Search

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Kidney transplant recipients (KTRs) develop decreased antibody titers to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination compared to healthy controls (HCs), but whether KTRs generate antibodies against key epitopes associated with neutralization is unknown. Plasma from 78 KTRs from a clinical trial of third doses of SARS-CoV-2 vaccines and 12 HCs underwent phage display immunoprecipitation and sequencing (PhIP-Seq) to map antibody responses against SARS-CoV-2. KTRs had lower antibody reactivity to SARS-CoV-2 than HCs, but KTRs and HCs recognized similar epitopes associated with neutralization. Thus, epitope gaps in antibody breadth of KTRs are unlikely responsible for decreased efficacy of SARS-CoV-2 vaccines in this immunosuppressed population. Clinical Trials Registration.  NCT04969263. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background Invasive aspergillosis (IA) in immunocompromised hosts carries high morbidity and mortality. Diagnosis is often delayed because definitive diagnosis requires invasive specimen collection, while noninvasive testing with galactomannan is moderately accurate. Plasma cell-free DNA polymerase chain reaction (cfDNA PCR) represents a novel testing modality for the noninvasive diagnosis of invasive fungal disease (IFD). We directly compared the performance of Aspergillus plasma cfDNA PCR with serum galactomannan for the diagnosis of IA during routine clinical practice. Methods We conducted a retrospective study of all patients with suspected IFD who had Aspergillus plasma cfDNA PCR testing at Stanford Health Care from 1 September 2020 to 30 October 2022. Patients were categorized into proven, probable, possible, and no IA based on the EORTC/MSG definitions. Primary outcomes included the clinical sensitivity and specificity for Aspergillus plasma cfDNA PCR and galactomannan. Results Overall, 238 unique patients with Aspergillus plasma cfDNA PCR test results, including 63 positives and 175 nonconsecutive negatives, were included in this study. The majority were immunosuppressed (89.9%) with 22.3% 30-day all-cause mortality. The overall sensitivity and specificity of Aspergillus plasma cfDNA PCR were 86.0% (37 of 43; 95% confidence interval [CI], 72.7–95.7) and 93.1% (121 of 130; 95% CI, 87.4–96.3), respectively. The sensitivity and specificity of serum galactomannan in hematologic malignancies/stem cell transplants were 67.9% (19 of 28; 95% CI, 49.3–82.1) and 89.8% (53 of 59; 95% CI, 79.5–95.3), respectively. The sensitivity of cfDNA PCR was 93.0% (40 of 43; 95% CI, 80.9–98.5) in patients with a new diagnosis of IA. Conclusions Aspergillus plasma cfDNA PCR represents a more sensitive alternative to serum galactomannan for noninvasive diagnosis of IA. [ABSTRACT FROM AUTHOR]

Background Despite preventive measures, infections continue to pose significant risks to pediatric allogeneic hematopoietic cell transplantation (allo-HCT) recipients. The gut microbiota has been linked to clinical outcomes following adult allo-HCT. This study evaluated whether similar disruptions or differing microbiota patterns were associated with infection risk in pediatric allo-HCT. Methods In a prospective observational study, fecal samples were obtained from 74 children before conditioning and upon neutrophil recovery. Microbiome signatures identified through sequencing were examined for their associations with infections or acute graft-versus-host disease (aGVHD) in the first-year post-HCT using Cox proportional hazards analysis. Results Microbiome disruption in adults, did not predict infection risk in pediatric allo-HCT. Unique microbiota signatures were associated with different infections or aGVHD. A ratio of strict and facultative anaerobes (eg, Lachnoclostridium , Parabacteroides) prior to conditioning predicted bacteremia risk (Cox hazard ratio [HR], 3.89). A distinct ratio of oral (eg, Rothia , Veillonella) to intestinal anaerobes (eg, Anaerobutyricum , Romboutsia) at neutrophil recovery predicted likelihood of bacterial infections (Cox HR, 1.81) and viral enterocolitis (Cox HR, 1.96). Conclusions Interactions between medical interventions, pediatric hosts, and microbial communities contribute to microbiota signatures that predict infections. Further multicenter study is necessary to validate the generalizability of these ratios as biomarkers. [ABSTRACT FROM AUTHOR]

Introduction: Remdesivir (REM) and monoclonal antibodies (mAbs) could alleviate severe COVID-19 in at-risk outpatients. However, data on their use in hospitalized patients, particularly in elderly or immunocompromised hosts, are lacking. Methods: All consecutive patients hospitalized with COVID-19 at our unit from 1 July 2021 to 15 March 2022 were retrospectively enrolled. The primary outcome was the progression to severe COVID-19 (P/F < 200). Descriptive statistics, a Cox univariate–multivariate model, and an inverse probability treatment-weighted (IPTW) analysis were performed. Results: Overall, 331 subjects were included; their median (q1–q3) age was 71 (51–80) years, and they were males in 52% of the cases. Of them, 78 (23%) developed severe COVID-19. All-cause in-hospital mortality was 14%; it was higher in those with disease progression (36% vs. 7%, p < 0.001). REM and mAbs resulted in a 7% (95%CI = 3–11%) and 14% (95%CI = 3–25%) reduction in the risk of severe COVID-19, respectively, after adjusting the analysis with the IPTW. In addition, by evaluating only immunocompromised hosts, the combination of REM and mAbs was associated with a significantly lower incidence of severe COVID-19 (aHR = 0.06, 95%CI = 0.02–0.77) when compared with monotherapy. Conclusions: REM and mAbs may reduce the risk of COVID-19 progression in hospitalized patients. Importantly, in immunocompromised hosts, the combination of mAbs and REM may be beneficial. [ABSTRACT FROM AUTHOR]

