Recurrent bacterial infections, but not fungal infections, characterise patients with ELANE ‐related neutropenia: a French Severe Chronic Neutropenia Registry study

Abstract Abstract 3268 Chronic Neutropenia of Childhood (CNC) is defined as an absolute neutrophil count that is persistently below 0.5×109/L and leaves patients at risk of severe, systemic bacterial and fungal infections. The standard treatment to raise the neutrophil count is daily injections of recombinant G-CSF to maintain the neutrophil count above 1.0 × 109/L and the child infection free. A long acting Pegylated G-CSF (PEG G-CSF) is available but is unlicensed for use in chronic neutropenia and in children. Concern has been expressed regarding long term exposure to PEG G-CSF and the potential for neutralising antibodies; there is a lack of clinical evidence and experience in its use for CNC. Potential advantages exist in its use including a more stable and sustained neutrophil count and fewer subcutaneous injections; the latter an important consideration in a paediatric population. We report a single centre experience of seven consecutive cases using PEG G-CSF in CNC. Five boys and two girls age range five months to six years had a total of thirty four presentations in Accident and Emergency for bacterial infection; eleven episodes required hospital admission and intravenous antibiotics. All had a history of persistent neutropenia ranging from one to thirty two months. Prophylactic oral anti-infectives; ciprofloxacin and itraconazole were prescribed and once bone marrow examination had excluded evidence for other causes of persistent neutropenia standard G-CSF was commenced. All seven patients were responsive to G-CSF and so following two – four weeks of treatment a switch to PEG G-CSF was made. Neutrophil response kinetics was monitored to tailor individual dose and frequency of injections. In all cases there was an increased longevity of neutrophil response over time. Treatment with PEG G-CSF was required initially every seven days, but the neutrophil count was ultimately sustained by one injection every three to four weeks. We hypothesise that this is due to gradual recruitment of immature precursors and stem cells towards the neutrophil lineage; whereas the initial neutrophil responses are the result of more mature committed precursors. Once on PEG G-CSF there was a marked reduction in serious bacterial infections with a total of only six urgent medical assessments sought. This resulted in one admission each for three of the children. Four children had no further hospital admissions. The neutrophil count responded and was maintained in all seven cases. Prophylactic anti-infectives were discontinued once a stable neutrophil count was achieved. Six patients continued the PEG G-CSF successfully whilst one discontinued its use due to maternal concerns of an associated behaviour change and sleep disturbance, not an expected side effect of PEG G-CSF. These cases demonstrate the effective, safe use of PEG G-CSF in chronic neutropenia of childhood, with a more sustained neutrophil count and thus reduced risk of infection. There was no evidence of a reduced response to PEG C-CSF suggesting no development of neutralising antibodies. The decreased frequency of injections has led to an improved quality of life for these children and their families, with fewer hospital visits for treatment, blood sampling and review. Disclosures: Off Label Use: PEGylated G-CSF used in chronic neutropaenia of childhood.

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Application of Innovative Hydroxyapatite Materials in 3D Printing for Biocompatible Voice Implants

Revista de Chimie ◽

10.37358/rc.18.4.6211 ◽

2018 ◽

Vol 69 (4) ◽

pp. 840-842

Author(s):

Wojciech Musialik ◽

Marcin Nabialek ◽

Slawomir Letkiewicz ◽

Andrei Victor Sandu ◽

Katarzyna Bloch

Keyword(s):

3D Printing ◽

Surgical Procedures ◽

Bacterial Infections ◽

Fungal Infections ◽

Colloidal Silver ◽

Bone Implants ◽

External Ring ◽

Voice Prostheses ◽

3D Printers ◽

Silver Composite

The paper presents the possibility of using an innovative hydroxyapatite filament Ca10(PO4)6(OH)2 for printing in 3D printers of bone implants and the possibility of using it during implantation with voice prostheses. The introduction of an additional colloidal silver composite in voice implants will contribute to the reduction of bacterial infections, fungal infections and granulomatous hyperplasia. The creation of a stable external ring of the vocal fistula will remove complications associated with it with enlargement of the fistula and leakiness of voice implants. The ability to print with a hydroxyapatite filament will allow digital pre-surgery modeling of bone implants suited to the needs of surgical procedures.

