Non-sterile Sites Research Articles

Serotype distribution and antimicrobial susceptibility of Streptococcus pneumoniae isolates cultured from Japanese adult patients with community-acquired pneumonia in Goto City, Japan.

Streptococcus pneumoniae is an important cause of community-acquired pneumonia (CAP) in Japan. Here, we report the serotype distribution and antimicrobial susceptibility of cultured pneumococcal isolates from Japanese adults aged ≥18 years with CAP. This was a prospective, population-based, active surveillance study conducted in Goto City, Japan from December 2015 to November 2020. Pneumococcal isolates from sterile sites (blood and pleural fluid) and non-sterile sites (sputum and bronchoalveolar lavage) were cultured as part of the standard of care. S. pneumoniae were serotyped using the Quellung reaction. Antimicrobial susceptibility was tested using microdilution and interpreted according to the Clinical and Laboratory Standards Institute criteria. Isolates resistant to erythromycin were phenotyped using the triple-risk test and genotyped by polymerase chain reaction. A total of 156 pneumococcal isolates were collected (138 from sputum, 15 from blood, and 3 from bronchoalveolar lavage) from 1992 patients. Of these, 142 were non-duplicate isolates from unique patients and were included in the analyses. Serotypes contained within the 13-valent pneumococcal conjugate vaccine (PCV13) (including 6C), PCV15 (including 6C), and PCV20 (including 6C and 15C) were detected in 39 (27%), 45 (32%), and 80 (56%) of 142 isolates, respectively. The most common serotypes were 35B (12%), 11A (11%), and 3 (11%). Multidrug resistance (MDR) was detected in 96/142 (68%) isolates. Of the 96 MDR isolates, 31, 32, and 59% were PCV13, PCV15, and PCV20 serotypes, respectively; the most common MDR serotypes were 35B (16%), 6C, 10A, and 15A (9% each), and 3 and 11A (8% each). A total of 119 isolates were resistant to macrolides; 41 (35%) had an M phenotype, 53 (45%) had an iMcLS phenotype, and 25 (21%) had a cMLS phenotype. In conclusion, pneumococcal serotypes 35B, 11A and 3 were most frequently associated with pneumonia and antimicrobial resistance was common among pneumococcal isolates from adults with CAP in Goto City, Japan. Implementing higher-valency PCVs May help reduce vaccine-type CAP among Japanese adults.

Divergent effects of emm types 1 and 12 on invasive group A streptococcal infections-results of a retrospective cohort study, Germany 2023.

As a potential side effect of the severe acute respiratory syndrome coronavirus type 2 pandemic, invasive group A Streptococcus (iGAS) infections in Europe have increased dramatically in both children and adults in the end of 2022. This epidemiological and molecular study describes the distributions of streptococcal genes encoding the M antigen (emm types) and superantigens in patients with invasive and non-invasive GAS infections. From December 2022 to December 2023, a total of 163 GAS isolates were collected from sterile and non-sterile sites of patients at five hospitals in Germany including two tertiary care centers. Genes encoding M protein and superantigens were determined following the guidelines of CDC Streptococcus laboratory. Patients' characteristics were reviewed retrospectively. Correlations of clinical factors, emm types, and superantigens with rates of invasive infections were analyzed. Of the 163 included GAS cases, 112 (69%) were considered as invasive. In total, 33 different emm types were observed, of which emm1.0 (n = 49; 30%), emm89.0 (n = 15; 9%), and emm12.0 (n = 14; 9%) were most prevalent. In total, 70% of emm1.0 isolates belonged to M1UK lineage. No difference in invasive infections was observed for the M1UK lineage compared with other emm1.0 isolates. However, the emm1.0 type, presence of speA1-3, speG, or speJ, as well as adulthood were significantly associated with invasive infections. In contrast, emm12.0 isolates were significantly less associated with invasive infections. Multivariable analysis confirmed a significant influence of speJ and adulthood on iGAS infections. This study underlines the importance of continuous monitoring of genomic trends and identification of emerging GAS variants. This may aid in delineating pathogenicity factors of Streptococcus pyogenes that propel invasive infections.

Aspergillosis coinfection in patients with proven mucormycosis.

