Non-neutropenic Patients Research Articles

Seroprevalence and prognostic value of Aspergillus-specific IgG among non-neutropenic invasive pulmonary aspergillosis patients: a prospective multicenter study

BackgroundThis study aimed to assess the diagnostic and prognostic value of Aspergillus-specific IgG (Asp-IgG) for invasive pulmonary aspergillosis (IPA) in non-neutropenic non-hematologic patients.MethodsBetween November 2019 and February 2022, we recruited 40 non-neutropenic, non-hematologic IPA patients from Taiwan and measured serum Asp-IgG levels using Phadia, Thermofisher. A positive Asp-IgG test was defined as a level > 40 mgA/L. We evaluated the association between Asp-IgG levels and overall survival, as well 90-day mortality rate of IPA patients.ResultsOf the 40 participants, 11 (27.5%) tested positive for Asp-IgG, while 16 (40%) had positive galactomannan antigen (optical density > 1). Higher Asp-IgG levels were associated with improved overall survival (HR: 0.22, 95% CI: 0.05–0.99, p = 0.035) in multivariable Cox regression. The overall 90-day mortality rate was 65% (26/40). We found that patients with low Asp-IgG levels (≤ 40 mgA/L) had a borderline higher 90-day mortality rate compared to patients with high Asp-IgG levels (OR: 3.15, 95% CI: 0.75–13.28, p = 0.118). Stratifying by serum galactomannan and Aspergillus IgG levels, patients with elevated serum GM and low Asp-IgG had the highest 90-day mortality (80%, 8/10), followed by patients with low serum GM and low Asp-IgG (68.4%, 13/19).ConclusionsAsp-IgG was positive in approximately one-fourth of non-neutropenic IPA patients. Asp-IgG may hold potential as a clinical prognostic factor for IPA. Further studies are required to validate this finding.

Rezafungin versus caspofungin for patients with candidaemia or invasive candidiasis in the intensive care unit: pooled analyses of the ReSTORE and STRIVE randomised trials

BackgroundRezafungin is an echinocandin approved in the US and EU to treat candidaemia and/or invasive candidiasis. This post-hoc, pooled analysis of the Phase 2 STRIVE and Phase 3 ReSTORE trials assessed rezafungin versus caspofungin in patients with candidaemia and/or invasive candidiasis (IC) in the intensive care unit (ICU) at randomisation.MethodsSTRIVE and ReSTORE were randomised double-blind trials in adults with systemic signs and mycological confirmation of candidaemia and/or IC in blood or a normally sterile site ≤ 96 h before randomisation. Data were pooled for patients in the ICU at randomisation who received intravenous rezafungin (400 mg loading dose then 200 mg once weekly) or caspofungin (70 mg loading dose then 50 mg once daily) for ≤ 4 weeks. Outcomes were Day 30 all-cause mortality (primary outcome), Day 5 and 14 mycological eradication, time to negative blood culture, mortality attributable to candidaemia/invasive candidiasis, safety, and pharmacokinetics.ResultsOf 294 patients in STRIVE/ReSTORE, 113 were in the ICU at randomisation (rezafungin n = 46; caspofungin n = 67). At baseline, ~ 30% of patients in each group had impaired renal function and/or an Acute Physiologic Assessment and Chronic Health Evaluation II score ≥ 20. One patient (in the caspofungin group) was neutropenic at baseline. Day 30 all-cause mortality was 34.8% for rezafungin versus 25.4% for caspofungin. Day 5 and 14 mycological eradication was 78.3% and 71.7% for rezafungin versus 59.7% and 65.7% for caspofungin, respectively. Median time to negative blood culture was 18 (interquartile range, 12.6–43.0) versus 38 (interquartile range, 15.9–211.3) h for rezafungin versus caspofungin (stratified log-rank P = 0.001; nominal, not adjusted for multiplicity). Candidaemia/IC-attributable deaths occurred in two rezafungin patients versus one caspofungin patient. Safety profiles were similar between groups. Overall, 17.4% (rezafungin) versus 29.9% (caspofungin) of patients discontinued due to treatment-emergent adverse events. Rezafungin exposure following the initial 400-mg dose was comparable between patients in the ICU at randomisation (n = 50) and non-ICU patients (n = 117).ConclusionsRezafungin was well tolerated and efficacious in critically ill, mainly non-neutropenic patients with candidaemia and/or IC. This analysis provides additional insights into the efficacy and safety of rezafungin in the ICU population.

