Acute Myocardial Infarction and Community-acquired Staphylococcus aureus Bloodstream Infection: An Observational Cohort Study.

BACKGROUND: The relationship between acute myocardial infarction and infection was recognized in the early 20th century during influenza epidemics. Most recently, a case control study and a self-control design study have identified an association between Staphylococcus aureus infection and acute myocardial infarction. We assessed the association of community-acquired Staphylococcus aureus bloodstream infection (CA-SABSI) and myocardial infarction in the 365 days following blood culture. METHODS: This was a cohort study assessing the incidence of myocardial infarction 365 days after blood culture for Staphylococcus aureus. Culture-negative patients had blood cultures collected at hospital attendance and were matched to the CA-SABSI participants by sex, 5-year age strata, and year of culture collection. Pathology information was linked to hospital administrative data and index of relative socioeconomic advantage and disadvantage (ISRAD). RESULTS: The study included 5157 CA-SABSI cases matched to 10 146 blood culture-negative cases. The mortality rate was significantly higher in the CA-SABSI group (10.9%; 562/5157) than in culture-negative cases (5.1%; 521/10 146) at 365 days (P < .0001). In the 7 days following the index blood culture, excluding recurrent events, there were 89 (1.7%) and 37 (.4%) myocardial infarction diagnoses in the CA-SABSI and culture-negative cases, respectively. Multivariable logistic regression for myocardial infarction demonstrated a significant association with CA-SABSI after adjusting for known risk factors (odds ratio [OR], 5; 95% confidence interval [CI], 3.3-7.5; P < .0001). Myocardial infarctions occurring in this short-term risk period were associated with all-cause mortality in a Cox proportional hazard model (OR, 1.7; 95% CI, 1.2-2.4; P < .005). CONCLUSIONS: CA-SABSI is associated with an increased short-term risk of myocardial infarction, which is associated with subsequent mortality.

Diagnosing sepsis in the ICU: Comparison of a gene expression signature to pre-existing biomarkers.

PURPOSE: We aimed to identify a gene signature that discriminates between sepsis and aseptic inflammation in patients administered antibiotics in the intensive care unit and compare it to commonly utilised sepsis biomarkers. METHODS: 91 patients commenced on antibiotics were retrospectively diagnosed as having: (i) blood culture positive sepsis; (ii) blood culture negative sepsis; or (iii) aseptic inflammation. Bloods were collected after <24 h of antibiotic commencement for both gene expression sequencing analysis and measurement of previously identified biomarkers. RESULTS: 53 differentially expressed genes were identified that accurately discriminated between blood culture positive sepsis and aseptic inflammation in a cohort of patients given antibiotics [aROC 0.97 (95% CI, 0.95-0.99)]. This gene signature was validated in a publicly available database. The gene signature outperformed previously identified sepsis biomarkers including C-reactive protein [aROC 0.72 (95% CI, 0.57-0.87)], NT-Pro B-type Natriuretic Peptide [aROC 0.84 (95% CI, 0.73-0.96)], and Septicyte™ LAB [aROC 0.8 (95% CI, 0.68-0.93)], but was comparable to Procalcitonin [aROC 0.96 (95% CI, 0.9-1)]. CONCLUSIONS: A gene expression signature was identified that accurately discriminates between sepsis and aseptic inflammation in patients given antibiotics in the intensive care unit.

Long term sepsis readmission, mortality and cause of death following Gram negative bloodstream infection: a propensity matched observational linkage study.

OBJECTIVES: Understand the long-term mortality, risk of readmission for sepsis and cause of death following a gram-negative bloodstream infection (GN-BSI). METHODS: This was a propensity-matched study using data linkage of Queensland hospital data, Australia. GN-BSIs were collected from 2005 to 2010 and matched 1:1 to hospital admissions without BSI for age, gender, year of culture collection, frequency of admissions in the prior year and Charlson-Deyo Comorbidity score and each comorbidity within the Charlson-Deyo score. Readmissions for sepsis, mortality and causes of death were evaluated. RESULTS: Cases of GN-BSI were propensity-matched 1:1 to culture-negative hospital admissions (n = 14016). Readmissions for sepsis were higher in the GN-BSI cohort from 91 to 365 days (P < 0.001) and in the four subsequent years (P < 0.001). The five-year survival in the GN-BSI cohort was 52% versus 65% in the culture-negative cases (P < 0.001). Infection was only a common underlying cause of death within the first 90 days. Sepsis was the most common contributing cause of death (CCOD) for the two years following index culture in the GN-BSI cohort. CONCLUSIONS: Compared to a similarly vulnerable group of hospital attendees, GN-BSI had higher mortality and demonstrated a persistent long-term risk of readmission for sepsis and sepsis as a CCOD.