Background Determination of the release from isolation for coronavirus disease 2019 (COVID-19) in immunocompromised patients who need additional hospitalization for treatment of non-COVID-19 related disease is important to prevent nosocomial transmission. However, there is insufficient evidence for an extended isolation period. Materials and Methods In September 2021, when the Delta variant was dominant, a nosocomial outbreak of COVID-19 occurred in the nephrology ward of a tertiary hospital in Gwangju, Korea. We conducted epidemiological investigations and whole-genome sequencing (WGS) of this virus. Results A man who underwent kidney transplantation was admitted to our hospital for the treatment of acute kidney injury. He was diagnosed with asymptomatic COVID-19 infection during a pre-admission screening test on September 1, 2021 and underwent isolation. After 10 days of isolation in the COVID-19-designated ward, he was transferred to the general nephrology ward. He underwent steroid pulse therapy (September 17 to September 23, >60 mg/day prednisolone) due to acute T-cell rejection. On September 28, 2021, the first patient with COVID-19 was identified in the nephrology ward, and a rapid-response team was activated to identify additional patients with COVID-19 and prevent the spread of COVID-19. Epidemiological investigations revealed that 12 patients, two caregivers, and three healthcare workers from the nephrology ward were diagnosed with COVID-19. The WGS of specimens from 14 nosocomial outbreak samples and released an index patient exhibited the same Delta variant originating from the B.1.617.2 lineage. This hospital-acquired COVID-19 outbreak in the nephrology ward resulted in two (11.7%) deaths in patients who underwent kidney transplantation. Conclusion We demonstrated that an immunocompromised patient can cause a nosocomial outbreak due to the prolonged shedding of infectious viruses. Prolonged isolation in patients under active immunosuppressive therapy may be necessary to prevent transmission, especially in the hospital setting. [ABSTRACT FROM AUTHOR]

Objective: We aim to describe the safety and efficacy of sotrovimab in severe cases of COVID-19 in immunocompromised hosts. Methods: We used a retrospective multicenter cohort including immunocompromised hospitalized patients with severe COVID-19 treated with sotrovimab between October 2021 and December 2021. Results: We included 32 patients. The main immunocompromising conditions were solid organ transplantation (46.9%) and hematological malignancy (37.5%). Seven patients (21.9%) had respiratory progression: 12.5% died and 9.4% required mechanical ventilation. Patients treated within the first 14 days of their symptoms had a lower progression rate: 12.0% vs. 57.1%, p = 0.029. No adverse event was attributed to sotrovimab. Conclusions: Sotrovimab was safe and may be effective in its use for immunocompromised patients with severe COVID-19. More studies are needed to confirm these preliminary data. [ABSTRACT FROM AUTHOR]

Antibody responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination are reduced in solid organ transplant recipients (SOTRs). We report that increased levels of preexisting antibodies to seasonal coronaviruses are associated with decreased antibody response to SARS-CoV-2 vaccination in SOTRs, supporting that antigenic imprinting modulates vaccine responses in SOTRs. [ABSTRACT FROM AUTHOR]

Antibiotic allergy labels (AALs) are commonly reported, with well‐defined prevalence in the general population; several studies have now focused efforts on immunocompromised hosts. Understanding the prevalence of reported allergy labels and methods of antibiotic allergy evaluation and delabeling strategies has the potential to improve prescribing practices and clinical outcomes in this high‐antibiotic use group. In this review, we will discuss the current literature on the prevalence, impact, and evaluations of AALs in immunocompromised hosts with a focus on beta‐lactam (penicillin) allergy and sulfa‐antibiotic (antimicrobial sulfurs) allergy labels. [ABSTRACT FROM AUTHOR]

Background: Solid organ transplant (SOT) recipients are at increased risk of severe outcomes associated with antimicrobial resistance (AMR). Antimicrobial stewardship programs (ASPs) play a vital role in mitigating the negative impacts of AMR. Pediatric evidence regarding ASP for SOT recipients is scarce, although many pediatric SOT centers have implemented different forms of ASP. Methods: This article summarized the available evidence relating to AMR among pediatric SOT recipients and discussed key strategies for the successful implementation of ASP among this population. The focus is primarily on antibacterial and secondarily on antifungal management. Results: The development of multidisciplinary antimicrobial stewardship teams for pediatric SOT recipients is essential for successful stewardship implementation. Key stakeholders may include but are not limited to SOT recipients and their caregivers, primary SOT teams (transplant physicians, transplant pharmacists, transplant unit nurses, and transplant outpatient care team), transplant surgery teams, transplant infectious diseases teams, hospital AST, microbiology teams, infection prevention teams, quality improvement teams, and information technology teams. Conclusion: As the evidence for optimal ASP in pediatric SOT is still evolving, it is important to measure the impact of implemented interventions. [ABSTRACT FROM AUTHOR]

Tixagevimab-cilgavimab is authorized for preexposure prophylaxis against coronavirus disease 2019 (COVID-19) in immunocompromised hosts. Herein, we report the clinical characteristics of 8 patients who developed COVID-19 soon after receiving tixagevimab-cilgavimab. This study emphasizes the need to maintain additional measures to prevent COVID-19 during periods of high severe acute respiratory syndrome coronavirus 2 transmission. [ABSTRACT FROM AUTHOR]

The Trypanosomatidae family encompasses unicellular flagellates and obligate parasites of invertebrates, vertebrates, and plants. Trypanosomatids are traditionally divided into heteroxenous, characterized by the alternation of the life cycle between an insect vector and a plant or a vertebrate host, including humans being responsible for severe diseases; and monoxenous, which are presumably unique parasites of invertebrate hosts. Interestingly, studies reporting the occurrence of these monoxenous trypanosomatids in humans have been gradually increasing, either associated with Leishmania co-infection, or supposedly alone either in immunocompromised or even more sporadically in immunocompetent hosts. This review summarizes the first reports that raised the hypothesis that monoxenous trypanosomatids could be found in vertebrate hosts till the most current reports on the occurrence of Crithidia spp. alone in immunocompetent human patients. [ABSTRACT FROM AUTHOR]