Evaluation of colonization index and (1,3)- ß- D glucan as diagnostic tools of invasive candidiasis in a pediatric Intensive Care Unit

PurposeThe study aimed to evaluate the corrected colonization index (CCI) and (1, 3)-ß-D Glucan (BDG) in diagnosis of Invasive Candidiasis (IC) in critically ill pediatric patients. MethodsA prospective observational study in a tertiary care (PICU) were surveyed for Candida colonization and CCI was calculated. For cases with suspicious clinical presentation, samples were cultured, and double(1,3) ß-D- glucan (BDG) performed. ResultsAccording to the European Organization for Research and Treatment of Cancer EORTC case definition for critically ill non-neutropenic patients, only 7.14 % (9/188) were diagnosed as IC (4 proven and 5 probable cases). The combined use of CCI with BDG proved to have excellent discriminative power AUC= 0.946, improved sensitivity 87.5 % and specificity 85.71 %. ConclusionThe key in diagnosis of IC relies in compiling proofs from the clinical context, high CCI (≥ 0.4) and BDG.

The plasma viral communities associate with clinical profiles in a large-scale haematological patients cohort

BackgroundHaematological patients exhibit immune system abnormalities that make them susceptible to viral infections. Understanding the relationship between the virome in the blood plasma of haematological patients and their clinical characteristic is crucial for disease management. We aimed to explore the presence of viral pathogens and identify close associations between viral infections and various clinical features.ResultsA total of 21 DNA viruses and 6 RNA viruses from 12 virus families were identified from 1383 patients. Patients with haematological diseases exhibited significantly higher diversity, prevalence, and co-detection rates of viral pathogens. During fever episodes, pathogen detection was notably higher, with Epstein-Barr virus (EBV) and Mucorales infections being the most probable culprits for fever symptoms in non-haematological patients. The detection rate of torque teno virus (TTV) significantly increases in haematological patients after transplantation and during primary lung infections. Additionally, TTV-positive patients demonstrate significantly higher absolute neutrophil counts, while C-reactive protein and procalcitonin levels are notably lower. Furthermore, TTV, cytomegalovirus, and parvovirus B19 (B19V) were found to be more prevalent in non-neutropenic patients, while non-viral pathogenic infections, such as Gram-negative bacteria and Mucorales, were more common in neutropenic patients. Pegivirus C (HPgV-C) infection often occurred post-transplantation, regardless of neutropenia. Additionally, some viruses such as TTV, B19V, EBV, and HPgV-C showed preferences for age and seasonal infections.ConclusionsAnalysis of the plasma virome revealed the susceptibility of haematological patients to plasma viral infections at specific disease stages, along with the occurrence of mixed infections with non-viral pathogens. Close associations were observed between the plasma virome and various clinical characteristics, as well as clinical detection parameters. Understanding plasma virome aids in auxiliary clinical diagnosis and treatment, enabling early prevention to reduce infection rates in patients and improve their quality of life.EnXnzQJ5tBc4iYM41USpCeVideo

Multifocal candidiasis can be considered a form of invasive candidiasis in critically non-neutropenic patients

Candida infections can be serious in intensive care unit (ICU) patients, as Candida is an organism that specially colonizes the digestive system. In immunocompromised patients, treatment is protocolized, but in non-neutropenic patients, it is not well established. On the other hand, the treatment of this type of infection is not absent of adverse effects. The prevalence of fungal infections, especially candidiasis, and its mortality in the ICU is high, mainly due to the lack of diagnosis and absence of treatment criteria, because they are often detected in the disseminated candidiasis phase, such as candidemia. One of the indicators of the progression of the disease is the presence of Candida in more than two different foci, named Candida multifocality, within the concept of invasive candidiasis. In fact, the invasive fungal diseases in adult patients i intensive care unit (FUNDICU) project was created to optimize the management of candidiasis. The management of candidiasis in ICU patients first requires the identification of patients at high risk of candidiasis, which must be performed based on the evidence of immune dysregulation, higher severity index (acute physiologic assessment and chronic health evaluation and multiple organ dysfunction syndrome), long ICU stays or other factors such as mechanical ventilation or us of broad-spectrum antibiotics. To increase detection and dispense the appropriate antifungal at an early stage, it is necessary to include the concept of multifocality in invasive candidiasis with screening of different foci. Antifungal treatment reduces mortality both overall and attributable to Candida. Detecting a high invasive candidiasis risk is a patient safety concept and should be treated as such. Identifying patients (critically non-neutropenic adult patients with severe multiple organ dysfunction syndrome and the first isolation of Candida spp. in a study sample of possible secondary infection) and demonstrating invasive candidiasis (multifocal or disseminated) require urgent initiation of antifungal treatment to minimize mortality attributable to invasive candidiasis in the ICU and eliminate mortality rates above 50%.

