Fungal Bloodstream Infections Research Articles

Clinical features and prognosis of children with fungal bloodstream infection following chemotherapy for acute leukemia

To investigate the clinical features and prognosis of children with fungal bloodstream infection (BSI) following chemotherapy for acute leukemia (AL). A retrospective analysis was performed on 23 children with fungal BSI following chemotherapy for AL in three hospitals in Fujian Province, China, from January 2015 to December 2023. Their clinical features and prognosis were analyzed. Among all children following chemotherapy for AL, the incidence rate of fungal BSI was 1.38% (23/1 668). At the time of fungal BSI, 87% (20/23) of the children had neutrophil deficiency for more than one week, and all the children presented with fever, while 22% (5/23) of them experienced septic shock. All 23 children exhibited significant increases in C-reactive protein and procalcitonin levels. A total of 23 fungal isolates were detected in peripheral blood cultures, with Candida tropicalis being the most common isolate (52%, 12/23). Caspofungin or micafungin combined with liposomal amphotericin B had a relatively high response rate (75%, 12/16), and the median duration of antifungal therapy was 3.0 months. The overall mortality rate in the patients with fungal BSI was 35% (8/23), and the attributable death rate was 22% (5/23). Fungal BSI following chemotherapy in children with AL often occurs in children with persistent neutrophil deficiency and lacks specific clinical manifestations. The children with fungal BSI following chemotherapy for AL experience a prolonged course of antifungal therapy and have a high mortality rate, with Candida tropicalis being the most common pathogen.

A Chart Review for Epidemiology and Outcome of Fungal Bloodstream Infections Among Neonates in a Tertiary Care Hospital at North India

Background and Aims The risk of fungal bloodstream infection (BSI) and accompanying mortality in neonates varies widely in between centres depending on the region, the population characteristics and the risk factors. Methods This chart review of neonatal cases with fungal BSI admitted in a tertiary care teaching hospital in North India aimed to comprehensively investigate the epidemiology, profile of fungal species (and their susceptibility to various antifungal agents), risk factors, clinical profile and outcomes in these neonates. The study spanned over a one-year period, from September 2022 to August 2023, included all symptomatic neonates with positive blood cultures for fungal pathogen. Results Over one year, 24 out of 1,174 neonates at risk were diagnosed with fungal BSI, with a cumulative risk of 2.0 per 100 neonates. A peak in cases occurred in February. Candida pelliculosa was the predominant species (75% of isolates), while Candida albicans constituted 4.2%. Most isolates were sensitive to fluconazole, except for some fluconazole-resistant Candida pelliculosa (5.5%) and Candida tropicalis (25.0%), which remained susceptible to amphotericin-B and voriconazole. Around 60% of neonates were preterm, 40% had very low birth weight and 37% were small for gestational age. Nearly all had received prior broad-spectrum antibiotics, with 92% receiving prolonged courses over five days. Respiratory support, including intubation and mechanical ventilation, was used in 83% before onset of fungal sepsis. Intriguingly, all neonates had some invasive device in place for more than seven days. Mortality rate of 25% was observed, with preterm birth and gastrointestinal anomalies contributing to adverse outcomes. Conclusions This study confirms the ongoing shift in trend from albicans to non-albicans Candida infections in our region as well. A seasonal peak of fungal sepsis noted in the month of February hinted at potential seasonal variation or lapses in infection control practices during colder months. The analysis of trends in fungal BSI might hold a significance within neonatal intensive care units (NICUs) for the prompt detection of outbreaks. Simultaneously, understanding and analysing risk factors associated with fungal BSI are essential for targeted prevention.

The impact of delayed versus early administration of granulocyte colony-stimulating factor following autologous hematopoietic stem cell transplantation on transplantation outcome.