Cytomegalovirus (CMV) is a double-stranded DNA virus. It is an opportunistic infection that usually affects individuals with AIDS or with profound immunosuppression. CMV retinitis is the most frequent ocular manifestation. Infrequently, this pathology has been observed in patients undergoing immunosuppressive treatment due to autoimmune diseases. This article presents a case of Crohn's disease with systemic and ocular involvement by CMV after starting treatment with infliximab (anti-tumor necrosis factor-alpha antibody). [ABSTRACT FROM AUTHOR]

Post-hematopoietic stem cell transplant secondary solid neoplasms are uncommon and usually host-derived. We describe a 6-year-old female who developed a mixed donor-recipient origin mesenchymal stromal tumor-like lesion in the liver following an unrelated hematopoietic stem cell transplant complicated by severe graft-versus-host disease. This lesion arose early post-transplant in association with hepatic graft-versus-host disease. At 12 years post-transplant, the neoplasm has progressively shrunken in size and the patient remains well with no neoplasm-associated sequelae. This report characterizes a novel lesion of mixed origin post-transplant and offers unique insights into the contribution of bone marrow-derived cells to extra-medullary tissues. [ABSTRACT FROM AUTHOR]

We completed a real-world analysis of 498 consecutive high-risk nonimmunocompromised and immunocompromised patients who received sotrovimab during the B.1.1.529 surge. Emergency department visits/hospitalizations and 30-day all-cause mortality between the 2 groups were similar. When administered early, sotrovimab is effective at preventing coronavirus disease 2019 progression in immunocompromised and nonimmunocompromised patients. [ABSTRACT FROM AUTHOR]

Serial galactomannan (GM) monitoring can aid the diagnosis of invasive aspergillosis (IA) and optimise treatment decisions. However, widespread adoption of mould-active prophylaxis has reduced the incidence of IA and challenged its use. We evaluated the cost-effectiveness of prophylaxis-biomarker strategies. A Markov model simulating high-risk patients undergoing routine GM surveillance with mould-active versus non-mould-active prophylaxis was constructed. The incremental cost for each additional quality-adjusted life-year (QALY) gained over a lifetime horizon was calculated. In 40- and 60-year-old patients receiving mould-active prophylaxis coupled with routine GM surveillance, the total cost accrued was the lowest at SGD 11,227 (USD 8255) and SGD 9234 (USD 6790), respectively, along with higher QALYs gained (5.3272 and 1.1693). This strategy, being less costly and more effective, dominated mould-active prophylaxis with no GM monitoring or GM surveillance during non-mould-active prophylaxis. The prescription of empiric antifungal treatment was influential in the cost-effectiveness. When the GM test sensitivity was reduced from 80% to 30%, as might be anticipated with the use of mould-active prophylactic agents, the conclusion remained unchanged. The likelihood of GM surveillance with concurrent mould-active prophylaxis being cost-effective was 77%. Routine GM surveillance remained cost-effective during mould-active prophylaxis despite lower IA breakthroughs. Cost-saving from reduced empirical antifungal treatment was an important contributing factor. [ABSTRACT FROM AUTHOR]

Background Immune checkpoint inhibitors (ICIs) have revolutionized nonsmall cell lung cancer (NSCLC) treatment and significantly increased overall survival of patients. However, the incidence of concurrent infections and their management is still debated. Methods From August 2015 to October 2019, all consecutive patients with NSCLC who received nivolumab or pembrolizumab as first- or second-line therapy were retrospectively evaluated. At the time of analysis all patients had died. Clinical characteristics of patients, type of infections, and predictors of mortality were analyzed. Results A total of 118 patients were identified: 74 in the nivolumab group and 44 in the pembrolizumab group. At least 1 infection was recorded in 22% of the nivolumab-group versus 27% of the pembrolizumab-group (P  = .178). In both groups, the main infection was pneumonia, followed by skin and soft tissue infections, urinary tract infections, and gastroenteritis. Crude mortality for first infection was 10.7%, followed by 25% and 40% for the second and third recurrence, respectively (p for trend = .146). No opportunistic infections were recorded. It is notable that, by Cox-regression model, the independent predictor of mortality was a higher Eastern Cooperative Oncology Group performance status at baseline (P  < .001), whereas the multidisciplinary diagnosis and treatment of concurrent infections was associated with a reduced probability of mortality (adjusted hazard ratio = 0.50; 95% confidence interval = 0.30–0.83; P  < .001). Conclusions In patients with NSCLC treated with ICIs, multidisciplinary management of concurrent infections may reduce the risk of mortality. Further studies to investigate risk factors for infections, as well as appropriate management strategies and preventive measures in this setting, are warranted. [ABSTRACT FROM AUTHOR]

Classic Hodgkin lymphoma (CHL) is the rarest post-transplant lymphoproliferative disorder (PTLD) subtype. Few cases of patients with metachronous discordant PTLD episodes including CHL-PTLD have been reported, but the incidence of and risk factors for this phenomenon are unknown. Patients with CHL-PTLD were identified from an institutional PTLD database. Of 13 patients identified with CHL-PTLD six (46%) had antecedent non-CHL-PTLD: three had polymorphic PTLD, two monomorphic PTLD, and one nondestructive PTLD. Patients with prior metachronous non-CHL-PTLD were younger at transplant and had a longer latency time to CHL-PTLD post-transplant. The prevalence of EBV seronegativity at transplant was high in both groups, but prolonged high-level EBV DNAemia only occurred in some with metachronous non-CHL-PTLD. In conclusion, patients with CHL-PTLD have metachronous non-CHL-PTLD diagnoses with discordant histology more commonly than previously recognized. Primary EBV infection with chronically elevated EBV viral loads may represent unique risk factors for CHL-PTLD following an initial non-CHL-PTLD event. [ABSTRACT FROM AUTHOR]