Predictors of radiographic pneumonia in febrile children with cancer presenting to the emergency department

BackgroundFever is a common presenting complaint to the pediatric emergency department (PED), especially among oncology patients. While bacteremia has been extensively studied in this population, pneumonia has not. Some studies suggest that chest X-ray (CXR) does not have a role in the investigation of neutropenic fever in the absence of respiratory symptoms, yet non-neutropenic pediatric oncology patients were excluded from these studies. ObjectiveWe aimed to determine the incidence of CXRs ordered for febrile pediatric oncology patients, irrespective of their absolute neutrophil count (ANC), and to evaluate the rates of radiographic pneumonia as well as predictors of the latter in this group. MethodThis study was conducted in the PED at the American University of Beirut Medical Center (AUBMC), an Eastern Mediterranean tertiary-care hospital. We conducted a retrospective cohort study of acutely febrile pediatric cancer patients, younger than 18 years, presenting to a tertiary center from 2014 to 2018. We included one randomly selected febrile visit per patient. Fever was defined as a single oral temperature ≥38 °C within 24 h of presentation. We collected data on patient characteristics and outcomes. Our primary outcome was radiographic pneumonia; our secondary outcome was whether a CXR was done or not. We defined radiographic pneumonia as a consolidation, pleural effusion, infiltrate, pneumonia, “infiltrate vs. atelectasis,” or possible pneumonia mentioned by the radiologist. SPSS was used for the statistical analysis. ResultsWe reviewed a total of 664 medical charts and included data from 342 febrile pediatric patients in our analysis. Of these, 64 (18.7%) had a CXR performed. Overall, 16 (25%) had radiographic pneumonia while 48 (75%) did not. Patients were significantly more likely to have a CXR performed if they presented with upper respiratory tract symptoms, cough (p < 0.001 for both), or abnormal lung auscultation at the bedside (p = 0.004). Patients were also less likely to have a CXR done if they were asymptomatic upon admission to the PED (p < 0.001). However, neither cough nor shortness of breath nor abnormal lung examinations were significant predictors of a positive CXR (p = 0.17, 0.43, and 0.669, respectively). Patients with radiographic pneumonia were found to be significantly younger (4.29 vs. 6 years, p = 0.03), with a longer time since their last chemotherapy (15 vs. 7 days, p = 0.005), and were given intravenous (IV) bolus in the PED (87.5% vs. 56.3%, p = 0.02). Interestingly, patients with higher white blood cell (WBC) counts were more likely to have radiographic pneumonia (4850 vs. 1750, p = 0.01). Having a cough and an abnormal lung examination on presentation increased the odds of having a CXR (adjusted odds ratio [aOR]: 6.6; 95% confidence interval [CI]: 3.4–12.8 and aOR: 4.5; 95% CI: 1.1–18.3, respectively). Returning to the PED for the same complaint within 2 weeks was associated with lower odds of a CXR at the index visit (aOR: 0.3; 95% CI: 0.1–0.6). For every year the child is older, the odds of having radiographic pneumonia decreased by 0.8 (95% CI: 0.6–0.98). However, for every day since the last chemotherapy session, the odds increased by 1.1 (95% CI: 1.01–1.12). ConclusionIn our sample, CXR was not commonly performed in the initial assessment of febrile cancer patients in the PED, unless respiratory symptoms or an abnormal lung examination was noted. However, these were not significant predictors of radiographic pneumonia. Further studies are needed to identify better predictors of pneumonia in this high-risk population.

Performance of rapid on-site evaluation of touch imprints of bronchoscopic biopsies or lung tissue biopsies for the diagnosis of invasive pulmonary filamentous fungi infections in non-neutropenic patients.