Assessment of the Clinical Pulmonary Infection Scores for prediction of ventilator associated pneumonia in patients with out of hospital cardiac arrest.

BACKGROUND: Patients suffering out-of-hospital cardiac arrest (OHCA) are at an increased risk of aspiration pneumonitis and development of subsequent aspiration pneumonia. The diagnostic uncertainty in this context can lead to a large proportion receiving broad spectrum antibiotics. METHODS: This was a three-year, retrospective cohort study of consecutive patients admitted with OHCA. Data were collected in an Australian tertiary centre intensive care unit (ICU) between December 2016-December 2019. We assessed the incidence of Ventilator associated pneumonia (VAP), admission Clinical Pulmonary Infection Scores (CPIS) in patients with OHCA and its' association with VAP at day 3 [1]. We also assessed antibiotics prescribing (timing of initiation and drug choice) and intensive care mortality relative to the day 1 CPIS. RESULTS: Over the three years, 100 patients were admitted with OHCA. The incidence of VAP was 6%. The CPIS on admission was not associated with development of VAP at day 3 (p = 0.75) and no significant association was found between choice of antibiotic regimens and VAP incidence. Timing of initiation of antibiotics was associated with VAP (12hrs vs 48hrs, p = 0.035) but not the choice of antibiotic (penicillin and cephalosporins vs antipseudomonal antibiotics). CPIS score at day 1 was not associated with ICU mortality in a multivariate analysis. CONCLUSION: We demonstrated a very low incidence of VAP in OHCA patients in comparison to published studies. In this context, there was no evidence for an association between CPIS score and VAP at day 3. The CPIS may have utility as a decision support tool for targeted antibiotic prescribing in this cohort.

Genomic surveillance, characterization and intervention of a polymicrobial multidrug-resistant outbreak in critical care.

Background. Infections caused by carbapenem-resistant Acinetobacter baumannii (CR-Ab) have become increasingly prevalent in clinical settings and often result in significant morbidity and mortality due to their multidrug resistance (MDR). Here we present an integrated whole-genome sequencing (WGS) response to a persistent CR-Ab outbreak in a Brisbane hospital between 2016-2018.Methods. A. baumannii, Klebsiella pneumoniae, Serratia marcescens and Pseudomonas aeruginosa isolates were sequenced using the Illumina platform primarily to establish isolate relationships based on core-genome SNPs, MLST and antimicrobial resistance gene profiles. Representative isolates were selected for PacBio sequencing. Environmental metagenomic sequencing with Illumina was used to detect persistence of the outbreak strain in the hospital.Results. In response to a suspected polymicrobial outbreak between May to August of 2016, 28 CR-Ab (and 21 other MDR Gram-negative bacilli) were collected from Intensive Care Unit and Burns Unit patients and sent for WGS with a 7 day turn-around time in clinical reporting. All CR-Ab were sequence type (ST)1050 (Pasteur ST2) and within 10 SNPs apart, indicative of an ongoing outbreak, and distinct from historical CR-Ab isolates from the same hospital. Possible transmission routes between patients were identified on the basis of CR-Ab and K. pneumoniae SNP profiles. Continued WGS surveillance between 2016 to 2018 enabled suspected outbreak cases to be refuted, but a resurgence of the outbreak CR-Ab mid-2018 in the Burns Unit prompted additional screening. Environmental metagenomic sequencing identified the hospital plumbing as a potential source. Replacement of the plumbing and routine drain maintenance resulted in rapid resolution of the secondary outbreak and significant risk reduction with no discernable transmission in the Burns Unit since.Conclusion. We implemented a comprehensive WGS and metagenomics investigation that resolved a persistent CR-Ab outbreak in a critical care setting.

Acute kidney injury with combination vancomycin and piperacillin-tazobactam therapy in the ICU: A retrospective cohort study.

Vancomycin and piperacillin-tazobactam are commonly used antibiotics. There is increasing evidence to indicate that these therapies in combination predispose patients to acute kidney injury (AKI). However, studies of intensive care unit (ICU) patients with these antibiotics have produced conflicting results. In this single-centre, retrospective cohort study, data was collected on ICU patients prescribed combination vancomycin and piperacillin-tazobactam (VPT) for at least 48 h, compared with patients prescribed vancomycin with either cefepime or meropenem (VMC) for the same time period. Primary outcome was incidence of AKI; secondary outcomes included a desirability of outcome ranking (DOOR) scale, and association between antibiotic duration and kidney injury. A total of 260 patients were included. AKI was observed in 27% of cases overall. Incidence of AKI was higher with VPT compared with VMC on bivariate (relative risk reduction [RRR] 1.9, 95% confidence interval [CI] 0.9-4.1, P = 0.08) and multivariate (RRR 2.2, 95% CI 1.0-4.9, P = 0.05) analyses. Longer duration of antibiotic therapy was associated with increased rates of AKI independent of which antibiotics were prescribed: RRR 4.9, 95% CI 2.1-11.1, P = <0.001 for 5-6 days compared with <5 days, and RRR 2.3, 95% CI 1.0-5.5, P = 0.05 for >7 days compared with <5 days. This study demonstrated an association between increased risk of nephrotoxicity and combination VPT therapy in ICU patients. The concept remains controversial, with recent suggestions that VPT does not truly cause nephrotoxicity. Given our findings and the weight of previous studies, there is a strong mandate to undertake prospective trials to resolve the issue.

