Empirical Antifungal Treatment Research Articles

Disseminated Mucormycosis Masquerading as Invasive Pulmonary Aspergillosis

Pulmonary mucormycosis can closely resemble invasive pulmonary aspergillosis. If the infection is not contained at its primary site, it can lead to dissemination. A middle-aged woman, initially diagnosed with acute promyelocytic leukaemia, presented with atypical non-resolving pneumonia. Despite empirical antifungal treatment targeting Candida and Aspergillus, her clinical condition continued to deteriorate, resulting in the spread of the infection. Subsequent follow-up, combined with a high index of suspicion and isolation of Mucorales from an extrapulmonary site, identified mucormycosis as the causative pathogen. Early recognition of subtle clinical and radiological cues and prompt initiation of a classical medico-surgical approach is crucial for treating invasive mucormycosis and managing the underlying immunosuppressive condition. This case underscores the importance of early suspicion of Mucorales based on clinical and radiological signs, distinguishing it from invasive aspergillosis. The atypical presentation of pulmonary, splenic, and renal mucormycosis in this patient highlights the need for vigilance and timely intervention to prevent the most severe outcomes of disseminated mucormycosis.

Should Empiric Anti-Fungals Be Administered Routinely for All Patients with Perforated Peptic Ulcers? A Critical Review of the Existing Literature.

A perforated peptic ulcer (PPU) is a surgical emergency with a high mortality rate. PPUs cause secondary peritonitis due to bacterial and fungal peritoneal contamination. Surgery is the main treatment modality and patient's comorbidites impacts perioperative morbidity and surgical outcomes. Even after surgery, resuscitation efforts should continue. While empiric antibiotics are recommended, the role of empiric anti-fungal treatment is unclear due to a lack of scientific evidence. This literature review demonstrated a paucity of studies evaluating the role of empiric anti-fungals in PPUs, and with conflicting results. Studies were heterogeneous in terms of patient demographics and underlying surgical pathology (PPUs vs. any gastrointestinal perforation), type of anti-fungal agent, timing of administration and duration of use. Other considerations include the need to differentiate between fungal colonization vs. invasive fungal infection. Despite positive fungal isolates from fluid culture, it is important for clinical judgement to identify the right group of patients for anti-fungal administration. Biochemistry investigations including new fungal biomarkers may help to guide management. Multidisciplinary discussions may help in decision making for this conundrum. Moving forward, further research may be conducted to select the right group of patients who may benefit from empiric anti-fungal use.

Clinical performance of metagenomic next-generation sequencing for diagnosis of invasive fungal disease after hematopoietic cell transplant.

Timely diagnosis and appropriate antifungal therapy are critical for improving the prognosis of patients with invasive fungal disease (IFD) after hematopoietic stem cell transplantation (HSCT). We evaluated the performance of metagenomic next-generation sequencing (mNGS) and conventional microbiological testing (CMT), as well as the diagnosis, therapeutic management, and outcomes of IFD after HSCT. We retrospectively studied 189 patients who underwent HSCT and were considered at risk for IFD. In total, 46 patients with IFD were enrolled in this study. The IFD consensus was followed for classifying IFD incidents. Forty-six patients were diagnosed with proven/probable (n = 12), possible (n = 27), and undefined (n = 7) IFD. Aspergillus was the most commonly detected fungal genus. Mucormycosis was found in 15 patients; two had Aspergillus, and one had Candida infections. Compared to CMT, mNGS significantly reduced the time required to identify pathogens (P = 0.0016). mNGS had a much higher sensitivity than CMT (84.78% vs. 36.96%; P < 0.0001). A total of 76.09% of patients received antifungal prophylaxis during fungal infections. All Pneumocystis infections occurred later than 100 days after transplantation. Among patients with Pneumocystis infection, 71.43% occurred following sulfonamide withdrawal, and subsequent treatment with sulfonamide alone or in combination with other drugs was effective. Based on the empirical antifungal treatment, the dosages, modes of administration, frequency of administration, or antifungal of 55.26% of the patients were changed according to the mNGS results. The 4-year overall survival rate of patients diagnosed with IFD after transplantation was 71.55% (95% CI, 55.18%-85.82%). Hypoproteinemia and corticosteroid use are independent risk factors for IFD. mNGS, which has a high sensitivity and a short detection time, aids in the diagnosis and prognosis of pathogenic fungi. As a powerful technology, mNGS can influence treatment decisions in patients with IFD following HSCT.