BACKGROUND: Community-acquired pneumonia (CAP) in autoimmune diseases (AID)-induced immunocompromised host (ICH) had a high incidence and poor prognosis. However, only a few studies had determined the clinical characteristics of these patients. Our study was to explore the characteristics and predictors of mortality in CAP patients accompanied with AID-induced ICH. METHODS: From 2013 to 2018, a total of 94 CAP patients accompanied with AID-induced ICH, admitted to Emergency Department of Zhongshan Hospital, Fudan University, were enrolled in this study. Clinical data and the risk regression estimates of repeated predictors were evaluated by generalized estimating equations (GEEs) analysis. An open-cohort approach was used to classify patient's outcomes into the survival or non-survival group. RESULTS: The hospital mortality of patients with CAP occurring in AID-induced ICH was 60.64%. No significant differences were found with respect to clinical symptoms and lung images between survival and non-survival groups, while renal insufficiency and dysfunction of coagulation had higher proportions in non-survival patients (P<0.05). Both noninvasive ventilation (NIV) and invasive mechanical ventilation (IMV) were performed more frequently in non-survival group (P< 0.05). By the multivariate GEEs analysis, the repeated measured longitudinal indices of neutrophilto-lymphocyte ratio (NLR) (odds ratio [OR]=1.055, 95% confidence interval [95%CI] 1.025-1.086), lactate dehydrogenase (LDH) (OR=1.004, 95%CI 1.002-1.006) and serum creatinine (sCr) (OR=1.018, 95%CI 1.008-1.028), were associated with a higher risk of mortality. CONCLUSION: The CAP patients in AID-induced ICH had a high mortality. A signifi cant relationship was demonstrated between the factors of NLR, LDH, sCr and mortality risk in these patients. [ABSTRACT FROM AUTHOR]

The effect of Lactobacillus rhamnosus CRL1505 (Lr) on macrophages (Ma) and dendritic cells (DC) in the orchestration of anti-pneumococcal immunity was studied using malnutrition and pneumococcal infection mouse models. Monocytes (Mo), Ma, and DC in two groups of malnourished mice fed with balanced diet (BCD) were studied through flow cytometry; one group was nasally administered with Lr (BCD+Lr group), and the other group was not (BCD group). Well-nourished (WNC) and malnourished (MNC) mice were used as controls. Malnutrition affected the number of respiratory and splenic mononuclear phagocytes. The BCD+Lr treatment, unlike BCD, was able to increase and normalize lung Mo and Ma. The BCD+Lr mice were also able to upregulate the expression of the activation marker MHC II in lung DC and to improve this population showing a more significant effect on CD11b+ DC subpopulation. At post-infection, lung Mo values were higher in BCD+Lr mice than in BCD mice and similar to those obtained in WNC group. Although both repletion treatments showed similar values of lung Ma post-infection, the Ma activation state in BCD+Lr mice was higher than that in BCD mice. Furthermore, BCD+Lr treatment was able to normalize the number and activation of splenic Ma and DC after the challenge. Lr administration stimulates respiratory and systemic mononuclear phagocytes. Stimulation of Ma and DC populations would increase the microbicide activity and improve the adaptive immunity through its antigen-presenting capacity. Thus, Lr contributes to improved outcomes of pneumococcal infection in immunocompromised hosts. [ABSTRACT FROM AUTHOR]

Background: Varicella-zoster virus (VZV) causes herpes zoster. Pneumocystis jirovecii (PJ) also causes pneumonia in immunocompromised hosts. Although both cause opportunistic infections, it is rare to have a co-infection in a non-human immunodeficiency virus carrier.Case Presentation: An 84-year-old woman with hemolytic anemia referred because of acute respiratory failure. She had received prednisolone without PJ pneumonia prevention. She developed dyspnea and desaturation while eating, and thus was treated based on a presumptive diagnosis of aspiration pneumonia. Physical examination revealed a vesicular rash on the left side of her neck suggesting herpes zoster infection. Polymerase chain reaction of her sputum for PJ and VZV was positive, which confirmed a diagnosis of pneumonia due to PJ and VZV co-infection. Despite acyclovir and sulfamethoxazole and trimethoprim administration, she died on hospital day 19.Conclusions: Clinicians should suspect PJP when patients on systemic corticosteroids develop pneumonia and they have not received prophylactic treatment for PJP in non-HIV carriers. When such patients have a VZV rash, clinicians should aggressively seek signs of opportunistic infections. Our case hereby highlights the importance of recognizing the possibility of a VZV and PJ co-infection. [ABSTRACT FROM AUTHOR]

Introduction: Trichosporon asahii is an emerging cause of systemic fungal infection in an immunocompromised host. Several life threatening disseminated T. asahii infection in single solid organ (liver or kidney) transplant recipients, in neutropenic and hematological malignancy patients have been reported. Case presentation (Methods and Results): A 49‐year old gentleman who underwent simultaneous living‐donor liver transplantation (donor sister) and kidney transplant (donor wife) developed fever and subsegmental patchy consolidation with right sided pleural effusion on fourth postoperative day. Central line blood stream infection was suspected. Blood culture grew creamy white colonies of T. asahii on blood agar with characteristic dirty‐green colonies on CHROMagar. Laboratory analysis of pleural fluid also revealed budding yeast cells identified as T. asahii. Microscopy of the isolates showed hyphae, arthroconidia, and blastospores. The isolates were identified as T. asahii by VITEK MS which uses matrix‐assisted laser desorption/ionization time‐of‐flight (MALDI‐TOF) technology. Initially liposomal amphotericin B and micafungin was initiated, but due to lack of clinical and microbiological response, patient was switched to voriconazole. Simultaneously, tacrolimus doses were reduced to one‐third in view of interaction with voriconazole. Subsequently, patient improved with resolution of fever and microbiological cure. Conclusion: This is the first case report of disseminated T. asahii infection in a combined liver‐kidney transplant recipient successfully treated with voriconazole. Azole antifungal are the promising drug of choice for systemic T. asahii infection. Drug interactions should be considered while using these antifungal agents. [ABSTRACT FROM AUTHOR]

