

Although severe coronavirus disease 2019 (COVID-19) and hospitalization associated with COVID-19 are generally preventable among healthy vaccine recipients, patients with immunosuppression have poor immunogenic responses to COVID-19 vaccines and remain at high risk of infection with SARS-CoV-2 and hospitalization. In addition, monoclonal antibody therapy is limited by the emergence of novel SARS-CoV-2 variants that have serially escaped neutralization. In this context, there is interest in understanding the clinical benefit associated with COVID-19 convalescent plasma collected from persons who have been both naturally infected with SARS-CoV-2 and vaccinated against SARS-CoV-2 (\"vax-plasma\"). Thus, we report the clinical outcome of 386 immunocompromised outpatients who were diagnosed with COVID-19 and who received contemporary COVID-19-specific therapeutics (standard-of-care group) and a subgroup who also received concomitant treatment with very high titer COVID-19 convalescent plasma (vax-plasma group) with a specific focus on hospitalization rates. The overall hospitalization rate was 2.2% (5 of 225 patients) in the vax-plasma group and 6.2% (10 of 161 patients) in the standard-of-care group, which corresponded to a relative risk reduction of 65% (P = 0.046). Evidence of efficacy in nonvaccinated patients cannot be inferred from these data because 94% (361 of 386 patients) of patients were vaccinated. In vaccinated patients with immunosuppression and COVID-19, the addition of vax-plasma or very high titer COVID-19 convalescent plasma to COVID-19-specific therapies reduced the risk of disease progression leading to hospitalization.IMPORTANCEAs SARS-CoV-2 evolves, new variants of concern (VOCs) have emerged that evade available anti-spike monoclonal antibodies, particularly among immunosuppressed patients. However, high-titer COVID-19 convalescent plasma continues to be effective against VOCs because of its broad-spectrum immunomodulatory properties. Thus, we report clinical outcomes of 386 immunocompromised outpatients who were treated with COVID-19-specific therapeutics and a subgroup also treated with vaccine-boosted convalescent plasma. We found that the administration of vaccine-boosted convalescent plasma was associated with a significantly decreased incidence of hospitalization among immunocompromised COVID-19 outpatients. Our data add to the contemporary data providing evidence to support the clinical utility of high-titer convalescent plasma as antibody replacement therapy in immunocompromised patients.

SUMMARYEvery human being is presumed to be infected by the fungus Pneumocystis jirovecii at least once in his or her lifetime. This fungus belongs to a large group of species that appear to exclusively infect mammals, with P. jirovecii being the only one known to cause disease in humans. The mystery of P. jirovecii origin and speciation is just beginning to unravel. Here, we provide a review of the major steps of P. jirovecii evolution. The Pneumocystis genus likely originated from soil or plant-associated organisms during the period of Cretaceous ~165 million years ago and successfully shifted to mammals. The transition coincided with a substantial loss of genes, many of which are related to the synthesis of nutrients that can be scavenged from hosts or cell wall components that could be targeted by the mammalian immune system. Following the transition, the Pneumocystis genus cospeciated with mammals. Each species specialized at infecting its own host. Host specialization is presumably built at least partially upon surface glycoproteins, whose protogene was acquired prior to the genus formation. P. jirovecii appeared at ~65 million years ago, overlapping with the emergence of the first primates. P. jirovecii and its sister species P. macacae, which infects macaques nowadays, may have had overlapping host ranges in the distant past. Clues from molecular clocks suggest that P. jirovecii did not cospeciate with humans. Molecular evidence suggests that Pneumocystis speciation involved chromosomal rearrangements and the mounting of genetic barriers that inhibit gene flow among species.

The Pantoea genus of bacteria is a group of Gram-negative rod-shaped bacteria in the Enterobacteriaceae family. It is an uncommon cause of infection in humans except in specific settings, including hospital-acquired infections and in immunocompromised patients. In this report, we describe the case of a 12-year-old girl with sickle cell disease who presented with a picture of sepsis and was found to have Pantoea species in her blood culture which was treated with antibiotics with a good response. From our literature review, risk factors were identified in the reported cases, for which further exploration is highly recommended.