Clinical Features and Outcomes of Invasive Fusariosis in Pediatric Patients with Acute Lymphoblastic Leukemia (ALL): A Case Series in a Single Tertiary Center in North-Eastern Mexico

Abstract Background Fusariosis is a pathology that is of great clinical concern in certain at-risk patient groups. Pediatric patients with ALL are in the greatest at-risk population as they are frequently in a post-chemotherapy state. The diagnosis for IFIs can be carried out by the criteria established in the European Organization for Research and Treatment of Cancer/Mycoses Study Group (EORTC/MSG) and the notable intrinsic resistance of the Fusarium species to most of the antifungal agents available lead to high mortality rates in immunocompromised patients. Starting in 2002, the use of voriconazole was approved as empiric monotherapy as a first line therapy for the treatment of disseminated fusariosis. Other options are liposomal amphotericin B (LAB), Posaconazole or Isavuconazole. There are a few reports combined antifungal treatment in a pediatric population. In pediatric patients, the empirical and specific antifungal treatment is mostly inferred from clinical experience in adult patients. Methods We identified six patients with culture-proven fusariosis at a tertiary healthcare center in North-Eastern Mexico from May 2018- August 2021. We reported six cases of fusariosis categorized according to the EORTC/MSG. B cell ALL diagnosis was defined as a positive result in a B-cell leukemia panel. In terms of the descriptive statistics, continuous variables were reported as medians and [Interquartile range], while categorical variables were described via counts, frequencies, and (prevalence). Results The median age was 8 [6-12], 2 of the patients were female. All of the included patients were in the remission induction phase of their therapy and all patients had a confirmed B cell ALL and all patients presented with neutropenia. Four patients had a central venous catheter present, 3 of patients had a bacterial co-infection (E. coli, S. pneumoniae, Klebsiella blee). LAB was given as empirical therapy in 3 of patients while one patient received a combination of amphotericin B and voriconazole and the remaining patient received voriconazole monotherapy. Five patients had resistance to LAB, two patients showed voriconazole resistance. The definitive treatment was LAB plus Voriconazole in 5 (83.3%) patients. Five (83.3%) patients survived. Conclusions There are no clearly established guidelines for treatment options for fusariosis in pediatric patients. The majority of our reported patients presented with LAB-resistance and the combination of LAB with voriconazole has been used to control this pathology. There is still much more to explore and further research is needed into the indicated treatment plan and the susceptibility and therapeutic strategy for this specific population.

Impact of posaconazole prophylaxis and antifungal treatment on BAL GM performance in hematology malignancy patients with febrile neutropenia: a real life experience.

Diagnostic accuracy of galactomannan measurements is highly variable depending on the study population, diagnostic procedures, and treatment procedures. We aimed to evaluate the effect of posaconazole prophylaxis and empiric antifungal treatment upon diagnostic accuracy of GM measurements in bronchoalveolar lavage (BAL), bronchial lavage (BL), and serum in hematological malignancy population. Patients hospitalized in a single tertiary care center with hematologic malignancies undergoing fiberoptic bronchoscopy (FOB) with a preliminary diagnosis of IPA were retrospectively included. In all the study population (n = 327), AUC for BAL, BL, and serum GM were as follows: 0.731 [0.666-0.790], 0.869 [0.816-0.912], and 0.610 [0.540-0.676] with BL samples having the best diagnostic value. GM measurements in patients under posaconazole prophylaxis (n = 114) showed similar diagnostic performance. While specificity was similar between patients with and without posaconazole prophylaxis, sensitivity of GM measurements was lower in patients with prophylaxis. Analyses with patient classified according to antifungal treatment at the time of FOB procedure (n = 166) showed a decreased diagnostic accuracy in serum GM and BAL GM measurements related with the duration of treatment. However, BAL, BL, and serum GM measurements presented similar sensitivity and specificity in higher cut-off values in longer durations of antifungal treatment. Our study shows that posaconazole prophylaxis and active short-term (3days) antifungal treatment do not significantly affect overall diagnostic performance of GM measurements in bronchoalveolar lavage and bronchial lavage samples. However, using different cut-off values for patients receiving active treatment might be suggested to increase sensitivity.

Culture-negative necrotizing otitis externa: diagnosis and management

ObjectiveWe aim to describe the clinical features and therapeutic management of necrotizing otitis externa (NOE) with negative culture.Patients and methodsWe included all patients with NOE, who were treated in the period between 2008 and 2020 in our department.ResultsA total of 25 cases of NOE were included. The result of the culture was negative in 13 cases (52%). All patients received a local treatment prior to hospitalization, and eight patients (61.5%) received oral antibiotic. A sampling of the otorrhea was done for all patients. Fungal serology was performed for six patients; it was positive in two cases. The prescribed first-line was ciprofloxacin in combination with ceftazidime for 10 patients, while it was based on the use of imipenem with ciprofloxacin for 2 patients and one patient only received ciprofloxacin. An improvement was noted in 10 cases (77%). The second-line treatment in the three cases of resistance was imipenem with ciprofloxacin in one case. For the two patients with a positive aspergillus serology, one patient received teicoplanin, fusidic acid, imipenem, and voriconazole and the other patient received voriconazole. The total duration of the treatment was a minimum of 6 weeks. An improvement was noted in all cases, and recurrence was noted in 3 cases.ConclusionIn our study, there were no clinical or radiological specificities noted in NEO with negative culture. Sampling must be repeated. Fungal origin should be suspected in refractory forms and empiric antifungal treatment may be useful.