Sporotrichosis is a global implantation or subcutaneous mycosis caused by several members of the genus Sporothrix, a thermo-dimorphic fungus. This disease may also depict an endemic profile, especially in tropical to subtropical zones around the world. Interestingly, sporotrichosis is an anthropozoonotic disease that may be transmitted to humans by plants or by animals, especially cats. It may be associated with rather isolated or clustered cases but also with outbreaks in different periods and geographic regions. Usually, sporotrichosis affects immunocompetent hosts, presenting a chronic to subacute evolution course. Less frequently, sporotrichosis may be acquired by inhalation, leading to disseminated clinical forms. Both modes of infection may occur in immunocompromised patients, especially associated with human immunodeficiency virus (HIV) infection, but also diabetes mellitus, chronic alcoholism, steroids, anti-TNF treatment, hematologic cancer and transplanted patients. Similar to other endemic mycoses caused by dimorphic fungi, sporotrichosis in immunocompromised hosts may be associated with rather more severe clinical courses, larger fungal burden and longer periods of systemic antifungal therapy. A prolonged outbreak of cat-transmitted sporotrichosis is in progress in Brazil and potentially crossing the border to neighboring countries. This huge outbreak involves thousands of human and cats, including immunocompromised subjects affected by HIV and FIV (feline immunodeficiency virus), respectively. We reviewed the main epidemiologic, clinical, diagnostic and therapeutic aspects of sporotrichosis in immunocompromised hosts. [ABSTRACT FROM AUTHOR]

Background: Stenotrophomonas maltophilia ubiquitously occurs in the hospital environment. This opportunistic pathogen can cause severe infections in immunocompromised hosts such as hematopoietic stem cell transplantation (HSCT) recipients. Between February and July 2016, a cluster of four patients on the HSCT unit suffered from S. maltophilia bloodstream infections (BSI). Methods: For epidemiological investigation we retrospectively identified the colonization status of patients admitted to the ward during this time period and performed environmental monitoring of shower heads, shower outlets, washbasins and toilets in patient rooms. We tested antibiotic susceptibility of detected S. maltophilia isolates. Environmental and blood culture samples were subjected to whole genome sequence (WGS)-based typing. Results: Of four patients with S. maltophlilia BSI, three were found to be colonized previously. In addition, retrospective investigations revealed two patients being colonized in anal swab samples but not infected. Environmental monitoring revealed one shower outlet contaminated with S. maltophilia. Antibiotic susceptibility testing of seven S. maltophlia strains resulted in two trimethoprim/sulfamethoxazole resistant and five susceptible isolates, however, not excluding an outbreak scenario. WGS-based typing did not result in any close genotypic relationship among the patients' isolates. In contrast, one environmental isolate from a shower outlet was closely related to a single patient's isolate. Conclusion: WGS-based typing successfully refuted an outbreak of S. maltophilia on a HSCT ward but uncoverd that sanitary installations can be an actual source of S. maltophilia transmissions. [ABSTRACT FROM AUTHOR]

Iron‐oxide nanoparticles (IONPs) have been widely favoured due to their biodegradable, low cytotoxic effects and having reactive surface which can be altered with biocompatible coatings. Considering various medical applications of IONPs, the authors were encouraged to study whether IONPs could be effective against fungal infections caused by Candida species. In this study, IONPs were characterised by scanning electron microscopy, X‐ray diffraction, Fourier transform infrared spectroscopy and vibrating sample magnetometer. The goal of this study was to evaluate the antifungal activity of IONPs against different Candida spp. compared with fluconazole (FLC). IONPs were spherical with the size of 30–40 nm. The minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) values of IONPs ranged from 62.5 to 500 µg/ml and 500 to 1000 μg/ml, respectively. The MIC and MFC of FLC were in range of 16–128 μg/ml and 64–512 μg/ml, respectively. The growth inhibition value indicated that Candida tropicalis, Candida albicans and Candida glabrata spp. were most susceptible to IONPs. The finding showed that the IONPs possessed antifungal potential against pathogenic Candida spp. and could inhibit the growth of all the tested Candida spp. Further studies, both in vitro and in vivo (including susceptibility, toxicity, Probability of kill (PK) and efficacy studies) are needed to determine whether IONPs are suitable for medicinal purposes. [ABSTRACT FROM AUTHOR]

Background. Infections by multidrug-resistant Pseudomonas aeruginosa (MDRPa) are an important cause of morbidity and mortality in patients after allogeneic hematopoietic stem cell transplantation (HSCT). Humid environments can serve as a reservoir and source of infection by this pathogen. To minimize the risk of infection from these reservoirs, we performed extensive remodeling of sanitation and water installations as the focus of our hygiene bundle. Methods. During the reconstruction of our transplantation unit (April 2011–April 2014) we implemented several technical modifications to reduce environmental contamination by and subsequent spreading of MDRPa, including a newly designed shower drain, disinfecting siphons underneath the sinks, and rimless toilets. During a 3-year study period (2012–2014), we tracked the number of patients affected by MDRPa (colonized and/or infected) and the outcome of infected patients, and monitored the environmental occurrence of this pathogen. We further performed whole-genome sequencing of nosocomial MDRPa strains to evaluate genotypic relationships between isolates. Results. Whereas 31 (9.2%; 18 colonized, 13 infected) patients were affected in 2012 and 2013, the number decreased to 3 in 2014 (17%; 3 colonized, 0 infected). Lethality by MDRPa similarly decreased from 3.6% to 0%. Environmental detection of MDRPa decreased in toilets from 18.9% in 2012–2013 to 6.1% in the following year and from 8.1% to 3.0%, respectively, in shower outlets. Whole-genome sequencing showed close relationships between environmental and patient-derived isolates. Conclusions. Hospital construction measures aimed at controlling environmental contamination by and spread of MDRPa are effective at minimizing the risk of highly lethal MDRPa infections. [ABSTRACT FROM AUTHOR]