The diagnosis of invasive pulmonary fungal disease depends on histopathology and mycological culture; there are few studies on touch imprints of bronchoscopic biopsies or lung tissue biopsies for the diagnosis of pulmonary filamentous fungi infections. The purpose of the present study was to explore the detection accuracy of rapid on-site evaluation of touch imprints of bronchoscopic biopsies or lung tissue biopsies for the filamentous fungi, and it aims to provide a basis for initiating antifungal therapy before obtaining microbiological evidence. We retrospectively analyzed the diagnosis and treatment of 44 non-neutropenic patients with invasive pulmonary filamentous fungi confirmed by glactomannan assay, histopathology, and culture from February 2017 to December 2023. The diagnostic positive rate and sensitivity of rapid on-site evaluation for these filamentous fungi identification, including diagnostic turnaround time, were calculated. Compared with the final diagnosis, the sensitivity of rapid on-site evaluation was 81.8%, and the sensitivity of histopathology, culture of bronchoalveolar lavage fluid, and glactomannan assay of bronchoalveolar lavage fluid was 86.4%, 52.3%, and 68.2%, respectively. The average turnaround time of detecting filamentous fungi by rapid on-site evaluation was 0.17 ± 0.03 hours, which was significantly faster than histopathology, glactomannan assay, and mycological culture. A total of 29 (76.3%) patients received earlier antifungal therapy based on ROSE diagnosis and demonstrated clinical improvement. Rapid on-site evaluation showed good sensitivity and accuracy that can be comparable to histopathology in identification of pulmonary filamentous fungi. Importantly, it contributed to the triage of biopsies for further microbial culture or molecular detection based on the preliminary diagnosis, and the decision on early antifungal therapy before microbiological evidence is available.

Safety and effectiveness of isavuconazole in real-life non-neutropenic patients

Information is scarce on clinical experiences with non-neutropenic patients with invasive fungal infection (IFI) receiving isavuconazole. We aimed to report the safety and effectiveness of this drug as a first-line treatment or rescue in real life. A retrospective, observational multicentric study of non-neutropenic patients who received isavuconazole as an IFI treatment at 12 different university hospitals (January 2018-2022). All patients met criteria for proven, probable or possible IFI according to EORTC-MSG. A total of 238 IFIs were treated with isavuconazole during the study period. Combination therapy was administered in 27.7% of cases. The primary IFI was aspergillosis (217, 91.2%). Other IFIs treated with isavuconazole were candidemia (n = 10), mucormycosis (n = 8), histoplasmosis (n = 2), cryptococcosis (n = 2), and others (n = 4). Median time of isavuconazole treatment was 29 days. Only 5.9% (n = 14) of cases developed toxicity, mainly hepatic-related (10 patients, 4.2%). Nine patients (3.8%) had treatment withdrawn. Successful clinical response at 12 weeks was documented in 50.5% of patients. Isavuconazole is an adequate treatment for non-neutropenic patients with IFIs. Toxicity rates were low and its effectiveness was comparable to other antifungal therapies previously reported.

Diagnosis and management of invasive fungal diseases in non-neutropenic ICU patients, with focus on candidiasis and aspergillosis: a comprehensive review.

Invasive fungal diseases pose a significant threat to non-neutropenic ICU patients, with Candida and Aspergillus infections being the most common. However, diagnosing these infections in the ICU population remains challenging due to overlapping clinical features, poor sensitivity of blood cultures, and invasive sampling requirements. The classical host criteria for defining invasive fungal disease do not fully apply to ICU patients, leading to missed or delayed diagnoses. Recent advancements have improved our understanding of invasive fungal diseases, leading to revised definitions and diagnostic criteria. However, the diagnostic difficulties in ICU patients remain unresolved, highlighting the need for further research and evidence generation. Invasive candidiasis is the most prevalent form of invasive fungal disease in non-neutropenic ICU patients, presenting as candidemia and deep-seated candidiasis. Diagnosis relies on positive blood cultures or histopathology, while non-culture-based techniques such as beta-D-glucan assay and PCR-based tests show promise. Invasive aspergillosis predominantly manifests as invasive pulmonary aspergillosis in ICU patients, often associated with comorbidities and respiratory deterioration in viral pneumonia. Diagnosis remains challenging due to poor sensitivity of blood cultures and difficulties in performing lung biopsies. Various diagnostic criteria have been proposed, including mycological evidence, clinical/radiological factors and expanded list of host factors. Non-culture-based techniques such as galactomannan assay and PCR-based tests can aid in diagnosis. Antifungal management involves tailored therapy based on guidelines and individual patient factors. The complexity of diagnosing and managing invasive fungal diseases in ICU patients underscore the importance of ongoing research and the need for updated diagnostic criteria and treatment approaches. Invasive fungal disease, Invasive fungal infection, Invasive candidiasis, Invasive aspergillosis, Antifungal drugs.