Although research on aspergillosis and mucormycosis confection is important to optimize antifungal therapy, data on this issue is scarce. Thus, we systematically investigated aspergillosis coinfection in patients with proven mucormycosis. Medical records of adult patients with proven mucormycosis whose formalin-fixed paraffin-embedded (FFPE) tissue sections were available, in a tertiary hospital from August 2007 to July 2023 were retrospectively reviewed to assess coinfection with aspergillosis. We noted cultures of fungi from sterile and non-sterile sites and performed polymerase chain reaction (PCR) assays on FFPE tissues to detect Aspergillus- and Mucorales-specific DNA. Sixty-seven patients with proven mucormycosis, including 12 (18%) with a positive culture of the mucormycosis agent from sterile site cultures, were enrolled. Fungal cultures from sterile and non-sterile sites revealed Aspergillus spp. growth in nine (13%) of the 67 patients, including two sterile and seven non-sterile cultures. The fungal PCR analysis from the FFPE sections was positive for Aspergillus-specific PCR in five (7%) and positive for both Aspergillus- and Mucorales-specific PCR results in eight (12%). Overall, 21 (31%) of the 67 patients with proven mucormycosis had microbiologic and/or molecular evidence of aspergillosis coinfection. Positive blood or bronchoalveolar lavage fluid galactomannan results were more common in the coinfection group (67% [14/21]) than in the mucormycosis group (37% [17/46], P=.024). No significant difference in mortality between the two groups was observed. Approximately one-third of patients with proven mucormycosis exhibited molecular and/or microbiologic evidence of aspergillosis coinfection. Further research is needed to identify patients with aspergillosis and mucormycosis coinfections, for optimal antifungal therapy.

Multicenter Candida auris outbreak caused by azole-susceptible clade IV in Pernambuco, Brazil.

Candida auris is an emerging multidrug-resistant yeast, frequently causing outbreaks in health care facilities. The pathogen persistently colonises human skin and inanimate surfaces such as catheters, aiding to its spread. Moreover, colonisation is a risk factor to develop invasive infection. We investigated 61 C. auris strains isolated from non-sterile human body sites (n = 53) and the hospital environment (n = 8), originating from four different centres in a single Brazilian state. Antifungal susceptibility testing (AFST) against common antifungals was performed, and resistance-associated genes were evaluated. Genetic relatedness was investigated with short tandem repeat (STR) genotyping and validated with whole-genome sequencing (WGS) single nucleotide polymorphism (SNP) analysis. Antifungal susceptibility testing demonstrated that all isolates were susceptible to azoles, echinocandins and amphotericin B. No mutations were detected in ERG11 and FKS1 genes. With STR typing, isolates were allocated to clade IV and appeared closely related. This was confirmed by WGS SNP analysis of 6 isolates, which demonstrated a maximal difference of only 41 SNPs between these strains. Furthermore, the Brazilian isolates formed a distinct autochthonous branch within clade IV, excluding recent introductions from outside the country. A molecular clock analysis of clade IV isolates from various countries suggests that early in the previous century there was a unique event causing environmental spread of a C. auris ancestor throughout the Latin-American continent, followed by human introduction during the last decades. We report the emergence of C. auris patient colonisation in multiple centres by fluconazole-susceptible clade IV close-related strains in Pernambuco State, Brazil.

Using a human colonoid-derived monolayer to study bacteriophage translocation

ABSTRACT Bacteriophages (phages) are estimated to be the most abundant microorganisms on Earth. Their presence in human blood suggests that they can translocate from non-sterile sites such as the gastrointestinal tract where they are concentrated. To examine phage translocation ex vivo, we adapted a primary colonoid monolayer model possessing cell diversity and architecture, and a thick layer of mucus akin to the colonic environment in vivo. We show that the colonoid monolayer is superior to the Caco-2 cell-line model, possessing intact and organized tight junctions and generating a physiologically relevant mucus layer. We showed, using two different phages, that translocation across the colonoid monolayer was largely absent in differentiated monolayers that express mucus, unlike Caco-2 cultures that expressed little to no mucus. By stimulating mucus production or removing mucus, we further demonstrated the importance of colonic mucus in preventing phage translocation. Finally, we used etiological drivers of gut permeability (alcohol, fat, and inflammatory cytokines) to measure their effects on phage translocation, demonstrating that all three stimuli have the capacity to amplify phage translocation. These findings suggest that phage translocation does occur in vivo but may be largely dependent on colonic mucus, an important insight to consider in future phage applications.