The number of granulocytes is maintained by a regulated balance between granulopoiesis in the bone marrow and clearance and destruction in peripheral tissues. Granulopoiesis plays a fundamental role in the innate immune response. Therefore, factors affecting the normal granulopoiesis lead to alterations in innate defenses and reduce the resistance against infections. In this study, we give a description on recent advances regarding the molecular and cellular events that regulate steady-state and emergency granulopoiesis, which are crucial processes for the generation of protective innate immune responses. Particular attention will be given to emergency granulopoiesis alterations in immunosuppression states caused by malnutrition and chemotherapy. The role of microbiota in maintaining a steady-state granulopoiesis and the immunological mechanisms involved are also discussed. Moreover, we describe the findings of our laboratory demonstrating that the dietary supplementation with immunobiotics is an interesting alternative to improve steady-state and emergency granulopoiesis, the respiratory innate immune response, and the resistance against respiratory pathogens in immunocompromised hosts. [ABSTRACT FROM AUTHOR]

Strongyloides stercoralis, an intestinal parasitic nematode, infects more than 100 million people worldwide. Strongyloides are unique in their ability to exist as a free-living and autoinfective cycle. Strongyloidiasis infection usually remains asymptomatic, but in immunocompromised hosts hyperinfection and dissemination can occur, which has a high mortality. We report a 30-year-old male patient with membranous nephropathy who was receiving oral corticosteroids and cyclophosphamide who presented with disseminated strongyloidiasis. Larvae of S. stercoralis were isolated from the stool and the sputum specimens. Seven days later despite anti-helminthic therapy and intensive care support the patient died. Early detection and diagnosis of this condition is based on a high index of clinical suspicion, especially in immunocompromised hosts. Screening for Strongyloidiasis infection before the initiation of immunosuppressive therapy can be considered. [ABSTRACT FROM AUTHOR]

Objectives: To correlate the microbiological and clinical features of infections caused by Nocardia species. Methods: We determined the species and drug susceptibility of 138 Nocardia strains isolated from 132 patients at the University of Texas M. D. Anderson Cancer Center (Houston, TX) from 2002 through 2012 and analyzed the clinical features. Results: The 132 patients included 82 men and 50 women with a mean age of 59.1 years. All except two had underlying cancer, and 47 (35.6%) also received a stem cell transplant. These patients experienced 136 episodes of Nocardia infection, including pulmonary infection, abscess of deep skin and soft tissue, bacteremia and dissemination, and brain abscess. The 138 Nocardia strains involved 27 species, of which 20 species have been described since 2000. Common species included Nocardia nova, Nocardia cyriacigeorgica, Nocardia farcinica, and Nocardia abscessus, together accounting for 59.4%. N nova caused most bacteremia cases, whereas N farcinica caused most of the skin and brain infections. Infections with a few recent species likely represented first confirmation or report of human infections. Antimicrobial susceptibility tests of 117 strains showed that they were all susceptible to trimethoprim-sulfamethoxazole and linezolid but variably susceptible to other drugs depending on species. Most patients who were treated for the infection showed improvement or resolution. Conclusions: Diverse Nocardia species can cause secondary infections in patients with cancer. Timely species identification and antimicrobial susceptibility tests may guide treatment. [ABSTRACT FROM AUTHOR]

We summarize the current knowledge of the epidemiology of carbapenem-resistant Enterobacteriaceae infections in transplant recipients and patients with hematologic malignancies, and provide recommendations for antimicrobial therapy and strategies to minimize this emerging threat in these vulnerable populations.Carbapenem-resistant Enterobacteriaceae (CRE) are emerging global pathogens. The spread of CRE to transplant recipients and patients with hematologic malignancies has ominous implications. These patients rely on timely, active antibacterial therapy to combat gram-negative infections; however, recommended empirical regimens are not active against CRE. Approximately 3%–10% of solid organ transplant (SOT) recipients in CRE-endemic areas develop CRE infection, and the infection site correlates with the transplanted organ. Mortality rates associated with CRE infections approach 40% in SOT recipients and 65% in patients with hematologic malignancies. Given that the current antimicrobial armamentarium to combat CRE is extremely limited, a multifaceted approach that includes antimicrobial stewardship and active surveillance is needed to prevent CRE infections in immunocompromised hosts. Improving outcomes of established infections will require the use of risk factor–based prediction tools and molecular assays to more rapidly administer CRE-active therapy and the development of new antimicrobial agents with activity against CRE. [ABSTRACT FROM PUBLISHER]

Pathogenic fungi have substantial effects on global biodiversity, and 2 emerging pathogenic species-the chytridiomycete Batrachochytrium dendrobatidis, which causes chytridiomycosis in amphibians, and the ascomycete Geomyces destructans, which causes white-nose syndrome in hibernating bats-are implicated in the widespread decline of their vertebrate hosts. We synthesized current knowledge for chytridiomycosis and white-nose syndrome regarding disease emergence, environmental reservoirs, life history characteristics of the host, and host-pathogen interactions. We found striking similarities between these aspects of chytridiomycosis and white-nose syndrome, and the research that we review and propose should help guide management of future emerging fungal diseases. [ABSTRACT FROM AUTHOR]

Background: Invasive fungal infections cause considerable morbidity and mortality in immunocompromised hosts. Pigeon droppings could especially be a potential carrier in the spread of pathogenic yeasts and mold fungi into the environment. The objective of this study was to isolation of Cryptococcus neoformans and other opportunistic fungi from pigeon droppings. Materials and Methods: One hundred twenty samples of pigeon droppings were suspended 1:10 in saline solution and then cultured. Identification of C. neoformans was performed on bird seed agar, presence of a capsule on India ink preparation, urease production on urea agar medium and RapID yeast plus system. The identification of candida species was based on micro‑morphological analysis on corn meal‑Tween 80 agar, RapID yeast plus system and growth in CHROMagar candida. The identification of other fungi was based on macromorphologic, microscopic, biochemical and physiological characteristics. Results: The highest frequency of yeasts and mold fungi were observed in Candida albicans 6.6% and Penicillium spp. 25%. The frequency rate of C. neoformans isolation was 2.5%. Conclusion: Several types of fungi are present in pigeon droppings that can spread in environment and transmit to children and elderly as well as immunocompromised patients who are at increased risk of contracting opportunistic diseases. [ABSTRACT FROM AUTHOR]