Diagnostic accuracy of procalcitonin in adult non-neutropenic cancer patients with suspected infection: a systematic review and meta-analysis

BackgroundProcalcitonin (PCT) has garnered attention as a potential diagnostic biomarker for infection in cancer patients. We performed a systematic review and meta-analysis to evaluate the diagnostic accuracy of procalcitonin (PCT) and to compare it with C‐reactive protein (CRP) in adult non-neutropenic cancer patients with suspected infection.MethodsA systematic literature search was performed in MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials to identify all relevant diagnostic accuracy studies. Original articles reporting the diagnostic accuracy of PCT for infection detection in adult patients with solid or hematological malignancies were included. The pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio, area under the hierarchical summary receiver operator characteristic (HSROC) curve, and corresponding 95% confidence interval (CI) were calculated.ResultsSeven studies were included in the meta-analysis. The pooled sensitivity and specificity of PCT were 60% (95% CI [45–74%]) and 78% (95% CI [69–86%]). The diagnostic odds ratio was estimated at 5.47 (95% CI [2.86–10.46]). Three studies compared the diagnostic accuracies of PCT and CRP. The pooled sensitivity and specificity values for PCT were 57% (95% CI [26–83%]) and 75% (95% CI [68–82%]), and those for CRP were 67% (95% CI [35–88%]) and 73% (95% CI [69–77%]). The pooled sensitivity and specificity of PCT and CRP did not differ significantly (p = 0.61 and p = 0.63). The diagnostic accuracy of PCT was similar to that of CRP as measured by the area under the HSROC curve (0.73, CI = 0.61–0.91 vs. 0.74, CI = 0.61–0.95, p = 0.93).ConclusionWhile elevated PCT levels can be indicative of potential infection, they should not be solely relied upon to exclude infection. We recommend not using the PCT test in isolation; Instead, it should be carefully interpreted in the context of clinical findings.

Comparison of The Effect of Candida Score and Candida Colonization Index on Decrease in Candidemia Incidence in Our Intensive Care Unit

Aim: Since candidemia is an important cause of mortality and morbidity in hospitals, especially in intensive care units (ICU), those hospitalized in the ICU; In patients with risk factors such as invasive device use and undergoing abdominal surgery, early empirical antifungal therapy is recommended to reduce mortality according to the results of candida score (CS) and candida colonization index (CCI). In this study, the data of the patients who were followed up in the ICU, who were started on empirical treatment according to KS and CCI, were evaluated and their effects on the incidence of candidemia were analyzed. Method: Cultures taken from 100 patients hospitalized in the intensive care unit where adult patients were followed between 01.06.2018 and 01.08.2021 were examined. While investigating the colonization index of each patient, swab samples were taken once during the hospitalization from five main sites: mouth, nose, skin, perineum, and catheter. Samples taken with sterile swabs were inoculated on Sabouraud dextrose agar (SDA) plates and the plates were incubated at 35°C for 48 hours. The yeast colonies formed were defined according to their microscopic appearance and biochemical properties. CCI and CS of the patients were evaluated and fluconazole prophylaxis was started in patients with KS ≥3 or CCI ≥0.5. Results: A total of 500 culture samples from 100 non-neutropenic adult patients were analyzed (Mean of 5 cultures/patient). No growth was detected in any of the samples in 32 (32 %) of 100 patients, and growth was detected in at least one of the samples taken from 68 patients (68 %). Reproduction was detected from a total of 118 samples. Of the yeasts, 104 were identified as Candida albicans, 10 as Candida glabrata and 4 as Candida inconspicua. CS≥ 3 and CCI ≥0.5 in 11 (11%) patients, and CS≥3, CCI

IL-17 in plasma and bronchoalveolar lavage fluid in non-neutropenic patients with invasive pulmonary aspergillosis.

The purpose of this study was to investigate the diagnostic value of IL-17 detection in bronchoalveolar lavage fluid (BALF) and plasma samples from nonneutropenic patients with invasive pulmonary aspergillosis. We retrospectively collected data on non-neutropenic patients who were suspected to have IPA admitted to the Third Affiliated Hospital of Soochow University between March 2020 to January 2023. IL-17 and GM were measured using enzyme-linked immunosorbent assays. A total of 281 patients were enrolled in this study, of which 62 had proven or probable IPA and the remaining 219 patients were controls. The plasma and BALF IL-17 levels were significantly higher in the IPA group compared with the control group. The plasma GM, plasma IL17, BALF GM, and BALF IL17 assays had sensitivities of 56.5%, 72.6%, 68.7%, and 81.2%, respectively, and specificities of 87.7%, 69.4%, 91.9%, and 72.6%, respectively. The sensitivity of IL17 in plasma and BALF was higher than that of GM. Plasma GM in combination with IL-17 increases the sensitivity but does not decrease the diagnostic specificity of GM testing. The diagnostic sensitivity and specificity of BALF GM combined with IL-17 for IPA in non-neutropenic patients were greater than 80% and there was a significant increase in sensitivity compared with BALF GM. Plasma and BALF IL-17 levels were significantly higher in non-neutropenic patients with IPA. The sensitivity of plasma and BLAF IL-17 for diagnosing IPA in non-neutropenic patients was superior to that of GM. Combined detection of lavage fluid GM and IL17 significantly improves the diagnosis of IPA in non-neutropenic patients. The combined detection of GM and IL-17 in plasma also contributes to the diagnosis of IPA in patients who cannot tolerate invasive procedures.