The Use of Host Biomarkers for the Management of Invasive Fungal Disease.

Invasive fungal disease (IFD) causes severe morbidity and mortality, and the number of IFD cases is increasing. Exposure to opportunistic fungal pathogens is inevitable, but not all patients with underlying diseases increasing susceptibility to IFD, develop it. IFD diagnosis currently uses fungal biomarkers and clinical risk/presentation to stratify high-risk patients and classifies them into possible, probable, and proven IFD. However, the fungal species responsible for IFD are highly diverse and present numerous diagnostic challenges, which culminates in the empirical anti-fungal treatment of patients at risk of IFD. Recent studies have focussed on host-derived biomarkers that may mediate IFD risk and can be used to predict, and even identify IFD. The identification of novel host genetic variants, host gene expression changes, and host protein expression (cytokines and chemokines) associated with increased risk of IFD has enhanced our understanding of why only some patients at risk of IFD actually develop disease. Furthermore, these host biomarkers when incorporated into predictive models alongside conventional diagnostic techniques enhance predictive and diagnostic results. Once validated in larger studies, host biomarkers associated with IFD may optimize the clinical management of populations at risk of IFD. This review will summarise the latest developments in the identification of host biomarkers for IFD, their use in predictive modelling and their potential application/usefulness for informing clinical decisions.

Pre-emptive antifungal therapy versus empirical antifungal therapy for febrile neutropenia in people with cancer.

Intensive cytotoxic chemotherapy for people with cancer can cause severe and prolonged cytopenia, especially neutropenia, a critical condition that is potentially life-threatening. When manifested by fever and neutropenia, it is called febrile neutropenia (FN).Invasive fungal disease (IFD) is one of the serious aetiologies of chemotherapy-induced FN. In pre-emptive therapy, physicians only initiate antifungal therapy when an invasive fungal infection is detected by a diagnostic test. Compared to empirical antifungal therapy, pre-emptive therapy may reduce the use of antifungal agents and associated adverse effects, but may increase mortality. The benefits and harms associated with the two treatment strategies have yet to be determined. OBJECTIVES: To assess the relative efficacy, safety, and impact on antifungal agent use of pre-emptive versus empirical antifungal therapy in people with cancer who have febrile neutropenia. We searched CENTRAL, MEDLINE Ovid, Embase Ovid, and ClinicalTrials.gov to October 2021. We included randomised controlled trials (RCTs) that compared pre-emptive antifungal therapy with empirical antifungal therapy for people with cancer. We identified 2257 records from the databases and handsearching. After removing duplicates, screening titles and abstracts, and reviewing full-text reports, we included seven studies in the review. We evaluated the effects on all-cause mortality, mortality ascribed to fungal infection, proportion of antifungal agent use (other than prophylactic use), duration of antifungal use (days), invasive fungal infection detection, and adverse effects for the comparison of pre-emptive versus empirical antifungal therapy. We presented the overall certainty of the evidence for each outcome according to the GRADE approach. This review includes 1480 participants from seven randomised controlled trials. Included studies only enroled participants at high risk of FN (e.g. people with haematological malignancy); none of them included participants at low risk (e.g. people with solid tumours). Low-certainty evidence suggests there may be little to no difference between pre-emptive and empirical antifungal treatment for all-cause mortality (risk ratio (RR) 0.97, 95% confidence interval (CI) 0.72 to 1.30; absolute effect, reduced by 3/1000); and for mortality ascribed to fungal infection (RR 0.92, 95% CI 0.45 to 1.89; absolute effect, reduced by 2/1000). Pre-emptive therapy may decrease the proportion of antifungal agent used more than empirical therapy (other than prophylactic use; RR 0.71, 95% CI 0.47 to 1.05; absolute effect, reduced by 125/1000; very low-certainty evidence). Pre-emptive therapy may reduce the duration of antifungal use more than empirical treatment (mean difference (MD) -3.52 days, 95% CI -6.99 to -0.06, very low-certainty evidence). Pre-emptive therapy may increase invasive fungal infection detection compared to empirical treatment (RR 1.70, 95% CI 0.71 to 4.05; absolute effect, increased by 43/1000; very low-certainty evidence). Although we were unable to pool adverse events in a meta-analysis, there seemed to be no apparent difference in the frequency or severity of adverse events between groups. Due to the nature of the intervention, none of the seven RCTs could blind participants and personnel related to performance bias. We identified considerable clinical and statistical heterogeneity, which reduced the certainty of the evidence for each outcome. However, the two mortality outcomes had less statistical heterogeneity than other outcomes. For people with cancer who are at high-risk of febrile neutropenia, pre-emptive antifungal therapy may reduce the duration and rate of use of antifungal agents compared to empirical therapy, without increasing over-all and IFD-related mortality; but the evidence regarding invasive fungal infection detection and adverse events was inconsistent and uncertain.