Granulocyte colony-stimulating factor (G-CSF) is routinely administered after autologous hematopoietic stem cell transplantation (auto-HSCT) to decrease the duration of neutropenia and diminish the incidence of febrile neutropenia. Nevertheless, the most advantageous timeframe for administering G-CSF in the transplantation setting remains elusive. We conducted a cross-sectional study of 200 patients diagnosed with hematological malignancies who underwent auto-HSCT between July 2017 and January 2022. Patients were divided into two groups of 100 individuals based on the timing of G-CSF administration after auto-HSCT. In the first group, G-CSF was administered on post-transplantation day +1, while in the second group, G-CSF was administered on post-transplantation day +5. Patient demographics and clinical outcomes, including time to neutrophil engraftment, time to platelet engraftment, length of hospital stay, duration of fever, and incidence of bacterial and fungal bloodstream infections, were compared between the two groups. We identified a significantly shorter platelet engraftment time in the day +5 group than in the day +1 group (P<0.001), though the groups were similar regarding neutrophil engraftment time. The total number of G-CSF injections differed significantly according to the administration schedule. The number of red blood cells and length of hospital stay was greater in the day +1 group (all P<0.001). The incidence of bacterial and fungal bloodstream infections and duration of fever did not differ between the groups. Delayed administration of G-CSF on day +5 is as effective as early administration and can positively influence platelet engraftment, transfusion support, and hospitalization time.

Antifungal susceptibility and virulence determinants profile of candida species isolated from patients with candidemia

Candida is the most prevalent fungal bloodstream infection (BSI) with a high mortality rate among hospitalized patients. Another concern facing physicians is rising global incidence of drug-resistant Candida. This study aimed to characterize the prevalence, antifungal susceptibility, biofilm formation, and virulence genes (HWP1, ALS1, SAP2) of different Candida spp. isolated from patients with candidemia. 52 isolates of Candida spp. were identified from blood cultures by chromogenic Candida agar and confirmed by the VITEK 2 system. Isolates were tested for antifungal susceptibility by disk diffusion and VITEK 2 system. Biofilm formation and investigated genes were detected by the Congo red method and conventional PCR, respectively. Candida spp. caused 2.3% of detected BSIs, of which 32.7% were caused by Candida albicans (C. albicans) and 67.3% by non-albicans Candida (NAC), with the predominance of C. tropicalis (25%), followed by C. parapsilosis (17.3%), and C. krusei (13.5%). The susceptibility rates to fluconazole, voriconazole, caspofungin, micafungin, amphotericin B, and flucytosine were 64.7%, 76.5%, 100.0%, 100%, 100.0%, and 100.0% in C. albicans, while 53.6%, 71.4%, 91.4%, 91.4%, 94.3%, and 94.3% in NAC, respectively. Biofilm production, HWP1, ALS1, and SAP2 were detected in 70.6%, 82.4%, 76.5%, and 52.9% of C. albicans and 74.3%, 85.7%, 80.0%, and 48.6% of NAC, respectively. There is remarkable shift to NAC BSIs and high azole resistance. Antifungal stewardship and analysis of risk factors associated with this shift are needed.

Pseudo-NRBC in the Mindray BC-6800Plus analyzer: A clue for diagnostic anticipation of fungemia. Experimental and preliminary clinical reports.

Candidemia can be a significant cause of death in immunosuppressed or debilitated patients particularly. Abnormalities of the instrumental cytograms of some hematological analyzers, such as Mindray BC-6800Plus, can be related to circulating Candida. We studied the possible diagnostic usefulness of this information. A fungal bloodstream infection has been simulated by adding aliquots of Candida albicans, Candida parapsilosis, and Candida glabrata to 75 leftovers and anonymized peripheral blood samples. Cytographic abnormalities like those of experimental samples were used to select patients with possible fungemia. The microscopic review of peripheral blood smears constituted the confirmatory method. In all experimental samples, the various Candida types caused pseudo-NRBC and morphological abnormalities of WNB and DIFF cytograms. Circulating blastospores, free or engulfed by neutrophils, were the microscopic findings in the peripheral blood smears. In the clinical verification, 72 patients were recruited based on the presence of an evocative cluster in the WNB and DIFF cytograms. The microscopic review of 39 out of 72 samples was positive for NRBC. According to blood cultures, light microscopy revealed fungal forms of several Candida or non-Candida types in the remaining 33 samples. Nine of these cases were not yet known to suffer from bloodstream infection. Although further confirmatory clinical studies are required for these diagnostic abilities, the BC 6800Plus cytographic abnormalities related to fungemia have proven helpful in rapidly monitoring persistent fungemia in already diagnosed patients. In unknown or undiagnosed cases, they could be the trigger point for the subsequent diagnostic-therapeutic pathway.