SUMMARYAs Chagas disease remains prevalent in the Americas, it is important that healthcare professionals and researchers are aware of the screening, diagnosis, monitoring, and treatment recommendations for the populations of patients they care for and study. Management of Trypanosoma cruzi infection in immunocompromised hosts is challenging, particularly because, regardless of antitrypanosomal treatment status, immunocompromised patients with Chagas disease are at risk for T. cruzi reactivation, which can be lethal. Evidence-based practices to prevent and manage T. cruzi reactivation vary depending on the type of immunocompromise. Here, we review available data describing Chagas disease epidemiology, testing, and management practices for various populations of immunocompromised individuals, including people with HIV and patients undergoing solid organ and hematopoietic stem cell transplantation.

Severe, refractory asthma requires a combination of multiple maintenance inhalers and medications including high-dose inhaled corticosteroids and immunomodulators to achieve control of symptoms. The use of inhaled corticosteroids, however, increases the susceptibility of opportunistic bacterial infections, such as Nocardia, resulting in pulmonary nocardiosis. This case describes a 46-year-old patient with a history of severe, refractory asthma who presented with progressively worsening asthma exacerbation symptoms. She was treated with immunomodulators, high-dose inhaled corticosteroids and oral steroids, and several courses of antibiotics. CT imaging revealed bibasilar peri-bronchial thickening and tree-in-bud nodularity in the right lower lobe. Pulmonary cultures collected from bronchoscopy grew Nocardia nova complex. This was a rare case of persistent asthma exacerbation by N. nova complex bronchopulmonary infection. Broad differentials should be considered in patients with severe, refractory asthma who were previously controlled and were found to fail treatment therapies. Immunocompromised patients with chronic lung disease are at higher risk of severe infection with disseminated nocardiosis. These patients have a higher mortality and morbidity risk if early diagnosis of pulmonary nocardiosis does not occur.

Retinal necrosis is a severe condition that threatens visual function. It is caused by viruses that are known to cause acute retinal necrosis (ARN) and progressive outer retinal necrosis (PORN), which are called necrotizing herpetic retinopathies (NHR). ARN causes severe intraocular inflammation, including anterior chamber intravitreal cells, keratic precipitate, vitreous opacity, and retinal vasculitis, whereas intraocular inflammation in PORN is considered mild or virtually absent. In addition, PORN is a disease that manifests in immunosuppressive patients, such as those with acquired immunodeficiency syndrome. Here, we present a case of unilateral retinal necrosis after chemotherapy, allogeneic peripheral blood stem cell transplantation, and cord blood transplantation for acute myelogenous leukemia (AML) in a 31-year-old male patient. AML treatment resulted in metabolic remission, and oral steroids and tacrolimus were continued. After two days, the patient visited an ophthalmologist because he noticed a sudden onset of floaters and visual field disturbance in the left eye. The peripheral retina was already necrotic in all layers, causing total retinal detachment. Intraocular inflammation, retinal opacity, or hemorrhagic spots in the fundus were not observed. His previous CD4 count was 43 cells/µL. A polymerase chain reaction test of the anterior chamber fluid revealed varicella-zoster virus (VZV), and vitrectomy was performed four days after disease onset. The excised vitreous demonstrated minimal opacity. The peripheral necrotic retina was excised, photocoagulation was performed on the residual retinal limbus, and silicone oil was injected to maintain retinal attachment. The retinal restoration was maintained under silicone oil tamponade, and corrected visual acuity improved to 20/32 without strong inflammation after vitrectomy. However, two months postoperatively, he contracted coronavirus disease 2019 (COVID-19), his general condition rapidly deteriorated, and he died. This case of retinal necrosis without inflammatory results in an immunocompromised patient and VZV detection in an intraocular sample led us to suspect PORN. However, the patchy or spread retinal whitening characteristic of PORN was completely absent, whereas the well-defined, peripheral, full-layer retinal necrosis characteristic of ARN was present. Thus, this is a rare case of VZV-induced NHR with partial features of PORN and ARN that progressed very silently.