Examining geospatial and temporal distribution of invasive non-typhoidal Salmonella disease occurrence in sub-Saharan Africa: a systematic review and modelling study

BackgroundInvasive non-typhoidal Salmonella (iNTS) disease is a significant health concern in sub-Saharan Africa. While our knowledge of a larger-scale variation is growing, understanding of the subnational variation in iNTS disease...

Draft genome sequences of Listeria monocytogenes strains of sequence type 1733 which constituted a pseudo-outbreak due to contaminated blood agar media.

We report genome sequences of Listeria monocytogenes sequence type (ST) 1733 from a 2013 pseudo-outbreak, where L. monocytogenes isolation from non-sterile sites (urine, wound, or abscess) was an artifact from contaminated sheep blood in the isolation media. Two ST1733 strains from wound and urine in 2005 are also reported.

Atypical Influx: Navigating Invasive Group A Streptococcus Cases in Emergency General Surgery

Abstract Aim To highlight the rising national incidence of iGAS infections, particularly during the post emergency phase of the COVID-19 pandemic, and emphasise its significance as a differential diagnosis in acutely unwell emergency surgical patients. Methods Data was gathered retrospectively from December 2022 - August 2023. Inclusion criteria were emergency surgical patients testing positive for GAS isolated from sterile sites, or non-sterile sites in case of septic shock. Results Six cases (four females, two males), with a mean age of 55 (36-67) were identified. Four had necrotizing fasciitis, one bacterial peritonitis in the presence of a ventriculo-peritoneal shunt, and one streptococcal bacteremia. All presented in septic shock, with metabolic acidosis and multiorgan impairment. The initial diagnosis was clinical in 66% of cases. iGAS was confirmed via wound, peritoneal fluid, tissue or blood culture in five patients and via genital swab in one. 50% of cases were sensitive to clindamycin and amoxicillin. Two received IV immunoglobulins. All cases were managed according to Sepsis 6 protocols, involving multidisciplinary teams. Five patients underwent immediate surgery for debridement and washout. The mortality rate was 16.6%. Three patients were transferred to tertiary centres once stabilised (1 for neurosurgical input, and 2 for plastics grafting). Conclusion It is crucial for frontline doctors to consider iGAS as a differential when encountering critically ill surgical patients. Simultaneous systemic resuscitation, early surgical intervention, multidisciplinary care, tailored antibiotic therapy and immunoglobulins are essential to minimise morbidity and mortality.

2784. Rates of Susceptibility and Heteroresistance to Novel Antibiotic Combinations in Carbapenem-Resistant Enterobacterales Isolates - Emory Healthcare, 2016-2021