Molecular method of 16S rRNA sequencing is reported to be helpful in the accurate identification of organisms with ambiguous phenotypic profiles. We analyzed the use of 16S rRNA sequencing method to identify clinically significant, 'difficult-to-identify' bacteria recovered from clinical specimens, and evaluated its role in patient management and consequent clinical outcome. Among the 172 'difficult-to-identify' bacteria recovered over a 4-year period, 140 were gram-positive cocci or gram-negative bacilli; identification by 16S rRNA did not play a role in the management of patients infected with these bacteria. From 32 patients, 33 'difficult-to-identify' gram-positive bacilli were identified; the organisms were mycobacteria, N ocardia, T sukamurella, R hodococcus, and G ordonia. In 24 patients for whom clinical data were available, results from the 16S rRNA sequencing method led to treatment change in 14 immunocompromised patients (including 7 hematopoietic stem cell recipients and 1 liver transplant recipient). Therapy was modified in 9 patients, initiated in 3 patients, and discontinued in 2 patients. Most patients' therapy was switched to oral antibiotics with discontinuation of intravascular catheters, facilitating early hospital discharge. All 14 patients were alive 30 days after infection onset. The present study demonstrates the clinical application of 16S rRNA sequencing method to identify 'difficult-to-identify' mycobacteria and other gram-positive bacilli in clinical specimens, particularly in immunocompromised hosts. [ABSTRACT FROM AUTHOR]

Liposomal amphotericin B is a "true" liposomal formulation of amphotericin B with greatly reduced nephrotoxicity and minimal infusion-related toxicity. This broad spectrum polyene is well tolerated and effective against most invasive fungal infections. In view of the current limitations on diagnostic capability of invasive fungal infections, most clinicians are often compelled to use antifungal drugs in an empiric manner; liposomal amphotericin B continues to play an important role in the empiric management of invasive fungal infections, despite the recent availability of several other drugs in the azole and echinocandin classes. [ABSTRACT FROM AUTHOR]

Pulmonary mycoses are among the most feared infections encountered in immunocompromised patients. The problem is amplified by the increasing numbers of chronically immunocompromised patients that have substantially increased both the prevalence and clinical severity of infections caused by fungi. Moreover, fungal infections in this patient population pose challenges in diagnosis and management. Fortunately, recent advances in diagnostics and antifungal therapy, and their direct application to specific diseases, provide important new approaches to this complex and often seriously ill patient population. In this article we review the commonly occurring pulmonary fungal infections in the immunocompromised population with a particular focus on their management. [ABSTRACT FROM PUBLISHER]

The spectrum of invasive fungal infections (IFIs) continues to evolve with the emergence of rare and resistant fungal pathogens. Clinicians are faced with difficult diagnostic and treatment challenges in the management of immunocompromised patients at high risk of developing IFIs. Early and appropriate antifungal therapy is essential for a successful outcome when treating invasive mycoses. The armamentarium of antifungal drugs continues to grow; the three main classes of commonly administered drugs are the polyenes, azoles and echinocandins. The newer triazoles and the echinocandins have changed primary treatment options for some fungal infections, such as aspergillosis and candidiasis. However, despite their toxic potential, the oldest antifungal drugs, polyenes, remain useful in the treatment of IFIs because of their broad-spectrum activity, low rates of resistance and established clinical record, particularly in immunocompromised patients with breakthrough fungal infections. This review highlights important issues in the treatment of IFIs for consideration by clinicians. [ABSTRACT FROM PUBLISHER]

Severe burns result in T lymphocyte specific immunologic changes. In addition to decreased levels of circulating lymphocytes, changes in cytokine secretion and receptor expression also take place. Our finer understanding of the inflammatory response has led to the development of immune-targeted therapeutics, requiring specialized gene-expression monitoring. The emerging field of bio-micro-electromechanical systems can be used to isolate highly pure T lymphocytes in a clinically relevant and timely manner for downstream genomic analysis. Blood samples from healthy volunteers and burn-injured patients were introduced into microfluidic devices developed in our laboratory. Utilizing cell-affinity chromatography for positive selection of T lymphocytes, the devices served as a platform for RNA extraction and downstream cytokine analysis via quantitative real-time polymerase chain reaction (PCR). From a 0.5-mL whole blood sample, the microfluidic devices captured highly pure T lymphocytes from healthy volunteers and burn-injured patients. Cell capture was of sufficient quantity, and extracted RNA was of sufficient quality, for evaluating the gene expression of cytokines: interferon-gamma, interleukin-2, interleukin-4, and interleukin-10. Microfluidics is a useful tool in processing blood from burn-injured patients. Though in its very early stages of development, cell-specific information obtained by this platform/technology will likely be an important component of near-patient molecular diagnostics and personalized medicine. Clin Trans Sci 2011; Volume 4: 63-68 [ABSTRACT FROM AUTHOR]

We describe 2 transplant patients with herpes simplex virus (HSV) hepatitis who were minimally symptomatic throughout their illness. The spectrum of disease caused by HSV hepatitis is more variable than previously reported in this population. HSV hepatitis should be considered in immunocompromised hosts with elevated transaminases without evidence of fulminant hepatic necrosis. [ABSTRACT FROM AUTHOR]

