Neutropenic Sepsis in the Intensive Care Unit: Differences in Clinical Profile and Outcomes According to the Cause of Neutropenia.

Background: Neutropenic sepsis frequently requires admission to an intensive care unit (ICU). Differences between subgroups of patients with neutropenic sepsis are not well characterized. Aims: To investigate clinical outcomes among patients with neutropenic sepsis and hematological malignancy, metastatic solid cancer, or no cancer diagnosis. Methods: 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. Results: 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). Conclusions: 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.

Diagnostic Challenge for Positive 1,3-ß-D-Glucan in an Immunocompromised Patient Receiving Intravenous Immunoglobulin Presenting With Respiratory Failure.

Diagnosing Pneumocystis jirovecii pneumonia (PJP) can be complex, particularly in cases of significant respiratory failure. The 1,3-ß-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.

Immunosuppression at ICU admission is not associated with a higher incidence of ICU-acquired bacterial bloodstream infections: the COCONUT study.

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. CONCLUSION: The 28-day cumulative incidence of ICU-acquired bacterial BSI was not statistically different between patients with and without immunosuppression at ICU admission.

Microbiological risk factors, ICU survival, and 1-year survival in hematological patients with pneumonia requiring invasive mechanical ventilation.

PURPOSE: 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.

Retracing the evolution of Pneumocystis species, with a focus on the human pathogen Pneumocystis jirovecii.

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.

Pantoea Species Bacteremia in a Child With Sickle Cell Disease: A Case Report.

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.

Outpatient treatment with concomitant vaccine-boosted convalescent plasma for patients with immunosuppression and COVID-19.

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.

Chagas disease in immunocompromised patients.

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.

Atypical Peripheral Retinal Necrosis Without Ocular Inflammation and Retinal Whitening in a Patient With Acute Myelogenous Leukemia: A Case Report.

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.

Unremitting Asthma as a Presentation of Pulmonary Nocardiosis: A Case Report.

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.

Diffuse Alveolar Hemorrhage Caused by Disseminated Cryptococcosis in a Patient With Systemic Lupus Erythematosus.

A teenage girl with systemic lupus erythematosus (SLE) was admitted with fever, dry cough, and dyspnea on exertion. Chest computed tomography revealed bilateral diffuse infiltration and swelling of the mediastinal lymph nodes. The bronchoalveolar lavage (BAL) fluid was light red, suggesting diffuse alveolar hemorrhage (DAH). Therefore, glucocorticoid pulse therapy was initiated. However, blood and BAL fluid cultures showed the growth of Cryptococcus neoformans. The patient was diagnosed with disseminated cryptococcosis. The patient was treated with liposomal amphotericin B and flucytosine; the prednisolone dose was rapidly tapered. Infections should be thoroughly ruled out in patients with SLE and DAH.

Rhodococcus infection: a 10-year retrospective analysis of clinical experience and antimicrobial susceptibility profile.

Rhodococcus equi is an opportunistic pathogen known to cause pulmonary and extrapulmonary disease among immunocompromised patients. Treatment is frequently challenging due to intrinsic resistance to multiple antibiotic classes. While non-equi Rhodococcus spp. are prevalent, their clinical significance is poorly defined. There is also limited data on antibiotic susceptibility testing (AST) of Rhodococcus infection in humans. We conducted a single-center, retrospective cohort study evaluating clinical characteristics, microbiologic profile, and AST of Rhodococcus infections between June 2012 and 2022 at our tertiary academic medical center. Identification of Rhodococcus spp. was performed by Sanger 16S rRNA gene sequencing and/or matrix-assisted laser desorption ionization-time of flight mass spectrometry, and AST was performed by agar dilution. Three hundred twenty-two isolates of Rhodococcus spp. were identified from blood (50%), pulmonary (26%), and bone/joint (12%) sources. R. equi/hoagii, R. corynebacterioides, and R. erythropolis were the most frequently isolated species, with 19% of isolates identified only to genus level. One hundred ninety-nine isolates evaluated for AST demonstrated high-level resistance to amoxicillin/clavulanate, cephalosporins, and aminoglycosides. More than 95% susceptibility to imipenem, vancomycin, linezolid, rifampin, and clarithromycin was observed. Non-equi species showed a significantly more favorable AST profile relative to R. equi. Clinically significant Rhodococcus infection was rare with 10 cases diagnosed (majority due to R. equi) and managed. The majority of patients received 2- or 3-drug combination therapy for 2-6 months, with favorable clinical response. Significant differences in AST were observed between R. equi and non-equi species. Despite high antimicrobial resistance to several antibiotic classes, imipenem and vancomycin remain appropriate empiric treatment options for R. equi. Future research evaluating mechanisms underlying antimicrobial resistance is warranted.

A Rare Case of Uterine Blastomycosis and Its Management: A Case Report and Literature Review.

The report delineates the rare occurrence of uterine blastomycosis, an atypical systemic presentation of Blastomyces dermatitidis infection prevalent in North America. Focused on a 51-year-old immunocompetent female displaying abdominal pain and irregular vaginal bleeding, it underscores the intricate diagnostic hurdles posed by symptoms mirroring common gynecological conditions. Despite fewer than 10 recorded cases, the rarity of uterine involvement highlights the imperative for heightened clinical suspicion. The multifaceted diagnostic strategy integrates risk factors, travel history, imaging, and histopathological examinations. Emphasizing a multidisciplinary treatment helmed by gynecologists, pathologists, and infectious disease specialists, the utilization of antifungal agents, notably itraconazole, is pivotal. Addressing the scarcity of literature and the condition's clinical resemblance to prevalent ailments, further research becomes paramount in devising tailored diagnostic and treatment protocols for uterine blastomycosis. This study enriches the existing literature by providing critical insights into a scarcely documented condition, contributing novel perspectives essential for clinical understanding and management strategies.