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Heterocycle Compounds with Antimicrobial Activity

Current Pharmaceutical Design ◽

10.2174/1381612826666200206093815 ◽

2020 ◽

Vol 26 (8) ◽

pp. 867-904 ◽

Cited By ~ 2

Author(s):

Maria Fesatidou ◽

Anthi Petrou ◽

Geronikaki Athina

Keyword(s):

Heterocyclic Compounds ◽

Bacterial Infections ◽

Scientific Community ◽

Antimicrobial Agents ◽

Fungal Infections ◽

Biological Activities ◽

Literature Survey ◽

New Findings ◽

Wide Range ◽

Number Of Microorganisms

Background: Bacterial infections are a growing problem worldwide causing morbidity and mortality mainly in developing countries. Moreover, the increased number of microorganisms, developing multiple resistances to known drugs, due to abuse of antibiotics, is another serious problem. This problem becomes more serious for immunocompromised patients and those who are often disposed to opportunistic fungal infections. Objective: The objective of this manuscript is to give an overview of new findings in the field of antimicrobial agents among five-membered heterocyclic compounds. These heterocyclic compounds especially five-membered attracted the interest of the scientific community not only for their occurrence in nature but also due to their wide range of biological activities. Method: To reach our goal, a literature survey that covers the last decade was performed. Results: As a result, recent data on the biological activity of thiazole, thiazolidinone, benzothiazole and thiadiazole derivatives are mentioned. Conclusion: It should be mentioned that despite the progress in the development of new antimicrobial agents, there is still room for new findings. Thus, research still continues.

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Community-acquired and hospital-acquired respiratory tract infection and bloodstream infection in patients hospitalized with COVID-19 pneumonia

Journal of Intensive Care ◽

10.1186/s40560-021-00526-y ◽

2021 ◽

Vol 9 (1) ◽

Author(s):

Kirstine K. Søgaard ◽

Veronika Baettig ◽

Michael Osthoff ◽

Stephan Marsch ◽

Karoline Leuzinger ◽

...

Keyword(s):

Intensive Care ◽

Tract Infection ◽

Respiratory Tract ◽

Respiratory Tract Infection ◽

Bloodstream Infection ◽

Bacterial Infections ◽

Fungal Infections ◽

Icu Patients ◽

Hospital Acquired Infections ◽

Hospital Acquired

Abstract Objectives SARS-CoV-2 may cause acute lung injury, and secondary infections are thus relevant complications in patients with COVID-19 pneumonia. However, detailed information on community- and hospital-acquired infections among patients with COVID-19 pneumonia is scarce. Methods We identified 220 SARS-CoV-2-positive patients hospitalized at the University Hospital Basel, Switzerland (between 25 February and 31 May 2020). We excluded patients who declined the general consent (n = 12), patients without clinical evidence of pneumonia (n = 29), and patients hospitalized for < 24 h (n = 17). We evaluated the frequency of community- and hospital-acquired infections using respiratory and blood culture materials with antigen, culture-based, and molecular diagnostics. For ICU patients, all clinical and microbial findings were re-evaluated interdisciplinary (intensive care, infectious disease, and clinical microbiology), and agreement reached to classify patients with infections. Results In the final cohort of 162 hospitalized patients (median age 64.4 years (IQR, 50.4–74.2); 61.1% male), 41 (25.3%) patients were admitted to the intensive care unit, 34/41 (82.9%) required mechanical ventilation, and 17 (10.5%) of all hospitalized patients died. In total, 31 infections were diagnosed including five viral co-infections, 24 bacterial infections, and three fungal infections (ventilator-associated pneumonia, n = 5; tracheobronchitis, n = 13; pneumonia, n = 1; and bloodstream infection, n = 6). Median time to respiratory tract infection was 12.5 days (IQR, 8–18) and time to bloodstream infection 14 days (IQR, 6–30). Hospital-acquired bacterial and fungal infections were more frequent among ICU patients than other patients (36.6% vs. 1.7%). Antibiotic or antifungal treatment was administered in 71 (43.8%) patients. Conclusions Community-acquired viral and bacterial infections were rare among COVID-19 pneumonia patients. By contrast, hospital-acquired bacterial or fungal infections were frequently complicating the course among ICU patients.