Abstract Background CRE infections are frequently treated with new beta-lactam/beta-lactamase inhibitors (BL/BLI): imipenem-relebactam (I-R), ceftazidime-avibactam (CZA), and meropenem-vaborbactam (MVB). However, the frequency of susceptibility and heteroresistance (HR), defined as the presence of an antibiotic-resistant subpopulation within a primary susceptible population, to these newer antibiotics is unknown. Here we evaluate rates of susceptibility and HR to newer BL/BLI in a convenience sample of clinical CRE isolates as potential reasons for clinical failure. Methods We created an antibiogram for carbapenem-resistant Enterobacter cloacae, Escherichia coli and Klebsiella pneumoniae isolates collected between 2016–2021 as part of routine clinical care from two >500-bed academic hospitals. We tested the first isolate per patient for susceptibility to I-R, CZA, and MVB by broth microdilution. We used population analysis profiling (PAP) to test for HR to CZA and I-R. Results Of 328 CRE isolates, 74 (22%) were from sterile sites, 151 (46%) from urine, 43 (13%) from the respiratory tract, and 60 (18%) from other non-sterile sites. For E. cloacae (n=152), 93% were susceptible to I-R, 98% to CZA, and 99% to MVB. For E. coli (n=53), 89% were susceptible to I-R, 94% to CZA, and 93% to MVB. For K. pneumoniae (n=123), 90% were susceptible to I-R, 94% to CZA, and 93% to MVB (Table 1). Over time, decreases in the activity of all 3 BL/BLI were noted. Compared to 2016, the percentage of susceptible CRE isolates decreased by 11% (98% to 87%) for I-R, 7% (98% to 91%) for CZA, and 8% (98% to 90%) for MVB (Figure 1). The percentage of isolates with HR to CZA was 7.2% for E. cloacae, 1.9% for E. coli, and 4.9% for K. pneumoniae. For I-R, the percentage of HR isolates was 4.1% for E. cloacae, 9.6% for E. coli, and 10.3% for K. pneumoniae.Table 1.Proportion of carbapenem-resistant Enterobacterales isolates susceptible to new beta-lactam/beta-lactamase inhibitors in two academic hospitals. N = number of antibiotic susceptible isolates, followed by percentage (%) of susceptible isolates. Asterisk (*) indicates if not all isolates were tested against the specified antibiotic. I-R = imipenem-relebactam CZA = ceftazidime-avibactam MVB = meropenem-vaborbactam The percent susceptibility of carbapenem-resistant Enterobacterales isolates to the specified antibiotic was graphed per year for all isolates and by individual species. The isolates from two academic hospitals were combined. I-R Sus % = Percent susceptibility to imipenem-relebactam MVB Sus % = Percent susceptibility to meropenem-vaborbactam CZA Sus % = Percent susceptibility to ceftazidime-avibactam Conclusion In our study on the activity of newer BL/BLI against CRE, susceptibility remains high and HR is rare. While newer BL/BLIs remain highly active against CRE, the observed decrease in susceptibility over time suggests a need for ongoing antibiotic stewardship. Disclosures Ahmed Babiker, MBBS, Roche: Advisor/Consultant

Comparison of contemporary invasive and non-invasive Streptococcus pneumoniae isolates reveals new insights into circulating anti-microbial resistance determinants.

Streptococcus pneumoniae is a major human pathogen with a high burden of disease. Non-invasive isolates (those found in non-sterile sites) are thought to be a key source of invasive isolates (those found in sterile sites) and a reservoir of anti-microbial resistance (AMR) determinants. Despite this, pneumococcal surveillance has almost exclusively focused on invasive isolates. We aimed to compare contemporaneous invasive and non-invasive isolate populations to understand how they interact and identify differences in AMR gene distribution. We used a combination of whole-genome sequencing and phenotypic anti-microbial susceptibility testing and a data set of invasive (n = 1,288) and non-invasive (n = 186) pneumococcal isolates, collected in Victoria, Australia, between 2018 and 2022. The non-invasive population had increased levels of antibiotic resistance to multiple classes of antibiotics including beta-lactam antibiotics penicillin and ceftriaxone. We identified genomic intersections between the invasive and non-invasive populations and no distinct phylogenetic clustering of the two populations. However, this analysis revealed sub-populations overrepresented in each population. The sub-populations that had high levels of AMR were overrepresented in the non-invasive population. We determined that WamR-Pneumo was the most accurate in silico tool for predicting resistance to the antibiotics tested. This tool was then used to assess the allelic diversity of the penicillin-binding protein genes, which acquire mutations leading to beta-lactam antibiotic resistance, and found that they were highly conserved (≥80% shared) between the two populations. These findings show the potential of non-invasive isolates to serve as reservoirs of AMR determinants.

Post-report antibiotic initiation following community non-sterile-site microbiology results: an opportunity for labs to lead stewardship?