Epidemiological patterns of candidaemia: A comprehensive analysis over a decade.

The prevalence of fungal bloodstream infections (BSI), especially candidaemia, has been increasing globally during the last decades. Fungal diagnosis is still challenging due to the slow growth of fungal microorganisms and need for special expertise. Fungal polymicrobial infections further complicate the diagnosis and extend the time required. Epidemiological data are vital to generate effective empirical treatment strategies. The overall aim of this project is to describe the epidemiology of monomicrobial candidaemia and polymicrobial BSI, both with mixed fungaemia and with mixed Candida/bacterial BSIs. We conducted a single-centre retrospective epidemiological study that encompasses 950,161 blood cultures during the years 2010 to 2020. The epidemiology of monomicrobial and polymicrobial candidaemia episodes were investigated from the electronic records. We found that 1334 candidaemia episodes were identified belonging to 1144 individual patients during 2010 to 2020. Candida albicans was the most prevalent species detected in candidaemia patients, representing 57.7% of these episodes. Nakaseomyces (Candida) glabrata and Candida parapsilosis complex showed an increasing trend compared to previous studies, whereas Candida albicans demonstrated a decrease. 19.8% of these episodes were polymicrobial and 17% presented with mixed Candida/bacterial BSIs while 2.8% were mixed fungaemia. C. albicans and N. glabrata were the most common combination (51.4%) in mixed fungaemia episodes. Enterococcus and Lactobacillus spp. were the most common bacteria isolated in mixed Candida/bacterial BSIs. Polymicrobial growth with candidaemia is common, mostly being mixed Candida/bacterial BSIs. C. albicans was detected in more than half of all the candidaemia patients however showed a decreasing trend in time, whereas an increase is noteworthy in C. parapsilosis complex and N. glabrata.

Alpha1-antitrypsin impacts innate host–pathogen interactions with Candida albicans by stimulating fungal filamentation

ABSTRACT Our immune system possesses sophisticated mechanisms to cope with invading microorganisms, while pathogens evolve strategies to deal with threats imposed by host immunity. Human plasma protein α1-antitrypsin (AAT) exhibits pleiotropic immune-modulating properties by both preventing immunopathology and improving antimicrobial host defence. Genetic associations suggested a role for AAT in candidemia, the most frequent fungal blood stream infection in intensive care units, yet little is known about how AAT influences interactions between Candida albicans and the immune system. Here, we show that AAT differentially impacts fungal killing by innate phagocytes. We observed that AAT induces fungal transcriptional reprogramming, associated with cell wall remodelling and downregulation of filamentation repressors. At low concentrations, the cell-wall remodelling induced by AAT increased immunogenic β-glucan exposure and consequently improved fungal clearance by monocytes. Contrastingly, higher AAT concentrations led to excessive C. albicans filamentation and thus promoted fungal immune escape from monocytes and macrophages. This underscores that fungal adaptations to the host protein AAT can differentially define the outcome of encounters with innate immune cells, either contributing to improved immune recognition or fungal immune escape.

Universal antifungal prophylaxis effectively prevents fungal bloodstream infection in pediatric liver transplant recipients: a retrospective real-world study

