Association of microbiological factors with mortality in Escherichia coli bacteraemia presenting with sepsis/septic shock: a prospective cohort study.

OBJECTIVES: This study aimed to determine the association of Escherichia coli microbiological factors with 30-day mortality in patients with bloodstream infection (BSI) presenting with a dysregulated response to infection (i.e. sepsis or septic shock). METHODS: Whole-genome sequencing was performed on 224 E coli isolates of patients with sepsis/septic shock, from 22 Spanish hospitals. Phylogroup, sequence type, virulence, antibiotic resistance, and pathogenicity islands were assessed. A multivariable model for 30-day mortality including clinical and epidemiological variables was built, to which microbiological variables were hierarchically added. The predictive capacity of the models was estimated by the area under the receiver operating characteristic curve (AUROC) with 95% confidence intervals (CI). RESULTS: Mortality at day 30 was 31% (69 patients). The clinical model for mortality included (adjusted OR; 95% CI) age (1.04; 1.02-1.07), Charlson index ≥3 (1.78; 0.95-3.32), urinary BSI source (0.30; 0.16-0.57), and active empirical treatment (0.36; 0.11-1.14) with an AUROC of 0.73 (95% CI, 0.67-0.80). Addition of microbiological factors selected clone ST95 (3.64; 0.94-14.04), eilA gene (2.62; 1.14-6.02), and astA gene (2.39; 0.87-6.59) as associated with mortality, with an AUROC of 0.76 (0.69-0.82). DISCUSSION: Despite having a modest overall contribution, some microbiological factors were associated with increased odds of death and deserve to be studied as potential therapeutic or preventive targets.

Whole-genome characterisation of Escherichia coli isolates from patients with bacteraemia presenting with sepsis or septic shock in Spain: a multicentre cross-sectional study.

BACKGROUND: Escherichia coli is the most frequent cause of bloodstream infections (BSIs). About one-third of patients with BSIs due to E coli develop sepsis or shock. The objective of this study is to characterise the microbiological features of E coli blood isolates causing sepsis or septic shock to provide exploratory information for future diagnostic, preventive, or therapeutic interventions. METHODS: E coli blood isolates from a multicentre cross-sectional study of patients older than 14 years presenting with sepsis or septic shock (according to the Third International Consensus Definitions for Sepsis and Septic Shock criteria) from hospitals in Spain between Oct 4, 2016, and Oct 15, 2017, were studied by whole-genome sequencing. Phylogroups, sequence types (STs), serotype, FimH types, antimicrobial resistance (AMR) genes, pathogenicity islands, and virulence factors were identified. Susceptibility testing was performed by broth microdilution. The main outcome of this study was the characterisation of the E coli blood isolates in terms of population structure by phylogroups, groups (group 1: phylogroups B2, F, and G; group 2: A, B1, and C; group 3: D), and STs and distribution by geographical location and bloodstream infection source. Other outcomes were virulence score and prevalence of virulence-associated genes, pathogenicity islands, AMR, and AMR-associated genes. Frequencies were compared using χ² or Fisher's exact tests, and continuous variables using the Mann-Whitney test, with Bonferroni correction for multiple comparisons. FINDINGS: We analysed 224 isolates: 140 isolates (63%) were included in phylogenetic group 1, 52 (23%) in group 2, and 32 (14%) in group 3. 85 STs were identified, with four comprising 44% (n=98) of the isolates: ST131 (38 [17%]), ST73 (25 [11%]), ST69 (23 [10%]), and ST95 (12 [5%]). No significant differences in phylogroup or ST distribution were found according to geographical areas or source of bloodstream infection, except for ST95, which was more frequent in urinary tract infections than in other sources (11 [9%] of 116 vs 1 [1%] of 108, p=0·0045). Median virulence score was higher in group 1 (median 25·0 [IQR 20·5-29·0) than in group 2 (median 14·5 [9·0-20·0]; p<0·0001) and group 3 (median 21 [16·5-23·0]; p<0·0001); prevalence of several pathogenicity islands was higher in group 1. No significant differences were found between phylogenetic groups in proportions of resistance to antibiotics. ST73 had higher median virulence score (32 [IQR 29-35]) than the other predominant clones (median range 21-28). Some virulence genes and pathogenicity islands were significantly associated with each ST. ST131 isolates had higher prevalence of AMR and a higher proportion of AMR genes, notably blaCTX-M-15 and blaOXA-1. INTERPRETATION: In this exploratory study, the population structure of E coli causing sepsis or shock was similar to previous studies that included all bacteraemic isolates. Virulence genes, pathogenicity islands, and AMR genes were not randomly distributed among phylogroups or STs. These results provide a comprehensive characterisation of invasive E coli isolates causing severe response syndrome. Future studies are required to determine the contribution of these microbiological factors to severe clinical presentation and worse outcomes in patients with E coli bloodstream infection. FUNDING: Instituto de Salud Carlos III.