Rapid Etiological Detection Value of Metagenomic Next-Generation Sequencing for Bloodstream Infections in Patients with High-Risk Hematologic Malignancies

Background: Patients with hematological malignancies often suffer from infectious fever, rapid and accurate diagnosis of pathogens facilitates optimal and precise treatment of infectious diseases. In recent years, metagenomic next-generation sequencing (mNGS) technology has been widely used in the etiological detection of patients with respiratory tract infection, sepsis, etc, due to its advantages of rapid detection.However, at present, the clinical diagnosis of mNGS in patients with hematological malignancies in secondary bloodstream infections remains scarce. Objective: In this study, the application value of mNGS in the rapid etiological detection of bloodstream infection pathogens in patients with high-risk hematological malignancies was explored by comparing two etiological detection methods of mNGS and traditional pathogen culture. Methods: This study retrospectively analyzed 66 peripheral blood samples of patients with high-risk hematologic malignancies in our hospital from May 2020 to January 2022. SPSS 20.0 software was used to analyze the positive rate, species distribution and consistency of pathogens between mNGS and traditional pathogen culture method. The diagnostic efficiency of the two etiological detection methods was compared, and the risk factors affecting the positive rate of mNGS were investigated. Results: A total of 66 patients were enrolled in this study, including 38 males and 28 females, with an average age of (43.39±14.427) years. Among the 66 patients, 48 cases were acute myeloid leukemia (48/66, 72.7%), the rest included 2 cases of acute lymphoblastic leukemia (2/66, 3.0%), 3 cases of chronic myeloid leukemia (3/66, 4.5%), 3 cases of myelodysplastic syndrome (3/66, 4.5%), 4 cases of non-Hodgkin lymphoma (4/66, 6.0%), 4 cases of malignant tumor after autologous hematopoietic stem cell transplantation (4/66, 6.0%), and Hemophagocytic syndrome was found in 2 cases (2/66, 3.0%). Peripheral blood samples from 66 patients were both tested for mNGS and traditional pathogen culture. The positive rate of mNGS was 54.5% (36/66), while the traditional culture was 18.1% (12/66). There was a significant statistical difference between the two methods (P=0.000). Multivariate analysis was conducted on the influence of factors such as patient age, gender, disease diagnosis, and time from fever to the mNGS detection, and no statistical difference was found. Among the 36 mNGS-positive patients, a total of 64 pathogens were detected, including 19 bacteria (19/64, 29.7%), 12 fungus (12/64, 18.8%), 31 virus (31/64, 48.4%), and 2 special pathogens (2/64, 3.1%). Six drug-resistant bacteria were detected by mNGS in 5 patients .Among the 12 patients with positive traditional culture, 15 pathogens were detected, including 14 bacteria (14/15, 93.3%) and 1 fungus (1/12, 3.7%). In this study, 8 patients (8/66, 36.4%) were both positive for mNGS and traditional culture tests, and 5 of them (5/8, 62.5%) developed the same type of clinical infection with all or part identical detected pathogens. The time for positive and negative blood culture report was 72h and 7 days respectively, and 24h for mNGS. Among the 54 patients with negative results of traditional culture, 28 cases (28/54, 51.9%) were positive for mNGS, of which 15 cases (15/28, 53.6%) were made corresponding anti-infection regimens according to the positive results of mNGS, and the clinical efficacy was significantly improved. Seven of the 26 patients with both negative traditional culture and mNGS results were considered to have fungal infection based on chest imaging. After empirical antifungal treatment, the imaging results and clinical symptoms were improved; while only 4 of the remaining 19 patients (4/19, 21.5%) had clinical benefit from empirical anti-infective therapy. It demonstrated that pathogen-oriented therapy was significantly better than empirical anti-infective therapy (P=0.000). Conclusions: mNGS enhanced the positive rate of bloodstream pathogens detection and provided more accurate pathogen species in patients with high-risk hematologic malignancies.It could effectively detect multidrug-resistant bacteria and special pathogens,which provide an important reference for clinical antimicrobial treatment and improved their prognosis.

Effect of empirical antifungal treatment on mortality in non-neutropenic critically ill patients: a propensity-matched retrospective cohort study.