ObjectivesFungal bloodstream infection (fBSI) following pediatric liver transplantation presents a significant challenge; however, there remains a paucity of guidance regarding antifungal prophylaxis in this population. This study aimed to evaluate the effectiveness of universal antifungal prophylaxis and propose a desirable strategy. MethodsWe enrolled 604 pediatric patients who underwent liver transplantation between 2020 and 2023, including 242 patients with empirical prophylaxis and 362 patients with universal prophylaxis. Univariate and multivariate logistic regression analyses were performed to identify independent factors for fBSI. ResultsEight (2.2%) pediatric recipients in the universal prophylaxis group and 13 (5.4%) in the empirical group developed fBSI (P = 0.038). Universal prophylaxis was a protective factor (P = 0.044), while high-volume intraoperative plasma transfusion and deceased donor liver transplantation were independent risk factors for fBSI (P = 0.035 and 0.008, respectively). Universal antifungal strategy showed an increased overall survival trend after liver transplantation although without significant statistical difference (P = 0.217). Patients with fBSI had poorer survival than those without fBSI (P <0.001). ConclusionsUniversal prophylaxis strategy for fBSI in pediatrics after liver transplantation is desirable as it could markedly decrease the occurrence of fBSI. Pediatric patients with deceased donors and high-volume intraoperative transfusion should be paid more attention to preventing fBSI.

Bloodstream infections: trends and evolution of incidence and etiology in a 12-year period (2010–2021)

Introduction The epidemiological evolution of bloodstream infections (BSIs) in the last decade is not clearly defined. Our aim was to analyze the changes in the workload in our institution and to describe the evolution of the incidence and etiology of BSIs in a 12-year period, including the COVID-19 pandemic. Methods All blood cultures received in the laboratory of a tertiary general hospital between 2010 and 2021 were analyzed. Bloodstream infection episodes refer to each episode of bacteremia or fungemia in each patient. Incidence rates per 1000 admissions and per 100,000 population were calculated. Results No significant changes in the incidence of BSI episodes/1000 admissions were observed (mean, 31.1), while estimated population-based incidences showed declining trends (mean, 182.8/100,000 inhabitants). There was a slight increase in BSI episodes per 1000 admissions caused by Gram-negatives (mean, 16.6/1000 admissions) and E. coli was the most frequent pathogen (mean, 8.5/1000 admissions). There was no significant rise in episodes caused by ESBL- and carbapenemase-producing E. coli or K. pneumoniae, with a decline in those caused by methicillin-resistant S. aureus. A spike in BSI episodes, fungal BSIs and catheter-related infections was detected in 2020, during the COVID-19 outbreak. Conclusions No clear increase in the incidence of BSI episodes was detected in our center over this period. Gram-negatives are the most frequent etiology, with no clear rise in antimicrobial resistance phenotypes. The COVID-19 pandemic accounted for a small increase in BSI episodes in 2020, probably related to the increase of catheter-related infections.

Cytomegalovirus Reactivation in Severe Coronavirus Disease 2019: Case Series from a Tertiary Care Center in the Western State of India

Abstract Introduction: Cytomegalovirus (CMV) reactivation in patients who have been admitted to the intensive care unit (ICU) is linked to higher mortality and health-care costs. There is a dearth of published research on CMV reactivation in patients with severe SARS-CoV-2. Materials and Methods: Objectives: The objective of this study was to describe clinical and laboratory profiles and outcomes of CMV reactivation in patients with severe SARS-CoV-2 illness. In this retrospective study carried out at a tertiary care hospital ICU in the Western state of India, patients with severe SARS-CoV-2 who were admitted from January 1, 2021, to May 31, 2021, and who got CMV viral load testing by reverse transcriptase polymerase chain reaction were analyzed. Results: During the study period, 27 out of 277 admitted patients were subjected to plasma CMV viral load testing, of which 13 patients had detectable viral load giving a prevalence of 4.7%. Patients who tested positive for CMV had significantly higher mortality (P = 0.020) and ventilator support needs (P = 0.004). Both fungal and bacterial bloodstream infections were frequent in CMV-positive patients, but neither was statistically significant (P = 0.065 and P = 0.571, respectively). In this case series, there was no difference in CMV reactivations according to the degree of lymphopenia (P = 0.149), usage of steroids (P = 0.766), or immunomodulatory medications (tocilizumab/bevacizumab, P = 0.926). Conclusions: In SARS-CoV-2 patients with severe illness, CMV reactivation was associated with an increased need for ventilator support, a higher incidence of nosocomial infection (bacterial and fungal), and overall mortality.

Enhanced in-vitro anti-Candida efficacy of Euphorbia milii Des Moul mediated copper nanoparticles against clinically isolated Candida albicans.