Positive culture results from non-sterile sites (NSSs) are poorly predictive of clinical infection. Despite this, these results are often interpreted as an indication for antibiotics, even in patients with limited signs of infection. We sought to quantify the influence of NSS culture results on post-report antibiotic initiation (PRAI) in patients who had not been started on antibiotics pre-report. All community wound/skin swab and sputum cultures were matched to antibiotic dispensing records from February 2017 to July 2022. Prescribing behaviour was assessed pre- and post-report. Sampling without treatment pre-report was termed 'test-and-wait' (TaW). Following TaW, PRAI was identified if antibiotics were started within 5 days post-report. There were 65 480 wound/skin swabs and 8126 sputum samples, with TaW occurring in 21 740 (35.1%) and 4185 (54.4%), respectively. Following a TaW approach PRAI occurred in 43.3% when an organism was reported, versus 10.8% (P < 0.01) for a 'no growth' report for wound/skin swabs. For the same comparison with sputum, PRAI occurred in 47.9% versus 10.8% (P < 0.01). On multivariate analysis reporting an organism remained strongly associated with PRAI. Reporting an organism in those not already on antibiotics was strongly associated with PRAI. We hypothesize that for many patients TaW suggests limited evidence of infection (i.e. insufficient to justify antibiotic treatment at time of sampling), meaning positive NSS results may be driving a considerable volume of potentially unnecessary antibiotic use. Further study on this topic is required, but strategies to reduce PRAI may offer laboratories an opportunity to meaningfully impact antimicrobial stewardship efforts.

Impact of improving infection control and antibiotic stewardship practices on nosocomial infections and antimicrobial resistance in an oncology centre from India

BackgroundImproving basic infection control (IC) practices, diagnostics and anti-microbial stewardship (AMS) are key tools to handle antimicrobial resistance (AMR). Materials and methodsThis is a retrospective study done over 6 years (2016–2021) in an oncology centre in North India with many on-going interventions to improve IC practices, diagnostics and AMS. This study looked into AMR patterns from clinical isolates, rates of hospital acquired infections (HAI) and clinical outcomes. ResultsOver all, 98,915 samples were sent for culture from 158,191 admitted patients. Most commonly isolated organism was E. coli (n ​= ​6951; 30.1%) followed by Klebsiella pneumoniae (n ​= ​5801; 25.1%) and Pseudomonas aeroginosa (n ​= ​3041; 13.1%). VRE (Vancomycin resistant Enterococcus) rates fell down from 43.5% in Jan–June 2016 to 12.2% in July–Dec 2021, same was seen in CR (carbapenem resistant) Pseudomonas (23.0%–20.6%, CR Acinetobacter (66.6%–17.02%) and CR E. coli (21.6%–19.4%) over the same study period. Rate of isolation of Candida spp. from non-sterile sites also showed reduction (1.68 per 100 patients to 0.65 per 100 patients). Incidence of health care associated infections also fell from 2.3 to 1.19 per 1000 line days for CLABSI, 2.28 to 1.88 per 1000 catheter days for CAUTI. There was no change in overall mortality rates across the study period. ConclusionThis study emphasizes the point that improving compliance to standard IC recommendations and improving diagnostics can help in reducing the burden of antimicrobial resistance.

A Repertoire of Clinical Non-Dermatophytes Moulds.

Humans are constantly exposed to micromycetes, especially filamentous fungi that are ubiquitous in the environment. In the presence of risk factors, mostly related to an alteration of immunity, the non-dermatophyte fungi can then become opportunistic pathogens, causing superficial, deep or disseminated infections. With new molecular tools applied to medical mycology and revisions in taxonomy, the number of fungi described in humans is rising. Some rare species are emerging, and others more frequent are increasing. The aim of this review is to (i) inventory the filamentous fungi found in humans and (ii) provide details on the anatomical sites where they have been identified and the semiology of infections. Among the 239,890 fungi taxa and corresponding synonyms, if any, retrieved from the Mycobank and NCBI Taxonomy databases, we were able to identify 565 moulds in humans. These filamentous fungi were identified in one or more anatomical sites. From a clinical point of view, this review allows us to realize that some uncommon fungi isolated in non-sterile sites may be involved in invasive infections. It may present a first step in the understanding of the pathogenicity of filamentous fungi and the interpretation of the results obtained with the new molecular diagnostic tools.

Evaluating the Follow-up of Post-discharge Positive Sterile Site Cultures and the Impact on Infection-Related Complications.