Necrotizing fasciitis is an uncommon but life-threatening complication in immunocompromised hosts. We reported four patients with rheumatic diseases complicated by necrotizing fasciitis and reviewed 14 others from literature search. Most patients were on corticosteroid treatment. Septic shock, disseminated intravascular coagulopathy and acute renal deterioration were common giving rise to an overall mortality rate of 27.8%. Septic arthritis may also complicate the condition. Statistical analysis on the series showed the lack of major surgical debridement as the only risk factor associated with increased mortality (RR 7.5, 95% CI 2.1–27.3, P = 0.01). Timely debridement of necrotic tissue is important for reducing mortality. [ABSTRACT FROM AUTHOR]

is an important but often overlooked opportunistic infection agent in immunocompromised hosts. Nocardiosis is primarily pulmonary; central nervous system involvement, usually in the form of brain abscess, is less common. Primary nocardial meningitis without associated brain abscess and pulmonary lesion is extremely rare and poses a formidable diagnostic challenge. We report on a patient with systemic lupus erythematosus who presented with a clinical picture of chronic meningitis which failed to respond to empirical antibiotic treatment. She deterioriated and succumbed. Post-mortem examination showed nocardial meningitis without associated brain abscesses. Nocardial meningitis should be considered a differential diagnosis of subacute meningitis in immunocompromised hosts. [ABSTRACT FROM PUBLISHER]

ABSTRACT- Liver biopsies of six previously normal hosts (Group I, NH), with recent or acute CMV infection, and autopsy liver samples of four immunocompromised hosts (Group II, ICH) with overwhelming CMV infection have been studied in an occasional survey. In both groups, portal tract involvement, bile duct inflammation, liver cell degeneration and parenchymal granulomas were present. In Group I, a randomly distributed hepatitis with predominant involvement of the periportal areas was present, including sinusoidal arrays of lymphocytes and lymphohistiocytic aggregates. In contrast, in Group II liver cell damage was more extensive and the inflammatory infiltration only scarce. Intracellular viral inclusion bodies were found only in Group II, both in liver cells and in bile duct epithelium. Morphologically, the presence of viral inclusion bodies correlated well with the immunohistologic demonstration of CMV specific 'late' (CMV-LA) or structural antigens. In addition, CMV-specific 'early' (CMV-EA) or non-structural antigens were present in liver cell nuclei of 2/6 NH and 2/4 ICH. The possible relations between the inflammation and the lack of structural antigenic viral expression are discussed. It is concluded that ICH with CMV infection have a prominent cytopathogenic effect and widespread lytic viral infection in the liver in the absence of adequate immunologic reactivity, whereas the opposite is found in NH. [ABSTRACT FROM AUTHOR]

Cefiderocol is a new cephalosporin displaying against extensively resistant (XDR) Gram-negative bacteria. We report our experience with cefiderocol-based combination therapies as "rescue" treatments in immunocompromised or critically ill patients or in patients with post-surgical infections who had failed previous regimens. A total of 13 patients were treated from 1 September 2020 to 31 March 2021. In total, 5/13 (38%) patients were classified as critically ill, due to severe COVID-19 lung failure; 4/13 (31%) patients had post-surgical infections and 4/13 (31%) had severe infections in immunocompromised subjects due to solid organ transplantation (2/4) or hematological malignancy (2/4). Overall, 10/13 infections were caused by carbapenem-resistant Acinetobacter baumannii, one by KPC-positive ceftazidime/avibactam-resistant Klebsiella pneumonia and two by Pseudomonas aeruginosa XDR. Based on clinical, microbiological and hematobiochemical evaluation, cefiderocol was associated with different companion drugs, particularly with fosfomycin, high-dose tigecycline and/or colistin. Microbiological eradication was achieved in all cases and the 30-day survival rate was 10/13; two patients died due to SARS-CoV-2 lung failure, whereas one death was attributed to subsequent infections. No recurrent infections within 30 days were reported. Finally, we hereby discuss the therapeutic potential of cefiderocol and the possible place in the therapy of this novel drug. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "Mycobacterium mucogenicum infections in immunocompromised hosts" by S. Chalkias and colleagues in the 2014 issue.

Invasive fungal disease (IFD), predominantly aspergillosis, is associated with significant morbidity and mortality in immunocompromised patients, especially those with haematological malignancies and recipients of allogeneic haematopoietic stem cell transplantation. There has been a great deal of scientific debate as to the effectiveness of antifungal prophylaxis in preventing infection in different patient groups and in which patients it is an appropriate management option. Deciding on an appropriate prophylaxis regimen for IFD is challenging as the incidence varies among different patient groups, due to the varied nature of their underlying haematological disease, and in different regions and centres. Attempts have been made to define risk factors and include them in treatment protocols. Impaired immune status of the patient, especially neutropenia, is a key risk factor for IFD and can sometimes be related to specific polymorphisms of genes controlling innate immunity. Risk factors also vary according to the type of fungal pathogen. Consequently, prophylaxis needs to be tailored to individual patient groups. Furthermore, the choice of antifungal agent for prophylaxis depends on the potential for drug–drug interactions with the patients' concomitant medications. Additional challenges are optimal timing of antifungal prophylaxis, when to change from prophylaxis to antifungal treatment and how to prevent recurrence of IFD. This article considers the use of antifungal prophylaxis for patients at risk of IFD in daily clinical practice, with clinical profiles that may be distinct from those covered by guidelines, and aims to provide practical advice for treatment of these patient groups. [ABSTRACT FROM PUBLISHER]

Implementation of evidence-based guidelines for the treatment of invasive fungal disease (IFD) requires collaboration among numerous clinical and laboratory services, as partners in patient care. The multidisciplinary team (MDT) approach has emerged as a way of providing comprehensive medical care by bringing together professionals from a wide range of disciplines in a coordinated and effective manner. Here, we propose an MDT model for IFD management aimed at facilitating communication among consultants, adherence to clinical pathways and optimized use of resources available at each centre. [ABSTRACT FROM PUBLISHER]