Emergence of fungi as a pathogenic threat presents a significant challenge to public health, notably in intensive care units (ICUs) and among immunocompromised patients. Various factors, including sepsis-induced barrier disruptions, immune system dysfunction, and extremes of age, contribute to increased susceptibility to fungal infections. Hospital practices, such as prolonged surgeries, broad-spectrum antibiotic use, and invasive procedures, further exacerbate the risk. Fungal bloodstream infections, particularly those caused by Candida albicans, rank among the most common hospital-acquired infections, leading to substantial morbidity and mortality. The global rise in invasive candidiasis, particularly due to non-albicans Candida species, presents challenges in the diagnosis and treatment due to nonspecific symptoms and emerging antifungal resistance. Nanotechnology interventions particularly by utilizing green synthesized copper nanoparticles could possibly provide a novel solution to combat microbial colonization, biofilm formation, and drug resistance. This study aimed to assess the prevalence of candidemia, identify the distribution of causative Candida species, and understand their susceptibility patterns to commonly used antifungal agents for effective management in ICU settings. Additionally, the study sought to explore the in vitro anti-Candida activity of green copper nanoparticles synthesized using Euphorbia milii des moul extract. This study was conducted at Microbiology Laboratory of Maharishi Markandeshwar Institute of Medical Sciences and Research from January to December 2022, focused on ICU patients suspected of bloodstream infections. Blood samples were collected aseptically and processed using BD BACTECTM culture vials. Identification of organisms was performed via the Vitek-2 system by confirming candidemia with positivity in both blood samples. After that antifungal susceptibility testing was also performed against Clinical and Laboratory Standards Institute recommended antifungal drug using Vitek 2 system. G-CuNPs were synthesized using E. milii Des moul extract and possessed for physiochemical characterization. The anti-Candida activity of G-CuNPs was evaluated through the MTT assay and time kill assay. After that generation of intracellular reactive oxygen species and DNA degradation were evaluated to understand its mechanism. This study identified a candidemia rate of 7.3% (58/789). Age and gender analysis revealed higher Candida colonization rates in individuals above 60 years old and females. Antifungal sensitivity profiling indicated notable resistance to fluconazole (27.59%) and voriconazole (25.86%). Synthesizing G-CuNPs using E. milii des moul extract represents a novel approach exhibiting significant fungicidal potency against clinically isolated C. albicans, supporting potential therapeutic applications. the findings concluded that synthesized G-CuNPs have tremendous potential to battle against medical device-borne infections by surface coating.

Evaluation of Different Blood Culture Bottles for the Diagnosis of Bloodstream Infections in Patients with HIV.

Bloodstream infection (BSI) is a significant factor contributing to hospitalization and high mortality rates among human immunodeficiency virus(HIV)-positive patients. Therefore, the timely detection of this condition is of utmost importance. Blood culture is considered the gold standard for diagnosing BSIs. Currently, BD BACTEC™ Plus Aerobic/F culture bottles and the BD BACTEC™ Myco/F Lytic culture bottles can be used for blood culture. This study aimed to evaluate the efficacy of two different types of culture bottles in diagnosing BSIs in patients with HIV. A retrospective analysis was conducted on HIV-positive patients hospitalized in the Infection Department of Wenzhou Central Hospital between July 2019 and October 2021. A total of 246 pairs of blood samples were included, consisting of an aerobic culture vial and a Myco/F culture vial. Blood culture results and clinical diagnosis were utilized to identify the presence of BSI. Out of 246 cases, 84 cases had positive blood cultures. Fungal BSIs, particularly Talaromycesmarneffei BSIs, were the most prevalent among patients with HIV. The positive rate of Myco/F culture bottles (89.29%) was significantly higher compared with aerobic culture bottles (69.05%; P = 0.001). In the diagnosis of fungal BSIs, the positive rate of Myco/F culture bottles was 88.57%, which was significantly higher than that of aerobic culture bottles (72.86%; P = 0.018). The Myco/F culture bottle has more advantages in diagnosing Talaromyces marneffei BSIs (P=0.028).In addition, mycobacteria were exclusively detected in Myco/F culture bottles. Fungal BSIs are the predominant type of infections in HIV-positive patients. Myco/F culture bottles exhibit noteworthy attributes of high positive rate in diagnosing HIV combined with BSI. These advantages are conducive to obtaining accurate culture results and minimizing missed diagnoses.