Diagnosis of invasive pulmonary fungal infections by a real-time panfungal PCR assay in non-neutropenic patients.

This study explored the utility of quantitative real-time panfungal PCR assay in diagnosing invasive pulmonary fungal diseases (IPFD) in non-neutropenic patients. Panfungal PCR assay was performed on respiratory tract specimens from patients whose clinical signs could not exclude fungal infection. At the same time, the samples were subjected to bacterial and fungal culture, microscopic examination and galactomannan antigen (GM) test in order to find the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of the 4 diagnostic methods in proven and probable cases. 518 specimens were collected while 63 respiratory tract specimens tested by PCR had positive results. According to diagnostic criteria, 40 patients were diagnosed with IPFD, with 12 proven, 20 probable and 8 possible cases. Among these, 33 patients of PCR results were positive, most of which were from BALF samples (44.12%). 23 cases were caused by Aspergillus species, with Aspergillus fumigatus was the major cause. Other Aspergillus species, including Aspergillus flavus, Aspergillus terreus and Aspergillus nidulans were found in 1 sample respectively. Candida species were found in 5 samples, Pneumocystis jeroveci pneumonia (PJP) in 4 samples and Mucormycosis in 1 sample. An analysis of proven/probable diagnosis showed a sensitivity of 78.13%, specificity of 92.18%, PPV of 39.68% and NPV of 98.46% for PCR and 50%, 85.27%, 35.7%, 95.65% for GM test respectively. The Ct value difference between proven/probable and possible cases had no statistical significance (P = .824). Fungal culture showed a sensitivity of 17.5% while microscopic examination sensitivity of 32.5%. Through stratified analysis, no apparent correlation was found between the Ct value of the PCR assay and GM value (r: 0.223, P = .294). But a conjunction of the 2 tests raised the PPV of Aspergillus to 90%. As shown in this study, the panfungal RT-PCR assay has high sensitivity and consistency with serological test and culture. Its high PPV in the detection of Aspergillus and PJP were also evident.

Early picc-line infections in non-neutropenic patients are mainly due to E. coli suggesting that third-generation cephalosporin may be used as a first-line antibiotic therapy

PurposeTo describe the rate of peripherally inserted central catheter (PICC) -associated bloodstream infections, and the pathogens involved. MethodsWe prospectively analyzed data collected from all adult patients with a PICC insertion in a hematology unit in a tertiary care center between January 1, 2017 and June 30, 2020. ResultsA total of 370 PICCs were inserted in 275 patients with hematological malignancies: 54 (15 %) confirmed cases of central-line associated bloodstream infection (CLABSI) were identified. Enterobacteria were the most frequent bacteria identified, involved in 35 % of CLABSIs. Group 1 enterobacteria bacteremia occurred a much shorter time after insertion (median time to CLABSI 16 days) than group 2 or group 3 enterobacteria (median time to CLABSI 64 days, p-value = 0.049). ConclusionAmong Gram-negative bacilli CLABSI among non-neutropenic patients, E. coli identification was the most frequent and occurred earlier after insertion, suggesting that third-generation cephalosporin may be used as a first-line antibiotic therapy for enterobacteria bacteremia among non-neutropenic patients.