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Not just vegetations: focal myocardial changes in patients with fungal infections

Cardiology in the Young ◽

10.1017/s1047951120003674 ◽

2020 ◽

pp. 1-6

Author(s):

Nicole M. Cresalia ◽

Sonal T. Owens ◽

Terri L. Stillwell ◽

Mark D. Norris ◽

Sunkyung Yu ◽

...

Keyword(s):

Length Of Stay ◽

Bacterial Infections ◽

Fungal Infections ◽

Positive Culture ◽

Hospital Length ◽

Hospital Length Of Stay ◽

Similar Proportion ◽

Retrospective Case ◽

Fungal Endocarditis ◽

Catheter Tip

Abstract Background: Fungal endocarditis classically involves dense heterogenous vegetations. However, several patients with fungal infections were noted to have myocardial changes ranging from focal brightening to nodular thickening of chordae or papillary muscles. This study evaluates whether these findings are associated with fungal infections. Methods: In a retrospective case–control study, paediatric inpatients with fungal infections (positive blood, urine, or catheter tip culture) in a 5-year period were matched 1:1 to inpatients without positive fungal cultures. Echocardiograms were scored on a 5-point scale by two independent readers for presence of myocardial brightenings, nodular thickenings, and vegetations. Clinical data were compared. Results: Of 67 fungal cases, positive culture sites included blood (n = 44), vascular catheter tip (n = 7), and urine (n = 29); several had multiple positive sites. “Positive” echo findings (score ≥ 2+) were more frequent in the Fungal Group (33 versus 18%, p = 0.04). Fungal Group patients with “positive” versus “negative” echo findings had similar proportion of bacterial infections. Among fungal cases, those with “positive” echo findings had longer hospital length of stay than cases with “negative” echos (median 58 versus 40 days, p = 0.03) but no difference in intensive care unit admission, extracorporeal membranous oxygenation support, or mortality. Conclusions: Myocardial and papillary muscle brightening with nodular thickening on echocardiogram appear to be associated with fungal infections. There may be prognostic implications of these findings as patients with “positive” echo have longer length of stay. Further studies are needed to better understand the mechanism and temporal progression of these changes and determine the prognostic value of this scoring system.

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C-Reactive Protein as A Fungal Infection Marker in Acute Leukemia Patients

INDONESIAN JOURNAL OF CLINICAL PATHOLOGY AND MEDICAL LABORATORY ◽

10.24293/ijcpml.v27i2.1639 ◽

2021 ◽

Vol 27 (2) ◽

pp. 212

Author(s):

Brigitte Rina Aninda Sidharta ◽

JB. Suparyatmo ◽

Avanti Fitri Astuti

Keyword(s):