October 2023 Critical Care Case of the Month: Multi-Drug Resistant K. pneumoniae

No abstract available. Article truncated after 150 words. History of Present Illness: A 75-year-old man presented from a skilled nursing facility with altered mental status and hypotension. He had a seven-year-long history of steroid-dependent myasthenia gravis, but had previously declined Covid vaccination, and subsequently experienced a severe case of COVID-19 pneumonia five months prior to admission. This resulted in chronic respiratory failure and renal failure for which he subsequently underwent tracheostomy, tunneled subclavian vein dialysis catheter placement and percutaneous endoscopic gastrostomy (PEG). He had resided in a skilled nursing facility since then, requiring four subsequent hospital readmissions for complications. These sequentially included septic shock due to a catheter associated blood stream infection, an intra-abdominal abscess due to PEG migration into the peritoneum resulting in fungal blood stream infection, recurrent intra-abdominal infection with multiple organisms, and bacterial pneumonia. Treatment of these infectious complications included replacement of the tunneled dialysis catheter and exploratory laparotomy with debridement of multiple abscesses. The …

Microbiology and Clinical Outcome of Bloodstream Infections in Patients After Hematopoietic Stem Cell Transplantation.

Patients after hematopoietic stem cell transplantation (HSCT) are often followed by bloodstream infections (BSIs). BSI is an important cause of non-relapse mortality (NRM) in HSCT patients. We conducted a retrospective cohort study of patients (aged >14 years) who underwent HSCT at our hospital from 2017 to 2021. Population characteristics, BSI microbiology, resistance to common antibiotics, and 30-day all-cause mortality were analyzed. Of 3054 patients, 169 (5.5%) had BSIs after HSCT. Male, not in complete remission at transplantation and longer duration of neutropenia were risk factors for the development of BSI after HSCT. These BSIs were Gram-negative bacterial (n=123, 69.49%), Gram-positive bacterial (n=27, 15.25%), fungal (n=11, 6.36%), and polymicrobial (n=16, 9.25%). Among the Gram-negative bacteria, the proportions of isolates resistant to ceftazidime, cefepime, and piperacillin-tazobactam were similar (72.93%, 74.80%, and 77.42%, respectively). The overall drug resistance rates of amikacin and imipenem were 16.13% and 43.90%, respectively. Staphylococcus isolates were methicillin-resistant. In Enterococcus isolates, the penicillin resistance rate was 84.62%. Eleven isolates of Candida tropicalis were resistant to fluconazole and were sensitive to amphotericin B and flucytosine. The 30-day all-cause mortality rate of the 169 patients with BSIs was 8.88%. The 30-day all-cause mortality of patients with Gram-negative bacterial BSIs was 7.32%, 25.00% for polymicrobial BSIs, and 36.36% for fungal BSIs. The 30-day all-cause mortality of patients with fungal BSIs was significantly higher than that of patients with Gram-negative (P=0.0023) and Gram-positive bacteria (P=0.0023). Fungal BSI and non-Hodgkin's lymphoma (NHL) were associated with higher 30-day mortality. Our study reveals the microbiological characteristics and 30-day all-cause mortality in patients with bloodstream infections after HSCT. Our data provides strong support for empirical antimicrobial therapy and infection prevention strategies for patients with BSIs after HSCT.