Numerous patients have cultures pending at discharge which, if not addressed, may delay diagnosis and initiation of appropriate antimicrobials. The purpose of the study is to evaluate the appropriateness of discharge antimicrobial therapy and result documentation in patients with positive cultures finalized post-discharge. This was a cross-sectional cohort study of patients admitted from July 1 to December 31, 2019 with positive sterile-site microbiologic cultures finalized post-discharge. Pertinent inclusion and exclusion factors were admission≥48h and non-sterile sites, respectively. The primary objective was to determine the frequency of discharged patients warranting antimicrobial changes based on finalized cultures. Secondary objectives included prevalence and timeliness of result documentation and rates of 30-day readmission, among intervention warranted versus not warranted. Chi-squared or Fisher's exact tests were used as appropriate. Binary multivariable logistic regression was completed for 30-day readmission stratified by infectious disease (ID) involvement due to the potential for effect modification. A total of 208 of 768 patients screened were included. Most patients were discharged from a surgical service (45.7%); deep tissue and blood were the most common culture sites (29.3%). Change in discharge antimicrobial was warranted in 36.5% of patients (n=76). Result documentation was overall low (35.5%). Time to documentation was significantly shorter in patients warranting antimicrobial intervention (4days vs. 9days, P=0.039), although rates of hospital readmission were higher in this group (32.9% vs. 22.7%, P=0.109). Finally, in patients not being followed by ID, documentation of finalized results was associated with decreased odds of 30-day readmission (aOR 0.19; 95% CI 0.07-0.53). A significant number of patients with cultures finalized post-discharge warranted antimicrobial intervention. Acknowledgment of finalized culture results may decrease the risk of 30-day hospital readmission, particularly in patients not followed by ID. Quality improvement efforts should focus on methods to improve documentation and action on pending cultures to positively impact patient outcomes.

902. Evaluation of Post-Discharge Sterile-Site Positive Microbiology Results and the Impacts on Patient Care

Abstract Background Half of patients have cultures pending at discharge. Failure to address these results may delay diagnosis and time to appropriate antimicrobials. The purpose of the study is to evaluate appropriateness of antimicrobial therapy and result documentation in patients with positive cultures finalized post-discharge. Methods Retrospective cohort study of patients from 7/2019-12/2019 with positive sterile-site microbiologic cultures finalized post-discharge. Pertinent inclusion and exclusion factors were admission ≥48 hours and non-sterile sites, respectively. The primary objective was to determine the frequency of discharged patients warranting antimicrobial intervention based on finalized culture results. Secondary objectives included incidence and timeliness of result documentation and rates of 30-day hospital readmission, among intervention warranted vs not warranted. Chi-squared or Fisher’s exact tests were used as appropriate. Binary multivariable logistic regression was completed for 30-day hospital re-admission stratified by infectious disease (ID) team involvement. Results 208 of 768 patients screened were included. Most patients were discharged from a surgical service (45.7%); deep tissue and blood were the most common culture sites (29.3%). Antimicrobial intervention was warranted in 36.5% of patients (n=76). Rates of result documentation were overall low (35.5%). Time to documentation of results was significantly shorter in patients warranting intervention compared to those who did not, but hospital readmission was higher (Table 1). Finally, result documentation in patients not being followed by ID was associated with decreased odds of 30-day readmission (OR 0.19, 95% CI, 0.07-0.53) (Table 2). Conclusion A significant number of patients with cultures finalized post-discharge warranted antimicrobial intervention. Acknowledgment of final culture data can decrease the risk of 30-day hospital readmission, especially in patients not followed by ID. Quality improvement efforts should focus on methods to improve documentation and follow-up of pending cultures to improve patient outcomes. Disclosures Kimberly C. Claeys, PharmD, BioFire Diagnostics: Honoraria|La Jolla Pharmaceuticals: Advisor/Consultant.