To evaluate the effect of empirical antifungal treatment (EAFT) on mortality in critically ill patients without invasive fungal infections (IFIs). This was a single-center propensity score-matched retrospective cohort study involving non-transplanted, non-neutropenic critically ill patients with risk factors for invasive candidiasis (IC) in the absence of IFIs. We compared all-cause hospital mortality and infection-attributable hospital mortality in patients who was given EAFT for suspected IC as the cohort group and those without any systemic antifungal agents as the control group. Among 640 eligible patients, 177 patients given EAFT and 177 control patients were included in the analyses. As compared with controls, EAFT was not associated with the lower risks of all-cause hospital mortality [odds ratio (OR), 0.911; 95% CI, 0.541-1.531; P = 0.724] or infection-attributable hospital mortality (OR, 1.149; 95% CI, 0.632-2.092; P = 0.648). EAFT showed no benefit of improvement of infection at discharge, duration of mechanical ventilation, and antibiotic-free days. However, the later initiation of EAFT was associated with higher risks of all-cause hospital mortality (OR, 1.039; 95% CI, 1.003 to 1.076; P = 0.034) and infection-attributable hospital mortality (OR, 1.046; 95% CI, 1.009 to 1.085; P = 0.015) in patients with suspected IC. This effect was also found in infection-attributable hospital mortality (OR, 1.042; 95% CI, 1.005 to 1.081; P = 0.027) in septic patients with suspected IC. EAFT failed to decrease hospital mortality in non-neutropenic critically ill patients without IFIs. The timing may be critical for EAFT to improve mortality in these patients with suspected IC. ChiCTR2000038811, registered on Oct 3, 2020.

Appropriate empirical antifungal therapy is associated with a reduced mortality rate in intensive care unit patients with invasive fungal infection: A real-world retrospective study based on the MIMIC-IV database.

ObjectiveThe study aimed to determine the prevalence and pathogens of invasive fungal infection (IFI) among intensive care unit (ICU) patients. The next goal was to investigate the association between empirical antifungal treatment and mortality in ICU patients.MethodsUsing microbiological events, we identified all ICU patients with IFI and then retrieved electronic clinical data from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. The data were statistically analyzed using t-tests, chi-square tests, log-rank tests, and Cox regression.ResultsThe most commonly reported fungi were Candida (72.64%) and Aspergillus (19.08%). The most frequently prescribed antifungal medication was fluconazole (37.57%), followed by micafungin (26.47%). In the survival study of ICU patients and patients with sepsis, survivors were more likely to receive empirical antifungal treatment. In contrast, non-empirical antifungal therapy was significantly associated with poor survival in patients with positive blood cultures. We found that the current predictive score makes an accurate prediction of patients with fungal infections challenging.ConclusionsOur study demonstrated that empirical antifungal treatment is associated with decreased mortality in ICU patients. To avoid treatment delays, novel diagnostic techniques should be implemented in the clinic. Until such tests are available, appropriate empirical antifungal therapy could be administered based on a model that predicts the optimal time to initiate antifungal therapy. Additional studies should be conducted to establish more accurate predictive models in the future.

Epidemiology, Clinical Characteristics, Risk Factors, and Outcomes of Candidemia in a Large Tertiary Teaching Hospital in Western China: A Retrospective 5-Year Study from 2016 to 2020.

The aim of this study was to investigate the current status of candidemia and evaluate the clinical characteristics, risk factors and outcomes among different species. We conducted a retrospective study by univariate and multivariate analysis between Candida albicans and non-albicans Candida (NAC) species in a Chinese national medical center from 2016 to 2020. Among the 259 episodes, C. albicans (38.6%) was the leading species, followed by C. tropicalis (24.3%), C. parapsilosis (20.5%), and C. glabrata (12.4%). Most C. albicans and C. parapsilosis were susceptible to nine tested antifungal agents, whereas C. tropicalis showed 30.2~65.9% resistance/non-wild-type to four azoles with great cross-resistance, indicating that fluconazole should not be used for empirical antifungal treatment. In multivariable models, the factor related to an increased risk of NAC was glucocorticoid exposure, whereas gastrointestinal hemorrhage and thoracoabdominal drainage catheters were associated with an increased risk in C. albicans. Subgroup analysis revealed leukemia and lymphoma, as well as glucocorticoid exposure, to be factors independently associated with C. tropicalis in comparison with C. albicans candidemia. No significant differences in 7-day mortality or 30-day mortality were observed between C. albicans and NAC. This study may provide useful information with respect to choosing empirical antifungal agents and exploring differences in molecular mechanisms.

Diagnostic Utility of Bronchoalveolar Lavage in Patients with Acute Leukemia under Broad-Spectrum Anti-Infective Treatment.