Assessment of Fungal Blood Stream Infection in Patients with Liver Cirrhosis Admitted to The Intensive Care Unit

Assessment of Fungal Blood Stream Infection in Patients with Liver Cirrhosis Admitted to The Intensive Care Unit

Pol32, an accessory subunit of DNA polymerase delta, plays an essential role in genome stability and pathogenesis of Candida albicans

ABSTRACT Candida albicans is a pathobiont that inflicts serious bloodstream fungal infections in individuals with compromised immunity and gut dysbiosis. Genomic diversity in the form of copy number alteration, ploidy variation, and loss of heterozygosity as an adaptive mechanism to adverse environments is frequently observed in C. albicans. Such genomic variations also confer a varied degree of fungal virulence and drug resistance, yet the factors propelling these are not completely understood. DNA polymerase delta (Polδ) is an essential replicative DNA polymerase in the eukaryotic cell and is yet to be characterized in C. albicans. Therefore, this study was designed to gain insights into the role of Polδ, especially its non-essential subunit Pol32, in the genome plasticity and life cycle of C. albicans. PCNA, the DNA clamp, recruits Polδ to the replication fork for processive DNA replication. Unlike in Saccharomyces cerevisiae, the PCNA interaction protein (PIP) motif of CaPol32 is critical for Polδ’s activity during DNA replication. Our comparative genetic analyses and whole-genome sequencing of POL32 proficient and deficient C. albicans cells revealed a critical role of Pol32 in DNA replication, cell cycle progression, and genome stability as SNPs, indels, and repeat variations were largely accumulated in pol32 null strain. The loss of pol32 in C. albicans conferred cell wall deformity; Hsp90 mediated azoles resistance, biofilm development, and a complete attenuation of virulence in an animal model of systemic candidiasis. Thus, although Pol32 is dispensable for cell survival, its function is essential for C. albicans pathogenesis; and we discuss its translational implications in antifungal drugs and whole-cell vaccine development.

Bacterial and fungal etiology of bloodstream infections in leukemic children under chemotherapy

Bloodstream infections are severe complications in children with leukemia during chemotherapy and represent a major public health problem. The purpose of this study is to investigate patterns of bacterial and fungal bloodstream infection in children with leukemia during chemotherapy and to provide a rational basis for the use of antibiotics to reduce bacterial resistance. This study was conducted at the Centre for Hematology and Oncology of the children's Protection Teaching Hospital in the Medical City in Baghdad between January and December 2021. We registered children aged under 18 with leukemia and undergoing chemotherapy. A total of 197 bloodstream infection episodes were diagnosed in 165 children. Gram-positive bacteria are the most frequent pathogens (58%) (Staphylococcus aureus 22.8% was the predominant pathogen followed by Staphylococcus epidermidis 13.7%). Among Gram-negative isolates (38%), E. coli 15.2%was the most prevalent isolate followed by pseudomonas aeruginosa 11.7%). The most common isolate of fungi (4%) was candida. albicans 2%.During testing the bacterial pathogen to empirical antibiotics we did find multidrug resistance among bacterial groups. The Gram-positive isolates showed a high resistance rate to oxacillin (99%) and a low resistance rate to Linezolid (6%)while Gram-negative isolates exhibited( 100%) resistance to Ampicillin and the least resistance(5%) to cefoxitin. The incidence of bloodstream infection in children with leukemia is caused by multidrug-resistant organisms, without changes during different chemotherapy phases. Further study is needed to reduce this infection and antibiotic sensitivity tests are essential to avoid bacterial resistance and improve advanced therapeutic prophylaxis strategies.

Epidemiology, management and outcome of candidaemia in patients with diabetes.

Candidaemia is the commonest fungal bloodstream infection in hospitalised patients. Diabetes is one of the risk factors for mortality from candidaemia. We compared the epidemiology, clinical characteristics and management of candidaemia in patients with and without diabetes. Over a 10-year period, 200 episodes of Candida bloodstream infection were documented. Patients with diabetes were younger (58.7 vs 65.5 years), less likely to be suffering from cancer (21.8% vs 36%), and had significantly lower 30-day and 90-day crude mortality (17.2% vs 35.6% and 28.4% vs 48.6%, respectively). Candida glabrata was more common in patients with diabetes (39.3% vs 29.7%). Based on European Confederation of Medical Mycology (ECMM) quality indicators, the management of patients with and without diabetes was similar. Our study highlights the importance of epidemiological data in relation to candidaemia in patients with diabetes and the growing threat of invasive C. glabrata infection in this subset of patients.