Acute Leukemia ◽

Predictive Value ◽

Bacterial Infections ◽

Fungal Infections ◽

Lymphoblastic Leukemia ◽

Negative Likelihood Ratio ◽

Receiver Operating Curve ◽

High Morbidity ◽

C Reactive Protein ◽

Reactive Protein

Invasive Fungal Infections (IFIs) can cause serious problems in cancer patients and may result in high morbidity andmortality. C-reactive protein levels increase in response to injury, infection, and inflammation. C-reactive protein increasesin bacterial infections (mean of 32 mg/L) and in fungal infections (mean of 9 mg/L). This study aimed to determineC-Reactive Protein (CRP) as a marker of fungal infections in patients with acute leukemia by establishing cut-off values ofCRP. This study was an observational analytical study with a cross-sectional approach and was carried out at the Departmentof Clinical Pathology and Microbiology of Dr. Moewardi Hospital in Surakarta from May until August 2019. The inclusioncriteria were patients with acute leukemia who were willing to participate in this study, while exclusion criteria were patientswith liver disease. There were 61 samples consisting of 30 male and 31 female patients with ages ranging from 1 to 70 years.Fifty-four patients (88.5%) were diagnosed with Acute Lymphoblastic Leukemia (ALL) and 30 (49.18%) were in themaintenance phase. The risk factors found in those patients were neutropenia 50-1500 μL (23.8%), use of intravenous line(22%), and corticosteroid therapy for more than one week (20.9%). The median of CRP in the group of patients with positiveculture results was 11.20 mg/L (11.20-26.23 mg/L) and negative culture results in 0.38 mg/L (0.01-18.63 mg/L). The cut-offvalue of CRP using the Receiver Operating Curve (ROC) was 9.54 mg/L (area under curve 0.996 and p. 0.026), with a sensitivityof 100%, specificity of 93.2%, Positive Predictive Value (PPV) of 33.3%, Negative Predictive Value (PPV) of 100%, PositiveLikelihood Ratio (PLR) of 1.08, Negative Likelihood Ratio (NLR) of 0 and accuracy of 93.4%. C-reactive protein can be used asa screening marker for fungal infections in patients with acute leukemia.

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Same-Day Simultaneous Diagnosis of Bacterial and Fungal Infections in Clinical Practice by Nanopore Targeted Sequencing

10.1101/2020.04.08.20057604 ◽

2020 ◽

Author(s):

Ming Wang ◽

Aisi Fu ◽

Ben Hu ◽

Gaigai Shen ◽

Ran Liu ◽

...

Keyword(s):

Clinical Practice ◽

Bacterial Infections ◽

Fungal Infections ◽

Culture Method ◽

Targeted Sequencing ◽

Therapeutic Monitoring ◽

Rrna Gene ◽

Culture Methods ◽

Detection Range ◽

Sequencing Platform

AbstractBACKGROUNDAs approximately 19% of global deaths are attributable to infectious diseases, early diagnosis of infection is very important to reduce mortality. Traditional infection detection strategies have limited sensitivity, detection range, and turnaround times; a detection technology that can simultaneously detect bacterial and fungal infections within 24 h is urgently need in clinical settings.METHODSWe developed nanopore targeted sequencing (NTS) for same-day simultaneous Diagnosis of fungal and bacterial infections. NTS was developed by amplification of 16s rRNA gene (for bacteria), IST1/2 gene (for fungal), and rpoB (for Mycobacterium spp.) using multiple primers, and sequenced by a real-time nanopore sequencing platform. An in-house bioinformatic analyze pipeline was used to diagnose the infectious pathogens by mapping the sequencing results with the constructed databases.RESULTSComparison of 1312 specimens from 1257 patients using NTS and culture method; NTS detected pathogens in 58.71% of specimens from patients, compared to 22.09% detected using the culture method. NTS showed significantly higher sensitivity than culture methods for many pathogens. Importantly, a turnaround time of <24 h for all specimens, and a pre-report within 6 h in emergency cases was possible in clinical practice. Modification of antibiotic therapy and maintenance of original anti-infection regimens in 51.52% (17/33) and 36.36% (12/33) of patients was in accordance with NTS results, and quantitative monitoring of clinical treatment effects was evaluated in four patients by continuous NTS tests.CONCLUSIONSApplication of NTS in clinically detected pathogens can improve targeted antibiotic treatment and therapeutic monitoring.

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Differential Requirements for Mediator Complex Subunits in Drosophila melanogaster Host Defense Against Fungal and Bacterial Pathogens

Frontiers in Immunology ◽

10.3389/fimmu.2020.478958 ◽

2021 ◽

Vol 11 ◽

Author(s):

Chuqin Huang ◽

Rui Xu ◽

Samuel Liégeois ◽

Di Chen ◽

Zi Li ◽

...