Pseudomonas aeruginosa Community-Onset Bloodstream Infections: Characterization, Diagnostic Predictors, and Predictive Score Development-Results from the PRO-BAC Cohort.

Community-onset bloodstream infections (CO-BSI) caused by gram-negative bacilli are common and associated with significant mortality; those caused by Pseudomonas aeruginosa are associated with worse prognosis and higher rates of inadequateempirical antibiotic treatment. The aims of this study were to describe the characteristics of patients with CO-BSI caused by P. aeruginosa, to identify predictors, and to develop a predictive score for P. aeruginosa CO-BSI. Materials/methods: PROBAC is a prospective cohort including patients >14 years with BSI from 26 Spanish hospitals between October 2016 and May 2017. Patients with monomicrobial P. aeruginosa CO-BSI and monomicrobial Enterobacterales CO-BSI were included. Variables of interest were collected. Independent predictors of Pseudomonas aeruginosa CO-BSI were identified by logistic regression and a prediction score was developed. Results: A total of 78patients with P. aeruginosa CO-BSI and 2572 with Enterobacterales CO-BSI were included. Patients with P. aeruginosa had a median age of 70 years (IQR 60−79), 68.8% were male, median Charlson score was 5 (IQR 3−7), and 30-daymortality was 18.5%. Multivariate analysis identified the following predictors of CO-BSI-PA [adjusted OR (95% CI)]: male gender [1.89 (1.14−3.12)], haematological malignancy [2.45 (1.20−4.99)], obstructive uropathy [2.86 (1.13−3.02)], source of infection other than urinary tract, biliary tract or intra-abdominal [6.69 (4.10−10.92)] and healthcare-associated BSI [1.85 (1.13−3.02)]. Anindex predictive of CO-BSI-PA was developed; scores ≥ 3.5 showed a negative predictive value of 89% and an area under the receiver operator curve (ROC) of 0.66. Conclusions: We did not find a good predictive score of P. aeruginosa CO-BSI due to its relatively low incidence in the overall population. Our model includes variables that are easy to collect in real clinical practice and could be useful to detect patients with very low risk of P. aeruginosa CO-BSI.

Submaxilitis aguda bilateral asociada con listeriosis en un paciente inmunodeprimido / Acute bilateral submaxillitis associated to listeriosis in immunosuppressed patient

Acute bilateral submaxillitis is a rare event, except when it is caused by sialolithiasis. It has been described secondary to allergic, infectious, suppurative or viral processes, autoimmune such as Sjögren's syndrome, drugs such as thiopurines, nitrofurantoin, phenylbutazone, captopril, and after upper airway procedures such as upper endoscopy, orotracheal intubation bronchoscopy and ERCP (endoscopic retrograde cholangiopancreatography for choledocholithiasis). Treatment with tumour necrosis factor-alpha (TNF-alpha) antagonist drugs is associated with an increased risk of reactivation of intracellular bacterial infections, so that listeriosis has been described in pathologies that require such treatment, such as rheumatic, dermatological and intestinal diseases, which present other comorbidities or are immunocompromised. Listeriosis mainly causes bacteremia and meningitis, when symptomatic, and infects immunosuppressed persons, where it has a lethality despite 30% antibiotherapy. We present the clinical case of a male immunosuppressed patient, secondary to a treatment with azathioprine and prednisone followed by adalimumab, for indeterminate inflammatory bowel disease, superinfected by CMV, who after eating meat contaminated by Listeria monocytogenes, suffered a picture of listeriosis bacteremia, which improved with antibiotic treatment, followed by a transient acute bilateral submaxillitis, which subsided with symptomatic treatment (oral hydration). It is the only case described in the literature, in which an immunosuppressed patient treated with adalimumab, suffers from acute bilateral submaxillitis in the context of listeriosis, caused by the mumps virus.