P419 Galactomannan enzyme immunoassay in invasive pulmonary aspergillosis: a cross sectional study in 2021 in a New Delhi

Poster session 3, September 23, 2022, 12:30 PM - 1:30 PMObjectiveThis study aims to determine the role of GM EIA in the diagnosis of IPA as per revised EORTC/MSG 2019 criteria.Material and MethodsA prospective cross-sectional study was performed on 87 children (from 1 to 12 years) admitted to pediatric hematology ward from Oct 2020 to February 2022. Serum of these patients was collected and GM EIA was performed using BIO-RAD Platelia™ Aspergillus Ag. Clinical, mycological workup (potassium-hydroxide mount, fungal culture) was done and furthermore, these patients were classified into proven, probable, and possible IA as per EORTC-MSG guidelines, 2019. Galactomannan indices (GMI) measured in terms of sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were validated with revised EORTC -MSG, 2019 of IPA.ResultsA total of 53 patients out of 87 were categorized into probable IPA with routine mycological findings. On culture Aspergillus flavus was the most common pathogen, identified in 56% (25), followed by A. fumigatus 31.8% (14), A. niger 9% (4), etc. 44 (50.5%) had GMI value of >0.7, 9 (10.3%) in the range of 0.5-0.7 and 34 (39%) had GMI <0.5.The maximal Youden index ‘J’ [95% confidence interval (CI) of 0.4167-0.6875] was calculated as 0.678 and sensitivity, specificity, PPV, and NPV in IPA were calculated corresponding to a GM index of >1.0, 0.7, 0.5 to determine the best cutoff point. The best cutoff was found to be 0.695 where in the 84.1% and specificity was 83.7% respectively.ConclusionGM EIA can prove as an excellent diagnostic test for IPA when done in addition to culture from nonsterile sites in high-risk populations like pediatric patients with hematological malignancy. This study reinforces the definition of the probable category of EORTC-MSG criteria, 2019 in overall diagnosis, prognosis, and management of IPA in pediatric patients with hematological malignancy.

Invasive candidiasis among high prevalence neurological patients.

Invasive candidiasis is a severe form of infection. The incidence of invasive fungal infections has increased, due to the increasing number of patients with impaired immunity who are being treated through prolonged stay in hospital facilities. Neurological patient treatment methods such as antimicrobials, corticosteroid, central venous catheter (CVC), total parenteral nutrition, and mechanical ventilation use are associated with common risk factors for invasive candidiasis. Our study demonstrated invasive candidiasis prevalence among neurological patients. A cross-sectional study was done with consecutive sampling of neurological patients who were hospitalized from January 2017 to February 2020 at the Mahar Mardjono National Brain Center Hospital East Jakarta Indonesia. Patients with sepsis, septic shock, or fever (> 38.5 °C), and who had not received antifungals before culture were enrolled in the study. Clinical specimens were obtained from blood, liquor cerebrospinal or other sterile sites, CVC, respiratory tract specimens, and urine or other non-sterile sites. Socio-demographic data, potential risk factors based on previous studies, clinical, and other tests data were obtained from medical records. Classification of invasive candidiasis was according to the Paphitou classification criteria. One hundred and two subjects met the study criteria. The prevalence of invasive candidiasis in neurological patients was 13.7%. All of the isolates were C. parapsilosis. The prevalence of invasive candidiasis was high in the samples studied. The infection was associated with septic shock, tracheostomy, and duration of use of central venous catheter, ventilator, and steroids.

Diagnosis and analysis of unexplained cases of childhood encephalitis in Australia using metatranscriptomic sequencing.

Encephalitis is most often caused by a variety of infectious agents identified through diagnostic tests utilizing cerebrospinal fluid. We investigated the clinical characteristics and potential aetiological agents of unexplained encephalitis through metagenomic sequencing of residual clinical samples from multiple tissue types and independent clinical review. Forty-three specimens were collected from 18 encephalitis cases with no cause identified by the Australian Childhood Encephalitis study. Samples were subjected to total RNA sequencing ('metatranscriptomics') to determine the presence and abundance of potential pathogens, and to describe the possible aetiologies of unexplained encephalitis. Using this protocol, we identified five RNA and two DNA viruses associated with human infection from both non-sterile and sterile sites, which were confirmed by PCR. These comprised two human rhinoviruses, two human seasonal coronaviruses, two polyomaviruses and one picobirnavirus. Human rhinovirus and seasonal coronaviruses may be responsible for five of the encephalitis cases. Immune-mediated encephalitis was considered likely in six cases and metatranscriptomics did not identify a possible pathogen in these cases. The aetiology remained unknown in nine cases. Our study emphasizes the importance of respiratory viruses in the aetiology of unexplained child encephalitis and suggests that non-central-nervous-system sampling in encephalitis clinical guidelines and protocols could improve the diagnostic yield.