Granulocyte Transfusions in Children Undergoing Hematopoietic Stem Cell Transplantation

Introduction Neutropenia, often encountered in patients undergoing hematopoietic stem cell transplantation (HSCT) increases the risk of bacterial and/or fungal infections. Granulocyte transfusions (GT) have been indicated for neutropenic patients with severe infections that are often refractory to antimicrobial therapy. There is paucity of pediatric studies on the use of GT in children, leading to reluctance in using GT even when severe documented infections are present. This retrospective study was done on all patients who received at least a single GT at our institution until 2021 to study the indications, dosage, safety, and tolerability of GT. As mandated by the nursing policy all but one patient received their infusion(s) in the pediatric intensive care unit (PICU) for concern of possible reaction or decompensation following GT. Results Thirteen patients who underwent 16 transplants (hematological malignancies = 11, immune dysregulation = 1, severe aplastic anemia = 1) and received GT during their stay for transplant. All patients had prolonged neutropenia and were given 1- to 69 GT (median = 5) for fungal or bacterial infections (n = 5 each), fungal and bacterial infection (n=1) and perianal cellulitis (n =2). The dose of GT for each patient ranged from 145-470 mL per infusion. GT were given no more than once a day, and varied with 3, 5, 1, 1, 2 and 1 patients getting 1, 5, 8, 11, 13 and 69 days of granulocytes. The patient who got 69 GT, got them over 4 separate time periods during his prolonged stay in hospital for graft failure after first and second transplants. Nine patients received premedication with acetaminophen, diphenhydramine, and/or hydrocortisone. None of the patients had any major transfusion reaction or hemodynamic instability during or after the GT. The primary indication for which GT were given, improved in 8/13 (61.5%) of the patients, with partial response in an additional patient, and no response in the remaining 4 patients. At the time of this study, 3/13 patients were alive and the cause of death of the remaining 10 patients was relapse (n=2), primary or secondary graft failure (n=3), VOD (n=2), steroid refractory acute GvHD (n=1), and disseminated fungal disease (n=2). Of the 3 patients still living, all are in remission with 2 having chronic GVHD. Conclusion In our study, GT were well tolerated without any reported significant side effects and after our study, all GT were allowed to be given on the regular floor avoiding the need for transfer to PICU. While GT appear to be safe, those who received infusions for localized infections in the setting of neutropenia had better outcomes compared to those who received infusions for disseminated or systemic disease. A small sample size and retrospective study are the major limitations of our study. We propose that in children undergoing HSCT, in the setting of prolonged neutropenia of any cause, GT can be helpful in ameliorating infectious complications like perianal cellulitis/fistulas, and bacterial or fungal blood stream infections. A larger prospective study is needed to address the effects of GT on overall survival.

Long-term survival following fungal catheter-related bloodstream infection for patients with intestinal failure receiving home parenteral support.

A fungal-related catheter-related bloodstream infection (CRBSI) is less frequent than those induced by bacteria. In the past, a single episode of fungal CRBSI has been used as a marker of home parenteral nutrition (HPN) failure and thus a possible indication for intestinal transplantation. Survival outcomes were assessed from a prospectively maintained database of patients initiated on HPN for underlying chronic intestinal failure between 1993 and 2018, with a censoring date of December 31, 2020. Cox regression was performed to assess predictors of mortality with univariable and multivariable analysis. A total of 1008 patients were included in the study, with a total of 1 364 595 catheter days. There were 513 CRBSI events recorded in 262 patients, equating to a CRBSI rate of 0.38/1000 catheter days. A total of 38/262 (14.5%) patients had at least one episode of fungal CRBSI, whereas 216/262 (82.4%) had at least one bacterial but no fungal CRBSI. The median time between HPN initiation and the first CRBSI episode was 20.6 months (95% confidence interval, 16.5-24.1). Episodes of fungal or bacterial CRBSI and the number of CRBSI episodes were not associated with increased mortality. Overall, 15 CRBSI-related deaths were observed in the observation period (0.01 CRBSI deaths/1000 catheter days), two of these were fungal in origin. The occurrence of a fungal CRBSI does not increase the risk of death compared with patients who have bacterial CRBSI or those without a CRBSI event.