Host response signature trends in persistent bacteraemia and metastatic infection due to Staphylococcus aureus and Gram-negative bacilli: a prospective multicentre observational study.

BACKGROUND: A prompt diagnosis of bacteraemia and sepsis is essential. Markers to predict the risk of persistent bacteraemia and metastatic infection are lacking. SeptiCyte RAPID is a host response assay stratifying patients according to the risk of infectious vs sterile inflammation through a scoring system (SeptiScore). In this study we explore the association between SeptiScore and persistent bacteraemia as well as metastatic and persistent infection in the context of a proven bacteraemia episode. METHODS: This is a prospective multicentre observational 14-month study on patients with proven bacteraemia caused by Staphylococcus aureus or Gram-negative bacilli. Samples for assessment by SeptiCyte were collected with paired blood cultures for 4 consecutive days after the index blood culture. RESULTS: We included 86 patients in the study, 40 with S. aureus and 46 with Gram-negative bacilli bacteraemia. SeptiScores over the follow-up were higher in patients with Gram-negative compared to S. aureus bacteraemia (median 6.4, IQR 5.5-7.4 vs 5.6 IQR 5.1-6.2, p = 0.002). Higher SeptiScores were found to be associated with positive blood cultures at follow-up (AUC = 0.86, 95%CI 0.68-1.00) and with a diagnosis of metastatic infection at day 1 and 2 of follow-up (AUC = 0.79, 95%CI 0.57-1.00 and AUC = 0.82, 95%CI 0.63-1.00 respectively) in the context of Gram-negative bacteraemia while no association between SeptiScore and the outcomes of interest was observed in S. aureus bacteraemia. Mixed models confirmed the association of SeptiScore with positive blood cultures at follow-up (p = 0.04) and metastatic infection (p = 0.03) in the context of Gram-negative bacteraemia but not S. aureus bacteraemia after adjusting for confounders. CONCLUSIONS: SeptiScores differ in the follow-up of S. aureus and Gram-negative bacteraemia. In the setting of Gram-negative bacteraemia SeptiScore demonstrated a good negative predictive value for the outcomes of interest and might help rule out the persistence of infection defined as metastatic spread, lack of source control or persistent bacteraemia.

Persistence of Detectable Pathogens by Culture-Independent Systems (T2 Magnetic Resonance) in Patients With Bloodstream Infection: Prognostic Role and Possible Clinical Implications.

BACKGROUND: Persistent Staphylococcus aureus bacteremia is associated with metastatic infection and adverse outcomes, whereas gram-negative bacteremia is normally transient and shorter course therapy is increasingly advocated for affected patients. Whether the prolonged detection of pathogen DNA in blood by culture-independent systems could have prognostic value and guide management decisions is unknown. METHODS: We performed a multicenter, prospective, observational study on 102 patients with bloodstream infection (BSI) to compare time to bloodstream clearance according to T2 magnetic resonance and blood cultures over a 4-day follow-up. We also explored the association between duration of detectable pathogens according to T2 magnetic resonance (magnetic resonance-DNAemia [MR-DNAemia]) and clinical outcomes. RESULTS: Time to bloodstream clearance according to T2 magnetic resonance was significantly longer than blood culture clearance (HR, .54; 95% CI, .39-.75) and did not differ according to the causative pathogen (P = .5). Each additional day of MR-DNAemia increased the odds of persistent infection (defined as metastatic infection or delayed source control) both in the overall population (OR, 1.98; 95% CI, 1.45-2.70) and in S. aureus (OR, 1.92; 95% CI, 1.12-3.29) and gram-negative bacteremia (OR, 2.21; 95% CI, 1.35-3.60). MR-DNAemia duration was also associated with no improvement in Sequential Organ Failure Assessment score at day 7 from infection onset (OR, 1.76; 95% CI, 1.21-2.56). CONCLUSIONS: T2 magnetic resonance may help diagnose BSI in patients on antimicrobials with negative blood cultures as well as to identify patients with metastatic infection, source control failure, or adverse short-term outcome. Future studies may inform its usefulness within the setting of antimicrobial stewardship programs.

Risk factors, treatment and outcomes of subacute thyroiditis secondary to COVID-19: a systematic review.

BACKGROUND: COVID-19 is known to cause an acute respiratory illness, although clinical manifestations outside of the respiratory tract may occur. Early reports have identified SARS-CoV-2 as a cause of subacute thyroiditis (SAT). METHODS: A systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. MEDLINE, Web of Science and PubMed databases were queried in February 2021 for studies from December 2019 to February 2021. MeSH search terms 'COVID-19', 'SARS-CoV-2' and 'coronavirus' along with search terms 'thyroiditis', 'thyrotoxicosis' and 'thyroid' were used. Descriptive statistics for continuous variables and proportions for categorical variables were calculated. RESULTS: Fifteen publications reporting on 17 individual cases of COVID-19-induced SAT were identified. Age ranged from 18 to 69 years. The majority (14 of 17; 82%) of cases were female. The delay between onset of respiratory symptoms and diagnosis of SAT ranged from 5 to 49 days (mean, 26.5). Systemic inflammatory response syndrome related to viral infection was uncommonly reported at the time of SAT diagnosis. Thyroid ultrasonography frequently reported an enlarged hypoechoic thyroid with decreased vascularity and heterogenous echotexture. Elevated C-reactive protein (CRP) was common at the time of SAT diagnosis, with results ranging from 4.5 to 176 mg/L (mean, 41 mg/L). Antithyroid antibodies were frequently negative. SAT-specific treatment included corticosteroids for 12 of 17 (70.5%) patients. Most returned to normal thyroid status. CONCLUSION: COVID-19-associated SAT may be difficult to identify in a timely manner due to potential absence of classic symptoms, as well as cross-over of common clinical features between COVID-19 and thyrotoxicosis.