Utility of Echocardiogram in Neutropenic Patients with Gram Positive Bacteremia: A Retrospective Study

Introduction: Hemato-oncology patients are vulnerable to bloodstream infections (BSI) due to their immunocompromised and neutropenic state, and the common use of intravascular catheters. The risk of infective endocarditis (IE) among non-neutropenic patients with gram positive bacteremia is substantial, however the risk is considered to be lower among neutropenic patients, though data is limited. We aimed to evaluate the incidence of IE among neutropenic hemato-oncology patients' cohort, and to explore the yield of echocardiogram in this specific population. Methods: A single center, retrospective study. Between 01/2007 and 12/2019, hospitalized patients in the Hematology department consisting of the hemato-oncology and bone marrow transplantation units were included, if they had positive blood cultures for specific organisms known to cause IE while neutropenic. Patient characteristics, results and timing of blood cultures and echocardiogram obtained during hospitalization were collected. Results: Two hundred seventy-four patients had positive blood cultures with pathogens known to be associated with IE. Overall, 340 isolates have been identified. After excluding 57 coagulase negative staphylococcus (CONS) isolates which were suspected as a contamination (identified in a single collection), 241 patients were included with 283 isolates. CONS were the most commonly isolates found, followed by streptococcus viridans, comprising 31.4% (89) and 24.3% (69) of isolates, respectively. Trans thoracic echocardiography (TTE) was performed in 108 (45%) patients overall, of which 14 (5.8%) had additional trans esophageal echocardiogram (TEE). Only one case of IE was diagnosed in our series, of a forty-seven-year-old female patient with a diagnosis of multiple myeloma in relapse after autologous stem cell transplantation. The patient presented with a stroke caused by septic emboli, fever and streptococcus viridans bacteremia. Lab works showed neutropenia of 0K/micl and thrombocytopenia of 8K/micl. TTE and TEE failed to demonstrate valvular pathology consistent with IE in this case. Valvular vegetations have not been identified on TTE nor on TTE in any other case as well. Conclusion In our experience, the yield of echocardiogram in hemato-oncological neutropenic patients with gram positive bacteremia is extremely low, owing to reduced probability of IE in this population, and thus could be avoided in most cases.

Pulmonary Aspergillosis in Naïve Non-neutropenic Lung Cancer Patients

Abstract: Pulmonary aspergillosis is the most common mould infection of the lungs. Patients with chronic lung disease or mild immunodeficiency are at risk. Lung cancer represents an oncological challenge. Limited data are available about aspergillosis in newly diagnosed non-neutropenic lung cancer patients. Objectives:: The aim of this work was to evaluate naïve lung cancer patients for the presence of as-pergillosis, identify fungal isolates, and determine antifungal susceptibility. The inhibitory effect of secondary metabolites of fungal isolates on the human fibroblast cell line was also assessed. Results:: Aspergillus isolates were detected in 33 BAL samples out of the 69 patients (47.8%). The commonest isolate was A. niger. There was no significant correlation between total fungal count and age of patients. The antifungal Micafungin had a broad-spectrum and potent fungistatic activity against all fungal species, with A. niger being the most sensitive. MTT assay was performed to evaluate the cytotoxic effect of both A. niger and A. fumigatus on normal lung cells (WI-38) and re-vealed that toxicity was concentration-dependent and A. niger had significantly lower IC 50, indi-cating more toxicity. Conclusion:: In the context of the diagnosis of lung cancer, maintaining vigilance is crucial to diag-nose fungal infection as aspergillosis. Initiation of proper management can help improve patient outcomes.

Performance of mNGS in bronchoalveolar lavage fluid for the diagnosis of invasive pulmonary aspergillosis in non-neutropenic patients.

The diagnosis of invasive pulmonary aspergillosis (IPA) diseases in non-neutropenic patients remains challenging. It is essential to develop optimal non-invasive or minimally invasive detection methods for the rapid and reliable diagnosis of IPA. Metagenomic next-generation sequencing (mNGS) in bronchoalveolar lavage fluid (BALF) can be a valuable tool for identifying the microorganism. Our study aims to evaluate the performance of mNGS in BALF in suspected IPA patients and compare it with other detection tests, including serum/BALF galactomannan antigen (GM) and traditional microbiological tests (BALF fungal culture and smear and lung biopsy histopathology). Ninety-four patients with suspicion of IPA were finally enrolled in our study. Thirty-nine patients were diagnosed with IPA, and 55 patients were non-IPA. There was significance between the IPA and non-IPA groups, such as BALF GM (P < 0.001), history of glucocorticoid use (P = 0.004), and pulmonary comorbidities (P = 0.002), as well as no significance of the other demographic data including age, sex, BMI, history of cigarette, blood GM assay, T-SPOT.TB, and NEUT#/LYMPH#. The sensitivity of the BALF mNGS was 92.31%, which was higher than that of the traditional tests or the GM assays. The specificity of BALF mNGS was 92.73%, which was relatively similar to that of the traditional tests. The AUC of BALF mNGS was 0.925, which presented an excellent performance compared with other traditional tests or GM assays. Our study demonstrated the important role of BALF detection by the mNGS platform for pathogen identification in IPA patients with non-neutropenic states, which may provide an optimal way to diagnose suspected IPA disease.