Simple SummaryInfections of bacterial, viral, or fungal origin pose a major threat to patients with acute leukemia. Empiric antibiotic and antifungal treatment is a commonly used approach in leukemia patients with febrile neutropenia. To investigate the utility of flexible bronchoscopy (FB) with bronchoalveolar lavage (BAL) in acute leukemia (AL) patients with pneumonia who were already treated with broad-spectrum antibiotics and antifungal agents, we investigated bronchoalveolar samples of 88 patients. Our results indicate that despite broad-spectrum anti-infective treatment, in approximately half of all patients, pathogens could still be isolated in bronchoalveolar samples. Nevertheless, the detection of pathogens does not lead to frequent changes in anti-infective treatments, with most changes performed in patients with herpes simplex and influenza virus detection, and these pathogens might also be detected in less invasive examinations. The need for FB with BAL in patients with AL who are already receiving broad-spectrum empiric anti-infective treatment should therefore be weighed carefully.Despite therapeutic advances in the prevention and treatment of febrile neutropenia, acute leukemia (AL) patients still have considerable febrile neutropenia-related mortality. However, the diagnostic yield of flexible bronchoscopy (FB) and bronchoalveolar lavage (BAL) in acute leukemia patients is unclear. In this retrospective single-center study, we analyzed 88 BAL samples of patients with acute leukemia and pulmonary infiltrates in spite of treatment with broad-spectrum anti-infective agents. The aim was to investigate the impact of FB with BAL on detecting causative organisms, which would result in a change in treatment regimens. The median age was 59 years, and 86% had acute myeloid leukemia. In 47%, pathogens were detectable in BAL fluid (pathogen bacteria, viruses, and fungi in 2, 15, and 18%, respectively), with Aspergillus fumigatus detected most frequently. BAL-guided anti-infective therapy changes were performed in 15%. The detection of herpes simplex and influenza viruses were the main reasons for treatment changes. Despite broad-spectrum anti-infective treatment, in approximately half of all patients, pathogens could still be isolated in BAL samples. However, consecutive changes in anti-infective treatment were considerably less frequent, with most changes performed in patients with Herpes simplex virus and Influenza A detection. The need for FB with BAL in patients with AL receiving broad-spectrum empiric anti-infective treatment should therefore be weighed carefully.

Evaluation of Posaconazole for Primary Prophylaxis of IFI in Acute Myeloid Leukemia under Intensive Induction Chemotherapy. Comparative Real Life Study with Fluconazole in two Hematological Centers in Algeri

Introduction: Acute myeloid leukemia (AML) is a hematological malignancy with a poor prognosis. The early consequences of induction chemotherapy are represented by pancytopenia with severe immunosuppression, which favors the emergence of so-called “opportunistic” infections and in particular invasive fungal infections (IFI) such as invasive aspergillosis (IA). This justifies the implementation of early, empirical, pre-emptive or prophylactic antifungal treatment. The objective of this study is the evaluation of a comparative study before and after the use of primary prevention with posaconazole versus fluconazole, in terms of incidence and mortality of invasive fungal infections (IFIs) during AML inductions, in real life in Algeria. Patients and methods: This study was performed in two periods in the 2 centers concerning the same AML patients receiving the same induction chemotherapy (daunorubicin 60 mg/m2 for 3 days and cytarabine 100 mg/m2 for 7 days) but with a different type of hospitalization with common rooms for Tlemcen and protected single rooms for Oran. Period 1: The retrospective study was performed from 2014 to 2016 and involved 188 patients. 70 patients were hospitalized in a common room (Tlemcen) and 118 patients in a protected single room (Oran). All patients received as primary IFI prophylaxis fluconazole 400 mg/day. Period 2: The prospective study was conducted from April 2017 to September 2018 and involved 55 patients. Fourteen patients were hospitalized in Tlemcen and 41 patients in an Oran. These patients received posaconazole prophylaxis at a dose of 200 mgx3/day. The evaluation and comparison of descriptive and incidence data was performed using Chi2 statistical tests using SPSS version 19 software. Overall survival (OS) were calculated using the Kaplan-Meier estimate and were compared using the log-rank test with a significance level α of 0.05. Results: Period 1: The incidence rate of IFI: 34% at the Oran hospital versus 49% at the Tlemcen hospital (p=0.049). Among the 74 patients who presented with IFI, 39 (53%) died from IFI as the main cause of death, among these deaths, 16 (40%) were recorded at Oran and 23 (68%) at Tlemcen (p=0.011). Period 2: The IFI rate with fluconazole was 39% and that observed with posaconazole 22% (p=0.001) and the cumulative incidence was 39% at 21 days versus 10% at 15 days (p=0.046) with a highly significant decrease in IFI-related deaths: 53% versus 25% (p=0.004). Conclusion: This work has demonstrated the interest in terms of IFI incidence (17% versus 33%, p=0.04) and IFI-related mortality of posaconazole prophylaxis (25% versus 53%, p=0.004) used during AML in the context of hospitalization in common rooms. Furthermore, this work highlights that the combination of posaconazole prophylaxis and hospitalization in a protected single room allows an optimization of the management of this type of patients.&#x0D; &#x0D; &#x0D;

SARS-CoV-2 related ARDS and invasive fungal infections in intensive care patients.