La submaxilitis aguda bilateral es un evento raro, salvo cuando está causada por sialolitiasis. Se la ha descrito secundaria a procesos alérgicos, infecciosos, supurativos, virales o autoinmunes como el síndrome de Sjögren; a la administración de fármacos como tiopurinas, nitrofurantoina, fenilbutazona, captopril, y tras procedimientos sobre la vía aérea superior, como endoscopia digestiva alta, broncoscopia, intubación orotraqueal y colangiopancreatografía retrógrada endoscópica por coledocolitiasis (CPRE). El tratamiento con fármacos antagonistas del factor de necrosis tumoral alfa (TNF-alfa) se asocia con riesgo acentuado de reactivación de infecciones bacterianas intracelulares, de forma que se ha descrito la listeriosis en afecciones que requieren dicho tratamiento, como enfermedades reumáticas, dermatológicas y del intestino en sujetos que presentaban otras comorbilidades o estaban inmunocomprometidos. La listeriosis provoca bacteriemia y meningitis predominantemente, cuando es sintomática, e infecta a los sujetos inmunodeprimidos, en los que, a pesar de la antibioticoterapia, tiene una letalidad del 30%. Se presenta el caso clínico de un paciente varón, inmunodeprimido, secundario a tratamiento por azatioprina y prednisona seguido de adalimumab, por enfermedad inflamatoria intestinal indeterminada, sobreinfectada por citomegalovirus, que tras la ingesta de carne contaminada por Listeria monocytogenes, sufrió un cuadro de bacteriemia por listeriosis que mejoró con tratamiento con antibióticos, seguido de submaxilitis aguda bilateral transitoria, que cedió con tratamiento sintomático (hidratación oral). Es el único caso descrito en la literatura en el que un paciente inmunodeprimido tratado con adalimumab presenta submaxilitis aguda bilateral en el contexto de la listeriosis, provocada por el virus de la parotiditis.

Revisiting the epidemiology of bloodstream infections and healthcare-associated episodes: results from a multicentre prospective cohort in Spain (PRO-BAC Study).

The epidemiology of bloodstream infections (BSIs) is dynamic as it depends on microbiological, host and healthcare system factors. The aim of this study was to update the information regarding the epidemiology of BSIs in Spain considering the type of acquisition. An observational, prospective cohort study in 26 Spanish hospitals from October 2016 through March 2017 including all episodes of BSI in adults was performed. Bivariate analyses stratified by type of acquisition were performed. Multivariate analyses were performed by logistic regression. Overall, 6345 BSI episodes were included; 2510 (39.8%) were community-acquired (CA), 1661 (26.3%) were healthcare-associated (HCA) and 2056 (32.6%) hospital-acquired (HA). The 30-day mortality rates were 11.6%, 19.5% and 22.0%, respectively. The median age of patients was 71 years (interquartile range 60-81 years) and 3656 (58.3%; 95% confidence interval 57.1-59.6%) occurred in males. The proportions according to patient sex varied according to age strata. Escherichia coli (43.8%), Klebsiella spp. (8.9%), Staphylococcus aureus (8.9%) and coagulase-negative staphylococci (7.4%) were the most frequent pathogens. Multivariate analyses confirmed important differences between CA and HCA episodes, but also between HCA and HA episodes, in demographics, underlying conditions and aetiology. In conclusion, we have updated the epidemiological information regarding patients' profiles, underlying conditions, frequency of acquisition types and aetiological agents of BSI in Spain. HCA is confirmed as a distinct type of acquisition.

Neisseria meningitidis Infecting a Prosthetic Knee Joint: A New Case of an Unusual Disease.

Primary meningococcal meningitis is an infrequent but known disease. However, the infection of a prosthetic joint with Neisseria meningitidis is rare. We hereby describe the second case of an arthroplasty infected with Neisseria meningitidis that responded favourably to prosthesis retention with surgical debridement, in combination with antibiotics treatment.

Predictors of early mortality in very elderly patients with bacteremia: a prospective multicenter cohort.

OBJECTIVES: The proportion of very elderly people in the population is increasing, and infectious diseases in this patient group may present with specific characteristics. The objective of this study was to investigate the outcome predictors of bacteremia among the very elderly. METHODS: This was a multicenter prospective cohort study of bloodstream infections (BSI) in patients ≥ 80 years old in 15 hospitals in Spain. The outcome variables were 14-day and 30-day mortality. Multivariate analysis was performed. RESULTS: One hundred and twenty episodes were included. Mortality was 22% (n = 26) on day 14 and 28% (n = 34) on day 30. In the univariate analysis, the variables associated with mortality were neutropenia, recent surgery, Pitt score ≥ 2, intensive care unit (ICU) admission, severe sepsis or shock, and abdominal, unknown, and respiratory tract sources. In the multivariate analysis, variables associated with mortality on day 14 were high-risk source (abdominal, unknown, and respiratory tract sources; odds ratio (OR) 7.9, 95% confidence interval (CI) 1.8-33.9), Pitt score ≥ 2 (OR 5.6, 95% CI 1.3-23.3), inadequate empirical treatment (OR 11.24, 95% CI 1.6-80.2), and severe sepsis or shock at presentation (OR 5.3, 95% CI 1.4-20.7); the interaction between empiric treatment and high-risk source was significant. On day 30, mortality was independently related to a high-risk source (OR 2.92, 95% CI 1.1-7.5) and presentation with severe sepsis or shock (OR 3.81, 95% CI 1.2-12.4). CONCLUSIONS: Presentation with severe sepsis or shock and a high-risk source of BSI were independent predictors of 14-day and 30-day mortality. Inadequate empirical treatment was also a predictor of early mortality in patients with a high-risk source.