Keyword(s):

Immune Response ◽

Host Defense ◽

Bacterial Infections ◽

Fungal Infections ◽

Transcriptional Response ◽

Erwinia Carotovora ◽

Mediator Complex ◽

Toll Pathway ◽

Metarhizium Robertsii ◽

Immune Factor

The humoral immune response to bacterial or fungal infections in Drosophila relies largely on a transcriptional response mediated by the Toll and Immune deficiency NF-κB pathways. Antimicrobial peptides are potent effectors of these pathways and allow the organism to attack invading pathogens. Dorsal-related Immune Factor (DIF), a transcription factor regulated by the Toll pathway, is required in the host defense against fungal and some Gram-positive bacterial infections. The Mediator complex is involved in the initiation of transcription of most RNA polymerase B (PolB)-dependent genes by forming a functional bridge between transcription factors bound to enhancer regions and the gene promoter region and then recruiting the PolB pre-initiation complex. Mediator is formed by several modules that each comprises several subunits. The Med17 subunit of the head module of Mediator has been shown to be required for the expression of Drosomycin, which encodes a potent antifungal peptide, by binding to DIF. Thus, Mediator is expected to mediate the host defense against pathogens controlled by the Toll pathway-dependent innate immune response. Here, we first focus on the Med31 subunit of the middle module of Mediator and find that it is required in host defense against Aspergillus fumigatus, Enterococcus faecalis, and injected but not topically-applied Metarhizium robertsii. Thus, host defense against M. robertsii requires Dif but not necessarily Med31 in the two distinct infection models. The induction of some Toll-pathway-dependent genes is decreased after a challenge of Med31 RNAi-silenced flies with either A. fumigatus or E. faecalis, while these flies exhibit normal phagocytosis and melanization. We have further tested most Mediator subunits using RNAi by monitoring their survival after challenges to several other microbial infections known to be fought off through DIF. We report that the host defense against specific pathogens involves a distinct set of Mediator subunits with only one subunit for C. glabrata or Erwinia carotovora carotovora, at least one for M. robertsii or a somewhat extended repertoire for A. fumigatus (at least eight subunits) and E. faecalis (eight subunits), with two subunits, Med6 and Med11 being required only against A. fumigatus. Med31 but not Med17 is required in fighting off injected M. robertsii conidia. Thus, the involvement of Mediator in Drosophila innate immunity is more complex than expected.

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Skin Infections

10.2310/fm.1081 ◽

2018 ◽

Author(s):

Jan V. Hirschmann

Keyword(s):

Bacterial Infections ◽

Tinea Pedis ◽

Viral Infections ◽

Fungal Infections ◽

Treatment Options ◽

Tinea Corporis ◽

Microsporum Canis ◽

Plantar Surface ◽

Fournier Gangrene ◽

Tinea Versicolor

The skin can become infected by viruses, fungi, and bacteria, including some that ordinarily are harmless colonizing organisms. The most common fungal infections are caused by dermatophytes, which can involve the hair, nails, and skin. Potassium hydroxide (KOH) preparations of specimens from affected areas typically demonstrate hyphae, and either topical or systemic antifungal therapy usually cures or controls the process. The most common bacterial pathogens are Staphylococcus aureus and group A streptococci, which, alone or together, can cause a wide variety of disorders, including impetigo, ecthyma, and cellulitis. Topical antibiotics may suffice for impetigo, but ecthyma and cellulitis require systemic treatment. S. aureus, including methicillin-resistant strains, can also cause furuncles, carbuncles, and cutaneous abscesses. For these infections, incision and drainage without antibiotics are usually curative. Warts are the most common cutaneous viral infection, and eradication can be difficult, especially where the skin is thick, such as the palms and soles, or the patient is immunocompromised. Most therapies consist of trying to destroy the viruses by mechanical, chemical, or immune mechanisms. This review covers dermatophyte infections, yeast infections, bacterial infections, and viral infections of the skin. Figures show the classic annular lesion of tinea corporis, a typical kerion presenting as a zoophilic Microsporum canis infection of the scalp (tinea capitis), tinea corporis, tinea barbae, tinea pedis between and under the toes and on the plantar surface, inflammatory tinea pedis, tinea unguium, tinea manuum, angular cheilitis, prominent satellite lesions of discrete vesicles associated with candidiasis, facial candidiasis, Candida paronychia, tinea versicolor, nonbullous impetigo, bullous impetigo, ecthyma, leg cellulitis, erythema and edema on the cheeks, eyelids, and nose, furuncle, carbuncle, nasal folliculitis, pitted keratolysis, trichomycosis axillaris, necrotizing fasciitis, Fournier gangrene, folliculitis, plantar wart, condyloma acuminatum, and benign lesions of bowenoid papulosis. Tables list dermatophyte species, terminology of dermatophyte infections, topical agents for dermatophyte infections, treatment options for impetigo (adult doses), and treatment options for erythrasma. This review contains 28 highly rendered figures, 5 tables, and 33 references