Expanding the definition beyond surveillance criteria reveals a large burden of osteomyelitis caused by group B Streptococcus in the United States Veterans Health Administration

BackgroundPopulation-based surveillance studies may underestimate osteomyelitis caused by Group B Streptococcus (GBS). We analyzed cases of GBS osteomyelitis, including patients diagnosed using an expanded case definition that incorporates cultures from non-sterile sites, as well as cultures from normally sterile sites.MethodsWe retrospectively examined a cohort of veterans with the diagnosis of osteomyelitis between 2008 and 2017. Cases of definite GBS osteomyelitis required GBS isolation from normally sterile sites, (e.g., blood or bone). Cases of probable GBS osteomyelitis permitted GBS isolation from non-sterile sites (e.g., surgical sites, wounds). We compared comorbid conditions, lower extremity amputation and mortality rates in these groups.ResultsAmong 1281 cases of GBS osteomyelitis, the median age was 63 years, 87% had diabetes mellitus and 37% had peripheral vascular disease. Similar characteristics were found in 768 (60%) cases classified as definite and 513 (40%) classified as probable GBS osteomyelitis. Polymicrobial infection was less frequent in patients with definite than with probable GBS osteomyelitis (45% vs. 85%; P < 0.001). Mortality rates within 1-year were similar for definite and probable GBS osteomyelitis (12% vs. 10%). Amputation within 1-year occurred in 21% of those with definite and 10% of those with probable GBS osteomyelitis of the lower extremity, with comparable rates in the subset with monomicrobial infection.ConclusionsExpanding the definition of GBS osteomyelitis to include cases with cultures from non-sterile sites may be warranted, increasing the estimated burden of GBS osteomyelitis. This can help guide preventive efforts to reduce the impact of GBS osteomyelitis.

Epidemiology and impact of colonization by multidrug-resistant Gram-negative bacteria on bloodstream infections in early phase of allogeneic hematopoietic stem cell transplantation

Objective. To study epidemiology and impact of colonization by multidrug-resistant Gram-negative bacteria (MDRGNB) on bloodstream infections (BSI) during allogeneic hematopoietic stem cell transplantation (allo-HSCT). Materials and Methods. The retrospective study included 288 patients received the first allo-HSCT between 2018 and 2019. The median age was 32 (18–66) years, male – 53% (n = 152). The majority of patients had acute leukemia – 62% (n = 178) and received transplant from matched unrelated – 42% (n = 120) or haploidentical donor – 26% (n = 75). Relapse of underlying disease at the moment of all-HSCT was registered in 23% (n = 66) of patients. Results. Colonization of non-sterile sites before allo-HSCT by at least one MDRGNB was detected in 28% (n = 64). In most cases resistance is due to extended spectrum beta-lactamases (ESBL) – 86% (n = 55), while carbapenemases in combination with ESBL were detected in 14% (n = 9) of patients. After allo-HSCT the colonization was significantly higher than before transplantation (n = 161, 56%, p = 0.001), mainly due to carbapenemase- and ESBL-producing bacteria – 73% (n = 118) (p = 0.001). BSI in the early period after transplantation developed in 26% (n = 76), and in 56% (n = 43) was caused by MDRGNB. The etiology of BSI included K. pneumoniae – 51% in mostly cases. The etiology of BSI was the same bacteria that colonized non-sterile sites 2 weeks before the detection bacteria in bloodstream in 69% (n = 30) patients. Colonization by MDRGNB was associated with the development of BSI (p &lt; 0.0001). The 100-day overall survival (OS) after all-HSCT was significantly lower in patients with colonization of non-sterile sites by MDRGNB compared with patients without colonization (60.6% vs 88.2%, p = 0.001). Conclusions. Colonization of MDRGNB after allo-HSCT reached 56%. K. pneumoniae was predominant etiology in both colonization and bloodstream infections. Colonization by MDRGNB was associated with the development of BSI and decreased OS after allo-HSCT.