Determining Pneumocystis jirovecii Colonisation from Infection Using PCR-Based Diagnostics in HIV-Negative Individuals.

BACKGROUND: Pneumocystis jirovecii pneumonia is increasingly diagnosed with highly sensitive PCR diagnostics in immunocompromised, HIV-negative individuals. We assessed the performance of our in-house quantitative PCR with the aim to optimise interpretation. METHODS: Retrospective audit of all positive P. jirovecii qPCRs on induced sputum or BAL fluid at a single centre from 2012 to 2023. Medical and laboratory records were analysed and people with HIV were excluded. Cases were categorised as colonisation, high-probability PCP or uncertain PCP infection against a clinical gold standard incorporating clinico-radiological data. Quantitative PCR assay targeting the 5s gene was utilised throughout the time period. RESULTS: Of the 82 positive qPCRs, 28 were categorised as high-probability PCP infection, 30 as uncertain PCP and 24 as colonisation. There was a significant difference in qPCR values stratified by clinical category but not respiratory sample type. Current assay performance with a cutoff of 2.5 × 105 copies/mL had a sensitivity of 50% (95% CI, 30.65-69.35%) and specificity of 83.33% (95% CI, 62.62-95.26%). Youden Index calculated at 6.5 × 104 copies/mL had a sensitivity of 75% (56.64-87.32%, 95% CI) and specificity of 66.67% (46.71-82.03%, 95% CI). High and low cutoffs were explored. Significant variables associated with infection were age > 70 years old, the presence of fever, hypoxia or ground glass changes. CONCLUSIONS: A single qPCR cutoff cannot reliably determine P. jirovecii infection from colonisation. Low and high cutoffs are useful, however, a large "possible infection" cohort will remain where interpretation of clinic-radiological factors remains essential. Standardisation of assays with prospective validation in specific immunocompromised groups will allow greater generalisability and allow large-scale prospective assay validation to be performed.

Viral Pneumonias.

Viral pneumonia is usually community acquired and caused by influenza, parainfluenza, respiratory syncytial virus, human metapneumovirus, and adenovirus. Many of these infections are airway centric and chest imaging demonstrates bronchiolitis and bronchopneumonia, With the exception of adenovirus infections, the presence of lobar consolidation usually suggests bacterial coinfection. Community-acquired viral pathogens can cause more severe pneumonia in immunocompromised hosts, who are also susceptible to CMV and varicella infection. These latter 2 pathogens are less likely to manifest the striking airway-centric pattern. Airway-centric pattern is distinctly uncommon in Hantavirus pulmonary syndrome, a rare environmentally acquired infection with high mortality.

Opportunistic Infections Post-Lung Transplantation: Viral, Fungal, and Mycobacterial.

Opportunistic infections are a leading cause of lung transplant recipient morbidity and mortality. Risk factors for infection include continuous exposure of the lung allograft to the external environment, high levels of immunosuppression, impaired mucociliary clearance and decreased cough reflex, and impact of the native lung microbiome in single lung transplant recipients. Infection risk is mitigated through careful pretransplant screening of recipients and donors, implementation of antimicrobial prophylaxis strategies, and routine surveillance posttransplant. This review describes common viral, fungal, and mycobacterial infectious after lung transplant and provides recommendations on prevention and treatment.

Efficacy and safety of antiviral plus anti-spike monoclonal antibody combination therapy vs. monotherapy for high-risk immunocompromised patients with mild-to-moderate SARS-CoV2 infection during the Omicron era: A prospective cohort study.

INTRODUCTION: Antivirals and monoclonal antibodies lower the risk of progression in immunocompromised patients. However, combination therapy with both types of agents has not been studied. PATIENTS AND METHODS: This was a single-centre, prospective, cohort study. All immunocompromised patients who received treatment for mild-to-moderate COVID-19 from 1 January 2022 to 30 October 2022 were enrolled. The primary endpoint was COVID-19 progression at 90 days, defined as hospital admission or death due to COVID-19 and/or seronegative persistent COVID-19. RESULTS: A total of 304 patients were included: 43 patients (14.1%) received sotrovimab plus a direct-acting antiviral, and 261 (85.9%) received monotherapy. Primary outcome occurred more frequently after monotherapy (4.6% vs. 0%, P=0.154). Among patients with anti-spike immunoglobulin G (anti-S IgG) titre <750 BAU/mL, COVID-19 progression was more common after monotherapy (23.9% vs. 0%, P=0.001), including more frequent COVID-related admission (15.2% vs. 0%, P=0.014) and seronegative persistent COVID-19 (10.9% vs. 0%, P=0.044). Combination therapy was associated with lower risk of progression (odds ratio [OR] 0.08, 95% confidence interval [95% CI] 0.01-0.64). Anti-S IgG titre <750 BAU/mL and previous anti-CD20 were associated with higher risk of progression (OR 13.70, 95% CI 2.77-67.68; and OR 3.05, 95% CI 1.20-10.94, respectively). CONCLUSIONS: In immunocompromised patients, combination therapy with sotrovimab plus an antiviral may be more effective than monotherapy for SARS-CoV2.