SARS-CoV-2 infection can potentially necessitate intensive care management. An increasing number of case reports are found in the literature indicating patients admitted in an intensive care setting with COVID-19 pneumonitis being complicated with invasive fungal infections.In a retrospective assessment of a three-month period at the national hospital of Malta, examining patients who were suffering from SARS-CoV-2 acute respiratory distress syndrome, 6 out of 63 patients (9.5%) were found to have confirmation or high probability of invasive fungal infection. The consensus definition for invasive fungal disease developed by the European Organization for Research and Treatment of Cancer and the Mycoses Study Group Education and Research Consortium was utilised to aid in the identification of these patients.In total, 15 patients received treatment with an anti-fungal agent in this three-month period, the decision being led by both clinical suspicion and the use of fungal markers obtained from the serum and bronchoalveolar lavage. Although several risk factors are attributed for the development of invasive fungal disease, the main factors identified in our cohort of patients is the SARS-CoV-2 ARDS in itself, along with the use of high dose corticosteroids. The average period of time between admission in intensive care and diagnosis of invasive fungal infection was noted to be 10.5 days.This high incidence of invasive fungal disease in mechanically ventilated patients suffering from SARS-CoV-2 ARDS, relatively early in their course of disease, should guide the clinician to investigate further with fungal biomarkers and cultures in those patients who are clinically deteriorating despite optimal medical treatment, as well as possibly considering empirical anti-fungal treatment if suspicion remains high.

Single and Repeated Episodes of Candida Species Isolated From Cerebrospinal Fluid for Diagnosing Probable Candida meningitis.

Background: The clinical relevance of single or repeated episodes of Candida spp. in cerebrospinal fluid (CSF) in adult patients is debatable.Methods: Forty-two patients with positive Candida episodes in CSF were enrolled in this retrospective study.Results: A total of 42.9% (18/42) were determined to have probable Candida meningitis (PCM). Neurosurgery [odds ratio (OR) (95% confidence interval), OR: 14.4 (1.6–126.1), P = 0.004], lumbar drainage [OR: 5.8 (1.5–23.3), P = 0.009], VP shunt [(OR: 5.6 (1.2–25.8), P = 0.020)], external ventricular drainage [OR: 4.7 (1.3–17.7), P = 0.018], CRP ≥ 10.0 mg/L [OR: 4.9 (1.3–18.1), P = 0.034], and postsurgical broad-spectrum antibiotics [OR: 9.5 (1.8–50.5), P = 0.004] were risk factors associated with PCM. A single CSF Candida episode for the diagnosis of PCM had 7.7% (0.4–37.9%) sensitivity and 20.7% (8.7–40.3%) specificity, whereas repeated episodes of Candida had 66.7% (41.2–85.6%) sensitivity and 95.8% (76.9–99.8%) specificity. No significant difference was found in radiological imaging or CSF profiles between PCM and non-PCM patients. A total of 37.5% (9/24) of patients without PCM received empirical antifungal treatment, and 88.9% (16/18) of patients with PCM received preemptive antifungal treatment. PCM patients had hospitalized mortality rates of 50.0% (9/18). The odds ratio of mortality was 23.0 (2.5–208.6) for PCM patients compared with non-PCM patients (P = 0.001).Conclusion: Both single and repeated positive CSF samples have low validity for the diagnosis of PCM, suggesting that novel strategies for diagnosis algorithms of PCM are urgently needed. Empirical antifungal treatment should be started immediately for suspicious patients with risk factors.

Secondary Infections After Diagnosis of Severe Radiation Pneumonitis (SRP) Among Patients With Non-Small Cell Lung Cancer: Pathogen Distributions, Choice of Empirical Antibiotics, and the Value of Empirical Antifungal Treatment