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Serum biomarkers to differentiate Gram-negative, Gram-positive and fungal infection in febrile patients

Journal of Medical Microbiology ◽

10.1099/jmm.0.001360 ◽

2021 ◽

Vol 70 (7) ◽

Author(s):

Dongguang Niu ◽

Qian Huang ◽

Fan Yang ◽

Weiliang Tian ◽

Chen Li ◽

...

Keyword(s):

Bloodstream Infection ◽

Bacterial Infections ◽

Fungal Infections ◽

Serum Levels ◽

Serum Biomarker ◽

Diagnostic Efficiency ◽

Gram Positive ◽

Gram Negative ◽

Neutrophil Lymphocyte Ratio ◽

Bacteria And Fungi

Introduction. Contamination of specimens and overuse of broad spectrum antibiotics contribute to false positives and false negatives, respectively. Therefore, useful and applicable biomarkers of bacteremia are still required. Hypothesis/Gap Statement. IL-6 can be used as a serum biomarker to discriminate among bacterial infections and fungal infections in febrile patients with a bloodstream infection. Aim. We aimed to evaluate the diagnostic efficiency of neutrophil/lymphocyte ratio (NLR), procalcitonin (PCT) and interleukin-6 (IL-6) in discriminating Gram-negative (G−) bacteria from Gram-positive (G+) bacteria and fungi in febrile patients. Methodology. A total of 567 patients with fever were evaluated. Serum levels of IL-6, PCT, NLR and CRP were compared among a G− group (n=188), a G+ group (n=168), a fungal group (n=38) and a culture negative group (n=173). Sensitivity, specificity, Yuden’s index and area under the Receiver operating characteristic (ROC) curve (AUC) were obtained to analyse the diagnostic abilities of these biomarkers in discriminating bloodstream infection caused by different pathogens. Results. Serum IL-6 and PCT in the G− group increased significantly when compared with both the G+ group and fungal group (P <0.05). AUC of IL-6 (0.767, 95 % CI:0.725–0.805) is higher than AUC of PCT (0.751, 95 % CI:0.708–0.796) in discriminating the G− group from G+ group. When discriminating the G− group from fungal group, the AUC of IL-6 (0.695, 95 % CI:0.651–0.747) with a cut-off value of 464.3 pg ml−1 was also higher than the AUC of PCT (0.630, 95 % CI:0.585–0.688) with a cut-off value of 0.68 ng ml−1. Additionally, AUC of NLR (0.685, 95 % CI:0.646–0.727) in discriminating the fungal group from G+ group at the cut-off value of 9.03, was higher than AUC of IL-6, PCT and CRP. Conclusion. This study suggests that IL-6 could be used as a serum biomarker to discriminate among bacterial infections and fungal infections in febrile patients with a bloodstream infection. In addition, NLR is valuable to discriminate fungal infections from Gram-positive infections in febrile patients with a bloodstream infection.

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