Evaluation of quick sequential organ failure assessment and systemic inflammatory response syndrome in patients with gram negative bloodstream infection.

BACKGROUND: The quick sequential organ failure assessment (qSOFA) score predicts mortality in patients with suspected infection. We sought to understand how well qSOFA and the Systemic Inflammatory Response Syndrome (SIRS) criteria predict gram negative bacteraemia. METHODS: We prospectively evaluated 99 patients with gram negative bloodstream infection from a single tertiary centre. We assessed the utility of SIRS and qSOFA for their rate of positivity and association with early delivery of antibiotics (<3 h). RESULTS: The SIRS criteria had the highest positivity rate amongst patients with gram negative bacteraemia (85%) compared to the qSOFA criteria (25%) on the day of first positive culture. Positive SIRS criteria was the only score associated with delivery of antibiotics within 3 h (Relative risk 3.5, 95% Confidence interval 1.3 to 12.5, p = < 0.02). CONCLUSION: In patients with gram negative bloodstream infection SIRS criteria was the most common positive risk score and had a higher association with early delivery of antibiotics when compared to qSOFA.

Long-term morbidity and mortality following bloodstream infection: A systematic literature review.

OBJECTIVES: Bloodstream infection results in significant short-term morbidity and mortality. No literature review has studied the long-term outcome following a bloodstream infection. This PROSPERO registered systematic review evaluated studies, which measured the association of a bloodstream infection with long-term morbidity and mortality. METHODS: Databases were systematically searched for studies of adult patients reporting morbidity and/or mortality one year or more following a bloodstream infection in comparison to a matched cohort without a bloodstream infection. RESULTS: Ten observational studies were included in the final analysis. Five studies assessed only mortality, two assessed morbidity and mortality and three studies assessed morbidity only. The one year mortality ranged from between 8 and 48% for patients with bloodstream infection. The pooled risk ratio of death at one year was significantly higher for patients with bloodstream infection when compared to the matched cohort (RR 4.04 [95% CI 1.84-8.87]). CONCLUSIONS: Bloodstream infection was associated with poor long-term outcome measured at one year when compared to matched controls. More evidence is needed to determine if this association is causative.

Detection of carbapenemase activity in Enterobacteriaceae using LC-MS/MS in comparison with the neo-rapid CARB kit using direct visual assessment and colorimetry.

It has been described that the sensitivity of the Carba NP test may be low in the case of OXA-48-like carbapenamases and mass spectrometry based methods as well as a colorimetry based method have been described as alternatives. We evaluated 84 Enterobacteriaceae isolates including 31 OXA-48-like producing isolates and 13 isolates that produced either an imipenemase (IMP; n=8), New Delhi metallo-ß-lactamase (NDM; n=3), or Klebsiella pneumoniae carbapenemase (KPC; n=2), as well as 40 carbapenemase negative Enterobacteriaceae isolates. We used the Neo-Rapid CARB kit, assessing the results with the unaided eye and compared it with a colorimetric approach. Furthermore, we incubated the isolates in growth media with meropenem and measured the remaining meropenem after one and 2h of incubation, respectively, using liquid chromatography tandem mass spectrometry (LC-MS/MS). Whilst all carbapenemase producing isolates with the exception of the OXA-244 producer tested positive for both the Neo-rapid CARB test using the unaided eye or colorimetry, and the 13 isolates producing either IMP, NDM or KPC hydrolysed the meropenem in the media almost completely after 2h of incubation, the 31 OXA-48-like producing isolates exhibited very variable hydrolytic activity when incubated in growth media with meropenem. In our study, the Neo-Rapid CARB test yielded a sensitivity of 98% for both the traditional and the colorimetric approach with a specificity of 95% and 100% respectively. Our results indicate that the Neo-Rapid CARB test may have use for the detection of OXA-48 type carbapenemases and that it may be particularly important to ensure bacterial lysis for the detection of these weaker hydrolysers.