Epidemiology of Aeromonas Species Bloodstream Infection in Queensland, Australia: Association with Regional and Climate Zones.

Aeromonas species can cause severe bloodstream infection (BSI) however, few studies have examined their epidemiology in non-selected populations. The objective of this study was to describe the incidence and determinants of Aeromonas species BSI in Queensland, Australia. A retrospective population-based cohort study was conducted during 2000-2019. Aeromonas species BSI were identified by laboratory surveillance and clinical and outcome information through data linkages to statewide databases. A total of 407 incident Aeromonas species BSI were identified with an age- and sex-standardized incidence of 5.2 per million residents annually. No trend in annual incidence rate during two decades of surveillance was demonstrated. Significant variable monthly occurrences were observed with highest rates during warmer, wetter months, and lowest rates during winter and dry periods. There was significant variability in incidence accordingly to region and climate zones, with higher rates observed in tropical north regions and lowest in southeastern corner. The highest incidence was observed in very remote and hot areas in Queensland. Cases were infrequent in children and risk was highest in elderly and males. Seventy-eight patients died within 30 days with a case-fatality rate of 19%. Older age, non-focal infection, higher Charlson score, and monomicrobial bacteremia were independent risk factors for death. Demographic and climatic changes may increase the burden of these infections in future years.

MOLECULAR IDENTIFICATION OF MEMBERS OF THE FAMILY PASTEURELLACEAE FROM THE ORAL CAVITY OF KOALAS (PHASCOLARCTOS CINEREUS) AND THEIR RELATIONSHIP WITH ISOLATES FROM KOALA BITE WOUNDS IN HUMANS.

A total of 22 Pasteurellaceae isolates obtained from the oral cavity of koalas (Phascolarctos cinereus) at different wildlife centers in Australia were investigated using amplification and sequencing of two housekeeping genes, rpoA and recN. The available sequences from the Lonepinella koalarum type strain (ACM3666T) and the recent isolates of Lonepinella-like bacteria obtained from human infected wounds associated with koala bites were also included. Phylogenetic analysis was performed on the concatenated rpoA-recN genes and genome relatedness was calculated based on the recN sequences. The oral cavity isolates, the koala bite wound isolates, and L. koalarum ACM3666T resulted in four clusters (Clusters 1-4). Clusters 1-3 were clearly not members of the genus Lonepinella. Cluster 1 was closely related to the genus Fredericksenia, and Clusters 2 and 3 appeared to be novel genera. Cluster 4 consisted of three subclusters: Cluster 4a with one koala bite wound isolate and L. koalarum ACM3666T, Cluster 4b with three oral cavity isolates and two Lonepinella-like wound isolates, and Cluster 4c with three nearly identical oral cavity isolates that may represent a different species within the genus Lonepinella. The rich Pasteurellaceae population, including potential novel taxa in the oral cavity of koalas supports an important role of these highly adapted microorganisms in the physiology of koalas. Moreover, the pathogenic potential of Lonepinella-like species is an important consideration when investigating infected koala bites in humans.

Draft Genome Sequence of Aeromonas dhakensis, Isolated from a Patient with Fatal Necrotizing Fasciitis.

Aeromonas hydrophila and Aeromonas dhakensis are ubiquitous in marine and aquatic environments. Both species, which cause significant skin and soft tissue infection, are often associated with water activities and floods. Here, we describe the draft genome sequence of A. dhakensis, isolated from a fatal case of necrotizing fasciitis.

Identification of Lonepinella sp. in Koala Bite Wound Infections, Queensland, Australia.

We report 3 cases of koala bite wound infection with Lonepinella koalarum-like bacteria requiring antimicrobial and surgical management. The pathogens could not be identified by standard tests. Phylogenetic analysis of 16S rRNA and housekeeping genes identified the genus. Clinicians should isolate bacteria and determine antimicrobial susceptibilities when managing these infections.

Genotypic and phenotypic identification of Aeromonas species and CphA-mediated carbapenem resistance in Queensland, Australia.

Infection caused by Aeromonas spp. ranges from superficial wound infection to life-threatening septicemia. Carbapenem resistance due to metallo-beta-lactamase, CphA encoded by the cphA gene, is a significant problem. This study defines Aeromonas spp. causing clinical disease in Queensland, Australia. Phenotypic tests for carbapenemase detection were assessed. One hundred Aeromonas isolates from blood (22), wound (46), sterile sites (11), stool (18), eye (2), and sputum (1) were characterized by rpoB and gyrB sequencing. Meropenem susceptibility by VITEK2, disk diffusion, and E-test MIC were determined. Carbapenemase production was assessed by Carba NP test and cphA by PCR. Gene sequencing identified isolates as Aeromonas dhakensis (39), Aeromonas veronii (21), Aeromonas hydrophila (20), Aeromonas caviae (14), Aeromonas jandaei (4), Aeromonas bestiarum (1), and Aeromonas sanarellii (1). Disk diffusion and E-test failed to detect resistance in isolates with presence of cphA. Carba NP was performed with 97.4% sensitivity and 95.7% specificity. Carbapenem resistance gene cphA was detected in A. veronii (21; 100%), A. hydrophila (18; 90%), A. dhakensis (34; 87.2%), A. jandaei (3; 75%), and A. bestiarum (1; 100%) but not A. caviae. We found that A. dhakensis was the predominant species, a previously unrecognized pathogen in this region.