Bloodstream infections in neutropenic and non-neutropenic patients with haematological malignancies: epidemiological trends and clinical outcomes in Queensland, Australia over the last 20 years

Knowledge of the epidemiology of bloodstream infection (BSI) in haematology patients is essential to guide patient management. We investigated the epidemiology of BSI in patients with haematological malignancies in Queensland over the last 20 years (2000–2019), including all episodes diagnosed by the state-wide microbiology service. We identified 7749 BSI in 5159 patients, 58% associated with neutropenia. Gram-negatives were the main causative pathogens (58.3%), more frequent in neutropenic than non-neutropenic patients (3308/5309, 62.3% vs 1932/3678, 52.5%, p < 0.001). Amongst 8987 isolates the most common were E.coli (15.4%) and Pseudomonas spp. (14.2%). Pseudomonas spp. (16.6% vs 10.7%, p < 0.001), Klebsiella spp. (11.6% vs 6.8%, p < 0.001), viridans-group streptococci (4.4% vs 1.2%, p < 0.001) and E.faecium (2.4% vs 0.9%, p < 0.001) were more common in neutropenic than non-neutropenic patients, while S.aureus was less common (5.9% vs 15.6%, p < 0.001). Several antimicrobial resistance rates increased over time and had higher prevalence in neutropenic than non-neutropenic patients, including ciprofloxacin-resistant E.coli (94/758, 12.4% vs 42/506, 8.3%, p = 0.021), trimethoprim-sulfamethoxazole-resistant E.coli (366/764, 47.9% vs 191/517, 36.9%, p < 0.001), penicillin-resistant streptococci (51/236, 21.6% vs 28/260, 10.8%, p < 0.001) and vancomycin-resistant enterococci (46/250, 18.4% vs 9/144, 6.3%, p < 0.001). Carbapenem-resistant Pseudomonas spp. (OR 7.32, 95%CI 2.78–19.32) and fungi, including yeasts and moulds (OR 3.33, 95%CI 2.02–5.48) were associated to the highest odds of 30-day case-fatality at a multivariable logistic regression analysis. Neutropenia was associated with survival (OR 0.66, 95%CI 0.55–0.78). Differences were observed in the BSI epidemiology according to neutropenic status, with an overall increase of resistance over time associated to adverse outcome.

Clinical characteristics and prognostic risk factors of candidemia in non-neutropenic patients: a retrospective cohort study.

This study aimed to determine the clinical characteristics and the prognostic risk factors in non-neutropenic patients with candidemia. Data were retrospectively collected through the medical record information system. Non-neutropenic patients with candidemia were relatively aged, with a more than one-third rate of in-hospitalization mortality. In multivariate analysis, APACHE II score (adjusted odds ratio [aOR], 1.138; 95% confidence interval [CI], 1.067-1.213), septic shock (aOR, 5.704; 95% CI, 2.639-12.326) and RRT (aOR, 16.152; 95% CI, 2.628-99.275) (all P < 0.01) were independent related with non-survivors. In conclusion, non-neutropenic patients with candidemia have a high in-hospitalization mortality, and APACHE II, septic shock, and RRT are independently factors.

Cancer patients in the emergency department

A growing number of patients are living with cancer or have a history of cancer leading to increasing adverse effects of treatment or disease necessitating emergency department (ED) consultation. Long-term cancer survivors are at higher risk of comorbidities causing a substantial increase in health care resource utilization. The most frequent reasons for cancer-related ED visits are dyspnea, fever, pain, gastrointestinal or neurological symptoms leading to high hospital and intensive care unit admission rates. Acute respiratory failure in cancer patients necessitates timely diagnostic testing, whereby computed tomography is superior to chest X‑ray. Delay in intensive care unit (ICU) admission or mechanical ventilation increases mortality. Febrile neutropenia is an emergency with urgent need for antibiotic treatment. Treatment of neutropenic and nonneutropenic patients with sepsis does not differ. Cardiovascular disease is now the second leading cause of long-term morbidity and mortality among cancer survivors. Immunotherapy can lead to substantial and in some patients life-threatening complications that may not easily be recognized in the ED. Cancer-specific emergencies such as leukostasis, tumorlysis or hypercalcemia rarely present to ED and require interdisciplinary care. The constantly growing cancer population is likely to increase ED utilization. Knowledge about cancer treatment and disease-associated complications is crucial for emergency physicians. Palliative care education should secure appropriate end-of-life care avoiding futile interventions.