This study aimed to assess pathogen distributions and antimicrobial sensitivity characteristics in patients with non-small cell lung cancer (NSCLC) with severe radiation pneumonitis (SRP) and secondary infections. Data from 1746 patients with NSCLC and SRP after thoracic radiation therapy from January 2009 to December 2020 were retrospectively analyzed. Pneumonia incidence, causative pathogens, and antibiotic resistance characteristics in patients with secondary lung infections were analyzed. Risk factors associated with mortality were identified through univariate and multivariate analyses. Antifungal drug efficacy and duration-related effects were assessed with Forest plots and receiver operating characteristic curves. Overall, 44.5% of patients with NSCLC and SRP (777 of 1746 patients) were diagnosed with secondary lung infections. In total, 899 bacterial strains were isolated from these patients, with Acinetobacter baumannii (n=206; 27%), Klebsiella pneumonia (n=200; 26.2%), and Pseudomonas aeruginosa (n=104; 13.6%) being the most common. Carbapenem and cefoperazone-sulbactam resistance rates of 52.7% and 32.2%, 28.8% and 26.4%, and 23.7% and 20.2% were observed for these isolates, respectively. Infection-related deaths occurred in 22.4% of patients with SRP. Independent risk factors for infection-related death included poor performance status scores, inappropriate empirical antimicrobial treatment, bacteria/fungal coinfection, and lack of empirical antifungal treatment. Receiver operating characteristic curves showed that the cutoff value of empirical antifungal treatment duration was 9 (area under the curve: 0.819). For patients with SRP and secondary lung infections, appropriate empirical antimicrobial treatment could decrease infection-related mortality, and cefoperazone-sulbactam may be an appropriate antibacterial drug. Empirical antifungal treatment for a minimum of 9 days might contribute to better outcomes. Although this represents a promising treatment approach for patients with SRP and secondary lung infections before antibacterial susceptibility testing, further prospective validation is essential.

Cost-Effectiveness of Serum Galactomannan Surveillance during Mould-Active Antifungal Prophylaxis

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.

Candidemia in Non-neutropenic Pediatric Patients in an Intensive Care Unit

Aim: Candidemia has high morbidity and mortality rate in critically ill patients hospitalized in intensive care units. Prompt initiation of accurate anti-fungal therapy is essential for survival. In this study, a 6-year retrospective candidemia analysis of pediatric intensive care unit (PICU) was performed to review candida species distribution, risk factors for candidemia and change in the antifungal resistance in years. Material and Method: The candidemia episodes of children followed in the PICU of XXX Hospital between January 2014 and January 2020 were analyzed. The demographic and clinical characteristics, laboratory findings, treatments and outcomes of the patients were obtained from the medical records. Results: Fifty-nine episodes of candidemia (54.2% female) were reported in six years, median age at diagnosis was 43 months (range 1-225), median hospital stay was 48 days (range 3-664). All patients had used broad-spectrum antibiotics, majority had comorbidities (89.8%), nasogastric tube (84.7), central venous catheter (78.0%), and on mechanic ventilation (76.3%). Type of candida species was identified in 36 episodes of candidemia; 47.2% of these episodes were caused by C. parapsilosis, 38,9% by C. albicans, 8.3% by C. glabrata (8.3%), 2.8% by C. lusitaniae, and 2.8% by C. tropicalis. Length of hospital stay was longer among patients with nonalbicans candidemia, and these patients had higher leucocyte count at diagnosis. The rate of antifungal resistance increased over the years. Overall, thirty-day mortality rate was 16.9%. Conclusion: For critically ill patients with markedly elevated leucocyte count and long hospital stay, empiric antifungal treatment should cover nonalbicans candida with antifungal resistance.

Risk Factors and Outcomes of Non-albicans Candida Bloodstream Infection in Patients with Candidemia at Siriraj Hospital-Thailand's Largest National Tertiary Referral Hospital.

This study aimed to investigate the risk factors for and the outcomes of patients with candidemia caused by non-albicans Candida. Candidemia patients treated at Siriraj Hospital (Bangkok, Thailand) during January 2016 to December 2017 were enrolled. A total of 156 patients (mean age: 65 years, 56.4% male) were included. The most prevalent underlying conditions were diabetes (32.1%), chronic cardiac disease (28.2%), chronic kidney disease (26.9%), and hematologic malignancies (21.2%). Candida species isolated from patient blood were C. tropicalis (49.4%), C. albicans (28.8%), C. glabrata (16.7%), and C. parapsilosis (5.1%). Fluconazole resistance was significantly increased in C. tropicalis (37.8%). No independent risk factors were associated with patients with non-albicans Candida candidemia compared to those with C. albicans candidemia. There was no significant difference in mortality between patients with non-albicans Candida candidemia and patients with C. albicans candidemia (OR: 1.35, 95% CI: 0.64–2.85). When compared with C. albicans candidemia, multivariate analysis revealed chronic liver disease (OR: 11.39, 95% CI: 1.38–94.02), neutropenia (OR: 4.31, 95% CI: 1.34–13.87), and male gender (OR: 2.34, 95% CI: 1.04–5.29) to be independent risk factors for C. tropicalis candidemia. The observed high resistance of C. tropicalis to fluconazole indicates that fluconazole should not be used for empirical antifungal treatment in these patients.